Assessment of radiation doses from residential smoke detectors that contain americium-241

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

O'Donnell, F.R.; Etnier, E.L.; Holton, G.A.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq (3 ..mu..Ci) americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv (0.4 prem) to 20 nSv (2 ..mu..rem) for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 ..mu..Svmore » (0.0006 to 8 mrem) to total body and from 0.06 to 800 ..mu..Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft/sup 2/).« less

Comparative dosimetry of volumetric modulated arc therapy and limited-angle static intensity-modulated radiation therapy for early-stage larynx cancer

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

Riegel, Adam C.; Antone, Jeffrey; Schwartz, David L., E-mail: dschwartz3@nshs.edu

2013-04-01

To compare relative carotid and normal tissue sparing using volumetric-modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) for early-stage larynx cancer. Seven treatment plans were retrospectively created on 2 commercial treatment planning systems for 11 consecutive patients with T1-2N0 larynx cancer. Conventional plans consisted of opposed-wedged fields. IMRT planning used an anterior 3-field beam arrangement. Two VMAT plans were created, a full 360° arc and an anterior 180° arc. Given planning target volume (PTV) coverage of 95% total volume at 95% of 6300 cGy and maximum spinal cord dose below 2500 cGy, mean carotid artery dose was pushed asmore » low as possible for each plan. Deliverability was assessed by comparing measured and planned planar dose with the gamma (γ) index. Full-arc planning provided the most effective carotid sparing but yielded the highest mean normal tissue dose (where normal tissue was defined as all soft tissue minus PTV). Static IMRT produced next-best carotid sparing with lower normal tissue dose. The anterior half-arc produced the highest carotid artery dose, in some cases comparable with conventional opposed fields. On the whole, carotid sparing was inversely related to normal tissue dose sparing. Mean γ indexes were much less than 1, consistent with accurate delivery of planned treatment. Full-arc VMAT yields greater carotid sparing than half-arc VMAT. Limited-angle IMRT remains a reasonable alternative to full-arc VMAT, given its ability to mediate the competing demands of carotid and normal tissue dose constraints. The respective clinical significance of carotid and normal tissue sparing will require prospective evaluation.« less

Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer.

PubMed

Chandra, Anurag; Guerrero, Thomas M; Liu, H Helen; Tucker, Susan L; Liao, Zhongxing; Wang, Xiaochun; Murshed, Hasan; Bonnen, Mark D; Garg, Amit K; Stevens, Craig W; Chang, Joe Y; Jeter, Melinda D; Mohan, Radhe; Cox, James D; Komaki, Ritsuko

2005-12-01

To evaluate the feasibility whether intensity-modulated radiotherapy (IMRT) can be used to reduce doses to normal lung than three-dimensional conformal radiotherapy (3 DCRT) in treating distal esophageal malignancies. Ten patient cases with cancer of the distal esophagus were selected for a retrospective treatment-planning study. IMRT plans using four, seven, and nine beams (4B, 7B, and 9B) were developed for each patient and compared with the 3 DCRT plan used clinically. IMRT and 3 DCRT plans were evaluated with respect to PTV coverage and dose-volumes to irradiated normal structures, with statistical comparison made between the two types of plans using the Wilcoxon matched-pair signed-rank test. IMRT plans (4B, 7B, 9B) reduced total lung volume treated above 10 Gy (V(10)), 20 Gy (V(20)), mean lung dose (MLD), biological effective volume (V(eff)), and lung integral dose (P<0.05). The median absolute improvement with IMRT over 3DCRT was approximately 10% for V(10), 5% for V(20), and 2.5 Gy for MLD. IMRT improved the PTV heterogeneity (P<0.05), yet conformity was better with 7B-9B IMRT plans. No clinically meaningful differences were observed with respect to the irradiated volumes of spinal cord, heart, liver, or total body integral doses. Dose-volume of exposed normal lung can be reduced with IMRT, though clinical investigations are warranted to assess IMRT treatment outcome of esophagus cancers.

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

Wagemaker, G.; Visser, T.P.; van Bekkum, D.W.

alpha-Thalassemic heterozygous (Hbath/+) mice were used to investigate the possible selective advantage of transplanted normal (+/+) hemopoietic cells. Without conditioning by total-body irradiation (TBI), infusion of large numbers of normal bone marrow cells failed to correct the thalassemic peripheral blood phenotype. Since the recipients' stem cells are normal with respect to number and differentiation capacity, it was thought that the transplanted stem cells were not able to lodge, or that they were not stimulated to proliferate. Therefore, a nonlethal dose of TBI was given to temporarily reduce endogenous stem cell numbers and hemopoiesis. TBI doses of 2 or 3 Gymore » followed by infusion of normal bone marrow cells proved to be effective in replacing the thalassemic red cells by normal red cells, whereas a dose of 1 Gy was ineffective. It is concluded that cure of thalassemia by bone marrow transplantation does not necessarily require eradication of thalassemic stem cells. Consequently, the objectives of conditioning regimens for bone marrow transplantation of thalassemic patients (and possibly other nonmalignant hemopoietic disorders) should be reconsidered.« less

Changes in circulating IGF1 receptor stimulating activity do not parallel changes in total IGF1 during GH treatment of GH-deficient adults.

PubMed

Varewijck, Aimee J; Lamberts, Steven W J; van der Lely, A J; Neggers, Sebastian J C M M; Hofland, Leo J; Janssen, Joseph A M J L

2015-08-01

Previously we demonstrated that IGF1 receptor stimulating activity (IGF1RSA) offers advantages in diagnostic evaluation of adult GH deficiency (GHD). It is unknown whether IGF1RSA can be used to monitor GH therapy. To investigate the value of circulating IGF1RSA for monitoring GH therapy. 106 patients (54 m; 52 f) diagnosed with GHD were included; 22 were GH-naïve, 84 were already on GH treatment and discontinued therapy 4 weeks before baseline values were established. IGF1RSA was determined by the IGF1R kinase receptor activating assay, total IGF1 by immunoassay (Immulite). GH doses were titrated to achieve total IGF1 levels within the normal range. After 12 months, total IGF1 and IGF1RSA increased significantly (total IGF1 from 8.1 (95% CI 7.3-8.9) to 14.9 (95% CI 13.5-16.4) nmol/l and IGF1RSA from 115 (95% CI 104-127) to 181 (95% CI 162-202) pmol/l). After 12 months, total IGF1 normalized in 81% of patients, IGF1RSA in 51% and remained below normal in more than 40% of patients in whom total IGF1 had normalized. During 12 months of GH treatment, changes in IGF1RSA did not parallel changes in total IGF1. Despite normalization of total IGF1, IGF1RSA remained subnormal in a considerable proportion of patients. At present our results have no short-term consequences for GH therapy of GHD patients. However, based on our findings we propose future studies to examine whether titrating GH dose against IGF1RSA results in a better clinical outcome than titrating against total IGF1. © 2015 European Society of Endocrinology.

Successful pregnancy following very high-dose total body irradiation (1575 cGy) and bone marrow transplantation in a woman with acute myeloid leukemia.

PubMed

Wang, W S; Tzeng, C H; Hsieh, R K; Chiou, T J; Liu, J H; Yen, C C; Chen, P M

1998-02-01

A 22-year-old woman had a normal full-term delivery 6 years after a successful allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI) to a total of 1575 cGy in seven fractions (225 cGy x 7, at a dose rate of 3.5 cGy/min). Graft-versus-host disease prophylaxis was with methotrexate and cyclosporin A. Grade I acute GVHD developed after BMT but there was no chronic GVHD. She became amenorrhoeic after BMT and serial gonadal testing indicated hypergonadotrophic hypogonadism. She became pregnant and delivered a full-term, healthy baby 6 years after BMT. Successful pregnancy after TBI of more than 1200 cGy is extremely rare. This case, to the best of our knowledge, is the second patient who received a higher dose of TBI (1575 cGy) to have a successful pregnancy. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 1200 cGy.

In vitro production of sheep embryos using laparoscopic folliculocentesis: alternative gonadotrophin treatments for stimulation of oocyte donors.

PubMed

Baldassarre, H; Furnus, C C; De Matos, D G; Pessi, H

1996-02-01

Three different gonadotrophin regimens for the stimulation of donors for laparoscopic folliculocentesis were tested in a total of 142 ewes. The recovered oocytes were subjected to in vitro maturation, fertilization, and culture (IVM/IVF/IVC) for 7 d using standard procedures for sheep. The estrous cycles of all ewes were synchronized using intravaginal sponges containing 60 mg of medroxyprogesterone acetate (MPA) inserted for 14 d. In Experiment 1, all ewes were superovulated with a total dose of 125 IU FSH and 125 IU LH. One-half of the ewes received the gonadotrophin treatment in 4 decreasing doses at 12-h intervals starting 48 h before follicle aspiration (Control), while the other half received the total dose in a single injection at -24 h before collection (Oneshot). There were no significant differences between treatments for recovery rate (81.6 +/- 5.3 vs 77.4 +/- 10.3), cleavage rate (60.6 +/- 20.8 vs 61.4 +/- 23.4), or normal development to the blastocyst stage (20.8 +/- 18.2 vs 13.1 +/- 10.3). However, a higher percentage of ewes produced at least 1 normal blastocyst in the Control group (56.4 vs 31.6%; P < 0.05). In Experiment 2, the control regimen was repeated in half of the ewes, while the remainder were treated with half of the FSH total dose plus 500 IU eCG in a single injection at -24 h before oocyte collection (Oneshot-eCG). The recovery rate (80.9 +/- 5.6 vs 73.3 +/- 15.3), cleavage rate (76.8 +/-19.9 vs 79.7 +/- 22.6), normal development to blastocysts (19.2 +/- 15.3 vs 23.3 +/- 10.7), and percentage of ewes producing at least 1 normal blastocyst (55.9 vs 51.6%) did not differ between treatments. The large variability observed between ewes in the production of normal blastocysts is comparable to that observed with standard MOET procedures, in which a proportion of donors fail to produce good embryos. With the in vitro procedures described here, we were able to produce normal embryos from more than half of the treated ewes, indicating that the technology is useful for the multiplication of genetically valuable animals affected by temporary or irreversible infertility.

Normalized dose data for upper gastrointestinal tract contrast studies performed to infants

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

Damilakis, John; Stratakis, John; Raissaki, Maria

The aim of the current study was to (a) provide normalized dose data for the estimation of the radiation dose from upper gastrointestinal tract contrast (UGIC) studies carried out to infants and (b) estimate the average patient dose and risks associated with radiation from UGIC examinations performed in our institution. Organ and effective doses, normalized to entrance skin dose (ESD) and dose area product (DAP) were estimated for UGIC procedures utilizing the Monte Carlo N-particle (MCNP) transport code and two mathematical phantoms, one corresponding to the size of a newborn and one to the size of a 1-year-old child. Themore » validity of the MCNP results was verified by comparison with dose data obtained in physical anthropomorphic phantoms simulating a newborn and a 1-year-old infant using thermoluminescence dosimetry (TLD). Data were also collected from 25 consecutive UGIC examinations performed to infants. Study participants were (a) 12 infants aged from 0.5 to 5.9 months (group 1) and (b) 13 infants aged from 6 to 15 months (group 2). For each examination, ESD and dose to comforters were measured using TLD. Patient effective doses were estimated using normalized dose data obtained in the simulation study. The risk for fatal cancer induction was estimated using appropriate coefficients. The results consist of tabulated dose data normalized to ESD or DAP for the estimation of patient dose. Conversion coefficients were estimated for various tube potentials and beam filtration values. The mean total fluoroscopy time was 1.26 and 1.62 min for groups 1 and 2, respectively. The average effective dose was 1.6 mSv for group 1 and 1.9 mSv for group 2. The risk of cancer attributable to the radiation exposure associated with a typical UGIC study was found to be up to 3 per 10 000 infants undergoing an UGIC examination. The mean radiation dose absorbed by the hands of comforters was 47 {mu}Gy. In conclusion, estimation of radiation doses associated with UGIC studies performed to infants can be made using the normalized dose data provided in the current study. Radiation dose values associated with UGIC examinations carried out to infants are not low and should be minimized as much as possible.« less

Congenital hypothyroidism from complete iodide transport defect: long-term evolution with iodide treatment.

PubMed Central

Albero, R.; Cerdan, A.; Sanchez Franco, F.

1987-01-01

Hypothyroidism from iodide transport deficiency is a rare disease, especially when found in two affected siblings. Treatment with high doses of iodide has been recommended, but no long term results have been reported. Two siblings with congenital hypothyroidism due to total failure to transport iodide have been followed up during twelve and a half years of treatment with oral potassium iodide. Iodine doses varied between 10.3 and 22 mg/day, and serum total iodine concentrations between 100 and 210 micrograms/dl. Total triiodothyronine (T3), thyroxine (T4) and free T4 were in the normal range during the time of study. Basal thyroid stimulating hormones (TSH) and maximum TSH response to thyrotrophin releasing hormone (TRH) were also in the range of normal values. These data along with clinical findings confirmed the potential usefulness of iodine in hypothyroidism due to complete iodide transport defect. PMID:3451231

Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

NASA Astrophysics Data System (ADS)

Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

Analysis of Electronic Densities and Integrated Doses in Multiform Glioblastomas Stereotactic Radiotherapy

NASA Astrophysics Data System (ADS)

Barón-Aznar, C.; Moreno-Jiménez, S.; Celis, M. A.; Lárraga-Gutiérrez, J. M.; Ballesteros-Zebadúa, P.

2008-08-01

Integrated dose is the total energy delivered in a radiotherapy target. This physical parameter could be a predictor for complications such as brain edema and radionecrosis after stereotactic radiotherapy treatments for brain tumors. Integrated Dose depends on the tissue density and volume. Using CT patients images from the National Institute of Neurology and Neurosurgery and BrainScansoftware, this work presents the mean density of 21 multiform glioblastomas, comparative results for normal tissue and estimated integrated dose for each case. The relationship between integrated dose and the probability of complications is discussed.

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function

PubMed Central

Hoover, Randall K.; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K.; Quintas, Megan

2017-01-01

Abstract Delafloxacin, a fluoroquinolone, has activity against gram‐positive organisms including methicillin‐resistant Staphylococcus aureus and fluoroquinolone‐susceptible and –resistant gram‐negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open‐label, parallel‐group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14‐day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC0–∞. After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC0–∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CLCR. Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). PMID:29251785

Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

PubMed

Kakkis, E; McEntee, M; Vogler, C; Le, S; Levy, B; Belichenko, P; Mobley, W; Dickson, P; Hanson, S; Passage, M

2004-01-01

Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges. An initial dose-response study showed that doses of 0.46-4.14 mg of IT rhIDU successfully penetrated the brain of normal dogs and reached tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep brain sections lacking CSF contact. To assess the efficacy and safety in treating lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold normal levels of iduronidase in total brain and meninges, respectively. Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment reduced mean total brain GAG to normal levels and achieved a 57% reduction in meningeal GAG levels accompanied by histologic improvement in lysosomal storage in all cell types. The dogs did develop a dose-dependent immune response against the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate. The IT route of ERT administration may be an effective way to treat the CNS disease in MPS I and could be applicable to other lysosomal storage disorders.

Tolrestat kinetics

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

Hicks, D.R.; Kraml, M.; Cayen, M.N.

The kinetics of tolrestat, a potent inhibitor of aldose reductase, were examined. Serum concentrations of tolrestat and of total /sup 14/C were measured after dosing normal subjects and subjects with diabetes with /sup 14/C-labeled tolrestat. In normal subjects, tolrestat was rapidly absorbed and disappearance from serum was biphasic. Distribution and elimination t 1/2s were approximately 2 and 10 to 12 hr, respectively, after single and multiple doses. Unchanged tolrestat accounted for the major portion of /sup 14/C in serum. Radioactivity was rapidly and completely excreted in urine and feces in an approximate ratio of 2:1. Findings were much the samemore » in subjects with diabetes. In normal subjects, the kinetics of oral tolrestat were independent of dose in the 10 to 800 mg range. Repetitive dosing did not result in unexpected cumulation. Tolrestat was more than 99% bound to serum protein; it did not compete with warfarin for binding sites but was displaced to some extent by high concentrations of tolbutamide or salicylate.« less

SU-E-I-42: Normalized Embryo/fetus Doses for Fluoroscopically Guided Pacemaker Implantation Procedures Calculated Using a Monte Carlo Technique

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

Damilakis, J; Stratakis, J; Solomou, G

Purpose: It is well known that pacemaker implantation is sometimes needed in pregnant patients with symptomatic bradycardia. To our knowledge, there is no reported experience regarding radiation doses to the unborn child resulting from fluoroscopy during pacemaker implantation. The purpose of the current study was to develop a method for estimating embryo/fetus dose from fluoroscopically guided pacemaker implantation procedures performed on pregnant patients during all trimesters of gestation. Methods: The Monte Carlo N-Particle (MCNP) radiation transport code was employed in this study. Three mathematical anthropomorphic phantoms representing the average pregnant patient at the first, second and third trimesters of gestationmore » were generated using Bodybuilder software (White Rock science, White Rock, NM). The normalized embryo/fetus dose from the posteroanterior (PA), the 30° left-anterior oblique (LAO) and the 30° right-anterior oblique (RAO) projections were calculated for a wide range of kVp (50–120 kVp) and total filtration values (2.5–9.0 mm Al). Results: The results consist of radiation doses normalized to a) entrance skin dose (ESD) and b) dose area product (DAP) so that the dose to the unborn child from any fluoroscopic technique and x-ray device used can be calculated. ESD normalized doses ranged from 0.008 (PA, first trimester) to 2.519 μGy/mGy (RAO, third trimester). DAP normalized doses ranged from 0.051 (PA, first trimester) to 12.852 μGy/Gycm2 (RAO, third trimester). Conclusion: Embryo/fetus doses from fluoroscopically guided pacemaker implantation procedures performed on pregnant patients during all stages of gestation can be estimated using the method developed in this study. This study was supported by the Greek Ministry of Education and Religious Affairs, General Secretariat for Research and Technology, Operational Program ‘Education and Lifelong Learning’, ARISTIA (Research project: CONCERT)« less

Total marrow irradiation using Helical TomoTherapy

NASA Astrophysics Data System (ADS)

Garcia-Fernandez, Lourdes Maria

Clinical dose response data of human tumours are limited or restricted to a radiation dose range determined by the level of toxicity to the normal tissues. This is the case for the most common disseminated plasma cell neoplasm, multiple myeloma, where the maximum dose deliverable to the entire bony skeleton using a standard total body irradiation (TBI) technique is limited to about 12 Gy. This study is part of scientific background of a phase I/II dose escalation clinical trial for multiple myeloma using image-guided intensity modulated radiotherapy (IG-IMRT) to deliver high dose to the entire volume of bone marrow with Helical TomoTherapy (HT). This relatively new technology can deliver highly conformal dose distributions to complex target shapes while reducing the dose to critical normal tissues. In this study tools for comparing and predicting the effectiveness of different approaches to total marrow irradiation (TMI) using HT were provided. The expected dose response for plasma cell neoplasms was computed and a radiobiological evaluation of different treatment cohorts in a dose escalating study was performed. Normal tissue complication probability (NTCP) and tumour control probability (TCP) models were applied to an actual TMI treatment plan for a patient and the implications of using different longitudinal field widths were assessed. The optimum dose was ˜39 Gy for which a predicted tumour control of 95% (+/-3%) was obtained, with a predicted 3% (0, 8%) occurrence of radiation pneumonitis. Tissue sparing was seen by using smaller field widths only in the organs of the head. This suggests it would be beneficial to use the small fields in the head only since using small fields for the whole treatment would lead to long treatment times. In TMI it may be necessary to junction two longitudinally adjacent treatment volumes to form a contiguous planning target volume PTV. For instance, this is the case when a different SUP-INF spatial resolution is required or when the PTV length exceeds the bed travel distance. In this work, the dosimetric challenges associated with junctioning longitudinally adjacent PTVs with HT were analyzed and the feasibility of PTV junctioning was demonstrated. The benefits of spatially dividing or splitting the treatment into a few sub-treatments along the longitudinal direction were also investigated.

MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

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

Wu, Q; Snyder, K; Liu, C

Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas weremore » the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.« less

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy.

PubMed

Kobashi, Keiji; Prayongrat, Anussara; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-03-01

Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy

PubMed Central

Kobashi, Keiji; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-01-01

Abstract Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance–covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold. PMID:29538699

The effect of flurbiprofen on the development of anencephaly in early stage chicken embryos.

PubMed

Özeren, Ersin; Er, Uygur; Güvenç, Yahya; Demirci, Adnan; Arıkök, Ata Türker; Şenveli, Engin; Ergün, Rüçhan Behzat

2015-04-01

The study investigated the effect of flurbiprofen on the development of anencephaly in early stage chicken embryos. We looked at four groups with a total of 36 embryos. There was a control group, a normal saline group, a normal-dose group and a high-dose group with ten, ten, eight and eight eggs with embryo respectively. Two embryos in the control group, studied with light microscopy at 48 h, were consistent with 28-29 hours' incubation in the Hamburger-Hamilton System. They had open neural tubes. The other embryos in this group were considered normal. One embryo in the normal saline group was on the occlusion stage at 48 h. One embryo showed an open neural tube. They were compatible with 28-29 hours' incubation in the Hamburger-Hamilton system. The remaining eight embryos showed normal development. In the normal dose group, one embryo showed underdevelopment of the embryonic disc and the embryo was dead. In four embryos, the neural tubes were open. One cranial malformation was found that was complicated with anencephaly in one embryo. In two embryos the neural tubes were closed, as they showed normal development, and they reached their expected stages according to the Hamburger-Hamilton classification. There was no malformation or growth retardation. Four experimental embryos were anencephalic in the high dose group, and three embryos had open neural tubes. One embryo exhibited both anencephaly and a neural tube closure defect. None of the embryos in this group showed normal development. Even the usual therapeutic doses of flurbiprofen increased the risk of neural tube defect. Flurbiprofen was found to significantly increase the risk of anencephaly. The provision of improved technical materials and studies with larger sample sizes will reveal the stage of morphological disruption during the development of embryos.

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning

2016-09-30

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

Control of acid and duodenogastroesophageal reflux (DGER) in patients with Barrett's esophagus.

PubMed

Yachimski, Patrick; Maqbool, Sabba; Bhat, Yasser M; Richter, Joel E; Falk, Gary W; Vaezi, Michael F

2015-08-01

Symptom eradication in patients with Barrett's esophagus (BE) does not guarantee control of acid or duodenogastroesophageal reflux (DGER). Continued reflux of acid and/or DGER may increase risk of neoplastic progression and may decrease the likelihood of columnar mucosa eradication after ablative therapy. To date, no study has addressed whether both complete acid and DGER control is possible in patients with BE. This prospective study was designed to assess the effect of escalating-dose proton pump inhibitor (PPI) therapy on esophageal acid and DGER. Patients with BE (≥3 cm in length) underwent simultaneous ambulatory prolonged pH and DGER monitoring after at least 1 week off PPI therapy followed by testing on therapy after 1 month of twice-daily rabeprazole (20 mg). In those with continued acid and/or DGER, the tests were repeated after 1 month of double-dose (40 mg twice daily) rabeprazole. The primary study outcome was normalization of both acid and DGER. Symptom severity was assessed on and off PPI therapy employing a four-point ordinal scale. A total of 29 patients with BE consented for pH monitoring, of whom 23 also consented for both pH and DGER monitoring off and on therapy (83% male; mean age 58 years; mean body mass index 29; mean Barrett's length 6.0 cm). Median (interquartile range) total % time pH <4 and bilirubin absorbance >0.14 off PPI therapy were 18.4 (11.7-20.0) and 9.7 (5.0-22.2), respectively. In addition, 26/29 (90%) had normalized acid and 18/23 (78%) had normalized DGER on rabeprazole 20 mg. Among those not achieving normalization on 20 mg twice daily, 3/3 (100%) had normalized acid and 4/5 (80%) had normalized DGER on rabeprazole 40 mg twice daily. All subjects had symptoms controlled on rabeprazole 20 mg twice daily. Univariate analysis found no predictor for normalization of physiologic parameters based on demographics. Symptom control does not guarantee normalization of acid and DGER at standard dose of twice-daily PPI therapy. Normalization of acid and DGER can be achieved in 79% of BE patients on rabeprazole 20 mg p.o. twice daily, and in the majority of the remainder at high-dose twice-daily PPI. In patients undergoing ablative therapy, pH or DGER monitoring may not be needed to ensure normalization of reflux if patients are treated with high-dose PPI therapy.

Analysis of Electronic Densities and Integrated Doses in Multiform Glioblastomas Stereotactic Radiotherapy

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

Baron-Aznar, C.; Moreno-Jimenez, S.; Celis, M. A.

2008-08-11

Integrated dose is the total energy delivered in a radiotherapy target. This physical parameter could be a predictor for complications such as brain edema and radionecrosis after stereotactic radiotherapy treatments for brain tumors. Integrated Dose depends on the tissue density and volume. Using CT patients images from the National Institute of Neurology and Neurosurgery and BrainScan(c) software, this work presents the mean density of 21 multiform glioblastomas, comparative results for normal tissue and estimated integrated dose for each case. The relationship between integrated dose and the probability of complications is discussed.

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Cammarata, Sue K

2018-04-01

Delafloxacin, a fluoroquinolone, has activity against gram-positive organisms including methicillin-resistant Staphylococcus aureus and fluoroquinolone-susceptible and -resistant gram-negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open-label, parallel-group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14-day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC 0-∞ . After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC 0-∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CL CR . Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

[Effects of soybean isoflavone on born metabolism and morphology in animal model of osteoporosis rats].

PubMed

Yu, Qing; Su, Yi-xiang; Wang, Wen-wei; Li, An-le; Liu, Cun-li; Wang, Yi-long; Hu, Wan-li

2007-07-01

To study the effects of soybean isoflavone (SI) on born metabolism and morphology in animal model of osteoporosis rats. All 70 female Sprague-Dawley (SD) rats were randomly divided into 7 groups according to the levels of total cholesterol (TC) in serum: hyper-lipoid group, estrogen group, low-dose SI group, middle-dose SI group, high-dose SI group, sham group and normal control groups. Bilateral ovaries were extirpated except sham and normal control groups. Except the rats in normal control group, the other rats were fed with high fat diet. Body weight was weighted ad unam vice per week. The estrogen, different dose of SI or deionized water were fed with intragastric administration for 12 weeks. Vena caudalis serum were collected after being ovariectomized, administered for 4 w, 8 w and killed. Serum alkaline phosphatase (AKP) activity and bone density were measured etc. To interfere of estrogen and SI might recover AKP enzyme activity after its being ovariectomized. There almost sowed no differences between high dose SI intervention and estrogen on bone density and microstructure. Bone loss due to being ovariectomized was relieved after SI intervention. SI might protect cardiocyte myofilament and mitochondrial ultramicrostructure. There was mirror image in estrogen, high dose SI group resembling the normal control group, and there was obvious damage in hyper-lipoids group. There should be effects of high dose SI on bone metabolism and morphology in animal model of osteoporosis rats. Serum AKP enzyme activity and bone density should have significantly recovered, the serum level of calcium and phosphorus were maintained after high dose intervened but no significant effects for low dose of SI.

[Total flavones derived from Lagotis brevituba maxim reduce the levels of inflammatory cytokines in cerebral cortex and hippocampus of Alzheimer's disease mice].

PubMed

Yang, Bailing; Hou, Qian; Hu, Feng; Zhang, Fan

2016-07-01

Objective To investigate the mechanism behind the treatment of Alzheimer's disease (AD) with total flavones derived from Lagotis brevituba maxim (TF-LBM). Methods Fifty SAMP8 mice (aged 8 months) were randomly divided into 5 groups, (150, 300, 600) mg/kg TF-LBM groups, 0.65 g/kg donepezil HCl group and AD model group; 10 SAMR1 mice (aged 8 months) were used as a control group of normal aging. The AD model group and the normal aging control group were given the same volume of distilled water as TF-LBM groups. Eight weeks after intragastric administration, Morris water maze experiment was conducted to calculate the latency of place navigation. After the behavioral experiment, the brain cortical tissue and hippocampus (CA1 region) of the mice from various groups were taken to observe the morphological changes of the cortical tissue and hippocampus and test IL-1β, IL-6, TNF-α content. Results Compared with the model group, the escape latency of the normal aging group, the high-dose TF-LBM group and the donepezil HCl group were evidently shortened; compared with the normal aging group, IL-1β, IL-6, TNF-αof the model group increased significantly; compared with the model group, IL-1β content of the low-dose TF-LBM group had no obvious difference, while IL-1β content of the median-dose and high-dose TF-LBM groups and the donepezil HCl group decreased significantly; IL-6 content decreased in all TF-LBM groups and the donepezil HCl group; TNF-α level in the low-dose and median-dose TF-LBM groups had no evident difference, while it was reduced significantly in the high-dose TF-LBM group and the donepezil HCl group. Compared with the normal aging group, IL-1β, IL-6 and TNF-α content of the model group increased significantly; compared with the model group, IL-1β, IL-6 and TNF-α content of all TF-LBM groups and the donepezil HCl group decreased. Conclusion TF-LBM can improve the behavior change of SAMP8 mice with AD. TF-LBM can reduce the content of IL-6, IL-1β and TNF-α in cerebral cortex and hippocampus CA1.

UNIVERSAL RELATIONSHIP OF TOTAL LUNG DEPOSITION OF PARTICLES IN NORMAL ADULTS WITH PARTICLE SIZE AND BREATHING PATTERN

EPA Science Inventory

Particulate matter in the air is known for causing adverse health effects and yet estimating lung deposition dose is difficult because exposure conditions vary widely. We measured total deposition fraction (TDF) of monodisperse aerosols in the size range of 0.04 - 5 micron in dia...

Changes in radiation dose with variations in human anatomy: larger and smaller normal-stature adults.

PubMed

Marine, Patrick M; Stabin, Michael G; Fernald, Michael J; Brill, Aaron B

2010-05-01

A systematic evaluation has been performed to study how specific absorbed fractions (SAFs) vary with changes in adult body size, for persons of different size but normal body stature. A review of the literature was performed to evaluate how individual organ sizes vary with changes in total body weight of normal-stature individuals. On the basis of this literature review, changes were made to our easily deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed; SAFs for photons were generated for 10th, 25th, 75th, and 90th percentile adults; and comparisons were made to the reference (50th) percentile SAF values. Differences in SAFs for organs irradiating themselves were between 0.5% and 1.0%/kg difference in body weight, from 15% to 30% overall, for organs within the trunk. Differences in SAFs for organs outside the trunk were not greater than the uncertainties in the data and will not be important enough to change calculated doses. For organs irradiating other organs within the trunk, differences were significant, between 0.3% and 1.1%/kg, or about 8%-33% overall. The differences are interesting and can be used to estimate how different patients' dosimetry might vary from values reported in standard dose tables.

Pharmacokinetics of anthocyanidin-3-glycosides following consumption of Hibiscus sabdariffa L. extract.

PubMed

Frank, Thomas; Janssen, Marlies; Netzel, Michael; Strass, Gabriele; Kler, Adolf; Kriesl, Erwin; Bitsch, Irmgard

2005-02-01

Pharmacokinetic parameters of several dietary anthocyanins following consumption of Hibiscus sabdariffa L. extract were determined in 6 healthy volunteers. Subjects were given a single oral dose of 150 mL of Hibiscus sabdariffa L. extract yielding 62.6 mg of cyanidin-3-sambubioside, 81.6 mg of delphindin-3-sambubioside, and 147.4 mg of total anthocyanins (calculated as cyanidin equivalents). Within 7 hours, the urinary excretion of cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins (ie, the sum of all quantifiable anthocyanidin glycosides) was 0.016%, 0.021%, and 0.018% of the administered doses, respectively. Maximum excretion rates were determined at 1.5 to 2.0 hours after intake. The dose-normalized plasma area under the curve estimates were 0.076, 0.032, and 0.050 ng x h/mL/mg for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The dose-normalized C(max) estimates were 0.036, 0.015, and 0.023 ng/mL/mg in the same sequence. They were reached each at 1.5 hours (median) after intake. The geometric means of t1/2 were 2.18, 3.34, and 2.63 hours for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The urinary excretion of intact anthocyanins was fast and appeared to be monoexponential. To evaluate the contribution of anthocyanins to the health-protecting effects of Hibiscus sabdariffa L. extract, it will be necessary to perform further studies on both the intact glycosides and their in vivo metabolites or conjugates in human plasma and urine.

Evaluation of dose variation during total skin electron irradiation using thermoluminescent dosimeters.

PubMed

Weaver, R D; Gerbi, B J; Dusenbery, K E

1995-09-30

To determine acceptable dose variation using thermoluminescent dosimeters (TLD) in the treatment of Mycosis Fungoides with total skin electron beam (TSEB) irradiation. From 1983 to 1993, 22 patients were treated with total skin electron beam therapy in the standing position. A six-field technique was used to deliver 2 Gy in two days, treating 4 days per week, to a total dose of 35 to 40 Gy using a degraded 9 MeV electron beam. Thermoluminescent dosimeters were placed on several locations of the body and the results recorded. The variations in these readings were analyzed to determine normal dose variation for various body locations during TSEB. The dose to flat surfaces of the body was essentially the same as the dose to the prescription point. The dose to tangential surfaces was within +/- 10% of the prescription dose, but the readings showed much more variation (up to 24%). Thin areas of the body showed large deviations from the prescription dose along with a large amount of variation in the readings (up to 22%). Special areas of the body, such as the perineum and eyelid, showed large deviations from the prescription dose with very large (up to 40%) variations in the readings. The TLD results of this study will be used as a quality assurance check for all new patients treated with TSEB. The results of the TLDs will be compared with this baseline study to determine if the delivered dose is within acceptable ranges. If the TLD results fall outside the acceptable limits established above, then the patient position can be modified or the technique itself evaluated.

A novel acenocoumarol pharmacogenomic dosing algorithm for the Greek population of EU-PACT trial.

PubMed

Ragia, Georgia; Kolovou, Vana; Kolovou, Genovefa; Konstantinides, Stavros; Maltezos, Efstratios; Tavridou, Anna; Tziakas, Dimitrios; Maitland-van der Zee, Anke H; Manolopoulos, Vangelis G

2017-01-01

To generate and validate a pharmacogenomic-guided (PG) dosing algorithm for acenocoumarol in the Greek population. To compare its performance with other PG algorithms developed for the Greek population. A total of 140 Greek patients participants of the EU-PACT trial for acenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study. CYP2C9 and VKORC1 genotypes, age and weight affected acenocoumarol dose and predicted 53.9% of its variability. EU-PACT PG algorithm overestimated acenocoumarol dose across all different CYP2C9/VKORC1 functional phenotype bins (predicted dose vs stable dose in normal responders 2.31 vs 2.00 mg/day, p = 0.028, in sensitive responders 1.72 vs 1.50 mg/day, p = 0.003, in highly sensitive responders 1.39 vs 1.00 mg/day, p = 0.029). The PG algorithm previously developed for the Greek population overestimated the dose in normal responders (2.51 vs 2.00 mg/day, p < 0.001). Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.

Total dural irradiation: RapidArc versus static-field IMRT: A case study

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

Kelly, Paul J., E-mail: paulj.kelly@hse.ie; Mannarino, Edward; Lewis, John Henry

2012-07-01

The purpose of this study was to compare conventional fixed-gantry angle intensity-modulated radiation therapy (IMRT) with RapidArc for total dural irradiation. We also hypothesize that target volume-individualized collimator angles may produce substantial normal tissue sparing when planning with RapidArc. Five-, 7-, and 9-field fixed-gantry angle sliding-window IMRT plans were generated for comparison with RapidArc plans. Optimization and normal tissue constraints were constant for all plans. All plans were normalized so that 95% of the planning target volume (PTV) received at least 100% of the dose. RapidArc was delivered using 350 Degree-Sign clockwise and counterclockwise arcs. Conventional collimator angles of 45more » Degree-Sign and 315 Degree-Sign were compared with 90 Degree-Sign on both arcs. Dose prescription was 59.4 Gy in 33 fractions. PTV metrics used for comparison were coverage, V{sub 107}%, D1%, conformality index (CI{sub 95}%), and heterogeneity index (D{sub 5}%-D{sub 95}%). Brain dose, the main challenge of this case, was compared using D{sub 1}%, Dmean, and V{sub 5} Gy. Dose to optic chiasm, optic nerves, globes, and lenses was also compared. The use of unconventional collimator angles (90 Degree-Sign on both arcs) substantially reduced dose to normal brain. All plans achieved acceptable target coverage. Homogeneity was similar for RapidArc and 9-field IMRT plans. However, heterogeneity increased with decreasing number of IMRT fields, resulting in unacceptable hotspots within the brain. Conformality was marginally better with RapidArc relative to IMRT. Low dose to brain, as indicated by V5Gy, was comparable in all plans. Doses to organs at risk (OARs) showed no clinically meaningful differences. The number of monitor units was lower and delivery time was reduced with RapidArc. The case-individualized RapidArc plan compared favorably with the 9-field conventional IMRT plan. In view of lower monitor unit requirements and shorter delivery time, RapidArc was selected as the optimal solution. Individualized collimator angle solutions should be considered by RapidArc dosimetrists for OARs dose reduction. RapidArc should be considered as a treatment modality for tumors that extensively involve in the skull, dura, or scalp.« less

SU-F-T-395: Evaluation of Best Dosimetry Achievable with VMAT and IMRT Treatment Techniques Targeting Borderline Resectable Pancreatic Cancer

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

Harpool, K; Schnell, E; Herman, T

Purpose: To determine from retrospective study the most appropriate technique for targeting small borderline operable pancreatic cancer surrounding blood vessels by evaluating the dosimetry and normal tissue sparing achievable using Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT). Methods: Treatment plans from ten patients who have undergone treatment with a prescribed dose of 4950 cGy, at 275 cGy per fraction, were analyzed. All plans were replanned using Eclipse TPS (Varian Medical Systems, Palo Alto, CA) with complementary VMAT or IMRT techniques to obtain paired data sets for comparison. The coverage to at least 95% of the plannedmore » target volume (PTV) was normalized to receive 100% of the prescription dose. The normal tissue constraints followed the quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines and the organs at risks (OARs) were liver, kidneys, spinal cord and bowel. The plan evaluation was based on conformity index (CI), homogeneity index (HI), uniformity index (UI), DVH parameters, and student’s-t statistics (2 tails). Results: The VMAT technique delivered less maximum dose to the right kidney, left kidney, total kidney, liver, spinal cord, and bowel by 9.3%, 5.9%, 6.7%, 3.9%, 15.1%, 3.9%, and 4.3%, respectively. The averaged V15 for the total kidney was 10.21% for IMRT and 7.29% for VMAT. The averaged V20 for the bowel was 19.89% for IMRT and 14.06% for VMAT. On average, the CI for IMRT was 1.20 and 1.16 for VMAT (p = 0.20). The HI was 0.08 for both techniques (p = 0.91) and UI was 1.05 and 1.06 for IMRT and VMAT respectively (p = 0.59). Conclusion: Both techniques achieve adequate PTV coverage. Although VMAT techniques show better normal tissue sparing from excessive dose, no significant differences were observed. Slight discrepancies may rise from different versions of calculation algorithms.« less

SU-E-T-549: A Combinatorial Optimization Approach to Treatment Planning with Non-Uniform Fractions in Intensity Modulated Proton Therapy

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

Papp, D; Unkelbach, J

2014-06-01

Purpose: Non-uniform fractionation, i.e. delivering distinct dose distributions in two subsequent fractions, can potentially improve outcomes by increasing biological dose to the target without increasing dose to healthy tissues. This is possible if both fractions deliver a similar dose to normal tissues (exploit the fractionation effect) but high single fraction doses to subvolumes of the target (hypofractionation). Optimization of such treatment plans can be formulated using biological equivalent dose (BED), but leads to intractable nonconvex optimization problems. We introduce a novel optimization approach to address this challenge. Methods: We first optimize a reference IMPT plan using standard techniques that deliversmore » a homogeneous target dose in both fractions. The method then divides the pencil beams into two sets, which are assigned to either fraction one or fraction two. The total intensity of each pencil beam, and therefore the physical dose, remains unchanged compared to the reference plan. The objectives are to maximize the mean BED in the target and to minimize the mean BED in normal tissues, which is a quadratic function of the pencil beam weights. The optimal reassignment of pencil beams to one of the two fractions is formulated as a binary quadratic optimization problem. A near-optimal solution to this problem can be obtained by convex relaxation and randomized rounding. Results: The method is demonstrated for a large arteriovenous malformation (AVM) case treated in two fractions. The algorithm yields a treatment plan, which delivers a high dose to parts of the AVM in one of the fractions, but similar doses in both fractions to the normal brain tissue adjacent to the AVM. Using the approach, the mean BED in the target was increased by approximately 10% compared to what would have been possible with a uniform reference plan for the same normal tissue mean BED.« less

SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

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

Cao, Y; Li, R; Chi, Z

2014-06-01

Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose receivedmore » by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.« less

Radiobiological and treatment planning study of a simultaneously integrated boost for canine nasal tumors using helical tomotherapy.

PubMed

Gutíerrez, Alonso N; Deveau, Michael; Forrest, Lisa J; Tomé, Wolfgang A; Mackie, Thomas R

2007-01-01

Feasibility of delivering a simultaneously integrated boost to canine nasal tumors using helical tomotherapy to improve tumor control probability (TCP) via an increase in total biological equivalent uniform dose (EUD) was evaluated. Eight dogs with varying size nasal tumors (5.8-110.9 cc) were replanned to 42 Gy to the nasal cavity and integrated dose boosts to gross disease of 45.2, 48.3, and 51.3 Gy in 10 fractions. EUD values were calculated for tumors and mean normalized total doses (NTD(mean)) for organs at risk (OAR). Normal Tissue Complication Probability (NTCP) values were obtained for OARs, and estimated TCP values were computed using a logistic dose-response model and based on deliverable EUD boost doses. Significant increases in estimated TCP to 54%, 74%, and 86% can be achieved with 10%, 23%, and 37% mean relative EUD boosts to the gross disease, respectively. NTCP values for blindness of either eye and for brain necrosis were < 0.01% for all boosts. Values for cataract development were 31%, 42%, and 46% for studied boost schemas, respectively. Average NTD(mean) to eyes and brain for mean EUD boosts were 10.2, 11.3, and 12.1 Gy3, and 7.5, 7.2, and 7.9 Gy2, respectively. Using helical tomotherapy, simultaneously integrated dose boosts can be delivered to increase the estimated TCP at 1-year without significantly increasing the NTD(mean) to eyes and brain. Delivery of these treatments in a prospective trial may allow quantification of a dose-response relationship in canine nasal tumors.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

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

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

Dosimetric impact of daily setup variations during treatment of canine nasal tumors using intensity-modulated radiation therapy.

PubMed

Deveau, Michael A; Gutiérrez, Alonso N; Mackie, Thomas R; Tomé, Wolfgang A; Forrest, Lisa J

2010-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5 mm (0-10.0 mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9 +/- 3.3 mm. Due to variations, a loss of equivalent uniform dose for target volumes of up to 5.6% was noted which corresponded to a potential loss in tumor control probability of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose and highest normalized dose given to 2% of the volume. Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain.

DOSIMETRIC IMPACT OF DAILY SETUP VARIATIONS DURING TREATMENT OF CANINE NASAL TUMORS USING INTENSITY-MODULATED RADIATION THERAPY

PubMed Central

Deveau, Michael A.; Gutiérrez, Alonso N.; Mackie, Thomas R.; Tomé, Wolfgang A.; Forrest, Lisa J.

2009-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5mm (0-10.0mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9±3.3mm. Due to variations, a loss of equivalent uniform dose (EUD) for target volumes of up to 5.6% was noted which corresponded to a potential loss in TCP of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose (NTDmean) and highest normalized dose given to 2% of the volume (NTD2%). Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain. PMID:20166402

Dose conformation to the spine during palliative treatments using dynamic wedges

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

Ormsby, Matthew A., E-mail: Matthew.Ormsby@usoncology.com; Herndon, R. Craig; Kaczor, Joseph G.

2013-07-01

Radiation therapy is commonly used to alleviate pain associated with metastatic disease of the spine. Often, isodose lines are manipulated using dynamic or physical wedges to encompass the section of spine needing treatment while minimizing dose to normal tissue. We will compare 2 methods used to treat the entire thoracic spine. The first method treats the thoracic spine with a single, nonwedged posterior-anterior (PA) field. Dose is prescribed to include the entire spine. Isodose lines tightly conform to the top and bottom vertebrae, but vertebrae between these 2 received more than enough coverage. The second method uses a combination ofmore » wedges to create an isodose line that mimics the curvature of the thoracic spine. This “C”-shaped curvature is created by overlapping 2 fields with opposing dynamic wedges. Machine constraints limit the treatment length and therefore 2 isocenters are used. Each of the 2 PA fields contributes a portion of the total daily dose. This technique creates a “C”-shaped isodose line that tightly conforms to the thoracic spine, minimizing normal tissue dose. Spinal cord maximum dose is reduced, as well as mean dose to the liver, esophagus, and heart.« less

Adjunctive Local Application of Lidocaine during Scleral Buckling under General Anesthesia.

PubMed

Dehghani, Alireza; Montazeri, Kamran; Masjedi, Amin; Karbasi, Najmeh; Ashrafi, Leila; Saeedian, Behrooz

2011-07-01

To evaluate the effect of local lidocaine application on the incidence of the oculocardiac reflex (OCR) during scleral buckling (SB) for rhegmatogenous retinal detachment (RRD) under general anesthesia. In a randomized clinical trial, eyes with RRD scheduled for SB under general anesthesia were randomized to adjunctive local application of 1 ml lidocaine 2% versus normal saline to the muscles after conjunctival opening. Surgical stimulation was initiated 5 minutes afterwards. Additionally, 100 mg of lidocaine 2% was added to 50 ml of normal saline in the treatment group which was used for irrigation during surgery; control eyes were irrigated with normal saline. The incidence of the OCR, rate of postoperative nausea/vomiting (PONV), total intravenous (IV) analgesic dose, duration of surgery, and period of hospitalization were compared between the study groups. Thirty eyes of 30 patients including 22 (73.3%) male and 8 (26.7%) subjects with mean age of 49.4±16.3 years were operated. OCR and PONV occurred less frequently, and total intravenous analgesic dose was significantly lower in the lidocaine group (P < 0.05 for all comparisons). However, no significant difference was noted between the study groups in terms of duration of surgery and period of hospitalization. Adjunctive local application of lidocaine during SB under GA for RRD decreases the rate of OCR and PONV, reduces the intravenous analgesic dose, but does not affect the duration of surgery or hospitalization.

Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

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

Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth

2008-08-01

Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissuemore » dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.« less

Cyclic, low-dose total body irradiation for metastatic neuroblastoma

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

D'Angio, G.J.; Evans, A.E.

1983-12-01

Total body irradiation (TBI) can be thought of as a systemic anticancer agent. It therefore might best be given like an adjuvant drug, i.e., in tolerable doses, cyclically. The therapeutic ratio between normal bone marrow stem cells and suitably sensitive cancer cells should be widened by these means. Fourteen children with advanced (Stage IV) neuroblastomas were given 100-150 rad TBI in 50 rad daily fractions along with each three-week cycle of standard triple-agent chemotherapy (vincristine, DTIC, cyclophosphamide). Two patients died of toxicity and one is still undergoing therapy. Four of the remaining 12 survive free of disease for 12+ tomore » 31+ months. The regimen is well tolerated, but prolonged, pronounced bone marrow depression, especially thrombocytopenia, commonly occurs after doses of 300-450 rad.« less

RADIATION THERAPY COMMUNICATION-REIRRADIATION OF A NASAL TUMOR IN A BRACHYCEPHALIC DOG USING INTENSITY MODULATED RADIATION THERAPY.

PubMed

Rancilio, Nicholas J; Custead, Michelle R; Poulson, Jean M

2016-09-01

A 5-year-old spayed female Shih Tzu was referred for evaluation of a nasal transitional carcinoma. A total lifetime dose of 117 Gy was delivered to the intranasal mass in three courses over nearly 2 years using fractionated intensity modulated radiation therapy (IMRT) to spare normal tissues. Clinically significant late normal tissue side effects were limited to bilaterally diminished tear production. The patient died of metastatic disease progression 694 days after completion of radiation therapy course 1. This case demonstrates that retreatment with radiation therapy to high lifetime doses for recurrent local disease may be well tolerated with IMRT. © 2016 American College of Veterinary Radiology.

Public member dose assessment of Bushehr Nuclear Power Plant under normal operation by modeling the fallout from stack using the HYSPLIT atmospheric dispersion model.

PubMed

Zali, A; Shamsaei Zafarghandi, M; Feghhi, S A; Taherian, A M

2017-05-01

In this work, public dose resulting from fission products released from Bushehr Nuclear Power Plant (BNPP) under normal operation is assessed. Due to the long range transport of radionuclides in this work (80 km) and considering terrain and meteorological data, HYbrid Single-Particle Lagrangian Integrated Trajectory (HYsplit) model, which uses three dimensional long-range numerical models, has been employed to calculate atmospheric dispersion. Annual effective dose calculation is carried out for inhalation, ingestion, and external exposure pathways in 16directions and within 80 km around the site for representative person. The results showed the maximum dose of inhalation and external exposure for adults is 3.8 × 10 -8 Sv/y in the SE direction and distance of 600 m from the BNPP site which is less than ICRP 103 recommended dose limit (1 mSv). Children and infants' doses are higher in comparison with adults, although they are less than 1 mSv. Ingestion dose percentage in the total dose is less than 0.1%. The results of this study underestimate the Final Safety Analysis Report ofBNPP-1 (FSAR)data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use Dose Bricks Concept to Implement Nasopharyngeal Carcinoma Treatment Planning

PubMed Central

Wu, Jia-Ming; Yu, Tsan-Jung; Yeh, Shyh-An; Chao, Pei-Ju; Huang, Chih-Jou

2014-01-01

Purpose. A “dose bricks” concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Materials and Methods. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. Results. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10–15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Conclusions. Compared with IMRT, the expenditure of planning time and costing, “dose bricks” may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed. PMID:24967395

Low-dose dynamic myocardial perfusion CT image reconstruction using pre-contrast normal-dose CT scan induced structure tensor total variation regularization

NASA Astrophysics Data System (ADS)

Gong, Changfei; Han, Ce; Gan, Guanghui; Deng, Zhenxiang; Zhou, Yongqiang; Yi, Jinling; Zheng, Xiaomin; Xie, Congying; Jin, Xiance

2017-04-01

Dynamic myocardial perfusion CT (DMP-CT) imaging provides quantitative functional information for diagnosis and risk stratification of coronary artery disease by calculating myocardial perfusion hemodynamic parameter (MPHP) maps. However, the level of radiation delivered by dynamic sequential scan protocol can be potentially high. The purpose of this work is to develop a pre-contrast normal-dose scan induced structure tensor total variation regularization based on the penalized weighted least-squares (PWLS) criteria to improve the image quality of DMP-CT with a low-mAs CT acquisition. For simplicity, the present approach was termed as ‘PWLS-ndiSTV’. Specifically, the ndiSTV regularization takes into account the spatial-temporal structure information of DMP-CT data and further exploits the higher order derivatives of the objective images to enhance denoising performance. Subsequently, an effective optimization algorithm based on the split-Bregman approach was adopted to minimize the associative objective function. Evaluations with modified dynamic XCAT phantom and preclinical porcine datasets have demonstrated that the proposed PWLS-ndiSTV approach can achieve promising gains over other existing approaches in terms of noise-induced artifacts mitigation, edge details preservation, and accurate MPHP maps calculation.

High dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis

PubMed Central

Imam, Mohamad H.; Sinakos, Emmanouil; Gossard, Andrea A.; Kowdley, Kris V.; Luketic, Velimir A. C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Keach, Jill; DeCook, Alisha C.; Enders, Felicity; Lindor, Keith D.

2013-01-01

Background Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. Aim Our aim was to compare the risk of adverse clinical endpoints in patients with varying disease status. Methods We reviewed records from patients previously enrolled in a study evaluating the effects of high-dose (28–30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histologic stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, esophageal varices and cholangiocarcinoma was sought. Results One hundred fifty patients were included of which 49 patients developed endpoints. There was an increased development of endpoints amongst patients using UDCA vs. placebo (14 vs. 4, p = 0.0151) with early histologic disease (stage 1–2, n = 88) but not with late stage (stage 3–4, n = 62) disease (17 vs. 14, p = 0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, p = 0.0008) with normal bilirubin levels (total bilirubin ≤ 1.0 mg/dl) but not in patients with elevated bilirubin levels (15 vs. 16, p = 0.6018). Among patients not reaching endpoints 31.68% had normalization of their alkaline phosphatase levels as compared to 14.29% in patients who reached endpoints (p = 0.073). Conclusion The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin. PMID:21957881

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women.

PubMed

Aguilera-Barreiro, María de Los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo Y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35-55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women

PubMed Central

Aguilera-Barreiro, María de los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

Background The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. Objective To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). Methods The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35–55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. Results After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). Conclusion The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels. PMID:23704856

SU-E-T-625: Potential for Reduced Radiation Induced Toxicity for the Treatment of Inoperable Non-Small-Cell Lung Cancer Using RapidArc Planning

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

Pokhrel, D; Sood, S; Badkul, R

2015-06-15

Purpose: To investigate the feasibility of using RapidArc (RA) treatment planning to reduce irradiation volume of normal lung and other organs at risk (OARs) in the treatment of inoperable non-small-cell lung cancer (NSCLC) patients. Methods: A retrospective treatment planning and delivery study was performed to compare target coverage and the volumes of the normal lung, spinal cord, heart and esophagus on 4D-CT scan above their dose tolerances delivered by RA vs. IMRT for ten inoperable NSCLC patients (Stage I-IIIB). RA plans consisted of either one-full or two-partial co-planar arcs used to treat 95% of the planning target volume (PTV) withmore » 6MV beam to a prescription of 66Gy in 33 fractions. IMRT plans were generated using 5–7 co-planar fields with 6MV beam. PTV coverage, dose-volume histograms, homogeneity/conformity indices (CI), total number of monitor units(MUs), beam-on time and delivery accuracy were compared between the two treatment plans. Results: Similar target coverage was obtained between the two techniques. RA (CI=1.02) provided more conformal plans without loss of homogeneity compared to IMRT plans (CI=1.12). Compared to IMRT, RA achieved a significant median dose reduction in V10 (3%), V20 (8%), and mean lung dose (3%) on average, respectively. On average, V5 was comparable between the two treatment plans. RA reduced mean esophagus (6%), mean heart (18%), and maximum spinal cord dose (7%), on average, respectively. Total number of MUs and beam-on time were each reduced almost by a factor of 2 when compared to IMRT-patient comfort, reduced intra-fraction-motion and leakage dose. The average IMRT and RA QA pass rate was about 98% for both types of plans for 3%/3mm criterion. Conclusion: Compared to IMRT plans, RA provided not only comparable target coverage, but also improved conformity, treatment time, and significant reduction in irradiation of OARs. This may potentially allow for target dose escalation without increase in normal tissue toxicity.« less

Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi rats.

PubMed

Aissaoui, Abderrahmane; Zizi, Soumia; Israili, Zafar H; Lyoussi, Badiâa

2011-09-01

The use of an aqueous extract of coriander (Coriandrum sativum L.; Apiaceae, Umbelliferae) seeds (CS-extract) in Moroccan traditional treatment of diabetes remains to be experimentally validated. The study aim was to investigate potential hypoglycemic (and hypolipidemic) activity of CS-extract after a single oral dose and after daily dosing for 30 days (sub-chronic study) in normal and obese-hyperglycemic-hyperlipidemic (OHH) Meriones shawi rats. After a single oral dose of CS-extract (20mg/kg; predetermined as optimum), plasma glucose, insulin, total cholesterol (TC), and triglycerides (TG) were measured in normal and OHH rats (hypercaloric diet and forced limited physical activity); glibenclamide (GLB; 2.5mg/kg) was used as reference. In the sub-chronic study, the effect of CS-extract and GLB (at the above doses) on body weight (BW), plasma glucose, insulin, TC, LDL-cholesterol, HDL-cholesterol, TG, urea and creatinine was determined in normal and OHH rats; insulin resistance (IR as HOMA-IR), atherosclerotic and cardioprotective indices were calculated. A single dose of CS-extract or GLB suppressed hyperglycemia in OHH rats, and normo-glycemia was achieved at 6-h post-dose; there was no effect on lipids, TG or insulin, but IR decreased significantly. The hypoglycemic effect was lower in normal rats. In the sub-chronic study in OHH rats, the test substances (CS-extract>GLB) reduced plasma glucose (normoglycemia on Day 21), insulin and IR, TC, LDL-cholesterol, and TG. Atherosclerotic index decreased while cardioprotective indices increased only by CS-extract, with no effect on BW, urea or creatinine. Sub-chronic administration of CS-extract in OHH Meriones shawi rats normalized glycemia and decreased the elevated levels of insulin, IR, TC, LDL-cholesterol and TG. Since, the CS-extract decreased several components of the metabolic syndrome and decreased atherosclerotic and increased cardioprotective indices, CS-extract may have cardiovascular protective effect. The present study validates the traditional use of coriander in diabetes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

PubMed

Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

2018-01-01

Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Adjunctive Local Application of Lidocaine during Scleral Buckling under General Anesthesia

PubMed Central

Dehghani, Alireza; Montazeri, Kamran; Masjedi, Amin; Karbasi, Najmeh; Ashrafi, Leila; Saeedian, Behrooz

2011-01-01

Purpose To evaluate the effect of local lidocaine application on the incidence of the oculocardiac reflex (OCR) during scleral buckling (SB) for rhegmatogenous retinal detachment (RRD) under general anesthesia. Methods In a randomized clinical trial, eyes with RRD scheduled for SB under general anesthesia were randomized to adjunctive local application of 1 ml lidocaine 2% versus normal saline to the muscles after conjunctival opening. Surgical stimulation was initiated 5 minutes afterwards. Additionally, 100 mg of lidocaine 2% was added to 50 ml of normal saline in the treatment group which was used for irrigation during surgery; control eyes were irrigated with normal saline. The incidence of the OCR, rate of postoperative nausea/vomiting (PONV), total intravenous (IV) analgesic dose, duration of surgery, and period of hospitalization were compared between the study groups. Results Thirty eyes of 30 patients including 22 (73.3%) male and 8 (26.7%) subjects with mean age of 49.4±16.3 years were operated. OCR and PONV occurred less frequently, and total intravenous analgesic dose was significantly lower in the lidocaine group (P < 0.05 for all comparisons). However, no significant difference was noted between the study groups in terms of duration of surgery and period of hospitalization. Conclusion Adjunctive local application of lidocaine during SB under GA for RRD decreases the rate of OCR and PONV, reduces the intravenous analgesic dose, but does not affect the duration of surgery or hospitalization. PMID:22454732

Effects of X-ray irradiation on the microbial growth and quality of flue-cured tobacco during aging

NASA Astrophysics Data System (ADS)

Wang, J. J.; Xu, Z. C.; Fan, J. L.; Wang, Y.; Tian, Z. J.; Chen, Y. T.

2015-06-01

X-ray irradiation was evaluated for improving microbial safety and the quality of flue-cured tobacco during aging. Tobacco samples were irradiated at doses of 0, 1, 2, 3 and 5 kGy and stored for 12 months under normal storage conditions or in a high-humidity (RH>70%) room. Microbiological data indicated that the population of total aerobic bacteria was significantly decreased with increasing irradiation doses. In particular, a dose of 2 kGy was effective for the decontamination of fungi from the tested samples, with a 0.93 log CFU/g reduction for bacteria. The control and 1 kGy X-ray treated tobacco samples were became rotted and moldy after the 12th month, whereas those treated with 2, 3 and 5 kGy had no detectable mold during 12 months of storage at high humidity. Chemical measurements showed that irradiation up to 3 kGy did not affect the total nitrogen, nicotine, reducing and total sugars, ratio of total nitrogen to nicotine and sugar-to-nicotine ratio. Furthermore, sensory evaluation results also showed that X-ray irradiation did not affect sensory scores with irradiation at a dose <3 kGy. Based on these results, X-ray irradiation dose in the range of 2-3 kGy is recommended for the decontamination of fungi from flue-cured tobacco.

Evaluation of MLC leaf transmission on IMRT treatment plan quality of patients with advanced lung cancer.

PubMed

Chen, Jiayun; Fu, Guishan; Li, Minghui; Song, Yixin; Dai, Jianrong; Miao, Junjie; Liu, Zhiqiang; Li, Yexiong

2017-12-14

The purpose of this paper was to evaluate the impact of leaf treatment of multileaf collimator (MLC) in plan quality of intensity-modulated radiotherapy (IMRT) of patients with advanced lung cancer. Five MLCs with different leaf transmissions (0.01%, 0.5%, 1.2%, 1.8%, and 3%) were configured for an accelerator in a treatment planning system. Correspondingly, 5 treatment plans with the same optimization setting were created and evaluated quantitatively for each patient (11 patients total) who was diagnosed with advanced lung cancer. All of the 5 plans for each patient met the dose requirement for the planning treatment volumes (PTVs) and had similar target dose homogeneity and conformity. On average, the doses to selected organs were as follows: (1) V 5 , V 20 , and the mean dose of total lung; (2) the maximum and mean dose to spinal cord planning organ-at-risk volume (PRV); and (3) V 30 and V 40 of heart, decreased slightly when MLC transmission was decreased, but with no statistical differences. There is a clear grouping of plans having total quality score (S D ) value, which is used to evaluate plan quality: (1) more than 1 (patient nos. 1 to 3, 5, and 8), and more than 2.5 (patient no. 6); (2) less than 1 (patient nos. 7 and 10); (3) around 1 (patient nos. 4, 9, and 11). As MLC transmission increased, overall S D values increased as well and plan dose requirement was harder to meet. The clinical requirements were violated increasingly as MLC transmission became large. Total S D with and without normal tissue (NT) showed similar results, with no statistically significant differences. Therefore, decrease of MLC transmission did have minimum impact on plan, and it improved target coverage and reduced normal tissue radiation slightly, with no statistical significance. Plan quality could not be significantly improved by MLC transmission reduction. However, lower MLC transmission may have advantages on lung sparing to low- and intermediate-dose exposure. Besides conventional fraction, hyperfraction, or stereotactic body radiotherapy (SBRT), the reduction on lung sparing is still essential because it is highly relevant to radiation pneumonitis (RP). It has potential to diminish incidence of RP and improve patient's quality of life after irradiation with lowered MLC transmission. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

A randomized, double-blinded, controlled trial of the effects of fluid rate and/or presence of dextrose in intravenous fluids on the labor course of nulliparas.

PubMed

Fong, Alex; Serra, Allison E; Caballero, Deysi; Garite, Thomas J; Shrivastava, Vineet K

2017-08-01

Prolonged labor has been demonstrated to increase adverse maternal and neonatal outcome. A practice that may decrease the risk of prolonged labor is the modification of fluid intake during labor. Several studies demonstrated that increased hydration in labor as well as addition of dextrose-containing fluids may be associated with a decrease in length of labor. The purpose of our study was to characterize whether high-dose intravenous fluids, standard-dose fluids with dextrose, or high-dose fluids with dextrose show a difference in the duration of labor in nulliparas. Nulliparous subjects with singletons who presented in active labor were randomized to 1 of 3 groups of intravenous fluids: 250 mL/h of normal saline, 125 mL/h of 5% dextrose in normal saline, or 250 mL/h of 2.5% dextrose in normal saline. The primary outcome was total length of labor from initiation of intravenous fluid in vaginally delivered subjects. Secondary outcomes included cesarean delivery rate and length of second stage of labor, among other maternal and neonatal outcomes. In all, 274 subjects who met inclusion criteria were enrolled. There were no differences in baseline characteristics among the 3 groups. There was no difference in the primary outcome of total length of labor in vaginally delivered subjects among the 3 groups. First stage of labor duration, second stage of labor duration, and cesarean delivery rates were also equivalent. There were no differences identified in other secondary outcomes including clinical chorioamnionitis, postpartum hemorrhage, blood loss, Apgar scores, or neonatal intensive care admission. There is no difference in length of labor or delivery outcomes when comparing high-dose intravenous fluids, addition of dextrose, or use of high-dose intravenous fluids with dextrose in nulliparous women who present in active labor. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the Hepato and Nephron-Protective Effect of a Polyherbal Mixture using Wistar Albino Rats

PubMed Central

Adebesin, Olumide Adedapo; Okpuzor, Joy

2014-01-01

Aim: A polyherbal formulation prepared from a mixture of leaves of Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina (GOV) was evaluated for hepato-nephro protective properties against acetaminophen-induced toxicity in Wistar albino rats. Materials and Methods: Normal Wistar albino rats were orally treated with different doses of GOV extract (2, 4 and 8 g/kg b. wt), distilled water and some standard hepatoprotective drugs such as Liv 52 and silymarin for 14 days. However, a day prior to the 14th day, 3 g/kg body weight dose of Acetaminophen (APAP) was administered p.o. 1h before GOV and the standard drugs to induce hepatic and renal damage. The normal control was setup which received only distilled water. The serum levels of liver marker enzymes, biochemical analytes, antioxidant enzymes and hematological parameters were monitored. Results: The results showed that pretreatment of experimental animals with a different doses of the polyherbal formulation dose dependently caused a significant (p≤0.05) increase in the levels of most of the measured hematological parameters but significantly (p≤0.05) reduced the levels of MCV and monocytes when compared to the APAP induced toxin control group. Rats pretreated with GOV exhibited significant (p < 0.05) increase in serum levels of ALP, ALT, AST, GGT, LDH, Cholesterol, Triglycerides, Urea and a subsequent decrease in Albumin, Creatine and Total protein when compared to the normal rats. This trend in enzyme and biochemical analytes levels were significantly (p < 0.05) reversed when compared to toxin control group. GOV significantly (p < 0.05) and dose dependently increased the serum, kidney and hepatic CAT, GPx, GSH, GST, SOD and total protein activity in APAP induced damage in rats compared to the toxin control groups. Conclusion: The data from this study suggest that the polyherbal formulation possess hepato and nephron-protective potential against acetaminophen induced hepatotoxicity in rats, thus providing scientific rationale for its use in traditional medicine for the treatment of liver diseases. PMID:25121002

Effects of Low Dose Metformin in Adolescents with Type I Diabetes Mellitus: A Randomized, Double-Blinded Placebo-Controlled Study

PubMed Central

Nadeau, Kristen; Chow, Kelsey; Alam, Lyla; Lindquist, Kara; Cambell, Sarah; McFann, Kim; Klingensmith, Georgeanna; Walravens, Phillipe

2014-01-01

Background Insulin resistance increases during adolescence in those with type 1 diabetes (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, Setting, and Participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages 13–20 years) with T1DM. Participants were randomized to receive either metformin or placebo for six months. HbA1c, insulin dose, waist circumference, BMI, and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI Z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. PMID:24698216

Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

PubMed

Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

2015-01-01

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

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

Girigesh, Y; Kumar, L; Raman, K

Purpose: Aim of this study is to determine the dosimetric influence of Filtered and Flatting Filter Free Photon Beam of 10 MV energy on RA planning for Ca. Cervix. Methods: CT data sets of eleven patients reported with carcinoma cervix were used for RA planning for 10MV -FFB and 10MV-FFFB. RA plans were generated using two full arcs.All RA plans were generated to deliver a dose of 50.4Gy in 28 fractions for PTV and ALARA for OAR’s. All plans were analysed for PTV Coverage, conformity Index, homogeneity index, dose to OAR’s, integral dose to normal tissue and total monitor unitsmore » were studied. Results: DVH was used to evaluate RA plans for both 10MV-FFB and 10MV-FFFB photon beam. Planning results show a comparable PTV coverage for both energies. Results shows volume of PTV receiving prescription dose were 95.10+ 0.09% and 95.09 +0.11%, and volume of PTV receiving a dose of 107% is 0.45+0.96% and 5.25+8.9%, homogeneity index (HI) were 1.051+0.007 and 1.066+0.008, Conformity Index(CI) were 1.003+0.019 and 1.012+0.013, Mean Integral dose were 2.65+0.34 and 2.60+0.33(*10−5Gy.cm3) for 10MV-FFB and 10MV-FFFB respectively. 10MV-FB shows statistically significant (p<0.05) improvement in mean doses to bladder, rectum, bowel and mean total number of MU’s and also shows remarkable decrease in mean total no. of MU’s by 43.7% in comparison to 10MV-FFFB. There is statistically significant (p<0.05) difference found in CI and HI for 10MV-FB in comparison to 10MV -FFF beam. 10MV-FFFB shows statistically significant (p<0.05) for mean NTID and delivers 1.65 % less NTID in comparison to 10 MV- FB. Conclusion: 10MV-FB is superior to 10MV-FFFB for rapid arc planning in case of Cervix carcinomas, it offers better target coverage and OAR’s sparing, comparable mean Integral dose to normal tissues and 10 MV- FB also produced highly conformal and homogeneous dose distribution in comparison to 10MV-FFFB.« less

Prediction of terrestrial gamma dose rate based on geological formations and soil types in the Johor State, Malaysia.

PubMed

Saleh, Muneer Aziz; Ramli, Ahmad Termizi; bin Hamzah, Khaidzir; Alajerami, Yasser; Moharib, Mohammed; Saeed, Ismael

2015-10-01

This study aims to predict and estimate unmeasured terrestrial gamma dose rate (TGDR) using statistical analysis methods to derive a model from the actual measurement based on geological formation and soil type. The measurements of TGDR were conducted in the state of Johor with a total of 3873 measured points which covered all geological formations, soil types and districts. The measurements were taken 1 m above the soil surface using NaI [Ti] detector. The measured gamma dose rates ranged from 9 nGy h(-1) to 1237 nGy h(-1) with a mean value of 151 nGy h(-1). The data have been normalized to fit a normal distribution. Tests of significance were conducted among all geological formations and soil types, using the unbalanced one way ANOVA. The results indicated strong significant differences due to the different geological formations and soil types present in Johor State. Pearson Correlation was used to measure the relations between gamma dose rate based on geological formation and soil type (D(G,S)) with the gamma dose rate based on geological formation (D(G)) or soil type (D(s)). A very good correlation was found between D(G,S) and D(G) or D(G,S) and D(s). A total of 118 pairs of geological formations and soil types were used to derive the statistical contribution of geological formations and soil types to gamma dose rates. The contribution of the gamma dose rate from geological formation and soil type were found to be 0.594 and 0.399, respectively. The null hypotheses were accepted for 83% of examined data, therefore, the model could be used to predict gamma dose rates based on geological formation and soil type information. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early Dose Response to Yttrium-90 Microsphere Treatment of Metastatic Liver Cancer by a Patient-Specific Method Using Single Photon Emission Computed Tomography and Positron Emission Tomography

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

Campbell, Janice M.; Department of Radiation Oncology, Wayne State University, Detroit, MI; Wong, C. Oliver

2009-05-01

Purpose: To evaluate a patient-specific single photon emission computed tomography (SPECT)-based method of dose calculation for treatment planning of yttrium-90 ({sup 90}Y) microsphere selective internal radiotherapy (SIRT). Methods and Materials: Fourteen consecutive {sup 90}Y SIRTs for colorectal liver metastasis were retrospectively analyzed. Absorbed dose to tumor and normal liver tissue was calculated by partition methods with two different tumor/normal liver vascularity ratios: an average 3:1 and a patient-specific ratio derived from pretreatment technetium-99m macroaggregated albumin SPECT. Tumor response was quantitatively evaluated from fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography scans. Results: Positron emission tomography showed a significant decrease in total tumor standardizedmore » uptake value (average, 52%). There was a significant difference in the tumor absorbed dose between the average and specific methods (p = 0.009). Response vs. dose curves fit by linear and linear-quadratic modeling showed similar results. Linear fit r values increased for all tumor response parameters with the specific method (+0.20 for mean standardized uptake value). Conclusion: Tumor dose calculated with the patient-specific method was more predictive of response in liver-directed {sup 90}Y SIRT.« less

Improving the estimation of mealtime insulin dose in adults with type 1 diabetes: the Normal Insulin Demand for Dose Adjustment (NIDDA) study.

PubMed

Bao, Jiansong; Gilbertson, Heather R; Gray, Robyn; Munns, Diane; Howard, Gabrielle; Petocz, Peter; Colagiuri, Stephen; Brand-Miller, Jennie C

2011-10-01

Although carbohydrate counting is routine practice in type 1 diabetes, hyperglycemic episodes are common. A food insulin index (FII) has been developed and validated for predicting the normal insulin demand generated by mixed meals in healthy adults. We sought to compare a novel algorithm on the basis of the FII for estimating mealtime insulin dose with carbohydrate counting in adults with type 1 diabetes. A total of 28 patients using insulin pump therapy consumed two different breakfast meals of equal energy, glycemic index, fiber, and calculated insulin demand (both FII = 60) but approximately twofold difference in carbohydrate content, in random order on three consecutive mornings. On one occasion, a carbohydrate-counting algorithm was applied to meal A (75 g carbohydrate) for determining bolus insulin dose. On the other two occasions, carbohydrate counting (about half the insulin dose as meal A) and the FII algorithm (same dose as meal A) were applied to meal B (41 g carbohydrate). A real-time continuous glucose monitor was used to assess 3-h postprandial glycemia. Compared with carbohydrate counting, the FII algorithm significantly decreased glucose incremental area under the curve over 3 h (-52%, P = 0.013) and peak glucose excursion (-41%, P = 0.01) and improved the percentage of time within the normal blood glucose range (4-10 mmol/L) (31%, P = 0.001). There was no significant difference in the occurrence of hypoglycemia. An insulin algorithm based on physiological insulin demand evoked by foods in healthy subjects may be a useful tool for estimating mealtime insulin dose in patients with type 1 diabetes.

Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt.

PubMed

Ibrahim, N A; Shalaby, A S; Farag, R S; Elbaroty, G S; Nofal, S M; Hassan, E M

2008-04-15

Flavonoid glycosides, orientin and apigenin 3, 8-di-C-glycosides in addition to, iridoid compound, aucubin were isolated from the ethanolic extract of Vitex agnus-castus fruits. Their structures were identified on the basis of the spectroscopic data. The estrogenic activity of the ethanolic extract in two dose levels 0.6 and 1.2 g kg(-1) per body weight (b.w.) was studied by the vaginal smear, and uterine weight methods for normal and ovariectomized female rats. The extract induced significant increase in the uterine weight of ovariectomized rats at two dose levels comparable to that of control group. The percentages of the total average number of scores were increased significantly too. Significant increases in plasma progesterone and total estrogens levels were shown at the two dose levels when compared to that of control group. On the other side, the extract induced significant reduction in luteinizing and plasma prolactin hormones.

Early initiation of low-dose hydrocortisone treatment for septic shock in adults: A randomized clinical trial.

PubMed

Lv, Qing-Quan; Gu, Xiao-Hua; Chen, Qi-Hong; Yu, Jiang-Quan; Zheng, Rui-Qiang

2017-12-01

Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome. A total of 118 patients with septic shock were recruited in the study. All eligible patients were randomized to receive hydrocortisone (n=58) or normal saline (n=60). The study medication (hydrocortisone and normal saline) was initiated simultaneously with vasopressors. The primary end-point was 28-day mortality. The secondary end-points were the reversal of shock, in-hospital mortality and the duration of ICU and hospital stay. The proportion of patients with reversal of shock was similar in the two groups (P=0.602); There were no significant differences in 28-day or hospital all-cause mortality; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline. The early initiation of low-dose of hydrocortisone did not decrease the risk of mortality, and the length of stay in the ICU or hospital in adults with septic shock. www.clinicaltrials.govNCT02580240. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight changes and their associations with demographic and clinical characteristics in risperidone maintenance treatment for schizophrenia.

PubMed

Xiang, Y-T; Wang, C-Y; Ungvari, G S; Kreyenbuhl, J A; Chiu, H F K; Lai, K Y C; Lee, E H M; Bo, Q-J; Dixon, L B

2011-06-01

This study aimed to characterize weight changes in schizophrenia patients taking risperidone as part of a randomized, controlled, open-label clinical trial. A total of 374 patients with schizophrenia who had been clinically stabilized following an acute episode were randomly assigned to a 'no-dose-reduction' group (initial optimal therapeutic doses continued throughout the study), a '4-week group' (initial optimal therapeutic doses continued for 4 weeks followed by a half dose reduction that was maintained until the end of the study) or a '26-week group' (initial optimal therapeutic doses continued for 26 weeks followed by a half dose reduction until the end of the study). Participants were assessed monthly using standardized assessment instruments during the first 6 months, and then every 2 months until the last recruited patient completed the 1-year follow-up. Weight gain was defined as gaining at least 7% of initial body weight, weight loss as losing at least 7% of initial body weight. A BMI <18.5 kg m⁻² was defined as underweight, 18.5-24.9 kg m⁻² as normal range, and ≥ 25 kg m⁻² as overweight or obese. At the end of follow-up, of the patients who started within the underweight range (n=22), 77.3% gained weight, whereas 4.5% lost weight. The corresponding figures were 39.6% and 4.8% in patients who started at normal weight (n=273), respectively, and 17.7% and 17.7% in patients who started at overweight (n=79), respectively. At the same time, 59.1% of the patients who started at underweight range went into the normal weight and 13.6% into the overweight/obese range, respectively, while 24.5% of those who started at normal weight went into the overweight/obese range, and 1.1% into underweight range, respectively; 20.3% of those who started at overweight range went into normal weight at the end of the follow-up. Multiple logistic regression analyses revealed that being underweight or normal weight at study entry predicted weight gain compared to being overweight, whereas being overweight at entry was associated with a higher likelihood of weight loss compared to being normal weight. No correlation was found between weight change and dose reduction. Weight change is a common, long-term, but heterogeneous side effect in risperidone maintenance treatment for stable schizophrenia patients. Special attention should be paid to fluctuations in weight that may occur throughout the course of treatment with risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer.

PubMed

Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

2016-01-01

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer

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

Yang, Ruijie, E-mail: ruijyang@yahoo.com; Zhao, Nan; Liao, Anyan

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR andmore » LDR plans, the dose prescription was D{sub 90} of 34 Gy in 8.5 Gy per fraction, and 145 Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2 Gy per fraction, EQD{sub 2}) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D{sub mean} (EQD{sub 2}) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D{sub mean} (EQD{sub 2}) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD{sub 2}) was 80.26, 70.23, and 104.91 Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.« less

Porcine field fertility with two different insemination doses and the effect of sperm morphology.

PubMed

Alm, K; Peltoniemi, O A T; Koskinen, E; Andersson, M

2006-06-01

In swine artificial insemination, several dose regimens are applied, ranging from 1.5 x 10(9) to 6.0 x 10(9) spermatozoa per intra-cervical insemination dose. A lower sperm dose is more profitable for artificial insemination centres and offers a more effective use of superior boars. To evaluate fertility, 50 boars were used for a total of 10 773 homospermic first inseminations at a dose of 2 billion spermatozoa. In addition, 96 boars were used at a dose of 3 billion spermatozoa for 34 789 homospermic first inseminations. Fertility was determined by a 60-day non-return rate (NR%) of first inseminations. Litter size was registered by total number of piglets born separately in primiparous and multiparous farrowings. On average, a sow was inseminated 1.5 times. A significant decrease was observed in all three fertility parameters (NR%, litter size of both primiparous and multiparous farrowings) with a dose of 2 billion spermatozoa compared with a dose of 3 billion spermatozoa. The NR% was 75.8% and 84.0% (p < 0.001), the mean litter size of primiparous farrowings 10.1 and 10.7 (p < 0.001) and the mean litter size of multiparous farrowings 11.7 and 12.1 (p < 0.001) for 2 and 3 billion spermatozoa/dose, respectively. The proportion of normal spermatozoa in the sperm morphology analysis correlated significantly with NR% in both insemination regimens: p < 0.001, r = 0.604 and p < 0.05, r = 0.223 for 2 and 3 billion spermatozoa/dose, respectively. These results confirm that quantity can at least partly compensate for poor sperm quality. When the boars with <70% normal spermatozoa in the morphology evaluation were excluded from the data there were no correlation between the sperm morphology and NR%. However, the difference between the NR% and litter size remained statistically significant (p < 0.001) in favour for the bigger insemination dose. In conclusion, a decrease in sperm dose from 3 to 2 billion spermatozoa on commercial farms will severely decrease prolificacy at least under field conditions, where a sow is inseminated an average of 1.5 times/heat, and the semen is typically used within 3 days after collection. We recommend that under commercial circumstances the homospermic semen doses contain no <3 billion spermatozoa/dose.

Neutron-gamma flux and dose calculations for feasibility study of DISCOMS instrumentation in case of severe accident in a GEN 3 reactor

NASA Astrophysics Data System (ADS)

Brovchenko, Mariya; Duhamel, Isabelle; Dechenaux, Benjamin

2017-09-01

The present paper presents the study carried out in the frame of the DISCOMS project, which stands for "DIstributed Sensing for COrium Monitoring and Safety". This study concerns the calculation of the neutron and gamma radiations received by the considered instrumentation during the normal reactor operation as well as in case of a severe accident for the EPR reactor, outside the reactor pressure vessel and in the containment basemat. This paper summarizes the methods and hypotheses used for the particle transport simulation outside the vessel during normal reactor operation. The results of the simulations are then presented including the responses for distributed Optical Fiber Sensors (OFS), such as the gamma dose and the fast neutron fluence, and for Self Powered Neutron Detectors (SPNDs), namely the neutron and gamma spectra. Same responses are also evaluated for severe accident situations in order to design the SPNDs being sensitive to the both types of received neutron-gamma radiation. By contrast, fibers, involved as transducers in distributed OFS have to resist to the total radiation gamma dose and neutron fluence received during normal operation and the severe accident.

Potential for intensity-modulated radiation therapy to permit dose escalation for canine nasal cancer.

PubMed

Vaudaux, Catherine; Schneider, Uwe; Kaser-Hotz, Barbara

2007-01-01

We evaluated the impact of inverse planned intensity-modulated radiation therapy (IMRT) on the dose-volume histograms (DVHs) and on the normal tissue complication probabilities (NTCPs) of brain and eyes in dogs with nasal tumors. Nine dogs with large, caudally located nasal tumors were planned using conventional techniques and inverse planned IMRT for a total prescribed dose of 52.5 Gy in 3.5 Gy fractions. The equivalent uniform dose for brain and eyes was calculated to estimate the normal tissue complication probability (NTCP) of these organs. The NTCP values as well as the DVHs were used to compare the treatment plans. The dose distribution in IMRT plans was more conformal than in conventional plans. The average dose delivered to one-third of the brain was 10 Gy lower with the IMRT plan compared with conventional planning. The mean partial brain volume receiving 43.6 Gy or more was reduced by 25.6% with IMRT. As a consequence, the NTCPs were also significantly lower in the IMRT plans. The mean NTCP of brain was two times lower and at least one eye could be saved in all patients planed with IMRT. Another possibility with IMRT is dose escalation in the target to improve tumor control while keeping the NTCPs at the same level as for conventional planning. Veterinary

Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease.

PubMed

Lenz, Robert A; Pritchett, Yili L; Berry, Scott M; Llano, Daniel A; Han, Shu; Berry, Donald A; Sadowsky, Carl H; Abi-Saab, Walid M; Saltarelli, Mario D

2015-01-01

ABT-089, an α4β2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.

SU-E-T-647: Quality Assurance of VMAT by Gamma Analysis Dependence On Low-Dose Threshold

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

Song, J; Kim, M; Lee, S

2015-06-15

Purpose: The AAPM TG-119 instructed institutions to use low-dose threshold (LDT) of 10% or a ROI determined by the jaw when they collected gamma analysis QA data of planar dose distribution. Also, based on a survey by Nelms and Simon, more than 70% of institutions use a LDT between 0% and 10% for gamma analysis. However, there are no clinical data to quantitatively demonstrate the impact of the LDT on the gamma index. Therefore, we performed a gamma analysis with LDTs of 0% to 15% according to both global and local normalization and different acceptance criteria: 3%/3 mm, 2%/2 mm,more » and 1%/1 mm. Methods: A total of 30 treatment plans—10 head and neck, 10 brain, and 10 prostate cancer cases—were randomly selected from the Varian Eclipse TPS, retrospectively. For the gamma analysis, a predicted portal image was acquired through a portal dose calculation algorithm in the Eclipse TPS, and a measured portal image was obtained using a Varian Clinac iX and an EPID. Then, the gamma analysis was performed using the Portal Dosimetry software. Results: For the global normalization, the gamma passing rate (%GP) decreased as the LDT increased, and all cases of low-dose thresholds exhibited a %GP above 95% for both the 3%/3 mm and 2%/2 mm criteria. However, for local normalization, the %GP increased as LDT increased. The gamma passing rate with LDT of 10% increased by 6.86%, 9.22% and 6.14% compared with the 0% in the case of the head and neck, brain and prostate for 3%/3 mm criteria, respectively. Conclusion: Applying the LDT in the global normalization does not have critical impact to judge patient-specific QA results. However, LDT for the local normalization should be carefully selected because applying the LDT could affect the average of the %GP to increase rapidly.« less

Radiation-induced second cancers: the impact of 3D-CRT and IMRT

NASA Technical Reports Server (NTRS)

Hall, Eric J.; Wuu, Cheng-Shie

2003-01-01

Information concerning radiation-induced malignancies comes from the A-bomb survivors and from medically exposed individuals, including second cancers in radiation therapy patients. The A-bomb survivors show an excess incidence of carcinomas in tissues such as the gastrointestinal tract, breast, thyroid, and bladder, which is linear with dose up to about 2.5 Sv. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at higher doses. Some animal and human data suggest a decrease at higher doses, usually attributed to cell killing; other data suggest a plateau in dose. Radiotherapy patients also show an excess incidence of carcinomas, often in sites remote from the treatment fields; in addition there is an excess incidence of sarcomas in the heavily irradiated in-field tissues. The transition from conventional radiotherapy to three-dimensional conformal radiation therapy (3D-CRT) involves a reduction in the volume of normal tissues receiving a high dose, with an increase in dose to the target volume that includes the tumor and a limited amount of normal tissue. One might expect a decrease in the number of sarcomas induced and also (less certain) a small decrease in the number of carcinomas. All around, a good thing. By contrast, the move from 3D-CRT to intensity-modulated radiation therapy (IMRT) involves more fields, and the dose-volume histograms show that, as a consequence, a larger volume of normal tissue is exposed to lower doses. In addition, the number of monitor units is increased by a factor of 2 to 3, increasing the total body exposure, due to leakage radiation. Both factors will tend to increase the risk of second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. The numbers may be larger for longer survival (or for younger patients), but the ratio should remain the same.

TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy

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

Unkelbach, J; Craft, D; Hong, T

2014-06-15

Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cellmore » repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes.« less

[The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory].

PubMed

Pang, Jing-yao; Bai, Zhao-fang; Niu, Ming; Tu, Can; Ma, Zhi-jie; Zhao, Yan-ling; Zhao, Kui-jun; You, Yun; Wang, Jia-bo; Xiao, Xiao-he

2015-08-01

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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

Hong, C; Ju, S; Ahn, Y

2015-06-15

Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directionalmore » block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.« less

Skin dose mapping for non-uniform x-ray fields using a backscatter point spread function

NASA Astrophysics Data System (ADS)

Vijayan, Sarath; Xiong, Zhenyu; Shankar, Alok; Rudin, Stephen; Bednarek, Daniel R.

2017-03-01

Beam shaping devices like ROI attenuators and compensation filters modulate the intensity distribution of the xray beam incident on the patient. This results in a spatial variation of skin dose due to the variation of primary radiation and also a variation in backscattered radiation from the patient. To determine the backscatter component, backscatter point spread functions (PSF) are generated using EGS Monte-Carlo software. For this study, PSF's were determined by simulating a 1 mm beam incident on the lateral surface of an anthropomorphic head phantom and a 20 cm thick PMMA block phantom. The backscatter PSF's for the head phantom and PMMA phantom are curve fit with a Lorentzian function after being normalized to the primary dose intensity (PSFn). PSFn is convolved with the primary dose distribution to generate the scatter dose distribution, which is added to the primary to obtain the total dose distribution. The backscatter convolution technique is incorporated in the dose tracking system (DTS), which tracks skin dose during fluoroscopic procedures and provides a color map of the dose distribution on a 3D patient graphic model. A convolution technique is developed for the backscatter dose determination for the nonuniformly spaced graphic-model surface vertices. A Gafchromic film validation was performed for shaped x-ray beams generated with an ROI attenuator and with two compensation filters inserted into the field. The total dose distribution calculated by the backscatter convolution technique closely agreed with that measured with the film.

Intermittent bolus injection versus continuous infusion of furosemide in normal adult greyhound dogs.

PubMed

Adin, Darcy B; Taylor, Aaron W; Hill, Richard C; Scott, Karen C; Martin, Frank G

2003-01-01

Several studies in human subjects have demonstrated greater diuresis with constant rate infusion (CRI) furosemide than intermittent bolus (IB) furosemide. This study was conducted to compare the diuretic efficacy of the same total dose of IB furosemide and CRI furosemide in 6 healthy, adult Greyhound dogs in a randomized crossover design with a 2-week washout period between treatments. For IB administration, dogs received 3 mg/kg at 0 and 4 hours. For CRI administration, dogs received a 0.66 mg/kg loading dose followed by 0.66 mg/kg/h over 8 hours. The same volume of fluid was administered for both methods. Urine output was quantified hourly. Urine electrolyte concentrations, urine specific gravity (USG), packed cell volume (PCV), total protein (TP), serum electrolyte concentrations, total carbon dioxide (TCO2), serum creatinine (sCr), and blood urea nitrogen (BUN) were determined every 2 hours. Urine production and water intake were greater (P < or = 0.05) for CRI than IB. Urine sodium and calcium losses were greater (P < 0.05) and urine potassium loss was less (P = 0.03) for CRI than IB, but there was no evidence of a difference between methods for urine magnesium and chloride losses. Serum chloride concentration was less (P < 0.001), sCr concentration greater (P = 0.04). TP greater (P = 0.01), and PCV greater (P = 0.003) for CRI than IB. No differences in USG, TCO2, BUN, or serum potassium, sodium, and magnesium concentrations were detected between methods. The same total dose of CRI furosemide resulted in more diuresis, natriuresis, and calciuresis and less kaliuresis than IB furosemide in these normal Greyhound dogs over 8 hours, suggesting that furosemide is a more effective diuretic when administered by CRI than by IB.

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study.

PubMed

Gawel, Marek; Aschoff, Jürgen; May, Arne; Charlesworth, Bruce R

2005-01-01

The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. In the double-blind first phase of the study, patients with migraine were randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. The intention-to-treat population comprised 461 zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. These findings confirm the efficacy demonstrated by zolmitriptan nasal spray in previous clinical trials.

AIR insulin capsules of different dose strengths may be combined to yield equivalent pharmacokinetics and glucodynamics.

PubMed

de la Peña, Amparo; Seger, Mary; Rave, Klaus; Heinemann, Lutz; Silverman, Bernard; Muchmore, Douglas B

2009-09-01

In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects. Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary function were enrolled in an open-label, randomized, crossover study. Subjects underwent up to five euglycemic glucose clamp procedures, separated by 5-18 days. The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq) capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD assessments were taken up to 10 h post-dose. Based on both PK (area under the curve from time 0 to time of return to baseline and maximum concentration) and GD (total amount of glucose infused and maximum glucose infusion rate) responses, administration of a 6 U-eq capsule was equivalent to three 2 U-eq capsules; 90% confidence intervals for the ratios were contained within the interval (0.8, 1.25). Similarly, both overall exposure and glucodynamic response after administration of a 10 U-eq capsule were comparable to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose proportionality and dose-dependent increases in GD responses over the 2.6-7.8 mg dose range. AIR insulin exhibited dose strength interchangeability and dose proportionality after single-dose administration in healthy subjects.

Operation of commercial R3000 processors in the low earth orbit (LEO) space environment

NASA Astrophysics Data System (ADS)

Kaschmitter, J. L.; Shaeffer, D. L.; Colella, N. J.; McKnett, C. L.; Coakley, P. G.

1991-12-01

Spacecraft processors must operate with minimal degradation of performance in the LEO radiation environment, which includes the effects of total accumulated ionizing dose and single event phenomena (SEP) caused by protons and cosmic rays. Commercially available microprocessors can offer a number of advantages relative to radiation-hardened devices but are not normally designed to tolerate effects induced by the LEO environment. Extensive testing of the MIPS R3000 Reduced Instruction Set Computer (RISC) microprocessor family for operation in LEO environments is reported. The authors have characterized total dose and SEP effects for altitudes and inclinations of interest to systems operating in LEO, and they postulate techniques for detection and alleviation of SEP effects based on experimental results.

Glucuronidation and Sulfation Kinetics of Diflunisal in Man.

NASA Astrophysics Data System (ADS)

Loewen, Gordon Rapheal

Diflunisal is a nonsteroidal anti-inflammatory drug used in the treatment of arthritis and musculoskeletal pain. Diflunisal exhibits concentration- and dose-dependent kinetics, the mechanism of which has not been determined. The purpose of this study was to determine the mechanism(s) responsible for non-linear disposition of diflunisal and to examine environmental factors which may affect the elimination of diflunisal. The metabolites of diflunisal, including a new metabolite, the sulphate conjugate, were purified by column and semi-preparative high pressure liquid chromatography. Assays for the quantitation of diflunisal and conjugates in urine and diflunisal in plasma were developed. Plasma protein binding of diflunisal in blank plasma and in plasma obtained following multiple doses of diflunisal was determined by equilibrium dialysis. Total body clearance of diflunisal decreased when dose increased from 100 to 750 mg. Total clearance increased when dose increased from 750 to 1000 mg. The percent of recovered dose eliminated as the acyl glucuronide decreased and the percent eliminated as the sulphate increased with increasing dose of diflunisal. Plasma protein binding of diflunisal was concentration dependent over a range of diflunisal plasma concentrations of 3 to 257 mug/ml. Total clearance, and to a lesser degree, unbound clearance of diflunisal were decreased following multiple dose administration of 250 and 500 mg diflunisal. Percent of recovered dose eliminated as the acyl glucuronide decreased and percent eliminated as the sulphate conjugate increased following multiple dosing. Plasma protein binding of diflunisal was similar in blank plasma and plasma obtained at steady state. Unbound clearance of diflunisal exceeded liver plasma flow. Frequency distributions of the elimination of the conjugates of diflunisal were normally distributed. Sex, smoking, and use of vitamins or oral contraceptives were identified as factors which may affect the elimination of diflunisal.

The internal dosimetry of Rubidium-82 based on dynamic PET/CT imaging in humans

NASA Astrophysics Data System (ADS)

Hunter, Chad R.

Rubidium-82 (Rb-82) is a useful blood flow tracer, and has become important in recent years due to the shutdown of the Chalk River reactor. Published effective dose estimates for Rb-82 vary widely, and as yet no comprehensive study in man has been conducted with PET/CT, and no effective dose estimates for Rb-82 during pharmacological stress testing has been published. 30 subjects were recruited for rest, and 25 subjects were recruited for stress. The subjects consisted of both cardiac patients and normal subjects. For rest, a total of 283 organs were measured across 60 scans. For stress, a total of 171 organs were measured across 25 scans. Effective dose estimates were calculated using the ICRP 60, 80, and 103 tissue weighting factors. Relative differences between this study and the published in-vivo estimates showed agreement for the lungs. Relative differences between this study and the blood flow models showed differences> 5 times in the thyroid contribution to the effective dose demonstrating a limitation in these models. Comparisons between rest and stress effective dose estimates revealed no significant difference. The average 'adult' effective dose for Rb-82 was found to be 0.00084+/-0.00018 mSv/MBq. The highest dose organs were the lungs, kidneys and stomach wall. These dose estimates for Rb-82 are the first to be measured directly with PET/CT in humans, and are 4 times lower than previous ICRP 60 values based on a theoretical blood flow model. The total adult effective dose from a typical Rb-82 study including CT for attenuation correction and potential Sr-85 breakthrough is 1.5 +/- 0.4 mSv.

SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

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

Yu, V; Nguyen, D; Pajonk, F

Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to exploremore » the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work is supported by the NSF Graduate Research Fellowship (DGE-1144087)« less

Population dose-response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures.

PubMed

Nielsen, Jace C; Hutmacher, Matthew M; Wesche, David L; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G

2015-01-01

Vigabatrin is an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS). The purpose of this investigation was to describe the relationship between vigabatrin dosage and daily seizure rate for adults and children with rCPS and identify relevant covariates that might impact seizure frequency. This population dose-response analysis used seizure-count data from three pediatric and two adult randomized controlled studies of rCPS patients. A negative binomial distribution model adequately described daily seizure data. Mean seizure rate decreased with time after first dose and was described using an asymptotic model. Vigabatrin drug effects were best characterized by a quadratic model using normalized dosage as the exposure metric. Normalized dosage was an estimated parameter that allowed for individualized changes in vigabatrin exposure based on body weight. Baseline seizure rate increased with decreasing age, but age had no impact on vigabatrin drug effects after dosage was normalized for body weight differences. Posterior predictive checks indicated the final model was capable of simulating data consistent with observed daily seizure counts. Total normalized vigabatrin dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%, and 48.5%, respectively. © 2014, The American College of Clinical Pharmacology.

VARIATIONS IN CARBOHYDRATE-PHOSPHORUS EXCHANGE IN MUSCLE TISSUE INDUCED BY $gamma$-IRRADIATION (in Russian)

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

Silaev, M.P.

1962-01-01

Normal female rabbits, 2.5 to 3.0 kilograms in weight, were given a Co/ sup 60/ gamma dose of 800 r. Tissue samples of the Musculus longissimus dorsi were analyzed for glycogen content by the anthranone method, for monosacharrides, inorganic phosphate, adenosine phosphate, and lactic acid. The maximum drop in glycogen content was found to occur 24 hours after the irradiation. A whole-body dose of 800 r resulted in a significant drop in total carbohydrate content (both monosacharride content and glycogen content). The content of adenosinephosphate remained essentially unchanged. Irradiated muscle tissue, stored at --5 to +3 deg C decomposed moremore » rapidly than normal tissue. The content of glycogen was lower, and the free phosphate content was higher than in normal tissue. The adenosinephosphate decomposed more readily in the irradiated tissue. These differences in autolytic processes may be due to shifts in fermentative activity as a result of irradiation. (TTT).« less

[Effects of body mass index and age on the treatment of in vitro fertilization-embryo transfer among patients with non-polycystic ovarian syndrome].

PubMed

Chen, Hong; Wang, Wen-jun; Chen, Yu-zhen; Mai, Mei-qi; Ouyang, Neng-yong; Chen, Jing-hua; Tuo, Ping

2010-05-01

To investigate the impacts of body mass index (BMI) and age on in vitro fertilization-embryo transfer (IVF) and intracytoplasmic sperm injection (ICSI) treatment in infertile patients without polycystic ovary syndrome (PCOS). A retrospective study of 1426 patients during Jun. 2001 - Nov. 2009 was carried out. Multiple regression was used to analyze the effects of BMI (low weight: BMI < 18.5 kg/m(2), normal weight: BMI 18.5 - 23.99 kg/m(2) and over weight-obesity: BMI ≥ 24 kg/m(2)) and age (young: 20 - 34 years old, eld: 35 - 45 years old) on controlled ovarian stimulation (COH) [including: dose and duration of Gn, E2 level on day of human chorionic gonadotropin (HCG) administration, number of oocytes collected and full-grown follicles], number of fertilization, cleavage, two-pronucleus, normal embryos and cryopreserved embryos and clinical pregnancy outcome. (1) Gn dose for the patients whose age were 35 and the above, had a positive correlation with age (P < 0.001), 12.70% of the total variation of Gn dose was related to age (standardized partial regression coefficient was 0.343). (2) Estradiol level on day of HCG administration had a negative correlation with BMI in overweight-obesity patients, and so were the patients whose age were 35 and above (P value respectively lower than 0.037 and 0.018). 0.80% of the total variation of estradiol (HCG day) is related to age and overweight-obesity while age took greater proportion (standardized partial regression coefficients were 0.066 and 0.058 respectively). (3) For older patients, age appeared to have negative relationships with duration of Gn and number of oocytes collected, full-grown follicles, fertilization, cleavage, two-pronucleus, normal embryos and cryopreserved embryos (P < 0.05). (4) Compared to young-normal weight patients, the odds ratio of pregnancy in eld-low weight and eld-overweight-obesity patients were 0.482 and 0.529 (P < 0.05) respectively. Age, but not the BMI, had significant effects on IVF/ICSI treatment. It seems that factors as losing weight before IVF or ICSI treatment effective in reducing the dose of Gn.

Thyroid gland morphology in young adults: normal subjects versus those with prior low-dose neck irradiation in childhood.

PubMed

Hanson, G A; Komorowski, R A; Cerletty, J M; Wilson, S D

1983-12-01

Thyroid glands obtained at autopsy from young adults were studied to establish more accurately the "normal" morphology in the groups 20 to 40 years of age. A total of 56 autopsy specimens (many obtained from trauma victims) were examined in detail by totally embedding and sectioning the thyroid glands. The morphology of these thyroid glands also was compared to that of surgically removed thyroid glands from 47 young adult patients with prior low-dose neck irradiation. The "normal" thyroid specimens frequently showed morphologic features, such as thyroid tissue outside the recognizable capsule of the gland (40 of 56 patients) and in the strap muscles of the neck (six of 56 patients), which are conditions commonly considered as evidence for invasive thyroid carcinoma. The thyroid glands from the "normal" young adult population were significantly different from those thyroid glands surgically removed from patients who had received irradiation. The irradiated thyroid glands invariably showed multiple nodules of a wide variety of histologic types, extensive lymphocytic infiltrates, and distorting fibrosis as well as a high incidence of malignancy (27 of 47 patients). A single 0.1 cm focus of papillary carcinoma was found in one specimen in the nonirradiated thyroid group. This study suggests that "occult" thyroid carcinomas in the group 20 to 40 years of age are rare and are significantly fewer in number than in the older population (P less than 0.02).

Studies of young female responses to acute ozone exposure. Final report

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

Adams, W.C.

The primary purposes of this research were to determine if: (1) young adult females respond with greater acute effects of ozone (O3) than their male counterparts at a dose relative to lung size as well as at the same total dose; (2) O3 response in females is influenced by the disparate levels of progesterone (a steroid hormone) that they experience during the various phases of their menstrual cycles; and (3) O3 exposure has an effect on the integrity of normal menstrual cycles of healthy young adult females.

High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

PubMed

Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

2007-03-01

The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*.

PubMed

Marwali, Eva M; Boom, Cindy E; Sakidjan, Indriwanto; Santoso, Anwar; Fakhri, Dicky; Kartini, Ay; Kekalih, Aria; Schwartz, Steven M; Haas, Nikolaus A

2013-09-01

This study was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. Randomized, placebo-controlled, doubleblind clinical trial Operating room and ICU. Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p < 0.01]; free triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p < 0.01]). There was no evidence of hyperthyroidism or suppression of the pituitary-thyroid axis in either treatment group Oral triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

SU-F-T-498: A Comparative Evaluation of 6MV Flatten Beam and Flattening Filter Free Photon Beam in Carcinoma Breast

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

Tamilarasu, Suresh; Saminathan, Madeswaran

Purpose: Aim of the current study is to look plan quality, treatment beam ON time for IMRT using 6MV FB (Flatten Beam) and FFFB (Flattening Filter Free Beam) in left breast cancer cases. Methods: Ten left breast cancer patients treated with breast conserving surgical (BCS) procedure approach and adjuvant radiotherapy were selected from the department database. Simultaneous Integrated boost (SIB) technique was used to irradiate the total left breast (PTV) to a dose of 50.40Gy with concomitant enhance to the lumpectomy cavity known as gross tumour volume (GTV) to a dose of 59.40Gy in 28 fractions. Plans 6MV FB IMRTmore » and 6MV FFFB IMRT had been generated to achieve dose to 95% target volume (TV) and spare Organ at risks (OAR’s). Homogeneity index (HI), conformity index (CI), treatment monitor unit (MU),normal tissues integral dose (NTID) and low dose volume of normal tissue were compared. Results: There was no statistically huge difference among the plans with respect to target volume coverage, CI HI, Ipsilateral Lung and Breast. But statistically significant difference (p< 0.05) as observed in Heart, V5Gy of Contralateral Lung, MU’s NTID and low dose volume of normal tissue. Conclusion: 6MV FB and FFF beam produce almost equivalent plans in IMRT modality with admire to target volume coverage, HI, CI. Beam on time and NTID was determined to be much less in 6MV FFFB IMRT. FFF beam leads to a time saving treatment delivery and fewer NTID in cancer of left breast cases.« less

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Geant4 beam model for boron neutron capture therapy: investigation of neutron dose components.

PubMed

Moghaddasi, Leyla; Bezak, Eva

2018-03-01

Boron neutron capture therapy (BNCT) is a biochemically-targeted type of radiotherapy, selectively delivering localized dose to tumour cells diffused in normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal neutron capture by stable [Formula: see text]B nuclei resulting in emission of short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose of the current work was to develop and validate a Monte Carlo BNCT beam model and to investigate contribution of individual dose components resulting of neutron interactions. A neutron beam model was developed in Geant4 and validated against published data. The neutron beam spectrum, obtained from literature for a cyclotron-produced beam, was irradiated to a water phantom with boron concentrations of 100 μg/g. The calculated percentage depth dose curves (PDDs) in the phantom were compared with published data to validate the beam model in terms of total and boron depth dose deposition. Subsequently, two sensitivity studies were conducted to quantify the impact of: (1) neutron beam spectrum, and (2) various boron concentrations on the boron dose component. Good agreement was achieved between the calculated and measured neutron beam PDDs (within 1%). The resulting boron depth dose deposition was also in agreement with measured data. The sensitivity study of several boron concentrations showed that the calculated boron dose gradually converged beyond 100 μg/g boron concentration. This results suggest that 100μg/g tumour boron concentration may be optimal and above this value limited increase in boron dose is expected for a given neutron flux.

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

Gearhart, A; Carver, D; Stabin, M

Purpose: To validate a radiographic simulation in order to estimate patient dose due to clinically-used radiography protocols. Methods: A Monte Carlo simulation was created to simulate a radiographic x-ray beam using GEANT4. Initial validation was performed according to a portion of TG 195. Computational NURBS-based phantoms were used simulate patients of varying ages and sizes. The deposited energy in the phantom is output by the simulation. The exposure in air from a clinically used radiography unit was measured at 100 cm for various tube potentials. 10 million photons were simulated with 1 cubic centimeter of air located 100 cm frommore » the source, and the total absorbed dose was noted. The normalization factor was determined by taking a ratio of the measured dose in air to the simulated dose in air. Dose to individual voxels is calculated using the energy deposition map along with the voxelized and segmented phantom and the normalization factor. Finally, the effective dose is calculated using the ICRP methodology and tissue weighting factors. Results: This radiography simulation allows for the calculation and visualization of the energy deposition map within a voxelized phantom. The ratio of exposure, measured using an ionization chamber, to air in the simulation was determined. Since the simulation output is calibrated to match the exposure of a given clinical radiographic x-ray tube, the dose map may be visualized. This will also allow for absorbed dose estimation in specific organs or tissues as well as a whole body effective dose estimation. Conclusion: This work indicates that our Monte Carlo simulation may be used to estimate the radiation dose from clinical radiographic protocols. This will allow for an estimate of radiographic dose from various examinations without the use of traditional methods such as thermoluminescent dosimeters and body phantoms.« less

Malignant induction probability maps for radiotherapy using X-ray and proton beams.

PubMed

Timlin, C; Houston, M; Jones, B

2011-12-01

The aim of this study was to display malignant induction probability (MIP) maps alongside dose distribution maps for radiotherapy using X-ray and charged particles such as protons. Dose distributions for X-rays and protons are used in an interactive MATLAB® program (MathWorks, Natick, MA). The MIP is calculated using a published linear quadratic model, which incorporates fractionation effects, cell killing and cancer induction as a function of dose, as well as relative biological effect. Two virtual situations are modelled: (a) a tumour placed centrally in a cubic volume of normal tissue and (b) the same tumour placed closer to the skin surface. The MIP is calculated for a variety of treatment field options. The results show that, for protons, the MIP increases with field numbers. In such cases, proton MIP can be higher than that for X-rays. Protons produce the lowest MIPs for superficial targets because of the lack of exit dose. The addition of a dose bath to all normal tissues increases the MIP by up to an order of magnitude. This exploratory study shows that it is possible to achieve three-dimensional displays of carcinogenesis risk. The importance of treatment geometry, including the length and volume of tissue traversed by each beam, can all influence MIP. Reducing the volume of tissue irradiated is advantageous, as reducing the number of cells at risk reduces the total MIP. This finding lends further support to the use of treatment gantries as well as the use of simpler field arrangements for particle therapy provided normal tissue tolerances are respected.

High dose of green tea infusion normalized spiral artery density in rats treated with the depot-medroxyprogesterone acetate.

PubMed

Emilda, A S; Veri, Nora; Alchalidi, Alchalidi

2017-01-01

The purpose of this study was to investigate the effects of green tea (GT) on the spiral artery density and endometrial thickness in female rats treated with the depot-medroxyprogesterone acetate (DMPA). A total of 24 female rats were randomly divided into four groups (n = 6 each): The control group (no treatment), the DMPA-treated group, treated with DMPA and GT doses of 165 mg/kg of body weight/day, and treated with DMPA and GT doses of 330 mg/kg of body weight/day. Spiral artery density and endometrial thickness were subjected to histopathological analysis. Spiral artery density decreased in the DMPA-treated group, despite the insignificant difference ( P > 0.05). With regard to the administration of GT at doses of 165 and 330 mg/g of body weight/day, only GT at the high dose was capable of significantly preventing a decrease in spiral artery density ( P < 0.05). At this dose, the spiral arteries achieved a density comparable to that of the control group ( P > 0.05). Meanwhile, the administration of DMPA and/or DMPA with GT did not cause significant changes in endometrial thickness relative to the control group ( P > 0.05). DMPA induced a decrease in spiral artery density, despite the insignificant differences, and these changes could be normalized by the administration of high doses of GT. Therefore, GT could be a candidate herb to prevent the adverse effects of the contraceptive DMPA.

Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

PubMed

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

HIGHER SERUM TOTAL CHOLESTEROL LEVELS IN LATE MIDDLE AGE ARE ASSOCIATED WITH GLUCOSE HYPOMETABOLISM IN BRAIN REGIONS AFFECTED BY ALZHEIMER’S DISEASE AND NORMAL AGING

PubMed Central

Reiman, Eric M.; Chen, Kewei; Langbaum, Jessica B.S.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E.; Caselli, Richard J.

2010-01-01

Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer’s disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late-middle-aged people, we demonstrated an association between apolipoprotein E (APOE) ε4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a presymptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and noncarriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE ε4 carriers than non-carriers in some of the AD-affected brain regions. We postulate the higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. PMID:19631758

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

PubMed

Khawar, Ambreen; Eppard, Elisabeth; Sinnes, Jean Phlippe; Roesch, Frank; Ahmadzadehfar, Hojjat; Kürpig, Stefan; Meisenheimer, Michael; Gaertner, Florian C; Essler, Markus; Bundschuh, Ralph A

2018-04-23

In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.

SU-F-T-528: Relationship Between Tumor Size and Plan Quality Using FFF and Non-FFF Modes in Rapidarc

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

Chen, F

2016-06-15

Purpose: For a give PTV dose, beam-on time is shorter in the FFF than the non-FFF mode because of higher MU/min. Larger tumors usually require more complex intensity modulation, which might affect plan quality and total MU. We investigated the relationship between PTV size and plan quality using FFF and non-FFF modes. Methods: Two different PTV volumes (PTV and PTV+1 cm margin) were drawn in brain, lung and liver. 3-full to 7-partial arc (Rapidarc) of 6 MV, 1400 MU/min were studied. Plan quality was evaluated by: (a) DVH for PTV and normal tissues, (b) total MU and beam-on time, andmore » (c) passing rate for IMRT plan QA. Results: For the same PTV coverage, DVH for normal tissue was the same or slightly lower in the FFF compared with non-FFF. Total MU was 13% higher in FFF than non-FFF in the 3-arc, 7 Gy treatment, but the difference became smaller when arc number increased to 6–7 for 10–24 Gy. Larger PTV did not affect the difference in the total MU. FFF required a short beam-on time and the ratio of FFF and non-FFF was 0.34 to 0.88 for 7- and 3-arc, respectively. For larger PTV, the ratio increased to 0.45–0.90. Ratio of total MU for large PTV was 3–8% lower in the non-FFF plans. Although the small difference in MU, beam-on time was 1.1 to-1.6 times longer in the 3- and 7-arc non-FFF plans. Plan verification showed the similar gamma index passing rate. Conclusion: While total MU was similar with FFF and non-FFF modes, the beam-on time was shorter in the FFF treatment. The advantage of FFF was greater in treatments with high dose per fraction using more arc numbers. For dose less than 10 Gy, using FFF and non-FFF modes, tumor size did not affect the relationship of total MU, beam-on time.« less

A database for estimating organ dose for coronary angiography and brain perfusion CT scans for arbitrary spectra and angular tube current modulation

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

Rupcich, Franco; Badal, Andreu; Kyprianou, Iacovos

Purpose: The purpose of this study was to develop a database for estimating organ dose in a voxelized patient model for coronary angiography and brain perfusion CT acquisitions with any spectra and angular tube current modulation setting. The database enables organ dose estimation for existing and novel acquisition techniques without requiring Monte Carlo simulations. Methods: The study simulated transport of monoenergetic photons between 5 and 150 keV for 1000 projections over 360 Degree-Sign through anthropomorphic voxelized female chest and head (0 Degree-Sign and 30 Degree-Sign tilt) phantoms and standard head and body CTDI dosimetry cylinders. The simulations resulted in tablesmore » of normalized dose deposition for several radiosensitive organs quantifying the organ dose per emitted photon for each incident photon energy and projection angle for coronary angiography and brain perfusion acquisitions. The values in a table can be multiplied by an incident spectrum and number of photons at each projection angle and then summed across all energies and angles to estimate total organ dose. Scanner-specific organ dose may be approximated by normalizing the database-estimated organ dose by the database-estimated CTDI{sub vol} and multiplying by a physical CTDI{sub vol} measurement. Two examples are provided demonstrating how to use the tables to estimate relative organ dose. In the first, the change in breast and lung dose during coronary angiography CT scans is calculated for reduced kVp, angular tube current modulation, and partial angle scanning protocols relative to a reference protocol. In the second example, the change in dose to the eye lens is calculated for a brain perfusion CT acquisition in which the gantry is tilted 30 Degree-Sign relative to a nontilted scan. Results: Our database provides tables of normalized dose deposition for several radiosensitive organs irradiated during coronary angiography and brain perfusion CT scans. Validation results indicate total organ doses calculated using our database are within 1% of those calculated using Monte Carlo simulations with the same geometry and scan parameters for all organs except red bone marrow (within 6%), and within 23% of published estimates for different voxelized phantoms. Results from the example of using the database to estimate organ dose for coronary angiography CT acquisitions show 2.1%, 1.1%, and -32% change in breast dose and 2.1%, -0.74%, and 4.7% change in lung dose for reduced kVp, tube current modulated, and partial angle protocols, respectively, relative to the reference protocol. Results show -19.2% difference in dose to eye lens for a tilted scan relative to a nontilted scan. The reported relative changes in organ doses are presented without quantification of image quality and are for the sole purpose of demonstrating the use of the proposed database. Conclusions: The proposed database and calculation method enable the estimation of organ dose for coronary angiography and brain perfusion CT scans utilizing any spectral shape and angular tube current modulation scheme by taking advantage of the precalculated Monte Carlo simulation results. The database can be used in conjunction with image quality studies to develop optimized acquisition techniques and may be particularly beneficial for optimizing dual kVp acquisitions for which numerous kV, mA, and filtration combinations may be investigated.« less

Akt1/NFκB signaling pathway activation by a small molecule DMA confers radioprotection to intestinal epithelium in xenograft model.

PubMed

Tiwari, Vinod; Kamran, Mohammad Zahid; Ranjan, Atul; Nimesh, Hemlata; Singh, Manish; Tandon, Vibha

2017-07-01

Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism. Administration of single DMA dose prior to radiation has enhanced survival of Balb/c mice against sublethal and supralethal total body irradiation. DMA ameliorated radiation-induced damage of normal tissues such as hematopoietic (HP) and gastrointestinal tract (GI) system. Oxidative stress marker Malondialdehyde level was decreased by DMA whereas it maintained endogenous antioxidant status by increasing the level of reduced glutathione, glutathione reductase, glutathione-s-transferase, superoxide dismutase and total thiol content in hepatic tissue of irradiated mice. Mechanistic studies revealed that DMA treatment prior to radiation leads to Akt1/NFκB signaling which reduced radiation-induced genomic instability in normal cells. However, these pathways were not activated in tumor tissues when subjected to DMA treatment in similar conditions. Abrogation of Akt1 and NFκB genes resulted in no radioprotection by DMA and enhanced apoptosis against radiation. Plasma half-life of DMA was 3.5h and 2.65h at oral and intravenous dose respectively and 90% clearance was observed in 16h. In conclusion, these data suggests that DMA has potential to be developed as a safe radioprotective agent for radiation countermeasures and an adjuvant in cancer therapy. Copyright © 2017. Published by Elsevier Inc.

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

Lin, M; Saboury, B

Purpose: Selective-internal-radiation-therapy (SIRT) and transarterial-chemoembolization (TACE) are commonly used for treatment of liver tumors. The use of TACE, which is macroembolic, prior to SIRT may cause hemodynamic changes in tumor vasculature that impair yttrium-90 (90Y) microsphere delivery to the targeted lesions. This work aims to quantify dosimetric tumor coverage using 90Y positron emission tomography (PET) dosimetry after SIRT alone compared to TACE followed by SIRT. Methods: A total of 40 consecutive hepatocellular carcinoma (HCC) SIRT patients who had a post-SIRT 90Y PET/CT scan were evaluated. The patient-specific-3D-dose was reconstructed from the PET images. Patients were categorized into two groups: patientsmore » received TACE prior SIRT procedure (n=18) and patient received SIRT alone (n=22). The lesions and liver were delineated by a senior radiologist. We evaluated both the lesion-specific dose-volume-histogram (DVH) and the selectivity index (SI) defined as the ratio of the average dose inside the total lesion(s) and the average dose of the normal liver. The SI values of patients were compared based on whether TACE was previously used. Results: A wide spectrum was observed in the lesion-specific DVH-evaluation and SI appeared to be suitable of evaluating the quality of each SIRT infusion. The average SI of the entire patient group was 3.0, i.e. targeted lesion receiving three times higher dose than normal liver. The average SI was 1.8 for patients who had prior TACE and 3.9 for patients who did not have prior TACE (p=0.008). 85% of the patients with prior TACE demonstrated poor 90Y-microsphere delivery (SI <2) while none demonstrated excellent delivery (SI >4). On the other hand, the incidence SI >4 among patients with no prior TACE was 37%. Conclusion: 3D dose evaluation using post-SIRT PET suggests that 90Y microsphere delivery to liver tumors is impaired among patients who received prior TACE compared to those who receive SIRT alone.« less

An international dosimetry exchange for boron neutron capture therapy. Part I: Absorbed dose measurements.

PubMed

Binns, P J; Riley, K J; Harling, O K; Kiger, W S; Munck af Rosenschöld, P M; Giusti, V; Capala, J; Sköld, K; Auterinen, I; Serén, T; Kotiluoto, P; Uusi-Simola, J; Marek, M; Viererbl, L; Spurny, F

2005-12-01

An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step (Part I) the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik (Sweden), VTT Espoo (Finland), and the Nuclear Research Institute (NRI) at Rez (Czech Republic). A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 microg g(-1) that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study.

Effect of continuous gamma-ray exposure on performance of learned tasks and effect of subsequent fractionated exposures on blood-forming tissue

NASA Technical Reports Server (NTRS)

Spalding, J. F.; Holland, L. M.; Prine, J. R.; Farrer, D. N.; Braun, R. G.

1972-01-01

Sixteen monkeys trained to perform continuous and discrete-avoidance and fixed-ratio tasks with visual and auditory cues were performance-tested before, during, and after 10-day gamma-ray exposures totaling 0, 500, 750, and 1000 rads. Approximately 14 months after the performance-test exposures, surviving animals were exposed to 100-rad gamma-ray fractions at 56-day intervals to observe injury and recovery patterns of blood-forming tissues. The fixed-ratio, food-reward task performance showed a transient decline in all dose groups within 24 hours of the start of gamma-ray exposure, followed by recovery to normal food-consumption levels within 48 to 72 hours. Avoidance tasks were performed successfully by all groups during the 10-day exposure, but reaction times of the two higher dose-rate groups in which animals received 3 and 4 rads per hour or total doses of 750 and 1000 rads, respectively, were somewhat slower.

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

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

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

PubMed

Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

Assessment of environmental consequences of the normal operations of the ESS facility

NASA Astrophysics Data System (ADS)

Ene, D.; Avila, R.; Hjerpe, T.; Bugay, D.; Stenberg, K.

2018-06-01

As other accelerator based facilities, the European Spallation Source ESS facility will interact with the environment. The Swedish legislation requires a demonstration that the sum of the doses resulting from the exposure of any member of the public to ionizing radiation dose does not exceed the specified limit of 50 μSv/year. A radiological assessment has been produced to provide that demonstration. This evaluation was based upon the actual status of the ESS design. A graded approach was adopted through over the assessment allowing estimating dose for all radionuclides and exposure pathways, but the degree of detail in the assessment depend upon their relative radiological importance. The total dose was obtained making the sum of the contribution of all-important radionuclides treated realistically with that of all screened out radionuclides, derived by means a conservative method.

Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem.

PubMed

Huber, Malin; Hadziosmanovic, Nermin; Berglund, Lars; Holte, Jan

2013-11-01

To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns. Retrospective cross-sectional study. University-affiliated private center. The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist-recombinant FSH protocol). None. The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome. OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield. The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Lung Size and the Risk of Radiation Pneumonitis

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

Briere, Tina Marie, E-mail: tmbriere@mdanderson.org; Krafft, Shane; Liao, Zhongxing

2016-02-01

Purpose: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. Methods and Materials: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a functionmore » of lung dose and other factors. Results: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. Conclusions: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis.« less

[Comparative study of the effect of decamethoxine, decamine and levorin on carbohydrate metabolic indices in the liver of white rats].

PubMed

Meshchishetn, I F; Iarmol'chuk, G M

1979-01-01

Intramuscular injection of decamin into the animals in a dose of 0.5 and 1 mg/kg has no significant effect on carbohydrate metabolism in the liver of white rats. Decamethoxin and levorin injected in the same doses, specifically in a dose of 1 mg/kg, reduced the level of glucose as well as that of total and free glycogen in the liver. The drugs lowered also the activity of phosphorylase and glocoso-6-phosphatase. Meanwhile the activity of hexokinase, lactate dehydrogenase and phosphoglucosiomerase was potentiated. The animals given decamethoxin showed the aforesaid parameters returning to normal 20 days after the drug was discontinued, whereas similar changes were not found in the rats on levorin.

Tolerance doses of cutaneous and mucosal tissues in ring-necked parakeets (Psittacula krameri) for external beam megavoltage radiation.

PubMed

Barron, Heather W; Roberts, Royce E; Latimer, Kenneth S; Hernandez-Divers, Stephen; Northrup, Nicole C

2009-03-01

Currently used dosages for external-beam megavoltage radiation therapy in birds have been extrapolated from mammalian patients and often appear to provide inadequate doses of radiation for effective tumor control. To determine the tolerance doses of cutaneous and mucosal tissues of normal birds in order to provide more effective radiation treatment for tumors that have been shown to be radiation responsive in other species, ingluvial mucosa and the skin over the ingluvies of 9 ring-necked parakeets (Psittacula krameri) were irradiated in 4-Gy fractions to a total dose of either 48, 60, or 72 Gy using an isocentric cobalt-60 teletherapy unit. Minimal radiation-induced epidermal changes were present in the high-dose group histologically. Neither dose-related acute nor chronic radiation effects could be detected in any group grossly in cutaneous or mucosal tissue over a 9-month period. Radiation doses of 72 Gy in 4-Gy fractions were well tolerated in the small number of ring-necked parakeets in this initial tolerance dose study.

Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells

PubMed Central

Panganiban, Ronald-Allan M.; Snow, Andrew L.; Day, Regina M.

2013-01-01

Radiation damage to biological systems is determined by the type of radiation, the total dosage of exposure, the dose rate, and the region of the body exposed. Three modes of cell death—necrosis, apoptosis, and autophagy—as well as accelerated senescence have been demonstrated to occur in vitro and in vivo in response to radiation in cancer cells as well as in normal cells. The basis for cellular selection for each mode depends on various factors including the specific cell type involved, the dose of radiation absorbed by the cell, and whether it is proliferating and/or transformed. Here we review the signaling mechanisms activated by radiation for the induction of toxicity in transformed and normal cells. Understanding the molecular mechanisms of radiation toxicity is critical for the development of radiation countermeasures as well as for the improvement of clinical radiation in cancer treatment. PMID:23912235

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

Brock, K; Lee, C; Samuels, S

Purpose: Tools are now available to perform daily dose assessment in radiotherapy, however, guidance is lacking as to when to replan to limit increase in normal tissue dose. This work performs statistical analysis to provide guidance for when adaptive replanning may be necessary for head/neck (HN) patients. Methods: Planning CT and daily kVCBCT images for 50 HN patients treated with VMAT were retrospectively evaluated. Twelve of 50 patients were replanned due to anatomical changes noted over their RT course. Daily dose assessment was performed to calculate the variation between the planned and delivered dose for the 38 patients not replannedmore » and the patients replanned using their delivered plan. In addition, for the replanned patients, the dose that would have been delivered if the plan was not modified was also quantified. Deviations in dose were analyzed before and after replanning, the daily variations in patients who were not replanned assessed, and the predictive power of the deviation after 1, 5, and 15 fractions determined. Results: Dose deviations were significantly reduced following replanning, compared to if the original plan would have been delivered for the entire course. Early deviations were significantly correlated with total deviations (p<0.01). Using the criteria that a 10% increase in the final delivered dose indicates a replan may be needed earlier in the treatment course, the following guidelines can be made with a 90% specificity after the first 5 fractions: deviations of 7% in the mean dose to the inferior constrictors and 5% in the mean dose to the parotid glands and submandibular glands. No significant dose deviations were observed in any patients for the CTV -70Gy (max deviation 4%). Conclusions: A 5–7% increase in mean dose to normal tissues within the first 5 fractions strongly correlate to an overall deviatios in the delivered dose for HN patients. This work is funded in part by NIH 2P01CA059827-16.« less

Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer.

PubMed

Toesca, Diego A S; Osmundson, Evan C; von Eyben, Rie; Shaffer, Jenny L; Koong, Albert C; Chang, Daniel T

This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/β of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008). ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Subcutaneous Injection of Testosterone Is an Effective and Preferred Alternative to Intramuscular Injection: Demonstration in Female-to-Male Transgender Patients.

PubMed

Spratt, Daniel I; Stewart, India I; Savage, Clara; Craig, Wendy; Spack, Norman P; Chandler, Donald Walt; Spratt, Lindsey V; Eimicke, Toni; Olshan, Jerrold S

2017-07-01

Testosterone (T) is commonly administered intramuscularly to treat hypogonadal males and female-to-male (FTM) transgender patients. However, these injections can involve significant discomfort and may require arrangements for administration by others. We assessed whether T could be administered effectively and safely subcutaneously as an alternative to intramuscular (IM) injections. Retrospective cohort study. Outpatient reproductive endocrinology clinic at an academic medical center. Sixty-three FTM transgender patients aged >18 years electing to receive subcutaneous (SC) T therapy for sex transition were included. Fifty-three patients were premenopausal. Patients were administered T cypionate or enanthate weekly at an initial dose of 50 mg. Dose was adjusted if needed to achieve serum total T levels within the normal male range. Serum concentrations of free and total T and total estradiol (E2), masculinization, and surveillance for reactions at injection sites. Serum T levels within the normal male range were achieved in all 63 patients with doses of 50 to 150 mg (median, 75/80 mg). Therapy was effective across a wide range of body mass index (19.0 to 49.9 kg/m2). Minor and transient local reactions were reported in 9 out of 63 patients. Among 53 premenopausal patients, 51 achieved amenorrhea and 35 achieved serum E2 concentrations <50 pg/mL. Twenty-two patients were originally receiving IM and switched to SC therapy. All 22 had a mild (n = 2) or marked (n = 20) preference for SC injections; none preferred IM injections. Our observations indicate that SC T injections are an effective, safe, and well-accepted alternative to IM T injections. Copyright © 2017 Endocrine Society

Evidence-based Critical Evaluation of Glycemic Potential of Cynodon dactylon

PubMed Central

Singh, Santosh Kumar; Rai, Prashant Kumar; Jaiswal, Dolly

2008-01-01

The present study is an extension of our previous work carried out on Cynodon dactylon. This study deals with the critical evaluation of glycemic potential of ethanolic extract of defatted C. dactylon. The doses of 250, 500 and 750 mg kg−1 bw of the extract were administered orally to normal as well as Streptozotocin-induced diabetic rats to study its glycemic potential. The effect of repeated oral administration of the same doses of ethanolic extract was also studied on serum lipid profile of severely diabetic (SD) rats. The dose of 500 mg kg−1 bw was identified as the most effective dose as it lowered the blood glucose levels of normal by 42.12% and of diabetic by 43.42% during fasting blood glucose (FBG) and glucose tolerance test respectively. The SD rats were also treated daily with this identified dose of 500 mg kg−1 bw for 2 weeks and a significant reduction of 56.34% was observed in FBG level. Total cholesterol, low density lipoprotein and triglyceride levels were also decreased by 32.94, 64.06 and 48.46% respectively in SD rats whereas, cardioprotective high density lipoprotein increased by 16.45%. The reduced urine sugar level and increased body weight are additional advantages. These evidences clearly indicate that the ethanolic extract of defatted C. dactylon has high antidiabetic potential along with good hypolipidemic profile. PMID:18955211

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer

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

Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals.more » Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.« less

Protective effect of N-acetylcysteine against ethanol-induced gastric ulcer: A pharmacological assessment in mice

PubMed Central

Jaccob, Ausama Ayoob

2015-01-01

Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-acetylcysteine (NAC) against ethanol-induced gastric ulcer models in mice. Materials and Methods: A total of 41 mice were allocated into six groups consisted of 7 mice each. Groups 1 (normal control) and 2 (ulcer control) received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg). All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg) was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by anti-secretory, cytoprotective, histological and biochemical data, but the molecular mechanisms behind such protection are complex. PMID:26401392

Renal dysfunction after total body irradiation: Dose-effect relationship

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

Kal, Henk B.; Kempen-Harteveld, M. Loes van

2006-07-15

Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated.more » Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.« less

Parotid Gland Function After Radiotherapy: The Combined Michigan and Utrecht Experience

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

Dijkema, Tim, E-mail: T.Dijkema@umcutrecht.n; Raaijmakers, Cornelis P.J.; Ten Haken, Randall K.

2010-10-01

Purpose: To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. Patients and Methods: A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. Results: Amore » total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD{sub 50} (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. Conclusions: A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD{sub 50} was equal to 40 Gy.« less

Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

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

Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A totalmore » of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

Terrestrial Gamma Radiation Dose Rate of West Sarawak

NASA Astrophysics Data System (ADS)

Izham, A.; Ramli, A. T.; Saridan Wan Hassan, W. M.; Idris, H. N.; Basri, N. A.

2017-10-01

A study of terrestrial gamma radiation (TGR) dose rate was conducted in west of Sarawak, covering Kuching, Samarahan, Serian, Sri Aman, and Betong divisions to construct a baseline TGR dose rate level data of the areas. The total area covered was 20,259.2 km2, where in-situ measurements of TGR dose rate were taken using NaI(Tl) scintillation detector Ludlum 19 micro R meter NaI(Tl) approximately 1 meter above ground level. Twenty-nine soil samples were taken across the 5 divisions covering 26 pairings of 9 geological formations and 7 soil types. A hyperpure Germanium detector was then used to find the samples' 238U, 232Th, and 40K radionuclides concentrations producing a correction factor Cf = 0.544. A total of239 measured data were corrected with Cf resulting in a mean Dm of 47 ± 1 nGy h-1, with a range between 5 nGy h-1 - 103 nGy h-1. A multiple regression analysis was conducted between geological means and soil types means against the corrected TGR dose rate Dm, generating Dg,s= 0.847Dg+ 0.637Ds- 22.313 prediction model with a normalized Beta equation of Dg,s= 0.605Dg+ 0.395Ds. The model has an 84.6% acceptance of Whitney- Mann test null hypothesis when tested against the corrected TGR dose rates.

Dose-specific transcriptional responses in thyroid tissue in mice after (131)I administration.

PubMed

Rudqvist, Nils; Schüler, Emil; Parris, Toshima Z; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2015-03-01

In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after (131)I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with (131)I exposure in normal mouse thyroid tissue and 2) propose biomarkers for (131)I exposure of the thyroid. Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of (131)I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. In total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to (131)I exposure of thyroid. During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from (131)I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to (131)I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

PubMed

Gnatzy, Richard; Hempel, Gunther; Kaisers, Udo X; Höhne, Claudia

2015-11-01

The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. A total of 62 children (11.5±2.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

Supplementation with a mixture of complex lipids derived from milk to growing rats results in improvements in parameters related to growth and cognition.

PubMed

Vickers, Mark H; Guan, Jian; Gustavsson, Malin; Krägeloh, Christian U; Breier, Bernhard H; Davison, Michael; Fong, Bertram; Norris, Carmen; McJarrow, Paul; Hodgkinson, Steve C

2009-06-01

Alterations in nutritional factors during early development can exert long-term effects on growth, neural function, and associated behaviors. The lipid component of milk provides a critical nutritional source for generating both energy and essential nutrients for the growth of the newborn. The present study, therefore, investigated the hypothesis that nutritional supplementation with a complex milk lipid (CML) preparation, derived from the milk fat globule membrane rich in phospholipids and gangliosides from young rats, has beneficial effects on learning behavior and postnatal growth and development. Male Wistar rat offspring from normal pregnancies were treated from neonatal day 10 until postnatal day 80 with either vehicle or CML at a dose of 0.2% (low) and 1.0% (high) based on total food intake (n = 16 per group). Neonatal dosing was via daily oral gavage, while postweaning dosing was via gel supplementation to a standard chow diet. Animals underwent behavioral tasks related to spatial memory, learning, and cognitive function. Complex milk lipid supplementation significantly increased linear growth rate (P < .05), and the improved growth trajectory was not related to changes in body composition as quantified by dual-energy x-ray absorptiometry scanning or altered plasma lipid profiles. Moreover, this effect was not dose dependent and not attributable to the contribution to total energy intake of the CML composition. Supplementation of the CML to growing rats resulted in statistically significant improvements in parameters related to novelty recognition (P < .02) and spatial memory (P < .05) using standard behavioral techniques, but operant testing showed no significant differences between treatment groups. Supplementation with a CML containing gangliosides had positive growth and learning behavioral effects in young normal growing rats.

Evaluation of hypolipidemic activity of leaf juice of Catharanthus roseus (Linn.) G. Donn. in guinea pigs.

PubMed

Patel, Yogesh; Vadgama, Vishalkumar; Baxi, Seema; Chandrabhanu; Tripathi, B

2011-01-01

Our aim of the study was to evaluate the hypolipidemic activity of leaf juice of Catharanthus roseus (Linn.) G. Donn. in guinea pigs. Adult guinea pigs of either sex were divided into seven groups: group 1 - normal diet; group 2 - high fat diet; group 3 and 4 - normal diet plus leaf juice of Catharanthus roseus (Linn.) G. Donn. in the dose of 0.5 and 1 mL/kg, respectively; group 5 and 6- high fat diet with leaf juice of Catharanthus roseus (Linn.) G. Donn. in the dose of 0.5 and 1 mL/kg, respectively; group 7 - high fat diet plus atorvastatin (3 mg/kg). Above diet treatment was given for six weeks and drug was given during last three weeks. Serum lipid profile (total cholesterol, triglycerides, LDL-c, VLDL-c, HDL-c) was performed in each group of animals before and at the end of six weeks. Histological study of aorta, liver and kidney was done in group 1, 2, 6 and 7 and blood cell count was done in animals that were treated juice of C. roseus (Linn.) G. Donn. before and after juice administration. Simultaneous administration of leaf juice of C. roseus (Linn.) G. Donn. in the dose of 0.5 mL/kg prevents the rise of serum lipid parameters and decreases the fatty changes in the tissue induced by high fat diet, whereas in the dose of 1 mL/kg not only counteracts the elevation, but also significantly (p < 0.05) reduces the serum level LDL-c and the ratio of total cholesterol and HDL-c. Leaf juice of C. roseus (Linn.) G. Donn. possesses significant lipid lowering and anti atherosclerotic activity.

Effect of the hydroalcoholic extract and juice of Prunus divaricata fruit on blood glucose and serum lipids of normal and streptozotocin-induced diabetic rats

PubMed Central

Minaiyan, M.; Ghannadi, A.; Movahedian, A.; Ramezanlou, P.; Osooli, F.S.

2014-01-01

Prunus divaricata (Alloocheh) is a small tree cultivating in Iran, Middle East and central Asia. Prunus genus has many species with anti-oxidant, anti-hyperlipidemia and anti-hyperglycemia effects. In the present study the anti-diabetic and anti-hyperlipidemic effects of P. divaricata fruits were examined in normal and streptozotocin (STZ)-induced diabetic rats. Both groups, control and reference rats received normal saline and glibenclamide respectively. Test groups were treated with Prunus freeze dried juice (PFDJ, 200, 400, 800 mg/kg) and Prunus freeze dried extract (PFDE, 100, 200, 400 mg/kg) started at the 3rd day of the experiment and continued for 27 days thereafter. Weight changes of animals were checked periodically. Fasting blood glucose (FBG) level as well as serum triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were determined. Different treatments had no significant effect on body weight increments of normal rats, while in diabetic rats, PFDJ (800 mg/kg) and PFDE (400 mg/kg) opposed with weight loss. In acute phase of experiment (0-8 h of 3rd day), none of tested fractions were effective in reducing FBG and serum lipids of normal rats. During the sub-acute phase (13th and 30th days) however, the greatest test doses of PFDJ (800 mg/kg) and PFDE (400 mg/kg) induced hypoglycema. In diabetic groups, PFDJ and PFDE, at all test doses, could diminish FBG during sub-acute phase of the experiment. In addition, PFDJ and PFDE at most examined doses could diminish TG significantly and they were also effective on cholesterol derivatives in different magnitude. PMID:26339257

Neuroprotective effects of diazoxide and its antagonism by glibenclamide in pyramidal neurons of rat hippocampus subjected to ischemia-reperfusion-induced injury.

PubMed

Zarch, Anoushiravan Vakili; Toroudi, Hamidreza Pazoki; Soleimani, Mansooreh; Bakhtiarian, Azam; Katebi, Majid; Djahanguiri, Bijan

2009-01-01

Mitochondrial ATP-sensitive potassium channel opener, diazoxide, is shown to have protective effect on the heart and brain following ischemia-reperfusion-induced injury (IR/II). However, the detailed effect of diazoxide and its antagonist on neuronal death, mitochondrial changes, and apoptosis in cerebral IR/II has not fully studied. IR/II was induced in rats by the 4-vessel occlusion model. Neuronal cell death and mitochondrial changes in CA1-CA4 pyramidal cells of the hippocampus were studied by light and electron microscopy, respectively. Apoptosis was assessed by measuring the amount of protein expressed by Bax and Bcl-2 genes. In light microscopy studies, the number of total and normal cells were increased only following 18 mg/kg of diazoxide. Lower doses (2 and 6 mg/kg) failed to change the cell numbers. All three doses of glibenclamide (1, 5, and 25 mg/kg) decreased the number of total and normal cell populations. In electron microscopy studies, different doses of diazoxide and glibenclamide prevented and aggravated the IR-induced morphological changes, respectively. Western blot analysis showed that diazoxide and glibenclamide inhibited and enhanced Bax protein expression respectively. Regarding Bcl-2 expression, only diazoxide showed a significant enhancement of gene expression. In conclusion, the results show that diazoxide can exhibit neuroprotective effects against IR/II in hippocampal regions, possibly through the opening of mitochondrial ATP-sensitive K(+) channels.

Influence of hepatic impairment on the pharmacokinetics of the dopamine agonist rotigotine.

PubMed

Cawello, Willi; Fichtner, Andreas; Boekens, Hilmar; Braun, Marina

2014-09-01

The transdermally applied dopamine receptor agonist rotigotine is extensively metabolized in the liver. An open-label, parallel-group study was conducted to evaluate the effects of moderate hepatic impairment on the pharmacokinetics, safety and tolerability of rotigotine. Eight subjects with normal hepatic function and nine with moderate hepatic impairment (Child-Pugh class B) received one rotigotine transdermal patch (providing a dose of 2 mg/24 h) daily for 3 days with a 24-h patch-on period. Blood and urine samples were collected to evaluate pharmacokinetic parameters characterizing drug bioavailability and elimination. Primary variables included plasma and urine concentrations of unconjugated rotigotine (active parent compound) and total rotigotine (unconjugated rotigotine plus sulfate and glucuronide conjugates) under steady-state (SS) conditions. For unconjugated rotigotine, point estimates for the ratios of AUC(0-24)SS and C max,SS between the two groups (normal vs. impaired hepatic function) were near 1: AUC(0-24)SS, 0.90 (90 % CI 0.59, 1.38) and C max,SS, 0.94 (90 % CI 0.66, 1.35); t max,SS and t 1/2 were lower in subjects with hepatic impairment, while renal clearance was unaffected and overall clearance was higher. For total rotigotine, C max,SS was higher in subjects with hepatic impairment compared with those with normal hepatic function (P = 0.0239, ANOVA). A tendency to reduced non-renal clearance was observed in subjects with hepatic impairment, consistent with their higher plasma concentrations of total rotigotine. Thus, moderate hepatic impairment did not influence the pharmacokinetics of unconjugated rotigotine under steady-state conditions suggesting that dose adjustment will not be required for patients with mild or moderate hepatic insufficiency. In addition, the rotigotine patch was well tolerated in subjects with moderate hepatic impairment.

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

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

Lao, Louis; Department of Radiation Oncology, Auckland City Hospital, Auckland; Hope, Andrew J.

2014-09-01

Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses atmore » the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.« less

Predicting Grade 3 Acute Diarrhea During Radiation Therapy for Rectal Cancer Using a Cutoff-Dose Logistic Regression Normal Tissue Complication Probability Model

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

Robertson, John M., E-mail: jrobertson@beaumont.ed; Soehn, Matthias; Yan Di

Purpose: Understanding the dose-volume relationship of small bowel irradiation and severe acute diarrhea may help reduce the incidence of this side effect during adjuvant treatment for rectal cancer. Methods and Materials: Consecutive patients treated curatively for rectal cancer were reviewed, and the maximum grade of acute diarrhea was determined. The small bowel was outlined on the treatment planning CT scan, and a dose-volume histogram was calculated for the initial pelvic treatment (45 Gy). Logistic regression models were fitted for varying cutoff-dose levels from 5 to 45 Gy in 5-Gy increments. The model with the highest LogLikelihood was used to developmore » a cutoff-dose normal tissue complication probability (NTCP) model. Results: There were a total of 152 patients (48% preoperative, 47% postoperative, 5% other), predominantly treated prone (95%) with a three-field technique (94%) and a protracted venous infusion of 5-fluorouracil (78%). Acute Grade 3 diarrhea occurred in 21%. The largest LogLikelihood was found for the cutoff-dose logistic regression model with 15 Gy as the cutoff-dose, although the models for 20 Gy and 25 Gy had similar significance. According to this model, highly significant correlations (p <0.001) between small bowel volumes receiving at least 15 Gy and toxicity exist in the considered patient population. Similar findings applied to both the preoperatively (p = 0.001) and postoperatively irradiated groups (p = 0.001). Conclusion: The incidence of Grade 3 diarrhea was significantly correlated with the volume of small bowel receiving at least 15 Gy using a cutoff-dose NTCP model.« less

Absorbed radiation dose in adults from iodine-131 and iodine-123 orthoiodohippurate and technetium-99m DTPA renography

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

Carlsen, O.

1988-03-01

A mathematic model for evaluation of absorbed dose in radionuclide renography has been developed and programmed for automatic calculation in the computer. Input data to the model are readily available from the results of the renography and, hence, the method described is suitable for individual dose determinations in adults. Apart from the situation with very considerable outflow obstructions (/sup 131/I)OIH single probe renography involves a 15-20 times smaller dose to radiation sensitive organs than (/sup 123/I)OIH gamma camera renography. Further, the latter examination results in a 2-10 times smaller dose than (/sup 99m/Tc)DTPA gamma camera renography under normal outflow conditions.more » Absorbed renal dose is large, approximately 70 mGy, in the three renographies in the borderline case with total outflow obstructions. For comparison, i.v. pyelography, which is the x-ray examination often used instead of radionuclide renography, involves an absorbed dose to ovaries 10-1000 times larger than in radionuclide renography« less

Kinetics of removal of intravenous testosterone pulses in normal men.

PubMed

Veldhuis, Johannes D; Keenan, Daniel M; Liu, Peter Y; Takahashi, Paul Y

2010-04-01

Testosterone is secreted into the bloodstream episodically, putatively distributing into total, bioavailable (bio) nonsex hormone-binding globulin (nonSHBG-bound), and free testosterone moieties. The kinetics of total, bio, and free testosterone pulses are unknown. Design Adrenal and gonadal steroidogenesis was blocked pharmacologically, glucocorticoid was replaced, and testosterone was infused in pulses in four distinct doses in 14 healthy men under two different paradigms (a total of 220 testosterone pulses). Testosterone kinetics were assessed by deconvolution analysis of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone concentration-time profiles. Independently of testosterone dose or paradigm, rapid-phase half-lives (min) of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone were comparable at 1.4+/-0.22 min (grand mean+/-S.E.M. of geometric means). Slow-phase testosterone half-lives were highest for SHBG-bound testosterone (32 min) and total testosterone (27 min) with the former exceeding that of free testosterone (18 min), bioavailable testosterone (14 min), and albumin-bound testosterone (18 min; P<0.001). Collective outcomes indicate that i) the rapid phase of testosterone disappearance from point sampling in the circulation is not explained by testosterone dose; ii) SHBG-bound testosterone and total testosterone kinetics are prolonged; and iii) the half-lives of bioavailable, albumin-bound, and free testosterone are short. A frequent-sampling strategy comprising an experimental hormone clamp, estimation of hormone concentrations as bound and free moieties, mimicry of physiological pulses, and deconvolution analysis may have utility in estimating the in vivo kinetics of other hormones, substrates, and metabolites.

IMRT: Improvement in treatment planning efficiency using NTCP calculation independent of the dose-volume-histogram

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

Grigorov, Grigor N.; Chow, James C.L.; Grigorov, Lenko

2006-05-15

The normal tissue complication probability (NTCP) is a predictor of radiobiological effect for organs at risk (OAR). The calculation of the NTCP is based on the dose-volume-histogram (DVH) which is generated by the treatment planning system after calculation of the 3D dose distribution. Including the NTCP in the objective function for intensity modulated radiation therapy (IMRT) plan optimization would make the planning more effective in reducing the postradiation effects. However, doing so would lengthen the total planning time. The purpose of this work is to establish a method for NTCP determination, independent of a DVH calculation, as a quality assurancemore » check and also as a mean of improving the treatment planning efficiency. In the study, the CTs of ten randomly selected prostate patients were used. IMRT optimization was performed with a PINNACLE3 V 6.2b planning system, using planning target volume (PTV) with margins in the range of 2 to 10 mm. The DVH control points of the PTV and OAR were adapted from the prescriptions of Radiation Therapy Oncology Group protocol P-0126 for an escalated prescribed dose of 82 Gy. This paper presents a new model for the determination of the rectal NTCP ({sub R}NTCP). The method uses a special function, named GVN (from Gy, Volume, NTCP), which describes the {sub R}NTCP if 1 cm{sup 3} of the volume of intersection of the PTV and rectum (R{sub int}) is irradiated uniformly by a dose of 1 Gy. The function was 'geometrically' normalized using a prostate-prostate ratio (PPR) of the patients' prostates. A correction of the {sub R}NTCP for different prescribed doses, ranging from 70 to 82 Gy, was employed in our model. The argument of the normalized function is the R{sub int}, and parameters are the prescribed dose, prostate volume, PTV margin, and PPR. The {sub R}NTCPs of another group of patients were calculated by the new method and the resulting difference was <{+-}5% in comparison to the NTCP calculated by the PINNACLE3 software where Kutcher's dose-response model for NTCP calculation is adopted.« less

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

PubMed

Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

2015-04-01

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Effects of Lentinula edodes consumption on biochemical, hematologic and oxidative stress parameters in rats receiving high-fat diet.

PubMed

Spim, Sara Rosicler Vieira; de Oliveira, Bruna Giovanna Corrêa Chrispim; Leite, Fernanda Gomes; Gerenutti, Marli; Grotto, Denise

2017-10-01

Functional foods can prevent/reduce the risks related to obesity. Lentinula edodes is a highly nutritious mushroom rich in protein, vitamins and minerals. Some studies have demonstrated the hypocholesterolemic effects from L. edodes in high doses, which does not represent the consumption in humans. We evaluated ingestion of a realistic dose of L. edodes associated with a high-fat diet (HFD) on hematologic, biochemical and oxidative stress parameters. Eighteen male Wistar rats were divided into three groups: control (normal diet); HFD; and HFD + L. edodes (100 mg/kg/day). After 30 days, blood was collected. Biochemical and hematologic parameters were analyzed, as well as oxidative stress biomarkers. The HFD increased levels of total cholesterol and triglycerides. Lentinula edodes reduced these parameters significantly to concentrations found in the control group. The HFD increased levels of alanine transaminase and aspartate transaminase (markers of liver damage). Lentinula edodes returned the levels of these enzymes to normal levels and normalized serum levels of urea (which were also increased owing to consumption of the HFD). Lentinula edodes reduced levels of urea and glucose. Lipid peroxidation was increased in rats receiving the HFD, and L. edodes reduced malondialdehyde levels, thereby preventing oxidation of fatty acids. Lentinula edodes was shown to have hypolipidemic, hypoglycemic, hepatoprotective and renoprotective features in doses that are suitable for humans.

Effects of a Tripeptide Iron on Iron-Deficiency Anemia in Rats.

PubMed

Xiao, Chen; Lei, Xingen; Wang, Qingyu; Du, Zhongyao; Jiang, Lu; Chen, Silu; Zhang, Mingjie; Zhang, Hao; Ren, Fazheng

2016-02-01

This study aims to investigate the effects of a tripeptide iron (REE-Fe) on iron-deficiency anemia rats. Sprague-Dawley rats were randomly divided into seven groups: a normal control group, an iron-deficiency control group, and iron-deficiency groups treated with ferrous sulfate (FeSO4), ferrous glycinate (Fe-Gly), or REE-Fe at low-, medium-, or high-dose groups. The rats in the iron-deficiency groups were fed on an iron-deficient diet to establish iron-deficiency anemia (IDA) model. After the model established, different iron supplements were given to the rats once a day by intragastric administration for 21 days. The results showed that REE-Fe had effective restorative action returning body weight, organ coefficients, and hematological parameters in IDA rats to normal level. In addition, comparing with FeSO4 or Fe-Gly, high-dose REE-Fe was more effective on improving the levels of renal coefficient, total iron-binding capacity, and transferrin. Furthermore, the liver hepcidin messenger RNA (mRNA) expression in the high-dose group was significantly higher (p < 0.05) than that in the FeSO4 or Fe-Gly group and showed no significant difference (p > 0.05) with the normal control group. The findings suggest that REE-Fe is an effective source of iron supplement for IDA rats and might be exploited as a new iron fortifier.

Acetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.

PubMed

Haroldsen, Peter E; Sisic, Zlatko; Datt, Joe; Musson, Donald G; Ingenito, Gary

2017-07-01

The purpose of this study is to evaluate safety, tolerability, and pharmacokinetic (PK) properties of amifampridine phosphate (Firdapse™) and its major inactive 3-N-acetyl metabolite in renally impaired and healthy individuals with slow acetylator (SA) and rapid acetylator (RA) phenotypes. This was a Phase I, multicenter, open-label study of the PK properties and safety profile of amifampridine phosphate in individuals with normal, mild, moderate, or severely impaired renal function. Amifampridine phosphate was given as a single 10 mg (base equivalent) dose, and the plasma and urine PK properties of amifampridine and its 3-N-acetyl metabolite were determined. The safety profile was evaluated by monitoring adverse events (AEs), clinical laboratory tests, and physical examinations. Amifampridine clearance was predominantly metabolic through N-acetylation, regardless of renal function in both acetylator phenotypes. In individuals with normal renal function, mean renal clearance represented approximately 3% and 18% of the total clearance of amifampridine in RA and SA, respectively. Large differences in amifampridine exposure were observed between acetylation phenotypes across renal function levels. Mean amifampridine exposure values of AUC 0-∞ and C max were up to 8.8-fold higher in the SA group compared with the RA group across renal function levels. By comparison, mean AUC 0-∞ was less affected by renal function within an acetylator group, only 2- to 3-fold higher in individuals with severe renal impairment (RI) compared with those with normal renal function. Exposure to amifampridine in the SA group with normal renal function was higher (AUC 0-∞, approximately 1.8-fold; C max, approximately 4.1-fold) than the RA group with severe RI. Exposure to the inactive 3-N-acetyl metabolite was higher than amifampridine in both acetylator groups, independent of renal function level. The metabolite is cleared by renal excretion, and exposure was clearly dependent on renal function with 4.0- to 6.8-fold increases in AUC 0-∞ from normal to severe RI. No new tolerability findings were observed. A single dose of 10 mg of amifampridine phosphate was well tolerated, independent of renal function and acetylator status. The results indicate that the PK profile of amifampridine is affected by metabolic acetylator phenotype to a greater extent than by renal function level, supporting Firdapse™ administration in individuals with RI in line with current labeling recommendations. Amifampridine should be dosed to effect per the individual patient need, altering administration frequency and dose in normal through severe RI. The therapeutic dose of amifampridine phosphate should be tailored to the individual patient needs by gradual dose titration up to the present maximum recommended dose (60-80 mg/day) or until dose-limiting AEs intervene to avoid overdosing and underdosing. EudraCT identifier: 2013-005349-35. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

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

Chen, Y; Souri, S; Gill, G

Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose tomore » its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.« less

Combined Administration of Recombinant Human Megakaryocyte Growth and Development Factor and Granulocyte Colony-Stimulating Factor Enhances Multilineage Hematopoietic Reconstitution in Nonhuman Primates after Radiation-Induced Marrow Aplasia

DTIC Science & Technology

1996-05-01

dose would yield an equivalent or better biological activity. Neupogen ® ( Filgrastim ), r-metHuG-CSF, was produced in E. coli as a...recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoi- etic recovery after otherwise lethal total body

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

Price, R; Meyer, J; Horwitz, E

Purpose: Medical advances have resulted in cancer patients living longer as evidenced by the number of patients seen for possible re-irradiation. Original normal tissue dose volume constraints remain in the re-irradiation setting to minimize normal tissue toxicity. This work correlates estimates of equivalent dose and repair with sequelae. Methods: CNS and GI tract re-irradiation patient follow-up records (including imaging studies) were reviewed with side effects correlated with the calculated EQD2 and repair estimates. Results: Follow-up records for 16 re-irradiation patients with potential overlap to the spinal cord were analyzed. The mean time interval between 1st and last courses was 76.6more » months. Three patients underwent a 3rd course of radiotherapy with a mean time interval between 2nd and final courses of 19.7 months. The mean values for assumed repair were 18.8% and 8.3%, respectively. The calculated total EQD2 doses were 48.09Gy and 50.98Gy with and without repair. At a mean follow-up time of 5.0 months, 6 patients were deceased and no records indicate radiation related neurological deficits. The records for 11 patients with potential overlap to the bowel were also analyzed. The mean time interval between 1st and last courses was 105.9 months. The mean value for assumed repair was 15.9%. The calculated total EQD2 doses were 64.96Gy and 70.80Gy with and without repair. At a mean follow-up time of 4.9 months, 6 patients were deceased, one having a potential enteric fistulization of the bladder. Clinical review of the case determined that the fistula was caused by tumor progression and not a side effect of radiotherapy treatments. Conclusion: Application of the EQD2 method in the re-irradiation setting using conservative estimates of repair is presented. Adhering to accepted dose volume limits following this application is demonstrated to be safe through empirical records as limited by this small patient cohort and short follow-up.« less

Super High Dosing with a Novel Buttiauxella Phytase Continuously Improves Growth Performance, Nutrient Digestibility, and Mineral Status of Weaned Pigs.

PubMed

Zeng, Zhikai; Li, Qingyun; Tian, Qiyu; Zhao, Panfeng; Xu, Xiao; Yu, Shukun; Piao, Xiangshu

2015-11-01

This study was conducted to evaluate the efficacy of a novel Buttiauxella phytase to pigs fed P-deficient, corn-soybean meal diets. One hundred and twenty crossbred piglets (9.53 ± 0.84 kg) were allocated to one of five treatments which consisted of four low P diets (0.61 % Ca and 0.46 % total P) supplemented with 0, 500, 1,000, or 20,000 FTU/kg phytase as well as a positive control diet (0.77 % Ca and 0.62 % total P). Each treatment had six replicated pens with four pigs per pen. Pigs were fed the experimental diets for 28 days. Phytase supplementation linearly improved (P < 0.05) average daily gain (ADG), feed conversion ratio (FCR), and apparent total tract digestibility (ATTD) of dry matter, gross energy, crude protein, Ca, and P in weaned pigs. Super high dosing with phytase (20,000 FTU/kg) further increased (P < 0.05) ADG compared with 500 FTU/kg phytase inclusion group, as well as ATTD of Ca and P. Metacarpal bone characteristics and several trace mineral concentration in bone, plasma, or organ tissues were linearly (P < 0.05) improved at increasing dose of phytase. Super high dosing with phytase (20,000 FTU/kg) supplementation improved (P < 0.05) Mn and Zn concentration in bone compared to normal dose of phytase supplementation (500 or 1,000 FTU/kg). In conclusion, supplementation of 500 FTU of Buttiauxella phytase/kg and above effectively hydrolyzed phytate in a low-P corn-soybean diet for pigs. In addition, a super high dosing with phytase (20,000 FTU/kg) improved macro- or micro mineral availability and growth performance.

Estimation of Rectal Dose Using Daily Megavoltage Cone-Beam Computed Tomography and Deformable Image Registration

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

Akino, Yuichi, E-mail: akino@radonc.med.osaka-u.ac.jp; Department of Radiology, Osaka University Hospital, Suita, Osaka; Yoshioka, Yasuo

2013-11-01

Purpose: The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Methods and Materials: Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CTmore » value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. Results: The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R{sup 2}=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R{sup 2}=0.61±0.16). Conclusion: We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume.« less

Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal.

PubMed

Rowe, A Shaun; Dietrich, Scott K; Phillips, John W; Foster, Kaci E; Canter, Joshua R

2018-06-01

To compare the international normalized ratio normalization efficacy of activated prothrombin complex concentrates and 4-factor prothrombin complex concentrates and to evaluate the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage. Retrospective, Multicenter Cohort. Large, Community, Teaching Hospital. Patients greater than 18 years old and received either activated prothrombin complex concentrate or 4-factor prothrombin complex concentrate for the treatment of warfarin-associated hemorrhage. We excluded those patients who received either agent for an indication other than warfarin-associated hemorrhage, pregnant, had a baseline international normalized ratio of less than 2, received a massive transfusion as defined by hospital protocol, received plasma for treatment of warfarin-associated hemorrhage, or were treated for an acute warfarin ingestion. Patients in the activated prothrombin complex concentrate group (enrolled from one hospital) with an international normalized ratio of less than 5 received 500 IU and those with an international normalized ratio greater than 5 received 1,000 IU. Patients in the 4-factor prothrombin complex concentrate (enrolled from a separate hospital) group received the Food and Drug Administration approved dosing algorithm. A total of 158 patients were included in the final analysis (activated prothrombin complex concentrate = 118; 4-factor prothrombin complex concentrate = 40). Those in the 4-factor prothrombin complex concentrate group had a higher pretreatment international normalized ratio (2.7 ± 1.8 vs 3.5 ± 2.9; p = 0.0164). However, the posttreatment international normalized ratio was similar between the groups. In addition, even when controlling for differences in the pretreatment international normalized ratio, there was no difference in the ability to achieve a posttreatment international normalized ratio of less than 1.4 (odds ratio, 0.753 [95% CI, 0.637-0.890]; p = 0.0009). Those in the activated prothrombin complex concentrate group did have higher odds of achieving a posttreatment international normalized ratio of less than 1.2 (odds ratio, 3.23 [95% CI, 1.34-7.81]; p = 0.0088). There was only one posttreatment thrombotic complication reported. A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events.

Organ biodistribution of Germanium-68 in rat in the presence and absence of [68Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body radiation dosimetry

PubMed Central

Velikyan, Irina; Antoni, Gunnar; Sörensen, Jens; Estrada, Sergio

2013-01-01

Positron Emission Tomography (PET) and in particular gallium-68 (68Ga) applications are growing exponentially worldwide contributing to the expansion of nuclear medicine and personalized management of patients. The significance of 68Ga utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the monographs that might limit the use of the generators and consequently expansion of 68Ga applications and that is the limit of 0.001% of Germanium-68 (68Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of 68Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and justification of the 68Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [68Ge]GeCl4 in the absence or presence of [68Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). 68Ge(IV) was evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose estimates indicated that the kidneys were the dose-limiting organs (185±54 μSv/MBq for female and 171±38 μSv/MBq for male) and the total effective dose was 15.5±0.1 and 10.7±1.2 μSv/MBq, respectively for female and male. The results of this dosimetry study conclude that the 68Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without exposing the patient to harm given the small absorbed doses to normal organs and fast excretion. PMID:23526484

Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro.

PubMed

Lopez-Cepero, M; Friedman, M; Klein, T; Friedman, H

1986-06-01

The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.

Detection of erythropoietin misuse by the Athlete Biological Passport combined with reticulocyte percentage.

PubMed

Bejder, Jacob; Aachmann-Andersen, Niels Jacob; Bonne, Thomas Christian; Olsen, Niels Vidiendal; Nordsborg, Nikolai Baastrup

2016-10-01

The sensitivity of the adaptive model of the Athlete Biological Passport (ABP) and reticulocyte percentage (ret%) in detection of recombinant human erythropoietin (rHuEPO) misuse was evaluated using both a long-term normal dose and a brief high dose treatment regime. Sixteen subjects received either 65 IU rHuEPO × kg -1 every second day for two weeks (normal-dose), 390 IU rHuEPO × kg -1 on three consecutive days (high-dose), or frequent placebo treatment for 13 days in a randomized, placebo-controlled, double-blind crossover design. Blood variables were measured 4, 11, and 25 days following treatment initiation. The ABP based on haemoglobin concentration ([Hb]) and OFF-hr score ([Hb] - 60 × √ret%) yielded atypical profiles following both normal-dose and high-dose treatment (0 %, 31 %, 13 % vs. 21 %, 33 %, 20 % at days 4, 11, and 25 after normal and high dose, respectively). Including ret% as a stand-alone marker for atypical blood profiles increased (P < 0.05) the sensitivity of the adaptive model at day 11 to 63 % and 67 % for normal-dose and high-dose rHuEPO administration, respectively. In conclusion, ~30 % of subjects injecting a normal-dose rHuEPO for two weeks or a high-dose rHuEPO for three days will present an atypical ABP profile. Including ret% as a stand-alone parameter improves the sensitivity two-fold. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation.

PubMed

Wong, Jeffrey Y C; Rosenthal, Joseph; Liu, An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

2009-01-01

Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches.

Metabolic Effects of Oral Versus Transdermal 17β-Estradiol (E2): A Randomized Clinical Trial in Girls With Turner Syndrome

PubMed Central

Torres-Santiago, L.; Mericq, V.; Taboada, M.; Unanue, N.; Klein, K. O.; Singh, R.; Hossain, J.; Santen, R. J.; Ross, J. L.

2013-01-01

Context: The long-term effects of pure 17β-estradiol (E2) depending on route of administration have not been well characterized. Objective: Our objective was to assess metabolic effects of oral vs transdermal (TD) 17β-E2 replacement using estrogen concentration-based dosing in girls with Turner syndrome (TS). Patients: Forty girls with TS, mean age 16.7 ± 1.7 years, were recruited. Design: Subjects were randomized to 17β-E2 orally or TD. Doses were titrated using mean E2 concentrations of normally menstruating girls as therapeutic target. E2, estrone (E1), and E1 sulfate (E1S) were measured by liquid chromatography tandem mass spectrometry and a recombinant cell bioassay; metabolites were measured, and dual-energy x-ray absorptiometry scan and indirect calorimetry were performed. Main Outcome: Changes in body composition and lipid oxidation were evaluated. Results: E2 concentrations were titrated to normal range in both groups; mean oral dose was 2 mg, and TD dose was 0.1 mg. After 6 and 12 months, fat-free mass and percent fat mass, bone mineral density accrual, lipid oxidation, and resting energy expenditure rates were similar between groups. IGF-1 concentrations were lower on oral 17β-E2, but suppression of gonadotropins was comparable with no significant changes in lipids, glucose, osteocalcin, or highly sensitive C-reactive protein between groups. However, E1, E1S, SHBG, and bioestrogen concentrations were significantly higher in the oral group. Conclusions: When E2 concentrations are titrated to the normal range, the route of delivery of 17β-E2 does not affect differentially body composition, lipid oxidation, and lipid concentrations in hypogonadal girls with TS. However, total estrogen exposure (E1, E1S, and total bioestrogen) is significantly higher after oral 17β-E2. TD 17β-E2 results in a more physiological estrogen milieu than oral 17β-E2 administration in girls with TS. PMID:23678038

Development and preclinical studies of 64Cu-NOTA-pertuzumab F(ab′)2 for imaging changes in tumor HER2 expression associated with response to trastuzumab by PET/CT

PubMed Central

Lam, Karen; Chan, Conrad; Reilly, Raymond M.

2017-01-01

ABSTRACT We previously reported that microSPECT/CT imaging with 111In-labeled pertuzumab detected decreased HER2 expression in human breast cancer (BC) xenografts in athymic mice associated with response to treatment with trastuzumab (Herceptin). Our aim was to extend these results to PET/CT by constructing F(ab′)2 of pertuzumab modified with NOTA chelators for complexing 64Cu. The effect of the administered mass (5–200 µg) of 64Cu-NOTA-pertuzumab F(ab′)2 was studied in NOD/SCID mice engrafted with HER2-positive SK-OV-3 human ovarian cancer xenografts. Biodistribution studies were performed in non-tumor bearing Balb/c mice to predict radiation doses to normal organs in humans. Serial PET/CT imaging was conducted on mice engrafted with HER2-positive and trastuzumab-sensitive BT-474 or trastuzumab-insensitive SK-OV-3 xenografted mice treated with weekly doses of trastuzumab. There were no significant effects of the administered mass of 64Cu-NOTA-pertuzumab F(ab′)2 on tumor or normal tissue uptake. The predicted total body dose in humans was 0.015 mSv/MBq, a 3.3-fold reduction compared to 111In-labeled pertuzumab. MicroPET/CT images revealed specific tumor uptake of 64Cu-NOTA-pertuzumab F(ab′)2 at 24 or 48 h post-injection in mice with SK-OV-3 tumors. Image analysis of mice treated with trastuzumab showed 2-fold reduced uptake of 64Cu-NOTA-pertuzumab F(ab′)2 in BT-474 tumors after 1 week of trastuzumab normalized to baseline, and 1.9-fold increased uptake in SK-OV-3 tumors after 3 weeks of trastuzumab, consistent with tumor response and resistance, respectively. We conclude that PET/CT imaging with 64Cu-NOTA-pertuzumab F(ab′)2 detected changes in HER2 expression in response to trastuzumab while delivering a lower total body radiation dose compared to 111In-labeled pertuzumab. PMID:27813707

Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption.

PubMed

Nollevaux, M-C; Guiot, Y; Horsmans, Y; Leclercq, I; Rahier, J; Geubel, A P; Sempoux, C

2006-03-01

Hypervitaminosis A-related liver toxicity may be severe and may even lead to cirrhosis. In the normal liver, vitamin A is stored in hepatic stellate cells (HSC), which are prone to becoming activated and acquiring a myofibroblast-like phenotype, producing large amounts of extracellular matrix. In order to assess the relationship between vitamin A intake, HSC activation and fibrosis, we studied nine liver biopsies from patients belonging to a well-characterized series of 41 patients with vitamin A hepatotoxicity. Fibrosis was underlined by Sirius-red staining, whereas activated HSC were immunohistochemically identified using an antibody against alpha smooth muscle actin. The volume density (Vv) of sinusoidal and total fibrosis and of sinusoidal and total activated HSC was quantified by the point-counting method. Morphology ranged from HSC hypertrophy and hyperplasia as the sole features to severe architectural distortion. There was a significant positive correlation between Vv of perisinusoidal fibrosis and the daily consumption of vitamin A (P=0.004). The close correlation between the severity of perisinusoidal fibrosis and the daily dose of the retinol intake suggests the existence of a dose-effect relationship.

Stereology techniques in radiation biology

NASA Technical Reports Server (NTRS)

Kubinova, Lucie; Mao, XiaoWen; Janacek, Jiri; Archambeau, John O.; Nelson, G. A. (Principal Investigator)

2003-01-01

Clinicians involved in conventional radiation therapy are very concerned about the dose-response relationships of normal tissues. Before proceeding to new clinical protocols, radiation biologists involved with conformal proton therapy believe it is necessary to quantify the dose response and tolerance of the organs and tissues that will be irradiated. An important focus is on the vasculature. This presentation reviews the methodology and format of using confocal microscopy and stereological methods to quantify tissue parameters, cell number, tissue volume and surface area, and vessel length using the microvasculature as a model tissue. Stereological methods and their concepts are illustrated using an ongoing study of the dose response of the microvessels in proton-irradiated hemibrain. Methods for estimating the volume of the brain and the brain cortex, the total number of endothelial cells in cortical microvessels, the length of cortical microvessels, and the total surface area of cortical microvessel walls are presented step by step in a way understandable for readers with little mathematical background. It is shown that stereological techniques, based on a sound theoretical basis, are powerful and reliable and have been used successfully.

Experimental study of electrolysis-induced hepatic necrosis.

PubMed

Robertson, G S; Wemyss-Holden, S A; Dennison, A R; Hall, P M; Baxter, P; Maddern, G J

1998-09-01

One of the most promising but unexplored methods for treating patients with irresectable liver tumours is electrolysis. This study examined the effect of increasing 'current dose' on the volume of the lesion induced in normal rat liver. A direct current generator, connected to platinum electrodes implanted in the rat liver, was used to examine the effect of (1) varying current doses from 1 to 5 coulombs and (2) electrode separation (2 or 20 mm), on the volume of liver necrosis. There was a significant correlation (P < 0.001) between the current dose and the volume of necrosis produced for each electrode separation. Placing the electrodes 2 mm apart resulted in smaller total volumes of necrosis than placing them 20 mm apart when anode lesions were significantly larger than cathode lesions (P< 0.05). Liver enzymes (aspartate aminotransferase, alanine aminotransferase) were significantly raised 1 day after treatment (P < 0.001) and predicted the total volume of hepatic necrosis (P < 0.001). Predictable and reproducible areas of liver necrosis are produced with electrolysis. If these results extrapolate to larger animal models, this technique has potential for patients with irresectable primary and secondary liver tumours.

[Human bioaging acceleration as Chernobyl radiation consequence].

PubMed

Neĭfakh, E A; Liuman, G K

2013-01-01

To monitor human bioaging as a health integral index by blood plasma markers as a molar ratio for biochemically coupled monomers of intracellular lipofuscin, an intracellular polymeric aging pigment with free-radical crossed shifts, has been developed. Lipofuscin includes cell debris with catabolites of lipoperoxic cascade and lipid antioxidants. The latter were detected in the plasma samples of normal adults and children, as well as in Chernobyl clean-up workers (24-62 years old by 1990) with external total gamma-doses of 0.9-145 cSv for 4.2 years. Dynamics for bioaging markers as the molar ratio of blood levels of lipoperoxic catabolites to their antioxidants reflected normal physiologic peculiarities for the studied age periods: oxygen stress for newborns, adaptation during childhood, stability for the middle age and an increased lipoperoxidation (mainly for aging men) due to the age weakening of the antioxidant control. The ratio for the fractions of ma- lone dialdehyde (MDA), a lipoperoxic final catabolite, showed the increase of its binding by plasma proteins in proportions to calendar ages for the norm, as it is the case for lipofuscin; The graph of the age normal molar ratio of protein-bound MDA to the free one was pre-set for calibrations into the developed computer Program to calculate Relative Aging Velocities (Wrel) by bioage increments during the period of human exposure to radiation from the CAPS damage. Wrel were increasing logarithmically to the obtained doses if the total radiation exceeded 4 cSv and exceeded their normal velocities at 50 cSv 10 times or more. Slowing down of Wrel in relation to the calendar age increment was found if the sum doses were lower than 4 cSv. Levels of the studied plasma metabolites as their bioage Moles/Moles markers relative to their norms are dynamically stationary in contrast to the lipofuscin intracellular irreversible accumulation. Earlier it was shown that the decreased vitamin E and A levels with the increased lipoperoxic metabolite blood levels that indicate health consequences for the irradiated CAPS personell with related cytogenetic deviations, as well as for the adult population and children from radio-polluted regions, were restored to norms or corrected by adequate peroral therapy with bioantioxidants.

Total Ionizing Dose Effects on Strained Ge pMOS FinFETs on Bulk Si

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

Zhang, En Xia; Fleetwood, Daniel M.; Hachtel, Jordan A.

2016-12-02

In this paper, we have characterized the total ionizing dose response of strained Ge p MOS FinFETs built on bulk Si using a fin replacement process. Devices irradiated to 1.0 Mrad(SiO 2) show minimal transconductance degradation (less than 5%), very small V th shifts (less than 40 mV in magnitude) and very little ON/OFF current ratio degradation (<5%), and only modest variation in radiation response with transistor geometry (typically less than normal part-to-part variation). Both before and after irradiation, the performance of these strained Ge p MOS FinFETs is far superior to that of past generations of planar Ge pmore » MOS devices. Finally, these improved properties result from significant improvements in processing technology, as well as the enhanced gate control provided by the strained Ge FinFET technology.« less

Memory Technologies and Data Recorder Design

NASA Technical Reports Server (NTRS)

Strauss, Karl F

2009-01-01

Missions, both near Earth and deep space, are under consideration that will require data recorder capacities of such magnitude as to be unthinkable just a few years ago. Concepts requiring well over 16,000 GB of storage are being studied. To achieve this capacity via "normal means" was considered incredible as recently as 2004. This paper is presented in two parts. Part I describes the analysis of data recorder capacities for missions as far back as 35 years and provides a projection of data capacities required 20 years from now based upon missions either nearing launch, or in the planning stage. The paper presents a similar projection of memory device capacities as baselined in the ITRS - the International Technology Roadmap for Semiconductors. Using known Total Ionizing Dose tolerance going back as far as a decade, a projection of total dose tolerance is made for two prime technologies out to the year 2028.

Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity.

PubMed

Liu, Yan; Li, Xuemei; Xie, Chen; Luo, Xiuzhen; Bao, Yonggang; Wu, Bin; Hu, Yuchi; Zhong, Zhong; Liu, Chang; Li, MinJie

2016-01-01

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE's effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration.

Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity

PubMed Central

Xie, Chen; Luo, Xiuzhen; Bao, Yonggang; Wu, Bin; Hu, Yuchi; Zhong, Zhong; Liu, Chang; Li, MinJie

2016-01-01

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE’s effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration. PMID:27054886

SU-E-T-616: Plan Quality Assessment of Both Treatment Planning System Dose and Measurement-Based 3D Reconstructed Dose in the Patient

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

Olch, A

2015-06-15

Purpose: Systematic radiotherapy plan quality assessment promotes quality improvement. Software tools can perform this analysis by applying site-specific structure dose metrics. The next step is to similarly evaluate the quality of the dose delivery. This study defines metrics for acceptable doses to targets and normal organs for a particular treatment site and scores each plan accordingly. The input can be the TPS or the measurement-based 3D patient dose. From this analysis, one can determine whether the delivered dose distribution to the patient receives a score which is comparable to the TPS plan score, otherwise replanning may be indicated. Methods: Elevenmore » neuroblastoma patient plans were exported from Eclipse to the Quality Reports program. A scoring algorithm defined a score for each normal and target structure based on dose-volume parameters. Each plan was scored by this algorithm and the percentage of total possible points was obtained. Each plan also underwent IMRT QA measurements with a Mapcheck2 or ArcCheck. These measurements were input into the 3DVH program to compute the patient 3D dose distribution which was analyzed using the same scoring algorithm as the TPS plan. Results: The mean quality score for the TPS plans was 75.37% (std dev=14.15%) compared to 71.95% (std dev=13.45%) for the 3DVH dose distribution. For 3/11 plans, the 3DVH-based quality score was higher than the TPS score, by between 0.5 to 8.4 percentage points. Eight/11 plans scores decreased based on IMRT QA measurements by 1.2 to 18.6 points. Conclusion: Software was used to determine the degree to which the plan quality score differed between the TPS and measurement-based dose. Although the delivery score was generally in good agreement with the planned dose score, there were some that improved while there was one plan whose delivered dose quality was significantly less than planned. This methodology helps evaluate both planned and delivered dose quality. Sun Nuclear Corporation has provded a license for the software described.« less

Ipsilateral kidney sparing in treatment of pancreatic malignancies using volumetric-modulated arc therapy avoidance sectors

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

Chan, Raymond W., E-mail: rwc3b@alumni.virginia.edu; Podgorsak, Matthew B.

Recent research has shown treating pancreatic cancer with volumetric-modulated arc therapy (VMAT) to be superior to either intensity-modulated radiation therapy or 3-dimensional conformal radiotherapy (3D-CRT), with respect to reducing normal tissue toxicity, monitor units, and treatment time. Furthermore, using avoidance sectors with RapidArc planning can further reduce normal tissue dose while maintaining target conformity. This study looks at the methods in reducing dose to the ipsilateral kidney, in pancreatic head cases, while observing dose received by other critical organs using avoidance sectors. Overall, 10 patients were retrospectively analyzed. Each patient had preoperative/unresectable pancreatic tumor and were selected based on themore » location of the right kidney being situated within the traditional 3D-CRT treatment field. The target planning target volume (286.97 ± 85.17 cm{sup 3}) was prescribed to 50.4 Gy using avoidance sectors of 30°, 40°, and 50° and then compared with VMAT as well as 3D-CRT. Analysis of the data shows that the mean dose to the right kidney was reduced by 11.6%, 15.5%, and 21.9% for avoidance angles of 30°, 40°, and 50°, respectively, over VMAT. The mean dose to the total kidney also decreased by 6.5%, 8.5%, and 11.0% for the same increasing angles. Spinal cord maximum dose, however, increased as a function of angle by 3.7%, 4.8%, and 6.1% compared with VMAT. Employing avoidance sector angles as a complement to VMAT planning can significantly reduce high dose to the ipsilateral kidney while not greatly overdosing other critical organs.« less

Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

PubMed Central

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

Acute toxicity study of zerumbone-loaded nanostructured lipid carrier on BALB/c mice model.

PubMed

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Yeap, Swee Keong; Abdul Samad, Nozlena; Andas, Reena Joys; Muhammad Nadzri, Nabilah; Anasamy, Theebaa; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

PubMed

Allen, Joshua E; Crowder, Roslyn N; Crowder, Roslyn; El-Deiry, Wafik S

2015-01-01

We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer.

First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent

PubMed Central

Allen, Joshua E.; Crowder, Roslyn; El-Deiry, Wafik S.

2015-01-01

We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer. PMID:26580220

Late ophthalmological complications after total body irradiation in non-human primates

NASA Technical Reports Server (NTRS)

Niemer-Tucker, M. M.; Sterk, C. C.; de Wolff-Rouendaal, D.; Lee, A. C.; Lett, J. T.; Cox, A.; Emmanouilidis-van der Spek, K.; Davelaar, J.; Lambooy, A. C.; Mooy, C. M.;

SU-F-J-147: Magnetic Field Dose Response Considerations for a Linac Monitor Chamber

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

Reynolds, M; Fallone, B

Purpose: The impact of magnetic fields on the readings of a linac monitor chamber have not yet been investigated. Herein we examine the total dose response as well as any deviations in the beam parameters of flatness and symmetry when a Varian monitor chamber is irradiated within an applied magnetic field. This work has direct application to the development of Linac-MR systems worldwide. Methods: A Varian monitor chamber was modeled in the Monte Carlo code PENELOPE and irradiated in the presence of a magnetic field with a phase space generated from a model of a Linac-MR prototype system. The magneticmore » field strength was stepped from 0 to 3.0T in both parallel and perpendicular directions with respect to the normal surface of the phase space. Dose to each of the four regions in the monitor chamber were scored separately for every magnetic field adaptation to evaluate the effect of the magnetic field on flatness and symmetry. Results: When the magnetic field is perpendicular to the phase space normal we see a change in dose response with a maximal deviation (10–25% depending on the chamber region) near 0.75T. In the direction of electron deflection we expectedly see opposite responses in chamber regions leading to a measured asymmetry. With a magnetic field parallel to the phase space normal we see no measured asymmetries, however there is a monotonic rise in dose response leveling off at about +12% near 2.5T. Conclusion: Attention must be given to correct for the strength and direction of the magnetic field at the location of the linac monitor chamber in hybrid Linac-MR devices. Elsewise the dose sampled by these chambers may not represent the actual dose expected at isocentre; additionally there may be a need to correct for the symmetry of the beam recorded by the monitor chamber. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).« less

SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

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

Zhang, Q; Lei, Y; Zheng, D

Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness weremore » created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing.« less

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.

Statistical distributions of ultra-low dose CT sinograms and their fundamental limits

NASA Astrophysics Data System (ADS)

Lee, Tzu-Cheng; Zhang, Ruoqiao; Alessio, Adam M.; Fu, Lin; De Man, Bruno; Kinahan, Paul E.

2017-03-01

Low dose CT imaging is typically constrained to be diagnostic. However, there are applications for even lowerdose CT imaging, including image registration across multi-frame CT images and attenuation correction for PET/CT imaging. We define this as the ultra-low-dose (ULD) CT regime where the exposure level is a factor of 10 lower than current low-dose CT technique levels. In the ULD regime it is possible to use statistically-principled image reconstruction methods that make full use of the raw data information. Since most statistical based iterative reconstruction methods are based on the assumption of that post-log noise distribution is close to Poisson or Gaussian, our goal is to understand the statistical distribution of ULD CT data with different non-positivity correction methods, and to understand when iterative reconstruction methods may be effective in producing images that are useful for image registration or attenuation correction in PET/CT imaging. We first used phantom measurement and calibrated simulation to reveal how the noise distribution deviate from normal assumption under the ULD CT flux environment. In summary, our results indicate that there are three general regimes: (1) Diagnostic CT, where post-log data are well modeled by normal distribution. (2) Lowdose CT, where normal distribution remains a reasonable approximation and statistically-principled (post-log) methods that assume a normal distribution have an advantage. (3) An ULD regime that is photon-starved and the quadratic approximation is no longer effective. For instance, a total integral density of 4.8 (ideal pi for 24 cm of water) for 120kVp, 0.5mAs of radiation source is the maximum pi value where a definitive maximum likelihood value could be found. This leads to fundamental limits in the estimation of ULD CT data when using a standard data processing stream

Postmastectomy radiotherapy with integrated scar boost using helical tomotherapy.

PubMed

Rong, Yi; Yadav, Poonam; Welsh, James S; Fahner, Tasha; Paliwal, Bhudatt

2012-01-01

The purpose of this study was to evaluate helical tomotherapy dosimetry in postmastectomy patients undergoing treatment for chest wall and positive nodal regions with simultaneous integrated boost (SIB) in the scar region using strip bolus. Six postmastectomy patients were scanned with a 5-mm-thick strip bolus covering the scar planning target volume (PTV) plus 2-cm margin. For all 6 cases, the chest wall received a total cumulative dose of 49.3-50.4 Gy with daily fraction size of 1.7-2.0 Gy. Total dose to the scar PTV was prescribed to 58.0-60.2 Gy at 2.0-2.5 Gy per fraction. The supraclavicular PTV and mammary nodal PTV received 1.7-1.9 dose per fraction. Two plans (with and without bolus) were generated for all 6 cases. To generate no-bolus plans, strip bolus was contoured and overrode to air density before planning. The setup reproducibility and delivered dose accuracy were evaluated for all 6 cases. Dose-volume histograms were used to evaluate dose-volume coverage of targets and critical structures. We observed reduced air cavities with the strip bolus setup compared with what we normally see with the full bolus. The thermoluminescence dosimeters (TLD) in vivo dosimetry confirmed accurate dose delivery beneath the bolus. The verification plans performed on the first day megavoltage computed tomography (MVCT) image verified that the daily setup and overall dose delivery was within 2% accuracy compared with the planned dose. The hotspot of the scar PTV in no-bolus plans was 111.4% of the prescribed dose averaged over 6 cases compared with 106.6% with strip bolus. With a strip bolus only covering the postmastectomy scar region, we observed increased dose uniformity to the scar PTV, higher setup reproducibility, and accurate dose delivered beneath the bolus. This study demonstrates the feasibility of using a strip bolus over the scar using tomotherapy for SIB dosimetry in postmastectomy treatments. Published by Elsevier Inc.

Postmastectomy radiotherapy with integrated scar boost using helical tomotherapy

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

Rong Yi, E-mail: rong@humonc.wisc.edu; University of Wisconsin Riverview Cancer Center, Wisconsin Rapids, WI; Yadav, Poonam

2012-10-01

The purpose of this study was to evaluate helical tomotherapy dosimetry in postmastectomy patients undergoing treatment for chest wall and positive nodal regions with simultaneous integrated boost (SIB) in the scar region using strip bolus. Six postmastectomy patients were scanned with a 5-mm-thick strip bolus covering the scar planning target volume (PTV) plus 2-cm margin. For all 6 cases, the chest wall received a total cumulative dose of 49.3-50.4 Gy with daily fraction size of 1.7-2.0 Gy. Total dose to the scar PTV was prescribed to 58.0-60.2 Gy at 2.0-2.5 Gy per fraction. The supraclavicular PTV and mammary nodal PTVmore » received 1.7-1.9 dose per fraction. Two plans (with and without bolus) were generated for all 6 cases. To generate no-bolus plans, strip bolus was contoured and overrode to air density before planning. The setup reproducibility and delivered dose accuracy were evaluated for all 6 cases. Dose-volume histograms were used to evaluate dose-volume coverage of targets and critical structures. We observed reduced air cavities with the strip bolus setup compared with what we normally see with the full bolus. The thermoluminescence dosimeters (TLD) in vivo dosimetry confirmed accurate dose delivery beneath the bolus. The verification plans performed on the first day megavoltage computed tomography (MVCT) image verified that the daily setup and overall dose delivery was within 2% accuracy compared with the planned dose. The hotspot of the scar PTV in no-bolus plans was 111.4% of the prescribed dose averaged over 6 cases compared with 106.6% with strip bolus. With a strip bolus only covering the postmastectomy scar region, we observed increased dose uniformity to the scar PTV, higher setup reproducibility, and accurate dose delivered beneath the bolus. This study demonstrates the feasibility of using a strip bolus over the scar using tomotherapy for SIB dosimetry in postmastectomy treatments.« less

TU-G-BRB-03: Iterative Optimization of Normalized Transmission Maps for IMRT Using Arbitrary Beam Profiles.

PubMed

Choi, K; Suh, T; Xing, L

2012-06-01

Newly available flattening filter free (FFF) beam increases the dose rate by 3∼6 times at the central axis. In reality, even flattening filtered beam is not perfectly flat. In addition, the beam profiles across different fields may not have the same amplitude. The existing inverse planning formalism based on the total-variation of intensity (or fluence) map cannot consider these properties of beam profiles. The purpose of this work is to develop a novel dose optimization scheme with incorporation of the inherent beam profiles to maximally utilize the efficacy of arbitrary beam profiles while preserving the convexity of the optimization problem. To increase the accuracy of the problem formalism, we decompose the fluence map as an elementwise multiplication of the inherent beam profile and a normalized transmission map (NTM). Instead of attempting to optimize the fluence maps directly, we optimize the NTMs and beam profiles separately. A least-squares problem constrained by total-variation of NTMs is developed to derive the optimal fluence maps that balances the dose conformality and FFF beam delivery efficiency. With the resultant NTMs, we find beam profiles to renormalized NTMs. The proposed method iteratively optimizes and renormalizes NTMs in a closed loop manner. The advantage of the proposed method is demonstrated by using a head-neck case with flat beam profiles and a prostate case with non-flat beam profiles. The obtained NTMs achieve more conformal dose distribution while preserving piecewise constancy compared to the existing solution. The proposed formalism has two major advantages over the conventional inverse planning schemes: (1) it provides a unified framework for inverse planning with beams of arbitrary fluence profiles, including treatment with beams of mixed fluence profiles; (2) the use of total-variation constraints on NTMs allows us to optimally balance the dose confromality and deliverability for a given beam configuration. This project was supported in part by grants from the National Science Foundation (0854492), National Cancer Institute (1R01 CA104205), and Leading Foreign Research Institute Recruitment Program by the Korean Ministry of Education, Science and Technology (K20901000001-09E0100-00110). To the authors' best knowledgement, there is no conflict interest. © 2012 American Association of Physicists in Medicine.

Early Experience of Helical Tomotherapy for Hepatobiliary Radiotherapy

PubMed Central

Massabeau, Carole; Marchand, Virginie; Zefkili, Sofia; Servois, Vincent; Campana, François; Giraud, Philippe

2011-01-01

Helical tomotherapy (HT), an image-guided, intensity-modulated, radiation therapy technique, allows for precise targeting while sparing normal tissues. We retrospectively assessed the feasibility and tolerance of the hepatobiliary HT in 9 patients. A total dose of 54 to 60 Gy was prescribed (1.8 or 2 Gy per fraction) with concurrent capecitabine for 7 patients. There were 1 hepatocarcinoma, 3 cholangiocarcinoma, 4 liver metastatic patients, and 1 pancreatic adenocarcinoma. All but one patient received previous therapies (chemotherapy, liver radiofrequency, and/or surgery). The median doses delivered to the normal liver and to the right kidney were 15.7 Gy and 4.4 Gy, respectively, below the recommended limits for all patients. Most of the treatment-related adverse events were transient and mild in severity. With a median followup of 12 months, no significant late toxicity was noted. Our results suggested that HT could be safely incorporated into the multidisciplinary treatment of hepatobiliary or pancreatic malignant disease. PMID:25954545

Gold nanoparticle imaging and radiotherapy of brain tumors in mice

PubMed Central

Hainfeld, James F; Smilowitz, Henry M; O'Connor, Michael J; Dilmanian, Farrokh Avraham; Slatkin, Daniel N

2013-01-01

Aim To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. Materials & methods Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. Results Gold uptake gave a 19:1 tumor-to-normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. Conclusion Intravenously injected gold nanoparticles cross the blood–tumor barrier, but are largely blocked by the normal blood–brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers. PMID:23265347

SU-F-T-648: Sharpening Dose Fall-Off Via Beam Number Enhancements For Stereotactic Brain Radiosurgery

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

Chiu, J; Braunstein, S; McDermott, M

Purpose: Sharp dose fall-off is the hallmark of brain radiosurgery to deliver a high dose of radiation to the target while minimizing dose to normal brain tissue. In this study, we developed a technique for the purpose of enhancing the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter via patient head tilt and simultaneous beam intensity modulations. Methods: Computer scripting for the proposed beam number enhancement (BNE) technique was developed. The technique was tested and then implemented on a clinical treatment planning system for a dedicated brain radiosurgical system (GK Perfexion, Elekta Oncology). Tomore » study technical feasibility and dosimetric advantages of the technique, we compared treatment planning quality and delivery efficiency for 20 radiosurgical cases previously treated at our institution. These cases included relatively complex treatments such as acoustic schwannoma, meningioma, brain metastasis and mesial temporal lobe epilepsy. Results: The BNE treatment plans were found to produce nearly identical target volume coverage (absolute value < 0.5%, P > 0.2) and dose conformity (BNE CI= 1.41±0.15 versus 1.41±0.20, P>0.9) as the original treatment plans. The total beam-on time for theBNE treatment plans were comparable (within 1.0 min or 1.8%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI = 2.9±0.3 versus original GI =3.0±0.3 p<0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 2.0% to 5.0% (p<0.02). Furthermore, with 4 to 5-fold increase in the total number of beams, the GI decreased by as much as 20% or 0.5 in absolute values. Conclusion: BNE via head tilt and simultaneous beam intensity modulation is an effective and efficient technique that physically sharpens the peripheral dose gradient for brain radiosurgery.« less

Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

PubMed

Niedzielski, Joshua S; Yang, Jinzhong; Mohan, Radhe; Titt, Uwe; Mirkovic, Dragan; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel R; Martel, Mary K; Briere, Tina M; Court, Laurence E

2017-11-15

To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ 2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

[Rivastigmine as treatment for patients with mild to moderately severe Alzheimer disease under normal clinical practice conditions. The ENTERPRISE study].

PubMed

Cruz Jentoft, A J; Hernández, B

2014-01-01

Alzheimer disease (AD) causes progressive cognitive decline leading to loss of independence for activities of daily living; rivastigmine is one of the drugs used for symptomatic management. To assess the therapeutic use of different pharmaceutical forms of rivastigmine in patients with AD in normal clinical practice. Cross-sectional, observational, multi-centre study conducted on patients with mild to moderate AD treated with rivastigmine in Spanish outpatient clinics specialising in Geriatrics, Psychiatry, and Neurology. Data regarding use of oral (OR) and transdermal (TDR) rivastigmine, compliance (degree of adherence), and caregiver satisfaction with treatment were evaluated. In total, 2252 patients with a mean age of 77.2 years were included; 60.2% were women. AD was moderate to moderately severe in 58.4%. Rivastigmine treatment was started orally in 54.4% of the patients and transdermally in 45.6%; 35.6% of those who started treatment by the OR route switched to TDR. A single dose adjustment was sufficient for 77.5% of patients on TDR treatment vs 11.8% of patients receiving OR treatment. More patients on TDR treatment (80.8% vs. 57.1% on OR treatment) reached the maximum therapeutic dose of rivastigmine and did so in a shorter period of time (51.6 vs 205.8 days). Compliance rates (60.5% vs 47.2%) and caregivers' satisfaction with treatment (89.4% vs 81.9%) were also higher for TDR. In normal clinical practice, using the TDR route of administration improves dose titration and drug compliance, allowing more patients to reach the maximum recommended dose of rivastigmine in a shorter time period. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

MicroPET/CT Imaging of an Orthotopic Model of Human Glioblastoma Multiforme and Evaluation of Pulsed Low-Dose Irradiation

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

Park, Sean S.; Chunta, John L.; Robertson, John M.

2011-07-01

Purpose: Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Methods: Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CTmore » (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Results: Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 x 10{sup 6} cells produced a 50- to 70-mm{sup 3} tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). Conclusion: This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage.« less

MicroPET/CT imaging of an orthotopic model of human glioblastoma multiforme and evaluation of pulsed low-dose irradiation.

PubMed

Park, Sean S; Chunta, John L; Robertson, John M; Martinez, Alvaro A; Oliver Wong, Ching-Yee; Amin, Mitual; Wilson, George D; Marples, Brian

2011-07-01

Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CT (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 × 10(6) cells produced a 50- to 70-mm(3) tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage. Copyright © 2011 Elsevier Inc. All rights reserved.

Pharmacokinetics of Modified Slow-Release Oral Testosterone Over 9 Days in Normal Men With Experimental Hypogonadism

PubMed Central

Lee, Ada; Rubinow, Katya; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Zhi, Hui; Roth, Mara Y; Page, Stephanie T.; Bremner, William J.; Amory, John K.

2014-01-01

Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 µg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone–binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P > .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency. PMID:21868746

[Estimated glucose disposal rate in patients under 18 years of age with type 1 diabetes mellitus and overweight or obesity].

PubMed

Palomo Atance, Enrique; Ballester Herrera, M José; Giralt Muiña, Patricio; Ruiz Cano, Rafael; León Martín, Alberto; Giralt Muiña, Juan

2013-01-01

To assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight. A total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age. No significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3±1.3 vs 10.1±0.8 mg kg(-1)min(-1); p<0.01). Insulin dose was higher in overweight and obese children, especially in IU/m2/day (37.7 vs 36.1 vs. 29.4 respectively; p<0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5mg/dL respectively; p<0.01). No correlation was found between waist circumference and the different markers of insulin resistance. Values of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m2/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Analysis of radiation safety for Small Modular Reactor (SMR) on PWR-100 MWe type

NASA Astrophysics Data System (ADS)

Udiyani, P. M.; Husnayani, I.; Deswandri; Sunaryo, G. R.

2018-02-01

Indonesia as an archipelago country, including big, medium and small islands is suitable to construction of Small Medium/Modular reactors. Preliminary technology assessment on various SMR has been started, indeed the SMR is grouped into Light Water Reactor, Gas Cooled Reactor, and Solid Cooled Reactor and from its site it is group into Land Based reactor and Water Based Reactor. Fukushima accident made people doubt about the safety of Nuclear Power Plant (NPP), which impact on the public perception of the safety of nuclear power plants. The paper will describe the assessment of safety and radiation consequences on site for normal operation and Design Basis Accident postulation of SMR based on PWR-100 MWe in Bangka Island. Consequences of radiation for normal operation simulated for 3 units SMR. The source term was generated from an inventory by using ORIGEN-2 software and the consequence of routine calculated by PC-Cream and accident by PC Cosyma. The adopted methodology used was based on site-specific meteorological and spatial data. According to calculation by PC-CREAM 08 computer code, the highest individual dose in site area for adults is 5.34E-02 mSv/y in ESE direction within 1 km distance from stack. The result of calculation is that doses on public for normal operation below 1mSv/y. The calculation result from PC Cosyma, the highest individual dose is 1.92.E+00 mSv in ESE direction within 1km distance from stack. The total collective dose (all pathway) is 3.39E-01 manSv, with dominant supporting from cloud pathway. Results show that there are no evacuation countermeasure will be taken based on the regulation of emergency.

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

PubMed

Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J

2014-11-26

Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period. An oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

Technical Note: A proposal of air ventilation system design criteria for a clinical room in a heavy-ion medical facility.

PubMed

Kum, Oyeon

2018-06-01

An optimized air ventilation system design for a treatment room in Heavy-ion Medical Facility is an important issue in the aspects of nuclear safety because the activated air produced in a treatment room can directly affect the medical staff and the general public in the radiation-free area. Optimized design criteria of air ventilation system for a clinical room in 430 MeV/u carbon ion beam medical accelerator facility was performed by using a combination of MCNPX2.7.0 and CINDER'90 codes. Effective dose rate and its accumulated effective dose by inhalation and residual gamma were calculated for a normal treatment scenario (2 min irradiation for one fraction) as a function of decay time. Natural doses around the site were measured before construction and used as reference data. With no air ventilation system, the maximum effective dose rate was about 3 μSv/h (total dose of 90 mSv/y) and minimum 0.2 μSv/h (total dose of 6 mSv/y), which are over the legal limits for medical staff and for the general public. Although inhalation dose contribution was relatively small, it was considered seriously because of its long-lasting effects in the body. The integrated dose per year was 1.8 mSv/y in the radiation-free area with the 20-min rate of air ventilation system. An optimal air ventilation rate of 20 min is proposed for a clinical room, which also agrees with the best mechanical design value. © 2018 American Association of Physicists in Medicine.

Activity concentrations of radionuclides in energy production from peat, wood chips and straw

NASA Astrophysics Data System (ADS)

Hedvall, Robert Hans

1997-11-01

In this thesis quantitative analyses of radionuclide concentrations in bioenergy fuels such as peat, wood chips and straw are presented. For comparison a brief description is included of radionuclide concentrations and radiation doses from other sources of power and also from some industrial applications. Radiation is a natural phenomenon and radionuclides occur naturally. The first man-made spread of concentrated radioactivity occurred some 100,000 years ago when the first fireplace was lit, with fallout as a later consequence. Radioactive potassium is found in most materials and is the most easily detected nuclide in fuels. Its activity concentration in Bq kg-1 normally dominates over the concentration of other natural radionuclides. The radiation dose from potassium in the emission is nevertheless negligible. The most important radionuclides in the dose to humans are the U- and Th-isotopes and also 210Pb and 210Po. Of fission products in fallout from the atmospheric nuclear tests and after the Chernobyl accident, 137Cs was shown to be the most common nuclide. Compared to natural nuclides, the contribution from emission of 137Cs was shown to be the most common nuclide. Compared to natural nuclides, the contribution from emission of 137Cs is less than a few percent of the total dose to the population. A total dose of approximately a few μSv from inhalation only can be calculated from the emission of a district heating plant in Sweden. This dose can be compared with the annual dose limit to the public from nuclear industry, which is 0.1 mSv and the global collective effective dose of 5 person Sv a-1.

Toxic effects of orally ingested oil from the Deepwater Horizon spill on laughing gulls.

PubMed

Horak, K E; Bursian, S J; Ellis, C K; Dean, K M; Link, J E; Hanson-Dorr, K C; Cunningham, F L; Harr, K E; Pritsos, C A; Pritsos, K L; Healy, K A; Cacela, D; Shriner, S A

2017-12-01

The explosion of the Deepwater Horizon oil rig released, millions of gallons of oil into the environment, subsequently exposing wildlife, including numerous bird species. To determine the effects of MC252 oil to species relevant to the Gulf of Mexico, studies were done examining multiple exposure scenarios and doses. In this study, laughing gulls (Leucophaeus atricilla, LAGU) were offered fish injected with MC252 oil at target doses of 5 or 10mL/kg bw per day. Dosing continued for 27 days. Of the adult, mixed-sex LAGUs used in the present study, ten of 20 oil exposed LAGUs survived to the end of the study; a total of 10 of the oil exposed LAGUs died or were euthanized within 20 days of initiation of the study. Endpoints associated with oxidative stress, hepatic total glutathione (tGSH), oxidized glutathione (GSSG) and reduced glutathione (rGSH) significantly increased as mean dose of oil increased, while the rGSH:GSSG ratio showed a non-significant negative trend with oil dose. A significant increase in 3-methyl histidine was found in oil exposed birds when compared to controls indicative of muscle wastage and may have been associated with the gross observation of diminished structural integrity in cardiac tissue. Consistent with previous oil dosing studies in birds, significant changes in liver, spleen, and kidney weight when normalized to body weight were observed. These studies indicate that mortality in response to oil dosing is relatively common and the mortality exhibited by the gulls is consistent with previous studies examining oil toxicity. Whether survival effects in the gull study were associated with weight loss, physiologic effects of oil toxicity, or a behavioral response that led the birds to reject the dosed fish is unknown. Published by Elsevier Inc.

Comparison of treatment plans: a retrospective study by the method of radiobiological evaluation

NASA Astrophysics Data System (ADS)

Puzhakkal, Niyas; Kallikuzhiyil Kochunny, Abdullah; Manthala Padannayil, Noufal; Singh, Navin; Elavan Chalil, Jumanath; Kulangarakath Umer, Jamshad

2016-09-01

There are many situations in radiotherapy where multiple treatment plans need to be compared for selection of an optimal plan. In this study we performed the radiobiological method of plan evaluation to verify the treatment plan comparison procedure of our clinical practice. We estimated and correlated various radiobiological dose indices with physical dose metrics for a total of 30 patients representing typical cases of head and neck, prostate and brain tumors. Three sets of plans along with a clinically approved plan (final plan) treated by either Intensity Modulated Radiation Therapy (IMRT) or Rapid Arc (RA) techniques were considered. The study yielded improved target coverage for final plans, however, no appreciable differences in doses and the complication probabilities of organs at risk were noticed. Even though all four plans showed adequate dose distributions, from dosimetric point of view, the final plan had more acceptable dose distribution. The estimated biological outcome and dose volume histogram data showed least differences between plans for IMRT when compared to RA. Our retrospective study based on 120 plans, validated the radiobiological method of plan evaluation. The tumor cure or normal tissue complication probabilities were found to be correlated with the corresponding physical dose indices.

SU-F-T-421: Dosimetry Change During Radiotherapy and Dosimetry Difference for Rigid and Deformed Registration in the Mid-Thoracic Esophageal Carcinoma

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

Tao, C; Liu, T; Chen, J

Purpose: This study aimed to analyze dosimetry changes during radiotherapy for the mid-thoracic esophageal carcinoma, and investigate dosimetry difference between rigid and deformed registration. Methods: Twelve patients with primary middle thoracic esophageal carcinoma were selected randomly. Based on first CT scanning of each patient, plans-o were generated by experience physicists. After 20 fractions treatment, the corresponding plans-re were created with second CT scanning. And then, these two CT images were rigid and deformed registration respectively, and the dose was accumulated plan-o with plan-re. The dosimetry variation of these plans (plan-o: with 30 fractions, plan-rig: the accumulated dose with rigid registrationmore » and plan-def: the accumulated dose with deformed registration) were evaluated by paired T-test. Results: The V20 value of total lung were 32.68%, 30.3% and 29.71% for plan-o, plan-rig and plan-def respectively. The mean dose of total lung was 17.19 Gy, 16.67 Gy and 16.51 Gy for plan-o plan-rig and plan-def respectively. There were significant differences between plan-o and plan-rig or plan-def for both V20 and mean dose of total lung (with p= 0.003, p= 0.000 for V20 and p=0.008, p= 0.000 for mean dose respectively). There was no significant difference between plan-rig and plan-def (with p=0.118 for V20 and p=0.384 for mean dose). The max dose of spinal-cord was 41.95 Gy, 41.48 Gy and 41.4 Gy for plan-o, plan-rig and plan-def respectively. There were no significant differences for the max dose of spinal-cord between these plans. Conclusion: The target volume changes and anatomic position displacement of mid-thoracic esophageal carcinoma should not be neglected in clinics. These changes would cause overdose in normal tissue. Therefore, it is necessary to have another CT scanning and re-plan during the mid-thoracic esophageal carcinoma radiotherapy. And the dosimetry difference between rigid and deformed fusions was not found in this study.« less

Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer

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

Hafeez, Shaista, E-mail: Shaista.Hafeez@icr.ac.uk; The Royal Marsden National Health Service Foundation Trust, London; Warren-Oseni, Karole

Purpose: Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. Methods and Materials: A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A “plan of the day” approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction fillingmore » and coverage. Results: A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D{sub 98} (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Conclusions: Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial.« less

TH-AB-207A-06: The Use of Realistic Phantoms to Predict CT Dose to Pediatric Patients

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

Carver, D; Kost, S; Fraser, N

Purpose: To predict pediatric patient dose from diagnostic CT scans using Monte Carlo simulation of realistic reference phantoms of various ages, weights, and heights. Methods: A series of deformable pediatric reference phantoms using Non-Uniform Rational B-Splines (NURBS) was developed for a large range of ages, percentiles, and reference anatomy. Individual bones were modeled using age-dependent factors, and red marrow was modeled as functions of age and spatial distribution based on Cristy1. Organ and effective doses for the phantom series were calculated using Monte Carlo simulation of chest, abdominopelvic, and chest-abdomen-pelvis CT exams. Non-linear regression was performed to determine the relationshipmore » between dose-length-product (DLP)-normalized organ and effective doses and phantom diameter. Patient-specific voxel computational phantoms were also created by manual segmentation of previously acquired CT images for 40 pediatric patients (0.7 to 17 years). Organ and effective doses were determined by Monte Carlo simulation of these patient-specific phantoms. Each patient was matched to the closest pediatric reference phantom based primarily on age and diameter for all major organs within the torso. Results: A total of 80 NURBS phantoms were created ranging from newborn to 15 years with height/weight percentiles from 10 to 90%. Organ and effective dose normalized by DLP correlated strongly with exponentially decreasing average phantom diameter (R{sup 2} > 0.95 for most organs). A similar relationship was determined for the patient-specific voxel phantoms. Differences between patient-phantom matched organ-dose values ranged from 0.37 to 2.39 mGy (2.87% to 22.1%). Conclusion: Dose estimation using NURBS-based pediatric reference phantoms offers the ability to predict patient dose before and after CT examinations, and physicians and scientists can use this information in their analysis of dose prescriptions for particular subjects and study types. This may lead to practices that minimize radiation dose while still achieving high quality images and, ultimately, improved patient care. NIH/NCI 1 R01 CA155400-01A1.« less

Extrapolation of Normal Tissue Complication Probability for Different Fractionations in Liver Irradiation

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

Tai An; Erickson, Beth; Li, X. Allen

2009-05-01

Purpose: The ability to predict normal tissue complication probability (NTCP) is essential for NTCP-based treatment planning. The purpose of this work is to estimate the Lyman NTCP model parameters for liver irradiation from published clinical data of different fractionation regimens. A new expression of normalized total dose (NTD) is proposed to convert NTCP data between different treatment schemes. Method and Materials: The NTCP data of radiation- induced liver disease (RILD) from external beam radiation therapy for primary liver cancer patients were selected for analysis. The data were collected from 4 institutions for tumor sizes in the range of of 8-10more » cm. The dose per fraction ranged from 1.5 Gy to 6 Gy. A modified linear-quadratic model with two components corresponding to radiosensitive and radioresistant cells in the normal liver tissue was proposed to understand the new NTD formalism. Results: There are five parameters in the model: TD{sub 50}, m, n, {alpha}/{beta} and f. With two parameters n and {alpha}/{beta} fixed to be 1.0 and 2.0 Gy, respectively, the extracted parameters from the fitting are TD{sub 50}(1) = 40.3 {+-} 8.4Gy, m =0.36 {+-} 0.09, f = 0.156 {+-} 0.074 Gy and TD{sub 50}(1) = 23.9 {+-} 5.3Gy, m = 0.41 {+-} 0.15, f = 0.0 {+-} 0.04 Gy for patients with liver cirrhosis scores of Child-Pugh A and Child-Pugh B, respectively. The fitting results showed that the liver cirrhosis score significantly affects fractional dose dependence of NTD. Conclusion: The Lyman parameters generated presently and the new form of NTD may be used to predict NTCP for treatment planning of innovative liver irradiation with different fractionations, such as hypofractioned stereotactic body radiation therapy.« less

Glaucoma in atomic bomb survivors.

PubMed

Kiuchi, Yoshiaki; Yokoyama, Tomoko; Takamatsu, Michiya; Tsuiki, Eiko; Uematsu, Masafumi; Kinoshita, Hirofumi; Kumagami, Takeshi; Kitaoka, Takashi; Minamoto, Atsushi; Neriishi, Kazuo; Nakashima, Eiji; Khattree, Ravindra; Hida, Ayumi; Fujiwara, Saeko; Akahoshi, Masazumi

2013-10-01

Radiation has been associated with increases in noncancerous diseases. An effect of low-dose radiation on the prevalence of clinically detected glaucoma has not been previously reported. We therefore investigated the prevalence of glaucoma in A-bomb survivors and its possible association with radiation dose. A total of 1,589 people who participated in the clinical examination program for A-bomb survivors at the Radiation Effects Research Foundation (RERF) between October 2006 and September 2008 and who had reconstructed radiation doses, were recruited into this cross-sectional screening study. The prevalence of glaucoma and its dose-response relationship to A-bomb radiation were measured. Each subject underwent an initial screening consisting of an interview and ophthalmological examination. Questionable cases with any indication of ocular disease, including glaucoma, were referred to local hospitals for more comprehensive evaluation. A diagnosis of glaucoma was made based on specific optic disc appearance, perimetric results and other ocular findings. Of 1,589 eligible people, we detected 284 (17.9%) cases of glaucoma overall, including 36 (2.3%) cases of primary open-angle glaucoma with intraocular pressure levels greater than 21 mmHg, 226 (14.2%) cases of normal-tension glaucoma and 25 (1.6%) cases of primary angle-closure glaucoma. Seven glaucoma risk factors were examined as potential confounders but only two needed to be included in the final model. Binary regression using a generalized estimating equation method, with adjustment for gender, age, city, cataract surgery or diabetes mellitus, revealed an odds ratio at 1 Gy of 1.31 (95% confidence interval 1.11-1.53, P = 0.001) in the case of normal-tension glaucoma, but no association for other types of glaucoma. The prevalence of normal-tension glaucoma may increase with A-bomb radiation dose, but uncertainties associated with nonparticipation (59% participation) suggest caution in the interpretation of these results until they are confirmed by other studies.

Alanine/EPR dosimetry applied to the verification of a total body irradiation protocol and treatment planning dose calculation using a humanoid phantom

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

Schaeken, B.; Lelie, S.; Meijnders, P.

2010-12-15

Purpose: To avoid complications in total body irradiation (TBI), it is important to achieve a homogeneous dose distribution throughout the body and to deliver a correct dose to the lung which is an organ at risk. The purpose of this work was to validate the TBI dose protocol and to check the accuracy of the 3D dose calculations of the treatment planning system. Methods: Dosimetry based on alanine/electron paramagnetic resonance (EPR) was used to measure dose at numerous locations within an anthropomorphic phantom (Alderson) that was irradiated in a clinical TBI beam setup. The alanine EPR dosimetry system was calibratedmore » against water calorimetry in a Co-60 beam and the absorbed dose was determined by the use of ''dose-normalized amplitudes'' A{sub D}. The dose rate of the TBI beam was checked against a Farmer ionization chamber. The phantom measurements were compared to 3D dose calculations from a treatment planning system (Pinnacle) modeled for standard dose calculations. Results: Alanine dosimetry allowed accurate measurements which were in accordance with ionization chamber measurements. The combined relative standard measurement uncertainty in the Alderson phantom was U{sub r}(A{sub D})=0.6%. The humanoid phantom was irradiated to a reference dose of 10 Gy, limiting the lung dose to 7.5 Gy. The ratio of the average measured dose midplane in the craniocaudal direction to the reference dose was 1.001 with a spread of {+-}4.7% (1 sd). Dose to the lung was measured in 26 locations and found, in average, 1.8% lower than expected. Lung dose was homogeneous in the ventral-dorsal direction but a dose gradient of 0.10 Gy cm{sup -1} was observed in the craniocaudal direction midline within the lung lobe. 3D dose calculations (Pinnacle) were found, in average, 2% lower compared to dose measurements on the body axis and 3% lower for the lungs. Conclusions: The alanine/EPR dosimetry system allowed accurate dose measurements which enabled the authors to validate their TBI dose protocol. Dose calculations based on a collapsed cone convolution dose algorithm modeled for regular treatments are accurate within 3% and can further be improved when the algorithm is modeled for TBI.« less

Applications of IMAT in cervical esophageal cancer radiotherapy: a comparison with fixed-field IMRT in dosimetry and implementation.

PubMed

Yin, Yong; Chen, Jinhu; Xing, Ligang; Dong, Xiaoling; Liu, Tonghai; Lu, Jie; Yu, Jinming

2011-01-13

This study aimed to compare fixed-field, intensity-modulated radiotherapy (f-IMRT) with intensity-modulated arc therapy (IMAT) treatment plans in dosimetry and practical application for cervical esophageal carcinoma. For ten cervical esophageal carcinoma cases, f-IMRT plan (seven fixed-fields) and two IMAT plans, namely RA (coplanar 360° arcs) and RAx (coplanar 360° arcs without sectors from 80° to 110°, and 250° to 280°), were generated. DVHs were adopted for the statistics of above parameters, as well as conformal index (CI), homogeneity index (HI), dose-volumetric parameters of normal tissues, total accelerator output MUs and total treatment time. There were differences between RAx and f-IMRT, as well as RA in PTV parameters such as HI, V(95%) and V(110%), but not in CI. RAx reduced lung V₅ from (50.9% ± 9.8% in f-IMRT and (51.4% ± 10.8% in RA to (49.3% ± 10.4% in RAx (p < 0.05). However, lung V₃₀, V₄₀, V₅₀ and MLD increased in RAx. There was no difference in the mean heart dose in three plans. Total MU was reduced from 1174.8 ± 144.6 in f-IMRT to 803.8 ± 122.2 in RA and 736.2 ± 186.9 in RAx (p < 0.05). Compared with f-IMRT, IMAT reduced low dose volumes of lung and total MU on the basis of meeting clinical requirements.

Improving the Estimation of Mealtime Insulin Dose in Adults With Type 1 Diabetes

PubMed Central

Bao, Jiansong; Gilbertson, Heather R.; Gray, Robyn; Munns, Diane; Howard, Gabrielle; Petocz, Peter; Colagiuri, Stephen; Brand-Miller, Jennie C.

2011-01-01

OBJECTIVE Although carbohydrate counting is routine practice in type 1 diabetes, hyperglycemic episodes are common. A food insulin index (FII) has been developed and validated for predicting the normal insulin demand generated by mixed meals in healthy adults. We sought to compare a novel algorithm on the basis of the FII for estimating mealtime insulin dose with carbohydrate counting in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS A total of 28 patients using insulin pump therapy consumed two different breakfast meals of equal energy, glycemic index, fiber, and calculated insulin demand (both FII = 60) but approximately twofold difference in carbohydrate content, in random order on three consecutive mornings. On one occasion, a carbohydrate-counting algorithm was applied to meal A (75 g carbohydrate) for determining bolus insulin dose. On the other two occasions, carbohydrate counting (about half the insulin dose as meal A) and the FII algorithm (same dose as meal A) were applied to meal B (41 g carbohydrate). A real-time continuous glucose monitor was used to assess 3-h postprandial glycemia. RESULTS Compared with carbohydrate counting, the FII algorithm significantly decreased glucose incremental area under the curve over 3 h (–52%, P = 0.013) and peak glucose excursion (–41%, P = 0.01) and improved the percentage of time within the normal blood glucose range (4–10 mmol/L) (31%, P = 0.001). There was no significant difference in the occurrence of hypoglycemia. CONCLUSIONS An insulin algorithm based on physiological insulin demand evoked by foods in healthy subjects may be a useful tool for estimating mealtime insulin dose in patients with type 1 diabetes. PMID:21949219

A statistical model of catheter motion from interventional x-ray images: application to image-based gating

NASA Astrophysics Data System (ADS)

Panayiotou, M.; King, A. P.; Ma, Y.; Housden, R. J.; Rinaldi, C. A.; Gill, J.; Cooklin, M.; O'Neill, M.; Rhode, K. S.

2013-11-01

The motion and deformation of catheters that lie inside cardiac structures can provide valuable information about the motion of the heart. In this paper we describe the formation of a novel statistical model of the motion of a coronary sinus (CS) catheter based on principal component analysis of tracked electrode locations from standard mono-plane x-ray fluoroscopy images. We demonstrate the application of our model for the purposes of retrospective cardiac and respiratory gating of x-ray fluoroscopy images in normal dose x-ray fluoroscopy images, and demonstrate how a modification of the technique allows application to very low dose scenarios. We validated our method on ten mono-plane imaging sequences comprising a total of 610 frames from ten different patients undergoing radiofrequency ablation for the treatment of atrial fibrillation. For normal dose images we established systole, end-inspiration and end-expiration gating with success rates of 100%, 92.1% and 86.9%, respectively. For very low dose applications, the method was tested on the same ten mono-plane x-ray fluoroscopy sequences without noise and with added noise at signal to noise ratio (SNR) values of √50, √10, √8, √6, √5, √2 and √1 to simulate the image quality of increasingly lower dose x-ray images. The method was able to detect the CS catheter even in the lowest SNR images with median errors not exceeding 2.6 mm per electrode. Furthermore, gating success rates of 100%, 71.4% and 85.7% were achieved at the low SNR value of √2, representing a dose reduction of more than 25 times. Thus, the technique has the potential to extract useful information whilst substantially reducing the radiation exposure.

Reduction of severe visual loss and complications following intra-arterial chemotherapy (IAC) for refractory retinoblastoma.

PubMed

Reddy, M Ashwin; Naeem, Zishan; Duncan, Catriona; Robertson, Fergus; Herod, Jane; Rennie, Adam; Liasis, Alki; Thompson, Dorothy Ann; Sagoo, Mandeep

2017-12-01

Intra-arterial chemotherapy (IAC) for retinoblastoma has been documented as causing visual loss and ocular motility problems. A lack of safety data has precluded its acceptance in all centres. Retrospective cohort study of patients with retinoblastoma from 2013 to 2015 who had a healthy foveola and relapsed following systemic chemotherapy. All required IAC. The correlation of complications with doses of melphalan +/- topotecan used and putative catheterisation complications was assessed. Ocular complications were determined using vision, macular (including pattern visual evoked potentials (PVEPs)), retinal electroretinograms (ERGs) and ocular motility functions. Efficacy (tumour control) was also assessed. All eyes had age appropriate doses of melphalan with five having additional doses of topotecan. Severe physiological reactions requiring adrenaline were seen in six patients during the catheterisation procedure. Difficulty was documented in accessing the ophthalmic artery in 7/27 catheterisations. The median/mean number of courses of chemotherapy was three. No child had severe visual loss as assessed by age appropriate tests (median follow-up 20.9 months, range 3.7-35.2 months). One child had nasal choroidal ischaemia and a sixth nerve palsy. Post-IAC PVEPs were performed in eight and reported as normal. All post-IAC ERGs were normal apart from one (total dose 20 mg melphalan 0.8 mg topotecan). Tumour control was achieved in six of nine cases. The proportion of visual and ocular motility complications may be reduced by providing age-adjusted doses of melphalan. Dose rather than complications from catheterisation is the most important risk factor for ocular injury. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

SU-E-J-83: CBCT Based Rectum and Bladder Dose Tracking in the Prostate Radiotherapy

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

Chen, Z; Wang, J; Yang, Z

2015-06-15

Purpose: The aim of this study is to monitor the volume changes of bladder and rectum and evaluate the dosimetric changes of bladder and rectum using daily cone-beam CT for prostate radiotherapy. Methods: The data of this study were obtained from 12 patients, totally 222 CBCTs. All the volume of the bladder and the rectum on the CBCT were normalized to the bladder and the rectum on their own original CT to monitory the volume changes. To evaluate dose delivered to the OARs, volumes that receive 70Gy (V70Gy), 60Gy, 50Gy, 40Gy and 30Gy are calculated for the bladder and themore » rectum, V20Gy and V10Gy for rectum additionally. And the deviation of the mean dose to the bladder and the rectum are also chosen as the evaluation parameter. Linear regression analysis was performed to identify the mean dose change of the volume change using SPSS 19. Results: The results show that the variances of the normalize volume of the bladder and the rectum are 0.15–0.58 and 0.13–0.50. The variances of V70Gy, V60Gy, V50Gy, V40Gy and V30Gy of bladder are bigger than rectum for 11 patients. The linear regression analysis indicated a negative correlation between the volume and the mean dose of the bladder (p < 0.05). A 10% increase in bladder volume will cause 5.1% (±4.3%) reduction in mean dose. Conclusion: The bladder volume change is more significant than that for rectum for the prostate cancer patient. The volume changes of rectum are not significant except air gap in the rectum. Bladder volume varies will cause significant dose change. The bladder volume monitoring before fractional treatment delivery would be crucial for accuracy dose delivery.« less

Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study.

PubMed

Brown, Jennifer; Plummer, Ruth; Bauer, Todd M; Anthony, Stephen; Sarantopoulos, John; De Vos, Filip; White, Mike; Schupp, Marco; Ou, Ying; Vaishampayan, Ulka

2017-01-01

Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles. The primary objective was to assess the influence of hepatic impairment on carfilzomib PK following 27 and 56 mg/m 2 doses. The majority of patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since patients with multiple myeloma do not tend to have severe hepatic impairment in the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14 moderate, and 4 severe hepatic impairment patients were enrolled. Compared with patients with normal hepatic function, patients with mild and moderate hepatic impairment had 44 and 26% higher carfilzomib AUC 0-last , respectively (27 mg/m 2 dose); increases at the 56 mg/m 2 dose were 45 and 21%, respectively. Considerable PK variability (% coefficient of variation in AUC ≤100%) was discerned and no consistent trend of increasing exposure resulting from increasing hepatic impairment severity (moderate vs. mild) was seen. The observed adverse event (AE) profile in patients of mostly solid tumors was consistent with the known safety profile of carfilzomib, with the exception of an increased frequency of AEs consistent with hepatic function abnormalities. In this population of primarily advanced solid tumor patients, patients with mild and moderate hepatic impairment had approximately 20-50% higher carfilzomib AUC vs. normal hepatic function patients. These increases are unlikely to be clinically significant, in light of the intrinsic PK variability and exposure-response relationship of carfilzomib. Trial registration http://clinicaltrials.gov NCT01949545; date of registration: September 6, 2013.

Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats.

PubMed

Singh, Santosh Kumar; Kesari, Achyut Narayan; Gupta, Rajesh Kumar; Jaiswal, Dolly; Watal, Geeta

2007-11-01

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.

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

Marsh, I; Otto, M; Weichert, J

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical {sup 131}I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the {sup 124}124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of {sup 124}I-CLR1404 were used to predict therapeutic doses from {sup 131}I-CLR1404 at each timemore » point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.« less

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy.

PubMed

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue; Wu, Yuan-Hung

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting.

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy

PubMed Central

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting. PMID:28662135

Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data

PubMed Central

Cammà, C; Bruno, S; Schepis, F; Lo Iacono, O; Andreone, P; Gramenzi, A G; Mangia, A; Andriulli, A; Puoti, M; Spadaro, A; Freni, M; Di Marco, V; Cino, L; Saracco, G; Chiesa, A; Crosignani, A; Caporaso, N; Morisco, F; Rumi, M G; Craxì, A

2002-01-01

Background and aims: Retreatment with a combination of α interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies. Methods: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000–1200 mg/daily depending on body weight) was given for 24–60 (mean 39.5) weeks. Results: Biochemical end of treatment and sustained responses were observed in 271/581 (46.6%; 95% confidence interval (CI) 42.6–50.7%) and in 109/581 (18.7%; 95% CI 15.6–22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% CI 34.6–42.9%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7%; 95% CI 12.8–18.8%). Fifty four of 581 patients (9.2%; 95% CI 7.0–11.7%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment γ-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008). Conclusions: The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal γ-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%. PMID:12427791

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

Ai, H; Zhang, H

Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant thatmore » represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients.« less

Exposure to Hexavalent Chromium Resulted in Significantly Higher Tissue Chromium Burden Compared With Trivalent Chromium Following Similar Oral Doses to Male F344/N Rats and Female B6C3F1 Mice

PubMed Central

Collins, Bradley J.; Stout, Matthew D.; Levine, Keith E.; Kissling, Grace E.; Fennell, Timothy R.; Walden, Ramsey; Abdo, Kamal; Pritchard, John B.; Fernando, Reshan A.; Burka, Leo T.; Hooth, Michelle J.

2010-01-01

In National Toxicology Program 2-year studies, hexavalent chromium [Cr(VI)] administered in drinking water was clearly carcinogenic in male and female rats and mice, resulting in small intestine epithelial neoplasms in mice at a dose equivalent to or within an order of magnitude of human doses that could result from consumption of chromium-contaminated drinking water, assuming that dose scales by body weight3/4 (body weight raised to the 3/4 power). In contrast, exposure to trivalent chromium [Cr(III)] at much higher concentrations may have been carcinogenic in male rats but was not carcinogenic in mice or female rats. As part of these studies, total chromium was measured in tissues and excreta of additional groups of male rats and female mice. These data were used to infer the uptake and distribution of Cr(VI) because Cr(VI) is reduced to Cr(III) in vivo, and no methods are available to speciate tissue chromium. Comparable external doses resulted in much higher tissue chromium concentrations following exposure to Cr(VI) compared with Cr(III), indicating that a portion of the Cr(VI) escaped gastric reduction and was distributed systemically. Linear or supralinear dose responses of total chromium in tissues were observed following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction capacity. When Cr(VI) exposure was normalized to ingested dose, chromium concentrations in the liver and glandular stomach were higher in mice, whereas kidney concentrations were higher in rats. In vitro studies demonstrated that Cr(VI), but not Cr(III), is a substrate of the sodium/sulfate cotransporter, providing a partial explanation for the greater absorption of Cr(VI). PMID:20843897

Exposure to hexavalent chromium resulted in significantly higher tissue chromium burden compared with trivalent chromium following similar oral doses to male F344/N rats and female B6C3F1 mice.

PubMed

Collins, Bradley J; Stout, Matthew D; Levine, Keith E; Kissling, Grace E; Melnick, Ronald L; Fennell, Timothy R; Walden, Ramsey; Abdo, Kamal; Pritchard, John B; Fernando, Reshan A; Burka, Leo T; Hooth, Michelle J

2010-12-01

In National Toxicology Program 2-year studies, hexavalent chromium [Cr(VI)] administered in drinking water was clearly carcinogenic in male and female rats and mice, resulting in small intestine epithelial neoplasms in mice at a dose equivalent to or within an order of magnitude of human doses that could result from consumption of chromium-contaminated drinking water, assuming that dose scales by body weight(3/4) (body weight raised to the 3/4 power). In contrast, exposure to trivalent chromium [Cr(III)] at much higher concentrations may have been carcinogenic in male rats but was not carcinogenic in mice or female rats. As part of these studies, total chromium was measured in tissues and excreta of additional groups of male rats and female mice. These data were used to infer the uptake and distribution of Cr(VI) because Cr(VI) is reduced to Cr(III) in vivo, and no methods are available to speciate tissue chromium. Comparable external doses resulted in much higher tissue chromium concentrations following exposure to Cr(VI) compared with Cr(III), indicating that a portion of the Cr(VI) escaped gastric reduction and was distributed systemically. Linear or supralinear dose responses of total chromium in tissues were observed following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction capacity. When Cr(VI) exposure was normalized to ingested dose, chromium concentrations in the liver and glandular stomach were higher in mice, whereas kidney concentrations were higher in rats. In vitro studies demonstrated that Cr(VI), but not Cr(III), is a substrate of the sodium/sulfate cotransporter, providing a partial explanation for the greater absorption of Cr(VI).

A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

PubMed

Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

2005-08-01

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

Low incidence of new biochemical hypogonadism after intensity modulated radiation therapy for prostate cancer.

PubMed

Markovina, Stephanie; Weschenfelder, Débora Cristina; Gay, Hiram; McCandless, Audrey; Carey, Bethany; DeWees, Todd; Knutson, Nels; Michalski, Jeff

2014-01-01

To evaluate serum testosterone and the incidence of biochemical hypogonadism in men treated with intensity modulated radiation therapy (IMRT) for prostate cancer. Serum testosterone was evaluated prospectively in 51 men at pretreatment and at 6-month time points for 2 years posttreatment with IMRT for prostate cancer. Forty-one patients (80%) were treated with definitive intent and 10 patients with postprostatectomy radiation to median total doses of 7380 cGy and 6480 cGy, respectively. No patients received hormone therapy within 12 months of any serum testosterone value. Biochemical hypogonadism was defined as a total serum testosterone level ≤ 300 ng/dL. Incidental testicular dose was calculated using planning software when computed tomography information was available (n = 21) and using a published method of estimation when not available (n = 24), and was available for 45 patients. A statistically significant decrease in testosterone, though small in magnitude, was seen at 6 months after completion of therapy, with no significant difference by 1 year after completion of therapy. There was no increase in biochemical hypogonadism after IMRT. Below-normal pretreatment testosterone was not associated with a transient decrease. Estimated cumulative testicular dose, including dose from daily imaging, was not associated with a change in testosterone, nor was radiation therapy prescription dose or treatment intent (postoperative vs definitive). The mild transient decrease in serum testosterone following IMRT monotherapy for prostate cancer is not associated with new biochemical hypogonadism.

SUMMARY OF FRUIT IRRADIATION AT WAGENINGEN

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

de Zeeuw, D.

Use was made of l Mev electrons produced by a normal Van de Graaff accelerator in fresh soft fruit. In order to obtain an even dose distribution over the surface of fruit, it was packed one layer thick in small plastic boxes. Both upper and lower sides of these boxes were irradiated. In case of firmer fruit species, such as plums, these were also placed on mechanically driven rollers on which they were slowly rotated during irradiation. With this method the irradiation time was chosen twice as long as for the packed fruit so as to meet the total dosemore » requirement. Dosimetry measurements were made by both chemical and physical methods. The dose rate was 2 Krad per second. Results obtained with 100 to 500 Krad doses are given for strawberries, raspberries, red and black currants, blackberries, cherries, and plums. (auth)« less

Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

NASA Astrophysics Data System (ADS)

Stavreva, N.; Stavrev, P.; Warkentin, B.; Fallone, B. G.

2002-10-01

This paper presents a complete set of formulae for the position (D50) and the normalized slope (γ50) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction.

Dose-Fractionation Sensitivity of Prostate Cancer Deduced From Radiotherapy Outcomes of 5,969 Patients in Seven International Institutional Datasets: {alpha}/{beta} = 1.4 (0.9-2.2) Gy

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

Miralbell, Raymond, E-mail: Raymond.Miralbell@hcuge.ch; Institut Oncologic Teknon, Barcelona; Roberts, Stephen A.

2012-01-01

Purpose: There are reports of a high sensitivity of prostate cancer to radiotherapy dose fractionation, and this has prompted several trials of hypofractionation schedules. It remains unclear whether hypofractionation will provide a significant therapeutic benefit in the treatment of prostate cancer, and whether there are different fractionation sensitivities for different stages of disease. In order to address this, multiple primary datasets have been collected for analysis. Methods and Materials: Seven datasets were assembled from institutions worldwide. A total of 5969 patients were treated using external beams with or without androgen deprivation (AD). Standard fractionation (1.8-2.0 Gy per fraction) was usedmore » for 40% of the patients, and hypofractionation (2.5-6.7 Gy per fraction) for the remainder. The overall treatment time ranged from 1 to 8 weeks. Low-risk patients comprised 23% of the total, intermediate-risk 44%, and high-risk 33%. Direct analysis of the primary data for tumor control at 5 years was undertaken, using the Phoenix criterion of biochemical relapse-free survival, in order to calculate values in the linear-quadratic equation of k (natural log of the effective target cell number), {alpha} (dose-response slope using very low doses per fraction), and the ratio {alpha}/{beta} that characterizes dose-fractionation sensitivity. Results: There was no significant difference between the {alpha}/{beta} value for the three risk groups, and the value of {alpha}/{beta} for the pooled data was 1.4 (95% CI = 0.9-2.2) Gy. Androgen deprivation improved the bNED outcome index by about 5% for all risk groups, but did not affect the {alpha}/{beta} value. Conclusions: The overall {alpha}/{beta} value was consistently low, unaffected by AD deprivation, and lower than the appropriate values for late normal-tissue morbidity. Hence the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy schedules for all risk groups, which is also very beneficial logistically in limited-resource settings.« less

A randomized controlled trial of preprocedure administration of parecoxib for therapeutic endoscopic retrograde cholangiopancreatography.

PubMed

Amornyotin, Somchai; Chalayonnawin, Wiyada; Kongphlay, Siriporn

2012-01-01

Parecoxib is occasionally used for analgesia in postprocedural patients. The clinical efficacy of parecoxib used for endoscopic retrograde cholangiopancreatography (ERCP) is controversial. The aim of the study was to determine the clinical efficacy of preprocedure administration of parecoxib for therapeutic ERCP patients. Eighty-five patients who underwent therapeutic ERCP in a single year were randomly assigned to normal saline group (C, n = 43) and parecoxib group (P, n = 42). Patients in group C received normal saline and those in group P received 40 mg of parecoxib intravenously in equivalent volume. Patients in both groups received the saline or parecoxib 60 seconds before administration of the sedative agents. All patients were monitored for the depth of sedation by using the Narcotrend(TM) monitor, maintaining stage D0-E0 during ERCP. All patients were oxygenated with 100% O(2) via nasal cannula and sedated with 0.03 mg/kg of intravenous midazolam and 1 μg/kg of intravenous fentanyl as well as the titration of intravenous propofol. After the ERCP procedure, pethidine in an intramuscular dose of 0.5-1.0 mg/kg was used as rescue medication. The pain scores (visual analog scale [VAS], 0-10) at 2, 12, and 24 hours post-ERCP, the total number of doses of pethidine used, the dose volume of pethidine used, patient satisfaction, endoscopist satisfaction, and complications were recorded. There were no significant differences in sedative and analgesic agents used during the procedure, pain at 24 hours post-ERCP, endoscopist satisfaction, and complications in both groups. The total number of doses of pethidine used post-ERCP in group C was significantly higher than in group P. Additionally, the mean pain score at 2 and 12 hours post-ERCP in group C was significantly greater than in group P. Patient satisfaction in group P was higher than in group C. Preprocedure administration of parecoxib for therapeutic ERCP patients was clinically effective. The analgesic efficacy of a standard dose of parecoxib was clearly demonstrated during the first 12 hours postprocedure. Additionally, patient satisfaction in the parecoxib group was also higher than in the control group.

MCNP simulation of radiation doses distributions in a water phantoms simulating interventional radiology patients

NASA Astrophysics Data System (ADS)

He, Wenjun; Mah, Eugene; Huda, Walter; Selby, Bayne; Yao, Hai

2011-03-01

Purpose: To investigate the dose distributions in water cylinders simulating patients undergoing Interventional Radiological examinations. Method: The irradiation geometry consisted of an x-ray source, dose-area-product chamber, and image intensifier as currently used in Interventional Radiology. Water cylinders of diameters ranging between 17 and 30 cm were used to simulate patients weighing between 20 and 90 kg. X-ray spectra data with peak x-ray tube voltages ranging from 60 to 120 kV were generated using XCOMP3R. Radiation dose distributions inside the water cylinder (Dw) were obtained using MCNP5. The depth dose distribution along the x-ray beam central axis was normalized to free-in-air air kerma (AK) that is incident on the phantom. Scattered radiation within the water cylinders but outside the directly irradiated region was normalized to the dose at the edge of the radiation field. The total absorbed energy to the directly irradiated volume (Ep) and indirectly irradiated volume (Es) were also determined and investigated as a function of x-ray tube voltage and phantom size. Results: At 80 kV, the average Dw/AK near the x-ray entrance point was 1.3. The ratio of Dw near the entrance point to Dw near the exit point increased from ~ 26 for the 17 cm water cylinder to ~ 290 for the 30 cm water cylinder. At 80 kV, the relative dose for a 17 cm water cylinder fell to 0.1% at 49 cm away from the central ray of the x-ray beam. For a 30 cm water cylinder, the relative dose fell to 0.1% at 53 cm away from the central ray of the x-ray beam. At a fixed x-ray tube voltage of 80 kV, increasing the water cylinder diameter from 17 to 30 cm increased the Es/(Ep+Es) ratio by about 50%. At a fixed water cylinder diameter of 24 cm, increasing the tube voltage from 60 kV to 120 kV increased the Es/(Ep+Es) ratio by about 12%. The absorbed energy from scattered radiation was between 20-30% of the total energy absorbed by the water cylinder, and was affected more by patient size than x-ray beam energy. Conclusion: MCNP offers a powerful tool to study the absorption and transmission of x-ray energy in phantoms that can be designed to represent patients undergoing Interventional Radiological procedures. This ability will permit a systematic investigation of the relationship between patient dose and diagnostic image quality, and thereby keep patient doses As Low As Reasonably Achievable (ALARA).

Phthalate exposure, even below US EPA reference doses, was associated with semen quality and reproductive hormones: Prospective MARHCS study in general population.

PubMed

Chen, Qing; Yang, Huan; Zhou, Niya; Sun, Lei; Bao, Huaqiong; Tan, Lu; Chen, Hongqiang; Ling, Xi; Zhang, Guowei; Huang, Linping; Li, Lianbing; Ma, Mingfu; Yang, Hao; Wang, Xiaogang; Zou, Peng; Peng, Kaige; Liu, Taixiu; Shi, Xiefei; Feng, Dejian; Zhou, Ziyuan; Ao, Lin; Cui, Zhihong; Cao, Jia

2017-07-01

Environment-Protection-Agency Reference Doses (EPA RfDs) for phthalate intakes are based on limited evidence, especially regarding low-dose male-reproductive toxicity. This study investigates the association between phthalate exposure and semen parameters and reproductive hormones in a general population with low phthalate exposure compared to the EPA RfDs. The MARHCS (Male-Reproductive-Health-in-Chongqing-College-Students) cohort recruited 796 male students, who experienced a relocation of campuses and shifting environmental exposure. Urine, semen and blood before and after the relocation was collected and investigated for: (1) the associations between 13 urinary phthalate metabolites and 11 semen/hormone outcomes (five semen parameters including semen volume, sperm concentration, total sperm number, progressive motility, normal morphology) and six serum reproductive hormones including estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, testosterone; (2) re-analysis of the metabolite-outcome associations in the subjects with estimated phthalate intakes below the RfDs; (3) a change in phthalate metabolites and change in semen/hormone outcomes after the relocation; (4) the association between these changes. (1) All but two semen/hormone outcomes were associated with at least one phthalate metabolite, e.g., each quartile monoethyl phthalate was associated with a 5.3%, 5.7% and 2.6% decrease of sperm concentration, total sperm number and progressive motility respectively. (2) In the subjects with phthalate intakes below the RfDs, these metabolite-outcome associations remained significant. (3) All metabolites except mono(2-ethylhexyl) phthalate declined after relocation (P<0.001 respectively); at the same time, semen volume, normal morphology, estradiol and luteinizing hormone increased (by 5.9%, 25.0%, 34.2% and 10.0%) and testosterone decreased (by 7.0%). (4) The changes in semen volume, normal morphology, estradiol and testosterone, but not the change in luteinizing hormone after relocation, were associated with the changes in the phthalate metabolites. Phthalate exposure is associated with interrupted semen quality and reproductive hormones in the human population even with a dose given below the RfDs. These effects, however, may only partially revert back when exposure decreases, thus emphasizing the urgency of stricter phthalate administration. Copyright © 2017. Published by Elsevier Ltd.

Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant.

PubMed

Parkinson, Craig; Burman, Pia; Messig, Michael; Trainer, Peter J

2007-01-01

To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease. Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects (39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF-I was at least 30% above age-related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant (80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF-I was normalized. At baseline, men had significantly higher mean serum IGF-I levels than women despite similar GH levels. After treatment with pegvisomant, IGF-I levels were similar in men and women. A significant correlation between baseline GH, IGF-I, body weight, and the dose of pegvisomant required to normalize serum IGF-I was observed (all P < 0.001). Women required an average of 0.04 mg/kg more pegvisomant than men and a mean weight-corrected dose of 19.2 mg/d to normalize serum IGF-I [14.5 mg/d (men); P < 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF-I despite similar baseline GH/IGF-I levels (15.2 vs. 18.5 mg/d for no previous radiotherapy; P = 0.002). Sex, body weight, previous radiotherapy, and baseline GH/IGF-I influence the dose of pegvisomant required to normalize serum IGF-I in patients with active acromegaly.

Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case-control study in long-term survivors from cancer in the head and neck region.

PubMed

Olsson, Erik; Eckerström, Carl; Berg, Gertrud; Borga, Magnus; Ekholm, Sven; Johannsson, Gudmundur; Ribbelin, Susanne; Starck, Göran; Wysocka, Anna; Löfdahl, Elisabet; Malmgren, Helge

2012-11-29

An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients' lowered QoL was coupled to a reduction in hippocampal volume. Patients (11 men and 4 women, age 31-65) treated for head and neck cancer 4-10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 - 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon's signed rank test were used for the main statistical analysis. There was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients. The study gives solid evidence against the hypothesis that the patients' lowered quality of life was due to a major reduction of hippocampal volume.

Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and Literature Review

PubMed Central

Alswat, Khaled A.

2015-01-01

Patient: Female, 52 Final Diagnosis: Refractory iodine induced hyperthyroidism Symptoms: Neck swelling • shortness of breath Medication: Cholestyramine Clinical Procedure: Total thyroidectomy Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Hyperthyroidism is a common disease that usually responds to the conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta-blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism fails to respond to the above therapy. Cholestyramine has been shown to decrease thyroid hormone level when added to the ongoing anti-thyroidal medications. Case Report: A 52-year-old woman with past medical history of enlarging goiter presented with obstructive symptoms of worsening shortness of breath and snoring. Admission thyroid function test showed mild hyperthyroidism (suppressed TSH, slightly high FT4, and high normal FT3) that worsened after she received a CT scan with contrast and failed to respond to a 3-week course of high-dose dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days after cholestyramine was added, her FT4 decreased by 30% and normalized after 12 days. The patient underwent total thyroidectomy as definitive treatment for the hyperthyroidism and for the obstructive symptoms. Conclusions: Cholestyramine is an effective additional treatment for hyperthyroidism and may be an effective treatment for refractory iodine-induced hyperthyroidism. The possibility of self-remission (natural course) is less likely given the dramatic and rapid response to cholestyramine. PMID:26207323

Is high–dose rate RapidArc-based radiosurgery dosimetrically advantageous for the treatment of intracranial tumors?

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

Zhao, Bo; Yang, Yong, E-mail: yangy2@upmc.edu; Li, Xiang

In linac-based stereotactic radiosurgery (SRS) and radiotherapy (SRT), circular cone(s) or conformal arc(s) are conventionally used to treat intracranial lesions. However, when the target is in close proximity to critical structures, it is frequently quite challenging to generate a quality plan using these techniques. In this study, we investigated the dosimetric characteristics of using high–dose rate RapidArc (RA) technique for radiosurgical treatment of intracranial lesions. A total of 10 intracranial SRS/SRT cases previously planned using dynamic conformal arc (DCA) or cone-based techniques have been included in this study. For each case, 3 treatment plans were generated: (1) a DCA planmore » with multiple noncoplanar arcs, (2) a high–dose rate RA plan with arcs oriented the same as DCA (multiple-arc RA), and 3) a high–dose rate RA plan with a single coplanar arc (single-arc RA). All treatment plans were generated under the same prescription and similar critical structure dose limits. Plan quality for different plans was evaluated by comparing various dosimetric parameters such as target coverage, conformity index (CI), homogeneity index (HI), critical structures, and normal brain tissue doses as well as beam delivery time. With similar critical structure sparing, high–dose rate RA plans can achieve much better target coverage, dose conformity, and dose homogeneity than the DCA plans can. Plan quality indices CI and HI, for the DCA, multiple-arc RA, and single-arc RA techniques, were measured as 1.67 ± 0.39, 1.32 ± 0.28, and 1.38 ± 0.30 and 1.24 ± 0.11, 1.10 ± 0.04, and 1.12 ± 0.07, respectively. Normal brain tissue dose (V{sub 12} {sub Gy}) was found to be similar for DCA and multiple-arc RA plans but much larger for the single-arc RA plans. Beam delivery was similar for DCA and multiple-arc RA plans but shorter with single-arc RA plans. Multiple-arc RA SRS/SRT can provide better treatment plans than conventional DCA plans, especially for complex cases.« less

Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

PubMed

Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

2007-03-01

Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications. Copyright 2007 Prous Science.

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

PubMed

Wang, Jian-tang; Dong, Ming-feng; Song, Guang-min; Ma, Zeng-shan; Ma, Sheng-jun

2014-12-01

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

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

Ene, D.; Andersson, K.; Jensen, M.

The European Spallation Source (ESS) will produce tritium via spallation and activation processes during operational activities. Within the location of ESS facility in Lund, Sweden site it is mandatory to demonstrate that the management strategy of the produced tritium ensures the compliance with the country regulation criteria. The aim of this paper is to give an overview of the different aspects of the tritium management in ESS facility. Besides the design parameter study of the helium coolant purification system of the target the consequences of the tritium releasing into the environment were also analyzed. Calculations show that the annual releasemore » of tritium during the normal operations represents a small fraction from the estimated total dose. However, more refined calculations of migration of activated-groundwater should be performed for higher hydraulic conductivities, with the availability of the results on soil examinations. With the assumption of 100% release of tritium to the atmosphere during the occurring of the extreme accidents, it was found as well that the total dose complies with the constraint. (authors)« less

Implantation of programmable infusion pumps for insulin delivery in type I diabetic patients.

PubMed

Walter, H; Günther, A; Kronski, D; Flaschenträger, T; Mehnert, H

1989-06-01

Five type I diabetic patients were followed prospectively during treatment with continuous subcutaneous insulin infusion by externally worn pumps and during the first 12 months after implantation of a remote-controlled insulin infusion device (ID1, Siemens AG). Stabilized insulin (Hoe 21 GH, Hoechst AG) was infused intravenously in two and intraperitoneally in three patients. Total observation time was 47.2 patient-months after implantation. Two devices had to be explanted prematurely, one because of a technical failure after 101 days, one due to a skin necrosis over the implant after 236 days. HbA1, frequency of hypoglycemia, total insulin dose, and basal rate infusion did not change after implantation. There was a reduction in the insulin antibodies 6 months after start of intravenous or intraperitoneal insulin delivery. Fasting plasma free insulin levels could be normalized only by intraperitoneal insulin infusion. Although a technical and a surgical problem was observed, our data show the successful implantation and clinical use of programmable dosing devices and stabilized insulin.

Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

PubMed

Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

1998-06-01

Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.

Risks of secondary malignancies with heterotopic bone radiation therapy for patients younger than 40 years

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

Cadieux, Catherine L., E-mail: ccadieux@umail.iu.edu; DesRosiers, Colleen; McMullen, Kevin

Heterotopic ossification (HO) of the bone is defined as a benign condition in which abnormal bone formation occurs in soft tissue. One of the most common prophylactic treatments for HO is radiation therapy (RT). This study retrospectively reviewed 20 patients younger than the age of 40 who received radiation to prevent HO in a single fraction of 7 Gray. The purpose of this study is to assess the risk of a second malignancy in these patients by recreating their treatment fields and contouring organs at risk to estimate the radiation dose absorbed by normal tissues outside the radiation treatment field.more » Diagnostic computed tomography (CT) scans for each patient were used to recreate treatment fields and to calculate dose to structures of interest. The distance from the field edge to each structure and its depth was recorded. Dose measurements in a water phantom were performed for the range of depths, distances, and field sizes used in the actual treatment plans. Computer-generated doses were compared to estimates based on measurement. The structure dose recorded was the higher dose generated between the 2 methods. Scatter dose was recorded to the rectum, bladder, sigmoid colon, small bowel, ovaries and utero-cervix in female patients, and prostate and gonads in male patients. In some patients, there is considerable dose received by certain organs from scatter because of their proximity to the radiation field. The average dose to the ovarian region was 4.125 Gy with a range of 1.085 to 6.228 Gy. The risk estimate for these patients ranged from 0.16% to 0.93%. The average total lifetime risk estimate for the bladder in all patients is 0.22% and the average total lifetime risk estimate for the remainder organs in all patients is 1.25%. In conclusions, proper shielding created from multileaf collimators (MLCs), blocks, and shields should always be used when possible.« less

Gold nanoparticle‐based brachytherapy enhancement in choroidal melanoma using a full Monte Carlo model of the human eye

PubMed Central

Vaez‐zadeh, Mehdi; Masoudi, S. Farhad; Rahmani, Faezeh; Knaup, Courtney; Meigooni, Ali S.

2015-01-01

The effects of gold nanoparticles (GNPs) in 125I brachytherapy dose enhancement on choroidal melanoma are examined using the Monte Carlo simulation technique. Usually, Monte Carlo ophthalmic brachytherapy dosimetry is performed in a water phantom. However, here, the compositions of human eye have been considered instead of water. Both human eye and water phantoms have been simulated with MCNP5 code. These simulations were performed for a fully loaded 16 mm COMS eye plaque containing 13 125I seeds. The dose delivered to the tumor and normal tissues have been calculated in both phantoms with and without GNPs. Normally, the radiation therapy of cancer patients is designed to deliver a required dose to the tumor while sparing the surrounding normal tissues. However, as the normal and cancerous cells absorbed dose in an almost identical fashion, the normal tissue absorbed radiation dose during the treatment time. The use of GNPs in combination with radiotherapy in the treatment of tumor decreases the absorbed dose by normal tissues. The results indicate that the dose to the tumor in an eyeball implanted with COMS plaque increases with increasing GNPs concentration inside the target. Therefore, the required irradiation time for the tumors in the eye is decreased by adding the GNPs prior to treatment. As a result, the dose to normal tissues decreases when the irradiation time is reduced. Furthermore, a comparison between the simulated data in an eye phantom made of water and eye phantom made of human eye composition, in the presence of GNPs, shows the significance of utilizing the composition of eye in ophthalmic brachytherapy dosimetry Also, defining the eye composition instead of water leads to more accurate calculations of GNPs radiation effects in ophthalmic brachytherapy dosimetry. PACS number: 87.53.Jw, 87.85.Rs, 87.10.Rt PMID:26699318

The impact of inter-fraction dose variations on biological equivalent dose (BED): the concept of equivalent constant dose.

PubMed

Zavgorodni, S

2004-12-07

Inter-fraction dose fluctuations, which appear as a result of setup errors, organ motion and treatment machine output variations, may influence the radiobiological effect of the treatment even when the total delivered physical dose remains constant. The effect of these inter-fraction dose fluctuations on the biological effective dose (BED) has been investigated. Analytical expressions for the BED accounting for the dose fluctuations have been derived. The concept of biological effective constant dose (BECD) has been introduced. The equivalent constant dose (ECD), representing the constant physical dose that provides the same cell survival fraction as the fluctuating dose, has also been introduced. The dose fluctuations with Gaussian as well as exponential probability density functions were investigated. The values of BECD and ECD calculated analytically were compared with those derived from Monte Carlo modelling. The agreement between Monte Carlo modelled and analytical values was excellent (within 1%) for a range of dose standard deviations (0-100% of the dose) and the number of fractions (2 to 37) used in the comparison. The ECDs have also been calculated for conventional radiotherapy fields. The analytical expression for the BECD shows that BECD increases linearly with the variance of the dose. The effect is relatively small, and in the flat regions of the field it results in less than 1% increase of ECD. In the penumbra region of the 6 MV single radiotherapy beam the ECD exceeded the physical dose by up to 35%, when the standard deviation of combined patient setup/organ motion uncertainty was 5 mm. Equivalently, the ECD field was approximately 2 mm wider than the physical dose field. The difference between ECD and the physical dose is greater for normal tissues than for tumours.

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

NASA Technical Reports Server (NTRS)

Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT cells and misrejoined breaks increased in both cell lines. The present study suggests that AT cells begin to rejoin breaks when a certain number of breaks are accumulated and an increased number of exchanges were observed in G0 AT cells, which is similar situation after high-dose-rate irradiation.

Estimation of low-dose radiation-responsive proteins in the absence of genomic instability in normal human fibroblast cells.

PubMed

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Nam, Seon Young; Kim, Cha Soon

2017-11-01

Low-dose radiation has various biological effects such as adaptive responses, low-dose hypersensitivity, as well as beneficial effects. However, little is known about the particular proteins involved in these effects. Here, we sought to identify low-dose radiation-responsive phosphoproteins in normal fibroblast cells. We assessed genomic instability and proliferation of fibroblast cells after γ-irradiation by γ-H2AX foci and micronucleus formation analyses and BrdU incorporation assay, respectively. We screened fibroblast cells 8 h after low-dose (0.05 Gy) γ-irradiation using Phospho Explorer Antibody Microarray and validated two differentially expressed phosphoproteins using Western blotting. Cell proliferation proceeded normally in the absence of genomic instability after low-dose γ-irradiation. Phospho antibody microarray analysis and Western blotting revealed increased expression of two phosphoproteins, phospho-NFκB (Ser536) and phospho-P70S6K (Ser418), 8 h after low-dose radiation. Our findings suggest that low-dose radiation of normal fibroblast cells activates the expression of phospho-NFκB (Ser536) and phospho-P70S6K (Ser418) in the absence of genomic instability. Therefore, these proteins may be involved in DNA damage repair processes.

Positioning accuracy during VMAT of gynecologic malignancies and the resulting dosimetric impact by a 6-degree-of-freedom couch in combination with daily kilovoltage cone beam computed tomography.

PubMed

Yao, Lihong; Zhu, Lihong; Wang, Junjie; Liu, Lu; Zhou, Shun; Jiang, ShuKun; Cao, Qianqian; Qu, Ang; Tian, Suqing

2015-04-26

To improve the delivery of radiotherapy in gynecologic malignancies and to minimize the irradiation of unaffected tissues by using daily kilovoltage cone beam computed tomography (kV-CBCT) to reduce setup errors. Thirteen patients with gynecologic cancers were treated with postoperative volumetric-modulated arc therapy (VMAT). All patients had a planning CT scan and daily CBCT during treatment. Automatic bone anatomy matching was used to determine initial inter-fraction positioning error. Positional correction on a six-degrees-of-freedom (6DoF) couch was followed by a second scan to calculate the residual inter-fraction error, and a post-treatment scan assessed intra-fraction motion. The margins of the planning target volume (MPTV) were calculated from these setup variations and the effect of margin size on normal tissue sparing was evaluated. In total, 573 CBCT scans were acquired. Mean absolute pre-/post-correction errors were obtained in all six planes. With 6DoF couch correction, the MPTV accounting for intra-fraction errors was reduced by 3.8-5.6 mm. This permitted a reduction in the maximum dose to the small intestine, bladder and femoral head (P=0.001, 0.035 and 0.032, respectively), the average dose to the rectum, small intestine, bladder and pelvic marrow (P=0.003, 0.000, 0.001 and 0.000, respectively) and markedly reduced irradiated normal tissue volumes. A 6DoF couch in combination with daily kV-CBCT can considerably improve positioning accuracy during VMAT treatment in gynecologic malignancies, reducing the MPTV. The reduced margin size permits improved normal tissue sparing and a smaller total irradiated volume.

Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model.

PubMed

Garabalino, Marcela A; Monti Hughes, Andrea; Molinari, Ana J; Heber, Elisa M; Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Nievas, Susana; Nigg, David W; Aromando, Romina F; Itoiz, Maria E; Trivillin, Verónica A; Schwint, Amanda E

2011-03-01

We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3. © Springer-Verlag 2010

Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

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

Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari

2011-03-01

Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studiesmore » at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.« less

[A dose-response analysis on the association of gestational weight gain rate and the normal term neonate birth weight].

PubMed

Mao, Yuanyuan; Hu, Wenbin; Liu, Qin; Liu, Li; Li, Yuanming; Shen, Yueping

2015-08-01

To examine the dose-response relationship between gestational weight gain rate and the neonate birth weight. A total of 18 868 women with singleton gestations who delivered between January 2006 and December 2013 were included in this study. Maternal and neonate details of these women were drawn from the Perinatal Monitoring System database. Gestational weight gain rate was defined as the total weight gain during the last and first prenatal care visits divided by the interval weeks. Both Multiple logistic regression analysis and restricted cubic spline methods were performed. Confounding factors included maternal age, education, pre-pregnancy body mass index (BMI), state of residence, parity, gestational weeks of prenatal care entry, and sex of the neonate. The adjusted odds ratio for macrosomia was associated with gestational weight gain rate in lower pre-pregnancy BMI (OR = 3.15, 95% CI: 1.40-7.07), normal (OR = 3.64, 95% CI: 2.84-4.66) or overweight (OR = 2.37, 95% CI: 1.71-3.27). The odds ratios of low birth weight appeared a decrease in those women with lower pre-pregnancy BMI (OR = 0.28, 95% CI: 0.13-0.61) while the normal weight (OR = 0.37, 95% CI: 0.22-0.64) group with gestational weight gain, the rate showed an increase. Association of gestational weight gain rate for macrosomia was found a S-curve in those term delivery women (non-linearity test P < 0.000 1). However, L-curve was observed for low birth weight and gestational weight gain rate in term births (non-linearity test P < 0.000 1). A S-curve was seen between gestational weight gain rate and term delivered macrosomia while L-curve was observed among term delivered low birth weight neonates.

Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study1234

PubMed Central

Miller, Carolyn A; Corbin, Karen D; da Costa, Kerry-Ann; Zhang, Shucha; Zhao, Xueqing; Galanko, Joseph A; Blevins, Tondra; Bennett, Brian J; O'Connor, Annalouise; Zeisel, Steven H

2014-01-01

Background: It is important to understand whether eating eggs, which are a major source of dietary choline, results in increased exposure to trimethylamine-N-oxide (TMAO), which is purported to be a risk factor for developing heart disease. Objective: We determined whether humans eating eggs generate TMAO and, if so, whether there is an associated increase in a marker for inflammation [ie, high-sensitivity C-reactive protein (hsCRP)] or increased oxidation of low-density lipoprotein (LDL). Design: In a longitudinal, double-blind, randomized dietary intervention, 6 volunteers were fed breakfast doses of 0, 1, 2, 4, or 6 egg yolks. Diets were otherwise controlled on the day before and day of each egg dose with a standardized low-choline menu. Plasma TMAO at timed intervals (immediately before and 1, 2, 4, 8, and 24 h after each dose), 24-h urine TMAO, predose and 24-h postdose serum hsCRP, and plasma oxidized LDL were measured. Volunteers received all 5 doses with each dose separated by >2-wk washout periods. Results: The consumption of eggs was associated with increased plasma and urine TMAO concentrations (P < 0.01), with ∼14% of the total choline in eggs having been converted to TMAO. There was considerable variation between individuals in the TMAO response. There was no difference in hsCRP or oxidized LDL concentrations after egg doses. Conclusions: The consumption of ≥2 eggs results in an increased formation of TMAO. Choline is an essential nutrient that is required for normal human liver and muscle functions and important for normal fetal development. Additional study is needed to both confirm the association between TMAO and atherosclerosis and identify factors, microbiota and genetic, that influence the generation of TMAO before policy and medical recommendations are made that suggest reduced dietary choline intake. This trial was registered at clinicaltrials.gov as NCT01906554. PMID:24944063

Harold Knapp and the geography of normal controversy: radioiodine in the historical environment.

PubMed

Kirsch, Scott

2004-01-01

In 1962, after high levels of the isotope Iodine-131 were detected in Utah milk supplies, Dr. Harold Knapp, a mathematician working for the AEC's Division of Biology and Medicine, developed a new model of estimating, first, the relation between a single deposition of radioactive fallout on pasturage and the levels of Iodine-131 in fresh milk and, second, the total dose to human thyroids, resulting from daily intake of the contaminated milk. The implications of Knapp's findings were enormous. They suggested that short-living radioiodine, rather than long-living nuclides such as radiostrontium, posed the greatest hazard from nuclear test fallout and that children raised in Nevada and Utah during the 1950s had been exposed to internal radiation doses far in excess of recommended guidelines. This paper explores the explicit historical revisionism of Knapp's study, his refusal, contra normal AEC practices of knowledge production and spatial representation, to distance himself from the people and places downwind from the Nevada Test Site, and the reactions his work provoked among his AEC colleagues.

Technical Note: Dosimetric evaluation of Monte Carlo algorithm in iPlan for stereotactic ablative body radiotherapy (SABR) for lung cancer patients using RTOG 0813 parameters.

PubMed

Pokhrel, Damodar; Badkul, Rajeev; Jiang, Hongyu; Kumar, Pravesh; Wang, Fen

2015-01-08

For stereotactic ablative body radiotherapy (SABR) in lung cancer patients, Radiation Therapy Oncology Group (RTOG) protocols currently require radiation dose to be calculated using tissue heterogeneity corrections. Dosimetric criteria of RTOG 0813 were established based on the results obtained from non-Monte Carlo (MC) algorithms, such as superposition/convolutions. Clinically, MC-based algorithms are now routinely used for lung SABR dose calculations. It is essential to confirm that MC calculations in lung SABR meet RTOG guidelines. This report evaluates iPlan MC plans for SABR in lung cancer patients using dose-volume histogram normalization per current RTOG 0813 compliance criteria. Eighteen Stage I-II non-small cell lung cancer (NSCLC) patients with centrally located tumors, who underwent MC-based lung SABR with heterogeneity correction using X-ray Voxel Monte Carlo (XVMC) algorithm (BrainLAB iPlan version 4.1.2), were analyzed. Total dose of 60 Gy in 5 fractions was delivered to planning target volume (PTV) with at least V100% = 95%. Internal target volumes (ITVs) were delineated on maximum intensity projection (MIP) images of 4D CT scans. PTV (ITV + 5 mm margin) volumes ranged from 10.0 to 99.9 cc (mean = 36.8 ± 20.7 cc). Organs at risk (OARs) were delineated on average images of 4D CT scans. Optimal clinical MC SABR plans were generated using a combination of non-coplanar conformal arcs and beams for the Novalis-TX consisting of high definition multileaf collimators (MLCs) and 6 MV-SRS (1000 MU/min) mode. All plans were evaluated using the RTOG 0813 high and intermediate dose spillage criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (D2 cm), and percent of normal lung receiving 20 Gy (V20) or more. Other organs-at-risk (OARs) doses were tabulated, including the volume of normal lung receiving 5 Gy (V5), maximum cord dose, dose to < 15 cc of heart, and dose to <5 cc of esophagus. Only six out of 18 patients met all RTOG 0813 compliance criteria. Eight of 18 patients had minor deviations in R100%, four in R50%, and nine in D2 cm. However, only one patient had minor deviation in V20. All other OARs doses, such as maximum cord dose, dose to < 15 cc of heart, and dose to < 5 cc of esophagus, were satisfactory for RTOG criteria, except for one patient, for whom the dose to < 15 cc of heart was higher than RTOG guidelines. The preliminary results for our limited iPlan XVMC dose calculations indicate that the majority (i.e., 2/3) of our patients had minor deviations in the dosimetric guidelines set by RTOG 0813 protocol in one way or another. When using an exclusive highly sophisticated XVMC algorithm, the RTOG 0813 dosimetric compliance criteria such as R100% and D2 cm may need to be revisited. Based on our limited number of patient datasets, in general, about 6% for R100% and 9% for D2 cm corrections could be applied to pass the RTOG 0813 compliance criteria in most of those patients. More patient plans need to be evaluated to make recommendation for R50%. No adjustment is necessary for OAR dose tolerances, including normal lung V20. In order to establish new MC specific dose parameters, further investigation with a large cohort of patients including central, as well as peripheral lung tumors, is anticipated and strongly recommended.

Effects of the Cynanchum wilfordii Ethanol Extract on the Serum Lipid Profile in Hypercholesterolemic Rats.

PubMed

Lee, Hye-Sung; Choi, Jun-Hyeok; Kim, Young-Eon; Kim, In-Ho; Kim, Byoung-Mok; Lee, Chang-Ho

2013-09-01

The purpose of this study was to investigate the effects of the ethanol extract of Cynanchum wilfordii (ECW) on the blood lipid profile of hypercholesterolemic rats. Thirty 7-week-old male Sprague-Dawley rats were allowed free access to either a normal diet (AIN-93 diet), or 1% high-cholesterol diet with or without 0.5% or 1% ECW for 5 weeks. After sacrifice, the rat serum lipid profile was analyzed. The diets containing ECW decreased body weight gains compared to the normal diet. Serum HDL-cholesterol levels of ECW-fed groups were significantly increased in the hypercholesterolemic groups and normal groups (P<0.05). When 1% ECW was fed to the normal group, total cholesterol level was increased. Moreover, treatment of ECW in hypercholesterolemic groups yielded a dose-dependent and highly significant decrease in the atherogenic index as compared to the control. These results suggest that intake of Cynanchum wilfordii may help reduce the risks of hypercholesterolemia by increasing blood HDL-cholesterol and lowering the atherogenic index.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis.

PubMed

Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

2016-12-01

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis. Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides). Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported. Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

Sharpening peripheral dose gradient via beam number enhancement from patient head tilt for stereotactic brain radiosurgery

NASA Astrophysics Data System (ADS)

Chiu, Joshua; Pierce, Marlon; Braunstein, Steve E.; Theodosopoulos, Philip V.; McDermott, Michael W.; Sneed, Penny K.; Ma, Lijun

2016-10-01

Sharp dose fall-off is the hallmark of brain radiosurgery for the purpose of delivering high dose radiation to the target while minimizing peripheral dose to regional normal brain tissue. In this study, a technique was developed to enhance the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter through pre-programmed patient head tilting. This technique was tested in clinical settings on a dedicated brain radiosurgical system (GKPFX, Gamma Knife Perfexion, Elekta Oncology) by comparing dosimetry as well as delivery efficiency for 20 radiosurgical cases previously treated with the system. The 3-fold beam number enhancement (BNE) treatment plans were found to produce nearly identical target volume coverage (absolute value  <  0.5%, P  >  0.2) and dose conformity (BNE CI  =  1.41  ±  0.22 versus 1.41  ±  0.11, P  >  0.99) as the original treatment plans. The total beam-on time for the 3-fold BNE treatment plans were also found to be comparable (<0.5 min or 2%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI  =  2.94  ±  0.27 versus original GI  =  2.98  ±  0.28 P  <  0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 1.7%-3.9% (P  <  0.03). With further 4-5-fold increase in the total number of beams, the absolute gradient index can decrease by as much as  -0.5 in absolute value or  -20% for a treatment. In conclusion, BNE via patient head tilt has been demonstrated to be a clinically suitable and efficient technique for physically sharpening the peripheral dose gradient for brain radiosurgery. This work was presented in part at the 2015 ISRS Congress in Yokohama Japan.

TH-E-BRF-04: Characterizing the Response of Texture-Based CT Image Features for Quantification of Radiation-Induced Normal Lung Damage

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

Krafft, S; Court, L; Briere, T

2014-06-15

Purpose: Radiation induced lung damage (RILD) is an important dose-limiting toxicity for patients treated with radiation therapy. Scoring systems for RILD are subjective and limit our ability to find robust predictors of toxicity. We investigate the dose and time-related response for texture-based lung CT image features that serve as potential quantitative measures of RILD. Methods: Pre- and post-RT diagnostic imaging studies were collected for retrospective analysis of 21 patients treated with photon or proton radiotherapy for NSCLC. Total lung and selected isodose contours (0–5, 5–15, 15–25Gy, etc.) were deformably registered from the treatment planning scan to the pre-RT and availablemore » follow-up CT studies for each patient. A CT image analysis framework was utilized to extract 3698 unique texture-based features (including co-occurrence and run length matrices) for each region of interest defined by the isodose contours and the total lung volume. Linear mixed models were fit to determine the relationship between feature change (relative to pre-RT), planned dose and time post-RT. Results: Seventy-three follow-up CT scans from 21 patients (median: 3 scans/patient) were analyzed to describe CT image feature change. At the p=0.05 level, dose affected feature change in 2706 (73.1%) of the available features. Similarly, time affected feature change in 408 (11.0%) of the available features. Both dose and time were significant predictors of feature change in a total of 231 (6.2%) of the extracted image features. Conclusion: Characterizing the dose and time-related response of a large number of texture-based CT image features is the first step toward identifying objective measures of lung toxicity necessary for assessment and prediction of RILD. There is evidence that numerous features are sensitive to both the radiation dose and time after RT. Beyond characterizing feature response, further investigation is warranted to determine the utility of these features as surrogates of clinically significant lung injury.« less

SU-E-T-21: A D-D Based Neutron Generator System for Boron Neutron Capture Therapy: A Feasibility Study

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

Hsieh, M; Liu, Y; Nie, L

2015-06-15

Purpose: To investigate the feasibility of a deuterium-deuterium (DD) neutron generator for application in boron neutron capture therapy (BNCT) of brain cancer Methods: MCNP simulations were performed using a head phantom and a monoenergetic neutron source, which resembles the point source in a DD generator that emits 2.45-MeV neutrons. Source energies ranging from 5eV to 2.45MeV were simulated to determine the optimal treatment energy. The phantom consisted of soft tissue, brain tissue, skull, skin layer, and a brain tumor of 5 cm in diameter. Tumor depth was varied from 5–10 cm. Boron-10 concentrations of 10 ppm, 15 ppm, and 30more » ppm were used in the soft/brain tissues, skin, and tumor, respectively. The neutron flux required to deliver 60 Gy to the tumor as well as the normal tissue doses were determined. Results: Beam energies between 5eV and 10keV obtained doses with the highest dose ratios (3.3–25.9) between the tumor and the brain at various depths. The dose ratio with 2.45-MeV neutrons ranged from 0.8–6.6. To achieve the desired tumor dose in 40 minutes, the required neutron flux for a DD generator was between 8.8E10 and 5.2E11 n/s and the resulting brain dose was between 2.3 and 18 Gy, depending on the tumor depth. The skin and soft tissue doses were within acceptable tolerances. The boron-neutron interaction accounted for 54–58% of the total dose. Conclusion: This study shows that the DD neutron generator can be a feasible neutron source for BNCT. The required neutron flux for treatment is achievable with the current DD neutron technology. With a well-designed beam shaping assembly and treatment geometry, the neutron flux can be further improved and a 60-Gy prescription can be accurately delivered to the target while maintaining tolerable normal tissue doses. Further experimental studies will be developed and conducted to validate the simulation results.« less

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma.

PubMed

Hirano, Yasuhiro; Onozawa, Masakatsu; Hojo, Hidehiro; Motegi, Atsushi; Zenda, Sadatomo; Hotta, Kenji; Moriya, Shunsuke; Tachibana, Hidenobu; Nakamura, Naoki; Kojima, Takashi; Akimoto, Tetsuo

2018-02-09

The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

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

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

The effect of decreasing computed tomography dosage on radiostereometric analysis (RSA) accuracy at the glenohumeral joint.

PubMed

Fox, Anne-Marie V; Kedgley, Angela E; Lalone, Emily A; Johnson, James A; Athwal, George S; Jenkyn, Thomas R

2011-11-10

Standard, beaded radiostereometric analysis (RSA) and markerless RSA often use computed tomography (CT) scans to create three-dimensional (3D) bone models. However, ethical concerns exist due to risks associated with CT radiation exposure. Therefore, the aim of this study was to investigate the effect of decreasing CT dosage on RSA accuracy. Four cadaveric shoulder specimens were scanned using a normal-dose CT protocol and two low-dose protocols, where the dosage was decreased by 89% and 98%. 3D computer models of the humerus and scapula were created using each CT protocol. Bi-planar fluoroscopy was used to image five different static glenohumeral positions and two dynamic glenohumeral movements, of which a total of five static and four dynamic poses were selected for analysis. For standard RSA, negligible differences were found in bead (0.21±0.31mm) and bony landmark (2.31±1.90mm) locations when the CT dosage was decreased by 98% (p-values>0.167). For markerless RSA kinematic results, excellent agreement was found between the normal-dose and lowest-dose protocol, with all Spearman rank correlation coefficients greater than 0.95. Average root mean squared errors of 1.04±0.68mm and 2.42±0.81° were also found at this reduced dosage for static positions. In summary, CT dosage can be markedly reduced when performing shoulder RSA to minimize the risks of radiation exposure. Standard RSA accuracy was negligibly affected by the 98% CT dose reduction and for markerless RSA, the benefits of decreasing CT dosage to the subject outweigh the introduced errors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of hepatic impairment on the pharmacokinetics of a single dose of cilostazol.

PubMed

Bramer, S L; Forbes, W P

1999-01-01

The pharmacokinetic profiles of cilostazol and its metabolites following a single oral dose of cilostazol 100 mg were compared between individuals with impaired and normal liver function. The study was conducted as a single-centre, open-label, single dose pharmacokinetic and tolerability trial. 12 patients with impaired and compensated liver function were compared with 12 volunteers with normal liver function. Participants in each group were matched for gender, age and weight. Of the 12 patients with hepatic impairment examined in this study, 10 had mild impairment (Child-Pugh class A) and 2 had moderate impairment (Child-Pugh class B). Blood and urine were collected up to 144 hours after drug administration. Pharmacokinetics were determined by noncompartmental methods. Protein binding did not differ between the groups (95.2% healthy volunteers, 94.6% hepatically impaired patients). Mean +/- SD unbound oral clearance of cilostazol decreased by 8.6% because of hepatic impairment (3380 +/- 1400 ml/min in healthy volunteers, 3260 +/- 2030 ml/min in hepatically impaired patients). Total urinary excretion of metabolites was significantly higher in healthy volunteers (26 vs 17% of dose). Overall, the pharmacokinetics of cilostazol and its metabolites, OPC-13213 and OPC-13015, were not substantially different in those with mild and moderate hepatic disease compared with values in healthy volunteers. Except for terminal-phase disposition half-life and apparent terminal-phase volume of distribution for cilostazol, the ratios of geometric means of pharmacokinetic parameters for plasma cilostazol, OPC-13213 and OPC-13015 in those with hepatic impairment versus healthy volunteers were close to 100%. Based on the results of the pharmacokinetic analysis, dose adjustment in patients with mild hepatic impairment is not necessary. However, caution should be exercised when cilostazol is administered to patients with moderate or severe hepatic impairment.

Toll-like Receptor 5 Agonist Protects Mice From Dermatitis and Oral Mucositis Caused by Local Radiation: Implications for Head-and-Neck Cancer Radiotherapy

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

Burdelya, Lyudmila G.; Gleiberman, Anatoli S.; Toshkov, Ilia

2012-05-01

Purpose: Development of mucositis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. We have recently reported that bacterial flagellin, an agonist of Toll-like receptor 5 (TLR5), can protect rodents and primates from acute radiation syndrome caused by total body irradiation. Here we analyzed the radioprotective efficacy of TLR5 agonist under conditions of local, single dose or fractionated radiation treatment. Methods and Materials: Mice received either single-dose (10, 15, 20, or 25 Gy) or fractioned irradiation (cumulative dose up to 30 Gy) of the head-and-neck area with or without subcutaneous injection of pharmacologically optimized flagellin, CBLB502, 30more » min before irradiation. Results: CBLB502 significantly reduced the severity of dermatitis and mucositis, accelerated tissue recovery, and reduced the extent of radiation induced weight loss in mice after a single dose of 15 or 20 Gy but not 25 Gy of radiation. CBLB502 was also protective from cumulative doses of 25 and 30 Gy delivered in two (10 + 15 Gy) or three (3 Multiplication-Sign 10 Gy) fractions, respectively. While providing protection to normal epithelia, CBLB502 did not affect the radiosensitivity of syngeneic squamous carcinoma SCCVII grown orthotopically in mice. Use of CBLB502 also elicited a radiation independent growth inhibitory effect upon TLR5-expressing tumors demonstrated in the mouse xenograft model of human lung adenocarcinoma A549. Conclusion: CBLB502 combines properties of supportive care (radiotherapy adjuvant) and anticancer agent, both mediated via activation of TLR5 signaling in the normal tissues or the tumor, respectively.« less

Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation.

PubMed

Granton, Patrick V; Palma, David A; Louie, Alexander V

2017-01-26

Palliative thoracic radiotherapy is an effective technique to alleviate symptoms of disease burden in advanced-stage lung cancer patients. Previous randomized controlled studies demonstrated a survival benefit in patients with good performance status at radiation doses of 35Gy 10 or greater but with an increased incidence of esophagitis. The objective of this planning study was to assess the potential impact of esophageal-sparing IMRT (ES-IMRT) compared to the current standard of care using parallel-opposed pair beams (POP). In this study, 15 patients with lung cancer treated to a dose of 30Gy in 10 fractions between August 2015 and January 2016 were identified. Radiation treatment plans were optimized using ES-IMRT by limiting the max esophagus point dose to 24Gy. Using published Lyman-Kutcher-Burman normal tissue complication probabilities (LKB-NTCP) models, both plans were evaluated for the likelihood of esophagitis (≥ grade 2) and pneumonitis (≥ grade 2). Using ES-IMRT, the median esophageal and lung mean doses reduced from 16 and 8Gy to 7 and 7Gy, respectively. Using the LKB models, the theoretical probability of symptomatic esophagitis and pneumonitis reduced from 13 to 2%, and from 5 to 3%, respectively. The median normalize total dose (NTD mean) accounting for fraction size for the GTV and PTV of the clinically approved POP plans compared to the ES-IMRT plans were similar. Advanced radiotherapy techniques such as ES-IMRT may have clinical utility in reducing treatment-related toxicity in advanced lung cancer patients. Our data suggests that the rate of esophagitis can be reduced without compromising local control.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

PubMed Central

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance

NASA Astrophysics Data System (ADS)

Gordon, J. J.; Snyder, K.; Zhong, H.; Barton, K.; Sun, Z.; Chetty, I. J.; Matuszak, M.; Ten Haken, R. K.

2015-09-01

In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence. Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP. Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ~20-40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner’s induced repair model. A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.

Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats

PubMed Central

Omidi, Arash; Riahinia, Narges; Montazer Torbati, Mohammad Bagher; Behdani, Mohammad-Ali

2014-01-01

Objectives: Acetaminophen (APAP) toxicity is known to be common and potentially fatal. This study aims to investigate the protective effects of hydroalcoholic extract, remaining from Crocus sativus petals (CSP) against APAP-induced hepatotoxicity by measuring the blood parameters and studying the histopathology of liver in male rats. Materials and Methods: Wister rats (24) were randomly assigned into four groups including: I) healthy, receiving normal saline; II) Intoxicated, receiving only APAP (600 mg/kg); III) pre-treated with low dose of CSP (10 mg /kg) and receiving APAP (600 mg/kg); IV) pre-treated with high dose of CSP (20 mg/kg) and receiving APAP (600 mg/kg). Results: The APAP treatment resulted in higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin, along with lower total protein and albumin concentration than the control group. The administration of CSP with a dose of 20 mg/kg was found to result in lower levels of AST, ALT and bilirubin, with a significant higher concentration of total protein and albumin. The histopathological results regarding liver pathology, revealed sever conditions including cell swelling, severe inflammation and necrosis in APAP-exposed rats, which was quiet contrasting compared to the control group. The pre-treated rats with low doses of ‍CSP showed hydropic degeneration with mild necrosis in centrilobular areas of the liver, while the same subjects with high doses of ‍CSP appeared to have only mild hepatocyte degeneration. Conclusions: Doses of 20 mg/kg of CSP ameliorates APAP–induced acute liver injury in rats. It was concluded that the antioxidant property of CSP resulted in reducing the oxidative stress complications of toxic levels of APAP in intoxicated rats. PMID:25386395

A multicenter study of plasma use in the United States.

PubMed

Triulzi, Darrell; Gottschall, Jerome; Murphy, Edward; Wu, Yanyun; Ness, Paul; Kor, Daryl; Roubinian, Nareg; Fleischmann, Debra; Chowdhury, Dhuly; Brambilla, Donald

2015-06-01

Detailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy. Ten US hospitals collected detailed medical information from the electronic health records for 1 year (2010-2011) for all adult patients transfused with plasma. A total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2-4; range 1-72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5-12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%-75% interquartile range, 1.6-2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4-2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%). This large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used. © 2014 AABB.

A multicenter study of plasma use in the United States

PubMed Central

Triulzi, Darrell; Gottschall, Jerome; Murphy, Edward; Wu, Yanyun; Ness, Paul; Kor, Daryl; Roubinian, Nareg; Fleischmann, Debra; Chowdhury, Dhuly; Brambilla, Donald

2016-01-01

Background Detailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy. Study Design and Methods Ten US hospitals collected detailed medical information from the electronic health records for 1 year (2010-2011) for all adult patients transfused with plasma. Results A total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2-4; range 1-72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5-12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%-75% interquartile range, 1.6-2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4-2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%). Conclusion This large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used. PMID:25522888

Maximizing Tumor Immunity With Fractionated Radiation

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

Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu; Ratikan, Josephine A.; Iwamoto, Keisuke S.

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma}more » enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.« less

Inclusion of dosimetric data as covariates in toxicity-related radiogenomic studies : A systematic review.

PubMed

Yahya, Noorazrul; Chua, Xin-Jane; Manan, Hanani A; Ismail, Fuad

2018-05-17

This systematic review evaluates the completeness of dosimetric features and their inclusion as covariates in genetic-toxicity association studies. Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates. A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity. A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.

Radiation measurements aboard the fourth Gemini flight.

PubMed

Janni, J F; Schneider, M F

1967-01-01

Two special tissue-equivalent ionization chambers and 5 highly sensitive passive dosimetry packages were flown aboard the recent Gemini 4 flight for the purpose of obtaining precise values of instantaneous dose rate, accumulated dose. and shielding effectiveness. This experiment marked the first time that well-defined tissue dose and radiation survey measurements have been carried out in manned spaceflight operations. Since all measurements were accomplished under normal spacecraft environmental conditions, the biological dose resulted primarily from trapped inner Van Allen Belt radiation encountered by the spacecraft in the South Atlantic Anomaly. The experiment determined the particle type, ionizing and penetrating power, and variation with time and position within the Gemini spacecraft. Measured dose rates ranged from 100 mrad/hr for passes penetrating deeply into the South Atlantic Anomaly to less than 0.1 mrad/hr from lower latitude cosmic radiation. The accumulated tissue dose measured by the active ionization chambers, shielded by 0.4 gm/cm2 for the 4-day mission, was 82 mrad. Since the 5 passive dosimetry packages were each located in different positions within the spacecraft, the total mission surface dose measured by these detectors varied from 73 to 27 mrad, depending upon location and shielding. The particles within the spacecraft were recorded in nuclear emulsion, which established that over 90% of the tissue dose was attributable to penetrating protons. This experiment indicates that the radiation environment under shielded conditions at Gemini altitudes was not hazardous.

Brain dose-sparing radiotherapy techniques for localized intracranial germinoma: Case report and literature review of modern irradiation.

PubMed

Leung, H W C; Chan, A L F; Chang, M B

2016-05-01

We examined the effects of intensity-modulated radiation therapy with dose-sparing and avoidance technique on a pediatric patient with localized intracranial germinoma. We also reviewed the literature regarding modern irradiation techniques in relation to late neurocognitive sequelae. A patient with a localized intracranial germinoma in the third ventricle anterior to the pineal gland received a dose-sparing intensity-modulated radiation therapy. The planning was compared to the radiation oncologist's guide of organs at risk and dose constraints for dosimetric analyses. The patient received radiation therapy alone. The total dose was 54Gy delivered in 2.0Gy fractions to the primary tumour and 37Gy in 1.4Gy fractions to whole ventricles using a dose-sculpting plan. Dosimetry analyses showed that dose-sparing intensity-modulated radiation therapy delivered reduced doses to the whole brain, temporal lobes, hippocampi, cochleae, and optic nerves. With a follow-up of 22 months, failure-free survival was 100% for the patient and no adverse events during radiation treatment process. Intensity-modulated radiation therapy with dose sparing and avoidance technique can spare the limbic circuit, central nervous system, and hippocampus for pineal germ cell tumours. This technique reduces the integral dose delivered to the uninvolved normal brain tissues and may reduce late neurocognitive sequelae caused by cranial radiotherapy. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

PubMed Central

Abd Rahman, Azrin N; Tett, Susan E; Abdul Gafor, Halim A; McWhinney, Brett C; Staatz, Christine E

2015-01-01

Aims The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. Methods Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0), maximum concentration (Cmax) and area under the concentration–time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. Results Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l–1 h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l–1, P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l–1 h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l–1 h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l–1 h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). Conclusions This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. PMID:25959850

Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis.

PubMed

Abd Rahman, Azrin N; Tett, Susan E; Abdul Gafor, Halim A; McWhinney, Brett C; Staatz, Christine E

2015-11-01

The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. © 2015 The British Pharmacological Society.

Analgesic efficacy of low-dose intrathecal neostigmine in combination with fentanyl and bupivacaine for total knee replacement surgery

PubMed Central

Jain, Amit; Jain, Kajal; Bhardawaj, Neerja

2012-01-01

Background and Aim: Intrathecal (IT) neostigmine has been used as an adjunct to spinal anesthesia. The purpose of this study was to determine whether a combination of low-dose neostigmine IT would enhance analgesia of a fixed dose of fentanyl IT, in patients undergoing unilateral total knee replacement (TKR) surgery with spinal anesthesia. Settings and Design: Forty-five patients scheduled for unilateral TKR were randomized to one of the three groups (n = 15) and prospectively studied using placebo-controlled, double-blinded design. Materials and Methods: A 19-G epidural catheter was introduced through the L3–L4 interspace with patient in the sitting position, followed by spinal anesthesia administration through the L3–L4 interspace. Fifteen milligrams of hyperbaric bupivacaine (3 ml) plus the test drug (0.5 ml) was administered IT. The test drug was normal saline (0.5 ml) in group I; fentanyl 20 mcg (0.4 ml) and normal saline (0.1 ml) in group II; and fentanyl 20 mcg (0.4 ml) and neostigmine 1 mcg (0.1 ml) in group III. Characteristics of sensory and motor block, heart rate, and blood pressure were recorded intraoperatively. Postoperatively, pain scores, postoperative nausea and vomiting (PONV) scores, and sedation scores, and postoperative analgesic dose were recorded. Results: Forty-five patients were enrolled in this study and 43 patients were subjected to statistical analysis. Overall 24-h visual analog score in group III was significantly less than in those who received fentanyl alone (P = 0.00). The durations of complete analgesia and effective analgesia were longer for all patients in group III compared with group II (P < 0.05) and group I (P < 0.005) patients. The total number of epidural top ups (rescue analgesia) required was less in group II (P < 0.05) and group III (P < 0.005) patients, compared with the control group. The incidence of nausea and vomiting was not increased in group III patients. Conclusions: The addition of 1 mcg neostigmine IT increased the duration of analgesia and decreased the analgesic consumption in 24 h in TKR. There was no increase in the incidence of adverse effects. PMID:23225930

Tissue responses to low protracted doses of high let radiations or photons: Early and late damage relevant to radio-protective countermeasures

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

Ainsworth, E.J.; Afzal, S.M.J.; Crouse, D.A.

1988-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for ..gamma..-radiation. When total doses of 96 or 247 cGy of neutrons or ..gamma.. rays were givenmore » as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and ..gamma..-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. 63 refs., 6 figs., 7 tabs.« less

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

Jeong, K; Basavatia, A; Mynampati, D

Purpose: To compare VMAT SRS plans, dynamic conformal arc (DCA) plans, and Brainlab iPlan’s capability of planning and delivering brain SRS plans by employing HybridArc. HybridArc utilizes both DCA and IMRT. Using HybridArc, the amount of DCA versus IMRT needs to be optimized. Methods: Four SRS patients with the aim of reducing brainstem dose were selected for this study. All patients were contoured in iPlan and transferred to Eclipse for VMAT planning. In iPlan, DCA plans were created for each case. Moreover, nine HybridArc plans with DCA-IMRT ratios between 9:1 through 1:9 were created with a single ring structure generatedmore » by subtracting 3 mm expansion of target from a 10 mm expansion of the target. Two static IMRT beams were used in each of the five DCA arcs for HybridArc. The dose was prescribed to DCA only and HybridArc plans and normalized so that the target volume (TV) receives 100% dose to 99.5% of the TV to achieve 120% ∼ 130% max dose within targets. Following metrics were compared: PITV, V12Gy, CGIc, CGIg, CGI, brainstem max dose, and total monitor units (MUs). Results: A brainstem max dose comparable with VMAT from 30% IMRT and less with 50% or more IMRT could be achieved. PITV decreased with increasing IMRT portion and begins to saturate past an IMRT portion of 30%. The CGIg index, which represents how fast the dose falls off, was better with HybridArc in all HybridArc plans. Total MUs increased with increasing IMRT but less than VMAT in all cases. Conclusion: Overall, a lower brainstem max dose and a lower V12Gy with fewer MUs can be achieved with HybridArc. Considering all factors, it would be best to use a DCA-IMRT ratio of either 7:3 or 6:4.« less

SU-E-P-30: Clinical Applications of Spatially Fractionated Radiation Therapy (GRID) Using Helical Tomotherapy

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

Zhang, X; Liang, X; Penagaricano, J

2015-06-15

Purpose: To present the first clinical applications of Helical Tomotherapy-based spatially fractionated radiotherapy (HT-GRID) for deep seated tumors and associated dosimetric study. Methods: Ten previously treated GRID patients were selected (5 HT-GRID and 5 LINAC-GRID using a commercially available GRID block). Each case was re-planned either in HT-GRID or LINAC-GRID for a total of 10 plans for both techniques using same prescribed dose of 20 Gy to maximum point dose of GRID GTV. For TOMO-GRID, a programmable virtual TOMOGRID template mimicking a GRID pattern was generated. Dosimetric parameters compared included: GRID GTV mean dose (Dmean) and equivalent uniform dose (EUD),more » GRID GTV dose inhomogeneity (Ratio(valley/peak)), normal tissue Dmean and EUD, and other organs-at-risk(OARs) doses. Results: The median tumor volume was 634 cc, ranging from 182 to 4646 cc. Median distance from skin to the deepest part of tumor was 22cm, ranging from 8.9 to 38cm. The median GRID GTV Dmean and EUD was 10.65Gy (9.8–12.5Gy) and 7.62Gy (4.31–11.06Gy) for HT-GRID and was 6.73Gy (4.44–8.44Gy) and 3.95Gy (0.14–4.2Gy) for LINAC-GRID. The median Ratio(valley/peak) was 0.144(0.05–0.29) for HT-GRID and was 0.055(0.0001–0.14) for LINAC-GRID. For normal tissue in HT-GRID, the median Dmean and EUD was 1.24Gy (0.34–2.54Gy) and 5.45 Gy(3.45–6.89Gy) and was 0.61 Gy(0.11–1.52Gy) and 6Gy(4.45–6.82Gy) for LINAC-GRID. The OAR doses were comparable between the HT-GRID and LINAC-GRID. However, in some cases it was not possible to avoid a critical structure in LINAC-GRID; while HT-GRID can spare more tissue doses for certain critical structures. Conclusion: HT-GRID delivers higher GRID GTV Dmean, EUD and Ratio(valley/peak) compared to LINAC-GRID. HT-GRID delivers higher Dmean and lower EUD for normal tissue compared to LINAC-GRID. TOMOGRID template can be highly patient-specific and allows adjustment of the GRID pattern to different tumor sizes and shapes when they are deeply-seated and cannot be safely treated with LINAC-GRID.« less

Pediatric chest and abdominopelvic CT: organ dose estimation based on 42 patient models.

PubMed

Tian, Xiaoyu; Li, Xiang; Segars, W Paul; Paulson, Erik K; Frush, Donald P; Samei, Ehsan

2014-02-01

To estimate organ dose from pediatric chest and abdominopelvic computed tomography (CT) examinations and evaluate the dependency of organ dose coefficients on patient size and CT scanner models. The institutional review board approved this HIPAA-compliant study and did not require informed patient consent. A validated Monte Carlo program was used to perform simulations in 42 pediatric patient models (age range, 0-16 years; weight range, 2-80 kg; 24 boys, 18 girls). Multidetector CT scanners were modeled on those from two commercial manufacturers (LightSpeed VCT, GE Healthcare, Waukesha, Wis; SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). Organ doses were estimated for each patient model for routine chest and abdominopelvic examinations and were normalized by volume CT dose index (CTDI(vol)). The relationships between CTDI(vol)-normalized organ dose coefficients and average patient diameters were evaluated across scanner models. For organs within the image coverage, CTDI(vol)-normalized organ dose coefficients largely showed a strong exponential relationship with the average patient diameter (R(2) > 0.9). The average percentage differences between the two scanner models were generally within 10%. For distributed organs and organs on the periphery of or outside the image coverage, the differences were generally larger (average, 3%-32%) mainly because of the effect of overranging. It is feasible to estimate patient-specific organ dose for a given examination with the knowledge of patient size and the CTDI(vol). These CTDI(vol)-normalized organ dose coefficients enable one to readily estimate patient-specific organ dose for pediatric patients in clinical settings. This dose information, and, as appropriate, attendant risk estimations, can provide more substantive information for the individual patient for both clinical and research applications and can yield more expansive information on dose profiles across patient populations within a practice. © RSNA, 2013.

[Clinical experience of carbon ion radiotherapy for malignant tumors].

PubMed

Ishikawa, Hitoshi; Tsuji, Hiroshi; Tsujii, Hirohiko

2006-04-01

The carbon ion (C-ion) beams provide unique advantageous biological and physical properties in radiotherapy (RT) for malignant tumors. C-ion beams have a high relative biological effectiveness (RBE) resulting from the high linear energy transfer (LET). In terms of their physical characteristics, C-ion beams exhibit a spread-out Bragg peak (SOBP) and make for a better dose distribution of the target volume by specified beam modulations. Between June 1994 and August 2005, a total of 2,371 patients with malignant tumors were registered in phase I/II dose-escalation studies and clinical phase II trials using C-ion beams generated at Heavy Ion Medical Accelerator in Chiba (HIMAC). In the initial dose-escalation studies, grade 3 or more late rectal complications had developed in some patients. However, the adverse effects were resolved because of the use of appropriate dose levels and modification of the radiation technique. C-ion beams can carry out hypofractionated radiotherapy with a large fraction dose and reduce the overall treatment times compared with conventional radiotherapy. They can also achieve better local tumor control even for radio-resistant tumors such as malignant melanoma, hepatocellular carcinoma and bone and soft tissue sarcomas with minimal morbidity to the normal surrounding tissues.

Effects of aspirin and enoxaparin in a rat model of liver fibrosis.

PubMed

Li, Chen-Jie; Yang, Zhi-Hui; Shi, Xiao-Liu; Liu, De-Liang

2017-09-21

To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models.

PubMed

Tian, Xiaoyu; Li, Xiang; Segars, W Paul; Frush, Donald P; Paulson, Erik K; Samei, Ehsan

2013-12-21

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDI(vol)-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDI(vol)-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models

NASA Astrophysics Data System (ADS)

Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Frush, Donald P.; Paulson, Erik K.; Samei, Ehsan

2013-12-01

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDIvol-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDIvol-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

Low-Dose, Ionizing Radiation and Age-Related Changes in Skeletal Microarchitecture

DOE PAGES

Alwood, Joshua S.; Kumar, Akhilesh; Tran, Luan H.; ...

2012-01-01

Osteoporosis can profoundly affect the aged as a consequence of progressive bone loss; high-dose ionizing radiation can cause similar changes, although less is known about lower doses (≤100 cGy). We hypothesized that exposure to relatively low doses of gamma radiation accelerates structural changes characteristic of skeletal aging. Mice (C57BL/6J-10 wk old, male) were irradiated (total body; 0-sham, 1, 10 or 100 cGy 137 Cs) and tissues harvested on the day of irradiation, 1 or 4 months later. Microcomputed tomography was used to quantify microarchitecture of high turnover, cancellous bone. Irradiation at 100 cGy caused transient microarchitectural changes over one month that were only evident atmore » longer times in controls (4 months). Ex vivo bone cell differentiation from the marrow was unaffected by gamma radiation. In conclusion, acute ionizing gamma irradiation at 100 cGy (but not at 1 cGy or 10 cGy) exacerbated microarchitectural changes normally found during progressive, postpubertal aging prior to the onset of age-related osteoporosis.« less

Dose-dependent effect of mitomycin C on human vocal fold fibroblasts

PubMed Central

Li, Nicole Y. K.; Chen, Fei; Dikkers, Frederik G.; Thibeault, Susan L.

2014-01-01

Background The purpose of this study was to evaluate in vitro cytotoxicity and antifibrotic effects of mitomycin C on normal and scarred human vocal fold fibroblasts. Methods Fibroblasts were subjected to mitomycin C treatment at 0.2, 0.5, or 1 mg/mL, or serum control. Cytotoxicity, immunocytochemistry, and Western blot for collagen I/III were performed at days 0, 1, 3, and 5. Results Significant decreases in live cells were measured for mitomycin C-treated cells on days 3 and 5 for all doses. Extracellular staining of collagen I/III was observed in mitomycin C-treated cells across all doses and times. Extracellular staining suggests apoptosis with necrosis, compromising the integrity of cell membranes and release of cytosolic proteins into the extracellular environment. Western blot indicates inhibition of collagen at all doses except 0.2 mg/mL at day 1. Conclusion A total of 0.2 mg/mL mitomycin C may provide initial and transient stimulation of collagen for necessary repair to damaged tissue without the long-term risk of fibrosis. PMID:23765508

[Ranking of radionuclides and pathways according to their contribution to the dose burden to the population resulting from NPP releases].

PubMed

Spiridonov, S I; Karpenko, E I; Sharpan, L A

2013-01-01

Approaches are described towards estimating the consequences of radioactive contamination of ecosystems by nuclear fuel cycle enterprises with the rationale for the optimal specification level for nuclear power plants (NPP) operating in the normal mode. Calculations are made based on the initial data of the IAEA project, INPRO ENV, dealing with the ranking of radionuclides escaping to the environment from the operating NPPs. Influence of various factors on rankings of radionuclides and pathways of public exposure is demon- strated. An important factor is the controlled radionuclide composition of atmospheric NPP releases. It has been found that variation in the dose coefficients for some radionuclides leads to significant changes not only in the ranking results but also in the estimates of total dose burdens. Invariability is shown of the estimation concerning the greatest contribution of the peroral route to the population dose of irradiation in the situation considered. A conclusion was drawn on the need of taking into consideration uncertainties of different factors when comparing effects on the environment from enterprises of conventional and innovative nuclear fuel cycles.

Dose-dependent effect of mitomycin C on human vocal fold fibroblasts.

PubMed

Li, Nicole Y K; Chen, Fei; Dikkers, Frederik G; Thibeault, Susan L

2014-03-01

The purpose of this study was to evaluate in vitro cytotoxicity and antifibrotic effects of mitomycin C on normal and scarred human vocal fold fibroblasts. Fibroblasts were subjected to mitomycin C treatment at 0.2, 0.5, or 1 mg/mL, or serum control. Cytotoxicity, immunocytochemistry, and Western blot for collagen I/III were performed at days 0, 1, 3, and 5. Significant decreases in live cells were measured for mitomycin C-treated cells on days 3 and 5 for all doses. Extracellular staining of collagen I/III was observed in mitomycin C-treated cells across all doses and times. Extracellular staining suggests apoptosis with necrosis, compromising the integrity of cell membranes and release of cytosolic proteins into the extracellular environment. Western blot indicates inhibition of collagen at all doses except 0.2 mg/mL at day 1. A total of 0.2 mg/mL mitomycin C may provide initial and transient stimulation of collagen for necessary repair to damaged tissue without the long-term risk of fibrosis. Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.

Low-Dose, Ionizing Radiation and Age-Related Changes in Skeletal Microarchitecture

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

Alwood, Joshua S.; Kumar, Akhilesh; Tran, Luan H.

Osteoporosis can profoundly affect the aged as a consequence of progressive bone loss; high-dose ionizing radiation can cause similar changes, although less is known about lower doses (≤100 cGy). We hypothesized that exposure to relatively low doses of gamma radiation accelerates structural changes characteristic of skeletal aging. Mice (C57BL/6J-10 wk old, male) were irradiated (total body; 0-sham, 1, 10 or 100 cGy 137 Cs) and tissues harvested on the day of irradiation, 1 or 4 months later. Microcomputed tomography was used to quantify microarchitecture of high turnover, cancellous bone. Irradiation at 100 cGy caused transient microarchitectural changes over one month that were only evident atmore » longer times in controls (4 months). Ex vivo bone cell differentiation from the marrow was unaffected by gamma radiation. In conclusion, acute ionizing gamma irradiation at 100 cGy (but not at 1 cGy or 10 cGy) exacerbated microarchitectural changes normally found during progressive, postpubertal aging prior to the onset of age-related osteoporosis.« less

Exposure-response relationship and risk assessment for cognitive deficits in early welding-induced manganism.

PubMed

Park, Robert M; Bowler, Rosemarie M; Roels, Harry A

2009-10-01

The exposure-response relationship for manganese (Mn)-induced adverse nervous system effects is not well described. Symptoms and neuropsychological deficits associated with early manganism were previously reported for welders constructing bridge piers during 2003 to 2004. A reanalysis using improved exposure, work history information, and diverse exposure metrics is presented here. Ten neuropsychological performance measures were examined, including working memory index (WMI), verbal intelligence quotient, design fluency, Stroop color word test, Rey-Osterrieth Complex Figure, and Auditory Consonant Trigram tests. Mn blood levels and air sampling data in the form of both personal and area samples were available. The exposure metrics used were cumulative exposure to Mn, body burden assuming simple first-order kinetics for Mn elimination, and cumulative burden (effective dose). Benchmark doses were calculated. Burden with a half-life of about 150 days was the best predictor of blood Mn. WMI performance declined by 3.6 (normal = 100, SD = 15) for each 1.0 mg/m3 x mo exposure (P = 0.02, one tailed). At the group mean exposure metric (burden; half-life = 275 days), WMI performance was at the lowest 17th percentile of normal, and at the maximum observed metric, performance was at the lowest 2.5 percentiles. Four other outcomes also exhibited statistically significant associations (verbal intelligence quotient, verbal comprehension index, design fluency, Stroop color word test); no dose-rate effect was observed for three of the five outcomes. A risk assessment performed for the five stronger effects, choosing various percentiles of normal performance to represent impairment, identified benchmark doses for a 2-year exposure leading to 5% excess impairment prevalence in the range of 0.03 to 0.15 mg/m3, or 30 to 150 microg/m3, total Mn in air, levels that are far below those permitted by current occupational standards. More than one-third of workers would be impaired after working 2 years at 0.2 mg/m3 Mn (the current threshold limit value).

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

Altazi, B; Fernandez, D; Zhang, G

Purpose: Site-specific investigations of the role of Radiomics in cancer diagnosis and therapy are needed. We report of the reproducibility of quantitative image features over different discrete voxel levels in PET/CT images of cervical cancer. Methods: Our dataset consisted of the pretreatment PET/CT scans from a cohort of 76 patients diagnosed with cervical cancer, FIGO stage IB-IVA, age range 31–76 years, treated with external beam radiation therapy to a dose range between 45–50.4 Gy (median dose: 45 Gy), concurrent cisplatin chemotherapy and MRI-based Brachytherapy to a dose of 20–30 Gy (median total dose: 28 Gy). Two board certified radiation oncologistsmore » delineated Metabolic Tumor volume (MTV) for each patient. Radiomics features were extracted based on 32, 64, 128 and 256 discretization levels (DL). The 64 level was chosen to be the reference DL. Features were calculated based on Co-occurrence (COM), Gray Level Size Zone (GLSZM) and Run-Length (RLM) matrices. Mean Percentage Differences (Δ) of features for discrete levels were determined. Normality distribution of Δ was tested using Kolomogorov - Smirnov test. Bland-Altman test was used to investigate differences between feature values measured on different DL. The mean, standard deviation and upper/lower value limits for each pair of DL were calculated. Interclass Correlation Coefficient (ICC) analysis was performed to examine the reliability of repeated measures within the context of the test re-test format. Results: 3 global and 5 regional features out of 48 features showed distribution not significantly different from a normal one. The reproducible features passed the normality test. Only 5 reproducible results were reliable, ICC range 0.7 – 0.99. Conclusion: Most of the radiomics features tested showed sensitivity to voxel level discretization between (32 – 256). Only 4 GLSZM, 3 COM and 1 RLM showed insensitivity towards mentioned discrete levels.« less

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

Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shinichiro

Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The {sup 1}B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumorsmore » and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D{sub 05} and D{sub 95}, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D{sub 05} to the normal ipsilateral lung was 5 Gy-Eq, the D{sub 95} and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D{sub 05} and D{sub 95} doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.« less

Proton Radiotherapy for Pediatric Bladder/Prostate Rhabdomyosarcoma: Clinical Outcomes and Dosimetry Compared to Intensity-Modulated Radiation Therapy

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

Cotter, Shane E.; Herrup, David A.; Friedmann, Alison

Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan wasmore » optimized for target coverage and normal tissue sparing. Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies incorporating extended follow-up, objective outcome measures, and quality-of-life analyses.« less

SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

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

Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho

Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kgmore » and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of repeated intermittent ethanol intoxication in the frontal cortex.« less

Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model.

PubMed

Liu, Mitchell; Moiseenko, Vitali; Agranovich, Alexander; Karvat, Anand; Kwan, Winkle; Saleh, Ziad H; Apte, Aditya A; Deasy, Joseph O

2010-10-01

Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ(2) test (p = 0.44). Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.

Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

PubMed

Ahmad, Feroz; Tabassum, Nahida

2013-01-01

To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls.

PubMed

Mendenhall, William M; Amdur, Robert J; Palta, Jatinder R

2006-06-10

The purpose of this article is to review the role of intensity-modulated radiotherapy (IMRT) in the standard management of patients with head and neck cancer through a critical review of the pertinent literature. IMRT may result in a dose distribution that is more conformal than that achieved with three-dimensional conformal radiotherapy (3D CRT), allowing dose reduction to normal structures and thus decreasing toxicity and possibly enhancing locoregional control through dose escalation. Disadvantages associated with IMRT include increased risk of a marginal miss, decreased dose homogeneity, increased total body dose, and increased labor and expense. Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, depending on the location and extent of the tumor, late toxicity may be lower. Despite limited data on clinical outcomes, IMRT has been widely adopted as a standard technique in routine practice and clinical trials. The use of IMRT involves a learning curve for the practitioner and will continue to evolve, requiring continuing education and monitoring of outcomes from routine practice. Additional standards pertaining to a variety of issues, including target definitions and dose specification, need to be developed. Phase III trials will better define the role of IMRT in coming years.

Clinical Pharmacokinetics of Sulfobutylether-β-Cyclodextrin in Patients With Varying Degrees of Renal Impairment.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Luke, David R; Cammarata, Sue K

2018-03-26

Delafloxacin, a fluoroquinolone, has activity against Gram-positive organisms including methicillin-resistant S aureus and fluoroquinolone-susceptible and -resistant Gram-negative organisms. The intravenous formulation of delafloxacin contains the excipient sulfobutylether-β-cyclodextrin (SBECD), which is eliminated by renal filtration. This study examined the pharmacokinetics and safety of SBECD after single intravenous (IV) infusions in subjects with renal impairment. The study was an open-label, parallel-group, crossover study in subjects with normal renal function or mild, moderate, or severe renal impairment, and those with end-stage renal disease undergoing hemodialysis. Subjects received 300 mg delafloxacin IV or placebo IV, containing 2400 mg SBECD, in 2 periods separated by ≥14-day washouts. SBECD total clearance decreased with decreasing renal function, with a corresponding increase in area under the concentration-time curve (AUC 0-∞ ). After IV delafloxacin 300 mg administration, SBECD mean total clearance was 6.28 and 1.24 L/h, mean AUC 0-∞ was 387 and 2130 h·μg/mL, and mean renal clearance was 5.36 and 1.14 L/h in normal and severe renal subjects, respectively. Similar values were obtained after IV placebo administration. In subjects with end-stage renal disease, delafloxacin 300 mg IV produced mean SBECD AUC 0-48 values of 2715 and 7861 h·μg/mL when dosed before and after hemodialysis, respectively. Total SBECD clearance exhibited linear relationships to estimated glomerular filtration rate and creatinine clearance. Single doses of IV delafloxacin 300 mg and IV placebo were well tolerated in all groups. In conclusion, decreasing renal function causes reduced SBECD clearance and increased exposures, but SBECD continues to exhibit a good safety and tolerability profile in IV formulations. © 2018, The American College of Clinical Pharmacology.

CT analysis of lung density changes in patients undergoing total body irradiation prior to bone marrow transplantation.

PubMed

Lee, J Y; Shank, B; Bonfiglio, P; Reid, A

1984-10-01

Sequential changes in lung density measured by CT are potentially sensitive and convenient monitors of lung abnormalities following total body irradiation (TBI). Methods have been developed to compare pre- and post-TBI CT of lung. The average local features of a cross-sectional lung slice are extracted from three peripheral regions of interest in the anterior, posterior, and lateral portions of the CT image. Also, density profiles across a specific region may be obtained. These may be compared first for verification of patient position and breathing status and then for changes between pre- and post-TBI. These may also be compared with radiation dose profiles through the lung. A preliminary study on 21 leukemia patients undergoing total body irradiation indicates the following: (a) Density gradients of patients' lungs in the antero-posterior direction show a marked heterogeneity before and after transplantation compared with normal lungs. The patients with departures from normal density gradients pre-TBI correlate with later pulmonary complications. (b) Measurements of average peripheral lung densities have demonstrated that the average lung density in the younger age group is substantially higher: pre-TBI, the average CT number (1,000 scale) is -638 +/- 39 Hounsfield unit (HU) for 0-10 years old and -739 +/- 53 HU for 21-40 years old. (c) Density profiles showed no post-TBI regional changes in lung density corresponding to the dose profile across the lung, so no differentiation of a radiation-specific effect has yet been possible. Computed tomographic density profiles in the antero-posterior direction are successfully used to verify positioning of the CT slice and the breathing level of the lung.

Elucidation of the pharmacokinetics of prednisone and prednisolone: elimination and the effect of estrogen

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

Gustavson, L.E.

Several aspects of the pharmacokinetics of the interconvertible glucocorticoids prednisone and prednisolone have been studied. The pharmacokinetics of prednisolone were examined in postmenopausal women taking conjugated estrogens and age-matched control women. The subjects received iv bolus doses of 0.14 and 0.55 mg/kg prednisolone. Expected increases in clearance and volume of distribution with increasing dose were observed for total prednisolone in all subjects. At both doses, significant decreases in total and unbound prednisolone clearance were observed in the women taking estrogen compared to the controls. Volume of distribution was unchanged. The decreases in clearance are smaller than those observed in youngmore » women taking oral contraceptives indicating that factors other than estrogen administration may influence prednisolone clearance in oral contraceptive users. While the protein binding of prednisolone is well characterized, little is known about the protein binding of prednisone. Equilibrium dialysis employing (/sup 3/H)prednisone was used to study the binding of prednisone in human plasma containing endogenous hydrocortisone. Plasma was obtained from volunteers with normal and elevated transcortin binding capacities (CAP/sub T/). Prednisolone binding exhibits marked concentration dependence and sensitivity to CAP/sub T/. In contrast, prednisone binding is independent of concentration and CAP/sub T/.« less

A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men.

PubMed

Hair, W M; Kitteridge, K; O'Connor, D B; Wu, F C

2001-11-01

This study investigated the effect of transdermal T and oral desogestrel on the reproductive axis of healthy men. Twenty-three men were randomized to 1 of 3 treatment groups and received a daily transdermal T patch plus oral desogestrel at a dose of 75, 150, or 300 microg/d for 24 wk. Baseline blood and semen samples were obtained and then every 4 wk thereafter for 32 wk. The outcome measures were sperm density and plasma levels of FSH, LH, total and free T. The results show a dose-dependent suppression of spermatogenesis and gonadotropins. Seven of the 17 subjects became azoospermic. Desogestrel (300 microg daily) in combination with 5 mg daily transdermal T was the most effective (57% azoospermic), whereas a dose of 75 microg was ineffective (0% azoospermic). Total and free plasma T were reduced by approximately 30%. High density lipoprotein cholesterol was significantly reduced. No serious side-effects were encountered. We conclude that daily self-administered desogestrel with transdermal T is capable of suppressing the male reproductive axis, although the efficacy was less marked and less consistent than injectable regimens. The lower efficacy is likely to be due to failure of the transdermal T system to maintain circulating T levels consistently in the required range.

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

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

Zhou, Rachel; Ng, Angela; Constine, Louis S.

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohortmore » and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.« less

SU-E-T-491: Influence of Applicator Dimensions On Doses to Bladder, Rectum and Sigmoid in HDR Brachytherapy for Cervical Cancer

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

Dumane, V; Rhome, R; Yuan, Y

2015-06-15

Purpose: To study the influence of dimensions of the tandem and ring applicator on bladder D2cc, rectum D2cc and sigmoid D2cc in HDR treatment planning for cervical cancer. Methods: 53 plans from 13 patients treated at our institution with the tandem and ring applicator were retrospectively reviewed. Prescription doses were one of the following: 8 Gy x 3, 7 Gy x 4 and 5.5 Gy x 5. Doses to the D2ccs of the bladder, rectum and the sigmoid were recorded. These doses were normalized to their relative prescriptions doses. Correlations between the normalized bladder D2cc, rectum D2cc and sigmoid D2ccmore » were investigated and linear regression models were developed to study the dependence of these doses on the ring diameter and the applicator angle. Results: Normalized doses to the D2cc of the bladder, rectum and sigmoid showed statistically significant correlation (P < 0.05) to the applicator angle. Significant correlation was also noted for the normalized D2cc of the rectum and the sigmoid with the ring diameter. The normalized bladder D2cc was found to decrease with applicator angle on an average by 22.65% ± 4.43% while the same for the rectum and sigmoid were found to increase on an average by 14.43% ± 1.65% and 14.01% ± 1.42% respectively. Both the rectum and sigmoid D2cc reduced with increasing ring diameter by 12.93% ± 1.95% and 11.27% ± 1.79%. No correlation was observed between the normalized bladder D2cc and the ring diameter. Conclusion: Preliminary regression models developed in this study can potentially aid in the choice of the appropriate applicator angle and ring diameter for tandem and ring implant so as to optimize doses to the bladder, rectum and sigmoid.« less

[The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

PubMed

Ding, Zhiwei; Li, Tiancheng; Liu, Yuhe; Xiao, Shuifang

2015-12-01

To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P<0.05). The levels of urinary calcium and serum BALP in rats of maximum rPTH(1-84) injection group (160 µg/kg) were higher than those of normal control group (P<0.05). The rats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus concentration compared with normal control group (P<0.05). The amount of urinary calcium also exceeded the other groups (P<0.05), but no with significant difference in BMD of bilateral femoral bone and lumbar vertebra between negative control group and normal control group (P>0.05). Calcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 µg/kg or 160 µg/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and increase BMD, but can not correspondingly decrease the phosphorus concentration and increase the excretion of calcium in urine.

Organ distribution of technetium-99m-labeled Corynebacterium parvum in normal and tumor-bearing mice

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

Barth, R.F.; Singla, O.

1978-01-01

The distribution patterns were studied for /sup 99m/Tc-labeled Corynebacterium parvum in normal and tumor-bearing mice. C57BL/6 mice were given i.v., i.p., or s.c. injections of 250 ..mu..g of /sup 99m/Tc-labeled C. parvum and killed at 10 min, 1, 4, and 24 hr. After iv. administration, labeled organisms were distributed primarily to the liver, the lungs, and the blood (46% of injected dose), followed by the gastrointestinal tract, the spleen, and the kidneys (11%). Total recoverable radioactivity, which was defined as the percentage of injected dose that was recovered, ranged from 59% at 10 min to 15% at 24 hr. Inmore » contrast to this, /sup 99m/TcS colloid, an inert particulate material, was localized almost entirely in the liver, and the amount recoverable remained constant over 24 hr. One hr after i.p. administration of /sup 99m/Tc-labeled C. parvum, the gastrointestinal tract accounted for 27% of the injected radioactivity, followed by liver, blood, and spleen (12%). This was rapidly excreted between 4 and 24 hr, at which time only 12% of the injected dose was recovered. The skin accounted for 54.6% of the injected radioactivity 1 hr after s.c. injection, 6% 4 hr after s.c. injection, and 0.8% at 24 hr after s.c. injection.« less

SU-F-T-618: Evaluation of a Mono-Isocentric Treatment Planning Software for Stereotactic Radiosurgery of Multiple Brain Metastases

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

Sham, E; Sattarivand, M; Mulroy, L

Purpose: To evaluate planning performance of an automated treatment planning software (BrainLAB; Elements) for stereotactic radiosurgery (SRS) of multiple brain metastases. Methods: Brainlab’s Multiple Metastases Elements (MME) uses single isocentric technique to treat up to 10 cranial planning target volumes (PTVs). The planning algorithm of the MME accounts for multiple PTVs overlapping with one another on the beam eyes view (BEV) and automatically selects a subset of all overlapping PTVs on each arc for sparing normal tissues in the brain. The algorithm also optimizes collimator angles, margins between multi-leaf collimators (MLCs) and PTVs, as well as monitor units (MUs) usingmore » minimization of conformity index (CI) for all targets. Planning performance was evaluated by comparing the MME-calculated treatment plan parameters with the same parameters calculated with the Volumetric Modulated Arc Therapy (VMAT) optimization on Varian’s Eclipse platform. Results: Figures 1 to 3 compare several treatment plan outcomes calculated between the MME and VMAT for 5 clinical multi-targets SRS patient plans. Prescribed target dose was volume-dependent and defined based on the RTOG recommendation. For a total number of 18 PTV’s, mean values for the CI, PITV, and GI were comparable between the MME and VMAT within one standard deviation (σ). However, MME-calculated MDPD was larger than the same VMAT-calculated parameter. While both techniques delivered similar maximum point doses to the critical cranial structures and total MU’s for the 5 patient plans, the MME required less treatment planning time by an order of magnitude compared to VMAT. Conclusion: The MME and VMAT produce similar plan qualities in terms of MUs, target dose conformation, and OAR dose sparing. While the selective use of PTVs for arc-optimization with the MME reduces significantly the total planning time in comparison to VMAT, the target dose homogeneity was also compromised due to its simplified inverse planning algorithm used.« less

Burosumab Therapy in Children with X-Linked Hypophosphatemia.

PubMed

Carpenter, Thomas O; Whyte, Michael P; Imel, Erik A; Boot, Annemieke M; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; Van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A

2018-05-24

X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).

Patient-specific dose estimation for pediatric abdomen-pelvis CT

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2009-02-01

The purpose of this study is to develop a method for estimating patient-specific dose from abdomen-pelvis CT examinations and to investigate dose variation across patients in the same weight group. Our study consisted of seven pediatric patients in the same weight/protocol group, for whom full-body computer models were previously created based on the patients' CT data obtained for clinical indications. Organ and effective dose of these patients from an abdomen-pelvis scan protocol (LightSpeed VCT scanner, 120-kVp, 85-90 mA, 0.4-s gantry rotation period, 1.375-pitch, 40-mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated for the same CT system. The seven patients had effective dose of 2.4-2.8 mSv, corresponding to normalized effective dose of 6.6-8.3 mSv/100mAs (coefficient of variation: 7.6%). Dose variations across the patients were small for large organs in the scan coverage (mean: 6.6%; range: 4.9%-9.2%), larger for small organs in the scan coverage (mean: 10.3%; range: 1.4%-15.6%), and the largest for organs partially or completely outside the scan coverage (mean: 14.8%; range: 5.7%-27.7%). Normalized effective dose correlated strongly with body weight (correlation coefficient: r = -0.94). Normalized dose to the kidney and the adrenal gland correlated strongly with mid-liver equivalent diameter (kidney: r = -0.97; adrenal glands: r = -0.98). Normalized dose to the small intestine correlated strongly with mid-intestine equivalent diameter (r = -0.97). These strong correlations suggest that patient-specific dose may be estimated for any other child in the same size group who undergoes the abdomen-pelvis scan.

SU-E-T-124: Dosimetric Comparison of HDR Brachytherapy and Intensity Modulated Proton Therapy

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

Wu, J; Wu, H; Das, I

2014-06-01

Purpose: Brachytherapy is known to be able to deliver more radiation dose to tumor while minimizing radiation dose to surrounding normal tissues. Proton therapy also provides superior dose distribution due to Bragg peak. Since both HDR and Intensity Modulated Proton Therapy (IMPT) are beneficial for their quick dose drop off, our goal in this study is to compare the pace of dose gradient drop-off between HDR and IMPT plans based on the same CT image data-set. In addition, normal tissues sparing were also compared among HDR, IMPT and SBRT. Methods: Five cervical cancer cases treated with EBRT + HDR boostmore » combination with Tandem and Ovoid applicator were used for comparison purpose. Original HDR plans with prescribed dose of 5.5 Gy x 5 fractions were generated and optimized. The 100% isodose line of HDR plans was converted to a dose volume, and treated as CTV for IMPT and SBRT planning. The same HDR CT scans were also used for IMPT plan and SBRT plan for direct comparison. The philosophy of the IMPT and SBRT planning was to create the same CTV coverage as HDR plans. All three modalities treatment plans were compared to each other with a set of predetermined criteria. Results: With similar target volume coverage in cervix cancer boost treatment, HDR provides a slightly sharper dose drop-off from 100% to 50% isodose line, averagely in all directions compared to IMPT. However, IMPT demonstrated more dose gradient drop-off at the junction of the target and normal tissues by providing more normal tissue sparing and superior capability to reduce integral dose. Conclusion: IMPT is capable of providing comparable dose drop-off as HDR. IMPT can be explored as replacement for HDR brachytherapy in various applications.« less

Postoperative radiotherapy following mastectomy for patients with left-sided breast cancer: A comparative dosimetric study

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

Wang, Jiahao, E-mail: mashenglin@medmail.com.cn; Li, Xiadong; Deng, Qinghua

2015-10-01

The purposes of this article were to compare the biophysical dosimetry for postmastectomy left-sided breast cancer using 4 different radiotherapy (RT) techniques. In total, 30 patients with left-sided breast cancer were randomly selected for this treatment planning study. They were planned using 4 RT techniques, including the following: (1) 3-dimensional conventional tangential fields (TFs), (2) tangential intensity-modulated therapy (T-IMRT), (3) 4 fields IMRT (4F-IMRT), and (4) single arc volumetric-modulated arc therapy (S-VMAT). The planning target volume (PTV) dose was prescribed 50 Gy, the comparison of target dose distribution, conformity index, homogeneity index, dose to organs at risk (OARs), tumor controlmore » probability (TCP), normal tissue complication probability (NTCP), and number of monitor units (MUs) between 4 plans were investigated for their biophysical dosimetric difference. The target conformity and homogeneity of S-VMAT were better than the other 3 kinds of plans, but increased the volume of OARs receiving low dose (V{sub 5}). TCP of PTV and NTCP of the left lung showed no statistically significant difference in 4 plans. 4F-IMRT plan was superior in terms of target coverage and protection of OARs and demonstrated significant advantages in decreasing the NTCP of heart by 0.07, 0.03, and 0.05 compared with TFs, T-IMRT, and S-VMAT plan. Compared with other 3 plans, TFs reduced the average number of MUs. Of the 4 techniques studied, this analysis supports 4F-IMRT as the most appropriate balance of target coverage and normal tissue sparing.« less

Pharmacokinetics, safety and tolerability of rotigotine transdermal patch in healthy Japanese and Caucasian subjects.

PubMed

Cawello, Willi; Kim, Seong R; Braun, Marina; Elshoff, Jan-Peer; Ikeda, Junji; Funaki, Tomoo

2014-02-01

Rotigotine is a dopamine receptor agonist with activity across the D1 through to D5 receptors as well as select serotonergic and adrenergic sites; continuous transdermal delivery of rotigotine with replacement of the patch once daily maintains stable plasma concentrations over 24 h. Rotigotine is indicated for the treatment of early and advanced-stage Parkinson's disease and moderate-to-severe idiopathic restless legs syndrome. The pharmacokinetics and pharmacodynamics of a drug may vary between subjects of different ethnic origin. This study evaluated the pharmacokinetics, safety, and tolerability of single-dose treatment with rotigotine transdermal patch in Japanese and Caucasian subjects. In this open-label, parallel-group study, healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by sex, body mass index, and age. A single transdermal patch delivering 2 mg/24 h rotigotine (patch content 4.5 mg) was applied to the ventral/lateral abdomen for 24 h. The main outcome measures were the plasma concentrations of unconjugated and total rotigotine and its desalkyl metabolites and derived pharmacokinetic parameters (area under the concentration-time curve from time zero to last quantifiable concentration [AUClast], maximum plasma concentration [Cmax], and body weight- and dose-normalized values). The pharmacokinetic analysis included 48 subjects (24 Japanese, 24 Caucasian). The mean apparent dose of rotigotine was 2.0±0.5 mg for Japanese subjects and 2.08±0.58 mg for Caucasians. Plasma concentration-time profiles of unconjugated rotigotine and of the main metabolites were similar for both ethnic groups. Parameters of model-independent pharmacokinetics, Cmax, time to Cmax (tmax), and AUClast, for unconjugated rotigotine showed no statistically significant differences between Japanese and Caucasian subjects. Values of concentration-dependent pharmacokinetic parameters were higher in female subjects; this difference was minimized after correction for body weight. A statistically significant difference between ethnic groups was observed for total rotigotine concentrations (total rotigotine=unconjugated rotigotine+conjugated rotigotine), with slightly lower values in Caucasians after correction for body weight and apparent dose. No relevant differences were observed between males and females. Inter-individual variability was high. The terminal half-life for unconjugated rotigotine was 5.3 h in Japanese subjects and 5.7 h in Caucasians; corresponding values for total rotigotine were 8.6 h and 9.6 h. Less than 0.1% of the apparent dose was renally excreted as the parent compound. Renal elimination of total rotigotine covers 11.7% of absorbed dose in Japanese subjects and 10.8% of the absorbed dose in Caucasians, whereas the renal elimination via total despropyl rotigotine was 8.2 and 7.1%, respectively. The corresponding values for total desthienylethyl rotigotine were 3.5% in Japanese subjects and 4.2% Caucasians. Most adverse events were mild in intensity and typical for dopamine agonists or for transdermal therapeutics. Administration of a single patch delivering 2 mg/24 h rotigotine resulted in comparable pharmacokinetic profiles in Japanese and Caucasian subjects. The rotigotine transdermal patch was generally well-tolerated. Our findings suggest similar dose requirements for Japanese and Caucasian populations.

Lens of the eye dose calculation for neuro-interventional procedures and CBCT scans of the head

NASA Astrophysics Data System (ADS)

Xiong, Zhenyu; Vijayan, Sarath; Rana, Vijay; Jain, Amit; Rudin, Stephen; Bednarek, Daniel R.

2016-03-01

The aim of this work is to develop a method to calculate lens dose for fluoroscopically-guided neuro-interventional procedures and for CBCT scans of the head. EGSnrc Monte Carlo software is used to determine the dose to the lens of the eye for the projection geometry and exposure parameters used in these procedures. This information is provided by a digital CAN bus on the Toshiba Infinix C-Arm system which is saved in a log file by the real-time skin-dose tracking system (DTS) we previously developed. The x-ray beam spectra on this machine were simulated using BEAMnrc. These spectra were compared to those determined by SpekCalc and validated through measured percent-depth-dose (PDD) curves and half-value-layer (HVL) measurements. We simulated CBCT procedures in DOSXYZnrc for a CTDI head phantom and compared the surface dose distribution with that measured with Gafchromic film, and also for an SK150 head phantom and compared the lens dose with that measured with an ionization chamber. Both methods demonstrated good agreement. Organ dose calculated for a simulated neuro-interventional-procedure using DOSXYZnrc with the Zubal CT voxel phantom agreed within 10% with that calculated by PCXMC code for most organs. To calculate the lens dose in a neuro-interventional procedure, we developed a library of normalized lens dose values for different projection angles and kVp's. The total lens dose is then calculated by summing the values over all beam projections and can be included on the DTS report at the end of the procedure.

VMAT vs. 7-Field-IMRT: Assessing the Dosimetric Parameters of Prostate Cancer Treatment with a 292-Patient Sample

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

Kopp, Robert W.; Duff, Michael, E-mail: mduff@cancercarewny.com; Catalfamo, Frank

2011-01-01

We compared normal tissue radiation dose for the treatment of prostate cancer using 2 different radiation therapy delivery methods: volumetric modulated arc therapy (VMAT) vs. fixed-field intensity-modulated radiation therapy (IMRT). Radiotherapy plans for 292 prostate cancer patients treated with VMAT to a total dose of 7740 cGy were analyzed retrospectively. Fixed-angle, 7-field IMRT plans were created using the same computed tomography datasets and contours. Radiation doses to the planning target volume (PTV) and organs at risk (bladder, rectum, penile bulb, and femoral heads) were measured, means were calculated for both treatment methods, and dose-volume comparisons were made with 2-tailed, pairedmore » t-tests. The mean dose to the bladder was lower with VMAT at all measured volumes: 5, 10, 15, 25, 35, and 50% (p < 0.05). The mean doses to 5 and 10% of the rectum, the high-dose regions, were lower with VMAT (p < 0.05). The mean dose to 15% of the rectal volume was not significantly different (p = 0.95). VMAT exposed larger rectal volumes (25, 35, and 50%) to more radiation than fixed-field IMRT (p < 0.05). Average mean dose to the penile bulb (p < 0.05) and mean dose to 10% of the femoral heads (p < 0.05) were lower with VMAT. VMAT therapy for prostate cancer has dosimetric advantages for critical structures, notably for high-dose regions compared with fixed-field IMRT, without compromising PTV coverage. This may translate into reduced acute and chronic toxicity.« less

A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

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

Houweling, Antonetta C., E-mail: A.Houweling@umcutrecht.n; Philippens, Marielle E.P.; Dijkema, Tim

2010-03-15

Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulatedmore » salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.« less

SU-F-T-613: Multi-Lesion Cranial SRS VMAT Plan Quality

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

Ballangrud, A; Kuo, L; Happersett, L

Purpose: Cranial SRS VMAT plans must have steep dose gradient around each target to reduce dose to normal brain. This study reports on the correlation between gradient index (GI=V50%/V100%), target size and target dose heterogeneity index (HI=PTV Dmax/prescription dose) for multi-lesion cranial SRS VMAT plans. Methods: VMAT plans for 10 cranial cases with 3 to 6 lesions (total 39 lesions) generated in Varian Eclipse V11.0.47 with a fine-tuned AAA beam model and 0.125 cm dose grid were analyzed. One or two iso centers were used depending on the spatial distribution of lesions. Two to nine coplanar and non-coplanar arcs weremore » used per isocenter. Conformity index (CI= V100%/VPTV), HI, and GI were determined for each lesion. Dose to critical structures were recorded. Results: Lesion size ranged from 0.05–11.00 cm3. HI ranged from 1.2–1.4, CI ranged from 1.0–2.8 and GI from 3.1–8.4. Maximum dose to brainstem, chiasm, lenses, optic nerves and eyes ranged from 120–1946 cGy, 47–463 cGy, 9–121 cGy, 14–512 cGy, and 17–294 cGy, respectively. Brain minus PTV (Brain-PTV) V7Gy was in the range 1.1–6.5%, and Brain-PTV Dmean was in the range 94–324 cGy. Conclusion: This work shows that a GI < 5 can be achieved for lesions > 0.4cc. For smaller lesions, GI increases rapidly. GI is lower when HI is increased. Based on this study, recommend HI is 1.4, and recommended GI is for volumes <0.1cc GI<9, 0.1–0.4cc GI<6, 0.4–0.1.0cc GI<5, and for volumes >1.0cc GI<4. CI is < 1.3 for all lesions except for targets < 0.1cc. Cranial SRS VMAT plans must be optimized to lower the GI to reduce the dose to normal brain tissue.« less

TU-AB-303-08: GPU-Based Software Platform for Efficient Image-Guided Adaptive Radiation Therapy

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

Park, S; Robinson, A; McNutt, T

2015-06-15

Purpose: In this study, we develop an integrated software platform for adaptive radiation therapy (ART) that combines fast and accurate image registration, segmentation, and dose computation/accumulation methods. Methods: The proposed system consists of three key components; 1) deformable image registration (DIR), 2) automatic segmentation, and 3) dose computation/accumulation. The computationally intensive modules including DIR and dose computation have been implemented on a graphics processing unit (GPU). All required patient-specific data including the planning CT (pCT) with contours, daily cone-beam CTs, and treatment plan are automatically queried and retrieved from their own databases. To improve the accuracy of DIR between pCTmore » and CBCTs, we use the double force demons DIR algorithm in combination with iterative CBCT intensity correction by local intensity histogram matching. Segmentation of daily CBCT is then obtained by propagating contours from the pCT. Daily dose delivered to the patient is computed on the registered pCT by a GPU-accelerated superposition/convolution algorithm. Finally, computed daily doses are accumulated to show the total delivered dose to date. Results: Since the accuracy of DIR critically affects the quality of the other processes, we first evaluated our DIR method on eight head-and-neck cancer cases and compared its performance. Normalized mutual-information (NMI) and normalized cross-correlation (NCC) computed as similarity measures, and our method produced overall NMI of 0.663 and NCC of 0.987, outperforming conventional methods by 3.8% and 1.9%, respectively. Experimental results show that our registration method is more consistent and roust than existing algorithms, and also computationally efficient. Computation time at each fraction took around one minute (30–50 seconds for registration and 15–25 seconds for dose computation). Conclusion: We developed an integrated GPU-accelerated software platform that enables accurate and efficient DIR, auto-segmentation, and dose computation, thus supporting an efficient ART workflow. This work was supported by NIH/NCI under grant R42CA137886.« less

SU-E-T-292: Dosimetric Advantage of Prone Breast Radiotherapy for Korean Left-Sided Breast Cancer Patients

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

Chung, Y; Shin, J; Yu, J

Purpose: To evaluate the dosimetric benefit of prone breast radiotherapy for Korean left-sided early-stage breast cancer patients who have relatively small breast Methods: From April to June, 2014, 10 left-sided breast cancer patients received the whole breast irradiation in prone position after partial mastectomy with sentinel lymph node biopsy or axillary lymph node dissection. All patients were pTmi-2N0-1mi. Each patient underwent two computed tomoradiography (CT) simulations in supine and prone positions. The whole breast, ipsilateral lung, heart, and left anterior descending coronary artery (LAD) were contoured on each simulation CT images, and then tangential-fields treatment plan in each position wasmore » designed for the whole breast irradiation with the total dose of 50 Gy in 2 Gy fractions. Dose-volume histograms of two setups were compared for target coverage and radiation dose to normal organs with Wilcoxon signed rank tests. Results: The median age of patients was 47 years (range, 37 to 53). The median chest size was 82.5 cm (range, 75 to 90) and bra cup size was A in 4, B in 4, and C in 2 patients. The radiation dose to the whole breast was similar when comparing mean dose (Dmean) and dose covering 95% of the breast volume, but maximum dose (Dmax) of breast was higher in supine (median 52.3 vs. 52.7 Gy, p=0.013). Prone position reduced significantly the radiation dose in ipsilateral lung, heart, and LAD by median 5.7, 1.1, and 6.9 Gy of Dmean (p=0.005, 0.007, and 0.005) and 28.2, 18.8, and 35.0 Gy of Dmax (p=0.005, 0.005, and 0.007), respectively. Conclusion: Prone breast radiotherapy could be beneficial for Korean breast cancer patients since it substantially spared normal organs while achieving adequate coverage of the breast tissue. Further prospective study is required to validate the potential benefit of prone breast radiotherapy.« less

Radioiodine treatment of hyperthyroidism in a pregnant women.

PubMed

Berg, G E; Nyström, E H; Jacobsson, L; Lindberg, S; Lindstedt, R G; Mattsson, S; Niklasson, C A; Norén, A H; Westphal, O G

1998-02-01

We describe the effects of radioiodine treatment of a pregnant thyrotoxic woman. The woman received 500 MBq of (131)I in her 20th gestational week. The pregnancy was discovered 10 days after radioiodine administration. A gamma camera examination of the abdomen at that time showed a distinct focus of activity, which was interpreted as the fetal thyroid. Gamma camera examinations of the mother and fetus were performed at 10, 11, 12, 13 and 18 days after administration of the therapeutic activity and were the basis of dose calculations. The child was examined by hormone tests and mental performance tests, up to 8 yr after birth. The uptake at 24 hr postadministration was calculated to be 10 MBq (2%) in the fetal thyroid gland. The effective half-life was 2.5 days, giving a calculated absorbed dose to the fetal thyroid gland of 600 Gy, which is considered to be an ablative dose. The calculated absorbed dose to the fetal body, including brain, was about 100 mGy, and 40 mGy to the fetal gonads. Doses were estimated taking contributions from radioiodine in the mother, the fetal body and the fetal thyroid into consideration. The woman was encouraged to continue her pregnancy and received levothyroxine in a dose to render her slightly thyrotoxic. At full term, an apparently healthy boy, having markedly raised cord blood serum thyroid-stimulating hormone concentration and subnormal thyroxine (T4) and low-normal triiodothyronine (T3) concentrations, was born. Treatment with thyroxine was initiated from the age of 14 days, when the somatosensoric evoked potential latency time increased to a pathological value and hormonal laboratory tests repeatedly confirmed the hypothyroid state. At 8 yr of age, the child attends regular school. A neuropsychological pediatric examination showed that the mental performance was within normal limits, but with an uneven profile. He has a low attention score and displays evidently subnormal capacity regarding figurative memory. Radioiodine treatment in pregnancy in the 20th gestational week does not give a total absorbed dose to the fetal body that justifies termination of pregnancy. A high absorbed dose to the fetal thyroid, however, should be the basis of the management of the pregnancy and offspring.

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

Lin, M; Choi, E; Chuong, M

Purpose: To evaluate weather the current radiobiological models can predict the normal liver complications of radioactive Yttrium-90 ({sup 90}Y) selective-internal-radiation-treatment (SIRT) for metastatic liver lesions based on the post-infusion {sup 90}Y PET images. Methods: A total of 20 patients with metastatic liver tumors treated with SIRT that received a post-infusion {sup 90}Y-PET/CT scan were analyzed in this work. The 3D activity distribution of the PET images was converted into a 3D dose distribution via a kernel convolution process. The physical dose distribution was converted into the equivalent dose (EQ2) delivered at 2 Gy based on the linear-quadratic (LQ) model consideringmore » the dose rate effect. The biological endpoint of this work was radiation-induce liver disease (RILD). The NTCPs were calculated with four different repair-times (T1/2-Liver-Repair= 0,0.5,1.0,2.0 hr) and three published NTCP models (Lyman-external-RT, Lyman 90Y-HCC-SIRT, parallel model) were compared to the incidence of RILD of the recruited patients to evaluate their ability of outcome prediction. Results: The mean normal liver physical dose (avg. 51.9 Gy, range 31.9–69.8 Gy) is higher than the suggested liver dose constraint for external beam treatment (∼30 Gy). However, none of the patients in our study developed RILD after the SIRT. The estimated probability of ‘no patient developing RILD’ obtained from the two Lyman models are 46.3% to 48.3% (T1/2-Liver-Repair= 0hr) and <1% for all other repair times. For the parallel model, the estimated probability is 97.3% (0hr), 51.7% (0.5hr), 2.0% (1.0hr) and <1% (2.0hr). Conclusion: Molecular-images providing the distribution of {sup 90}Y enable the dose-volume based dose/outcome analysis for SIRT. Current NTCP models fail to predict RILD complications in our patient population, unless a very short repair-time for the liver is assumed. The discrepancy between the Lyman {sup 90}Y-HCC-SIRT model predicted and the clinically observed outcomes further demonstrates the need of an NTCP model specific to the metastatic liver SIRT.« less

MO-F-CAMPUS-I-02: Accuracy in Converting the Average Breast Dose Into the Mean Glandular Dose (MGD) Using the F-Factor in Cone Beam Breast CT- a Monte Carlo Study Using Homogeneous and Quasi-Homogeneous Phantoms

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

Lai, C; Zhong, Y; Wang, T

2015-06-15

Purpose: To investigate the accuracy in estimating the mean glandular dose (MGD) for homogeneous breast phantoms by converting from the average breast dose using the F-factor in cone beam breast CT. Methods: EGSnrc-based Monte Carlo codes were used to estimate the MGDs. 13-cm in diameter, 10-cm high hemi-ellipsoids were used to simulate pendant-geometry breasts. Two different types of hemi-ellipsoidal models were employed: voxels in quasi-homogeneous phantoms were designed as either adipose or glandular tissue while voxels in homogeneous phantoms were designed as the mixture of adipose and glandular tissues. Breast compositions of 25% and 50% volume glandular fractions (VGFs), definedmore » as the ratio of glandular tissue voxels to entire breast voxels in the quasi-homogeneous phantoms, were studied. These VGFs were converted into glandular fractions by weight and used to construct the corresponding homogeneous phantoms. 80 kVp x-rays with a mean energy of 47 keV was used in the simulation. A total of 109 photons were used to image the phantoms and the energies deposited in the phantom voxels were tallied. Breast doses in homogeneous phantoms were averaged over all voxels and then used to calculate the MGDs using the F-factors evaluated at the mean energy of the x-rays. The MGDs for quasi-homogeneous phantoms were computed directly by averaging the doses over all glandular tissue voxels. The MGDs estimated for the two types of phantoms were normalized to the free-in-air dose at the iso-center and compared. Results: The normalized MGDs were 0.756 and 0.732 mGy/mGy for the 25% and 50% VGF homogeneous breasts and 0.761 and 0.733 mGy/mGy for the corresponding quasi-homogeneous breasts, respectively. The MGDs estimated for the two types of phantoms were similar within 1% in this study. Conclusion: MGDs for homogeneous breast models may be adequately estimated by converting from the average breast dose using the F-factor.« less

Evaluation of buparvaquone (BUTA-Kel KELA, Belgium) as a treatment of East Coast fever in cattle, in the peri-urban of Dar Es Salaam city, Tanzania.

PubMed

Mbwambo, H A; Magwisha, H B; Mfinanga, J M

2006-06-30

Evaluation trials of the efficacy of buparvaquone (BUTA-kel KELA Laboratoria, N.V. Belgium), as a treatment of field cases of Theileria parva infection (East Coast fever - ECF) were carried out on 63 cattle in the peri-urban of Dar Es Salaam city, Tanzania, during the period November 2004 to August 2005. Thirty-two cattle (56%) received single-dose treatment (2.5 mg buparvaquone per kg body weight), while two and three-dose treatment with interval(s) of 48 h was given to 33% and 11% of total treated cattle, respectively; 38 cattle (60.3%) were treated at an early stage of the disease, while 25 cattle (39.7%) were treated at an advanced stage of the disease. The rectal body temperature of 90.5% of buparvaquone-treated cattle dropped to normal values (37.5-39.5 degrees C) by day 7 of treatment, and by day 15 of treatment 96.8% of treated cattle showed normal values. Pulmonary signs were observed in 8/68 (11.8%) of total ECF diagnosed cattle and were successfully treated, albeit with parvaquone plus frusemide (Fruvexon); were not included in final evaluation of the efficacy of BUTA-kel. The present evaluation trials record a recovery rate of 95.2%. Buparvaquone (BUTA-kel KELA Laboratoria, N.V. Belgium), therefore, records another efficacious and valuable alternative treatment against East Coast fever in Tanzania.

Fetal radiation monitoring and dose minimization during intensity modulated radiation therapy for glioblastoma in pregnancy.

PubMed

Horowitz, David P; Wang, Tony J C; Wuu, Cheng-Shie; Feng, Wenzheng; Drassinower, Daphnie; Lasala, Anita; Pieniazek, Radoslaw; Cheng, Simon; Connolly, Eileen P; Lassman, Andrew B

2014-11-01

We examined the fetal dose from irradiation of glioblastoma during pregnancy using intensity modulated radiation therapy (IMRT), and describe fetal dose minimization using mobile shielding devices. A case report is described of a pregnant woman with glioblastoma who was treated during the third trimester of gestation with 60 Gy of radiation delivered via a 6 MV photon IMRT plan. Fetal dose without shielding was estimated using an anthropomorphic phantom with ion chamber and diode measurements. Clinical fetal dose with shielding was determined with optically stimulated luminescent dosimeters and ion chamber. Clinical target volume (CTV) and planning target volume (PTV) coverage was 100 and 98 % receiving 95 % of the prescription dose, respectively. Normal tissue tolerances were kept below quantitative analysis of normal tissue effects in the clinic (QUANTEC) recommendations. Without shielding, anthropomorphic phantom measurements showed a cumulative fetal dose of 0.024 Gy. In vivo measurements with shielding in place demonstrated a cumulative fetal dose of 0.016 Gy. The fetal dose estimated without shielding was 0.04 % and with shielding was 0.026 % of the target dose. In vivo estimation of dose equivalent received by the fetus was 24.21 mSv. Using modern techniques, brain irradiation can be delivered to pregnant patients in the third trimester with very low measured doses to the fetus, without compromising target coverage or normal tissue dose constraints. Fetal dose can further be reduced with the use of shielding devices, in keeping with the principle of as low as reasonably achievable.

Pulsed Versus Conventional Radiation Therapy in Combination With Temozolomide in a Murine Orthotopic Model of Glioblastoma Multiforme

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

Lee, David Y.; Chunta, John L.; Park, Sean S.

Purpose: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. Methods and Materials: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1{sup nu} mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as amore » single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry. Results: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ. Conclusions: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.« less

Protective effects of melatonin against 12C6+ beam irradiation-induced oxidative stress and DNA injury in the mouse brain

NASA Astrophysics Data System (ADS)

Wu, Z. H.; Zhang, H.; Wang, X. Y.; Yang, R.; Liu, B.; Liu, Y.; Zhao, W. P.; Feng, H. Y.; Xue, L. G.; Hao, J. F.; Niu, B. T.; Wang, Z. H.

2012-01-01

The purpose of this experiment was to estimate the protective effects of melatonin against radiation-induced brain damages in mice induced by heavy ion beams. Kun-Ming mice were randomly divided into five groups: normal control group, irradiation control group, and three different doses of melatonin (5, 10, and 20 mg/kg, i.p.) treated groups. Apart from the normal control group, the other four groups were exposed to whole-body 4.0 Gy carbon ion beam irradiation (approximately 0.5 Gy/min) after i.p. administration of normal saline or melatonin 1 h before irradiation. The oxidative redox status of brain tissue was assessed by measurement of malondiadehyde (MDA) levels, total superoxide dismutase (T-SOD), cytosolic superoxide dismutase (Cu/ZnSOD, SOD1) and mitochondrial superoxide dismutase (MnSOD, SOD2) activities at 8 h after irradiation. DNA damages were determined using the Comet assay and apoptosis and cell cycle distribution were detected by flow cytometric analyses. A dramatic dose-dependent decrease in MDA levels, tail moment, rates of tailing cells, and apoptosis, and a dose-dependent increase in T-SOD and SOD2 activities, in brain tissues in the melatonin-treated groups were detected compared with the irradiation only group. Furthermore, flow cytometric analysis demonstrated that the percentage of brain cells in the G0/G1 phase decreased significantly, while those in the S and G2/M stage increased dramatically, with mice pretreated with melatonin compared to the irradiation control group. These data indicate that melatonin has protective effects against irradiation-induced brain injury, and that its underlying protective mechanisms may relate to modulation of oxidative stress induced by heavy ionirradiation.

The fate of radiation induced giant-nucleated cells of human skin fibroblasts

NASA Astrophysics Data System (ADS)

Almahwasi, A. A.; Jeynes, J. C.; Bradley, D. A.; Regan, P. H.

2017-11-01

Radiation-induced giant-nucleated cells (GCs) have been observed to occur within survivors of irradiated cancerous and within healthy cells, both in vivo and in vitro. The expression of such morphological alterations is associated with genomic instability. This study was designed to investigate the fate of GCs induced in a normal human fibroblast cell line (AG1522) after exposure to 0.2, 1 or 2 Gy of X-ray or proton irradiation. The total of 79 individual AG1522 GCs present at 7, 14 or 21 days after each dose point were analysed from fluorescence microscopy images captured over approximately 120 h. The GCs were identified at the beginning of the observation period for each time point post-irradiation and the area of the cell nucleus was measured (μm2) using a cell-recognition MATLAB code. The results demonstrate that the majority of GCs had undergone a prolonged mitotic arrest, which might be an indication of the survival strategy. The live cell microscopy confirms that a giant-nucleated cell formed 14 days after exposure to 0.2 Gy of proton irradiation was divided into two asymmetrical normal-sized cells. These results suggest that a small fraction of GCs can proliferate and form progeny. Some of GCs had disappeared from the microscopy fields. The rate of their loss was decreased as the dose increased but there remains the potential for them to have progeny that could continue to proliferate, ultimately contributing to development of cancer risk. This important method to access delayed effects in normal tissues could act as a potential radioprotective assay for a dose-limiting parameter when applying radiotherapy. These results might have important implications in evaluating risk estimates for patients during radiation therapy treatment.

Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

PubMed

Wang, Li-hong; Wang, Xu; Yu, Xi-zhong; Xu, Wen-ting

2016-02-01

To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

Calculated and TLD-based absorbed dose estimates for I-131-labeled 3F8 monoclonal antibody in a human neuroblastoma xenograft nude mouse model.

PubMed

Ugur, O; Scott, A M; Kostakoglu, L; Hui, T E; Masterson, M E; Febo, R; Sgouros, G; Rosa, E; Mehta, B M; Fisher, D R

1995-01-01

Preclinical evaluation of the therapeutic potential of radiolabeled antibodies is commonly performed in a xenografted nude mouse model. To assess therapeutic efficacy it is important to estimate the absorbed dose to the tumor and normal tissues of the nude mouse. The current study was designed to accurately measure radiation does to human neuroblastoma xenografts and normal organs in nude mice treated with I-131-labeled 3F8 monoclonal antibody (MoAb) against disialoganglioside GD2 antigen. Absorbed dose estimates were obtained using two different approaches: (1) measurement with teflon-imbedded CaSO4:Dy mini-thermoluminescent dosimeters (TLDs) and (2) calculations using mouse S-factors. The calculated total dose to tumor one week after i.v. injection of the 50 microCi I-131-3F8 MoAb was 604 cGy. The corresponding decay corrected and not corrected TLD measurements were 109 +/- 9 and 48.7 +/- 3.4 cGy respectively. The calculated to TLD-derived dose ratios for tumor ranged from 6.1 at 24 h to 5.5 at 1 week. The light output fading rate was found to depend upon the tissue type within which the TLDs were implanted. The decay rate in tumor, muscle, subcutaneous tissue and in vitro, were 9.5, 5.0, 3.7 and 0.67% per day, respectively. We have demonstrated that the type of tissue in which the TLD was implanted strongly influenced the in vivo decay of light output. Even with decay correction, a significant discrepancy was observed between MIRD-based calculated and CaSO4:Dy mini-TLD measured absorbed doses. Batch dependence, pH of the tumor or other variables associated with TLDs which are not as yet well known may account for this discrepancy.

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats.

PubMed

Abdel-Kader, Maged S; Abulhamd, Ashraf T; Hamad, Abubaker M; Alanazi, Abdullah H; Ali, Rizwan; Alqasoumi, Saleh I

2018-05-01

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in  Glycyrrhiza glabra  (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.

Place of cabergoline in acromegaly: a meta-analysis.

PubMed

Sandret, Laure; Maison, Patrick; Chanson, Philippe

2011-05-01

Cabergoline is widely considered to be poorly effective in acromegaly. The aim of this study was to obtain a more accurate picture of the efficacy of cabergoline in acromegaly, both alone and in combination with somatostatin analogs. We systematically reviewed all trials of cabergoline therapy for acromegaly published up to 2009 in four databases (PubMed, Pascal, Embase, and Google Scholar). We identified 15 studies (11 prospective) with a total of 237 patients; none were randomized or placebo-controlled. A meta-analysis was conducted on individual data (n = 227). Cabergoline was used alone in nine studies. Fifty-one (34%) of the 149 patients achieved normal IGF-I levels. In multivariate analysis, the decline in IGF-I was related to the baseline IGF-I concentration (β = 1.16; P <0.001), treatment duration (β = 0.28; P < 0.001), and baseline prolactin concentration (β = -0.18; P = 0.01), and with a trend toward a relation with the cabergoline dose (β = 0.38; P =0.07). In five studies, cabergoline was added to ongoing somatostatin analog treatment that had failed to normalize IGF-I. Forty patients (52%) achieved normal IGF-I levels. The change in IGF-I was significantly related to the baseline IGF-I level (β = 0.74; P < 0.001) but not to the dose of cabergoline, the duration of treatment, or the baseline prolactin concentration. This meta-analysis suggests that cabergoline single-agent therapy normalizes IGF-I levels in one third of patients with acromegaly. When a somatostatin analog fails to control acromegaly, cabergoline adjunction normalizes IGF-I in about 50% of cases. This effect may occur even in patients with normoprolactinemia.

Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo.

PubMed

Morel, Katherine L; Ormsby, Rebecca J; Bezak, Eva; Sweeney, Christopher J; Sykes, Pamela J

2017-05-01

Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL/DMAPT-induced protection in normal tissues, nor did it affect tumor kill. These results support the use of the more bioavailable DMAPT and low-dose radiation, alone or in combination as useful radioprotectors of normal tissues to alleviate radiotherapy-induced side-effects in patients. The enhanced radiosensitisation in prostate tissues displaying high-grade PIN suggests that DMAPT also holds promise for targeted therapy of advanced prostate cancer, which may go on to become metastatic. The redox mechanisms involved in the differential radioprotection observed here suggest that increased radiotherapy efficacy by DMAPT is more broadly applicable to a range of cancer types.

Effects of pilocarpine hydrochloride and cevimeline on submandibular/sublingual salivation in rat xerostomia model produced by X-ray irradiation.

PubMed

Omori, Yasuhiro; Asari, Tetsuya; Maruyama, Kazuyasu; Kusama, Hiroshi; Kojima, Masami; Shibata, Nobuo

2003-01-01

The present study was performed to assess the effects of pilocarpine hydrochloride ((3S,4R)-3-ethyl-dihydro-4-[(1-methyl-1H-imidazole-5-yl)methyl]-2(3H)-furanone monohydrochloride, CAS 54-71-7) and cevimeline ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, CAS 153504-70-2), muscarinic receptor agonists, on salivary secretion from the submandibular/sublingual (SM/SL) glands in normal rats and in rats with xerostomia induced by X-ray (15 Gy) irradiation. To clarify their pharmacological safety profiles, the two drugs were further compared with regard to subtype selectivity for muscarinic receptors (M1, M2, and M3) and central nervous, respiratory, and cardiovascular effects. Pilocarpine hydrochloride (0.1-0.8 mg/kg i.d.) and cevimeline (3-30 mg/kg i.d.) dose-dependently increased salivary flow rate and total salivary volume in a 120-min period from SM/SL glands in both normal and irradiated rats, the minimum effective doses for their sialagogic effects being 0.2 and 10 mg/kg, respectively. Both drugs also increased protein output from SM/SL glands to a degree that depended on the increase in salivary volume in normal and irradiated rats. In a binding study using radiolabeled antagonists, neither pilocarpine hydrochloride nor cevimeline displayed subtype selectivity for muscarinic receptors, indicating non-selective muscarinic agonism. Effects on the central nervous system (CNS) were assessed by monitoring changes in body temperature in conscious normal rats. Pilocarpine hydrochloride (0.4-4 mg/kg p.o.) had no effect on body temperature, but cevimeline (30 and 100 mg/kg p.o.) caused a significant hypothermia. In terms of respiratory and cardiovascular effects in anesthetized normal rats, there was no clear difference in safety margin between pilocarpine hydrochloride and cevimeline, both drugs inducing significant changes in respiratory rate, heart rate, and blood pressure at doses close to those inducing sialagogic effects. These results suggest that pilocarpine hydrochloride could be used as a sialagogic drug for postirradiation-induced xerostomia with fewer adverse effects on the CNS.

Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

PubMed

George, Rani; Haywood, Alison; Good, Phillip; Hennig, Stefanie; Khan, Sohil; Norris, Ross; Hardy, Janet

2017-09-01

Methadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. Patients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. Fifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6-113.0 ng/mL) and 62.0 ng/mL (28.7-116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0-203.2 ng/mL) and 44.2 (16.2-149.7 ng/mL). No relationship could be established between plasma and saliva concentrations for l- and d-methadone (r 2 = 0.35 and 0.25). The saliva-to-plasma concentration analyzed with the methadone dose showed higher saliva concentrations at lower doses. Dose-normalized saliva concentrations followed a similar pattern over time compared with plasma concentrations. No correlation was found between l-methadone plasma, d-methadone plasma, l-methadone saliva, d-methadone saliva concentrations, and pain score. Saliva concentration was not a better predictor of pain control than plasma concentration for dose optimization and monitoring studies of methadone in patients with cancer. Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Body mass index had different effects on premenopausal and postmenopausal breast cancer risks: a dose-response meta-analysis with 3,318,796 subjects from 31 cohort studies.

PubMed

Chen, Yanzi; Liu, Li; Zhou, Quan; Imam, Mustapha Umar; Cai, Jialin; Wang, Yaxuan; Qi, Minjie; Sun, Panpan; Ping, Zhiguang; Fu, Xiaoli

2017-12-08

There is sufficient evidence supporting a relationship between increased body mass index (BMI) and an increased risk for breast cancer among postmenopausal women. However, most studies have found a decreased risk for premenopausal breast cancer. This study was conducted to find out the different effects of BMI on the risk of breast cancer among premenopausal and postmenopausal women, and explore the potential factors that influence the associations. A dose-response meta-analysis with 3,318,796 participants from 31 articles was conducted. Cohort studies that included BMI and corresponding breast cancer risk were selected through various databases including PubMed, Medline, Web of Science, the China National Knowledge Infrastructure (CNKI) and Chinese Scientific Journals (VIP). Random effects models were used for analyzing the data. The summary relative risks (RRs) were 1.33 (95%CI: 1.20-1.48) and 0.94(95%CI: 0.80-1.11) among postmenopausal and premenopausal women, respectively. The dose-response meta-analysis indicated a positive non-linear association between BMI and breast cancer risk among postmenopausal women, and compared to the mean level of the normal BMI category (21.5 kg/m 2 ) the RR in total postmenopausal women were1.03 (95% CI: 1.02-1.05) per 1 kg/m 2 increment. However, no statistically significant association among total premenopausal women was detected. In subgroup analysis among European premenopausal women, the summary RR was 0.79(95%CI: 0.70-0.88). The non-linear relationship showed a negative non-linear association between BMI and breast cancer risk among European premenopausal women. When compared to the mean level of the normal BMI category, the RRs were 0.98 (95%CI: 0.96-1.00) per 1 kg/m 2 increment, respectively. In line with previous studies BMI had different effects on pre-menopausal and postmenopausal breast cancer risk. However, contrary to previous studies, a high BMI was not associated with decreased risk in total pre-menopausal women. More research is needed to better understand these differences.

Recovery from Cyclophosphamide Overdose in a Dog.

PubMed

Finlay, Jessica Renee; Wyatt, Kenneth; North, Courtney

An adult female spayed dog was evaluated after inadvertently receiving a total dose of 1,750 mg oral cyclophosphamide, equivalent to 2,303 mg/m 2 , over 21 days (days -21 to 0). Nine days after the last dose of cyclophosphamide (day +9), the dog was evaluated at Perth Veterinary Specialists. Physical examination revealed mucosal pallor, a grade 2/6 systolic heart murmur, and severe hemorrhagic cystitis. Severe nonregenerative pancytopenia was detected on hematology. Broad spectrum antibiotics, two fresh whole blood transfusions, granulocyte colony stimulating factor, and tranexamic acid were administered. Five days after presentation (day +14), the peripheral neutrophil count had recovered, and by 12 days (day +21) the complete blood count was near normal. A second episode of thrombocytopenia (day +51) was managed with vincristine, prednisolone, and melatonin. The dog made a complete recovery with no long-term complications at the time of writing. To the author's knowledge, this is the highest inadvertently administered dose of cyclophosphamide to result in complete recovery.

Immunocyte responses of mouse exposure by low dose 12C6+ ion beam

NASA Astrophysics Data System (ADS)

Dang, B. R.

High LET radiations such as heavy ion or neutron have an increased biological effectiveness compared to low LET radiations for cell killing cell cycle perturbations and genetic instability In this paper we investigate the peripheral blood lymphocytes thymus cell and spleen lymphocytes cycle effects of exposure with different dose of 73 74MeV u 12 C 6 ion on mouse These BalB C were irradiated with 39cGy 55cGy and 1Gy of 12 C 6 ion at 20cGy min The cell cycle and apoptosis were determined by flow cytometry and the thymus and spleen index were measured by weight When these mice were irradiated by 12 C 6 the cycle of immunocyte had some changes and the percentage of apoptosis increased with doses increasing irradiation especially blood lymphocyte It might be suggested that irradiated by 12 C 6 total-body can result in more damage for immune system than normal irradiation

In vitro antioxidant and in vivo hepatoprotective activity of leave extract of Raphanus sativus in rats using CCL4 model.

PubMed

Syed, Shariq Naeem; Rizvi, Waseem; Kumar, Anil; Khan, Aijaz Ahmad; Moin, Shagufta; Ahsan, Akif

2014-01-01

Raphanus sativus is reported to have a variety of biological activities. This work screened the hepato-protective and antioxidant activity of ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in Carbon tetrachloride (CCl4), model in rats. The extracts were subjected to antioxidant tests (Total reducing power and Total phenolic content), and preliminary phytochemical screening. A pilot study was done on 100 and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The albino rats (200-250 grams), were divided into 5 groups of 6 animals each (n=6). There were three control groups comprising of normal control (normal saline -1ml/kg), negative control group (CCl4 1ml/kg in olive oil in a ratio of 1:1 v/v), and positive control group (Silymarin 50mg/kg). The Test drugs were given in a dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done. The phytochemical study showed the presence of flavanoids, terpenoids, alkaloids, saponins and sterols. A dose dependent increase in the oxidative potential was observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (p<0.001) increase in levels of AST, ALT and alkaline phosphatase as compared to negative control (percentage hepatoprotection =45.3%) while ARS 300 mg/kg (p<.01) group showed 30% hepatoprotection. The GSH (p<0.001) and CAT (p<0.05) in ERS and ARS were significantly increased while MDA levels were decreased (P< 0.01), as compared negative control. The findings were confirmed histo-pathological examination. The ethanol and aqueous extract of Raphanus sativus have partial hepatoprotection against CCl4 toxicity.

Dose reduction and cost-benefit analysis at Japan`s Tokai No. 2 Plant

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

Humamoto, Hisao; Suzuki, Seishiro; Taniguchi, Kazufumi

1995-03-01

In the Tokai No. 2 power plant of the Japan Atomic Power Company, about 80% of the annual dose equivalent is received during periodic maintenance outages. A project group for dose reduction was organized at the company`s headquarters in 1986; in 1988, they proposed a five-year program to reduce by half the collective dose of 4 person-Sv per normal outage work. To achieve the target dose value, some dose-reduction measures were undertaken, namely, permanent radiation shielding, decontamination, automatic, operating machines, and ALARA organization. As the result, the collective dose from normal outage work was 1.6 person-Sv in 1992, which wasmore » less than the initial target value.« less

Esophageal wall dose-surface maps do not improve the predictive performance of a multivariable NTCP model for acute esophageal toxicity in advanced stage NSCLC patients treated with intensity-modulated (chemo-)radiotherapy.

PubMed

Dankers, Frank; Wijsman, Robin; Troost, Esther G C; Monshouwer, René; Bussink, Johan; Hoffmann, Aswin L

2017-05-07

In our previous work, a multivariable normal-tissue complication probability (NTCP) model for acute esophageal toxicity (AET) Grade  ⩾2 after highly conformal (chemo-)radiotherapy for non-small cell lung cancer (NSCLC) was developed using multivariable logistic regression analysis incorporating clinical parameters and mean esophageal dose (MED). Since the esophagus is a tubular organ, spatial information of the esophageal wall dose distribution may be important in predicting AET. We investigated whether the incorporation of esophageal wall dose-surface data with spatial information improves the predictive power of our established NTCP model. For 149 NSCLC patients treated with highly conformal radiation therapy esophageal wall dose-surface histograms (DSHs) and polar dose-surface maps (DSMs) were generated. DSMs were used to generate new DSHs and dose-length-histograms that incorporate spatial information of the dose-surface distribution. From these histograms dose parameters were derived and univariate logistic regression analysis showed that they correlated significantly with AET. Following our previous work, new multivariable NTCP models were developed using the most significant dose histogram parameters based on univariate analysis (19 in total). However, the 19 new models incorporating esophageal wall dose-surface data with spatial information did not show improved predictive performance (area under the curve, AUC range 0.79-0.84) over the established multivariable NTCP model based on conventional dose-volume data (AUC  =  0.84). For prediction of AET, based on the proposed multivariable statistical approach, spatial information of the esophageal wall dose distribution is of no added value and it is sufficient to only consider MED as a predictive dosimetric parameter.

[Clinical applications of dosing algorithm in the predication of warfarin maintenance dose].

PubMed

Huang, Sheng-wen; Xiang, Dao-kang; An, Bang-quan; Li, Gui-fang; Huang, Ling; Wu, Hai-li

2011-12-27

To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population. The clinical data were collected and blood samples harvested from a total of 126 patients undergoing heart valve replacement. The genotypes of VKORC1 and CYP2C9 were determined by melting curve analysis after PCR. They were divided randomly into the study and control groups. In the study group, the first three doses of warfarin were prescribed according to the predicted warfarin maintenance dose while warfarin was initiated at 2.5 mg/d in the control group. The warfarin doses were adjusted according to the measured international normalized ratio (INR) values. And all subjects were followed for 50 days after an initiation of warfarin therapy. At the end of a 50-day follow-up period, the proportions of the patients on a stable dose were 82.4% (42/51) and 62.5% (30/48) for the study and control groups respectively. The mean durations of reaching a stable dose of warfarin were (27.5 ± 1.8) and (34.7 ± 1.8) days and the median durations were (24.0 ± 1.7) and (33.0 ± 4.5) days in the study and control groups respectively. Significant differences existed in the durations of reaching a stable dose between the two groups (P = 0.012). Compared with the control group, the hazard ratio (HR) for the duration of reaching a stable dose was 1.786 in the study group (95%CI 1.088 - 2.875, P = 0.026). The predicted dosing algorithm incorporating genetic and non-genetic factors may shorten the duration of achieving efficiently a stable dose of warfarin. And the present study validates the feasibility of its clinical application.

Esophageal wall dose-surface maps do not improve the predictive performance of a multivariable NTCP model for acute esophageal toxicity in advanced stage NSCLC patients treated with intensity-modulated (chemo-)radiotherapy

NASA Astrophysics Data System (ADS)

Dankers, Frank; Wijsman, Robin; Troost, Esther G. C.; Monshouwer, René; Bussink, Johan; Hoffmann, Aswin L.

2017-05-01

In our previous work, a multivariable normal-tissue complication probability (NTCP) model for acute esophageal toxicity (AET) Grade  ⩾2 after highly conformal (chemo-)radiotherapy for non-small cell lung cancer (NSCLC) was developed using multivariable logistic regression analysis incorporating clinical parameters and mean esophageal dose (MED). Since the esophagus is a tubular organ, spatial information of the esophageal wall dose distribution may be important in predicting AET. We investigated whether the incorporation of esophageal wall dose-surface data with spatial information improves the predictive power of our established NTCP model. For 149 NSCLC patients treated with highly conformal radiation therapy esophageal wall dose-surface histograms (DSHs) and polar dose-surface maps (DSMs) were generated. DSMs were used to generate new DSHs and dose-length-histograms that incorporate spatial information of the dose-surface distribution. From these histograms dose parameters were derived and univariate logistic regression analysis showed that they correlated significantly with AET. Following our previous work, new multivariable NTCP models were developed using the most significant dose histogram parameters based on univariate analysis (19 in total). However, the 19 new models incorporating esophageal wall dose-surface data with spatial information did not show improved predictive performance (area under the curve, AUC range 0.79-0.84) over the established multivariable NTCP model based on conventional dose-volume data (AUC  =  0.84). For prediction of AET, based on the proposed multivariable statistical approach, spatial information of the esophageal wall dose distribution is of no added value and it is sufficient to only consider MED as a predictive dosimetric parameter.

Non-nutritive sweeteners are not super-normal stimuli

PubMed Central

Antenucci, Rachel G.; Hayes, John E.

2014-01-01

Background It is often claimed that non-nutritive sweeteners (NNS) are ‘sweeter than sugar’, with the implicit implication high potency sweeteners are super-normal stimuli that encourage exaggerated responses. This study aimed to investigate the perceived sweetness intensity of a variety of nutritive (Sucrose, Maple Syrup, and Agave Nectar) and NNS (Acesulfame-K (AceK), Rebaudioside A (RebA), Aspartame, and Sucralose) in a large cohort of untrained participants using contemporary psychophysical methods. Methods Participants (n=401 total) rated the intensity of sweet, bitter, and metallic sensations for nutritive and NNS in water using the general labeled magnitude scale (gLMS). Results Sigmoidal Dose-Response functions were observed for all stimuli except AceK. That is, sucrose follows a sigmoidal function if the data are not artifactually linearized via prior training. More critically, there is no evidence that NNS have a maximal sweetness (intensity) greater than sucrose; indeed, the maximal sweetness for AceK, RebA and Sucralose were significantly lower than for concentrated sucrose. For these sweeteners, mixture suppression due to endogenous dose-dependent bitter or metallic sensations appears to limit maximal perceived sweetness. Conclusions In terms of perceived sweetness, non-nutritive sweeteners cannot be considered super-normal stimuli. These data do not support the view that non-nutritive sweeteners hijack or over-stimulate sweet receptors to product elevated sweet sensations. PMID:24942868

Antihypercholesterolemic and antioxidant effect of sterol rich methanol extract of stem of Musa sapientum (banana) in cholesterol fed wistar rats.

PubMed

Dikshit, Piyush; Tyagi, Mool Kumar; Shukla, Kirtikar; Gambhir, Jasvindar K; Shukla, Rimi

2016-03-01

Musa sapientum Linn. (English 'Banana' family Musaceae), is a plant with nutritive, as well as medicinal value. Antihypercholesterolemic and antioxidant effect of methanolic extract of stem of this plant was investigated in hypercholesterolemic rats. Rats were made hypercholesterolemic by feeding cholesterol (100 mg/kg/day) suspended in soya oil. Treatment groups received extract at a dose of 10, 20 and 40 mg/kg/day in addition to cholesterol orally once daily. Fasting blood samples were collected before and after 6 weeks treatment. Animals were sacrificed and liver stored at -80 °C. Total cholesterol, HDL-cholesterol and triacylglycerol were estimated in blood. Malondialdehyde, reduced glutathione, superoxide dismutase and catalase were measured in blood and liver. Total lipids, HMG CoA redutase and lipoprotein lipase were investigated in liver. Most effective dose was found to be 20 mg/kg/day. Rise in total cholesterol, LDL + VLDL-cholesterol and triacylglycerol in animals receiving only cholesterol was 179 %, 417 % and 74 % respectively, while in animals receiving 20 mg/kg dose rise in these parameters was restricted to 40 %, 106 % and 24 %. HDL-cholesterol decreased by 12 % in extract treated group, while it decreased to 36 % in untreated hypercholesterolemic rats. Malonaldialdehyde, marker of lipid peroxidation decreased while reduced glutathione and enzymes superoxide dismutase and catalase increased significantly in blood and liver (p < 0.01). Total lipids in liver decreased and enzymes of lipid metabolism viz. HMG CoA redutase and lipoprotein lipase were restored to near normal. Gas chromatography mass spectroscopy indicated high content of sterols in extract. Study demonstrated that methanol extract of stem of Musa sapientum has significant antihypercholesterolemic and antioxidant effects.

A Dosimetric Comparison of Proton and Intensity-Modulated Photon Radiotherapy for Pediatric Parameningeal Rhabdomyosarcomas

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

Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

PubMed

Abend, M; Pfeiffer, R M; Ruf, C; Hatch, M; Bogdanova, T I; Tronko, M D; Hartmann, J; Meineke, V; Mabuchi, K; Brenner, A V

2013-10-15

A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants.

PubMed

Huynh, Julie; Lu, Thao; Liew, Danny; Doery, James Cg; Tudball, Ronald; Jona, Madeleine; Bhamjee, Roisin; Rodda, Christine P

2017-02-01

There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L). Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: A randomized study of two dose-per-fraction levels

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

Sorbe, Bengt; Straumits, Andris; Karlsson, Leif

2005-08-01

Purpose To compare two different fractionation schedules for postoperative vaginal high-dose-rate (HDR) irradiation in endometrial carcinomas. Methods and Materials In a complete geographic series of 290 low-risk endometrial carcinomas, the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated. The patients were treated during the years 1989-2003. The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grades 1-2. The HDR MicroSelectron afterloading equipment (iridium-192) was used. Perspex vaginal applicators with diameters of 20-30 mm were used, and the dose was specified at 5 mm from the surface of the applicator.more » Six fractions were given, and the overall treatment time was 8 days. The size of the dose per fraction was randomly set to 2.5 Gy (total dose of 15.0 Gy) or 5.0 Gy (total dose of 30.0 Gy). One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction. Results The overall locoregional recurrence rate of the complete series was 1.4% and the rate of vaginal recurrences 0.7%. There was no difference between the two randomized groups. The vaginal shortening measured by colpometry was not significant (p = 0.159) in the 2.5-Gy group (mean, 0.3 cm) but was highly significant (p < 0.000001) in the 5.0-Gy group (mean 2.1 cm) after 5 years. Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group. Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women. Conclusion The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used.« less

[4D-CT-based plan target volume (PTV) definition compared with conventional PTV definition using general margin in radiotherapy for lung cancer].

PubMed

Ju, Xiao; Li, Minghui; Zhou, Zongmei; Zhang, Ke; Han, Wei; Fu, Guishan; Cao, Ying; Wang, Lyuhua

2014-01-01

To investigate the dosimetric benefit of 4D-CT in the planning target volume (PTV) definition process compared with conventional PTV definition using general margin in radiotherapy of lung cancer. A set of 4D-CT images and multiphase helical CT scans were obtained in 10 patients with lung cancer. The radiotherapeutic plans based on PTV determined by 4D-CT and in addition of general margin were performed, respectively. The 3D motion of the centroid of GTV and the 3D spatial motion vectors were calculated. The differences of the two kinds of PTVs, mean lung dose (MLD), V5,V10,V15,V20 of total lung, mean heart dose (MHD), V30 and V40 of heart, D99 and D95 were compared, and the correlation between them and the 3D spatial motion vector was analyzed. The PTV4D in eight patients were smaller than PTVconv, with a mean reduction of (13.0 ± 8.0)% (P = 0.018). In other two patients, whose respiration motion was great, PTV4D was larger than PTVconv. The mean 3D spatial motion vector of GTV centroid was (0.78 ± 0.72)cm. By using 4D-CT, the mean reduction of MLD was (8.6 ± 9.9)% (P = 0.037). V5, V10, V15, V20 of total lung were decreased averagely by (7.2 ± 10.5)%, (5.5 ± 8.9)%, (6.5 ± 8.4)% and (5.7 ± 7.4)%, respectively (P < 0.05 for all). There was a significant positive correlation between PTV4D/PTVconv and the 3D spatial motion vector of the GTV centroid (P = 0.008). A significant inverse correlation was found between D994D/D99conv and the 3D spatial motion vector of the GTV centroid (P = 0.002). D994D/D99conv, (MLDconv-MLD4D) /MLDconv, total lung (V5conv-V54D)/V5conv, total lung (V10conv-V104D)/V10conv, (MHDconv-MHD4D)/MHDconv, heart (V30conv-V304D)/V30conv were inversely correlated with PTV4D/PTVconv (P < 0.05 for all). 4D-CT can be used to evaluate the respiration motion of lung tumor accurately. The 4D-CT-based PTV definition and radiotherapeutic planing can reduce the volume of PTV in patients with small respiration motion, increase the intra-target dose, and decrease the dose of normal tissue sequentially. For patients with large respiration motion, especially those more than 1.5-2 cm, this method can avoid target miss, meanwhile, not increase the dose of normal tissue significantly.

Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

PubMed

Keyerleber, M A; Gieger, T L; Erb, H N; Thompson, M S; McEntee, M C

2012-12-01

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures. © 2011 Blackwell Publishing Ltd.

Application of the Low-dose One-stop-shop Cardiac CT Protocol with Third-generation Dual-source CT.

PubMed

Lin, Lu; Wang, Yining; Yi, Yan; Cao, Jian; Kong, Lingyan; Qian, Hao; Zhang, Hongzhi; Wu, Wei; Wang, Yun; Jin, Zhengyu

2017-02-20

Objective To evaluate the feasibility of a low-dose one-stop-shop cardiac CT imaging protocol with third-generation dual-source CT (DSCT). Methods Totally 23 coronary artery disease (CAD) patients were prospectively enrolled between March to September in 2016. All patients underwent an ATP stress dynamic myocardial perfusion imaging (MPI) (data acquired prospectively ECG-triggered during end systole by table shuttle mode in 32 seconds) at 70 kV combined with prospectively ECG-triggered high-pitch coronary artery angiography (CCTA) on a third-generation DSCT system. Myocardial blood flow (MBF) was quantified and compared between perfusion normal and abnormal myocardial segments based on AHA-17-segment model. CCTA images were evaluated qualitatively based on SCCT-18-segment model and the effective dose(ED) was calculated. In patients with subsequent catheter coronary angiography (CCA) as reference,the diagnosis performance of MPI (for per-vessel ≥50% and ≥70% stenosis) and CCTA (for≥50% stenosis) were assessed. Results Of 23 patients who had completed the examination of ATP stress MPI plus CCTA,12 patients received follow-up CCA. At ATP stress MPI,77 segments (19.7%) in 13 patients (56.5%) had perfusion abnormalities. The MBF values of hypo-perfused myocardial segments decreased significantly compared with normal segments [(93±22)ml/(100 ml·min) vs. (147±27)ml/(100 ml·min);t=15.978,P=0.000]. At CCTA,93.9% (308/328) of the coronary segments had diagnostic image quality. With CCA as the reference standard,the per-vessel and per-segment sensitivity,specificity,and accuracy of CCTA for stenosis≥50% were 94.1%,93.5%,and 93.7% and 90.9%,97.8%,and 96.8%,and the per-vessel sensitivity,specificity and accuracy of ATP stress MPI for stenosis≥50% and ≥70% were 68.7%,100%,and 89.5% and 91.7%,100%,and 97.9%. The total ED of MPI and CCTA was (3.9±1.3) mSv [MPI:(3.5±1.2) mSv,CCTA:(0.3±0.1) mSv]. Conclusion The third-generation DSCT stress dynamic MPI at 70 kV combined with prospectively ECG-triggered high-pitch CCTA is a feasible and reliable tool for clinical diagnosis,with remarkably reduced radiation dose.

SU-E-T-233: Cyberknife Versus Linac IMRT for Dose Comparision in Hypofractionated Hemi Larynx Irradiation of Early Stage True Vocal Cord Cancer: A Dosimetric Study

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

Ding, C; Lee, P; Jiang, S

2015-06-15

Purpose: To compare dosimetric data of patients treated for early-stage larynx cancer on Cyberknife and Linac IMRT. Methods: Nine patients were treated with Cyberknife to a dose of 45 Gy in 10 fractions of the involved hemilarynx. The prescription dose provided at least 95% of PTV coverage. After Cyberknife treatment, the CT images and contours were sent to Pinnacle treatment planning system for IMRT planning on a regular SBRT linac with same dose prescription and constrains. Dose to target and normal tissue, including the arytenoids, cord, carotid arteries, thyroid, and skin, were analyzed using dose volume histograms. Results: For Cyberknifemore » plan, the conformity indices are within 1.11–1.33. The average dose to the contralateral arytenoids for Cyberknife plans was 28.9±6.5Gy), which is lower than the same mean dose for IMRT plans (34.0±5.2 Gy). The average maximum dose to the ipsilateral and contralateral carotid artery were 20.6 ±9.1 Gy and 10.2±6.0 Gy respectively for Cybeknife comparing with 22.1±8.0 Gy and 12.0±5.1 Gy for IMRT. The mean dose to the thyroid was 3.6±2.2 Gy for Cyberknife and 3.4±2.4 Gy for IMRT. As shown in DVH, the Cyberknife can deliver less dose to the normal tissue which is close to target area comparing with IMRT Plans. However, IMRT plan’s can give more sparing for the critical organs which is far away from the target area. Conclusion: We have compared the dosimetric parameters of Cyberknife and linac IMRT plans for patients with early-stage larynx cancer. Both Cyberknife and IMRT plans can achieve conformal dose distribution to the target area. Cyberknife was able to reduce normal tissue dose in high doses region while IMRT plans can reduce the dose of the normal tissue at the low dose region. These dosimetric parameters can be used to guide future prospective protocols using SBRT for larynx cancer.« less

The relationship between total cholinesterase activity and mortality in four butterfly species

USGS Publications Warehouse

Bargar, Timothy A.

2012-01-01

The relationship between total cholinesterase activity (TChE) and mortality in four butterfly species (great southern white [Ascia monuste], common buckeye [Junonia coenia], painted lady [Vanessa cardui], and julia butterflies [Dryas julia]) was investigated. Acute contact toxicity studies were conducted to evaluate the response (median lethal dose [LD50] and TChE) of the four species following exposure to the organophosphate insecticide naled. The LD50 for these butterflies ranged from 2.3 to 7.6 μg/g. The average level of TChE inhibition associated with significant mortality ranged from 26 to 67%, depending on the species. The lower bounds of normal TChE activity (2 standard deviations less than the average TChE for reference butterflies) ranged from 8.4 to 12.3 μM/min/g. As a percentage of the average reference TChE activity for the respective species, the lower bounds were similar to the inhibition levels associated with significant mortality, indicating there was little difference between the dose resulting in significant TChE inhibition and that resulting in mortality.

Disposition of [14C]N,N-dimethyl-p-toluidine in F344 rats and B6C3F1 mice.

PubMed

Dix, Kelly J; Ghanbari, Katayoon; Hedtke-Weber, Briana M

2007-05-15

N,N-Dimethyl-p-toluidine (DMPT) is used as a polymerization accelerator, in industrial glues, and as an intermediate in dye and pesticide synthesis. There is potential for human exposure to DMPT. The disposition of oral and intravenous (i.v.) doses of [14C]DMPT in F344 rats and B6C3F1 mice was investigated. A single i.v. (2.5 mg/kg) or oral (2.5, 25, or 250 mg/kg) dose of [14C]DMPT (1-25 microCi) was administered in an aqueous vehicle to male rats and mice. The 25-mg/kg oral dose was administered to females to investigate possible gender differences in disposition. However, no striking gender differences were observed. Since toxicity studies conducted elsewhere used a corn oil vehicle, the 250-mg/kg oral dose also was administered in corn oil to male rats; disposition was not dependent on vehicle. Excreta (through 24 h) and tissues collected at sacrifice were analyzed for total radioactivity. Dose-dependent differences in toxicity and disposition were observed. Toxicity at the 250-mg/kg oral dose to male mice was consistent with acute renal failure. At the same dose, male rats exhibited clinical signs of toxicity through 12 h but were clinically normal by 24 h. At lower oral doses, [14C]DMPT-derived radioactivity was well absorbed and rapidly excreted, primarily in urine.

SU-E-T-618: Dosimetric Comparison of Manual and Beam Angle Optimization of Gantry Angles in IMRT for Cervical Cancer

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

Lin, X; Sun, T; Liu, T

2014-06-01

Purpose: To evaluate the dosimetric characteristics of intensity-modulated radiotherapy (IMRT) treatment plan with beam angle optimization. Methods: Ten post-operation patients with cervical cancer were included in this analysis. Two IMRT plans using seven beams were designed in each patient. A standard coplanar equi-space beam angles were used in the first plan (plan 1), whereas the selection of beam angle was optimized by beam angle optimization algorithm in Varian Eclipse treatment planning system for the same number of beams in the second plan (plan 2). Two plans were designed for each patient with the same dose-volume constraints and prescription dose. Allmore » plans were normalized to the mean dose to PTV. The dose distribution in the target, the dose to the organs at risk and total MU were compared. Results: For conformity and homogeneity in PTV, no statistically differences were observed in the two plans. For the mean dose in bladder, plan 2 were significantly lower than plan 1(p<0.05). No statistically significant differences were observed between two plans for the mean doses in rectum, left and right femur heads. Compared with plan1, the average monitor units reduced 16% in plan 2. Conclusion: The IMRT plan based on beam angle optimization for cervical cancer could reduce the dose delivered to bladder and also reduce MU. Therefore there were some dosimetric advantages in the IMRT plan with beam angle optimization for cervical cancer.« less

Clinical application of 3D-printed-step-bolus in post-total-mastectomy electron conformal therapy.

PubMed

Park, Kwangwoo; Park, Sungjin; Jeon, Mi-Jin; Choi, Jinhyun; Kim, Jun Won; Cho, Yoon Jin; Jang, Won-Seok; Keum, Yo Sup; Lee, Ik Jae

2017-04-11

The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0.47% versus -4.43%). On comparing the dose-volume histogram (DVH), it was found that the 3D-printed boluses resulted in a reduction in the mean dose to the ipsilateral lung by up to 20%. The precision of dose delivery was improved by 3% with the 3D-printed boluses; in contrast, the conventional step bolus resulted in a precision level of 5%. In conclusion, the use of the 3D-printed boluses resulted in better dose homogeneity and conformity to the chest wall as well as the sparing of the normal organs, especially the lung. This suggested that their routine use on the chest wall as a therapeutic approach during post-mastectomy radiation therapy offers numerous advantages over conventional step boluses.

Clinical application of 3D-printed-step-bolus in post-total-mastectomy electron conformal therapy

PubMed Central

Park, Kwangwoo; Park, Sungjin; Jeon, Mi-Jin; Choi, Jinhyun; Kim, Jun Won; Cho, Yoon Jin; Jang, Won-Seok; Keum, Yo Sup; Lee, Ik Jae

2017-01-01

The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0.47% versus -4.43%). On comparing the dose-volume histogram (DVH), it was found that the 3D-printed boluses resulted in a reduction in the mean dose to the ipsilateral lung by up to 20%. The precision of dose delivery was improved by 3% with the 3D-printed boluses; in contrast, the conventional step bolus resulted in a precision level of 5%. In conclusion, the use of the 3D-printed boluses resulted in better dose homogeneity and conformity to the chest wall as well as the sparing of the normal organs, especially the lung. This suggested that their routine use on the chest wall as a therapeutic approach during post-mastectomy radiation therapy offers numerous advantages over conventional step boluses. PMID:27784001

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

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

Storb, R.; Raff, R.F.; Graham, T.

1993-03-20

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionatedmore » total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.« less

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

PubMed

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Excretion of (3H)prednisolone in clinically normal and experimentally infected bovine udders

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

Geleta, J.N.; Shimoda, W.; Mercer, H.D.

1984-08-01

The excretion rate of (3H)prednisolone from clinically normal and experimentally infected udders of 10 lactating cows was studied. Each quarter of 6 cows was injected with a single dose of (3H)prednisolone mixed with non-radioactive prednisolone equivalent to 10 mg in 10 ml of peanut oil base. Each of the remaining 4 cows was given 40 mg of nonradioactive prednisolone and (3H)prednisolone in 60% ethanol IV. Control and postadministration samples of blood, milk, and urine were examined for radioactivity. The effects of (3H)prednisolone were evaluated in the same cows, first in clinically normal udders, then 2 weeks later in udders experimentallymore » infected with Streptococcus agalactiae. Absorption and elimination of prednisolone were the same before and after induced infection. Within 3 hours after intramammary injection, 95% of the labeled prednisolone was absorbed systemically, less than 5% of this dose was recovered in milk, and 29% was excreted in urine. After IV injection of (3H)prednisolone, less than 0.2% of the total radioactivity was recovered in milk and less than 46% was excreted in urine. Clinical mastitis induced by S agalactiae was moderate. Circulating blood leukocytes and somatic cells in the milk of normal cows remained essentially unchanged. The leukocyte response to induced infection was rapid in blood and milk. Large numbers of leukocytes were noticed in the milk and a severe leukopenia occurred. Prednisolone treatment did not alter the number of somatic cells in milk or reduce the inflammatory response of experimentally infected cows.« less

Assessing the Clinical Impact of Approximations in Analytical Dose Calculations for Proton Therapy

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

Schuemann, Jan, E-mail: jschuemann@mgh.harvard.edu; Giantsoudi, Drosoula; Grassberger, Clemens

2015-08-01

Purpose: To assess the impact of approximations in current analytical dose calculation methods (ADCs) on tumor control probability (TCP) in proton therapy. Methods: Dose distributions planned with ADC were compared with delivered dose distributions as determined by Monte Carlo simulations. A total of 50 patients were investigated in this analysis with 10 patients per site for 5 treatment sites (head and neck, lung, breast, prostate, liver). Differences were evaluated using dosimetric indices based on a dose-volume histogram analysis, a γ-index analysis, and estimations of TCP. Results: We found that ADC overestimated the target doses on average by 1% to 2%more » for all patients considered. The mean dose, D95, D50, and D02 (the dose value covering 95%, 50% and 2% of the target volume, respectively) were predicted within 5% of the delivered dose. The γ-index passing rate for target volumes was above 96% for a 3%/3 mm criterion. Differences in TCP were up to 2%, 2.5%, 6%, 6.5%, and 11% for liver and breast, prostate, head and neck, and lung patients, respectively. Differences in normal tissue complication probabilities for bladder and anterior rectum of prostate patients were less than 3%. Conclusion: Our results indicate that current dose calculation algorithms lead to underdosage of the target by as much as 5%, resulting in differences in TCP of up to 11%. To ensure full target coverage, advanced dose calculation methods like Monte Carlo simulations may be necessary in proton therapy. Monte Carlo simulations may also be required to avoid biases resulting from systematic discrepancies in calculated dose distributions for clinical trials comparing proton therapy with conventional radiation therapy.« less

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

Pokhrel, D; Sood, S; Badkul, R

Purpose: To compare dose distributions calculated using PB-hete vs. XVMC algorithms for SRT treatments of cavernous sinus tumors. Methods: Using PB-hete SRT, five patients with cavernous sinus tumors received the prescription dose of 25 Gy in 5 fractions for planning target volume PTV(V100%)=95%. Gross tumor volume (GTV) and organs at risk (OARs) were delineated on T1/T2 MRI-CT-fused images. PTV (range 2.1–84.3cc, mean=21.7cc) was generated using a 5mm uniform-margin around GTV. PB-hete SRT plans included a combination of non-coplanar conformal arcs/static beams delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000 MU/min) beam. Plans were re-optimized using XVMC algorithm with identicalmore » beam geometry and MLC positions. Comparison of plan specific PTV(V99%), maximal, mean, isocenter doses, and total monitor units(MUs) were evaluated. Maximal dose to OARs such as brainstem, optic-pathway, spinal cord, and lenses as well as normal tissue volume receiving 12Gy(V12) were compared between two algorithms. All analysis was performed using two-tailed paired t-tests of an upper-bound p-value of <0.05. Results: Using either algorithm, no dosimetrically significant differences in PTV coverage (PTVV99%,maximal, mean, isocenter doses) and total number of MUs were observed (all p-values >0.05, mean ratios within 2%). However, maximal doses to optic-chiasm and nerves were significantly under-predicted using PB-hete (p=0.04). Maximal brainstem, spinal cord, lens dose and V12 were all comparable between two algorithms, with exception of one patient with the largest PTV who exhibited 11% higher V12 with XVMC. Conclusion: Unlike lung tumors, XVMC and PB-hete treatment plans provided similar PTV coverage for cavernous sinus tumors. Majority of OARs doses were comparable between two algorithms, except for small structures such as optic chiasm/nerves which could potentially receive higher doses when using XVMC algorithm. Special attention may need to be paid on a case-by-case basis when planning for sinus SRT based on tumor size and location to OARs particularly the optic apparatus.« less

Comparison of heart and coronary artery doses associated with intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for distal esophageal cancer.

PubMed

Kole, Thomas P; Aghayere, Osarhieme; Kwah, Jason; Yorke, Ellen D; Goodman, Karyn A

2012-08-01

To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients with distal esophageal cancer undergoing chemoradiation. Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters were statistically evaluated using the Wilcoxon rank-sum test. Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT. Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D-CRT. Long-term studies are necessary to determine how this will impact on development of coronary artery disease and other cardiac complications. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-F-T-51: Investigating the Effect of Eye Size and Eccentricity On Normal Tissue Doses From Eye Plaque Brachytherapy

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

Polsdofer, E; Crilly, R

Purpose: This study investigates the effect of eye size and eccentricity on doses to critical tissues by simulating doses in the Plaque Simulator (v. 6.3.1) software. Present OHSU plaque brachytherapy treatment focuses on delivering radiation to the tumor measured with ocular ultrasound plus a small margin and assumes the orbit has the dimensions of a “standard eye.” Accurately modeling the dimensions of the orbit requires a high resolution ocular CT. This study quantifies how standard differences in equatorial diameters and eccentricity affect calculated doses to critical structures in order to query the justification of the additional CT scan to themore » treatment planning process. Methods: Tumors of 10 mm × 10 mm × 5 mm were modeled at the 12:00:00 hour with a latitude of 45 degrees. Right eyes were modeled at a number of equatorial diameters from 17.5 to 28 mm for each of the standard non-notched COMS plaques with silastic inserts. The COMS plaques were fully loaded with uniform activity, centered on the tumor, and prescribed to a common tumor dose (85 Gy/100 hours). Variations in the calculated doses to normal structures were examined to see if the changes were significant. Results: The calculated dose to normal structures show a marked dependence on eye geometry. This is exemplified by fovea dose which more than doubled in the smaller eyes and nearly halved in the larger model. Additional significant dependence was found in plaque size on the calculated dose in spite of all plaques giving the same dose to the prescription point. Conclusion: The variation in dose with eye dimension fully justifies the addition of a high resolution ocular CT to the planning technique. Additional attention must be made to plaque size beyond simply covering the tumor when considering normal tissue dose.« less

Pediatric Chest and Abdominopelvic CT: Organ Dose Estimation Based on 42 Patient Models

PubMed Central

Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Paulson, Erik K.; Frush, Donald P.

2014-01-01

Purpose To estimate organ dose from pediatric chest and abdominopelvic computed tomography (CT) examinations and evaluate the dependency of organ dose coefficients on patient size and CT scanner models. Materials and Methods The institutional review board approved this HIPAA–compliant study and did not require informed patient consent. A validated Monte Carlo program was used to perform simulations in 42 pediatric patient models (age range, 0–16 years; weight range, 2–80 kg; 24 boys, 18 girls). Multidetector CT scanners were modeled on those from two commercial manufacturers (LightSpeed VCT, GE Healthcare, Waukesha, Wis; SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). Organ doses were estimated for each patient model for routine chest and abdominopelvic examinations and were normalized by volume CT dose index (CTDIvol). The relationships between CTDIvol-normalized organ dose coefficients and average patient diameters were evaluated across scanner models. Results For organs within the image coverage, CTDIvol-normalized organ dose coefficients largely showed a strong exponential relationship with the average patient diameter (R2 > 0.9). The average percentage differences between the two scanner models were generally within 10%. For distributed organs and organs on the periphery of or outside the image coverage, the differences were generally larger (average, 3%–32%) mainly because of the effect of overranging. Conclusion It is feasible to estimate patient-specific organ dose for a given examination with the knowledge of patient size and the CTDIvol. These CTDIvol-normalized organ dose coefficients enable one to readily estimate patient-specific organ dose for pediatric patients in clinical settings. This dose information, and, as appropriate, attendant risk estimations, can provide more substantive information for the individual patient for both clinical and research applications and can yield more expansive information on dose profiles across patient populations within a practice. © RSNA, 2013 PMID:24126364

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

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

Chang, S; Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression andmore » cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide the added clinical benefit of improving treatment therapeutic ratio. Animal Studies were performed within the LCCC Animal Studies Core Facility at the University of North Carolina at Chapel Hill. The LCCC Animal Studies Core is supported in part by an NCI Center Core Support Grant (CA16086) to the UNC Lineberger Comprehensive Cancer Center.« less

Patient-specific dose calculations for pediatric CT of the chest, abdomen and pelvis

PubMed Central

Fraser, Nicholas D.; Carver, Diana E.; Pickens, David R.; Price, Ronald R.; Hernanz-Schulman, Marta; Stabin, Michael G.

2015-01-01

Background Organ dose is essential for accurate estimates of patient dose from CT. Objective To determine organ doses from a broad range of pediatric patients undergoing diagnostic chest–abdomen–pelvis CT and investigate how these relate to patient size. Materials and methods We used a previously validated Monte Carlo simulation model of a Philips Brilliance 64 multi-detector CT scanner (Philips Healthcare, Best, The Netherlands) to calculate organ doses for 40 pediatric patients (M:F=21:19; range 0.6–17 years). Organ volumes and positions were determined from the images using standard segmentation techniques. Non-linear regression was performed to determine the relationship between volume CT dose index (CTDIvol)-normalized organ doses and abdominopelvic diameter. We then compared results with values obtained from independent studies. Results We found that CTDIvol-normalized organ dose correlated strongly with exponentially decreasing abdominopelvic diameter (R2>0.8 for most organs). A similar relationship was determined for effective dose when normalized by dose-length product (R2=0.95). Our results agreed with previous studies within 12% using similar scan parameters (i.e. bowtie filter size, beam collimation); however results varied up to 25% when compared to studies using different bowtie filters. Conclusion Our study determined that organ doses can be estimated from measurements of patient size, namely body diameter, and CTDIvol prior to CT examination. This information provides an improved method for patient dose estimation. PMID:26142256

Poster — Thur Eve — 64: Preliminary investigation of arc configurations for optimal sparing of normal tissue in hypofractionated stereotactic radiotherapy (HF-SRT) of multiple brain metastases using a 5mm interdigitating micro-multileaf collimator

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

Leavens, C; Wronski, M; Lee, YK

2014-08-15

Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter andmore » arc configuration used in the SynBM plan, where closely spaced (<5cm) BMs used a dedicated isocenter and arcs. Agility plans were normalized for PTV coverage and heterogeneity. Results and Conclusion: Strategy A obtained the greatest improvements over the SynBM plan, where the maximum OAR dose, and mean dose to normal brain (averaged for all patients) were reduced by 55cGy and 25cGy, respectively. Strategy B was limited by having a single isocenter, hence less jaw shielding and increased MLC leakage. The maximum OAR dose was reduced by 13cGy, however mean dose to normal brain increased by 84cGy. Strategy C reduced the maximum OAR dose and mean dose to normal brain by 32cGy and 9cGy, respectively. The results from this study indicate that, for intra-cranial HF-SRT of multiple BMs, Agility plans are equal or better than SynBM plans. Further planning is needed to investigate dose sparing using Strategy A and the SynBM.« less

Dosimetric and radiobiological characterizations of prostate intensity-modulated radiotherapy and volumetric-modulated arc therapy: A single-institution review of ninety cases

PubMed Central

Khan, Muhammad Isa; Jiang, Runqing; Kiciak, Alexander; ur Rehman, Jalil; Afzal, Muhammad; Chow, James C. L.

2016-01-01

This study reviewed prostate volumetric-modulated arc therapy (VMAT) plans with intensity-modulated radiotherapy (IMRT) plans after prostate IMRT technique was replaced by VMAT in an institution. Characterizations of dosimetry and radiobiological variation in prostate were determined based on treatment plans of 40 prostate IMRT patients (planning target volume = 77.8–335 cm3) and 50 VMAT patients (planning target volume = 120–351 cm3) treated before and after 2013, respectively. Both IMRT and VMAT plans used the same dose-volume criteria in the inverse planning optimization. Dose-volume histogram, mean doses of target and normal tissues (rectum, bladder and femoral heads), dose-volume points (D99% of planning target volume; D30%, D50%, V30 Gy and V35 Gy of rectum and bladder; D5%, V14 Gy, V22 Gy of femoral heads), conformity index (CI), homogeneity index (HI), gradient index (GI), prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman-Burman-Kutcher algorithm were calculated for each IMRT and VMAT plan. From our results, VMAT plan was found better due to its higher (1.05%) CI, lower (0.83%) HI and (0.75%) GI than IMRT. Comparing doses in normal tissues between IMRT and VMAT, it was found that IMRT mostly delivered higher doses of about 1.05% to the normal tissues than VMAT. Prostate TCP and rectal NTCP were found increased (1%) for VMAT than IMRT. It is seen that VMAT technique can decrease the dose-volume evaluation criteria for the normal tissues. Based on our dosimetric and radiobiological results in treatment plans, it is concluded that our VMAT implementation could produce comparable or slightly better target coverage and normal tissue sparing with a faster treatment time in prostate radiotherapy. PMID:27651562

A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation.

PubMed

Lilleby, K; Garcia, P; Gooley, T; McDonnnell, P; Taber, R; Holmberg, L; Maloney, D G; Press, O W; Bensinger, W

2006-06-01

Forty patients with multiple myeloma scheduled to receive melphalan 200 mg/m(2) followed by autologous stem cell transplantation were randomly assigned to receive oral cryotherapy or room temperature normal saline rinses 30 min before and for 6 h after high-dose therapy. Patients were evaluated for the development of mucositis using the National Cancer Institute grading system as well as evaluation of secondary measures such as days of total parenteral nutrition (TPN), narcotic use, hospitalization, weight loss and resumption of oral caloric intake for 28 days after transplant. Patients self-scored their pain, swallowing, drinking, eating, sleeping and taste alterations for 28 days. The primary end point of this trial was the incidence of grades 3-4 mucositis. Compared to the normal saline group, patients using cryotherapy experienced less grade 3-4 mucositis, 14 vs 74%, P=0.0005. Patients receiving cryotherapy also had statistically lower uses of narcotics and TPN, although there were no differences in length of hospitalization or weight loss. Patient-reported pain was significantly lower and activities were significantly better in the cryotherapy group.

Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and Literature Review.

PubMed

Alswat, Khaled A

2015-07-24

Hyperthyroidism is a common disease that usually responds to the conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta-blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism fails to respond to the above therapy. Cholestyramine has been shown to decrease thyroid hormone level when added to the ongoing anti-thyroidal medications. A 52-year-old woman with past medical history of enlarging goiter presented with obstructive symptoms of worsening shortness of breath and snoring. Admission thyroid function test showed mild hyperthyroidism (suppressed TSH, slightly high FT4, and high normal FT3) that worsened after she received a CT scan with contrast and failed to respond to a 3-week course of high-dose dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days after cholestyramine was added, her FT4 decreased by 30% and normalized after 12 days. The patient underwent total thyroidectomy as definitive treatment for the hyperthyroidism and for the obstructive symptoms. Cholestyramine is an effective additional treatment for hyperthyroidism and may be an effective treatment for refractory iodine-induced hyperthyroidism. The possibility of self-remission (natural course) is less likely given the dramatic and rapid response to cholestyramine.

Therapeutic use of recombinant human G-CSF (RHG-CSF) in a canine model of sublethal and lethal whole-body irradiation

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

Macvittie, T.J.; Monroy, R.L.; Patchen, M.L.

The short biologic half-life of the peripheral neutrophil (PMN) requires an active granulopoietic response to replenish functional PMSs and to remain a competent host defence in irradiated animals. Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate hemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. For the normal dog, subcutaneous administration of rhG-CSF induced neutrophilia within hours after the first injection; total PMSs continued to increase (with plateau phases) to mean peak values of 1000 per cent of baseline at the end of themore » treatment period (12-14 days). Bone-marrow-derived granulocyte-macrophage colony-forming cells (GM-CFC) increased significantly during treatment. For a sublethal 200 cGy dose, treatment with rhG-CSF for 14 consecutive days decreased the severity and shortened the duration of neutropenia and thrombocytopenia. The radiation-induced lethality of 60 per cent after a dose of 350 cGy was associated with marrow-derived GM-CFC survival of 1 per cent.« less

The Bad Berka dose protocol: comparative results of dosimetry in peptide receptor radionuclide therapy using (177)Lu-DOTATATE, (177)Lu-DOTANOC, and (177)Lu-DOTATOC.

PubMed

Schuchardt, Christiane; Kulkarni, Harshad R; Prasad, Vikas; Zachert, Carolin; Müller, Dirk; Baum, Richard P

2013-01-01

The objective of this study is to analyze the in vivo behavior of the (177)Lu-labeled peptides DOTATATE, DOTANOC, and DOTATOC used for peptide receptor radionuclide therapy (PRRNT) of neuroendocrine tumors (NETs), by measuring organ and tumor kinetics and by performing dosimetric calculations. Two hundred fifty-three patients (group 1) with metastasized NET who underwent PRRNT were examined. Out of these, 185 patients received (177)Lu-DOTATATE, 9 were treated with (177)Lu-DOTANOC, and 59 with (177)Lu-DOTATOC. Additionally, 25 patients receiving, in consecutive PRRNT cycles, DOTATATE followed by DOTATOC (group 2) and 3 patients receiving DOTATATE and DOTANOC (group 3) were analyzed. Dosimetric calculations (according to MIRD scheme) were performed using OLINDA software. In group 1, DOTATOC exhibited the lowest and DOTANOC the highest uptake and therefore mean absorbed dose in normal organs (whole body, kidney, and spleen). In group 2, there was a significant difference between DOTATATE and DOTATOC concerning kinetics and normal organ doses. (177)Lu-DOTATOC had the lowest uptake/dose delivered to normal organs and highest tumor-to-kidney ratio. There were no significant differences between the three peptides concerning tumor kinetics and mean absorbed tumor dose. The study demonstrates a correlation between high affinity of DOTANOC in vitro and high uptake in normal organs/whole body in vivo, resulting in a higher whole-body dose. DOTATOC exhibited the lowest uptake and dose delivered to normal tissues and the best tumor-to-kidney ratio. Due to large interpatient variability, individual dosimetry should be performed for each therapy cycle.

[Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder].

PubMed

Zhou, Rong-Yi; Wang, Jiao-Jiao; You, Yue; Sun, Ji-Chao; Song, Yu-Chen; Yuan, Hai-Xia; Han, Xin-Min

2017-05-01

To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium- and high-dose baicalin groups had a significant increase in the ATPase activity (P<0.05), a significant reduction in the LDH activity (P<0.05), and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P<0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05); the medium- and high-dose baicalin groups had a significant reduction in the LDH activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05). Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

[Experimental study on the impact of photodynamic therapy on the normal vocal cord injury].

PubMed

Liu, Haiyan; Huang, Yongwang; Wang, Shanshan; Li, Yingxin; Yin, Huijuan; Gao, Xiaowei

2015-12-01

To investigate the reactive characteristics of normal vocal cord tissues to photodynamic therapy (PDT) and the damage effects of different concentration of photosensitizer and different light on normal rabbit vocal cord. Making the preliminary research of PDT in clinical treatment of chronic inflammation of the vocal cords and precancerous lesions. Twenty-five healthy Japanese big ear experimental rabbits were randomly divided into 5 groups: low work rate low dose group A (100 mW, 10%5-ALA), high work rate low dose group B (200 mW, 10%5-ALA), high work rate high dose group C (200 mW, 20%5-ALA), low work rate high dose group D (100 mW, 20%5-ALA) and normal control group E. The issue damage and wound recovery were observed in 1 d, 3 d, 7 d, 14 d, 28 d after intervention. A severe inflammation reaction was observed in group A, B, C, D after intervened with PDT compared to normal group. The reaction of group A was lighter, and the reaction of group C was the most serious. The content of collagenous fiber, hyaluronic acid and fibronectin in vocal fold lamina layer was significantly higher than that in normal group (P<0.05). Different degrees of fiber proliferation were observed in all groups. The content of each component of vocal fold lamina layer tended to be normal slightly higher level in 28 d. Observation by electron microscope showed that there were no significant differences in A, B, C, D, E in 28 d after intervention. Recoverable damage repair process can be detected in rabbit vocal after intervened with PDT, which began in 7 d and basically completed in 28 d. In a certain concentration (10%-20%) and dose range (100-200 mW). The higher of photodynamic dose, the more serious of the damage. And the damage was basically reversible.

Effects of the Cynanchum wilfordii Ethanol Extract on the Serum Lipid Profile in Hypercholesterolemic Rats

PubMed Central

Lee, Hye-Sung; Choi, Jun-Hyeok; Kim, Young-Eon; Kim, In-Ho; Kim, Byoung-Mok; Lee, Chang-Ho

2013-01-01

The purpose of this study was to investigate the effects of the ethanol extract of Cynanchum wilfordii (ECW) on the blood lipid profile of hypercholesterolemic rats. Thirty 7-week-old male Sprague-Dawley rats were allowed free access to either a normal diet (AIN-93 diet), or 1% high-cholesterol diet with or without 0.5% or 1% ECW for 5 weeks. After sacrifice, the rat serum lipid profile was analyzed. The diets containing ECW decreased body weight gains compared to the normal diet. Serum HDL-cholesterol levels of ECW-fed groups were significantly increased in the hypercholesterolemic groups and normal groups (P<0.05). When 1% ECW was fed to the normal group, total cholesterol level was increased. Moreover, treatment of ECW in hypercholesterolemic groups yielded a dose-dependent and highly significant decrease in the atherogenic index as compared to the control. These results suggest that intake of Cynanchum wilfordii may help reduce the risks of hypercholesterolemia by increasing blood HDL-cholesterol and lowering the atherogenic index. PMID:24471126

Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for Alzheimer disease.

PubMed

Protas, Hillary D; Chen, Kewei; Langbaum, Jessica B S; Fleisher, Adam S; Alexander, Gene E; Lee, Wendy; Bandy, Daniel; de Leon, Mony J; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W; Caselli, Richard J; Reiman, Eric M

2013-03-01

To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Academic medical center. A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P < .05, determined by use of pairwise Fisher z tests). Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease.

In vivo antidiabetic and antioxidant potential of Helichrysum plicatum ssp. plicatum capitulums in streptozotocin-induced-diabetic rats.

PubMed

Aslan, Mustafa; Deliorman Orhan, Didem; Orhan, Nilüfer; Sezik, Ekrem; Yesilada, Erdem

2007-01-03

Helichrysum species (Asteraceae) are widely found in Anatolia. Decoction prepared from the capitulums of Helichrysum plicatum ssp. plicatum is used to alleviate the symptoms of diabetes mellitus in folk medicine. In the present study, the hypoglycaemic and antioxidant potential of Helichrysum plicatum ssp. plicatum was evaluated by using in vivo methods in normal and streptozotocin-induced-diabetic rats. After the oral administration of water and ethanolic extracts at doses of 500mg/kg body weight prepared from the capitulums of plant, blood glucose levels were monitored at specific intervals. Tolbutamide was used as a reference drug at a dose of 100mg/kg. The experimental data indicated that water and ethanol extracts of capitulums demonstrate significant antihyperglycaemic and antioxidant activity in streptozotocin-induced rats which confirmed the folkloric utilization. In order to assess the role of polyphenolic components in the relevant activity, phenolic and flavonoid contents of each extract were also determined in terms of total phenols: 113.5+/-8.6mg (gallic acid equivalent/1g extract) and total flavanoids 50.5+/-1.9mg (quercetin equivalent/1g extract) for ethanol extract, total phenols: 75.9+/-3.7, flavonoids: 31.5+/-2.3 for water extract using Folin-Ciocalteu reagent.

A first-in-human pharmacodynamic and pharmacokinetic study of a fully human anti-glucagon receptor monoclonal antibody in normal healthy volunteers.

PubMed

Kostic, Ana; King, Thomas Alexander; Yang, Feng; Chan, Kuo-Chen; Yancopoulos, George D; Gromada, Jesper; Harp, Joyce B

2018-02-01

Glucagon receptor (GCGR) blockers are being investigated as potential therapeutics for type 1 and type 2 diabetes. Here we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of REGN1193, a fully human glucagon receptor blocking monoclonal antibody from a first-in-human healthy volunteer randomized double-blinded trial. Healthy men and women received single ascending doses of REGN1193 ranging from 0.05 to 0.6 mg/kg (n = 42) or placebo (n = 14) intravenously. Safety, tolerability and PK were assessed over 106 days. The glucose-lowering effect of REGN1193 was assessed after induction of hyperglycaemia by serial glucagon challenges. REGN1193 was generally well tolerated. There were small (<3× the upper limit of normal) and transient dose-dependent increases in hepatic aminotransferases. No increase in LDL-C was observed. Hypoglycaemia, assessed as laboratory blood glucose ≤70 mg/dL, occurred in 6/14 (43%) subjects on placebo and 27/42 (57%) on REGN1193 across all dose groups. All episodes of hypoglycaemia were asymptomatic, >50 mg/dL, and did not require treatment or medical assistance. Concentration-time profiles suggest a 2-compartment disposition and marked nonlinearity, consistent with target-mediated clearance. REGN1193 inhibited the glucagon-stimulated glucose increase in a dose-dependent manner. The 0.6 mg/kg dose inhibited the glucagon-induced glucose area under the curve for 0 to 90 minutes (AUC 0-90 minutes ) by 80% to 90% on days 3 and 15, while blunting the increase in C-peptide. REGN1193 dose-dependently increased total GLP-1, GLP-2 and glucagon, with plasma levels returning to baseline by day 29 in all dose groups. REGN1193, a GCGR-blocking monoclonal antibody, produced a safety, tolerability and PK/PD profile suitable for further clinical development. The occurrence of transient elevations in serum hepatic aminotransferases observed here and reported with several small molecule glucagon receptor antagonists suggests an on-target effect of glucagon receptor blockade. The underlying mechanism is unknown. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

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

Algan, O; Giem, J; Young, J

Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-testmore » analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

PubMed Central

Schuchardt, Christiane; Kulkarni, Harshad R.; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P.; Beer, Ambros J.

2016-01-01

In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25−29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1–3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably. PMID:27611841

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides.

PubMed

Kletting, Peter; Schuchardt, Christiane; Kulkarni, Harshad R; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P; Beer, Ambros J

2016-01-01

In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25-29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1-3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably.

Sulfur transfer in the distillate fractions of Arabian crude oils under gamma-irradiation

NASA Astrophysics Data System (ADS)

Basfar, Ahmed A.; Soliman, Yasser S.; Alkhuraiji, Turki S.

2017-05-01

Desulfurization of light distillation fractions including gasoline, kerosene and diesel obtained from the four Arabian crude oils (heavy, medium, light and extra light) upon γ-rays irradiation to different doses was investigated. In addition, yields vol%, FTIR analysis, kinematic viscosity and density of all distillation fractions of irradiated crude oils were evaluated. Limited radiation-induced desulfurization of those fractions was observed up to an irradiation dose of 200 kGy. FTIR analysis of those fractions indicates the absence of oxidized sulfur compounds, represented by S=O of sulfone group, indicating that γ-irradiation of the Arabian crude oils at normal conditions does not induce an oxidative desulfurization in those distillation fractions. Radiation-induced sulfur transfer decreases by 28.56% and increases in total sulfur by 16.8% in Arabian extra light oil and Arabian medium crude oil respectively.

Polonium-210 levels in different environmental samples.

PubMed

Fonollosa, E; Peñalver, A; Aguilar, C; Borrull, F

2015-12-01

Polonium-210 is analysed in different samples which can be affected by the presence of a dicalcium phosphate plant (DCP). Particularly, it was determined in sludge samples from a drinking water treatment plant located downstream of the phosphate plant. From the obtained results, it was not possible to establish a correlation with the industrial activities carried out in the DCP plant since the measured activities were comparable to the reported in the literature for normal soils. This isotope was also monitored in different biota species (as mussels) taken also downstream of the DCP, and the potential risk of their ingestion by calculating the total effective doses was evaluated. As a result, it is important to highlight that the ingestion of these mussels does not constitute a risk for the population since the found doses were lower than the values published by UNSCEAR.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

PubMed

Lensen, Sarah F; Wilkinson, Jack; Leijdekkers, Jori A; La Marca, Antonio; Mol, Ben Willem J; Marjoribanks, Jane; Torrance, Helen; Broekmans, Frank J

2018-02-01

During a cycle of in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. Generally, the dose of FSH is associated with the number of eggs retrieved. A normal response to stimulation is often considered desirable, for example the retrieval of 5 to 15 oocytes. Both poor and hyper-response are associated with increased chance of cycle cancellation. Hyper-response is also associated with increased risk of ovarian hyperstimulation syndrome (OHSS). Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response such as age. More recently, clinicians have begun using ovarian reserve tests (ORTs) to predict ovarian response based on the measurement of various biomarkers, including basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose based on these markers improves clinical outcomes. To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, LILACS, DARE, ISI Web of Knowledge, ClinicalTrials.gov, and the World Health Organisation International Trials Registry Platform search portal from inception to 27th July 2017. We checked the reference lists of relevant reviews and included studies. We included trials that compared different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal or high responders based on AMH, AFC, and/or bFSH) and trials that compared an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. Secondary outcomes included clinical pregnancy, moderate or severe OHSS, multiple pregnancy, oocyte yield, cycle cancellations, and total dose and duration of FSH administration. We included 20 trials (N = 6088); however, we treated those trials with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence quality ranged from very low to moderate. The main limitations were imprecision and risk of bias associated with lack of blinding.Direct dose comparisons in women according to predicted responseAll evidence was low or very low quality.Due to differences in dose comparisons, caution is warranted in interpreting the findings of five small trials assessing predicted low responders. The effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy.Similarly, in predicted normal responders (nine studies, three comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units: OR 0.88, 95% CI 0.57 to 1.36; N = 522; 2 studies; I 2 = 0%) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the outcome of OHSS to enable any inferences.In predicted high responders, lower doses may or may not have an impact on rates of live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; N = 521; 1 study), OHSS, and clinical pregnancy. However, lower doses probably reduce the likelihood of moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; N = 521; 1 study).ORT-algorithm studiesFour trials compared an ORT-based algorithm to a non-ORT control group. Rates of live birth/ongoing pregnancy and clinical pregnancy did not appear to differ by more than a few percentage points (respectively: OR 1.04, 95% CI 0.88 to 1.23; N = 2823, 4 studies; I 2 = 34%; OR 0.96, 95% CI 0.82 to 1.13, 4 studies, I 2 =0%, moderate-quality evidence). However, ORT algorithms probably reduce the likelihood of moderate or severe OHSS (Peto OR 0.58, 95% CI 0.34 to 1.00; N = 2823; 4 studies; I 2 = 0%, low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.54, 95% CI 0.14 to 1.99; N = 1494; 3 studies; I 2 = 0%, low quality evidence). Our findings suggest that if the chance of live birth with a standard dose is 26%, the chance with ORT-based dosing would be between 24% and 30%. If the chance of moderate or severe OHSS with a standard dose is 2.5%, the chance with ORT-based dosing would be between 0.8% and 2.5%. These results should be treated cautiously due to heterogeneity in the study designs. We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT), influenced rates of live birth/ongoing pregnancy but we could not rule out differences, due to sample size limitations. In predicted high responders, lower doses of FSH seemed to reduce the overall incidence of moderate and severe OHSS. Moderate-quality evidence suggests that ORT-based individualisation produces similar live birth/ongoing pregnancy rates to a policy of giving all women 150 IU. However, in all cases the confidence intervals are consistent with an increase or decrease in the rate of around five percentage points with ORT-based dosing (e.g. from 25% to 20% or 30%). Although small, a difference of this magnitude could be important to many women. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU, probably by facilitating dose reductions in women with a predicted high response. However, the size of the effect is unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates, and many of the included studies had a serious risk of bias.Current evidence does not provide a clear justification for adjusting the standard dose of 150 IU in the case of poor or normal responders, especially as increased dose is generally associated with greater total FSH dose and therefore greater cost. However, a decreased dose in predicted high responders may reduce OHSS.

Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose.

PubMed

Ieiri, Ichiro; Doi, Yohei; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Hirota, Takeshi; Chiyoda, Takeshi; Miyagawa, Mayuko; Irie, Shin; Iwasaki, Kazuhide; Sugiyama, Yuichi

2012-07-01

The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC(0-24) of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.

SU-F-T-130: [18F]-FDG Uptake Dose Response in Lung Correlates Linearly with Proton Therapy Dose

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

Kim, D; Titt, U; Mirkovic, D

2016-06-15

Purpose: Analysis of clinical outcomes in lung cancer patients treated with protons using 18F-FDG uptake in lung as a measure of dose response. Methods: A test case lung cancer patient was selected in an unbiased way. The test patient’s treatment planning and post treatment positron emission tomography (PET) were collected from picture archiving and communication system at the UT M.D. Anderson Cancer Center. Average computerized tomography scan was registered with post PET/CT through both rigid and deformable registrations for selected region of interest (ROI) via VelocityAI imaging informatics software. For the voxels in the ROI, a system that extracts themore » Standard Uptake Value (SUV) from PET was developed, and the corresponding relative biological effectiveness (RBE) weighted (both variable and constant) dose was computed using the Monte Carlo (MC) methods. The treatment planning system (TPS) dose was also obtained. Using histogram analysis, the voxel average normalized SUV vs. 3 different doses was obtained and linear regression fit was performed. Results: From the registration process, there were some regions that showed significant artifacts near the diaphragm and heart region, which yielded poor r-squared values when the linear regression fit was performed on normalized SUV vs. dose. Excluding these values, TPS fit yielded mean r-squared value of 0.79 (range 0.61–0.95), constant RBE fit yielded 0.79 (range 0.52–0.94), and variable RBE fit yielded 0.80 (range 0.52–0.94). Conclusion: A system that extracts SUV from PET to correlate between normalized SUV and various dose calculations was developed. A linear relation between normalized SUV and all three different doses was found.« less

Development of a method to estimate organ doses for pediatric CT examinations

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

Papadakis, Antonios E., E-mail: apapadak@pagni.gr; Perisinakis, Kostas; Damilakis, John

Purpose: To develop a method for estimating doses to primarily exposed organs in pediatric CT by taking into account patient size and automatic tube current modulation (ATCM). Methods: A Monte Carlo CT dosimetry software package, which creates patient-specific voxelized phantoms, accurately simulates CT exposures, and generates dose images depicting the energy imparted on the exposed volume, was used. Routine head, thorax, and abdomen/pelvis CT examinations in 92 pediatric patients, ranging from 1-month to 14-yr-old (49 boys and 43 girls), were simulated on a 64-slice CT scanner. Two sets of simulations were performed in each patient using (i) a fixed tubemore » current (FTC) value over the entire examination length and (ii) the ATCM profile extracted from the DICOM header of the reconstructed images. Normalized to CTDI{sub vol} organ dose was derived for all primary irradiated radiosensitive organs. Normalized dose data were correlated to patient’s water equivalent diameter using log-transformed linear regression analysis. Results: The maximum percent difference in normalized organ dose between FTC and ATCM acquisitions was 10% for eyes in head, 26% for thymus in thorax, and 76% for kidneys in abdomen/pelvis. In most of the organs, the correlation between dose and water equivalent diameter was significantly improved in ATCM compared to FTC acquisitions (P < 0.001). Conclusions: The proposed method employs size specific CTDI{sub vol}-normalized organ dose coefficients for ATCM-activated and FTC acquisitions in pediatric CT. These coefficients are substantially different between ATCM and FTC modes of operation and enable a more accurate assessment of patient-specific organ dose in the clinical setting.« less

Patient-specific radiation dose and cancer risk estimation in pediatric chest CT: a study in 30 patients

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2010-04-01

Radiation-dose awareness and optimization in CT can greatly benefit from a dosereporting system that provides radiation dose and cancer risk estimates specific to each patient and each CT examination. Recently, we reported a method for estimating patientspecific dose from pediatric chest CT. The purpose of this study is to extend that effort to patient-specific risk estimation and to a population of pediatric CT patients. Our study included thirty pediatric CT patients (16 males and 14 females; 0-16 years old), for whom full-body computer models were recently created based on the patients' clinical CT data. Using a validated Monte Carlo program, organ dose received by the thirty patients from a chest scan protocol (LightSpeed VCT, 120 kVp, 1.375 pitch, 40-mm collimation, pediatric body scan field-of-view) was simulated and used to estimate patient-specific effective dose. Risks of cancer incidence were calculated for radiosensitive organs using gender-, age-, and tissue-specific risk coefficients and were used to derive patientspecific effective risk. The thirty patients had normalized effective dose of 3.7-10.4 mSv/100 mAs and normalized effective risk of 0.5-5.8 cases/1000 exposed persons/100 mAs. Normalized lung dose and risk of lung cancer correlated strongly with average chest diameter (correlation coefficient: r = -0.98 to -0.99). Normalized effective risk also correlated strongly with average chest diameter (r = -0.97 to -0.98). These strong correlations can be used to estimate patient-specific dose and risk prior to or after an imaging study to potentially guide healthcare providers in justifying CT examinations and to guide individualized protocol design and optimization.

A method for deriving a 4D-interpolated balanced planning target for mobile tumor radiotherapy.

PubMed

Roland, Teboh; Hales, Russell; McNutt, Todd; Wong, John; Simari, Patricio; Tryggestad, Erik

2012-01-01

Tumor control and normal tissue toxicity are strongly correlated to the tumor and normal tissue volumes receiving high prescribed dose levels in the course of radiotherapy. Planning target definition is, therefore, crucial to ensure favorable clinical outcomes. This is especially important for stereotactic body radiation therapy of lung cancers, characterized by high fractional doses and steep dose gradients. The shift in recent years from population-based to patient-specific treatment margins, as facilitated by the emergence of 4D medical imaging capabilities, is a major improvement. The commonly used motion-encompassing, or internal-target volume (ITV), target definition approach provides a high likelihood of coverage for the mobile tumor but inevitably exposes healthy tissue to high prescribed dose levels. The goal of this work was to generate an interpolated balanced planning target that takes into account both tumor coverage and normal tissue sparing from high prescribed dose levels, thereby improving on the ITV approach. For each 4DCT dataset, 4D deformable image registration was used to derive two bounding targets, namely, a 4D-intersection and a 4D-composite target which minimized normal tissue exposure to high prescribed dose levels and maximized tumor coverage, respectively. Through definition of an "effective overlap volume histogram" the authors derived an "interpolated balanced planning target" intended to balance normal tissue sparing from prescribed doses with tumor coverage. To demonstrate the dosimetric efficacy of the interpolated balanced planning target, the authors performed 4D treatment planning based on deformable image registration of 4D-CT data for five previously treated lung cancer patients. Two 4D plans were generated per patient, one based on the interpolated balanced planning target and the other based on the conventional ITV target. Plans were compared for tumor coverage and the degree of normal tissue sparing resulting from the new approach was quantified. Analysis of the 4D dose distributions from all five patients showed that while achieving tumor coverage comparable to the ITV approach, the new planning target definition resulted in reductions of lung V(10), V(20), and V(30) of 6.3% ± 1.7%, 10.6% ± 3.9%, and 12.9% ± 5.5%, respectively, as well as reductions in mean lung dose, mean dose to the GTV-ring and mean heart dose of 8.8% ± 2.5%, 7.2% ± 2.5%, and 10.6% ± 3.6%, respectively. The authors have developed a simple and systematic approach to generate a 4D-interpolated balanced planning target volume that implicitly incorporates the dynamics of respiratory-organ motion without requiring 4D-dose computation or optimization. Preliminary results based on 4D-CT data of five previously treated lung patients showed that this new planning target approach may improve normal tissue sparing without sacrificing tumor coverage.

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.

Role of step size and max dwell time in anatomy based inverse optimization for prostate implants

PubMed Central

Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R.; Sresty, N.V. Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

2013-01-01

In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants. PMID:24049323

Radiation dose and image quality in pediatric chest CT: effects of iterative reconstruction in normal weight and overweight children.

PubMed

Yoon, Haesung; Kim, Myung-Joon; Yoon, Choon-Sik; Choi, Jiin; Shin, Hyun Joo; Kim, Hyun Gi; Lee, Mi-Jung

2015-03-01

New CT reconstruction techniques may help reduce the burden of ionizing radiation. To quantify radiation dose reduction when performing pediatric chest CT using a low-dose protocol and 50% adaptive statistical iterative reconstruction (ASIR) compared with age/gender-matched chest CT using a conventional dose protocol and reconstructed with filtered back projection (control group) and to determine its effect on image quality in normal weight and overweight children. We retrospectively reviewed 40 pediatric chest CT (M:F = 21:19; range: 0.1-17 years) in both groups. Radiation dose was compared between the two groups using paired Student's t-test. Image quality including noise, sharpness, artifacts and diagnostic acceptability was subjectively assessed by three pediatric radiologists using a four-point scale (superior, average, suboptimal, unacceptable). Eight children in the ASIR group and seven in the control group were overweight. All radiation dose parameters were significantly lower in the ASIR group (P < 0.01) with a greater than 57% dose reduction in overweight children. Image noise was higher in the ASIR group in both normal weight and overweight children. Only one scan in the ASIR group (1/40, 2.5%) was rated as diagnostically suboptimal and there was no unacceptable study. In both normal weight and overweight children, the ASIR technique is associated with a greater than 57% mean dose reduction, without significantly impacting diagnostic image quality in pediatric chest CT examinations. However, CT scans in overweight children may have a greater noise level, even when using the ASIR technique.

Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

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

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bussière, Marc R.; Chapman, Paul H.

2016-07-01

Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dosemore » delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in all fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.« less

Gating window dependency on scanned carbon-ion beam dose distribution and imaging dose for thoracoabdominal treatment.

PubMed

Mori, Shinichiro; Karube, Masataka; Yasuda, Shigeo; Yamamoto, Naoyoshi; Tsuji, Hiroshi; Kamada, Tadashi

2017-06-01

To explore the trade-off between dose assessment and imaging dose in respiratory gating with radiographic fluoroscopic imaging, we evaluated the relationship between dose assessment and fluoroscopic imaging dose in various gating windows, retrospectively. Four-dimensional (4D) CT images acquired for 10 patients with lung and liver tumours were used for 4D treatment planning for scanned carbon ion beam. Imaging dose from two oblique directions was calculated by the number of images multiplied by the air kerma per image. Necessary beam-on time was calculated from the treatment log file. Accumulated dose distribution was calculated. The gating window was defined as tumour position not respiratory phase and changed from 0-100% duty cycle on 4DCT. These metrics were individually evaluated for every case. For lung cases, sufficient dose conformation was achieved in respective gating windows [D 95 -clinical target volume (CTV) > 99%]. V 20 -lung values for 50%- and 30%-duty cycles were 2.5% and 6.0% of that for 100%-duty cycle. Maximum doses (cord/oesophagus) for 30%-duty cycle decreased 6.8%/7.4% to those for 100%-duty cycle. For liver cases, V 10 -liver values for 50%- and 30%-duty cycles were 9.4% and 12.8% of those for 100%-duty cycle, respectively. Maximum doses (cord/oesophagus) for 50%- and 30%-duty cycles also decreased 17.2%/19.3% and 24.6%/29.8% to those for 100%-duty cycle, respectively. Total imaging doses increased 43.5% and 115.8% for 50%- and 30%-duty cycles to that for the 100%-duty cycle. When normal tissue doses are below the tolerance level, the gating window should be expanded to minimize imaging dose and treatment time. Advances in knowledge: The skin dose from imaging might not be counterbalanced to the OAR dose; however, imaging dose is a particularly important factor.

Effect of Two Different Doses of Dexmedetomidine as Adjuvant in Bupivacaine Induced Subarachnoid Block for Elective Abdominal Hysterectomy Operations: A Prospective, Double-blind, Randomized Controlled Study

PubMed Central

Das, Anjan; Halder, Susanta; Chattopadhyay, Surajit; Mandal, Parthajit; Chhaule, Subinay; Banu, Rezina

2015-01-01

Objectives Improvements in perioperative pain management for lower abdominal operations has been shown to reduce morbidity, induce early ambulation, and improve patients’ long-term outcomes. Dexmedetomidine, a selective alpha-2 agonist, has recently been used intrathecally as adjuvant to spinal anesthesia to prolong its efficacy. We compared two different doses of dexmedetomidine added to hyperbaric bupivacaine for spinal anesthesia. The primary endpoints were the onset and duration of sensory and motor block, and duration of analgesia.   Methods A total of 100 patients, aged 35–60 years old, assigned to have elective abdominal hysterectomy under spinal anesthesia were divided into two equally sized groups (D5 and D10) in a randomized, double-blind fashion. The D5 group was intrathecally administered 3ml 0.5% hyperbaric bupivacaine with 5µg dexmedetomidine in 0.5ml of normal saline and the D10 group 3ml 0.5% bupivacaine with 10µg dexmedetomidine in 0.5ml of normal saline. For each patient, sensory and motor block onset times, block durations, time to first analgesic use, total analgesic need, postoperative visual analogue scale (VAS) scores, hemodynamics, and side effects were recorded.   Results Although both groups had a similar demographic profile, sensory and motor block in the D10 group (p<0.050) was earlier than the D5 group. Sensory and motor block duration and time to first analgesic use were significantly longer and the need for rescue analgesics was lower in the D10 group than the D5 group. The 24-hour VAS score was significantly lower in the D10 group (p<0.050). Intergroup hemodynamics were comparable (p>0.050) without any appreciable side effects.   Conclusion Spinal dexmedetomidine increases the sensory and motor block duration and time to first analgesic use, and decreases analgesic consumption in a dose-dependent manner. PMID:26366259

Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

PubMed Central

Ahmad, Feroz; Tabassum, Nahida

2013-01-01

Objective To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Methods Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Result Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. Conclusions The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential. PMID:23570019

Dose inspection and risk assessment on radiation safety for the use of non-medical X-ray machines in Taiwan

NASA Astrophysics Data System (ADS)

Hsu, Fang-Yuh; Hsu, Shih-Ming; Chao, Jiunn-Hsing

2017-11-01

The subject of this study is the on-site visits and inspections of facilities commissioned by the Atomic Energy Council (AEC) in Taiwan. This research was conducted to evaluate the possible dose and dose rate of cabinet-type X-ray equipment with nominal voltages of 30-150 kV and open-beam (portable or handheld) equipment, taking both normal operation and possibly abnormal operation conditions into account. Doses and dose rates were measured using a plastic scintillation survey meter and an electronic personal dosimeter. In total, 401 X-ray machines were inspected, including 139 units with nominal voltages of 30-50 kV X-ray equipment, 140 units with nominal voltages of 50-150 kV, and 122 open-beam (portable or handheld) X-ray equipment. The investigated doses for radiation workers and non-radiation workers operating cabinet-type X-ray equipment under normal safety conditions were all at the background dose level. Several investigated dose rates at the position of 10 cm away from the surface of open-beam (portable or handheld) X-ray equipment were very high, such X-ray machines are used by aeronautical police for the detection of suspected explosives, radiation workers are far away (at least 10 m away) from the X-ray machine during its operation. The doses per operation in X-ray equipment with a 30-50 kV nominal voltage were less than 1 mSv in all cases of abnormal use. Some doses were higher than 1 mSv per operation for X-ray equipment of 50-150 kV nominal voltage X-ray. The maximum dose rates at the beam exit have a very wide range, mostly less than 100 μSv/s and the largest value is about 3.92 mSv/s for open-beam (portable or handheld) X-ray devices. The risk induced by operating X-ray devices with nominal voltages of 30-50 kV is extremely low. The 11.5 mSv dose due to one operation at nominal voltage of 50-150 kV X-ray device is equivalent to the exposure of taking 575 chest X-rays. In the abnormal use of open-beam (portable or handheld) X-ray equipment, the effective dose of 3.92 mSv/s is equivalent to taking 196 chest radiographs within 1 s. This work assessed the annual doses (equivalent and effective doses) and risks of X-ray operator staff as reasonably as possible. The results of this research are helpful to the AEC (competent authority of ionization radiation) to improve the management and perform the safe control of X-ray equipment.

Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS.

PubMed

Yamazaki, A; Kumagai, Y; Yamane, N; Tozuka, Z; Sugiyama, Y; Fujita, T; Yokota, S; Maeda, M

2010-04-01

Fexofenadine is a P-glycoprotein substrate of low bioavailability. It is primarily excreted into faeces as a parent drug via biliary excretion. The predictability from microdose data for the drug absorbed via transporters such as P-glycoprotein is not known. Therefore, this study assessed the predictability of therapeutic-dose pharmacokinetics of fexofenadine from microdosing data using non-radioisotope-labelled drug and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). In a single dose, randomized, two-way crossover study, eight subjects received a microdose (100 microg) or a therapeutic dose (60 mg) of fexofenadine. Blood samples were collected until 12 h after dosing, and assayed using LC/MS/MS. Plasma concentration-time curves of fexofenadine between microdose and therapeutic dose were similar. The mean +/- SD of C(max) normalized to 60 mg dose after microdose and therapeutic dose were 379 +/- 147 and 275 +/- 145 ng/mL respectively. The mean AUC(last) normalized to 60 mg dose after microdose and therapeutic dose were 1914 +/- 738 and 1431 +/- 432 ng/h/mL respectively. The mean dose-adjusted C(max) and AUC(last) after microdose were higher compared with those after therapeutic dose. Individual plots of C(max) and AUC(last) normalized to 60 mg dose, were similar for microdose and therapeutic dose. None of the pharmacokinetic parameters were statistically different using anova. Overall, the microdose pharmacokinetics profile was similar to, and hence predictive of, that of the therapeutic dose. For the P-glycoprotein substrate fexofenadine, the predictability of therapeutic-dose pharmacokinetics from microdose data was good. A microdose study using a non-radioisotope-labelled drug and LC/MS/MS is convenient, and has the potential to aid the early selection of drug candidates.

Effects of ursolic acid on glucose metabolism, the polyol pathway and dyslipidemia in non-obese type 2 diabetic mice.

PubMed

Lee, Jin; Lee, Hae-In; Seo, Kown-Il; Cho, Hyun Wook; Kim, Myung-Joo; Park, Eun-Mi; Lee, Mi-Kyung

2014-07-01

Ursolic acid (UA) is a pentacyclic triterpenoid compound that naturally occurs in fruits, leaves and flowers of medicinal herbs. This study investigated the dose-response efficacy of UA (0.01 and 0.05%) on glucose metabolism, the polyol pathway and dyslipidemia in streptozotocin/nicotinamide-induced diabetic mice. Supplement with both UA doses reduced fasting blood glucose and plasma triglyceride levels in non-obese type 2 diabetic mice. High-dose UA significantly lowered plasma free fatty acid, total cholesterol and VLDL-cholesterol levels compared with the diabetic control mice, while LDL-cholesterol levels were reduced with both doses. UA supplement effectively decreased hepatic glucose-6-phosphatase activity and increased glucokinase activity, the glucokinase/glucose-6-phosphatase ratio, GLUT2 mRNA levels and glycogen content compared with the diabetic control mice. UA supplement attenuated hyperglycemia-induced renal hypertrophy and histological changes. Renal aldose reductase activity was higher, whereas sorbitol dehydrogenase activity was lower in the diabetic control group than in the non-diabetic group. However, UA supplement reversed the biochemical changes in polyol pathway to normal values. These results demonstrated that low-dose UA had preventive potency for diabetic renal complications, which could be mediated by changes in hepatic glucose metabolism and the renal polyol pathway. High-dose UA was more effective anti-dyslipidemia therapy in non-obese type 2 diabetic mice.

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats

PubMed Central

Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

2011-01-01

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

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

Yim, Jackie; Suttie, Clare; Bromley, Regina

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with themore » 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.« less

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

Dose estimation and dating of pottery from Turkey

NASA Astrophysics Data System (ADS)

Altay Atlıhan, M.; Şahiner, Eren; Soykal Alanyalı, Feriştah

2012-06-01

The luminescence method is a widely used technique for environmental dosimetry and dating archaeological, geological materials. In this study, equivalent dose (ED) and annual dose rate (AD) of an archaeological sample were measured. The age of the material was calculated by means of equivalent dose divided by the annual dose rate. The archaeological sample was taken from Antalya, Turkey. Samples were prepared by the fine grain technique and equivalent dose was found using multiple-aliquot-additive-dose (MAAD) and single aliquot regeneration (SAR) techniques. Also the short shine normalization-MAAD and long shine normalization-MAAD were applied and the results of the methods were compared with each other. The optimal preheat temperature was found to be 200 °C for 10 min. The annual doses of concentrations of the major radioactive isotopes were determined using a high-purity germanium detector and a low-level alpha counter. The age of the sample was found to be 510±40 years.

Hepatoprotective activity of Amaranthus spinosus in experimental animals.

PubMed

Zeashan, Hussain; Amresh, G; Singh, Satyawan; Rao, Chandana Venkateswara

2008-11-01

The hepatoprotective and antioxidant activity of 50% ethanolic extract of whole plant of Amaranthus spinosus (ASE) was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. The ASE at dose of 100, 200 and 400 mg/kg were administered orally once daily for fourteen days. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (SALP) and total bilirubin were restored towards normalization significantly by the ASE in a dose dependent manner. Higher dose exhibited significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, in vivo antioxidant activities as malondialdehyde (MDA), hydroperoxides, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also screened which were also found significantly positive in a dose dependent manner. The results of this study strongly indicate that whole plants of A. spinosus have potent hepatoprotective activity against carbon tetrachloride induced hepatic damage in experimental animals. This study suggests that possible mechanism of this activity may be due to the presence of flavonoids and phenolics compound in the ASE which may be responsible to hepatoprotective activity.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

PubMed

Fortin, Israël; Fortin, Bernard; Lambert, Louise; Clavel, Sébastien; Alizadeh, Moein; Filion, Edith J; Soulières, Denis; Bélair, Manon; Guertin, Louis; Nguyen-Tan, Phuc Felix

2014-09-01

In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria. Copyright © 2013 Wiley Periodicals, Inc.

Primary hypothyroidism in the community: Lower daily dosages of levothyroxine replacement therapy for Asian patients.

PubMed

Tan, Ngiap Chuan; Chew, Rong Quan; Koh, Yi Ling Eileen; Subramanian, Reena Chandini; Sankari, Usha; Meyappan, Meykkumar; Cho, Li Wei

2017-02-01

The goal of treatment in patients with primary hypothyroidism is to attain euthyroidism guided by the stipulated thyroid-stimulating hormone (TSH) levels range so as to minimize any potential long-term adverse effects. However, various factors may result in their Levothyroxine (T4) under and over-replacement.Our study aimed to evaluate the mean daily dose of L-T4 replacement for Asian patients with primary hypothyroidism. The secondary aims were to determine the proportion of those who were either over or under-replaced, and the factors associated with their thyroid function status and replacement adherence.Data collected using questionnaire survey from targeted patients managed in a typical public primary care center in Singapore: socio-demographic characteristics, clinical parameters, laboratory investigations, mean daily L-T4-replacement doses, and replacement regimens. The thyroid status of patients was classified based on thyroid function investigations.Complete data of 229 patients were analyzed. A total of 59.8% of patients had TSH within the normal range, 27.5% and 12.7% were under and over-replaced, respectively. About 60% of Asian patients with primary hypothyroidism achieved normal TSH status requiring average of 1.1 μg of daily L-T4/kgBW (kg body weight). Subjects who were over-replaced had a higher daily L-T4 dose/kgBW when compared to the euthyroid and the under replaced groups. Those with L-T4 over-replacement were largely due to excessive dosage. Patients who were younger, from lower socioeconomic strata, and higher BMI were more likely to be over or under-replaced.Majority of Asian patients with hypothyroidism required replacement of 1.1 μg of daily L-T4/kgBW. Their thyroid status was influenced by demographic and dosing factors.

Optimal radiotherapy dose schedules under parametric uncertainty

NASA Astrophysics Data System (ADS)

Badri, Hamidreza; Watanabe, Yoichi; Leder, Kevin

2016-01-01

We consider the effects of parameter uncertainty on the optimal radiation schedule in the context of the linear-quadratic model. Our interest arises from the observation that if inter-patient variability in normal and tumor tissue radiosensitivity or sparing factor of the organs-at-risk (OAR) are not accounted for during radiation scheduling, the performance of the therapy may be strongly degraded or the OAR may receive a substantially larger dose than the allowable threshold. This paper proposes a stochastic radiation scheduling concept to incorporate inter-patient variability into the scheduling optimization problem. Our method is based on a probabilistic approach, where the model parameters are given by a set of random variables. Our probabilistic formulation ensures that our constraints are satisfied with a given probability, and that our objective function achieves a desired level with a stated probability. We used a variable transformation to reduce the resulting optimization problem to two dimensions. We showed that the optimal solution lies on the boundary of the feasible region and we implemented a branch and bound algorithm to find the global optimal solution. We demonstrated how the configuration of optimal schedules in the presence of uncertainty compares to optimal schedules in the absence of uncertainty (conventional schedule). We observed that in order to protect against the possibility of the model parameters falling into a region where the conventional schedule is no longer feasible, it is required to avoid extremal solutions, i.e. a single large dose or very large total dose delivered over a long period. Finally, we performed numerical experiments in the setting of head and neck tumors including several normal tissues to reveal the effect of parameter uncertainty on optimal schedules and to evaluate the sensitivity of the solutions to the choice of key model parameters.

SU-E-T-230: Creating a Large Number of Focused Beams with Variable Patient Head Tilt to Improve Dose Fall-Off for Brain Radiosurgery

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

Chiu, J; Ma, L

2015-06-15

Purpose: To develop a treatment delivery and planning strategy by increasing the number of beams to minimize dose to brain tissue surrounding a target, while maximizing dose coverage to the target. Methods: We analyzed 14 different treatment plans via Leksell PFX and 4C. For standardization, single tumor cases were chosen. Original treatment plans were compared with two optimized plans. The number of beams was increased in treatment plans by varying tilt angles of the patient head, while maintaining original isocenter and the beam positions in the x-, y- and z-axes, collimator size, and beam blocking. PFX optimized plans increased beammore » numbers with three pre-set tilt angles, 70, 90, 110, and 4C optimized plans increased beam numbers with tilt angles increasing arbitrarily from range of 30 to 150 degrees. Optimized treatment plans were compared dosimetrically with original treatment plans. Results: Comparing total normal tissue isodose volumes between original and optimized plans, the low-level percentage isodose volumes decreased in all plans. Despite the addition of multiple beams up to a factor of 25, beam-on times for 1 tilt angle versus 3 or more tilt angles were comparable (<1 min.). In 64% (9/14) of the studied cases, the volume percentage decrease by >5%, with the highest value reaching 19%. The addition of more tilt angles correlates to a greater decrease in normal brain irradiated volume. Selectivity and coverage for original and optimized plans remained comparable. Conclusion: Adding large number of additional focused beams with variable patient head tilt shows improvement for dose fall-off for brain radiosurgery. The study demonstrates technical feasibility of adding beams to decrease target volume.« less

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

PubMed Central

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled. PMID:23635256

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

PubMed

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections.

PubMed

Zhang, You; Yin, Fang-Fang; Ren, Lei

2015-08-01

Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated on the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the "gold-standard" on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔDmin), maximum dose (ΔDmax), and mean dose (ΔDmean), and the absolute deviations of prescription dose coverage (ΔV100%) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔDmin, ΔDmax, ΔDmean, and ΔV100% (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔDmin, ΔDmax, ΔDmean, and ΔV100% of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.

Risk factors for neonatal thyroid dysfunction in pregnancies complicated by Graves' disease.

PubMed

Uenaka, Mizuki; Tanimura, Kenji; Tairaku, Shinya; Morioka, Ichiro; Ebina, Yasuhiko; Yamada, Hideto

2014-06-01

To determine the factors related to adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnancies complicated by Graves' disease. Thirty-five pregnancies complicated by Graves' disease were divided into two groups: adverse pregnancy outcome (n=15) and no adverse pregnancy outcome (n=20). Adverse pregnancy outcomes included spontaneous abortion, stillbirth, premature delivery, fetal growth restriction, and pregnancy-induced hypertension. The 31 pregnancies resulting in live births were also divided into two groups: neonatal thyroid dysfunction (n=9) and normal neonatal thyroid function (n=22). Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), TSH-receptor antibody (TRAb), the duration of hyperthyroidism in pregnancy, doses of antithyroid medication, and the duration of maternal antithyroid medication throughout pregnancy were compared. There were no significant differences in these factors between pregnancies with an adverse pregnancy outcome and those with no adverse pregnancy outcome. However, serum levels of FT4, TRAb, the duration of hyperthyroidism in pregnancy, the maximum daily dose of antithyroid medication, and the total dose of antithyroid medication were significantly different between pregnancies with neonatal thyroid dysfunction and those with normal neonatal thyroid function. Multivariate logistic regression analysis showed that the FT4 level in mothers was a significant factor related to the development of neonatal thyroid dysfunction (odds ratio 28.84, 95% confidence interval 1.65-503.62, p<0.05). Graves' disease activity in women of childbearing age should be well controlled prior to conception. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

Tobler, Matt; Watson, Gordon; Leavitt, Dennis

Radiotherapy plays a key role in the definitive or adjuvant management of patients with mesothelioma of the pleural surface. Many patients are referred for radiation with intact lung following biopsy or subtotal pleurectomy. Delivery of efficacious doses of radiation to the pleural lining while avoiding lung parenchyma toxicity has been a difficult technical challenge. Using opposed photon fields produce doses in lung that result in moderate-to-severe pulmonary toxicity in 100% of patients treated. Combined photon-electron beam treatment, at total doses of 4250 cGy to the pleural surface, results in two-thirds of the lung volume receiving over 2100 cGy. We havemore » developed a technique using intensity-modulated photon arc therapy (IMRT) that significantly improves the dose distribution to the pleural surface with concomitant decrease in dose to lung parenchyma compared to traditional techniques. IMRT treatment of the pleural lining consists of segments of photon arcs that can be intensity modulated with varying beam weights and multileaf positions to produce a more uniform distribution to the pleural surface, while at the same time reducing the overall dose to the lung itself. Computed tomography (CT) simulation is critical for precise identification of target volumes as well as critical normal structures (lung and heart). Rotational arc trajectories and individual leaf positions and weightings are then defined for each CT plane within the patient. This paper will describe the proposed rotational IMRT technique and, using simulated isodose distributions, show the improved potential for sparing of dose to the critical structures of the lung, heart, and spinal cord.« less

Chromosome aberrations in peripheral blood lymphocytes of individuals living in high background radiation areas of Ramsar, Iran.

PubMed

Zakeri, F; Rajabpour, M R; Haeri, S A; Kanda, R; Hayata, I; Nakamura, S; Sugahara, T; Ahmadpour, M J

2011-11-01

In order to investigate the biological effects of exposure to low-dose radiation and to assess the dose-effect relationship in residents of high background radiation areas (HBRAs) of Ramsar, cytogenetic investigation of unstable-type aberrations was performed in 15 healthy elderly women in a HBRA of Ramsar, Talesh mahalle, and in 10 elderly women living in a nearby control area with normal background radiation. In total, 77,714 cells were analyzed; 48,819 cells in HBRA residents and 28,895 cells in controls. On average, 3,108 cells per subject were analyzed (range 1,475-5,007 cells). Significant differences were found in the frequency of dicentric plus centric rings in 100 cells (0.207 ± 0.103 vs. 0.047 ± 0.027, p < 0.0005), total chromosome-type aberrations per 100 cells (0.86 ± 0.44 vs. 0.23 ± 0.17, p < 0.0005), and chromatid-type aberrations per 100 cells (3.31 ± 2.01 vs. 1.66 ± 0.63, p = 0.01) by the Mann-Whitney U test between HBRA and the control, respectively. Using chromosomal aberrations as the main endpoint to assess the dose-effect relationship in residents of HBRAs in Ramsar, no positive correlation was found between the frequency of dicentric plus centric ring aberrations and the cumulative dose of the inhabitants estimated by direct individual dosimetry; however, obvious trends of increase with age appeared in the control group. Based on these results, individuals residing in HBRAs of Ramsar have an increased frequency of detectable abnormalities in unstable aberrations.

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

Cederkrantz, Elin; Andersson, Håkan; Bernhardt, Peter

Purpose: Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of {sup 211}At-MX35 F(ab'){sub 2}. Methods and Materials: Patients in clinical remission after salvage chemotherapymore » for peritoneal recurrence of ovarian cancer underwent i.p. infusion of {sup 211}At-MX35 F(ab'){sub 2}. Potassium perchlorate was given to block unwanted accumulation of {sup 211}At in thyroid and other NIS-containing tissues. Mean absorbed doses to normal tissues were calculated from clinical data, including blood and i.p. fluid samples, urine, γ-camera images, and single-photon emission computed tomography/computed tomography images. Extrapolation of preclinical biodistribution data combined with clinical blood activity data allowed us to estimate absorbed doses in additional tissues. The equivalent dose was calculated using an RBE of 5 and the effective dose using the recommended weight factor of 20. All doses were normalized to the initial activity concentration of the infused therapy solution. Results: The urinary bladder, thyroid, and kidneys (1.9, 1.8, and 1.7 mGy per MBq/L) received the 3 highest estimated absorbed doses. When the tissue-weighting factors were applied, the largest contributors to the effective dose were the lungs, stomach, and urinary bladder. Using 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose. Conclusion: Intraperitoneal {sup 211}At-MX35 F(ab'){sub 2} treatment is potentially a well-tolerated therapy for locally confined microscopic ovarian cancer. Absorbed doses to normal organs are low, but because the effective dose potentially corresponds to a risk of treatment-induced carcinogenesis, optimization may still be valuable.« less

Potential for reduced toxicity and dose escalation in the treatment of inoperable non-small-cell lung cancer: a comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation.

PubMed

Grills, Inga S; Yan, Di; Martinez, Alvaro A; Vicini, Frank A; Wong, John W; Kestin, Larry L

2003-11-01

To systematically evaluate four different techniques of radiation therapy (RT) used to treat non-small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints while maximizing tumor coverage and achieving dose escalation. Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non-small-cell lung cancer using four different RT techniques to treat the primary lung tumor +/- the hilar/mediastinal lymph nodes: (1) Intensity-modulated radiation therapy (IMRT), (2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, (3) Limited 3D-CRT using only 2 to 3 beams, and (4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and (18)fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either > or =1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to > or =99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung V(20) < or =25%, mean lung dose < or =15 Gy, esophagus V(50) < or =25%, mean esophageal dose < or =25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses. Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%-8% greater than 3D-CRT and 14%-16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung V(20) was 36% with ENI vs. 23%-25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus V(50) was doubled with ENI, to 34% rather than 15%-18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability [NTCP] of approximately 10% and 2%-7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung V(20) and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus V(50) by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%-30% over 3D-CRT and 130%-140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung V(20), mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particul mean dose, and NTCP in node-positive patients. The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%-30% greater than 3D-CRT and 130%-140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.

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

Kole, Thomas P.; Aghayere, Osarhieme; Kwah, Jason

Purpose: To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients with distal esophageal cancer undergoing chemoradiation. Methods and Materials: Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters weremore » statistically evaluated using the Wilcoxon rank-sum test. Results: Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT. Conclusions: Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D-CRT. Long-term studies are necessary to determine how this will impact on development of coronary artery disease and other cardiac complications.« less

Glioma Invasiveness Responds Variably to Irradiation in a Co-Culture Model

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

Nakamura, Jean L.; Haas-Kogan, Daphne A.; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA

2007-11-01

Purpose: We developed a co-culture system to quantitate the growth and invasion of human malignant gliomas into a background of confluent normal human astrocytes, then used this assay to assess independently the effects of irradiating both cell types on glioma invasion. Methods and Materials: Enhanced green fluorescent protein (EGFP)-labeled immortalized human astrocytes, human malignant glioma cells, or transformed human astrocytes were focally plated onto a confluent layer of normal human astrocytes, and the invasiveness of EGFP-labeled cells was scored after 96 h. To address the consequences of irradiation on glioma invasion, the invasiveness of irradiated glioma cell lines and irradiatedmore » astrocytic backgrounds was assessed. Fluorescence-activated cell sorting was used to quantitate the total number of EGFP-labeled cells. Results: Growth in the co-culture assay consistently reflected transformation states of the plated cells. Immortalized, but untransformed human astrocytes failed even to establish growth on confluent normal human astrocytes. In contrast, all malignant human glioma cell lines and transformed human astrocytes demonstrated various degrees of infiltration into the astrocytic bed. Irradiation failed to alter the invasiveness of U87, A172, and U373. A 1-Gy dose slightly reduced the invasiveness of U251 MG by 75% (p < 0.05 by one-way analysis of variance and post hoc Neuman-Keuls), without reducing total cell numbers. Independently irradiating the human astrocytic bed did not alter the invasiveness of nonirradiated U251, whereas the matrix metalloproteinase (MMP) inhibitor GM6001 reduced U251 invasiveness in the co-culture assay. Conclusions: Growth in the co-culture assay reflects the transformation status and provides a useful in vitro model for assessing invasiveness. Human glioma invasiveness in the co-culture model responds variably to single low-dose fractions. MMP activity promotes invasiveness in the co-culture model. Reduced invasiveness in irradiated U251 appears to be mediated by MMP-independent mechanisms.« less

Therapeutic potential of octyl gallate isolated from fruits of Terminalia bellerica in streptozotocin-induced diabetic rats.

PubMed

Latha, R Cecily Rosemary; Daisy, P

2013-06-01

Medicinal plants are a potential source of antidiabetic drugs. Terminalia bellerica Roxb. (Combretaceae) is used in Indian traditional systems of medicine to treat diabetes mellitus. The aim of this study was to isolate and identify antihyperglycemic principle(s) from the fruits of T. bellerica and assess the bioactivity in streptozotocin (STZ)-induced diabetic rats. Bioassay-guided fractionation was followed to isolate the active compound(s), structure was elucidated using (1)H and (13)C NMR, IR and mass spectrometry and administered intragastrically to diabetic Wistar rats at different doses (5, 10 and 20 mg/kg, body weight) for 28 d. Plasma glucose, insulin, C-peptide and other biochemical parameters were studied. Octyl gallate (OG) isolated first time from the fruit rind of T. bellerica significantly (p < 0.05) reduced plasma glucose to near normal values (108.47 ± 6.9 mg/dl) after 14 d at the dose of 20 mg/kg. In addition, OG significantly increased plasma insulin, C-peptide, total protein, albumin, tissue glycogen, body weight and markedly decreased serum total cholesterol, triglyceride, LDL-cholesterol, urea, uric acid and creatinine in diabetic rats. Also OG restored the altered regulatory enzymes of carbohydrate metabolism. OG might have augmented the secretion of insulin by the modulation of cAMP and intracellular calcium levels in the β cells of the pancreas. Our findings indicate that OG isolated first time from the fruit rind of T. bellerica has potential antidiabetic effect as it augments insulin secretion and normalizes the altered biochemical parameters in experimental diabetic rat models.

Microionization chamber for reference dosimetry in IMRT verification: clinical implications on OAR dosimetric errors

NASA Astrophysics Data System (ADS)

Sánchez-Doblado, Francisco; Capote, Roberto; Leal, Antonio; Roselló, Joan V.; Lagares, Juan I.; Arráns, Rafael; Hartmann, Günther H.

2005-03-01

Intensity modulated radiotherapy (IMRT) has become a treatment of choice in many oncological institutions. Small fields or beamlets with sizes of 1 to 5 cm2 are now routinely used in IMRT delivery. Therefore small ionization chambers (IC) with sensitive volumes <=0.1 cm3are generally used for dose verification of an IMRT treatment. The measurement conditions during verification may be quite different from reference conditions normally encountered in clinical beam calibration, so dosimetry of these narrow photon beams pertains to the so-called non-reference conditions for beam calibration. This work aims at estimating the error made when measuring the organ at risk's (OAR) absolute dose by a micro ion chamber (μIC) in a typical IMRT treatment. The dose error comes from the assumption that the dosimetric parameters determining the absolute dose are the same as for the reference conditions. We have selected two clinical cases, treated by IMRT, for our dose error evaluations. Detailed geometrical simulation of the μIC and the dose verification set-up was performed. The Monte Carlo (MC) simulation allows us to calculate the dose measured by the chamber as a dose averaged over the air cavity within the ion-chamber active volume (Dair). The absorbed dose to water (Dwater) is derived as the dose deposited inside the same volume, in the same geometrical position, filled and surrounded by water in the absence of the ion chamber. Therefore, the Dwater/Dair dose ratio is the MC estimator of the total correction factor needed to convert the absorbed dose in air into the absorbed dose in water. The dose ratio was calculated for the μIC located at the isocentre within the OARs for both clinical cases. The clinical impact of the calculated dose error was found to be negligible for the studied IMRT treatments.

A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage

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

Palma, Giuseppe; Monti, Serena; D'Avino, Vittoria

Purpose: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). Methods and Materials: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. Themore » coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. Results: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose of the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. Conclusions: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose–RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high-dose range and RILD seems to lack a clear spatial signature.« less

Comparison of a new noncoplanar intensity-modulated radiation therapy technique for craniospinal irradiation with 3 coplanar techniques

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

Hansen, Anders T., E-mail: andehans@rm.dk; Lukacova, Slavka; Lassen-Ramshad, Yasmin

2015-01-01

When standard conformal x-ray technique for craniospinal irradiation is used, it is a challenge to achieve satisfactory dose coverage of the target including the area of the cribriform plate, while sparing organs at risk. We present a new intensity-modulated radiation therapy (IMRT), noncoplanar technique, for delivering irradiation to the cranial part and compare it with 3 other techniques and previously published results. A total of 13 patients who had previously received craniospinal irradiation with standard conformal x-ray technique were reviewed. New treatment plans were generated for each patient using the noncoplanar IMRT-based technique, a coplanar IMRT-based technique, and a coplanarmore » volumetric-modulated arch therapy (VMAT) technique. Dosimetry data for all patients were compared with the corresponding data from the conventional treatment plans. The new noncoplanar IMRT technique substantially reduced the mean dose to organs at risk compared with the standard radiation technique. The 2 other coplanar techniques also reduced the mean dose to some of the critical organs. However, this reduction was not as substantial as the reduction obtained by the noncoplanar technique. Furthermore, compared with the standard technique, the IMRT techniques reduced the total calculated radiation dose that was delivered to the normal tissue, whereas the VMAT technique increased this dose. Additionally, the coverage of the target was significantly improved by the noncoplanar IMRT technique. Compared with the standard technique, the coplanar IMRT and the VMAT technique did not improve the coverage of the target significantly. All the new planning techniques increased the number of monitor units (MU) used—the noncoplanar IMRT technique by 99%, the coplanar IMRT technique by 122%, and the VMAT technique by 26%—causing concern for leak radiation. The noncoplanar IMRT technique covered the target better and decreased doses to organs at risk compared with the other techniques. All the new techniques increased the number of MU compared with the standard technique.« less

[Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

PubMed

Kojima, Shuji

2006-10-01

We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels.

PubMed

Schver, Giovanna C R M; Lee, Ping I

2018-05-07

Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates sufficiently rapid initial supersaturation buildup above the critical supersaturation, resulting in more rapid precipitation. Above this smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of drug release gets slower, which results in a more modest rate of supersaturation buildup, leading to a maximum supersaturation below the critical-supersaturation level without appreciable precipitation. The area-under-the-curve (AUC) values of the in vitro kinetic-solubility concentration-time profiles were used to correlate the corresponding trends in dissolution enhancement. There are observed monotonic increases in AUC values with increasing particle sizes for high-dose ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously reported AUC maxima at some intermediate supersaturation rates or doses in soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the critical dose levels), crystallization would be negligible, leading to sustained supersaturation with all particle sizes (i.e., eventually reaching the same maximum supersaturation) and the smallest particle size reaching the maximum supersaturation the fastest. As a result, the smallest particle sizes yield the largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel matrixes. In addition to probing the interplay between the supersaturation-generation rates and total doses in ASDs based on insoluble hydrogel carriers, our results further support the fact that through either increasing the hydrogel-particle size or lowering the total dose to achieve maximum supersaturation still below the critical-supersaturation level, it is possible to avoid drug precipitation so as to maintain sustained supersaturation.

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

Balik, S; Weiss, E; Sleeman, W

Purpose: To evaluate the potential impact of several setup error correction strategies on a proposed image-guided adaptive radiotherapy strategy for locally advanced lung cancer. Methods: Daily 4D cone-beam CT and weekly 4D fan-beam CT images were acquired from 9 lung cancer patients undergoing concurrent chemoradiation therapy. Initial planning CT was deformably registered to daily CBCT images to generate synthetic treatment courses. An adaptive radiation therapy course was simulated using the weekly CT images with replanning twice and a hypofractionated, simultaneous integrated boost to a total dose of 66 Gy to the original PTV and either a 66 Gy (no boost)more » or 82 Gy (boost) dose to the boost PTV (ITV + 3mm) in 33 fractions with IMRT or VMAT. Lymph nodes (LN) were not boosted (prescribed to 66 Gy in both plans). Synthetic images were rigidly, bony (BN) or tumor and carina (TC), registered to the corresponding plan CT, dose was computed on these from adaptive replans (PLAN) and deformably accumulated back to the original planning CT. Cumulative D98% of CTV of PT (ITV for 82Gy) and LN, and normal tissue dose changes were analyzed. Results: Two patients were removed from the study due to large registration errors. For the remaining 7 patients, D98% for CTV-PT (ITV-PT for 82 Gy) and CTV-LN was within 1 Gy of PLAN for both 66 Gy and 82 Gy plans with both setup techniques. Overall, TC based setup provided better results, especially for LN coverage (p = 0.1 for 66Gy plan and p = 0.2 for 82 Gy plan, comparison of BN and TC), though not significant. Normal tissue dose constraints violated for some patients if constraint was barely achieved in PLAN. Conclusion: The hypofractionated adaptive strategy appears to be deliverable with soft tissue alignment for the evaluated margins and planning parameters. Research was supported by NIH P01CA116602.« less

Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

PubMed

Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

2017-11-01

It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P < 0.05). There were no significant differences between the two IMRT plans on V25, V30, V40, V50 and mean dose for heart. The maximum doses of cords in two type IMRT plans were nearly the same. IMRT plans with inhomogeneous target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

High Atomic Number Contrast Media Offer Potential for Radiation Dose Reduction in Contrast-Enhanced Computed Tomography.

PubMed

Roessler, Ann-Christin; Hupfer, Martin; Kolditz, Daniel; Jost, Gregor; Pietsch, Hubertus; Kalender, Willi A

2016-04-01

Spectral optimization of x-ray computed tomography (CT) has led to substantial radiation dose reduction in contrast-enhanced CT studies using standard iodinated contrast media. The purpose of this study was to analyze the potential for further dose reduction using high-atomic-number elements such as hafnium and tungsten. As in previous studies, spectra were determined for which the patient dose necessary to provide a given contrast-to-noise ratio (CNR) is minimized. We used 2 different quasi-anthropomorphic phantoms representing the liver cross-section of a normal adult and an obese adult patient with the lateral widths of 360 and 460 mm and anterior-posterior heights of 200 and 300 mm, respectively. We simulated and measured on 2 different scanners with x-ray spectra from 80 to 140 kV and from 70 to 150 kV, respectively. We determined the contrast for iodine-, hafnium-, and tungsten-based contrast media, the noise, and 3-dimensional dose distributions at all available tube voltages by measurements and by simulations. The dose-weighted CNR was determined as optimization parameter. Simulations and measurements were in good agreement regarding their dependence on energy for all parameters investigated. Hafnium provided the best performance for normal and for obese patient phantoms, indicating a dose reduction potential of 30% for normal and 50% for obese patients at 120 kV compared with iodine; this advantage increased further with higher kV values. Dose-weighted CNR values for tungsten were always slightly below the hafnium results. Iodine proved to be the superior choice at voltage values of 80 kV and below. Hafnium and tungsten both seem to be candidates for contrast-medium-enhanced CT of normal and obese adult patients with strongly reduced radiation dose at unimpaired image quality. Computed tomography examinations of obese patients will decrease in dose for higher kV values.

Relationship between plant growth and cytological effect in root apical meristem after exposure of wheat dry seeds to carbon ion beams

NASA Astrophysics Data System (ADS)

Liu, Qingfang; Wang, Zhuanzi; Zhou, Libin; Qu, Ying; Lu, Dong; Yu, Lixia; Du, Yan; Jin, Wenjie; Li, Wenjian

2013-06-01

In order to analyze the relationship between plant growth and cytological effects, wheat dry seeds were exposed to various doses of 12C6+ beams and the biological endpoints reflecting plant growth and root apical meristem (RAM) activities were investigated. The results showed that most of the seeds were able to germinate normally within all dose range, while the plant survival rate descended at higher doses. The seedling growth including root length and seedling height also decreased significantly at higher doses. Mitotic index (MI) in RAM had no changes at 10 and 20 Gy and decreased obviously at higher doses and the proportion of prophase cells had the same trend with MI. These data suggested that RAM cells experienced cell cycle arrest, which should be responsible for the inhibition of root growth after exposure to higher doses irradiation. Moreover, various types of chromosome aberrations (CAs) were observed in the mitotic cells. The frequencies of mitotic cells with lagging chromosomes and these with anaphase bridges peaked around 60 Gy, while the frequencies of these with fragments increased as the irradiation doses increased up to 200 Gy. The total frequencies of mitotic cells with CAs induced by irradiation increased significantly with the increasing doses. The serious damage of mitotic chromosomes maybe caused cell cycle arrest or cell death. These findings suggested that the influences of 12C6+ beams irradiation on plant growth were related to the alternation of mitotic activities and the chromosomal damages in RAM.

The relationship between organ dose and patient size in tube current modulated adult thoracic CT scans

NASA Astrophysics Data System (ADS)

Khatonabadi, Maryam; Zhang, Di; Yang, Jeffrey; DeMarco, John J.; Cagnon, Chris C.; McNitt-Gray, Michael F.

2012-03-01

Recently published AAPM Task Group 204 developed conversion coefficients that use scanner reported CTDIvol to estimate dose to the center of patient undergoing fixed tube current body exam. However, most performed CT exams use TCM to reduce dose to patients. Therefore, the purpose of this study was to investigate the correlation between organ dose and a variety of patient size metrics in adult chest CT scans that use tube current modulation (TCM). Monte Carlo simulations were performed for 32 voxelized models with contoured lungs and glandular breasts tissue, consisting of females and males. These simulations made use of patient's actual TCM data to estimate organ dose. Using image data, different size metrics were calculated, these measurements were all performed on one slice, at the level of patient's nipple. Estimated doses were normalized by scanner-reported CTDIvol and plotted versus different metrics. CTDIvol values were plotted versus different metrics to look at scanner's output versus size. The metrics performed similarly in terms of correlating with organ dose. Looking at each gender separately, for male models normalized lung dose showed a better linear correlation (r2=0.91) with effective diameter, while female models showed higher correlation (r2=0.59) with the anterior-posterior measurement. There was essentially no correlation observed between size and CTDIvol-normalized breast dose. However, a linear relationship was observed between absolute breast dose and size. Dose to lungs and breasts were consistently higher in females with similar size as males which could be due to shape and composition differences between genders in the thoracic region.

High-dose oral colecalciferol loading in obesity: impact of body mass index and its utility prior to bariatric surgery to treat vitamin D deficiency.

PubMed

King, R J; Chandrajay, D; Abbas, A; Orme, S M; Barth, J H

2017-04-01

Obesity is associated with lower vitamin D levels compared with normal weight subjects, and if levels are not replaced prior to bariatric surgery, this can increase fracture risk as bone density typically falls post-operatively. We analysed the effect of body mass index (BMI) on vitamin D levels in response to 300 000 IU of colecalciferol in patients with vitamin D deficiency (<30 nmol L -1 ). Patients were grouped according to their BMI as normal weight (20-24.9 kg m -2 ), overweight (25-29.9 kg m -2 ), obese class I (30-34.9 kg m -2 ) and obese class II and above (>35 kg m -2 ). The records were retrospectively analysed to investigate the effects of BMI on vitamin D (total 25-hydroxy vitamin D [25(OH)D]), serum Ca 2+ and parathyroid hormone (PTH) levels at 6, 12, 26 and 52 weeks compared with baseline. Compared with normal weight subjects, overweight and obese patients achieved lower mean peak total 25(OH)D levels (6 weeks post-loading), which was most significant in the class II and above group (mean total 25(OH)D levels 96.5 ± 24.2 nmol L -1 and 72.42 ± 24.9 nmol L -1 , respectively; P = 0.003). By 26 weeks, total 25(OH)D levels fell in all groups; however, there was now a significant difference between the normal weight subjects and all other groups (mean total 25(OH)D levels 84.1 ± 23.7 nmol L -1 ; 58 ± 20 nmol L -1 , P = 0.0002; 62.65 ± 19.2 nmol L -1 , P = 0.005; 59.2 ± 21 nmol L -1 , P = 0.005, respectively). Far fewer patients in the overweight and obese groups maintained levels above the recommended level of 75 nmol L -1 52 weeks post-loading (93%; 20%, P = 0.0003; 23%, P = 0.01; and 14%, P = 0.001, respectively). Alternative regimes for the treatment of vitamin D deficiency are needed in overweight and obese patients, especially those in whom bariatric surgery is planned. © 2017 World Obesity Federation.

Acceleration of intensity-modulated radiotherapy dose calculation by importance sampling of the calculation matrices.

PubMed

Thieke, Christian; Nill, Simeon; Oelfke, Uwe; Bortfeld, Thomas

2002-05-01

In inverse planning for intensity-modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look-up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low-dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well-known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan.

Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

PubMed Central

Selby, P. J.; Lopes, N.; Mundy, J.; Crofts, M.; Millar, J. L.; McElwain, T. J.

1987-01-01

A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID:3111515

Effect of radiation protraction on BED in the case of large fraction dose

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

Kuperman, V. Y.

2013-08-15

Purpose: To investigate the effect of radiation protraction on biologically effective dose (BED) in the case when dose per fraction is significantly greater than the standard dose of 2 Gy.Methods: By using the modified linear-quadratic model with monoexponential repair, the authors investigate the effect of long treatment times combined with dose escalation.Results: The dependences of the protraction factor and the corresponding BED on fraction time were determined for different doses per fraction typical for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). In the calculations, the authors consider changes in the BED to the normal tissue under the conditionmore » of fixed BED to the target.Conclusion: The obtained results demonstrate that simultaneous increase in fraction time and dose per fraction can be beneficial for SRS and SBRT because of the related decrease in BED to normal structures while BED to the target is fixed.« less

SU-F-T-43: Prediction of Dose Increments by Brain Metastases Resection Cavity Shrinkage Model with I-125 and Cs-131 LDR Seed Implantations

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

Han, D; Braunstein, S; Sneed, P

Purpose: This work aims to determine dose variability via a brain metastases resection cavity shrinkage model (RC-SM) with I-125 or Cs-131 LDR seed implantations. Methods: The RC-SM was developed to represent sequential volume changes of 95 consecutive brain metastases patients. All patients underwent serial surveillance MR and change in cavity volume was recorded for each patient. For the initial resection cavity, a prolate-ellipsoid cavity model was suggested and applied volume shrinkage rates to correspond to 1.7, 3.6, 5.9, 11.7, and 20.5 months after craniotomy. Extra-ring structure (6mm) was added on a surface of the resection volume and the same shrinkagemore » rates were applied. Total 31 LDR seeds were evenly distributed on the surface of the resection cavity. The Amersham 6711 I-125 seed model (Oncura, Arlington Heights, IL) and the Model Cs-1 Rev2 Cs-131 seed model (IsoRay, Richland, WA) were used for TG-43U1 dose calculation and in-house-programed 3D-volumetric dose calculation system was used for resection cavity rigid model (RC-RM) and the RC-SM dose calculation. Results: The initial resection cavity volume shrunk to 25±6%, 35±6.8%, 42±7.7%, 47±9.5%, and 60±11.6%, with respect to sequential MR images post craniotomy, and the shrinkage rate (SR) was calculated as SR=56.41Xexp(−0.2024Xt)+33.99 and R-square value was 0.98. The normal brain dose as assessed via the dose to the ring structure with the RC-SM showed 29.34% and 27.95% higher than the RC-RM, I-125 and Cs-131, respectively. The dose differences between I-125 and Cs-131 seeds within the same models, I-125 cases were 9.17% and 10.35% higher than Cs-131 cases, the RC-RM and the RC-SM, respectively. Conclusion: A realistic RC-SM should be considered during LDR brain seed implementation and post-implement planning to prevent potential overdose. The RC-SM calculation shows that Cs-131 is more advantageous in sparing normal brain as the resection cavity volume changes with the LDR seeds implementation.« less

Effects on reproduction in female offspring from Sprague-Dawley rats fed 10% snakeweed (Gutierrezia microcephala) throughout pregnancy and concurrent treatment with safflower oil.

PubMed

Staley, E C; Smith, G S; Greenberg, J A

1995-10-01

Previous studies determined that safflower oil administration provided protection against the embryotoxicity seen following ingestion of 10% snakeweed (Gutierrezia microcephala) throughout pregnancy. Sixty-two young primiparous female rats born in those studies were paired with adult male Sprague-Dawley rats. After 4 d they were removed and carried their litters to term. Observations were made of the presence and extent of reproductive effects attributable to the 10% snakeweed exposure and differences in fecundity that were attributable to dosing with safflower oil or normal saline during the snakeweed exposure. Of the 62 rats, 50 carried litters to term and approximated the reproductive efficiency of normal primiparous Sprague-Dawley rats. There was no significant difference between the fecundity of females born to rats fed the 10% snakeweed and dosed with safflower oil, those born of rats fed snakeweed dosed with normal saline, or those fed a snakeweed-free diet and dosed with normal saline. Regardless of the diet or treatment administered, dams carrying their litters to parturition gave birth to healthy, normo-reproductive offspring. While the toxic principles in Gutierrezia species plants may act as estrogenic or anti-estrogenic compounds, they did not impair fertility in the female offspring of dosed rats.

Novel Measure of Opioid Dose and Costs of Care for Diabetes Mellitus: Opioid Dose and Health Care Costs.

PubMed

Gautam, Santosh; Franzini, Luisa; Mikhail, Osama I; Chan, Wenyaw; Turner, Barbara J

2016-03-01

Diabetes mellitus (DM) has well known costly complications but we hypothesized that costs of care for chronic pain treated with opioid analgesic (OA) medications would also be substantial. In a statewide, privately insured cohort of 29,033 adults aged 18 to 64 years with DM and noncancer pain who filled OA prescription(s) from 2008 to 2012, our outcomes were costs for specific health care services and total costs per 6-month intervals after the first filled OA prescription. Average daily OA dose (4 categories) and total dose (quartiles) in morphine-equivalent milligrams were calculated per 6-month interval after the first OA prescription and combined into a novel OA dose measure. Associations of OA measures with costs of care (n = 126,854 6-month intervals) were examined using generalized estimating equations adjusted for clinical conditions, psychotherapeutic drugs, and DM treatment. Incremental costs for each type of health care service and total cost of care increased progressively with average daily and total OA dose versus no OAs. The combined OA measure identified the highest incremental total costs per 6-month interval that were increased by $8,389 for 50- to 99-mg average daily dose plus >900 mg total dose and, by $9,181 and $9,958 respectively, for ≥100 mg average daily dose plus 301- to 900-mg or >900 mg total dose. In this statewide DM cohort, total health care costs per 6-month interval increased progressively with higher average daily OA dose and with total OA dose but the greatest increases of >$8,000 were distinguished by combinations of higher average daily and total OA doses. The higher costs of care for opioid-treated patients appeared for all types of services and likely reflects multiple factors including morbidity from the underlying cause of pain, care and complications related to opioid use, and poorer control of diabetes as found in other studies. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Esophagus and Contralateral Lung-Sparing IMRT for Locally Advanced Lung Cancer in the Community Hospital Setting.

PubMed

Kao, Johnny; Pettit, Jeffrey; Zahid, Soombal; Gold, Kenneth D; Palatt, Terry

2015-01-01

The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT). From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity, and overall survival. Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 vs. 60.8 Gy, p = 0.04), patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, esophageal V60, and mean esophagus doses compared to patients treated with standard RT (p ≤ 0.001). Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0 vs. 11%, p < 0.001), acute grade ≥2 weight loss (2 vs. 16%, p = 0.04), and late grade ≥2 pneumonitis (7 vs. 21%, p = 0.02). The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p = 0.015). These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose-volume constraints are feasible in the community hospital setting without sacrificing disease control.

In vivo Investigation of Anti-diabetic Properties of Ripe Onion Juice in Normal and Streptozotocin-induced Diabetic Rats

PubMed Central

Lee, Chul-Won; Lee, Hyung-Seok; Cha, Yong-Jun; Joo, Woo-Hong; Kang, Dae-Ook; Moon, Ja-Young

2013-01-01

The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is “Black Onion Extract”) were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyper-glycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product “Black Onion Extract” may possess anti-hyperglycemic potential in diabetes. PMID:24471128

Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers.

PubMed

Rueangweerayut, Ronnatrai; Bancone, Germana; Harrell, Emma J; Beelen, Andrew P; Kongpatanakul, Supornchai; Möhrle, Jörg J; Rousell, Vicki; Mohamed, Khadeeja; Qureshi, Ammar; Narayan, Sushma; Yubon, Nushara; Miller, Ann; Nosten, François H; Luzzatto, Lucio; Duparc, Stephan; Kleim, Jörg-Peter; Green, Justin A

2017-09-01

Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol 487A glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose-response was evident in G6PD-heterozygous subjects ( N = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (-2.65 to -2.95 g/dL [ N = 3]) and primaquine (-1.25 to -3.0 g/dL [ N = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61-80% ( N = 2) and > 80% ( N = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days.

Volumetric-modulated arc therapy vs conventional fixed-field intensity-modulated radiotherapy in a whole-ventricular irradiation: A planning comparison study

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

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Sato, Sayaka

This study evaluated the dosimetric difference between volumetric-modulated arc therapy (VMAT) and conventional fixed-field intensity-modulated radiotherapy (cIMRT) in whole-ventricular irradiation. Computed tomography simulation data for 13 patients were acquired to create plans for VMAT and cIMRT. In both plans, the same median dose (100% = 24 Gy) was prescribed to the planning target volume (PTV), which comprised a tumor bed and whole ventricles. During optimization, doses to the normal brain and body were reduced, provided that the dose constraints of the target coverage were satisfied. The dose-volume indices of the PTV, normal brain, and body as well as monitor unitsmore » were compared between the 2 techniques by using paired t-tests. The results showed no significant difference in the homogeneity index (0.064 vs 0.065; p = 0.824) of the PTV and conformation number (0.78 vs 0.77; p = 0.065) between the 2 techniques. In the normal brain and body, the dose-volume indices showed no significant difference between the 2 techniques, except for an increase in the volume receiving a low dose in VMAT; the absolute volume of the normal brain and body receiving 1 Gy of radiation significantly increased in VMAT by 1.6% and 8.3%, respectively, compared with that in cIMRT (1044 vs 1028 mL for the normal brain and 3079.2 vs 2823.3 mL for the body; p<0.001). The number of monitor units to deliver a 2.0-Gy fraction was significantly reduced in VMAT compared with that in cIMRT (354 vs 873, respectively; p<0.001). In conclusion, VMAT delivers IMRT to complex target volumes such as whole ventricles with fewer monitor units, while maintaining target coverage and conformal isodose distribution comparable to cIMRT; however, in addition to those characteristics, the fact that the volume of the normal brain and body receiving a low dose would increase in VMAT should be considered.« less

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy.

PubMed

Watanabe, Tsubasa; Hattori, Yoshihide; Ohta, Youichiro; Ishimura, Miki; Nakagawa, Yosuke; Sanada, Yu; Tanaka, Hiroki; Fukutani, Satoshi; Masunaga, Shin-Ichiro; Hiraoka, Masahiro; Ono, Koji; Suzuki, Minoru; Kirihata, Mitsunori

2016-11-08

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [ 18 F]-L-FBPA, an 18 F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [ 18 F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [ 19 F]-L-FBPA as alternatives to [ 18 F]-L-FBPA. SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [ 19 F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [ 19 F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. There were no differences between L-BPA and [ 19 F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [ 19 F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to blood ratio of the boron concentrations derived from the values measured by PET on dose calculation.

Pharmacokinetic and pharmacodynamic studies of two different rabbit antithymocyte globulin dosing regimens: results of a randomized trial.

PubMed

Büchler, Matthias; Longuet, Hélène; Lemoine, Roxane; Herr, Florence; Gatault, Philippe; Thibault, Gilles; Ternant, David; Foulon, Christine; Pilorge, Bernadette; Lemay, Djamila; Sung, Crystal; Halimi, Jean-Michel; Baron, Christophe; Lebranchu, Yvon

2013-03-01

Rabbit antithymocyte globulin (rATG; Thymoglobulin(®)) is currently used to prevent acute rejection in kidney transplantation. The dose and regimen of rATG have not been optimized. Moreover, the impact of different treatment regimens on T-cell phenotype reconstitution remains unknown. We conducted a prospective randomized study of 17 renal transplant patients to determine the pharmacokinetics of total and active (bound to human cells) rATG and T-cell phenotype reconstitution after rATG administration. Patients received rATG at a total dose of 6mg/kg, administered either as 1.5mg/kg/day on days 0-3 (Group 1, n=8) or 3mg/kg on days 0 and 3 (Group 2, n=9). All patients received tacrolimus, mycophenolate mofetil and steroids. Blood samples were assayed for total rATG by enzyme linked immunosorbent assay and active rATG by flow cytometry. Maximum concentrations and terminal half-lives were similar between the two groups but at month 3 Group 1 had significantly lower values for total rATG (concentration was 6.2±1.1μg/mL versus 10.2±2.9μg/mL in Group 2, p=0.027) and total rATG dose-normalized AUC (374±83dayg/mL versus 508±149dayg/mL in Group 2, p=0.046). Time to sub-therapeutic levels (<1μg/mL) of active rATG was significantly shorter in Group 1 (18.75±6.9days versus 20±7.5days in Group 2, p<0.001). rATG induced significant depletion followed by slow reconstitution of CD3(+), CD4(+) and CD8(+) cells, with no marked differences between groups. B-cell count was unaffected, whereas CD3(-)CD56(+) NK-cell depletion was observed in both groups. rATG induced a significant decrease in the proportion of naïve CD4(+) T-cells, which plateaued after month 1 in Group 1 and after month 6 in Group 2. The proportion of central memory CD4(+) T-cells increased to a similar extent in both groups (Group 1: 38±18% at baseline, 74±23% at one year, p=0.009; Group 2: 32±14% at baseline, 65±14% at one year, p=0.001). In conclusion, our results suggest that the dosing regimen for rATG induction influences pharmacokinetic parameters without affecting the quality of immune reconstitution. Copyright © 2013 Elsevier B.V. All rights reserved.

Dosimetric evaluation of nanotargeted (188)Re-liposome with the MIRDOSE3 and OLINDA/EXM programs.

PubMed

Chang, Chih-Hsien; Chang, Ya-Jen; Lee, Te-Wei; Ting, Gann; Chang, Kwo-Ping

2012-06-01

The OLINDA/EXM computer code was created as a replacement for the widely used MIRDOSE3 code for radiation dosimetry in nuclear medicine. A dosimetric analysis with these codes was performed to evaluate nanoliposomes as carriers of radionuclides ((188)Re-liposomes) in colon carcinoma-bearing mice. Pharmacokinetic data for (188)Re-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine ((188)Re-BMEDA) and (188)Re-liposome were obtained for estimation of absorbed doses in normal organs. Radiation dose estimates for normal tissues were calculated using the MIRDOSE3 and OLINDA/EXM programs for a colon carcinoma solid tumor mouse model. Mean absorbed doses derived from(188)Re-BMEDA and (188)Re-liposome in normal tissues were generally similar as calculated by MIRDOSE3 and OLINDA/EXM programs. One notable exception to this was red marrow, wherein MIRDOSE3 resulted in higher absorbed doses than OLINDA/EXM (1.53- and 1.60-fold for (188)Re-BMEDA and (188)Re-liposome, respectively). MIRDOSE3 and OLINDA have very similar residence times and organ doses. Bone marrow doses were estimated by designating cortical bone rather than bone marrow as a source organ. The bone marrow doses calculated by MIRDOSE3 are higher than those by OLINDA. If the bone marrow is designated as a source organ, the doses estimated by MIRDOSE3 and OLINDA programs will be very similar.

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

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

Hardy, A; Bostani, M; McMillan, K

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generatedmore » using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Ethanol inhibits human bone cell proliferation and function in vitro

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

Friday, K.E.; Howard, G.A.

1991-06-01

The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantlymore » reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol.« less

Emission study on the gamma-ray irradiation effects on the ferroelectric Pb(Zr,Ti)O3 thin films

NASA Astrophysics Data System (ADS)

Lee, Yunsang; Lim, Junwhi; Yang, Sun A.; Bu, S. D.

We investigated the photoluminescence of the gammy-ray irradiated Pb(Zr,Ti)O3 (PZT) thin films with the various total doses up to 1000 kGy. The PZT thin films were prepared on the Pt/Ti/SiO2/Si substrates by using a sol-gel method with a spin-coating process. It was found that the visible emission emerges near 550 nm with the gamma-ray irradiation. The intensity of the emission increased with the increasing dose amount. The spectral feature of the gamma-ray induced emission was quite narrow, which was distinguished from that formed by normal defects such as oxygen vacancy. We suggest that the gamma-ray irradiation should generate a specific type of defect state inside the PZT films, which could be detected by the low temperature photoluminescence spectroscopy.

Optical evidence for the effect of gamma-ray irradiation on ferroelectric Pb(Zr0.52Ti0.48)O3 thin films

NASA Astrophysics Data System (ADS)

Lim, Junhwi; Lee, Y. S.; Yang, Sun A.; Bu, Sang Don

2016-06-01

We investigated the visible emission property of Pb(Zr,Ti)O3 (PZT) thin films irradiated with gammy-ray (γ-ray) irradiated at various total doses up to 1000 kGy. The PZT thin films were prepared on Pt/Ti/SiO2/Si substrates by using a sol-gel method with a spin-coating process. The visible emission was found to emerge near 550 nm upon γ-ray irradiation, and the intensity of the emission increased with increasing dose. The spectrum of the γ-ray-induced emission was quite narrow, which was quite different from that due to normal defects such as oxygen vacancies. We suggest that the γ-ray irradiation generates inside the PZT films a specific type of defect state that can be detected by using low-temperature photoluminescence spectroscopy.

SU-F-T-157: Physics Considerations Regarding Dosimetric Accuracy of Analytical Dose Calculations for Small Field Proton Therapy: A Monte Carlo Study

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

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Daartz, J

Purpose: To evaluate the accuracy of dose calculations by analytical dose calculation methods (ADC) for small field proton therapy in a gantry based passive scattering facility. Methods: 50 patients with intra-cranial disease were evaluated in the study. Treatment plans followed standard prescription and optimization procedures of proton stereotactic radiosurgery. Dose distributions calculated with the Monte Carlo (MC) toolkit TOPAS were used to represent delivered treatments. The MC dose was first adjusted using the output factor (OF) applied clinically. This factor is determined from the field size and the prescribed range. We then introduced a normalization factor to measure the differencemore » in mean dose between the delivered dose (MC dose with OF) and the dose calculated by ADC for each beam. The normalization was determined by the mean dose of the center voxels of the target area. We compared delivered dose distributions and those calculated by ADC in terms of dose volume histogram parameters and beam range distributions. Results: The mean target dose for a whole treatment is generally within 5% comparing delivered dose (MC dose with OF) and ADC dose. However, the differences can be as great as 11% for shallow and small target treated with a thick range compensator. Applying the normalization factor to the MC dose with OF can reduce the mean dose difference to less than 3%. Considering range uncertainties, the generally applied margins (3.5% of the prescribed range + 1mm) to cover uncertainties in range might not be sufficient to guarantee tumor coverage. The range difference for R90 (90% distal dose falloff) is affected by multiple factors, such as the heterogeneity index. Conclusion: This study indicates insufficient accuracy calculating proton doses using ADC. Our results suggest that uncertainties of target doses are reduced using MC techniques, improving the dosimetric accuracy for proton stereotactic radiosurgery. The work was supported by NIH/NCI under CA U19 021239. CG was partially supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087).« less

Real-time colour pictorial radiation monitoring during coronary angiography: effect on patient peak skin and total dose during coronary angiography.

PubMed

Wilson, Sharon M; Prasan, Ananth M; Virdi, Amy; Lassere, Marissa; Ison, Glenn; Ramsay, David R; Weaver, James C

2016-10-10

The aim of this study was to evaluate whether a real-time (RT) colour pictorial radiation dose monitoring system reduces patient skin and total radiation dose during coronary angiography and intervention. Patient demographics, procedural variables and radiation parameters were recorded before and after institution of the RT skin dose recording system. Peak skin dose as well as traditionally available measures of procedural radiation dose were compared. A total of 1,077 consecutive patients underwent coronary angiography, of whom 460 also had PCI. Institution of the RT skin dose recording system resulted in a 22% reduction in peak skin dose after accounting for confounding variables. Radiation dose reduction was most pronounced in those having PCI but was also seen over a range of subgroups including those with prior coronary artery bypass surgery, high BMI, and with radial arterial access. This was associated with a significant reduction in the number of patients placed at risk of skin damage. Similar reductions in parameters reflective of total radiation dose were also demonstrated after institution of RT radiation monitoring. Institution of an RT skin dose recording reduced patient peak skin and total radiation dose during coronary angiography and intervention. Consideration should be given to widespread adoption of this technology.

SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

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

Bichay, T; Mayville, A

2016-06-15

Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fractionmore » and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.« less

Phase I Study of Vandetanib With Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma

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

Drappatz, Jan; Norden, Andrew D.; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital, Boston, MA

Purpose: Increasing evidence has suggested that angiogenesis inhibition might potentiate the effects of radiotherapy and chemotherapy in patients with glioblastoma (GBM). In addition, epidermal growth factor receptor inhibition might be of therapeutic benefit, because the epidermal growth factor receptor is upregulated in GBM and contributes to radiation resistance. We conducted a Phase I study of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, in patients with newly diagnosed GBM combined with RT and temozolomide (TMZ). Methods and Materials: A total of 13 GBM patients were treated with vandetanib, radiotherapy, and concurrent and adjuvantmore » TMZ, using a standard '3 + 3' dose escalation. The maximal tolerated dose was defined as the dose with <1 of 6 dose-limiting toxicities during the first 12 weeks of therapy. The eligible patients were adults with newly diagnosed GBM, Karnofsky performance status of {>=}60, normal organ function, who were not taking enzyme-inducing antiepileptic drugs. Results: Of the 13 patients, 6 were treated with vandetanib at a dose of 200mg daily. Of the 6 patients, 3 developed dose-limiting toxicities within the first 12 weeks, including gastrointestinal hemorrhage and thrombocytopenia in 1 patient, neutropenia in 1 patient, and diverticulitis with gastrointestinal perforation in 1 patient. The other 7 patients were treated with 100 mg daily, with no dose-limiting toxicities observed, establishing this dose as the maximal tolerated dose combined with TMZ and RT. Conclusion: Vandetanib can be safely combined with RT and TMZ in GBM patients. A Phase II study in which patients are randomized to vandetanib 100 mg daily with RT and TMZ or RT and TMZ alone is underway.« less

Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia.

PubMed

Akdim, Fatima; Visser, Maartje E; Tribble, Diane L; Baker, Brenda F; Stroes, Erik S G; Yu, Rosie; Flaim, Joann D; Su, John; Stein, Evan A; Kastelein, John J P

2010-05-15

A randomized, double-blind, placebo-controlled, dose-escalation study was conducted to examine the efficacy and safety of mipomersen (ISIS 301012), an antisense inhibitor of apolipoprotein B, when added to conventional lipid-lowering therapy for patients with heterozygous familial hypercholesterolemia. A total of 44 patients were enrolled and were separated into 4 cohorts, with doses ranging from 50 to 300 mg (4:1 active treatment/placebo ratio). Patients received 8 doses subcutaneously during a 6-week treatment period. Patients assigned to the 300-mg dose continued for an additional 7 weeks with once-per-week dosing. The primary efficacy end point was the percentage of change from baseline to week 7 in low-density lipoprotein (LDL) cholesterol. Safety was assessed using the laboratory test results and according to the incidence, severity, and relation of adverse events to drug dose. Mipomersen produced significant reductions in LDL cholesterol and other atherogenic apolipoprotein B-containing lipoproteins. After 6 weeks of treatment, the LDL cholesterol level was reduced by 21% from baseline in the 200-mg/week dose group (p <0.05) and 34% from baseline in the 300-mg/week dose group (p <0.01), with a concomitant reduction in apolipoprotein B of 23% (p <0.05) and 33% (p <0.01), respectively. Injection site reactions were the most common adverse event. Elevations in liver transaminase levels (> or =3 times the upper limit of normal) occurred in 4 (11%) of 36 patients assigned to active treatment; 3 of these patients were in the highest dose group. In conclusion, mipomersen has an incremental LDL cholesterol lowering effect when added to conventional lipid-lowering therapy. Copyright 2010 Elsevier Inc. All rights reserved.

Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma

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

Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu, E-mail: hualinzhang@yahoo.com; Zhong, Hualiang; Barth, Rolf F.

2014-02-15

Purpose: To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models. Methods: A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was atmore » the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors’ model. Results: Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional radiotherapy. A significant portion of the tumor volume received a very large dose in grid therapy, which ensures significant tumor cell killing in these regions. Conversely, some areas received a relatively small dose, thereby sparing interspersed normal cells and increasing radiation tolerance. The radiobiology modeling results indicated that grid therapy could be useful for treating acutely responding melanomas infiltrating radiosensitive normal tissues. The theoretical model predictions were supported by the clinical outcomes. Conclusions: Grid therapy functions by selectively killing infiltrating tumor cells and concomitantly sparing interspersed normal cells. The TR depends on the radiosensitivity of the cell population, dose, tumor size, and location. Because the volumes of very high dose regions are small, the LQ model can be used safely to predict the clinical outcomes of grid therapy. When treating melanomas with a dose of 15 Gy or higher, single fraction grid therapy is clearly advantageous for sparing interspersed normal cells. The existence of a threshold fraction dose, which was found in the authors’ theoretical simulations, was confirmed by clinical observations.« less

WE-E-BRE-09: Investigation of the Association Between Radiation-Induced Pain and Radiation Dose in Head and Neck Cancer Patients

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

Gay, H; Dyk, P; Mullen, D

Purpose: Patients with head and neck cancer who undergo radiotherapy often experience several undesirable side-effects, including xerostomia, trismus, and pain in the head and neck area, but little is know about the dose-volume predictors of such pain. We investigated the association between radiation dose and both throat and esophagus pain during radiotherapy. Methods: We analyzed 124 head and neck patients who received radiotherapy at the Washington University School of Medicine in Saint Louis. For these patients, weekly PROs were recorded, including 16 pain and anatomical location questions. In addition, 17 observational symptoms were recorded. Patients were asked to describe theirmore » pain at each site according to a four-level scale: none (0), mild (1), moderate (2), and severe (3). We explored the association between throat pain and the mean dose received in oral cavity and between esophageal pain and the mean dose received in the esophagus. The severity of pain was determined by the difference between the baseline (week 1) pain score and the maximum pain score during treatment. The baseline pain score was defined as the first available pain score before receiving 10 Gy because radiotherapy pain originates later during treatment. Dose-volume metrics were extracted from treatment plans using CERR. To evaluate the correlation between pain and radiation dose, Spearman's correlation coefficient (Rs) was used. Results: The associations between throat pain and the mean dose to the oral cavity, and between esophagus pain and the mean dose to the esophagus, were both statistically significant, with Rs=0.320 (p=0.003) and Rs=0.424 (p<0.0001), respectively. Mean dose, for each structure, was a better predictor of pain than total integral dose. Conclusion: We demonstrated that pain during radiotherapy in head and neck patients highly correlates with the dose delivered. We will further investigate the association between other pain locations and relevant normal tissue dose characteristics.« less

Comparison of normal tissue pharmacokinetics with {sup 111}In/{sup 9}Y monoclonal antibody m170 for breast and prostate cancer

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

Lehmann, Joerg; Department of Radiodiagnosis and Therapy, Division of Hematology/Oncology, University of California Davis School of Medicine, Sacramento, CA; DeNardo, Gerald L.

Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: {sup 111}In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and {sup 111}In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for {sup 9}Y was calculated using {sup 111}In MAb pharmacokinetics from the initial imaging study for eachmore » patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies.« less

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

PubMed

Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

2016-10-01

Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Carbon-ion radiotherapy for marginal lymph node recurrences of cervical cancer after definitive radiotherapy: a case report.

PubMed

Tamaki, Tomoaki; Ohno, Tatsuya; Kiyohara, Hiroki; Noda, Shin-ei; Ohkubo, Yu; Ando, Ken; Wakatsuki, Masaru; Kato, Shingo; Kamada, Tadashi; Nakano, Takashi

2013-04-05

Recurrences of cervical cancer after definitive radiotherapy often occur at common iliac or para-aortic lymph nodes as marginal lymph node recurrences. Patients with these recurrences have a chance of long-term survival by optimal re-treatment with radiotherapy. However, the re-irradiation often overlaps the initial and the secondary radiotherapy fields and can result in increased normal tissue toxicities in the bowels or the stomach. Carbon-ion radiotherapy, a form of particle beam radiotherapy using accelerated carbon ions, offers more conformal and sharp dose distribution than X-ray radiotherapy. Therefore, this approach enables the delivery of high radiation doses to the target while sparing its surrounding normal tissues. Marginal lymph node recurrences in common iliac lymph nodes after radiotherapy were treated successfully by carbon-ion radiotherapy in two patients. These two patients were initially treated with a combination of external beam radiotherapy and intracavitary and interstitial brachytherapy. However, the diseases recurred in the lymph nodes near the border of the initial radiotherapy fields after 22 months and 23 months. Because re-irradiation with X-ray radiotherapy may deliver high doses to a section of the bowels, carbon-ion radiotherapy was selected to treat the lymph node recurrences. A total dose of 48 Gy (RBE) in 12 fractions over 3 weeks was given to the lymph node recurrences, and the tumors disappeared completely with no severe acute toxicities. The two patients showed no evidence of disease for 75 months and 63 months after the initial radiotherapy and for 50 months and 37 months after the carbon-ion radiotherapy, respectively. No severe late adverse effects are observed in these patients. The two presented cases suggest that the highly conformal dose distribution of carbon-ion radiotherapy may be beneficial in the treatment of marginal lymph node recurrences after radiotherapy. In addition, the higher biological effect of carbon-ion radiotherapy and its superior dose distribution may provide more effective tumor control in treatment for re-irradiation of the marginal recurrences in radiation resistant tumors other than cervical cancer.

Telemedicine-guided, very low-dose international normalized ratio self-control in patients with mechanical heart valve implants.

PubMed

Koertke, Heinrich; Zittermann, Armin; Wagner, Otto; Secer, Songuel; Sciangula, Alfonso; Saggau, Werner; Sack, Falk-Udo; Ennker, Jürgen; Cremer, Jochen; Musumeci, Francesco; Gummert, Jan F

2015-06-01

To study in patients performing international normalized ratio (INR) self-control the efficacy and safety of an INR target range of 1.6-2.1 for aortic valve replacement (AVR) and 2.0-2.5 for mitral valve replacement (MVR) or double valve replacement (DVR). In total, 1304 patients undergoing AVR, 189 undergoing MVR and 78 undergoing DVR were randomly assigned to low-dose INR self-control (LOW group) (INR target range, AVR: 1.8-2.8; MVR/DVR: 2.5-3.5) or very low-dose INR self-control once a week (VLO group) and twice a week (VLT group) (INR target range, AVR: 1.6-2.1; MVR/DVR: 2.0-2.5), with electronically guided transfer of INR values. We compared grade III complications (major bleeding and thrombotic events; primary end-points) and overall mortality (secondary end-point) across the three treatment groups. Two-year freedom from bleedings in the LOW, VLO, and VLT groups was 96.3, 98.6, and 99.1%, respectively (P = 0.008). The corresponding values for thrombotic events were 99.0, 99.8, and 98.9%, respectively (P = 0.258). The risk-adjusted composite of grade III complications was in the per-protocol population (reference: LOW-dose group) as follows: hazard ratio = 0.307 (95% CI: 0.102-0.926; P = 0.036) for the VLO group and = 0.241 (95% CI: 0.070-0.836; P = 0.025) for the VLT group. The corresponding values of 2-year mortality were = 1.685 (95% CI: 0.473-5.996; P = 0.421) for the VLO group and = 4.70 (95% CI: 1.62-13.60; P = 0.004) for the VLT group. Telemedicine-guided very low-dose INR self-control is comparable with low-dose INR in thrombotic risk, and is superior in bleeding risk. Weekly testing is sufficient. Given the small number of MVR and DVR patients, results are only valid for AVR patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

SU-F-T-388: Comparison of Biophysical Indices in Hippocampal-Avoidance Whole Brain VMAT and IMRT Radiation Therapy Treatment Plans

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

Kendall, E; Ahmad, S; Algan, O

2016-06-15

Purpose: To compare biophysical indices of Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) treatment plans for whole brain radiation therapy following the NRG-CC001 protocol. Methods: In this retrospective study, a total of fifteen patients were planned with Varian Eclipse Treatment Planning System using VMAT (RapidArc) and IMRT techniques. The planning target volume (PTV) was defined as the whole brain volume excluding a uniform three-dimensional 5mm expansion of the hippocampus volume. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 95% of the target volume receiving 100% of themore » prescribed dose. The NRG Oncology protocol guidelines were followed for contouring and dose-volume constraints. A single radiation oncologist evaluated all treatment plans. Calculations of statistical significance were performed using Student’s paired t-test. Results: All VMAT and IMRT plans met the NRG-CC001 protocol dose-volume criteria. The average equivalent uniform dose (EUD) for the PTV for VMAT vs. IMRT was respectively (19.05±0.33 Gy vs. 19.38±0.47 Gy) for α/β of 2 Gy and (19.47±0.30 Gy vs. 19.84±0.42 Gy) for α/β of 10 Gy. For the PTV, the average mean and maximum doses were 2% and 5% lower in VMAT plans than in IMRT plans, respectively. The average EUD and the normal tissue complication probability (NTCP) for the hippocampus in VMAT vs. IMRT plans were (15.28±1.35 Gy vs. 15.65±0.99 Gy, p=0.18) and (0.305±0.012 Gy vs. 0.308±0.008 Gy, p=0.192), respectively. The average EUD and NTCP for the optic chiasm were both 2% higher in VMAT than in IMRT plans. Conclusion: Though statistically insignificant, VMAT plans indicate a lower hippocampus EUD than IMRT plans. Also, a small variation in NTCP was found between plans.« less

Dietary docosahexaenoic acid-induced generation of liver lipid peroxides is not suppressed further by elevated levels of glutathione in ODS rats.

PubMed

Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

2006-04-01

We examined the effects of ascorbic acid (AsA) and glutathione (GSH; experiment 1) and of GSH in acetaminophen-fed rats (experiment 2) on dietary docosahexaenoic acid (DHA)-induced tissue lipid peroxidation. In experiment 1, AsA-requiring Osteogenic Disorder Shionogi/Shi-od/od (ODS) rats were fed soybean protein diets containing DHA (10.0% total energy) and AsA at 50 (low) or 300 (normal) mg/kg without (low) or with (normal) methionine at 2 g/kg for 32 d. In experiment 2, ODS rats were fed diets containing DHA (7.8% total energy) and acetaminophen (4 g/kg) with different levels of dietary methionine (low, moderate, high, and excessive at 0, 3, 6, and 9 g/kg, respectively) for 30 d. Tissue lipid peroxides and antioxidant levels were determined. In experiment 1, liver lipid peroxide levels in the low-AsA group were lower than those in the normal-AsA group, but kidney and testis lipid peroxide levels in the low-AsA group were higher than those in the normal-AsA group. Dietary methionine tended to decrease tissue lipid peroxide levels but did not decrease vitamin E (VE) consumption. In experiment 2, a high level of methionine (6 g/kg) decreased liver lipid peroxide levels and VE consumption. However, generation of tissue lipid peroxides and VE consumption were not decreased further by a higher dose of methionine (9 g/kg). Higher than normal levels of dietary methionine are not necessarily associated with decreased dietary DHA-induced generation of tissue lipid peroxides and VE consumption except that the GSH requirement is increased in a condition such as acetaminophen feeding.

Role of neuropeptide Y in renal sympathetic vasoconstriction: studies in normal and congestive heart failure rats.

PubMed

DiBona, G F; Sawin, L L

2001-08-01

Sympathetic nerve activity, including that in the kidney, is increased in heart failure with increased plasma concentrations of norepinephrine and the vasoconstrictor cotransmitter neuropeptide Y (NPY). We examined the contribution of NPY to sympathetically mediated alterations in kidney function in normal and heart failure rats. Heart failure rats were created by left coronary ligation and myocardial infarction. In anesthetized normal rats, the NPY Y(1) receptor antagonist, H 409/22, at two doses, had no effect on heart rate, arterial pressure, or renal hemodynamic and excretory function. In conscious severe heart failure rats, high-dose H 409/22 decreased mean arterial pressure by 8 +/- 2 mm Hg but had no effect in normal and mild heart failure rats. During graded frequency renal sympathetic nerve stimulation (0 to 10 Hz), high-dose H 409/22 attenuated the decreases in renal blood flow only at 10 Hz (-36% +/- 5%, P <.05) in normal rats but did so at both 4 (-29% +/- 4%, P <.05) and 10 Hz (-33% +/- 5%, P <.05) in heart failure rats. The glomerular filtration rate, urinary flow rate, and sodium excretion responses to renal sympathetic nerve stimulation were not affected by high-dose H 409/22 in either normal or heart failure rats. NPY does not participate in the regulation of kidney function and arterial pressure in normal conscious or anesthetized rats. When sympathetic nervous system activity is increased, as in heart failure and intense renal sympathetic nerve stimulation, respectively, a small contribution of NPY to maintenance of arterial pressure and to sympathetic renal vasoconstrictor responses may be identified.

Fertility and Pregnancy Outcome After Abdominal Irradiation That Included or Excluded the Pelvis in Childhood Tumor Survivors

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

Sudour, Helene, E-mail: h.sudour@hotmail.f; Chastagner, Pascal; Claude, Line

Purpose: To evaluate fertility after abdominal and/or pelvic irradiation in long-term female survivors. Methods and Materials: Puberty and pregnancy outcome were analyzed in female survivors of childhood cancer (aged <18 years) treated with abdominal and/or pelvic radiotherapy (RT) at one of two French centers (Nancy and Lyon) between 1975 and 2004. Data were obtained from medical records and questionnaires sent to the women. Results: A total of 84 patients who had received abdominal and/or pelvic RT during childhood and were alive and aged more than 18 years at the time of the study made up the study population. Of themore » 57 female survivors treated with abdominal RT that excluded the pelvis, 52 (91%) progressed normally through puberty and 23 (40%) had at least one recorded pregnancy. Of the 27 patients treated with pelvic RT, only 10 (37%) progressed normally through puberty and 5 (19%) had at least one recorded pregnancy. Twenty-two women (seventeen of whom were treated with pelvic RT) had certain subfertility. A total of 50 births occurred in 28 women, with one baby dying at birth; one miscarriage also occurred. There was a high prevalence of prematurity and low birth weight but not of congenital malformations. Conclusions: Fertility can be preserved in patients who undergo abdominal RT that excludes the pelvis, taking into account the other treatments (e.g., chemotherapy with alkylating agents) are taken into account. When RT includes the pelvis, fertility is frequently impaired and women can have difficulty conceiving. Nevertheless, pregnancies can occur in some of these women. The most important factor that endangers a successful pregnancy after RT is the total dose received by the ovaries and uterus. This radiation dose has to be systematically recorded to improve our ability to follow up patients.« less

EXCRETION OF P$sup 32$ AFTER THERAPY FOR POLYCYTHEMIA RUBRA VERA

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

Weijer, D.L.; Duggan, H.E.; Scott, D.B.

1962-09-01

Fifteen subjects undergoing treatment for polycythemia rubra vera were given P/sup 32/. Carrier-free P/sup 32/ was administered intravenously in 11 and orally in 6. Total excretion studies were carried out in each case for periods of 5 to 22 days. Average urinary excretion of P/sup 32/, as a percentage of the initial dose to the end of 3 days for the entire series, was 14.3%, with limits of 6.4 and 18.7%. The corresponding 5-day average amounted to 17.8%, with limits of 7.5 and 22.5%. In the six patients treated orally, the average 3-day urinary excretion was 11.2% and for 5more » days was 14.2%. For the 11 patients treated intravenously, the average 3-day excretion was 16.1%, the average 5-day excretion 19.8%. The average fecal excretion as a percentage of the initial dose to the end of 3 days was 1.7%, with limits of 0.1 and 5.5%, and the average 5-day excretion was 2.5%, with limits 0.5 and 5.9%. In the orally treated fasting group the total stool excretion to the end of 3 days was 2.0 and 2.5% at the end of 5 days. Of the 10 polycythemia patients treated intravenously, the stool excretion to the end of 3 days was 1.5% and at 5 days 2.5%. Under fasting conditions (both before and after the administration of P/sup 32/) with little or no carrier added, the fecal excretion of P/sup 32/is small. Thus, the total excretion of P/sup 32/ does not differ significantly for oral and intravenous administration. Hence, despite contrary reports, it appears that under fasting conditions of administration it is not necessary to increase the oral dose of P/ sup 32/ to 4/3 of the intravenous dose in order to obtain equivalent absorption of the administered dose. It is concluded that the P/sup 32/ content of urine in the first 24 hr after therapy, by either route of administration, indicates whether or not a particular patient will retain the dose within normal limits. (BBB)« less

SU-E-T-613: Dosimetric Consequences of Systematic MLC Leaf Positioning Errors

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

Kathuria, K; Siebers, J

2014-06-01

Purpose: The purpose of this study is to determine the dosimetric consequences of systematic MLC leaf positioning errors for clinical IMRT patient plans so as to establish detection tolerances for quality assurance programs. Materials and Methods: Dosimetric consequences were simulated by extracting mlc delivery instructions from the TPS, altering the file by the specified error, reloading the delivery instructions into the TPS, recomputing dose, and extracting dose-volume metrics for one head-andneck and one prostate patient. Machine error was simulated by offsetting MLC leaves in Pinnacle in a systematic way. Three different algorithms were followed for these systematic offsets, and aremore » as follows: a systematic sequential one-leaf offset (one leaf offset in one segment per beam), a systematic uniform one-leaf offset (same one leaf offset per segment per beam) and a systematic offset of a given number of leaves picked uniformly at random from a given number of segments (5 out of 10 total). Dose to the PTV and normal tissue was simulated. Results: A systematic 5 mm offset of 1 leaf for all delivery segments of all beams resulted in a maximum PTV D98 deviation of 1%. Results showed very low dose error in all reasonably possible machine configurations, rare or otherwise, which could be simulated. Very low error in dose to PTV and OARs was shown in all possible cases of one leaf per beam per segment being offset (<1%), or that of only one leaf per beam being offset (<.2%). The errors resulting from a high number of adjacent leaves (maximum of 5 out of 60 total leaf-pairs) being simultaneously offset in many (5) of the control points (total 10–18 in all beams) per beam, in both the PTV and the OARs analyzed, were similarly low (<2–3%). Conclusions: The above results show that patient shifts and anatomical changes are the main source of errors in dose delivered, not machine delivery. These two sources of error are “visually complementary” and uncorrelated (albeit not additive in the final error) and one can easily incorporate error resulting from machine delivery in an error model based purely on tumor motion.« less

High normal blood pressure in early pregnancy also contribute to early onset preeclampsia and severe preeclampsia.

PubMed

He, Dian; Wu, Shaowen; Zhao, Haiping; Zheng, Zihe; Zhang, Weiyuan

2017-11-27

This study was to evaluate effects of high normal blood pressure (HNBP) in early pregnancy on total preeclampsia, early preeclampsia, and severe preeclampsia. We conducted a multicenter, national representative retrospective cohort study. HNBP was defined as systolic blood pressure between 130 and 140 mmHg or diastolic blood pressure between 85 and 90 mmHg. We used multivariable logistic regression to examine the associations of HNBP and the risks of above three types of preeclampsia. We included 58 054 women who were normotensive and nulliparous in early pregnancy. 4 809 (8.3%) fulfilled the definition of having HNBP, 16 682 (28.7%) were in normal blood pressure group, and 36 563 (63.0%) were in optimal blood pressure group. The incidence rates of total preeclampsia, early preeclampsia, and severe preeclampsia were 2.1% (1 217), 0.8% (491), and 1.4% (814), respectively. Compared to having optimal blood pressure, women with HNBP had significantly higher odds of total preeclampsia (odds ratio (OR) = 4.028, 95% confidence interval (CI) 3.377, 4.804), severe preeclampsia (OR = 3.542, 95% CI 2.851, 4.400), and early preeclampsia (OR = 8.163, 95% CI 6.219, 10.715). Our restricted cubic spline results supported the dose-response relationship between continuous blood pressure and the odds ratio of three types of preeclampsia. The fraction of early preeclampsia associated with prehypertension was 58.6%, which was higher than those of total preeclampsia (42.2%) or severe preeclampsia (40.5%). Women in early pregnancy with HNBP more likely develop total preeclampsia, early preeclampsia and severe preeclampsia, compared to those with optimal blood pressure. HNBP contribute more to early preeclampsia than severe preeclampsia. Our study provided robust epidemiological evidences for monitoring HNBP in early pregnancy to reduce the risks of preeclampsia.

Dose evaluation of Grid Therapy using a 6 MV flattening filter-free (FFF) photon beam: A Monte Carlo study.

PubMed

Martínez-Rovira, Immaculada; Puxeu-Vaqué, Josep; Prezado, Yolanda

2017-10-01

Spatially fractionated radiotherapy is a strategy to overcome the main limitation of radiotherapy, i.e., the restrained normal tissue tolerances. A well-known example is Grid Therapy, which is currently performed at some hospitals using megavoltage photon beams delivered by Linacs. Grid Therapy has been successfully used in the management of bulky abdominal tumors with low toxicity. The aim of this work was to evaluate whether an improvement in therapeutic index in Grid Therapy can be obtained by implementing it in a flattening filter-free (FFF) Linac. The rationale behind is that the removal of the flattening filter shifts the beam energy spectrum towards lower energies and increase the photon fluence. Lower energies result in a reduction of lateral scattering and thus, to higher peak-to-valley dose ratios (PVDR) in normal tissues. In addition, the gain in fluence might allow using smaller beams leading a more efficient exploitation of dose-volume effects, and consequently, a better normal tissue sparing. Monte Carlo simulations were used to evaluate realistic dose distributions considering a 6 MV FFF photon beam from a standard medical Linac and a cerrobend mechanical collimator in different configurations: grid sizes of 0.3 × 0.3 cm 2 , 0.5 × 0.5 cm 2 , and 1 × 1 cm 2 and a corresponding center-to-center (ctc) distance of 0.6, 1, and 2 cm, respectively (total field size of 10 × 10 cm 2 ). As figure of merit, peak doses in depth, PVDR, output factors (OF), and penumbra values were assessed. Dose at the entrance is slightly higher than in conventional Grid Therapy. However, it is compensated by the large PVDR obtained at the entrance, reaching a maximum of 35 for a grid size of 1 × 1 cm 2 . Indeed, this grid size leads to very high PVDR values at all depths (≥ 10), which are much higher than in standard Grid Therapy. This may be beneficial for normal tissues but detrimental for tumor control, where a lower PVDR might be requested. In that case, higher valley doses in the tumor could be achieved by using an interlaced approach and/or adapting the ctc distance. The smallest grid size (0.3 × 0.3 cm 2 ) leads to low PVDR at all depths, comparable to standard Grid Therapy. However, the use of very thin beams might increase the normal tissue tolerances with respect to the grid size commonly used (1 × 1 cm 2 ). The gain in fluence provided by FFF implies that the important OF reduction (0.6) will not increase treatment time. Finally, the intermediate configuration (0.5 × 0.5 cm 2 ) provides high PVDR in the first 5 cm, and comparable PVDR to previous Grid Therapy works at depth. Therefore, this configuration might allow increasing the normal tissue tolerances with respect to Grid Therapy thanks to the higher PVDR and thinner beams, while a similar tumor control could be expected. The implementation of Grid Therapy in an FFF photon beam from medical Linac might lead to an improvement of the therapeutic index. Among the cases evaluated, a grid size of 0.5 × 0.5 cm 2 (1-cm-ctc) is the most advantageous configuration from the physics point of view. Radiobiological experiments are needed to fully explore this new avenue and to confirm our results. © 2017 American Association of Physicists in Medicine.

The influence of patient size on dose conversion coefficients: a hybrid phantom study for adult cardiac catheterization

NASA Astrophysics Data System (ADS)

Johnson, Perry; Lee, Choonsik; Johnson, Kevin; Siragusa, Daniel; Bolch, Wesley E.

2009-06-01

In this study, the influence of patient size on organ and effective dose conversion coefficients (DCCs) was investigated for a representative interventional fluoroscopic procedure—cardiac catheterization. The study was performed using hybrid phantoms representing an underweight, average and overweight American adult male. Reference body sizes were determined using the NHANES III database and parameterized based on standing height and total body mass. Organ and effective dose conversion coefficients were calculated for anterior-posterior, posterior-anterior, left anterior oblique and right anterior oblique projections using the Monte Carlo code MCNPX 2.5.0 with the metric dose area product being used as the normalization factor. Results show body size to have a clear influence on DCCs which increased noticeably when body size decreased. It was also shown that if patient size is neglected when choosing a DCC, the organ and effective dose will be underestimated to an underweight patient and will be overestimated to an underweight patient, with errors as large as 113% for certain projections. Results were further compared with those published for a KTMAN-2 Korean patient-specific tomographic phantom. The published DCCs aligned best with the hybrid phantom which most closely matched in overall body size. These results highlighted the need for and the advantages of phantom-patient matching, and it is recommended that hybrid phantoms be used to create a more diverse library of patient-dependent anthropomorphic phantoms for medical dose reconstruction.

Statistical methods for clinical verification of dose response parameters related to esophageal stricture and AVM obliteration from radiotherapy

NASA Astrophysics Data System (ADS)

Mavroidis, Panayiotis; Lind, Bengt K.; Theodorou, Kyriaki; Laurell, Göran; Fernberg, Jan-Olof; Lefkopoulos, Dimitrios; Kappas, Constantin; Brahme, Anders

2004-08-01

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and khgr2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Dosimetric effect of beam arrangement for intensity-modulated radiation therapy in the treatment of upper thoracic esophageal carcinoma

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

Fu, Yuchuan; Deng, Min; Zhou, Xiaojuan

To evaluate the lung sparing in intensity-modulated radiation therapy (IMRT) for patients with upper thoracic esophageal tumors extending inferiorly to the thorax by different beam arrangement. Overall, 15 patient cases with cancer of upper thoracic esophagus were selected for a retrospective treatment-planning study. Intensity-modulated radiation therapy plans using 4, 5, and 7 beams (4B, 5B, and 7B) were developed for each patient by direct machine parameter optimization (DMPO). All plans were evaluated with respect to dose volumes to irradiated targets and normal structures, with statistical comparisons made between 4B with 5B and 7B intensity-modulated radiation therapy plans. Differences among plansmore » were evaluated using a two-tailed Friedman test at a statistical significance of p < 0.05. The maximum dose, average dose, and the conformity index (CI) of planning target volume 1 (PTV1) were similar for 3 plans for each case. No significant difference of coverage for planning target volume 1 and maximum dose for spinal cords were observed among 3 plans in present study (p > 0.05). The average V{sub 5}, V{sub 13}, V{sub 20}, mean lung dose, and generalized equivalent uniform dose (gEUD) for the total lung were significantly lower in 4B-plans than those data in 5B-plans and 7B-plans (p < 0.01). Although the average V{sub 30} for the total lung were significantly higher in 4B-plans than those in 5B-plans and 7B-plans (p < 0.05). In addition, when comparing with the 4B-plans, the conformity/heterogeneity index of the 5B- and 7B-plans were significantly superior (p < 0.05). The 4B-intensity-modulated radiation therapy plan has advantage to address the specialized problem of lung sparing to low- and intermediate-dose exposure in the thorax when dealing with relative long tumors extended inferiorly to the thoracic esophagus for upper esophageal carcinoma with the cost for less conformity. Studies are needed to compare the superiority of volumetric modulated arc therapy with intensity-modulated radiation therapy technique.« less

Dose and detectability for a cone-beam C-arm CT system revisited

PubMed Central

Ganguly, Arundhuti; Yoon, Sungwon; Fahrig, Rebecca

2010-01-01

Purpose: The authors had previously published measurements of the detectability of disk-shaped contrast objects in images obtained from a C-arm CT system. A simple approach based on Rose’s criterion was used to scale the date, assuming the threshold for the smallest diameter detected should be inversely proportional to (dose)1∕2. A more detailed analysis based on recent theoretical modeling of C-arm CT images is presented in this work. Methods: The signal and noise propagations in a C-arm based CT system have been formulated by other authors using cascaded systems analysis. They established a relationship between detectability and the noise equivalent quanta. Based on this model, the authors obtained a relation between x-ray dose and the diameter of the smallest disks detected. A closed form solution was established by assuming no rebinning and no resampling of data, with low additive noise and using a ramp filter. For the case when no such assumptions were made, a numerically calculated solution using previously reported imaging and reconstruction parameters was obtained. The detection probabilities for a range of dose and kVp values had been measured previously. These probabilities were normalized to a single dose of 56.6 mGy using the Rose-criteria-based relation to obtain a universal curve. Normalizations based on the new numerically calculated relationship were compared to the measured results. Results: The theoretical and numerical calculations have similar results and predict the detected diameter size to be inversely proportional to (dose)1∕3 and (dose)1∕2.8, respectively. The normalized experimental curves and the associated universal plot using the new relation were not significantly different from those obtained using the Rose-criterion-based normalization. Conclusions: From numerical simulations, the authors found that the diameter of detected disks depends inversely on the cube root of the dose. For observer studies for disks larger than 4 mm, the cube root as well as square root relations appear to give similar results when used for normalization. PMID:20527560

Toward a real-time in vivo dosimetry system using plastic scintillation detectors

PubMed Central

Archambault, Louis; Briere, Tina M.; Pönisch, Falk; Beaulieu, Luc; Kuban, Deborah A.; Lee, Andrew; Beddar, Sam

2010-01-01

Purpose In this work, we present and validate a plastic scintillation detector (PSD) system designed for real-time multi-probe in vivo measurements. Methods and Materials The PSDs were built with a dose-sensitive volume of 0.4 mm3. PSDs were assembled into modular detector patches, each containing 5 closely packed PSDs. Continuous dose readings were performed every 150 ms, with a gap between consecutive readings of less than 0.3 ms. We first studied the effect of electron multiplication. We then assessed system performance in acrylic and anthropomorphic pelvic phantoms. Results The PSDs are compatible with clinical rectal balloons and are easily inserted into the anthropomorphic phantom. With an electron multiplication average gain factor of 40, a twofold increase in the signal-to-noise ratio was observed, making near real-time dosimetry feasible. Under calibration conditions, the PSDs agreed with ion chamber measurements to 0.08%. Precision, evaluated as a function of the total dose delivered, ranged from 2.3% at 2 cGy to 0.4% at 200 cGy. Conclusion Real-time PSD measurements are highly accurate and precise. These PSDs can be mounted onto rectal balloons, transforming these clinical devices into in vivo dose detectors without modifying current clinical practice. Real-time monitoring of the dose delivered near the rectum during prostate radiation therapy should help radiation oncologists protect this sensitive normal structure. PMID:20231074

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats.

PubMed

Kasote, D M; Badhe, Y S; Zanwar, A A; Hegde, M V; Deshmukh, K K

2012-07-01

to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats. Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl(4) in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl(4) intoxication. Hepatic lipid peroxidation elevated by CCl(4) intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl(4) -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl(4) -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). EPC-BF possesses the significant hepatoprotective activity against CCl(4) induced liver damage, which could be mediated through increase in antioxidant defenses.

Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

PubMed

Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2002-02-21

Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

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

Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as wellmore » as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.« less

Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

PubMed

Wu, Yue-Yue; Zha, Ying; Liu, Jun; Wang, Fang; Xu, Jiong; Chen, Zao-Ping; Ding, He-Yuan; Sheng, Li; Han, Xiao-Jie

2016-11-17

To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg -1 ·day -1 BBR (HF+LBBR group) and 380 mg·kg -1 ·day -1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR. Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

NASA Astrophysics Data System (ADS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or γ rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for γ rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

The effects of small field dosimetry on the biological models used in evaluating IMRT dose distributions

NASA Astrophysics Data System (ADS)

Cardarelli, Gene A.

The primary goal in radiation oncology is to deliver lethal radiation doses to tumors, while minimizing dose to normal tissue. IMRT has the capability to increase the dose to the targets and decrease the dose to normal tissue, increasing local control, decrease toxicity and allow for effective dose escalation. This advanced technology does present complex dose distributions that are not easily verified. Furthermore, the dose inhomogeneity caused by non-uniform dose distributions seen in IMRT treatments has caused the development of biological models attempting to characterize the dose-volume effect in the response of organized tissues to radiation. Dosimetry of small fields can be quite challenging when measuring dose distributions for high-energy X-ray beams used in IMRT. The proper modeling of these small field distributions is essential in reproducing accurate dose for IMRT. This evaluation was conducted to quantify the effects of small field dosimetry on IMRT plan dose distributions and the effects on four biological model parameters. The four biological models evaluated were: (1) the generalized Equivalent Uniform Dose (gEUD), (2) the Tumor Control Probability (TCP), (3) the Normal Tissue Complication Probability (NTCP) and (4) the Probability of uncomplicated Tumor Control (P+). These models are used to estimate local control, survival, complications and uncomplicated tumor control. This investigation compares three distinct small field dose algorithms. Dose algorithms were created using film, small ion chamber, and a combination of ion chamber measurements and small field fitting parameters. Due to the nature of uncertainties in small field dosimetry and the dependence of biological models on dose volume information, this examination quantifies the effects of small field dosimetry techniques on radiobiological models and recommends pathways to reduce the errors in using these models to evaluate IMRT dose distributions. This study demonstrates the importance of valid physical dose modeling prior to the use of biological modeling. The success of using biological function data, such as hypoxia, in clinical IMRT planning will greatly benefit from the results of this study.

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

Antidiabetic effect of Sida cordata in alloxan induced diabetic rats.

PubMed

Shah, Naseer Ali; Khan, Muhammad Rashid

2014-01-01

Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties.

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.

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-E-T-632: A Dosimetric Comparison of the 3D-CRT Planning of Chest Wall in Post-Mastectomy Breast Cancer Patients, with and Without Breast Board Setup

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

Muzaffar, Ambreen; Masood, Asif; Ullah, Haseeb

2014-06-15

Purpose: Breast boards are used in breast radiation which increases normal lung and heart doses, when supraclavicular field is included. Therefore, in this study through dose volume histogram (DVHs), lung and heart doses comparison was done between two different setups i.e. with and without breast board, for the treatment of left chest wall and supraclavicular fossa in postmastectomy left breast cancer. Methods: In this study, CT-Simulation scans of ten breast cancer patients were done with and without breast board, at Shifa International Hospitals Islamabad, to investigate the differences between the two different setups of the irradiation of left chest wallmore » in terms of lung and heart doses. For immobilization, support under the neck, shoulders and arms was used. Precise PLAN 2.15 treatment planning system (TPS) was used for 3D-CRT planning. The total prescribed dose for both the plans was 5000 cGy/25 fractions. The chest wall was treated with a pair of tangential photon fields and the upper supraclavicular nodal regions were treated with an anterior photon field. A mono-isocentric technique was used to match the tangential fields with the anterior field at the isocentre. The dose volume histogram was used to compare the doses of heart and ipsilateral lung. Results: Both the plans of each patient were generated and compared. DVH results showed that for the same PTV dose coverage, plans without breast board resulted in a reduction of lung and heart doses compared with the plans with breast board. There was significant reductions in V20, V<25 and mean doses for lung and V<9 and mean doses for heart. Conclusion: In comparison of both the plans, setup without breast board significantly reduced the dose-volume of the ipsilateral lung and heart in left chest wall patients. Waived registration request has been submitted.« less

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

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

Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from themore » histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.« less

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

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

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters {<=}20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55{+-}0.79 with HI 1.23{+-}0.06; the average R{sub 50}-R{sub 100} was 0.41{+-}0.08, 0.55{+-}0.10, and 0.65{+-}0.09 cm, respectively, for tumors {<=}20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.« less

Measurement of Total Scatter Factor for Stereotactic Cones with Plastic Scintillation Detector

PubMed Central

Chaudhari, Suresh H; Dobhal, Rishabh; Kinhikar, Rajesh A.; Kadam, Sudarshan S.; Deshpande, Deepak D.

2017-01-01

Advanced radiotherapy modalities such as stereotactic radiosurgery (SRS) and image-guided radiotherapy may employ very small beam apertures for accurate localized high dose to target. Accurate measurement of small radiation fields is a well-known challenge for many dosimeters. The purpose of this study was to measure total scatter factors for stereotactic cones with plastic scintillation detector and its comparison against diode detector and theoretical estimates. Measurements were performed on Novalis Tx™ linear accelerator for 6MV SRS beam with stereotactic cones of diameter 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm. The advantage of plastic scintillator detector is in its energy dependence. The total scatter factor was measured in water at the depth of dose maximum. Total scatter factor with plastic scintillation detector was determined by normalizing the readings to field size of 10 cm × 10 cm. To overcome energy dependence of diode detector for the determination of scatter factor with diode detector, daisy chaining method was used. The plastic scintillator detector was calibrated against the ionization chamber, and the reproducibility in the measured doses was found to be within ± 1%. Total scatter factor measured with plastic scintillation detector was 0.728 ± 0.3, 0.783 ± 0.05, 0.866 ± 0.55, 0.885 ± 0.5, and 0.910 ± 0.06 for cone sizes of 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm, respectively. Total scatter factor measured with diode detector was 0.733 ± 0.03, 0.782 ± 0.02, 0.834 ± 0.07, 0.854 ± 0.02, and 0.872 ± 0.02 for cone sizes of 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm, respectively. The variation in the measurement of total scatter factor with published Monte Carlo data was found to be −1.3%, 1.9%, −0.4%, and 0.4% for cone sizes of 7.5 mm, 10 mm, 12.5 mm, and 15 mm, respectively. We conclude that total scatter factor measurements for stereotactic cones can be adequately carried out with a plastic scintillation detector. Our results show a high level of consistency within our data and compared well with published data. PMID:28405102

Measurement of Total Scatter Factor for Stereotactic Cones with Plastic Scintillation Detector.

PubMed

Chaudhari, Suresh H; Dobhal, Rishabh; Kinhikar, Rajesh A; Kadam, Sudarshan S; Deshpande, Deepak D

2017-01-01

Advanced radiotherapy modalities such as stereotactic radiosurgery (SRS) and image-guided radiotherapy may employ very small beam apertures for accurate localized high dose to target. Accurate measurement of small radiation fields is a well-known challenge for many dosimeters. The purpose of this study was to measure total scatter factors for stereotactic cones with plastic scintillation detector and its comparison against diode detector and theoretical estimates. Measurements were performed on Novalis Tx ™ linear accelerator for 6MV SRS beam with stereotactic cones of diameter 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm. The advantage of plastic scintillator detector is in its energy dependence. The total scatter factor was measured in water at the depth of dose maximum. Total scatter factor with plastic scintillation detector was determined by normalizing the readings to field size of 10 cm × 10 cm. To overcome energy dependence of diode detector for the determination of scatter factor with diode detector, daisy chaining method was used. The plastic scintillator detector was calibrated against the ionization chamber, and the reproducibility in the measured doses was found to be within ± 1%. Total scatter factor measured with plastic scintillation detector was 0.728 ± 0.3, 0.783 ± 0.05, 0.866 ± 0.55, 0.885 ± 0.5, and 0.910 ± 0.06 for cone sizes of 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm, respectively. Total scatter factor measured with diode detector was 0.733 ± 0.03, 0.782 ± 0.02, 0.834 ± 0.07, 0.854 ± 0.02, and 0.872 ± 0.02 for cone sizes of 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm, respectively. The variation in the measurement of total scatter factor with published Monte Carlo data was found to be -1.3%, 1.9%, -0.4%, and 0.4% for cone sizes of 7.5 mm, 10 mm, 12.5 mm, and 15 mm, respectively. We conclude that total scatter factor measurements for stereotactic cones can be adequately carried out with a plastic scintillation detector. Our results show a high level of consistency within our data and compared well with published data.

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

PubMed

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

An international dosimetry exchange for BNCT part II: computational dosimetry normalizations.

PubMed

Riley, K J; Binns, P J; Harling, O K; Albritton, J R; Kiger, W S; Rezaei, A; Sköld, K; Seppälä, T; Savolainen, S; Auterinen, I; Marek, M; Viererbl, L; Nievaart, V A; Moss, R L

2008-12-01

The meaningful sharing and combining of clinical results from different centers in the world performing boron neutron capture therapy (BNCT) requires improved precision in dose specification between programs. To this end absorbed dose normalizations were performed for the European clinical centers at the Joint Research Centre of the European Commission, Petten (The Netherlands), Nuclear Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik, Nyköping (Sweden). Each European group prepared a treatment plan calculation that was bench-marked against Massachusetts Institute of Technology (MIT) dosimetry performed in a large, water-filled phantom to uniformly evaluate dose specifications with an estimated precision of +/-2%-3%. These normalizations were compared with those derived from an earlier exchange between Brookhaven National Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to biological weighting factors, large variations between calculated and measured dose are apparent that depend upon the 10B uptake in tissue. Assuming a boron concentration of 15 microg g(-1) in normal tissue, differences in the evaluated maximum dose to brain for the same nominal specification of 10 Gy(w) at the different facilities range between 7.6 and 13.2 Gy(w) in the trials using boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and 11.1 Gy(w) in the two boron sulfhydryl (BSH) studies. Most notably, the value for the same specified dose of 10 Gy(w) determined at the different participating centers using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC), and 74% (Studsvik). Conversion of dose specification is now possible between all active participants and should be incorporated into future multi-center patient analyses.

Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

PubMed

Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

2014-11-01

The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.