A kinematic model to estimate effective dose of radioactive substances in a human body

NASA Astrophysics Data System (ADS)

Sasaki, S.; Yamada, T.

2013-05-01

The great earthquake occurred in the north-east area in Japan in March 11, 2011. Facility system to control Fukushima Daiichi nuclear power station was completely destroyed by the following giant tsunami. From the damaged reactor containment vessels, an amount of radioactive substances had leaked and diffused in the vicinity of this station. Radiological internal exposure became a serious social issue both in Japan and all over the world. The present study provides an easily understandable, kinematic-based model to estimate the effective dose of radioactive substances in a human body by simplifying the complicated mechanism of metabolism. International Commission on Radiological Protection (ICRP) has developed a sophisticated model, which is well-known as a standard method to calculate the effective dose for radiological protection. However, owing to that ICRP method is fine, it is rather difficult for non-professional people of radiology to gasp the whole images of the movement and the influences of radioactive substances in a human body. Therefore, in the present paper we propose a newly-derived and easily-understandable model to estimate the effective dose. The present method is very similar with the traditional and conventional tank model in hydrology. Ingestion flux of radioactive substances corresponds to rain intensity and the storage of radioactive substances to the water storage in a basin in runoff analysis. The key of the present method is to estimate the energy radiated in the radioactive nuclear disintegration of an atom by using classical theory of β decay and special relativity for various kinds of radioactive atoms. The parameters used in this model are only physical half-time and biological half-time, and there are no operational parameters or coefficients to adjust our theoretical runoff to ICRP. Figure shows the time-varying effective dose with ingestion duration, and we can confirm the validity of our model. The time-varying effective dose with

Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

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

Sinha, Neeharika; Cifter, Gizem; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using themore » Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy

Collective dose estimates by the marine food pathway from liquid radioactive wastes dumped in the Sea of Japan.

PubMed

Togawa, O; Povinec, P P; Pettersson, H B

1999-09-30

IAEA-MEL has been engaged in an assessment programme related to radioactive waste dumping by the former USSR and other countries in the western North Pacific Ocean and its marginal seas. This paper focuses on the Sea of Japan and on estimation of collective doses from liquid radioactive wastes. The results from the Japanese-Korean-Russian joint expeditions are summarized, and collective doses for the Japanese population by the marine food pathway are estimated from liquid radioactive wastes dumped in the Sea of Japan and compared with those from global fallout and natural radionuclides. The collective effective dose equivalents by the annual intake of marine products caught in each year show a maximum a few years after the disposals. The total dose from all radionuclides reaches a maximum of 0.8 man Sv in 1990. Approximately 90% of the dose derives from 137Cs, most of which is due to consumption of fish. The total dose from liquid radioactive wastes is approximately 5% of that from global fallout, the contribution of which is below 0.1% of that of natural 210Po.

Maxine: A spreadsheet for estimating dose from chronic atmospheric radioactive releases

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

Jannik, Tim; Bell, Evaleigh; Dixon, Kenneth

MAXINE is an EXCEL© spreadsheet, which is used to estimate dose to individuals for routine and accidental atmospheric releases of radioactive materials. MAXINE does not contain an atmospheric dispersion model, but rather doses are estimated using air and ground concentrations as input. Minimal input is required to run the program and site specific parameters are used when possible. Complete code description, verification of models, and user’s manual have been included.

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

PubMed

Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

2016-01-01

To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

Collective doses to man from dumping of radioactive waste in the Arctic Seas.

PubMed

Nielsen, S P; Iosjpe, M; Strand, P

1997-08-25

A box model for the dispersion of radionuclides in the marine environment covering the Arctic Ocean and the North Atlantic Ocean has been constructed. Collective doses from ingestion pathways have been calculated from unit releases of the radionuclides 3H, 60Co, 63Ni, 90Sr, 129I, 137Cs, 239Pu and 241Am into a fjord on the east coast of NovayaZemlya. The results show that doses for the shorter-lived radionuclides (e.g. 137Cs) are derived mainly from seafood production in the Barents Sea. Doses from the longer-lived radionuclides (e.g. 239Pu) are delivered through marine produce further away from the Arctic Ocean. Collective doses were calculated for two release scenarios, both of which are based on information of the dumping of radioactive waste in the Barents and Kara Seas by the former Soviet Union and on preliminary information from the International Arctic Sea Assessment Programme. A worst-case scenario was assumed according to which all radionuclides in liquid and solid radioactive waste were available for dispersion in the marine environment at the time of dumping. Release of radionuclides from spent nuclear fuel was assumed to take place by direct corrosion of the fuel ignoring the barriers that prevent direct contact between the fuel and the seawater. The second scenario selected assumed that releases of radionuclides from spent nuclear fuel do not occur until after failure of the protective barriers. All other liquid and solid radioactive waste was assumed to be available for dispersion at the time of discharge in both scenarios. The estimated collective dose for the worst-case scenario was about 9 manSv and that for the second scenario was about 3 manSv. In both cases, 137Cs is the radionuclide predicted to dominate the collective doses as well as the peak collective dose rates.

Fixed-dose combination ezetimibe+atorvastatin lowers LDL-C equivalent to co-administered components in randomized trials: use of a dose-response model.

PubMed

Bays, Harold E; Chen, Erluo; Tomassini, Joanne E; McPeters, Gail; Polis, Adam B; Triscari, Joseph

2015-04-01

Co-administration of ezetimibe with atorvastatin is a generally well-tolerated treatment option that reduces LDL-C levels and improves other lipids with greater efficacy than doubling the atorvastatin dose. The objective of the study was to demonstrate the equivalent lipid-modifying efficacy of fixed-dose combination (FDC) ezetimibe/atorvastatin compared with the component agents co-administered individually in support of regulatory filing. Two randomized, 6-week, double-blind cross-over trials compared the lipid-modifying efficacy of ezetimibe/atorvastatin 10/20 mg (n = 353) or 10/40 mg (n = 280) vs. separate co-administration of ezetimibe 10 mg plus atorvastatin 20 mg (n = 346) or 40 mg (n = 280), respectively, in hypercholesterolemic patients. Percent changes from baseline in LDL-C (primary endpoint) and other lipids (secondary endpoints) were assessed by analysis of covariance; triglycerides were evaluated by longitudinal-data analysis. Expected differences between FDC and the corresponding co-administered doses were predicted from a dose-response relationship model; sample size was estimated given the expected difference and equivalence margins (±4%). LDL-C-lowering equivalence was based on 97.5% expanded confidence intervals (CI) for the difference contained within the margins; equivalence margins for other lipids were not prespecified. Ezetimibe/atorvastatin FDC 10/20 mg was equivalent to co-administered ezetimibe+atorvastatin 20 mg in reducing LDL-C levels (54.0% vs. 53.8%) as was FDC 10/40 mg and ezetimibe+atorvastatin 40 mg (58.9% vs. 58.7%), as predicted by the model. Changes in other lipids were consistent with equivalence (97.5% expanded CIs <±3%, included 0); triglyceride changes varied more. All treatments were generally well tolerated. Hypercholesterolemic patients administered ezetimibe/atorvastatin 10/20 and 10/40 mg FDC had equivalent LDL-C lowering. This FDC formulation proved to be an efficacious and generally well

Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

PubMed Central

Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

2017-01-01

Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity

Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose

PubMed Central

2013-01-01

Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that

Association between systemically administered radioisotopes and subsequent malignant disease

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

Berlin, N.I.; Wasserman, L.R.

1976-02-01

There is a long history recording the association of x radiation and the subsequent development of malignant tumors. For systemically administered isotopes this came into prominence when Martland discovered the association between cancer, particularly of the bone, and ingestion of radioactive isotopes by radium dial painters. This association was amplified by the development of cancer in patients given thorotrast as a contrast medium for diagnostic radiologic examination. Acute leukemia was reported 30 years ago in patients with polycythemia vera treated with $sup 32$P. Acute leukemia also occurs in patients with polycythemia vera treated only with phlebotomy or drugs. A controlledmore » study is now underway to provide a more definite answer to question what is the incidence of acute leukemia in patients with polycythemia vera treated by phlebotomy alone, chlorambucil, or $sup 32$P. $sup 131$I for the treatment of hyperthyroidism probably does not induce cancer, but in the doses used for thyroid cancer there was an increased incidence of neoplasms (12/200 in one study). This was higher than the expected incidence of neoplasms. The doses of radioactive isotopes used currently for diagnostic purposes have not induced cancer, but it is difficult and probably impossible to verify this with absolute certainty. (auth)« less

Spatial interpolation of gamma dose in radioactive waste storage facility

NASA Astrophysics Data System (ADS)

Harun, Nazran; Fathi Sujan, Muhammad; Zaidi Ibrahim, Mohd

2018-01-01

External radiation measurement for a radioactive waste storage facility in Malaysian Nuclear Agency is a part of Class G License requirement under Atomic Licensing Energy Board (AELB). The objectives of this paper are to obtain the distribution of radiation dose, create dose database and generate dose map in the storage facility. The radiation dose measurement is important to fulfil the radiation protection requirement to ensure the safety of the workers. There are 118 sampling points that had been recorded in the storage facility. The highest and lowest reading for external radiation recorded is 651 microSv/hr and 0.648 microSv/hour respectively. The calculated annual dose shows the highest and lowest reading is 1302 mSv/year and 1.3 mSv/year while the highest and lowest effective dose reading is 260.4 mSv/year and 0.26 mSv/year. The result shows that the ALARA concept along time, distance and shield principles shall be adopted to ensure the dose for the workers is kept below the dose limit regulated by AELB which is 20 mSv/year for radiation workers. This study is important for the improvement of planning and the development of shielding design for the facility.

Dose-response toxicity studies on tributoxyethyl phosphate orally administered to Sprague-Dawley rats

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

Laham, S.; Szabo, J.; Long, G.

The response of the peripheral nervous system to various dose levels of tributoxyethyl phosphate (TBOP) was investigated in Sprague-Dawley rats. Groups of randomized female and male rats (10 rats/gender/dose level) were administered a single oral dose of TBOP (1.0 to 3.2 g/kg for females;1.0 to 9.0 g/kg for males). Physiological parameters were measured in surviving rats three weeks following TBOP administration. A significant reduction (p<0.05) in caudal nerve conduction velocity (NCV) was observed in both female and male rats. Light and electron microscopic examination of sciatic nerve sections showed degenerative changes in both myelinated and unmyelinated fibers of female (2.0more » g/kg) and male (6.8 g/kg) groups. Advanced degeneration was observed only in the highest dose level of both genders (3.2 g/kg for females; 8.0 and 9.0 g/kg for males). Although similar morphological changes were observed in both genders, females were more susceptible than males to the toxic effects of this compound.« less

Influence of low-dose proton pump inhibitors administered concomitantly or separately on the anti-platelet function of clopidogrel.

PubMed

Furuta, Takahisa; Sugimoto, Mitsushige; Kodaira, Chise; Nishino, Masafumi; Yamade, Mihoko; Uotani, Takahiro; Sahara, Shu; Ichikawa, Hitomi; Kagami, Takuma; Iwaizumi, Moriya; Hamaya, Yasushi; Osawa, Satoshi; Sugimoto, Ken; Umemura, Kazuo

2017-04-01

Proton pump inhibitors (PPIs) at low doses can effectively prevent gastrointestinal bleeding due to aspirin and are widely used in Japan for gastroprotection in patients taking anti-platelet agents. We examined the influence of different PPIs at low doses administered concomitantly or separately on anti-platelet functions of clopidogrel. In 41 healthy Japanese volunteers with different CYP2C19 genotypes who took clopidogrel 75 mg in the morning alone, or with omeprazole 10 mg, esomeprazole 10 mg, lansoprazole 15 mg, or rabeprazole 10 mg, either concomitantly in the morning or separately in the evening, we measured the inhibition of platelet aggregation (IPA, %) using VerifyNow P2Y12 assay at 4 h after the last clopidogrel dose on Day 7 of each regimen. IPA by clopidogrel with rabeprazole administered at lunchtime, approximately 4 h after clopidogrel, was also measured. Mean IPAs in those concomitantly receiving omeprazole, esomeprazole, lansoprazole or rabeprazole (47.2 ± 21.1%, 43.2 ± 20.2%, 46.4 ± 18.8%, and 47.3 ± 19.2%, respectively) were significantly decreased compared with those receiving clopidogrel alone (56.0%) (all ps < 0.001). This decrease was observed when PPIs were administered separately in the evening. However, IPA by clopidogrel with rabeprazole administered at lunchtime was 51.6%, which was markedly similar to that of clopidogrel alone (p = 0.114). All tested PPIs reduce the efficacy of clopidogrel when administered concomitantly. Our preliminary data suggest that administration of rabeprazole 4 h following clopidogrel may minimize potential drug-drug interactions.

Calculation of the effective dose from natural radioactivity in soil using MCNP code.

PubMed

Krstic, D; Nikezic, D

2010-01-01

Effective dose delivered by photon emitted from natural radioactivity in soil was calculated in this work. Calculations have been done for the most common natural radionuclides in soil (238)U, (232)Th series and (40)K. A ORNL human phantoms and the Monte Carlo transport code MCNP-4B were employed to calculate the energy deposited in all organs. The effective dose was calculated according to ICRP 74 recommendations. Conversion factors of effective dose per air kerma were determined. Results obtained here were compared with other authors. Copyright 2009 Elsevier Ltd. All rights reserved.

Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

PubMed Central

Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa

2017-01-01

Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties

A kinematic model to estimate the effective dose of radioactive isotopes in the human body for radiological protection

NASA Astrophysics Data System (ADS)

Sasaki, S.; Yamada, T.

2013-12-01

The great earthquake attacked the north-east area in Japan in March 11, 2011. The system of electrical facilities to control Fukushima Daiichi nuclear power station was completely destroyed by the following tsunamis. From the damaged reactor containment vessels, an amount of radioactive substances had leaked and been diffused in the vicinity of this station. Radiological internal exposure becomes a serious social issue both in Japan and all over the world. The present study provides an easily understandable, kinematic-based model to estimate the effective dose of radioactive substances in a human body by simplified the complicated mechanism of metabolism. International Commission on Radiological Protection (ICRP) has developed an exact model, which is well-known as a standard method to calculate the effective dose for radiological protection. However, owing to that the above method accord too much with the actual mechanism of metabolism in human bodies, it becomes rather difficult for non-professional people of radiology to gasp the whole images of the movement and the influences of radioactive substances in a human body. Therefore, in the present paper we propose a newly-derived and easily-understandable model to estimate the effective dose. The present method is very similar with the traditional and conventional hydrological tank model. Ingestion flux of radioactive substances corresponds to rain intensity and the storage of radioactive substances to the water storage in a basin in runoff analysis. The key of this method is to estimate the energy radiated from the radioactive nuclear disintegration of an atom by using classical theory of E. Fermi of beta decay and special relativity for various kinds of radioactive atoms. The parameters used in this study are only physical half-time and biological half-time, and there are no intentional and operational parameters of coefficients to adjust our theoretical runoff to observation of ICRP. Figure.1 compares time

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

PubMed Central

Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

2017-01-01

Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

Outcome of treating thyrotoxic patients with a standard dose of radioactive iodine.

PubMed

Johnson, J K

1993-10-01

This is a report of an audit exercise that was designed to study the effectiveness of treating thyrotoxic patients with a standard dose--370 MBq--of radioactive iodine (131l). This treatment was received by 183 patients in one centre between 1977 and 1989. The results were assessed from the answers to 114 questionnaires that had been completed by the patients' general practitioners. The patients were aged between 28 and 85 years; 86% were female; 42% had been treated previously with anti-thyroid drugs. Ninety-five of the patients (83%) became euthyroid after a single dose of 131l; 18 required one further dose; and one required two further doses. At the time of the survey, 32 (28%) were euthyroid, while 82 patients (72%) had become hypothyroid and required treatment with thyroxine. Within five years of treatment, 85% of the patients had become hypothyroid. These results are compared with those from two other centres.

Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours

PubMed Central

2013-01-01

Background Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. Methods Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5–12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. Results Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m2, which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in Cmax and AUC0–t were dose proportional for the 6–12 mg/m2 doses. Conclusion The MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10 mg/m2. The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. Trial registration The study was registered with ClinicalTrials.gov as NCT01755390. PMID:24099585

Radioactive iodine therapy in cats with hyperthyroidism

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

Turrel, J.M.; Feldman, E.C.; Hays, M.

Eleven cats with hyperthyroidism were treated with radioactive iodine (/sup 131/I). Previous unsuccessful treatments for hyperthyroidism included hemithyroidectomy (2 cats) and an antithyroid drug (7 cats). Two cats had no prior treatment. Thyroid scans, using technetium 99m, showed enlargement and increased radionuclide accumulation in 1 thyroid lobe in 5 cats and in both lobes in 6 cats. Serum thyroxine concentrations were high and ranged from 4.7 to 18 micrograms/dl. Radioactive iodine tracer studies were used to determine peak radioactive iodine uptake (RAIU) and effective and biological half-lives. Activity of /sup 131/I administered was calculated from peak RAIU, effective half-life, andmore » estimated thyroid gland weight. Activity of /sup 131/I administered ranged from 1.0 to 5.9 mCi. The treatment goal was to deliver 20,000 rad to hyperactive thyroid tissue. However, retrospective calculations based on peak RAIU and effective half-life obtained during the treatment period showed that radiation doses actually ranged from 7,100 to 64,900 rad. Complete ablation of the hyperfunctioning thyroid tissue and a return to euthyroidism were seen in 7 cats. Partial responses were seen in 2 cats, and 2 cats became hypothyroid. It was concluded that /sup 131/I ablation of thyroid tumors was a reasonable alternative in the treatment of hyperthyroidism in cats. The optimal method of dosimetry remains to be determined.« less

Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats.

PubMed

Abelson, Klas S P; Höglund, A Urban

2002-04-01

Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10-300 microg/kg) and atropine (0.1, 10, 5000 microg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2-C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 microg/kg), or subcutaneously with oxotremorine (30, 100, 300 microg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 microg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 microg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

Simplifying anemia management in hemodialysis patients: ESAs administered at longer dosing intervals can enhance opportunities to provide patient-focused care.

PubMed

Schiller, Brigitte; Besarab, Anatole

2011-08-01

To review issues and challenges in caring for hemodialysis patients with anemia of chronic kidney disease, specifically focusing on the effects of longer erythropoiesis-stimulating agent (ESA) dosing intervals on processes of care. PubMed searches were performed limited to the last 10 years to February 2011, focusing on articles in English that were 'clinical trials,' assessed processes of care, measured associations of hemoglobin (Hb) with outcomes, and explored/analyzed extended dosing intervals of ESAs in hemodialysis patients and recommendations for increasing the quality of care of these patients. Some limitations included the fact that a meta-analysis was not conducted; many studies were associative and therefore unable to prove causality; and none of the clinical trials directly compared the impact of more frequent or less frequent ESA dosing strategies on patient care and outcomes. Progress over the past several decades has been substantial; however, unmet needs remain and there is room for improvement in efficiencies of care. Many patients fail to meet Hb targets, and nephrology professionals' time is consumed with preparing, administering, and monitoring therapy. Direct interaction between patients and care providers has been lost as attention has shifted to 'cost-effective' (not necessarily patient-centered) ways to deliver care. Use of ESAs at longer dosage intervals represents one opportunity to improve efficiency of care. Newer ESAs have been developed for less frequent dosing. Once-monthly dosing decreases time spent administering/monitoring therapy and allows nephrology professionals to provide comprehensive renal care, wherein the patient rather than task-oriented processes becomes the primary focus. A fragmented, uncoordinated care-delivery model heightens the urgency to systematically address issues related to delivery of care and improve efficiencies in anemia management as part of the patient-centered approach. ESAs designed for administration

A kinematic-based methodology for radiological protection: Runoff analysis to calculate the effective dose for internal exposure caused by ingestion of radioactive isotopes

NASA Astrophysics Data System (ADS)

Sasaki, Syota; Yamada, Tadashi; Yamada, Tomohito J.

2014-05-01

We aim to propose a kinematic-based methodology similar with runoff analysis for readily understandable radiological protection. A merit of this methodology is to produce sufficiently accurate effective doses by basic analysis. The great earthquake attacked the north-east area in Japan on March 11, 2011. The system of electrical facilities to control Fukushima Daiichi nuclear power plant was completely destroyed by the following tsunamis. From the damaged reactor containment vessels, an amount of radioactive isotopes had leaked and been diffused in the vicinity of the plant. Radiological internal exposure caused by ingestion of food containing radioactive isotopes has become an issue of great interest to the public, and has caused excessive anxiety because of a deficiency of fundamental knowledge concerning radioactivity. Concentrations of radioactivity in the human body and internal exposure have been studied extensively. Previous radiologic studies, for example, studies by International Commission on Radiological Protection(ICRP), employ a large-scale computational simulation including actual mechanism of metabolism in the human body. While computational simulation is a standard method for calculating exposure doses among radiology specialists, these methods, although exact, are too difficult for non-specialists to grasp the whole image owing to the sophistication. In this study, the human body is treated as a vessel. The number of radioactive atoms in the human body can be described by an equation of continuity, which is the only governing equation. Half-life, the period of time required for the amount of a substance decreases by half, is only parameter to calculate the number of radioactive isotopes in the human body. Half-life depends only on the kinds of nuclides, there are no arbitrary parameters. It is known that the number of radioactive isotopes decrease exponentially by radioactive decay (physical outflow). It is also known that radioactive isotopes

Cellular and Humoral Responses to a Second Dose of Herpes Zoster Vaccine Administered 10 Years After the First Dose Among Older Adults.

PubMed

Levin, Myron J; Schmader, Kenneth E; Pang, Lei; Williams-Diaz, Angela; Zerbe, Gary; Canniff, Jennifer; Johnson, Michael J; Caldas, Yupanqui; Cho, Alice; Lang, Nancy; Su, Shu-Chih; Parrino, Janie; Popmihajlov, Zoran; Weinberg, Adriana

2016-01-01

Herpes zoster vaccine (ZV) was administered as a second dose to 200 participants ≥ 70 years old who had received a dose of ZV ≥ 10 years previously (NCT01245751). Varicella zoster virus (VZV) antibody titers (measured by a VZV glycoprotein-based enzyme-linked immunosorbent assay [gpELISA]) and levels of interferon γ (IFN-γ) and interleukin 2 (IL-2; markers of VZV-specific cell-mediated immunity [CMI], measured by means of ELISPOT analysis) in individuals aged ≥ 70 years who received a booster dose of ZV were compared to responses of 100 participants aged 50-59 years, 100 aged 60-69 years, and 200 aged ≥ 70 years who received their first dose of ZV. The study was powered to demonstrate noninferiority of the VZV antibody response at 6 weeks in the booster-dose group, compared with the age-matched first-dose group. Antibody responses were similar at baseline and after vaccination across all age and treatment groups. Both baseline and postvaccination VZV-specific CMI were lower in the older age groups. Peak gpELISA titers and their fold rise from baseline generally correlated with higher baseline and postvaccination VZV-specific CMI. IFN-γ and IL-2 results for subjects ≥ 70 years old were significantly higher at baseline and after vaccination in the booster-dose group, compared with the first-dose group, indicating that a residual effect of ZV on VZV-specific CMI persisted for ≥ 10 years and was enhanced by the booster dose. These findings support further investigation of ZV administration in early versus later age and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ. NCT01245751. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Methods for Probabilistic Radiological Dose Assessment at a High-Level Radioactive Waste Repository.

NASA Astrophysics Data System (ADS)

Maheras, Steven James

Methods were developed to assess and evaluate the uncertainty in offsite and onsite radiological dose at a high-level radioactive waste repository to show reasonable assurance that compliance with applicable regulatory requirements will be achieved. Uncertainty in offsite dose was assessed by employing a stochastic precode in conjunction with Monte Carlo simulation using an offsite radiological dose assessment code. Uncertainty in onsite dose was assessed by employing a discrete-event simulation model of repository operations in conjunction with an occupational radiological dose assessment model. Complementary cumulative distribution functions of offsite and onsite dose were used to illustrate reasonable assurance. Offsite dose analyses were performed for iodine -129, cesium-137, strontium-90, and plutonium-239. Complementary cumulative distribution functions of offsite dose were constructed; offsite dose was lognormally distributed with a two order of magnitude range. However, plutonium-239 results were not lognormally distributed and exhibited less than one order of magnitude range. Onsite dose analyses were performed for the preliminary inspection, receiving and handling, and the underground areas of the repository. Complementary cumulative distribution functions of onsite dose were constructed and exhibited less than one order of magnitude range. A preliminary sensitivity analysis of the receiving and handling areas was conducted using a regression metamodel. Sensitivity coefficients and partial correlation coefficients were used as measures of sensitivity. Model output was most sensitive to parameters related to cask handling operations. Model output showed little sensitivity to parameters related to cask inspections.

High-dose intravenously administered iron versus orally administered iron in blood donors with iron deficiency: study protocol for a randomised, controlled trial.

PubMed

Macher, Susanne; Drexler, Camilla; Lindenau, Ines; Sareban, Nazanin; Schlenke, Peter; Amrein, Karin

2016-10-28

About 2-3 % of the population participates in blood donation programmes. Each whole blood donation or ten apheresis donations cause a loss of 200-250 mg of iron. As a result, one of the most common risks of regular blood donors is iron deficiency. Although this has been known for decades, in most countries, iron status is currently not assessed or treated in this population. Premenopausal women are particularly affected, as they have lower iron reserves and higher daily requirements. Besides anaemia, iron deficiency may lead to fatigue and impaired cognitive and physical performance. Current iron preparations for intravenous administration are well tolerated and allow for application of large doses up to 1 g in one visit. Our hypothesis is that in blood donors with iron deficiency, intravenously administered iron is more efficient and as safe as oral iron supplementation. Since anaemia is one of the most frequent reasons for permanent or intermittent donor deferral, maintaining an iron-replete donor pool may help to prevent shortages in blood supply and to avoid iron deficiency-related comorbidities. In this randomised clinical trial we include male and female blood donors aged ≥18 and ≤65 years with a ferritin value of ≤30 ng/ml. Stratified by gender, participants are randomized with a web-based randomisation tool in a 1:1 ratio to either 1 g of intravenously administered ferric carboxymaltose or 10 g of iron fumarate supplements at one to two daily doses of 100 mg each. Eight to 12 weeks after the first visit, iron status, blood count and symptoms are assessed in both groups. The primary endpoint is the difference in transferrin saturation (%) following the intervention between both groups. Secondary endpoints include other parameters of iron metabolism and red blood cell count, the number of patients with drug-related adverse events, and subjective symptoms including those of the restless legs syndrome, quality of life, and fatigue. Iron

Psychiatric side effects of ketamine in hospitalized medical patients administered subanesthetic doses for pain control.

PubMed

Rasmussen, Keith G

2014-08-01

To assess the psychiatric side effects of ketamine when administered in subanesthetic doses to hospitalized patients. It is hypothesized that such effects occur frequently. In this retrospective study, the medical records of 50 patients hospitalized on medical and surgical units at our facility who had continuous intravenous infusions of ketamine for pain or mild sedation were reviewed. Patient progress in the days following the start of ketamine infusion was reviewed and response to ketamine was noted. Twenty-two percent of the patients were noted to have some type of psychiatric reaction to ketamine, including agitation, confusion, and hallucinations. These reactions were relatively short lived, namely, occurring during or shortly after the infusions. No association was found between patient response to ketamine and gender, age, or infusion rate. Awareness of the psychiatric side effects of ketamine is an important consideration for clinicians administering this medication either for pain control or for depressive illness.

Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform

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

Philip, Binu K.; Anand, Sathanandam S.; Palkar, Prajakta S.

2006-10-01

Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethalmore » dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of {sup 14}C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of {sup 14}C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC{sub 15-360min}) in the

Dose Optimization of the Administered Activity in Pediatric Bone Scintigraphy: Validation of the North American Consensus Guidelines.

PubMed

Ayres, Karen L; Spottswood, Stephanie E; Delbeke, Dominique; Price, Ronald; Hodges, Pamela K; Wang, Li; Martin, William H

2015-09-01

The 2010 North American Consensus Guidelines (NACG) for pediatric administered doses and the European Association of Nuclear Medicine (EANM) Dosage Card guidelines recommend lower activities than those administered at our institution. We compared the quality of the lower-activity images with the higher-activity images to determine whether the reduction in counts affects overall image quality. Twenty patients presenting to our pediatric radiology department for bone scintigraphy were evaluated. Their mean weight was 20 kg. The patients were referred for oncologic (n = 10), infectious/inflammatory (n = 5), and pain (n = 5) evaluation. Dynamic anterior and posterior images were acquired for 5 min for each patient. Data were subsampled to represent different administered activities corresponding to the activities recommended by the NACG and the EANM Dosage Card. Images were evaluated twice, first for diagnostic quality and then for acceptability for daily clinical use. There was no statistically significant difference in the diagnostic quality of the images from any of the 3 protocols. Pathologic uptake was correctly identified independent of the administered activity, although there was a single false-positive result for an EANM image. When images were subjectively evaluated as acceptable for daily clinical use, there was a slight preference for the higher-activity images over the NACG (P = 0.04). The recommended administered activities of the NACG produce images of diagnostic quality while reducing patient radiation exposure. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

PubMed

Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

2006-12-01

Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

Radioactive iodine therapy: Effect on functioning metastases of adenocarcinoma of the thyroid

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

Seidlin, S.M.; Marinelli, L.D.; Oshry, E.

1990-09-01

A case of metastatic adenocarcinoma of the thyroid is reported in which treatment by means of radioactive iodine has been successful. The patient was completely thyroidectomized for malignant adenoma in 1923, with neither thyrotoxicosis then nor hypothyroidism postoperatively; 15 years later there developed classic symptoms of hyperthyroidism and severe pain in the lower back. In October 1939 a pulsating tumor removed from the level of the 12th thoracic vertebra proved to be metastatic thyroid adenocarcinoma (histologically well differentiated, with small follicles and colloid). In the next two years hyperthyroidism increased and roentgenograms revealed new metastases in the lungs, upper partmore » of the right femur, second rib on the left side, left ilium, and skull. Roentgenologic irradiation of the metastases proved ineffectual. In March 1943 a tracer dose of radioactive iodine revealed iodine retention by all the known lesions and no evidence of residual thyroid tissue in the neck. Therapeutic amounts of radioactive iodine were administered orally between May and October 1943. Definite and lasting clinical improvement followed. In April 1944 and March 1945 additional I* was administered with a resultant disappearance of pain, increase in weight, and progressive change in all clinical criteria in the direction of hypothyroidism. Roentgenographic evidence pointed to an arrest if not a regression of the disease. No untoward effects followed this therapy. Radioactive iodine seems to be an effective therapeutic agent in the control of this type of tumor.« less

Women Administered Standard Dose Imatinib for Chronic Myeloid Leukemia Have Higher Dose-Adjusted Plasma Imatinib and Norimatinib Concentrations Than Men.

PubMed

Belsey, Sarah L; Ireland, Robin; Lang, Kathryn; Kizilors, Aytug; Ho, Aloysius; Mufti, Ghulam J; Bisquera, Alessandra; De Lavallade, Hugues; Flanagan, Robert J

2017-10-01

The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg·d. A predose plasma imatinib concentration of >1 mg·L is associated with improved clinical response. This study aimed to assess the plasma imatinib and norimatinib concentrations attained in patients with chronic myeloid leukemia administered standard doses of imatinib adjusted for dose, age, sex, body weight, and response. We evaluated data from a cohort of patients treated between 2008 and 2014 with respect to dose, age, sex, body weight, and response. The study comprised 438 samples from 93 patients (54 male, 39 female). The median imatinib dose was 400 mg·d in men and in women. The plasma imatinib concentration ranged 0.1-5.0 mg·L and was below 1 mg·L in 20% and 16% of samples from men and women, respectively. The mean dose normalized plasma imatinib and norimatinib concentrations were significantly higher in women in comparison with men. This was partially related to body weight. Mixed effects ordinal logistic regression showed no evidence of an association between sex and plasma imatinib (P = 0.13). However, there was evidence of an association between sex and plasma norimatinib, with higher norimatinib concentrations more likely in women than in men (P = 0.02). Imatinib therapeutic drug monitoring only provides information on dosage adequacy and on short-term adherence; longer-term adherence cannot be assessed. However, this analysis revealed that approximately 1 in 5 samples had a plasma imatinib concentration <1 mg·L, which was suggestive of inadequate dosage and/or poor adherence and posed a risk of treatment failure. Higher imatinib exposure in women may be a factor in the increased rate of long-term, stable, deep molecular response (undetectable breakpoint cluster-Abelson (BCR-ABL) transcript levels with a PCR sensitivity of 4.5 log, MR4.5) reported in women.

Pharmacology of ayahuasca administered in two repeated doses.

PubMed

Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

2012-02-01

Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

Administering multiple doses of a non N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-containing tall larkspur (Delphinium occidentale) to cattle.

PubMed

Welch, K D; Stonecipher, C A; Green, B T; Gardner, D R; Cook, D; Pfister, J A

2017-03-15

Larkspurs (Delphinium spp.) are a serious toxic plant problem for cattle in western North America. There are two chemotypes of D. occidentale, a more toxic and a less toxic chemotype. The objective of this study was to evaluate the acute toxicity of the less toxic chemotype when administered in multiple doses to cattle. These results suggest that cattle could consume enough of the less toxic chemotype to be poisoned in a range setting. Published by Elsevier Ltd.

Feasibility of Administering High-Dose 131I-MIBG Therapy to Children with High-Risk Neuroblastoma without Lead-Lined Rooms

PubMed Central

Chu, Bae P.; Horan, Christopher; Basu, Ellen; Dauer, Lawrence; Williamson, Matthew; Carrasquillo, Jorge A.; Pandit-Taskar, Neeta; Modak, Shakeel

2015-01-01

Background Although 131I-metaiodobenzylguanidine therapy (131I-MIBG) is increasingly used for children with high-risk neuroblastoma, a paucity of lead-lined rooms limits its wider use. We implemented radiation safety procedures to comply with New York City Department of Health and Mental Hygiene regulations for therapeutic radioisotopes and administered 131I-MIBG using rolling lead shields. Procedure Patients received 0.67GBq (18mCi)/kg/dose 131I-MIBG on an IRB-approved protocol (NCT00107289). Radiation safety procedures included private room with installation of rolling lead shields to maintain area dose rates ≤0.02mSv/h outside the room, patient isolation until dose rate <0.07mSv/h at 1m and retention of a urinary catheter with collection of urine in lead boxes. Parents were permitted in the patient’s room behind lead shields, trained in radiation safety principles and given real-time radiation monitors. Results Records on 16 131I-MIBG infusions among 10 patients (age 2–11 years) were reviewed. Mean ± standard deviation 131I-MIBG administered was 17.67±11.14 (range: 6.11–40.59) GBq. Mean maximum dose rates outside treatment rooms were 0.013±0.008 mSv/hr. Median time-to-discharge was 3 days post-131I-MIBG. Exposure of medical staff and parents was below regulatory limits. Cumulative whole-body dose received by the physician, nurse and radiation safety officer during treatment was 0.098±0.058, 0.056±0.045, 0.055±0.050 mSv respectively. Cumulative exposure to parents was 0.978±0.579mSv. Estimated annual radiation exposure for inpatient nurses was 0.096±0.034mSv/nurse. Thyroid bioassay scans on all medical personnel were dose 131I-MIBG and may broaden its use without dedicated lead-lined rooms. PMID:26773712

Radioactive iodide (131 I-) excretion profiles in response to potassium iodide (KI) and ammonium perchlorate (NH4ClO4) prophylaxis.

PubMed

Harris, Curtis; Dallas, Cham; Rollor, Edward; White, Catherine; Blount, Benjamin; Valentin-Blasini, Liza; Fisher, Jeffrey

2012-08-01

Radioactive iodide ((131)I-) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish (131)I- urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered (131)I- and 3 hours later dosed with either saline, 30 mg/kg of NH(4)ClO(4) or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH(4)ClO(4) treated animals excreted significantly more (131)I- compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T(4)) was administered daily over a 3 day period. During the first 6-12 hour after (131)I- dosing, rats administered NH(4)ClO(4) excreted significantly more (131)I- than the other treatment groups. T(4) treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after (131)I- administration. We speculate that the T(4) treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to (131)I- compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland.

Retrospective dosimetry: dose evaluation using unheated and heated quartz from a radioactive waste storage building.

PubMed

Jain, M; Bøtter-Jensen, L; Murray, A S; Jungner, H

2002-01-01

In the assessment of dose received from a nuclear accident, considerable attention has been paid to retrospective dosimetry using heated materials such as household ceramics and bricks. However, unheated materials such as mortar and concrete are more commonly found in industrial sites and particularly in nuclear installations. These materials contain natural dosemeters such as quartz, which usually is less sensitive than its heated counterpart. The potential of quartz extracted from mortar in a wall of a low-level radioactive-waste storage facility containing distributed sources of 60Co and 137Cs has been investigated. Dose-depth proliles based on small aliquots and single grains from the quartz extracted from the mortar samples are reported here. These are compared with results from heated quartz and polymineral fine grains extracted from an adjacent brick, and the integrated dose recorded by environmental TLDs.

The Effect on Treatment Adherence of Administering Drugs as Fixed-Dose Combinations versus as Separate Pills: Systematic Review and Meta-Analysis.

PubMed

van Galen, Katy A; Nellen, Jeannine F; Nieuwkerk, Pythia T

2014-01-01

Administering drugs as fixed-dose combinations (FDCs) versus the same active drugs administered as separate pills is assumed to enhance treatment adherence. We synthesized evidence from randomized controlled trials (RCTs) about the effect of FDCs versus separate pills on adherence. We searched PubMed for RCTs comparing a FDC with the same active drugs administered as separate pills, including a quantitative estimate of treatment adherence, without restriction to medical condition. The odds ratio (OR) of optimal adherence with FDCs versus separate pills was used as common effect size and aggregated into a pooled effect estimate using a random effect model with inverse variance weights. Out of 1258 articles screened, only six studies fulfilled inclusion criteria. Across medical conditions, administering drugs as FDC significantly increased the likelihood of optimal adherence (OR 1.33 (95% CI, 1.03-1.71)). Within subgroups of specific medical conditions, the favourable effect of FDCs on adherence was of borderline statistical significance for HIV infection only (OR 1.46 (95% CI, 1.00-2.13)). We observed a remarkable paucity of RCTs comparing the effect on adherence of administering drugs as FDC versus as separate pills. Administering drugs as FDC improved medication adherence. However, this conclusion is based on a limited number of RCTs only.

Evaluation of ambient dose equivalent rates influenced by vertical and horizontal distribution of radioactive cesium in soil in Fukushima Prefecture.

PubMed

Malins, Alex; Kurikami, Hiroshi; Nakama, Shigeo; Saito, Tatsuo; Okumura, Masahiko; Machida, Masahiko; Kitamura, Akihiro

2016-01-01

The air dose rate in an environment contaminated with (134)Cs and (137)Cs depends on the amount, depth profile and horizontal distribution of these contaminants within the ground. This paper introduces and verifies a tool that models these variables and calculates ambient dose equivalent rates at 1 m above the ground. Good correlation is found between predicted dose rates and dose rates measured with survey meters in Fukushima Prefecture in areas contaminated with radiocesium from the Fukushima Dai-ichi Nuclear Power Plant accident. This finding is insensitive to the choice for modeling the activity depth distribution in the ground using activity measurements of collected soil layers, or by using exponential and hyperbolic secant fits to the measurement data. Better predictions are obtained by modeling the horizontal distribution of radioactive cesium across an area if multiple soil samples are available, as opposed to assuming a spatially homogeneous contamination distribution. Reductions seen in air dose rates above flat, undisturbed fields in Fukushima Prefecture are consistent with decrement by radioactive decay and downward migration of cesium into soil. Analysis of remediation strategies for farmland soils confirmed that topsoil removal and interchanging a topsoil layer with a subsoil layer result in similar reductions in the air dose rate. These two strategies are more effective than reverse tillage to invert and mix the topsoil. Copyright © 2015 Elsevier Ltd. All rights reserved.

Natural radioactivity in various water samples and radiation dose estimations in Bolu province, Turkey.

PubMed

Gorur, F Korkmaz; Camgoz, H

2014-10-01

The level of natural radioactivity for Bolu province of north-western Turkey was assessed in this study. There is no information about radioactivity measurement reported in water samples in the Bolu province so far. For this reason, gross α and β activities of 55 different water samples collected from tap, spring, mineral, river and lake waters in Bolu were determined. The mean activity concentrations were 68.11 mBq L(-1), 169.44 mBq L(-1) for gross α and β in tap water. For all samples the gross β activity is always higher than the gross α activity. All value of the gross α were lower than the limit value of 500 mBq L(-1) while two spring and one mineral water samples were found to have gross β activity concentrations of greater than 1000 mBq L(-1). The associated age-dependent dose from all water ingestion in Bolu was estimated. The total dose for adults had an average value exceeds the WHO recommended limit value. The risk levels from the direct ingestion of the natural radionuclides in tap and mineral water in Bolu were determinated. The mean (210)Po and (228)Ra risk the value of tap and mineral waters slightly exceeds what some consider on acceptable risk of 10(-4) or less. Copyright © 2014 Elsevier Ltd. All rights reserved.

DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS

EPA Science Inventory

DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and ...

Determination of Dose from the Disposal of Radioactive Waste Related with TENORM using Residual Radioactivity (RESRAD) Monte Carlo Code

NASA Astrophysics Data System (ADS)

lwin, Maung Tin Moe; Kassim, Hassan Abu; Amin, Yusoff Mohd.

2008-05-01

The working procedures in the RESRAD for specific evaluations of environmental pollutants are briefly mentioned. The risk of human health associated with Naturally Occurring Radioactive Materials (NORM) who are working in the Malaysian oil and gas industry are analyzed. The sources of NORM and Technologically Enhanced NORM (TENORM) in the oil and gas industry are described. Some measurements for the external and internal effective dose equivalent on the workers will be described. These data are entered into the RESRAD software program and the output reports are taken. Long-term effects of TENORM to the industrial workers are also discussed with graphical illustrations. These results are compared with previous research work within the same field to validate and verify.

Assessment of ambient gamma dose rate around a prospective uranium mining area of South India - A comparative study of dose by direct methods and soil radioactivity measurements

NASA Astrophysics Data System (ADS)

Karunakara, N.; Yashodhara, I.; Sudeep Kumara, K.; Tripathi, R. M.; Menon, S. N.; Kadam, S.; Chougaonkar, M. P.

Indoor and outdoor gamma dose rates were evaluated around a prospective uranium mining region - Gogi, South India through (i) direct measurements using a GM based gamma dose survey meter, (ii) integrated measurement days using CaSO4:Dy based thermo luminescent dosimeters (TLDs), and (iii) analyses of 273 soil samples for 226Ra, 232Th, and 40K activity concentration using HPGe gamma spectrometry. The geometric mean values of indoor and outdoor gamma dose rates were 104 nGy h-1 and 97 nGy h-1, respectively with an indoor to outdoor dose ratio of 1.09. The gamma dose rates and activity concentrations of 226Ra, 232Th, and 40K varied significantly within a small area due to the highly localized mineralization of the elements. Correlation study showed that the dose estimated from the soil radioactivity is better correlated with that measured directly using the portable survey meter, when compared to that obtained from TLDs. This study showed that in a region having localized mineralization in situ measurements using dose survey meter provide better representative values of gamma dose rates.

PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

PubMed

Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

2015-09-01

Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

A New Approach for the Determination of Dose Rate and Radioactivity for Detected Gamma Nuclides Using an Environmental Radiation Monitor Based on an NaI(Tl) Detector.

PubMed

Ji, Young-Yong; Kim, Chang-Jong; Lim, Kyo-Sun; Lee, Wanno; Chang, Hyon-Sock; Chung, Kun Ho

2017-10-01

To expand the application of dose rate spectroscopy to the environment, the method using an environmental radiation monitor (ERM) based on a 3' × 3' NaI(Tl) detector was used to perform real-time monitoring of the dose rate and radioactivity for detected gamma nuclides in the ground around an ERM. Full-energy absorption peaks in the energy spectrum for dose rate were first identified to calculate the individual dose rates of Bi, Ac, Tl, and K distributed in the ground through interference correction because of the finite energy resolution of the NaI(Tl) detector used in an ERM. The radioactivity of the four natural radionuclides was then calculated from the in situ calibration factor-that is, the dose rate per unit curie-of the used ERM for the geometry of the ground in infinite half-space, which was theoretically estimated by Monte Carlo simulation. By an intercomparison using a portable HPGe and samples taken from the ground around an ERM, this method to calculate the dose rate and radioactivity of four nuclides using an ERM was experimentally verified and finally applied to remotely monitor them in real-time in the area in which the ERM had been installed.

Estimation of Second Primary Cancer Risk After Treatment with Radioactive Iodine for Differentiated Thyroid Carcinoma.

PubMed

Corrêa, Nilton Lavatori; de Sá, Lidia Vasconcellos; de Mello, Rossana Corbo Ramalho

2017-02-01

An increase in the incidence of second primary cancers is the late effect of greatest concern that could occur in differentiated thyroid carcinoma (DTC) patients treated with radioactive iodine (RAI). The decision to treat a patient with RAI should therefore incorporate a careful risk-benefit analysis. The objective of this work was to adapt the risk-estimation models developed by the Biological Effects of Ionizing Radiation Committee to local epidemiological characteristics in order to assess the carcinogenesis risk from radiation in a population of Brazilian DTC patients treated with RAI. Absorbed radiation doses in critical organs were also estimated to determine whether they exceeded the thresholds for deterministic effects. A total of 416 DTC patients treated with RAI were retrospectively studied. Four organs were selected for absorbed dose estimation and subsequent calculation of carcinogenic risk: the kidney, stomach, salivary glands, and bone marrow. Absorbed doses were calculated by dose factors (absorbed dose per unit activity administered) previously established and based on standard human models. The lifetime attributable risk (LAR) of incidence of cancer as a function of age, sex, and organ-specific dose was estimated, relating it to the activity of RAI administered in the initial treatment. The salivary glands received the greatest absorbed doses of radiation, followed by the stomach, kidney, and bone marrow. None of these, however, surpassed the threshold for deterministic effects for a single administration of RAI. Younger patients received the same level of absorbed dose in the critical organs as older patients did. The lifetime attributable risk for stomach cancer incidence was by far the highest, followed in descending order by salivary-gland cancer, leukemia, and kidney cancer. RAI in a single administration is safe in terms of deterministic effects because even high-administered activities do not result in absorbed doses that exceed the

Individual dose due to radioactivity accidental release from fusion reactor.

PubMed

Nie, Baojie; Ni, Muyi; Wei, Shiping

2017-04-05

As an important index shaping the design of fusion safety system, evaluation of public radiation consequences have risen as a hot topic on the way to develop fusion energy. In this work, the comprehensive public early dose was evaluated due to unit gram tritium (HT/HTO), activated dust, activated corrosion products (ACPs) and activated gases accidental release from ITER like fusion reactor. Meanwhile, considering that we cannot completely eliminate the occurrence likelihood of multi-failure of vacuum vessel and tokamak building, we conservatively evaluated the public radiation consequences and environment restoration after the worst hypothetical accident preliminarily. The comparison results show early dose of different unit radioactivity release under different conditions. After further performing the radiation consequences, we find it possible that the hypothetical accident for ITER like fusion reactor would result in a level 6 accident according to INES, not appear level 7 like Chernobyl or Fukushima accidents. And from the point of environment restoration, we need at least 69 years for case 1 (1kg HTO and 1000kg dust release) and 34-52years for case 2 (1kg HTO and 10kg-100kg dust release) to wait the contaminated zone drop below the general public safety limit (1mSv per year) before it is suitable for human habitation. Copyright © 2016 Elsevier B.V. All rights reserved.

Aminothiol Receptors for Decorporation of Intravenously Administered 60Co in the Rat

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

Levitskaia, Tatiana G.; Morris, James E.; Creim, Jeffrey A.

2010-01-01

The reported investigation provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. L-histidine (His) was tested intravenously to compare in vivo efficacy of the aminothiol GSH and Cys chelators with that of aminoimidazole (His) chelator. 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potentmore » decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of a chelator. The intravenous GSH or Cys were most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. Oral administration of ReadiSorb reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.« less

Pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe (Part I).

PubMed

Asami, Akitoshi; Shimada, Tsutomu; Mizuhara, Yasuharu; Asano, Takayuki; Takeda, Shuichi; Aburada, Takashi; Miyamoto, Ken-Ichi; Aburada, Masaki

2010-07-01

To investigate the pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe, the pharmacokinetic parameters were determined by using (14)C-[6]-shogaol (labeled compound) and [6]-shogaol (non-labeled compound). When the labeled compound was orally administered to rats, the maximum plasma concentration (C (max)) and the area under the curve (AUC) of plasma radioactivity concentration increased in a dose-dependent manner. When the labeled compound was orally administered at a dose of 10 mg/kg, 20.0 + or - 1.8% of the radioactivity administered was excreted into urine, 64.0 + or - 12.9% into feces, and 0.2 + or - 0.1% into breath. Thus, more of the radioactivity was excreted into feces than into urine, and almost no radioactivity was excreted into breath. Furthermore, when the labeled compound was orally administered at a dose of 10 mg/kg, cumulative biliary radioactivity excretion over 48 h was 78.5 + or - 4.5% of the radioactivity administered, and cumulative urinary radioactivity excretion over 48 h was 11.8 + or - 2.7%, showing that about 90% of the dose administered orally was absorbed from the digestive tract and most of the fecal excretion was via biliary excretion. On the other hand, when the non-labeled compound [6]-shogaol was orally administered, the plasma concentration and biliary excretion of the unchanged form were extremely low. When these results are combined with those obtained with the labeled compound, it would suggest that [6]-shogaol is mostly metabolized in the body and excreted as metabolites.

RADIOACTIVE MATERIALS IN BIOSOLIDS: DOSE MODELING

EPA Science Inventory

The Interagency Steering Committee on Radiation Standards (ISCORS) has recently completed a study of the occurrence within the United States of radioactive materials in sewage sludge and sewage incineration ash. One component of that effort was an examination of the possible tra...

Determination of Dose from the Disposal of Radioactive Waste Related with TENORM using Residual Radioactivity (RESRAD) Monte Carlo Code

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

Lwin, Maung Tin Moe; Kassim, Hassan Abu; Amin, Yusoff Mohd.

2008-05-20

The working procedures in the RESRAD for specific evaluations of environmental pollutants are briefly mentioned. The risk of human health associated with Naturally Occurring Radioactive Materials (NORM) who are working in the Malaysian oil and gas industry are analyzed. The sources of NORM and Technologically Enhanced NORM (TENORM) in the oil and gas industry are described. Some measurements for the external and internal effective dose equivalent on the workers will be described. These data are entered into the RESRAD software program and the output reports are taken. Long-term effects of TENORM to the industrial workers are also discussed with graphicalmore » illustrations. These results are compared with previous research work within the same field to validate and verify.« less

Experimental and Monte Carlo measurements of dose perturbation around a non-radioactive brachytherapy seed in external beam radiotherapy

NASA Astrophysics Data System (ADS)

Steinman, James P.

I-125 seeds used in permanent prostate brachytherapy are composed of high-Z metals and may number from 40 to over 100 in a typical implant. If any supplemental external beam treatment is administered afterward (as for salvaging failed brachytherapy treatment), it is possible that the seeds may cause substantial dose perturbation which will depend on numerous factors (photon energy, depth, field size, number of seeds, etc.) and this effect needs to be thoroughly investigated. Film measurements were primarily done using Kodak XV2 layered above and below a non-radioactive I-125 seed placed in a groove on a Lucite plate with 5 cm buildup and 10 cm backscatter added at 95 cm SSD. The phantom was irradiated with and without seed with 6 MV photons for a 1 x 1 cm2 field size. Monte Carlo simulations were carried out using DOSXYZnrc using the same parameters and compared with Gafchromic EBT2 film. Other comparisons looked at changing energy, depth, and field size in both with and without seeds configuration. This study was further extended to include metals of various Z of the seed's dimensions and also looked into effect of 3 seeds spaced 0.5 cm vertically. Another measurement was done using two opposing fields using single as well as 3 seed configuration to see whether the dose enhancement and attenuation cancel out in multi-field treatments which is the norm clinically in a prostate treatment. For a single I-125 seed, on XV film a localized dose enhancement of 6.3% upstream and -10.9% downstream was noticed. With three seeds, this effect did not change. With two opposing fields, a cold spot around the seed of ~3% was noticed from film measurements. Increasing energy and field size decreased the effect while increase in Z of material greatly increased the effect. Increasing depth appeared to have no effect. DOSXYZnrc and EBT2 film verified maximum dose enhancement of +15% upstream and -20% downstream of the I-125 seed surface. In general, the range of the effect was

Gadolinium-enhanced cardiovascular magnetic resonance: administered dose in relationship to United States Food and Drug Administration (FDA) guidelines.

PubMed

Nacif, Marcelo S; Arai, Andrew E; Lima, Joao A C; Bluemke, David A

2012-02-29

Myocardial late gadolinium enhancement was originally validated using higher than label-recommended doses of gadolinium chelate. The objective of this study was to evaluate available evidence for various gadolinium dosing regimens used for CMR. The relationship of gadolinium dose warnings (due to nephrogenic systemic fibrosis) announced in 2008 to gadolinium dosing regimens was also examined. We conducted a meta-analysis of peer reviewed publications from January, 2004 to December, 2010. Major subject search headings (MeSh) terms from the National Library of Medicine's PubMed were: contrast media, gadolinium, heart, magnetic resonance imaging; searches were limited to human studies with abstracts published in English. Case reports, review articles, editorials, MRA related papers and all reports that did not indicate gadolinium type or weight-based dose were excluded. For all included references, full text was available to determine the total administered gadolinium dose on a per kg basis. Average and median dose values were weighted by the number of subjects in each study. 399 publications were identified in PubMed; 233 studies matched the inclusion criteria, encompassing 19,934 patients with mean age 54.2 ± 11.4 (range 9.3 to 76 years). 34 trials were related to perfusion testing and 199 to myocardial late gadolinium enhancement. In 2004, the weighted-median and weighted-mean contrast dose were 0.15 and 0.16 ± 0.06 mmol/kg, respectively. Median contrast doses for 2005-2010 were: 0.2 mmol/kg for all years, respectively. Mean contrast doses for the years 2005-2010 were: 0.19 ± 0.03, 0.18 ± 0.04, 0.18 ± 0.10, 0.18 ± 0.03, 0.18 ± 0.04 and 0.18 ± 0.04 mmol/kg, respectively (p for trend, NS). Gadopentetate dimeglumine was the most frequent gadolinium type [114 (48.9%) studies]. No change in mean gadolinium dose was present before, versus after the Food and Drug Administration (FDA) black box warning (p > 0.05). Three multi-center dose ranging trials have been

A methodological approach to a realistic evaluation of skin absorbed doses during manipulation of radioactive sources by means of GAMOS Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Italiano, Antonio; Amato, Ernesto; Auditore, Lucrezia; Baldari, Sergio

2018-05-01

The accurate evaluation of the radiation burden associated with radiation absorbed doses to the skin of the extremities during the manipulation of radioactive sources is a critical issue in operational radiological protection, deserving the most accurate calculation approaches available. Monte Carlo simulation of the radiation transport and interaction is the gold standard for the calculation of dose distributions in complex geometries and in presence of extended spectra of multi-radiation sources. We propose the use of Monte Carlo simulations in GAMOS, in order to accurately estimate the dose to the extremities during manipulation of radioactive sources. We report the results of these simulations for 90Y, 131I, 18F and 111In nuclides in water solutions enclosed in glass or plastic receptacles, such as vials or syringes. Skin equivalent doses at 70 μm of depth and dose-depth profiles are reported for different configurations, highlighting the importance of adopting a realistic geometrical configuration in order to get accurate dosimetric estimations. Due to the easiness of implementation of GAMOS simulations, case-specific geometries and nuclides can be adopted and results can be obtained in less than about ten minutes of computation time with a common workstation.

Misoprostol administered sublingually at a dose of 12.5 μg versus vaginally at a dose of 25 μg for the induction of full-term labor: a randomized controlled trial protocol.

PubMed

Gattás, Daniele Sofia Moraes Barros; da Silva Junior, José Roberto; Souza, Alex Sandro Rolland; Feitosa, Francisco Edson; de Amorim, Melania Maria Ramos

2018-04-18

Various methods are currently used for the induction of labor. Nevertheless, the most effective method with the fewest side effects remains to be established. Misoprostol, administered vaginally, has been routinely used for this purpose; however, other forms of administration are being proposed, including the use of sublingual tablets. No studies have yet compared the effectiveness and safety of 12.5-μg misoprostol administered sublingually compared to a 25-μg vaginal dose of the drug for the induction of labor. A triple-blind, multicenter, placebo-controlled, randomized clinical trial will be conducted in Brazil at the Instituto de Medicina Integral Prof. Fernando Figueira and at the Assis Chateaubriand Maternity Teaching Hospital of the Federal University of Ceará. A total of 140 patients with full-term pregnancies, a live fetus, a Bishop score ≤ 6 and a recommendation of induction of labor will be randomized to one of two groups. One group will receive 12.5-μg sublingual tablets of misoprostol and placebo vaginal tablets, while the other group will receive placebo sublingual tablets and vaginal tablets containing 25 μg of misoprostol. The principal endpoint is the rate of tachysystole. The secondary endpoints are vaginal delivery within 24 h of induction, uterine hyperstimulation, Cesarean section, severe neonatal morbidity or perinatal death, severe maternal morbidity or maternal death, and maternal preference regarding the route of administration of the drug. Student's t-test, and the chi-square test of association or Fisher's exact test, as appropriate, will be used in the data analysis. Risk ratios and their respective 95% confidence intervals will be calculated. Misoprostol has been identified as a safe, inexpensive, easily administered option for the induction of labor, with satisfactory results. An experimental study has shown that misoprostol administered sublingually at a dose of 25 μg appears to be effective and is associated with

40 CFR 147.3005 - Radioactive waste injection wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Radioactive waste injection wells. 147... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3005 Radioactive waste injection...

40 CFR 147.3005 - Radioactive waste injection wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Radioactive waste injection wells. 147... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3005 Radioactive waste injection...

40 CFR 147.3005 - Radioactive waste injection wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Radioactive waste injection wells. 147... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Lands of the Navajo, Ute Mountain Ute, and All Other New Mexico Tribes § 147.3005 Radioactive waste injection...

An open-label, single-dose, phase 1 study of the absorption, metabolism and excretion of quizartinib, a highly selective and potent FLT3 tyrosine kinase inhibitor, in healthy male subjects, for the treatment of acute myeloid leukemia.

PubMed

Sanga, Madhu; James, Joyce; Marini, Joseph; Gammon, Guy; Hale, Christine; Li, Jianke

2017-10-01

1. Quizartinib absorption, metabolism and excretion were characterized in six healthy men receiving a single oral dose of 60 mg (≈100 μCi) of [ 14 C]-quizartinib. Blood, plasma, urine and faeces were collected ≤336 h postdose. 2. Four hours postdose, maximum mean ± SD blood radioactivity concentrations were 296 ± 67.4 ng equivalents/g. A mean ± SD of 1.64 ± 0.482% and 76.3 ± 6.23% of the dose was recovered in urine and faeces, respectively, within 336 h postdose. 3. Radio-detector high-performance liquid chromatography (radio-HPLC) and liquid chromatography-mass spectrometry (LC-MS) showed two main radioactive peaks in plasma, unchanged quizartinib and mono-oxidative metabolite, AC886. Five additional metabolites in plasma were identified by LC-MS, but low levels prevented radio-HPLC detection. Although unchanged quizartinib was the main radioactive component in faeces (mean, 4.0% of administered dose), 15 metabolites representing a mean of 1.0-3.5% of administered dose were found. Quizartinib was predominantly metabolized by phase I biotransformations (oxidation, reduction, dealkylation, deamination, hydrolysis and combinations thereof). 4. This study indicated that quizartinib was rapidly and orally bioavailable, extensively metabolized, with AC886 as the major circulating metabolite, and predominantly eliminated in faeces. Quizartinib was well tolerated in the subjects.

Natural radioactivity in groundwater--a review.

PubMed

Dinh Chau, Nguyen; Dulinski, Marek; Jodlowski, Pawel; Nowak, Jakub; Rozanski, Kazimierz; Sleziak, Monika; Wachniew, Przemyslaw

2011-12-01

The issue of natural radioactivity in groundwater is reviewed, with emphasis on those radioisotopes which contribute in a significant way to the overall effective dose received by members of the public due to the intake of drinking water originating from groundwater systems. The term 'natural radioactivity' is used in this context to cover all radioactivity present in the environment, including man-made (anthropogenic) radioactivity. Comprehensive discussion of radiological aspects of the presence of natural radionuclides in groundwater, including an overview of current regulations dealing with radioactivity in drinking water, is provided. The presented data indicate that thorough assessments of the committed doses resulting from the presence of natural radioactivity in groundwater are needed, particularly when such water is envisaged for regular intake by infants. They should be based on a precise determination of radioactivity concentration levels of the whole suite of radionuclides, including characterisation of their temporal variability. Equally important is a realistic assessment of water intake values for specific age groups. Only such an evaluation may provide the basis for possible remedial actions.

Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989)

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

Meric, S.M.; Rubin, S.I.

The medical records of 62 hyperthyroid cats treated with a fixed dose of 4 mCi of radioactive iodine (131I) were reviewed. In 60 cats, serum thyroxine concentrations were determined after treatment, allowing evaluation of treatment success. Eighty-four percent of the cats had normal serum thyroxine concentrations after treatment. Five of the 60 cats (8%) remained hyperthyroxinemic after treatment. Five cats (8%) were hypothyroxinemic when evaluated within 60 days of treatment. Three of these cats had normal serum thyroxine concentrations 6 months after treatment, and none had clinical signs of hypothyroidism. The administration of a fixed dose of 4 mCi ofmore » 131I was determined to be an effective treatment for feline hyperthyroidism.« less

Vaccination coverage according to doses received and timely administered based on an electronic immunization registry, Araraquara-SP, Brazil, 2012-2014.

PubMed

Tauil, Márcia de Cantuária; Sato, Ana Paula Sayuri; Costa, Ângela Aparecida; Inenami, Marta; Ferreira, Vinícius Leati de Rossi; Waldman, Eliseu Alves

2017-01-01

to describe vaccine coverage by type of vaccine at 12 and 24 months of age. descriptive cohort study with children born in 2012, living in Araraquara-SP, Brazil, recorded in the Information System on Live Births (Sinasc); a manual linkage of Sinasc data with an electronic immunization registry (EIR) was performed; the assessment was based on vaccination status according to São Paulo State recommendations, and on doses received and timely administered. 2,740 children were registered on Sinasc and 99.6% of them were included into EIR; among the 2,612 (95.3%) children studied, the triple viral vaccine (measles, mumps and rubella) had the lowest coverage at 12 months for received dose (74.8%) and at 24 months for timely vaccination (53.5%) and received doses (88.0%). coverage was higher than 90% for most vaccines; however, delayed vaccination was observed, which indicates the need to intensify actions aimed at timely vaccination.

Comparison of total costs of administering calcium polycarbophil and psyllium mucilloid in an institutional setting.

PubMed

Mamtani, R; Cimino, J A; Cooperman, J M; Kugel, R

1990-01-01

The total cost of administering calcium polycarbophil per unit dose (two tablets) was compared with that of administering psyllium mucilloid (one packet dissolved in 8 oz of water) in 20 elderly nursing-home residents. Times for printing labels, checking and initialing labels, gathering materials needed, and preparing and administering the medications were recorded during at least 50 observations in each treatment group. Total cost included nurses' and pharmacists' time, materials, and medications. Calcium polycarbophil doses were prepared and administered more quickly (mean, 49.5 sec) than psyllium mucilloid (105.3 sec). The mean cost of preparing and administering a unit dose was 28.2 for calcium polycarbophil tablets and 59.9 for psyllium mucilloid. The results suggest that the use of calcium polycarbophil tablets would save time and money in institutions in which laxatives are frequently administered.

Placental transfer and pharmacokinetics of a single oral dose of [14C]p-nitrophenol in rats.

PubMed

Abu-Qare, A W; Brownie, C F; Abou-Donia, M B

2000-09-01

The pharmacokinetics and placental transfer of a single oral dose of 100 mg/kg (10 microCi/kg, 16% of acute oral LD50) of uniformly phenyl-labeled [14C]p-nitrophenol were investigated in pregnant Sprague-Dawley rats at 14-18 days of gestation. Three animals were killed on gestation day 18, at 0.5, 1, 2, 4, 12, 24, and 48 h after dosing. Radioactivity was rapidly absorbed and distributed throughout the maternal and fetal tissues. The gastrointestinal tract contents retained 20% and 2% of the dose at 0.5 h and 4 h after dosing. The peak maternal plasma concentration of radioactivity (microg p-nitrophenol equivalent/ml) was 7.17 compared with 0.37 for fetal plasma at 0.5 h. Maximum concentration of radioactivity (microg p-nitrophenol equivalent/g fresh tissue) was detected in most tissues 0.5 h after dosing and was in descending order: kidney 23.27, liver 12.37, placenta 3.56, fetus 2.17, and brain 1.99. Radioactivity was eliminated from plasma and all tissues beiexponentially. The half-lives of elimination of 14C were 34.65 h and 69.30 h for maternal and fetal plasma, respectively. p-Nitrophenol, detected by HPLC, was the major compound identified in plasma and tissues. While p-nitrophenol disappeared biphasically from maternal plasma and kidney, it was eliminated monophasically from brain, placenta, and liver. p-Nitrocatechol and p-aminophenol were detected in the liver with peak concentrations at 0.5 h of 1.13 and 1.00 microg/g fresh tissue, respectively. While the change in the concentration of p-nitrocatechol with time was monophasic, that of p-aminophenol showed a biphasic pattern with elimination half-lives of 1.93 h and 4.95 h, respectively. Radioactivity was rapidly excreted in the urine mostly as polar metabolites, while only 3% of the dose was recovered in the feces. Radioactive materials excreted in the urine comprised: glucuronides 4%, sulfates 8%, hot-acid hydrolysates 11%, nonconjugated compounds 16%, and water-soluble metabolites 61%. This study

Radioactivity of Tobacco Leaves and Radiation Dose Induced from Smoking

PubMed Central

Papastefanou, Constantin

2009-01-01

The radioactivity in tobacco leaves collected from 15 different regions of Greece and before cigarette production was studied in order to find out any association between the root uptake of radionuclides from soil ground by the tobacco plants and the effective dose induced to smokers from cigarette tobacco due to the naturally occurring primordial radionuclides, such as 226Ra and 210Pb of the uranium series and 228Ra of the thorium series and/or man-made radionuclides, such as 137Cs of Chernobyl origin. Gamma-ray spectrometry was applied using Ge planar and coaxial type detectors of high resolution and high efficiency. It was concluded that the activities of the radioisotopes of radium, 226Ra and 228Ra in the tobacco leaves reflected their origin from the soil by root uptake rather than fertilizers used in the cultivation of tobacco plants. Lead-210 originated from the air and was deposited onto the tobacco leaves and trapped by the trichomes. Potassium-40 in the tobacco leaves was due to root uptake either from soil or from fertilizer. The cesium radioisotopes 137Cs and 134Cs in tobacco leaves were due to root uptake and not due to deposition onto the leaf foliage as they still remained in soil four years after the Chernobyl reactor accident, but were absent from the atmosphere because of the rain washout (precipitation) and gravitational settling. The annual effective dose due to inhalation for adults (smokers) for 226Ra varied from 42.5 to 178.6 μSv/y (average 79.7 μSv/y), while for 228Ra from 19.3 to 116.0 μSv/y (average 67.1 μSv/y) and for 210Pb from 47.0 to 134.9 μSv/y (average 104.7 μSv/y), that is the same order of magnitude for each radionuclide. The sum of the effective doses of the three radionuclides varied from 151.9 to 401.3 μSv/y (average 251.5 μSv/y). The annual effective dose from 137Cs of Chernobyl origin was three orders of magnitude lower as it varied from 70.4 to 410.4 nSv/y (average 199.3 nSv/y). PMID:19440399

Re-suspension of the radioactive fallout after the Fukushima accident: risk of internal dose during the first week and the first two months

NASA Astrophysics Data System (ADS)

Yamauchi, M.; Takeda, M.; Makino, M.; Owada, T.

2012-04-01

The nuclear accident at the Fukushima Dai-ichi Nuclear Power Plant in March 2011 contaminated an area of more than 100 km in diameter by radioactive material with amount of about 10-20% of that by the Chernobyl accident. According to the Chernobyl experience, a part of fallout radionuclide is expected to be re-suspended by wind, causing possible risk of internal dose. However, this re-suspension process and its amounts have not been studied very much due to the difficulty of direct measurement of low-density dusts. To estimate forms and periods of the re-suspension of the radioactive fallout, we used both the radiation dose rate data and vertical (downward) component of the DC electric field near the ground, or potential gradient (PG) at Kakioka, 150 km away from the accident site. The data indicates: (1) During 14-15 March, the radioactive dust is most likely suspended in the air near the ground. (2) During 2-7 UT on 16 March, the radioactive dust is most likely blown up from the surface by the strong wind from the non-contaminated area. (3) During 16-20 March, the radioactive dust most likely stayed re-suspended. (4) After the wet contamination on 20 March until late April, the radioactive fallout on the ground are re-suspended during daytime by daily convection due to sunshine, and transported to downwind direction. (5) At more than 30 km distance from the accident site, the re-suspension most likely ceased by the end of April. However, no data is available within 20 km distance from the accident site. Yamauchi, et al. (2012): Settlement process of radioactive dust to the ground inferred from the atmospheric electric field measurement, Ann. Geophys., 30, 49-56, doi:10.5194/angeo-30-49-2012. Yamauchi (2012): Secondary wind transport of radioactive materials after the Fukushima accident, Earth Planet Space, accepted for publication.

Different definitions of esophagus influence esophageal toxicity prediction for esophageal cancer patients administered simultaneous integrated boost versus standard-dose radiation therapy.

PubMed

Huang, Bao-Tian; Huang, Rui-Hong; Zhang, Wu-Zhe; Lin, Wen; Guo, Long-Jia; Xu, Liang-Yu; Lin, Pei-Xian; Chen, Jian-Zhou; Li, De-Rui; Chen, Chuang-Zhen

2017-03-09

We aim to evaluate whether different definitions of esophagus (DEs) impact on the esophageal toxicity prediction for esophageal cancer (EC) patients administered intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) vs. standard-dose IMRT (SD-IMRT). The esophagus for 21 patients diagnosed with primary EC were defined in the following four ways: the whole esophagus, including the tumor (ESO whole ); ESO whole within the treatment field (ESO infield ); ESO infield , excluding the tumor (ESO infield-tumor ) and ESO whole , excluding the tumor (ESO whole-tumor ). The difference in the dose variation, acute esophageal toxicity (AET) and late esophageal toxicity (LET) of four DEs were compared. We found that the mean esophageal dose for ESO whole , ESO infield , ESO infield-tumor and ESO whole-tumor were increased by 7.2 Gy, 10.9 Gy, 4.6 Gy and 2.0 Gy, respectively, in the SIB-IMRT plans. Radiobiological models indicated that a grade ≥ 2 AET was 2.9%, 3.1%, 2.2% and 1.6% higher on average with the Kwint model and 14.6%, 13.2%, 7.2% and 3.4% higher with the Wijsman model for the four DEs. A grade ≥ 3 AET increased by 4.3%, 7.2%, 4.2% and 1.2%, respectively. Additionally, the predicted LET increased by 0.15%, 0.39%, 1.2 × 10 -2 % and 1.5 × 10 -3 %. Our study demonstrates that different DEs influence the esophageal toxicity prediction for EC patients administered SIB-IMRT vs. SD-IMRT treatment.

Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study.

PubMed

Lal, Himal; Poder, Airi; Campora, Laura; Geeraerts, Brecht; Oostvogels, Lidia; Vanden Abeele, Carline; Heineman, Thomas C

2018-01-02

In phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01 B Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months. In this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2. 346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination. Immune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals. Clinicaltrials.gov (NCT01751165

Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans.

PubMed

Aronis, K N; Diakopoulos, K N; Fiorenza, C G; Chamberland, J P; Mantzoros, C S

2011-09-01

Leptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors, but its role in regulating angiogenesis has never been studied in humans. The potential angiogenic effect of two doses of metreleptin (50 and 100 ng/ml) was evaluated in vitro, using a novel three-dimensional angiogenesis assay. Fifteen healthy, normoleptinaemic volunteers were administered both a physiological (0.1 mg/kg) and a pharmacological (0.3 mg/kg) single dose of metreleptin, in vivo, on two different inpatient admissions separated by 1-12 weeks. Serum was collected at 0, 6, 12 and 24 h after metreleptin administration. Twenty lean women, with leptin levels <5 ng/ml, were randomised in a 1:1 fashion to receive either physiological replacement doses of metreleptin (0.04-0.12 mg/kg q.d.) or placebo for 32 weeks. Serum was collected at 0, 8, 20 and 32 weeks after randomisation. Proteomic angiogenesis array analysis was performed to screen for angiogenic factors. Circulating concentrations of angiogenin, angiopoietin-1, platelet derived endothelial factor (PDGF)-AA, matrix metalloproteinase (MMP) 8 and 9, endothelial growth factor (EGF) and vascular EGF (VEGF) were also measured. Both metreleptin doses failed to induce angiogenesis in the in vitro model. Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration, circulating concentrations of angiogenesis markers did not change significantly in vivo. This is the first study that examines the effect of metreleptin administration in angiogenesis in humans. Metreleptin administration does not regulate circulating angiogenesis related factors in humans. ClinicalTrials.gov NCT00140205 and NCT00130117. This study was supported by National Institutes of Health-National Center for Research Resources grant M01-RR-01032 (Harvard Clinical and Translational Science Center) and grant number UL1 RR025758. Funding was also

Rapid Acute Dose Assessment Using MCNP6

NASA Astrophysics Data System (ADS)

Owens, Andrew Steven

Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.

The radiological exposure of man from radioactivity in the Baltic Sea.

PubMed

Nielsen, S P; Bengtson, P; Bojanowsky, R; Hagel, P; Herrmann, J; Ilus, E; Jakobson, E; Motiejunas, S; Panteleev, Y; Skujina, A; Suplinska, M

1999-09-30

A radiological assessment has been carried out considering discharges of radioactivity to the Baltic Sea marine environment since 1950. The sources of radioactivity that have been evaluated are atmospheric nuclear-weapons fallout, fallout from the Chernobyl accident in 1986, discharges of radionuclides from Sellafield and La Hague transported into the Baltic Sea, and discharges of radionuclides from nuclear installations located in the Baltic Sea area. Dose rates from man-made radioactivity to individual members of the public (critical groups) have been calculated based on annual intake of seafood and beach occupancy time. The dose rates to individuals from the regions of the Bothnian Sea and Gulf of Finland are predicted to be larger than from any other area in the Baltic Sea due to the pattern of Chernobyl fallout. The dose rates are predicted to have peaked in 1986 at a value of 0.2 mSv year-1. Collective committed doses to members of the public have been calculated based on fishery statistics and predicted concentrations of radionuclides in biota and coastal sediments. The total collective dose from man-made radioactivity in the Baltic Sea is estimated at 2600 manSv, of which approximately two-thirds originate from Chernobyl fallout, approximately one-quarter from atmospheric nuclear-weapons fallout, approximately 8% from European reprocessing facilities, and approximately 0.04% from nuclear installations bordering the Baltic Sea area. An assessment of small-scale dumping of low-level radioactive waste in the Baltic Sea in the 1960s by Sweden and the Soviet Union has showed that doses to man from these activities are negligible. Dose rates and doses from natural radioactivity dominate except for the year 1986 where dose rates to individuals from Chernobyl fallout in some regions of the Baltic Sea approached those from natural radioactivity.

An environmental dose experiment

NASA Astrophysics Data System (ADS)

Peralta, Luis

2017-11-01

Several radiation sources worldwide contribute to the delivered dose to the human population. This radiation also acts as a natural background when detecting radiation, for instance from radioactive sources. In this work a medium-sized plastic scintillation detector is used to evaluate the dose delivered by natural radiation sources. Calibration of the detector involved the use of radioactive sources and Monte Carlo simulation of the energy deposition per disintegration. A measurement of the annual dose due to background radiation to the body was then estimated. A dose value compatible with the value reported by the United Nations Scientific Committee on the Effects of Atomic Radiation was obtained.

[The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose].

PubMed

Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Publicado por Elsevier Editora Ltda.

The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose.

PubMed

Baykal, Mehmet; Gökmen, Necati; Doğan, Alper; Erbayraktar, Serhat; Yılmaz, Osman; Ocmen, Elvan; Erdost, Hale Aksu; Arkan, Atalay

The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. The rocuronium bromide seizure threshold value was found to be 0.056±0.009μmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286μmoL/kg -1 . A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures. Published by Elsevier Editora Ltda.

Estimating Radiological Doses to Predators Foraging in a Low-Level Radioactive Waste Management Area

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

L.Soholt; G.Gonzales; P.Fresquez

2003-03-01

Since 1957, Los Alamos National Laboratory has operated Area G as its low-level, solid radioactive waste management and disposal area. Although the waste management area is developed, plants, small mammals, and avian and mammalian predators still occupy the less disturbed and revegetated portions of the land. For almost a decade, we have monitored the concentrations of selected radionuclides in soils, plants, and small mammals at Area G. The radionuclides tritium, plutonium-238, and plutonium-239 are regularly found at levels above regional background in all three media. Based on radionuclide concentrations in mice collected from 1994 to 1999, we calculated doses tomore » higher trophic levels (owl, hawk, kestrel, and coyote) that forage on the waste management area. These predators play important functions in the regional ecosystems and are an important part of local Native American traditional tales that identify the uniqueness of their culture. The estimated doses are compared to Department of Energy's interim limit of 0.1 rad/day for the protection of terrestrial wildlife. We used exposure parameters that were derived from the literature for each receptor, including Environmental Protection Agency's exposure factors handbook. Estimated doses to predators ranged from 9E-06 to 2E-04 rad/day, assuming that they forage entirely on the waste management area. These doses are greater than those calculated for predators foraging exclusively in reference areas, but are still well below the interim dose limit. We believe that these calculated doses represent upper-bound estimates of exposure for local predators because the larger predators forage over areas that are much greater than the 63-acre waste management area. Based on these results, we concluded that predators foraging on this area do not face a hazard from radiological exposure under current site conditions.« less

Pharmacokinetics of a single dose of voriconazole administered orally with and without food to red-tailed hawks (Buteo jamaicensus).

PubMed

Parsley, Ruth A; Tell, Lisa A; Gehring, Ronette

2017-04-01

OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments. ANIMALS 7 adult red-tailed hawks. PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates. RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability). CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.

Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.

PubMed

Simons, P J; Cockshott, I D; Douglas, E J; Gordon, E A; Hopkins, K; Rowland, M

1988-04-01

1. An intravenous dose of 14C-propofol (0.47 mg/kg) administered to six male volunteers was rapidly eliminated with 88% recovered in the urine in 5 days and less than 2% in faeces. 2. The dose was cleared by metabolism with less than 0.3% excreted unchanged. The major metabolites were the glucuronic acid conjugate of propofol and the glucuronic acid and sulphate conjugates of its hydroxylated derivative, 2,6-diisopropyl-1,4-quinol. Propofol glucuronide accounted for about 53% of the urinary radioactivity and was the major metabolite in plasma from 30 min post dose. 3. The blood concentration of propofol declined in a biphasic manner from a maximum mean value of 0.44 microgram/ml, 2 min after injection. The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects. A proportion of the dose was cleared slowly, probably due to slow release from less well perfused tissues. Propofol accounted for 94% of the total blood radioactivity at 2 min but only about 6% from 3 to 8 h post dose. 4. Propofol has a volume of distribution equivalent to about 3 to 4 times body weight, and a mean total body clearance of 2.2 1/min.

Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats.

PubMed

Cossum, P A; Sasmor, H; Dellinger, D; Truong, L; Cummins, L; Owens, S R; Markham, P M; Shea, J P; Crooke, S

1993-12-01

5'-TTGCTTCCATCTTCCTCGTC-3' (ISIS 2105) is a phosphorothioate oligodeoxynucleotide currently being evaluated as an intralesional antiviral drug for the treatment of genital warts that are caused by the human papillomavirus. ISIS 2105, labeled with 14C (at the carbon-2 position of thymine) was administered as a single i.v. injection (3.6 mg/kg) to female Sprague-Dawley rats to assess the disposition of the drug. After i.v. administration of [14C]2105, blood radioactivity disappeared in a multiexponential manner with the half-lives of the phases equal to 0.4, 1.9, 7.1 and 5.1 hr. The initial volume of distribution was 22 ml and the postdistribution volume of distribution was 1076 ml, which indicated an extensive distribution of radioactivity. The apparent blood clearance was 14.7 ml/hr. The radioactivity in the expired air accounted for 51% of the administered dose over the 10-day period. Urinary and fecal radioactivity accounted for 15% and 5% of the administered dose, respectively. The major sites of radioactivity uptake were the liver (up to 22.6% of the dose), kidneys (renal cortex, up to 14% of the dose), bone marrow (up to 14% of the dose), skin (up to 13% of the dose) and skeletal muscle (up to 9% of the dose). Other tissues contained approximately 1% or less of the dose. The overall recovery of radioactivity 10 days postdosing was 95.1 +/- 7.5% (mean +/- S.D.) of the administered single dose. The radioactivity in the blood was almost completely in the plasma during the course of the study. In the plasma, the radioactivity was extensively bound to proteins, as assessed by size-exclusion high-performance liquid chromatography (HPLC), in samples up to 8 hr postdosing. Retention data on size-exclusion HPLC and in vitro incubations using purified proteins suggested that the plasma proteins that bound [14C]2105 were albumin and alpha 2-macroglobulin. The complex formed between the plasma proteins and [14C]2105-derived radioactivity was dissociated on anion

Radioactive Waste Characterization Strategies; Comparisons Between AK/PK, Dose to Curie Modeling, Gamma Spectroscopy, and Laboratory Analysis Methods- 12194

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

Singledecker, Steven J.; Jones, Scotty W.; Dorries, Alison M.

2012-07-01

In the coming fiscal years of potentially declining budgets, Department of Energy facilities such as the Los Alamos National Laboratory (LANL) will be looking to reduce the cost of radioactive waste characterization, management, and disposal processes. At the core of this cost reduction process will be choosing the most cost effective, efficient, and accurate methods of radioactive waste characterization. Central to every radioactive waste management program is an effective and accurate waste characterization program. Choosing between methods can determine what is classified as low level radioactive waste (LLRW), transuranic waste (TRU), waste that can be disposed of under an Authorizedmore » Release Limit (ARL), industrial waste, and waste that can be disposed of in municipal landfills. The cost benefits of an accurate radioactive waste characterization program cannot be overstated. In addition, inaccurate radioactive waste characterization of radioactive waste can result in the incorrect classification of radioactive waste leading to higher disposal costs, Department of Transportation (DOT) violations, Notice of Violations (NOVs) from Federal and State regulatory agencies, waste rejection from disposal facilities, loss of operational capabilities, and loss of disposal options. Any one of these events could result in the program that mischaracterized the waste losing its ability to perform it primary operational mission. Generators that produce radioactive waste have four characterization strategies at their disposal: - Acceptable Knowledge/Process Knowledge (AK/PK); - Indirect characterization using a software application or other dose to curie methodologies; - Non-Destructive Analysis (NDA) tools such as gamma spectroscopy; - Direct sampling (e.g. grab samples or Surface Contaminated Object smears) and laboratory analytical; Each method has specific advantages and disadvantages. This paper will evaluate each method detailing those advantages and disadvantages

Measurements of radioactivity and dose assessments in some building materials in Bitlis, Turkey.

PubMed

Kayakökü, Halime; Karatepe, Şule; Doğru, Mahmut

2016-09-01

In this study, samples of perlite, pumice and Ahlat stones (Ignimbrite) extracted from mines in Bitlis and samples of other building materials produced in facilities in Bitlis were collected and analyzed. Activity concentrations of (226)Ra, (232)Th and (40)K in samples of building materials were measured using NaI detector (NaI(Tl)) with an efficiency of 24%. The radon measurements of building material samples were determined using CR-39 nuclear track detectors. (226)Ra, (232)Th and (40)K radioactivity concentrations ranged from (29.6±5.9 to 228.2±38.1Bq/kg), (10.8±5.4 to 95.5±26.1Bq/kg) and (249.3±124.7 to 2580.1±266.9Bq/kg), respectively. Radon concentration, radium equivalent activities, absorbed dose rate, excess lifetime cancer risk and the values of hazard indices were calculated for the measured samples to assess the radiation hazards arising from using those materials in the construction of dwellings. Radon concentration ranged between 89.2±12.0Bq/m(3) and 1141.0±225.0Bq/m(3). It was determined that Raeq values of samples conformed to world standards except for perlite and single samples of brick and Ahlat stone. Calculated values of absorbed dose rate ranged from 81.3±20.5 to 420.6±42.8nGy/h. ELCR values ranged from (1.8±0.3)×10(-3) to (9.0±1.0)×10(-3). All samples had ELCR values higher than the world average. The values of Hin and Hex varied from 0.35±0.11 to 1.78±0.18 and from 0.37±0.09 to 1.17±0.13, respectively. The results were compared with standard radioactivity values determined by international organizations and with similar studies. There would be a radiation risk for people living in buildings made of perlite, Ahlat-1 and Brick-3. Copyright © 2016 Elsevier Ltd. All rights reserved.

SIMPLIFIED PRACTICAL TEST METHOD FOR PORTABLE DOSE METERS USING SEVERAL SEALED RADIOACTIVE SOURCES.

PubMed

Mikamoto, Takahiro; Yamada, Takahiro; Kurosawa, Tadahiro

2016-09-01

Sealed radioactive sources which have small activity were employed for the determination of response and tests for non-linearity and energy dependence of detector responses. Close source-to-detector geometry (at 0.3 m or less) was employed to practical tests for portable dose meters to accumulate statistically sufficient ionizing currents. Difference between response in the present experimentally studied field and in the reference field complied with ISO 4037 due to non-uniformity of radiation fluence at close geometry was corrected by use of Monte Carlo simulation. As a consequence, corrected results were consistent with the results obtained in the ISO 4037 reference field within their uncertainties. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Analysis of dose to patient, spouse/caretaker, and staff, from an implanted trackable radioactive fiducial for use in the radiation treatment of prostate cancer

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

Neustadter, David; Barnea, Gideon; Stokar, Saul

Purpose: A fiducial tracking system based on a novel radioactive tracking technology is being developed for real-time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a 100 {mu}Ci Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient. Methods: Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure ofmore » the medical staff was based on estimates of proximity to and time spent with the patient. Results: The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy. Conclusions: The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.« less

SU-G-201-16: Thermal Imaging in Source Visualization and Radioactivity Measurement for High Dose Rate Brachytherapy

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

Zhu, X; Lei, Y; Zheng, D

2016-06-15

Purpose: High Dose Rate (HDR) brachytherapy poses a special challenge to radiation safety and quality assurance (QA) due to its high radioactivity, and it is thus critical to verify the HDR source location and its radioactive strength. This study demonstrates a new method for measuring HDR source location and radioactivity utilizing thermal imaging. A potential application would relate to HDR QA and safety improvement. Methods: Heating effects by an HDR source were studied using Finite Element Analysis (FEA). Thermal cameras were used to visualize an HDR source inside a plastic applicator made of polyvinylidene difluoride (PVDF). Using different source dwellmore » times, correlations between the HDR source strength and heating effects were studied, thus establishing potential daily QA criteria using thermal imaging Results: For an Ir1?2 source with a radioactivity of 10 Ci, the decay-induced heating power inside the source is ∼13.3 mW. After the HDR source was extended into the PVDF applicator and reached thermal equilibrium, thermal imaging visualized the temperature gradient of 10 K/cm along the PVDF applicator surface, which agreed with FEA modeling. For Ir{sup 192} source activities ranging from 4.20–10.20 Ci, thermal imaging could verify source activity with an accuracy of 6.3% with a dwell time of 10 sec, and an accuracy of 2.5 % with 100 sec. Conclusion: Thermal imaging is a feasible tool to visualize HDR source dwell positions and verify source integrity. Patient safety and treatment quality will be improved by integrating thermal measurements into HDR QA procedures.« less

Evaluation of Terrorist Interest in Radioactive Wastes

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

McFee, J.N.; Langsted, J.M.; Young, M.E.

2006-07-01

Since September 11, 2001, intelligence gathered from Al Qaeda training camps in Afghanistan, and the ensuing terrorist activities, indicates nuclear material security concerns are valid. This paper reviews available information on sealed radioactive sources thought to be of interest to terrorists, and then examines typical wastes generated during environmental management activities to compare their comparative 'attractiveness' for terrorist diversion. Sealed radioactive sources have been evaluated in numerous studies to assess their security and attractiveness for use as a terrorist weapon. The studies conclude that tens of thousands of curies in sealed radioactive sources are available for potential use in amore » terrorist attack. This risk is mitigated by international efforts to find lost and abandoned sources and bring them under adequate security. However, radioactive waste has not received the same level of scrutiny to ensure security. This paper summarizes the activity and nature of radioactive sources potentially available to international terrorists. The paper then estimates radiation doses from use of radioactive sources as well as typical environmental restoration or decontamination and decommissioning wastes in a radioactive dispersal device (RDD) attack. These calculated doses indicate that radioactive wastes are, as expected, much less of a health risk than radioactive sources. The difference in radiation doses from wastes used in an RDD are four to nine orders of magnitude less than from sealed sources. We then review the International Atomic Energy Agency (IAEA) definition of 'dangerous source' in an adjusted comparison to common radioactive waste shipments generated in environmental management activities. The highest waste dispersion was found to meet only category 1-3.2 of the five step IAEA scale. A category '3' source by the IAEA standard 'is extremely unlikely, to cause injury to a person in the immediate vicinity'. The obvious conclusion of

Assessment of Annual Effective Dose for Natural Radioactivity of Gamma Emitters in Biscuit Samples in Iraq.

PubMed

Abojassim, Ali Abid; Al-Alasadi, Lubna A; Shitake, Ahmed R; Al-Tememie, Faeq A; Husain, Afnan A

2015-09-01

Biscuits are an important type of food, widely consumed by babies in Iraq and other countries. This work uses gamma spectroscopy to measure the natural radioactivity due to long-lived gamma emitters in children's biscuits; it also estimates radiation hazard indices, that is, the radium equivalent activity, the representative of gamma level index, the internal hazard index, and the annual effective dose in children. Ten samples were collected from the Iraqi market from different countries of origin. The average specific activities for (226)Ra, (232)Th, and (40)K were 9.390, 3.1213, and 214.969 Bq/kg, respectively, but the average of the radium equivalent activity and the internal hazard index were 33.101 Bq/kg and 0.107, respectively. The total average annual effective dose from consumption by adults, children, and infants is estimated to be 0.655, 1.009, and 0.875 mSv, respectively. The values found for specific activity, radiation hazard indices, and annual effective dose in all samples in this study were lower than worldwide median values for all groups; therefore, these values are found to be safe.

[Determination of radioactivity by smartphones].

PubMed

Hartmann, H; Freudenberg, R; Andreeff, M; Kotzerke, J

2013-01-01

The interest in the detection of radioactive materials has strongly increased after the accident in the nuclear power plant Fukushima and has led to a bottleneck of suitable measuring instruments. Smartphones equipped with a commercially available software tool could be used for dose rate measurements following a calibration according to the specific camera module. We examined whether such measurements provide reliable data for typical activities and radionuclides in nuclear medicine. For the nuclides 99mTc (10 - 1000 MBq), 131I (3.7 - 1800 MBq, therapy capsule) and 68Ga (50 - 600 MBq) radioactivity with defined geometry in different distances was measured. The smartphones Milestone Droid 1 (Motorola) and HTC Desire (HTC Corporation) were compared with the standard instruments AD6 (automess) and DoseGUARD (AEA Technology). Measurements with the smartphones and the other devices show a good agreement: linear signal increase with rising activity and dose rate. The long time measurement (131I, 729 MBq, 0.5 m, 60 min) demonstrates a considerably higher variation (by 20%) of the measured smartphone data values compared with the AD6. For low dose rates (< 1 µGy/h), the sensitivity decreases so that measurements of e. g. the natural radiation exposure do not lead to valid results. The calibration of the camera responsivity for the smartphone has a big influence on the results caused by the small detector surface of the camera semiconductor. With commercial software the camera module of a smartphone can be used for the measurement of radioactivity. Dose rates resulting from typical nuclear medicine procedures can be measured reliably (e. g., dismissal dose after radioiodine therapy). The signal shows a high correlation to measured values of conventional dose measurement devices.

The short- and long-term effects of orally administered high-dose reduced graphene oxide nanosheets on mouse behaviors.

PubMed

Zhang, Ding; Zhang, Zheyu; Liu, Yayun; Chu, Maoquan; Yang, Chengyu; Li, Wenhao; Shao, Yuxiang; Yue, Yan; Xu, Rujiao

2015-11-01

Reduced graphene oxide (rGO), a carbon-based nanomaterial, has enormous potential in biomedical research, including in vivo cancer therapeutics. Concerns over the toxicity remain outstanding and must be investigated before clinical application. The effect of rGO exposure on animal behaviors, such as learning and memory abilities, has not been clarified. Herein, we explored the short- and long-term effects of orally administered rGO on mouse behaviors, including general locomotor activity level, balance and neuromuscular coordination, exploratory and anxiety behaviors, and learning and memory abilities using open-field, rotarod, and Morris water maze tests. Compared with mice administered buffer-dispersed mouse chow or buffer alone, mice receiving a high dose of small or large rGO nanosheets showed little change in exploratory, anxiety-like, or learning and memory behaviors, although general locomotor activity, balance, and neuromuscular coordination were initially affected, which the mechanisms (e.g. the influence of rGO exposure on the activity of superoxide dismutase in mouse serum) were discussed. The results presented in this work look to provide a deep understanding of the in vivo toxicity of rGO to animals, especially its effect on learning and memory and other behaviors. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine.

PubMed

Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc

2015-01-01

This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.

[Investigation of radioactivity measurement of medical radioactive waste].

PubMed

Koizumi, Kiyoshi; Masuda, Kazutaka; Kusakabe, Kiyoko; Kinoshita, Fujimi; Kobayashi, Kazumi; Yamamoto, Tetsuo; Kanaya, Shinichi; Kida, Tetsuo; Yanagisawa, Masamichi; Iwanaga, Tetsuo; Ikebuchi, Hideharu; Kusama, Keiji; Namiki, Nobuo; Okuma, Hiroshi; Fujimura, Yoko; Horikoshi, Akiko; Tanaka, Mamoru

2004-11-01

To explore the possibility of which medical radioactive wastes could be disposed as general wastes after keeping them a certain period of time and confirming that their radioactivity reach a background level (BGL), we made a survey of these wastes in several nuclear medicine facilities. The radioactive wastes were collected for one week, packed in a box according to its half-life, and measured its radioactivity by scintillation survey meter with time. Some wastes could reach a BGL within 10 times of half-life, but 19% of the short half-life group (group 1) including 99mTc and 123I, and 8% of the middle half-life group (group 2) including 67Ga, (111)In, and 201Tl did not reach a BGL within 20 times of half-life. A reason for delaying the time of reaching a BGL might be partially attributed to high initial radiation dose rate or heavy package weight. However, mixing with the nuclides of longer half-life was estimated to be the biggest factor affecting this result. When disposing medical radioactive wastes as general wastes, it is necessary to avoid mixing with radionuclide of longer half-life and confirm that it reaches a BGL by actual measurement.

A Phase I Study to Investigate the Absorption, Pharmacokinetics, and Excretion of [(14)C]Prucalopride After a Single Oral Dose in Healthy Volunteers.

PubMed

Flach, Stephen; Scarfe, Graeme; Dragone, Jeffrey; Ding, Jie; Seymour, Mark; Pennick, Mike; Pankratz, Todd; Troy, Steven; Getsy, Jay

2016-09-01

Chronic constipation is a prevalent gastrointestinal disorder globally. It is often treated with medications such as laxatives. Newer therapies to improve gastric motility include the selective 5-hydroxytryptamine receptor-4 agonist prucalopride, which is licensed for the treatment of chronic constipation in adults. The aim of this study was to investigate the pharmacokinetic properties and excretion of prucalopride in healthy individuals, using a microtracer approach with (14)C radioactivity detection using liquid scintillation counting and accelerator mass spectrometry. This was a single-period, open-label, nonrandomized absorption, metabolism, and excretion study of [(14)C]prucalopride. Participants were 6 healthy men aged 18 to 50 years. After screening, participants were administered a single dose of [(14)C]prucalopride succinate 2 mg (~200 nCi). Postadministration, urine, feces, and blood samples were collected over a 10-day period. Safety and adverse event data were also collected. Almost 100% of the administered dose of radioactivity was recovered, with a mean (SD) of 84.2% (8.88%) recovered in urine and 13.3% (1.73%) recovered in feces. The mean blood-to-plasma concentration ratio of 1.9 indicated uptake of prucalopride into blood cells. The renal clearance of prucalopride was 17.0 (2.5) L/h, which is higher than the glomerular filtration rate in healthy individuals, suggesting active renal transport of prucalopride. Prucalopride was well tolerated, with no serious adverse events reported. Prucalopride was well absorbed and excreted mainly by the kidneys, including both passive and active transporter mechanisms. Quantitative recovery of the radioactive dose was achieved. Consistent with previous studies, prucalopride was generally well tolerated. ClinicalTrials.gov identifier: NCT01807000. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Radioactive 133-Xenon gas-filled balloon to prevent restenosis: dosimetry, efficacy, and safety considerations.

PubMed

Apple, Marc; Waksman, Ron; Chan, Rosanna C; Vodovotz, Yoram; Fournadjiev, Jana; Bass, Bill G

2002-08-06

Ionizing radiation administered intraluminally via catheter-based systems using solid beta and gamma sources or liquid-filled balloons has shown reduction in the neointima formation after injury in the porcine model. We propose a novel system that uses a 133-Xenon (133Xe) radioactive gas-filled balloon catheter system. Overstretch balloon injury was performed in the coronary arteries of 33 domestic pigs. A novel 133Xe radioactive gas-filled balloon (3.5/45 mm) was positioned to overlap the injured segment with margins. After vacuum was obtained in the balloon catheter, approximately 2.5 cc of 133Xe gas was injected to fill the balloon. Doses of 0, 7.5, 15, and 30 Gy were delivered to a distance of 0.25 mm from the balloon surface. The dwell time ranged from 1.0 to 4.0 minutes, depending on the dose. Localization of 133Xe in the balloon was verified by a gamma camera. The average activity in a 3.5/45-mm balloon was measured at 67.7+/-12.1 mCi, and the total diffusion loss of the injected dose was 0.26% per minute of the injected dose. Bedside radiation exposure measured between 2 and 6 mR/h, and the shallow dose equivalent was calculated as 0.037 mrem per treatment. Histomorphometric analysis at 2 weeks showed inhibition of the intimal area (intimal area corrected for medial fracture length [IA/FL]) in the irradiated segments of 0.26+/-0.08 with 30 Gy, 0.07+/-0.24 with 15 Gy, and 0.12+/-0.89 with 7.5 Gy versus 0.76+/-0.08 with control P<0.001. 133Xe gas-filled balloon is feasible and effective in the reduction of neointima formation in the porcine model and safe for use in coronary arteries.

Effects of Different Containers on Radioactivity Measurements using a Dose Calibrator with Special Reference to 111In and 123I.

PubMed

Inoue, Yusuke; Abe, Yutaka; Kikuchi, Kei; Miyatake, Hiroki; Watanabe, Atsushi

2017-01-01

Low-energy characteristic x-rays emitted by 111 In and 123 I sources are easily absorbed by the containers of the sources, affecting radioactivity measurements using a dose calibrator. We examined the effects of different containers on the estimated activities. The radioactivities of 111 In, 123 I, 201 Tl, and 99m Tc were measured in containers frequently employed in clinical practice in Japan. The 111 In measurements were performed in the vials A and B of the 111 In-pentetreotide preparation kit and in the plastic syringe. The activities of 123 I-metaiodobenzylguanidine and 201 Tl chloride were measured in the prefilled glass syringes and plastic syringes. The milking vial, vial A, vial B, and plastic syringe were used to assay 99m Tc. For 111 In and 123 I, measurements were performed with and without a copper filter. The filter was inserted into the well of the dose calibrator to absorb low-energy x-rays. The relative estimate was defined as the ratio of the activity estimated with the dose calibrator to the standard activity. The estimated activities varied greatly depending on the container when 111 In and 123 I sources were assayed without the copper filter. The relative estimates of 111 In were 0.908, 1.072, and 1.373 in the vial A, vial B, and plastic syringe, respectively. The relative estimates of 123 I were 1.052 and 1.352 in the glass syringe and plastic syringe, respectively. Use of the copper filter eliminated the container-dependence in 111 In and 123 I measurements. Container-dependence was demonstrated in neither 201 Tl nor 99m Tc measurements. The activities of 111 In and 123 I estimated with a dose calibrator differ greatly among the containers. Accurate estimation may be attained using the container-specific correction factor or using the copper filter.

Radioactive waste management and practice in Bangladesh

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

Mollah, A.S.; Rahman, M.M.

1993-12-31

A large amount of low- and medium-level radioactive wastes are being generated in different parts of Bangladesh. The solid wastes are being collected in steel containers and liquid wastes are collected in plastic carboys and drums. Gaseous Ar-41 is discharged into the atmosphere through the 25 m height stack under controlled conditions after proper monitoring. The solid radioactive wastes collected are approximately 5 m{sup 3} (1988--1992) with gross beta-gamma surface dose rates from 0.30 {micro}Sv/h to 250 {micro}Sv/h. The liquid radioactive wastes are approximately 200 liters (1988--1992) with gross-beta-gamma surface dose rates from 0.30 {micro}Sv/h to 1 mSv/h. The solidmore » and liquid wastes presently being collected are mostly short lived and low level and safely stored according to international safety codes of practice. Radioactive waste packages collected during the 5-yrs study totaled 16, representing a collective volume of {approximately} 7.5 m{sup 3}. The problem of management of radioactive waste in Bangladesh is not so serious at present because the wastes arising are small now. A computerized data base has been developed to document inventory of all radioactive waste arising in the country. The current practices of collection, handling, safe storage and management of the radioactive wastes are reported in this paper.« less

Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial.

PubMed

Berger, J S; Gonzalez, A; Hopkins, A; Alshaeri, T; Jeon, D; Wang, S; Amdur, R L; Smiley, R

2016-12-01

The appropriate dose of intrathecal morphine for post-cesarean analgesia is unclear. With the inclusion of routine non-steroidal anti-inflammatory drugs, the required dose of morphine may be significantly less than the 200-300μg common a decade ago. We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery. Patients received an intrathecal injection of hyperbaric bupivacaine 12mg, fentanyl 15μg and a randomized dose of 50, 100, or 150μg morphine in a volume of 2.2mL. Patients received intravenous ketorolac 30mg before leaving the operating room and 15mg intravenously every 6h for the duration of the study (24h). All received postoperative patient-controlled intravenous morphine. The primary endpoint was total intravenous morphine administered postoperatively over 24h, analyzed using mixed model regression. There were no differences between dose groups (or institutions) in intravenous morphine use over 24h. Visual analog scale scores for pain and nausea did not differ. Pruritus was greater in the 100 and 150μg groups than the 50μg group at 6h and 12h, but there was no difference between groups in nausea or pruritus treatments. Respiratory depression or significant sedation did not occur. The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50μg produces analgesia similar to that produced by either 100μg or 150μg. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m2 every 21 days in patients with cancer

PubMed Central

Iyengar, Tara; Ramanathan, Ramesh K.; Lewandowski, Karen; Anthony, Stephen P.; Donehower, Ross C.; Westin, Eric; Hurt, Karla; Hynes, Scott M.; McKane, Scott

2013-01-01

Summary Purpose This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. Experimental design This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40–195 mg/m2) were combined with 500 mg/m2 of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Anti-tumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. Results A total of 31 patients were enrolled into six cohorts (three at 40 mg/m2 over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m2, 70 mg/m2, and 195 mg/m2; 13 at 105 mg/m2; six at 150 mg/m2). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m2); reversible infusion-related reaction (150 mg/m2); thrombocytopenia (195 mg/m2); and fatigue (195 mg/m2). The maximum tolerated dose was defined as 150 mg/m2. The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m2. Conclusion LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles. PMID:22492020

Study of two different radioactive sources for prostate brachytherapy treatment

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

Pereira Neves, Lucio; Perini, Ana Paula; Souza Santos, William de

In this study we evaluated two radioactive sources for brachytherapy treatments. Our main goal was to quantify the absorbed doses on organs and tissues of an adult male patient, submitted to a brachytherapy treatment with two radioactive sources. We evaluated a {sup 192}Ir and a {sup 125}I radioactive sources. The {sup 192}Ir radioactive source is a cylinder with 0.09 cm in diameter and 0.415 cm long. The {sup 125}I radioactive source is also a cylinder, with 0.08 cm in diameter and 0.45 cm long. To evaluate the absorbed dose distribution on the prostate, and other organs and tissues of anmore » adult man, a male virtual anthropomorphic phantom MASH, coupled in the radiation transport code MCNPX 2.7.0, was employed.We simulated 75, 90 and 102 radioactive sources of {sup 125}I and one of {sup 192}Ir, inside the prostate, as normally used in these treatments, and each treatment was simulated separately. As this phantom was developed in a supine position, the displacement of the internal organs of the chest, compression of the lungs and reduction of the sagittal diameter were all taken into account. For the {sup 192}Ir, the higher doses values were obtained for the prostate and surrounding organs, as the colon, gonads and bladder. Considering the {sup 125}I sources, with photons with lower energies, the doses to organs that are far from the prostate were lower. All values for the dose rates are in agreement with those recommended for brachytherapy treatments. Besides that, the new seeds evaluated in this work present usefulness as a new tool in prostate brachytherapy treatments, and the methodology employed in this work may be applied for other radiation sources, or treatments. (authors)« less

Dose to the metaphyseal growth complexes in children undergoing /sup 99m/Tc-EHDP bone scans

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

Thomas, S.R.; Gelfand, M.J.; Kerelakes, J.G.

1978-01-01

The spatial and temporal distribution of radionuclides in children may differ greatly from that accepted for adults. Following injection of a bone-seeking agent (/sup 99m/Tc-EHDP), radioactivity in the metaphyseal growth complexes of the distal femur and proximal tibia was quantitated in a series of children 4 to 16 years of age, using a gamma camera/computer system. The dose to the growth plate was found to range from 0.8 to 4.7 rads when adjusted to an administered activity of 200 ..mu..ci/kg, compared to approximately 0.6 rad to the adult skeleton for a corresponding study.

Assessment of the sedative effects of buprenorphine administered with 20 microg/kg detomidine in horses.

PubMed

Love, E J; Taylor, P M; Murrell, J; Whay, H R; Waterman-Pearson, A E

2011-04-16

The aim of this randomised, observer-blinded, crossover study was to compare the effects of four treatments, administered intravenously to six horses: saline and saline; 10 µg/kg detomidine and 7.5 µg/kg buprenorphine; 20 µg/kg detomidine and 7.5 µg/kg buprenorphine; and 20 µg/kg detomidine and 10 µg/kg buprenorphine. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation and duration of sedation were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Increasing the dose of detomidine from 10 to 20 µg/kg increased the degree of sedation when administered with the same dose of buprenorphine (7.5 µg/kg). When administered with 20 µg/kg detomidine, increasing the dose of buprenorphine from 7.5 to 10 µg/kg did not influence the degree of sedation achieved.

Comparison of gatifloxacin and levofloxacin administered at various dosing regimens to hospitalised patients with community-acquired pneumonia: pharmacodynamic target attainment study using North American surveillance data for Streptococcus pneumoniae.

PubMed

Noreddin, Ayman M; Hoban, Daryl J; Zhanel, George G

2005-08-01

This work aimed at determining the target attainment potential of gatifloxacin and levofloxacin in specific age-related patient populations such as elderly (> or =65 years) versus younger (<65 years) hospitalised patients with community-acquired pneumonia (CAP). Previously described population pharmacokinetic models of gatifloxacin and levofloxacin administration in patients with serious CAP were utilised to simulate gatifloxacin and levofloxacin pharmacokinetics. Pharmacokinetic simulations and susceptibility data for Streptococcus pneumoniae from the ongoing national surveillance study, Canadian Respiratory Organism Susceptibility Study (CROSS), were then used to produce pharmacodynamic indices of free-drug area under the curve over 24h relative to the minimum inhibitory concentration (free-drug AUC(0-24)/MIC(all)). Monte Carlo simulations were then used to analyse target attainment both of gatifloxacin and levofloxacin to achieve free-drug AUC(0-24)/MIC(all)> or =30 against S. pneumoniae in patients with CAP. Dosing regimens for gatifloxacin were 400 mg once daily (qd) administered to younger patients (<65 years) and gatifloxacin 200 mg qd to elderly patients (> or =65 years). Dosing regimens for levofloxacin were simulated as 500 mg, 750 mg and 1000 mg qd administered to elderly patients as well as younger patients. Monte Carlo simulations using gatifloxacin 400mg against S. pneumoniae yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 96.6% for all patients, 92.3% for younger patients and 97.7% for elderly patients. When administered to elderly patients, a reduced dose of gatifloxacin 200mg qd could achieve a target attainment potential of 91.4%. Monte Carlo simulation using levofloxacin 500 mg qd yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 92.3% for all patients, 95.7% for elderly patients compared with 72.7% for younger patients. Using levofloxacin 750 mg and 1000 mg qd had probabilities of achieving free

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

PubMed

Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

2013-02-01

This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

Safety of florfenicol administered in feed to tilapia (Oreochromis sp.)

USGS Publications Warehouse

Gaikowski, Mark P.; Wolf, Jeffrey C.; Schleis, Susan M.; Tuomari, Darrell; Endris, Richard G.

2013-01-01

The safety of Aquaflor® (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2x the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5x the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

A gradient of radioactive contamination in Dolon village near the SNTS and comparison of computed dose values with instrumental estimates for the 29 August, 1949 nuclear test.

PubMed

Stepanenko, Valeriy F; Hoshi, Masaharu; Dubasov, Yuriy V; Sakaguchi, Aya; Yamamoto, Masayoshi; Orlov, Mark Y; Bailiff, Ian K; Ivannikov, Alexander I; Skvortsov, Valeriy G; Iaskova, Elena K; Kryukova, Irina G; Zhumadilov, Kassym S; Endo, Satoru; Tanaka, Kenichi; Apsalikov, Kazbek N; Gusev, Boris I

2006-02-01

Spatial distributions of soil contamination by 137Cs (89 sampling points) and 239+240Pu (76 points) near and within Dolon village were analyzed. An essential exponential decrease of contamination was found in Dolon village: the distance of a half reduction in contamination is about 0.87-1.25 km (in a northwest-southeast direction from the supposed centerline of the radioactive trace). This fact is in agreement with the available exposure rate measurements near Dolon (September 1949 archive data): on the basis of a few measurements the pattern of the trace was estimated to comprise a narrow 2 km corridor of maximum exposure rate. To compare computed external doses in air with local dose estimates by retrospective luminescence dosimetry (RLD) the gradient of radioactive soil contamination within the village was accounted for. The computed dose associated with the central axis of the trace was found to be equal to 2260 mGy (calculations based on archive exposure rate data). Local doses near the RLD sampling points (southeast of the village) were calculated to be in the range 466-780 mGy (averaged value: 645+/-70 mGy), which is comparable with RLD data (averaged value 460+/-92 mGy with range 380-618 mGy). A comparison of the computed mean dose in the settlement with dose estimates by ESR tooth enamel dosimetry makes it possible to estimate the "upper level" of the "shielding and behavior" factor in dose reduction for inhabitants of Dolon village which was found to be 0.28+/-0.068.

The radiation dosimetry of intrathecally administered radionuclides

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

Stabin, M.G.; Evans, J.F.

The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energymore » deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.« less

DOSE AND GAMMA-RAY SPECTRA FROM NEUTRON-INDUCED RADIOACTIVITY IN MEDICAL LINEAR ACCELERATORS FOLLOWING HIGH-ENERGY TOTAL BODY IRRADIATION.

PubMed

Keehan, S; Taylor, M L; Smith, R L; Dunn, L; Kron, T; Franich, R D

2016-12-01

Production of radioisotopes in medical linear accelerators (linacs) is of concern when the beam energy exceeds the threshold for the photonuclear interaction. Staff and patients may receive a radiation dose as a result of the induced radioactivity in the linac. Gamma-ray spectroscopy was used to identify the isotopes produced following the delivery of 18 MV photon beams from a Varian 21EX and an Elekta Synergy. The prominent radioisotopes produced include 187 W, 63 Zn, 56 Mn, 24 Na and 28 Al in both linac models. The dose rate was measured at the beam exit window (12.6 µSv in the first 10 min) following 18 MV total body irradiation (TBI) beams. For a throughput of 24 TBI patients per year, staff members are estimated to receive an annual dose of up to 750 μSv at the patient location. This can be further reduced to 65 μSv by closing the jaws before re-entering the treatment bunker. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acute toxicity of subcutaneously administered vitamin E isomers delta- and gamma-tocotrienol in mice.

PubMed

Swift, Sibyl N; Pessu, Roli L; Chakraborty, Kushal; Villa, Vilmar; Lombardini, Eric; Ghosh, Sanchita P

2014-01-01

The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs. © The Author(s) 2014.

The biological impacts of ingested radioactive materials on the pale grass blue butterfly

NASA Astrophysics Data System (ADS)

Nohara, Chiyo; Hiyama, Atsuki; Taira, Wataru; Tanahara, Akira; Otaki, Joji M.

2014-05-01

A massive amount of radioactive materials has been released into the environment by the Fukushima Dai-ichi Nuclear Power Plant accident, but its biological impacts have rarely been examined. Here, we have quantitatively evaluated the relationship between the dose of ingested radioactive cesium and mortality and abnormality rates using the pale grass blue butterfly, Zizeeria maha. When larvae from Okinawa, which is likely the least polluted locality in Japan, were fed leaves collected from polluted localities, mortality and abnormality rates increased sharply at low doses in response to the ingested cesium dose. This dose-response relationship was best fitted by power function models, which indicated that the half lethal and abnormal doses were 1.9 and 0.76 Bq per larva, corresponding to 54,000 and 22,000 Bq per kilogram body weight, respectively. Both the retention of radioactive cesium in a pupa relative to the ingested dose throughout the larval stage and the accumulation of radioactive cesium in a pupa relative to the activity concentration in a diet were highest at the lowest level of cesium ingested. We conclude that the risk of ingesting a polluted diet is realistic, at least for this butterfly, and likely for certain other organisms living in the polluted area.

The biological impacts of ingested radioactive materials on the pale grass blue butterfly.

PubMed

Nohara, Chiyo; Hiyama, Atsuki; Taira, Wataru; Tanahara, Akira; Otaki, Joji M

2014-05-15

A massive amount of radioactive materials has been released into the environment by the Fukushima Dai-ichi Nuclear Power Plant accident, but its biological impacts have rarely been examined. Here, we have quantitatively evaluated the relationship between the dose of ingested radioactive cesium and mortality and abnormality rates using the pale grass blue butterfly, Zizeeria maha. When larvae from Okinawa, which is likely the least polluted locality in Japan, were fed leaves collected from polluted localities, mortality and abnormality rates increased sharply at low doses in response to the ingested cesium dose. This dose-response relationship was best fitted by power function models, which indicated that the half lethal and abnormal doses were 1.9 and 0.76 Bq per larva, corresponding to 54,000 and 22,000 Bq per kilogram body weight, respectively. Both the retention of radioactive cesium in a pupa relative to the ingested dose throughout the larval stage and the accumulation of radioactive cesium in a pupa relative to the activity concentration in a diet were highest at the lowest level of cesium ingested. We conclude that the risk of ingesting a polluted diet is realistic, at least for this butterfly, and likely for certain other organisms living in the polluted area.

[Estimation of dietary intake of radioactive materials by total diet methods].

PubMed

Uekusa, Yoshinori; Nabeshi, Hiromi; Tsutsumi, Tomoaki; Hachisuka, Akiko; Matsuda, Rieko; Teshima, Reiko

2014-01-01

Radioactive contamination in foods is a matter of great concern after the Tokyo Electric Power Company's Fukushima Daiichi nuclear power plant disaster caused by the Great East Japan Earthquake. In order to estimate human intake and annual committed effective dose of radioactive materials, market basket and duplicate diet samples from various areas in Japan were analyzed for cesium-134 ((134)Cs), -137 ((137)Cs), and natural radionuclide potassium-40 ((40)K) by γ-ray spectroscopy. Dietary intake of radioactive cesium around Fukushima area was somewhat higher than in other areas. However, maximum committed effective doses obtained by the market basket and duplicate diet samples were 0.0094 and 0.027 mSv/year, respectively, which are much lower than the maximum permissible dose (1 mSv/year) in foods in Japan.

Chemical Dosing and First-Order Kinetics

ERIC Educational Resources Information Center

Hladky, Paul W.

2011-01-01

College students encounter a variety of first-order phenomena in their mathematics and science courses. Introductory chemistry textbooks that discuss first-order processes, usually in conjunction with chemical kinetics or radioactive decay, stop at single, discrete dose events. Although single-dose situations are important, multiple-dose events,…

Radiological environmental dose assessment methods and compliance dose results for 2015 operations at the Savannah River Site

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

Jannik, G. T.; Dixon, K. L.

This report presents the environmental dose assessment methods and the estimated potential doses to the offsite public from 2015 Savannah River Site (SRS) atmospheric and liquid radioactive releases. Also documented are potential doses from special-case exposure scenarios - such as the consumption of deer meat, fish, and goat milk.

Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension.

PubMed

Clemens, Pamela L; Cloyd, James C; Kriel, Robert L; Remmel, Rory P

2007-01-01

Maintenance of effective drug concentrations is essential for adequate treatment of epilepsy. Some antiepileptic drugs can be successfully administered rectally when the oral route of administration is temporarily unavailable. Oxcarbazepine is a newer antiepileptic drug that is rapidly converted to a monohydroxy derivative, the active compound. This study aimed to characterise the bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension using a randomised, crossover design in ten healthy volunteers. Two subjects received 300 mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450 mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1:1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time-point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (C(max)) and time to reach C(max) (t(max)) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C(max) and AUCs were compared using Wilcoxon signed-rank tests. Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C(max) and AUC values were significantly lower following rectal administration (p < 0.01). The total amount of monohydroxy derivative excreted in the urine following rectal administration was 10 +/- 5% of the amount excreted following oral administration. Oral absorption was consistent with previous studies. The most common adverse effects were headache and fatigue

A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV–negative volunteers

PubMed Central

Schöller-Gyüre, Monika; Kakuda, Thomas N; De Smedt, Goedele; Vanaken, Hilde; Bouche, Marie-Paule; Peeters, Monika; Woodfall, Brian; Hoetelmans, Richard M W

2008-01-01

Aims Etravirine is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV. Proton pump inhibitors and H2-antagonists are frequently used in the HIV-negative-infected population, and drug–drug interactions have been described with other antiretrovirals. This study evaluated the effect of steady-state omeprazole and ranitidine on the pharmacokinetics of a single dose of etravirine. Methods In an open-label, randomized, one-way, three-period crossover trial, HIV-negative volunteers randomly received a single dose of 100 mg etravirine alone (treatment A); 11 days of 150 mg ranitidine b.i.d. (treatment B); and 11 days of 40 mg omeprazole q.d. (treatment C). A single dose of 100 mg etravirine was co-administered on day 8 of sessions 2 and 3. Each session was separated by a 14-day wash-out. Results Nineteen volunteers (seven female) participated. When a single dose of etravirine was administered in the presence of steady-state ranitidine, etravirine least squares means ratios (90% confidence interval) for AUClast and Cmax were 0.86 (0.76, 0.97) and 0.94 (0.75, 1.17), respectively, compared with administration of etravirine alone. When administered with steady-state omeprazole, these values were 1.41 (1.22, 1.62) and 1.17 (0.96, 1.43), respectively. Co-administration of a single dose of etravirine and ranitidine or omeprazole was generally safe and well tolerated. Conclusions Ranitidine slightly decreased etravirine exposure, whereas omeprazole increased it by approximately 41%. The increased exposure of etravirine when co-administered with omeprazole is attributed to CYP2C19 inhibition. Considering the favourable safety profile of etravirine, these changes are not clinically relevant. Etravirine can be co-administered with proton pump inhibitors and H2 antagonists without dose adjustments. PMID:18492125

Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

PubMed Central

2013-01-01

Background This study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320–400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively. Results Plasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively

Dose fractionation and single subject studies in PET

NASA Astrophysics Data System (ADS)

Balakrishnan, Karthikayan

Conventional positron emission tomography (PET) for cognitive brain studies typically relies on information collected from the distribution of decays following an injection of 15O-labeled water. The number of injections that can be administered to the subject are constrained by radiation dose to the subject and total length of the PET scan. The standard protocol involves 8--10 injections of H152O separated by approximately 5--7 half-lives of 15O. The number of activation conditions that can be realistically studied in a standard PET session is between 8 and 10. This work investigates the physiological response of a simulated subject to H152O injections that are administered in small doses (1--5 mCi) with short inter-injection intervals (40--180 seconds). A larger number of activation conditions are presented to the subject with a wider variation in the activation paradigm. Repeat conditions are studies. Signal averaging methods are feasible with this method of dose administration. Sinograms from scans with similar activation conditions are summed together before reconstruction. The signal in the primary activation region of the brain is shown to increase while suppressing the contribution of secondary activation regions in the brain. The contrast of the final image is similarly increased which leads to easier identification of the primary activation region. An automated H152O -production unit controlled by a PC running LabView software was developed to produce the dose required for the injection sequence by controlling the flow of H152O -vapor that diffuses across a semi-permeable membrane into saline. The unit is capable of producing H152O rapidly for both the standard and the proposed dose administration methods. The system also detects the bolus arrival time at the subject's lungs using a small external plastic detector. Activation sequence commences with the rise in radioactivity observed by the detector. The simulations indicate that inter-injection intervals

The Model 9977 Radioactive Material Packaging Primer

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

Abramczyk, G.

2015-10-09

The Model 9977 Packaging is a single containment drum style radioactive material (RAM) shipping container designed, tested and analyzed to meet the performance requirements of Title 10 the Code of Federal Regulations Part 71. A radioactive material shipping package, in combination with its contents, must perform three functions (please note that the performance criteria specified in the Code of Federal Regulations have alternate limits for normal operations and after accident conditions): Containment, the package must “contain” the radioactive material within it; Shielding, the packaging must limit its users and the public to radiation doses within specified limits; and Subcriticality, themore » package must maintain its radioactive material as subcritical« less

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

PubMed Central

Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

2012-01-01

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

Effect of sonication on particle dispersion, administered dose and metal release of non-functionalized, non-inert metal nanoparticles.

PubMed

Pradhan, Sulena; Hedberg, Jonas; Blomberg, Eva; Wold, Susanna; Odnevall Wallinder, Inger

2016-01-01

In this study, we elucidate the effect of different sonication techniques to efficiently prepare particle dispersions from selected non-functionalized NPs (Cu, Al, Mn, ZnO), and corresponding consequences on the particle dose, surface charge and release of metals. Probe sonication was shown to be the preferred method for dispersing non-inert, non-functionalized metal NPs (Cu, Mn, Al). However, rapid sedimentation during sonication resulted in differences between the real and the administered doses in the order of 30-80 % when sonicating in 1 and 2.56 g/L NP stock solutions. After sonication, extensive agglomeration of the metal NPs resulted in rapid sedimentation of all particles. DLVO calculations supported these findings, showing the strong van der Waals forces of the metal NPs to result in significant NP agglomeration. Metal release from the metal NPs was slightly increased by increased sonication. The addition of a stabilizing agent (bovine serum albumin) had an accelerating effect on the release of metals in sonicated solutions. For Cu and Mn NPs, the extent of particle dissolution increased from <1.6 to ~5 % after sonication for 15 min. A prolonged sonication time (3-15 min) had negligible effects on the zeta potential of the studied NPs. In all, it is shown that it is of utmost importance to carefully investigate how sonication influences the physico-chemical properties of dispersed metal NPs. This should be considered in nanotoxicology investigations of metal NPs.

10 CFR 835.209 - Concentrations of radioactive material in air.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 835.209 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.209 Concentrations of radioactive material in air. (a) The derived air... exposures to airborne radioactive material. (b) The estimation of internal dose shall be based on bioassay...

ENHANCED RADIOACTIVE CONTENT OF 'BALANCE' BRACELETS.

PubMed

Tsroya, S; Pelled, O; Abraham, A; Kravchik, T; German, U

2016-09-01

During a routine whole body counting measurement of a worker at the Nuclear Research Center Negev, abnormal activities of (232)Th and (238)U were measured. After a thorough investigation, it was found that the radioactivity was due to a rubber bracelet ('balance bracelet') worn by the worker during the measurement. The bracelet was counted directly by an high pure germanium gamma spectrometry system, and the specific activities determined were 10.80 ± 1.37 Bq g(-1) for (232)Th and 5.68 ± 0.88 Bq g(-1) for natural uranium. These values are obviously high compared with normally occurring radioactive material (NORM) average values. The dose rate to the wrist surface was estimated to be ∼3.9 µGy h(-1) and ∼34 mGy for a whole year. The dose rate at the centre of the wrist was estimated to be ∼2.4 µGy h(-1) and ∼21 mGy for a whole year. The present findings stresses a more general issue, as synthetic rubber and silicone products are common and widely used, but their radioactivity content is mostly uncontrolled, thus causing unjustified exposure due to enhanced NORM radioactivity levels. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Measurement of the natural radioactivity in building materials used in Ankara and assessment of external doses.

PubMed

Turhan, S; Baykan, U N; Sen, K

2008-03-01

A total of 183 samples of 20 different commonly used structural and covering building materials were collected from housing and other building construction sites and from suppliers in Ankara to measure the natural radioactivity due to the presence of (226)Ra, (232)Th and (40)K. The measurements were carried out using gamma-ray spectrometry with two HPGe detectors. The specific activities of the different building materials studied varied from 0.5 +/- 0.1 to 144.9 +/- 4.9 Bq kg(-1), 0.6 +/- 0.2 to 169.9 +/- 6.6 Bq kg(-1) and 2.0 +/- 0.1 to 1792.3 +/- 60.8 Bq kg(-1) for (226)Ra, (232)Th and (40)K, respectively. The results show that the lowest mean values of the specific activity of (226)Ra, (232)Th and (40)K are 0.8 +/- 0.5, 0.9 +/- 0.4 and 4.1 +/- 1.4 Bq kg(-1), respectively, measured in travertine tile while the highest mean values of the specific activity of the same radionuclides are 78.5 +/- 18.1 (ceramic wall tile), 77.4 +/- 53.0 (granite tile) and 923.4 +/- 161.0 (white brick), respectively. The radium equivalent activity (Ra(eq)), the gamma-index, the indoor absorbed dose rate and the corresponding annual effective dose were evaluated to assess the potential radiological hazard associated with these building materials. The mean values of the gamma-index and the estimated annual effective dose due to external gamma radiation inside the room for structural building materials ranged from 0.15 to 0.89 and 0.2 to 1.1 mSv, respectively. Applying criteria recently recommended for building materials in the literature, four materials meet the exemption annual dose criterion of 0.3 mSv, five materials meet the annual dose limit of 1 mSv and only one material slightly exceeds this limit. The mean values of the gamma-index for all building materials were lower than the upper limit of 1.

Balanced propofol sedation administered by nonanesthesiologists: The first Italian experience

PubMed Central

Repici, Alessandro; Pagano, Nico; Hassan, Cesare; Carlino, Alessandra; Rando, Giacomo; Strangio, Giuseppe; Romeo, Fabio; Zullo, Angelo; Ferrara, Elisa; Vitetta, Eva; Ferreira, Daniel de Paula Pessoa; Danese, Silvio; Arosio, Massimo; Malesci, Alberto

2011-01-01

AIM: To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol, administered by non-anesthesiologists, in a large series of diagnostic colonoscopies. METHODS: Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam (0.05 mg/kg) and low-dose propofol (starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg). Induction time and deepest level of sedation, adverse and serious adverse events, as well as recovery times, were prospectively assessed. Cecal intubation and adenoma detection rates were also collected. RESULTS: Overall, 1593 eligible patients were included. The median dose of propofol administered was 70 mg (range: 40-120 mg), and the median dose of midazolam was 2.3 mg (range: 2-4 mg). Median induction time of sedation was 3 min (range: 1-4 min), and median recovery time was 23 min (range: 10-40 min). A moderate level of sedation was achieved in 1561 (98%) patients, whilst a deep sedation occurred in 32 (2%) cases. Transient oxygen desaturation requiring further oxygen supplementation occurred in 8 (0.46%; 95% CI: 0.2%-0.8%) patients. No serious adverse event was observed. Cecal intubation and adenoma detection rates were 93.5% and 23.4% (27.8% for male and 18.5% for female, subjects), respectively. CONCLUSION: A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy, resulting in a high safety profile for non-anesthesiologist propofol sedation. PMID:21987624

Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves.

PubMed

Brentnall, C; Cheng, Z; McKellar, Q A; Lees, P

2012-09-15

The pharmacodynamics (PD) of oxytetracycline was investigated against a strain of Mannheimia haemolytica. In vitro measurements, comprising minimum inhibitory concentration (MIC), minimum bactericidal concentration and time-kill curves, were conducted in five matrices; Mueller Hinton Broth (MHB), cation-adjusted MHB (CAMHB) and calf serum, exudate and transudate. MICs were much higher in the biological fluids than in MHB and CAMHB. Ratios of MIC were, serum: CAMHB 19 : 1; exudate:CAMHB 16.1; transudate:CAMHB 14 : 1. Ex vivo data, generated in the tissue cage model of inflammation, demonstrated that oxytetracycline, administered to calves intramuscularly at a dose rate of 20 mg/kg, did not inhibit the growth of M haemolytica in serum, exudate and transudate, even at peak concentration. However, using in vitro susceptibility in CAMHB and in vivo-determined pharmacokinetic (PK) variables, average and minimum oxytetracycline concentrations relative to MIC (C(av)/MIC and C(min)/MIC) predicted achievement of efficacy for approximately 48 hours after dosing. Similar C(av)/MIC and C(min)/MIC data were obtained when oxytetracycline was administered in the presence of carprofen. PK-PD integration of data for oxytetracycline, based on MICs determined in the three biological fluids, suggests that it possesses, at most, limited direct killing activity against M haemolytica. These data raise questions concerning the mechanism(s) of action of oxytetracycline, when administered at clinically recommended dose rates.

Establishment of the central radiation dose registration system for decontamination work involving radioactive fallout emitted by the Fukushima Daiichi APP accident.

PubMed

Yasui, Shojiro

2016-10-01

With respect to radiation protection for decontamination efforts involving radioactive fallout emitted by the accident at the Fukushima Daiichi Atomic Power Plant, new regulations were established and obligated employers to monitor, record, and store of workers' dose records, and to check their past dose records at the time of employment. However, cumulative doses may not be properly maintained if a worker declares incorrect values for past doses. In response, with facilitation from the Ministry of Health, Labour and Welfare, primary contractors of decontamination works decided to establish a central dose registration system. There are four major issues in the design of the system to be resolved, included the following: primary contractors (a) do not have a legal responsibility to perform dose control for subcontractors, (b) do not have the right to control decontamination sites, (c) often organize joint ventures, and (d) correspond to a wide range of ambient dose rates. To resolve the issues, requirements of the system included the following: (a) centralize the operation of radiation passbooks, which records past doses and the results of medical examinations to each worker; (b) develop a database system that could register all dose data and accept inquiry from primary contractors; (c) establish a permanent data storage system for transferred records; and (d) provide graded type of services that are appropriate to the risk of radiation exposure. The system started its operation in December 2013 and provided dose distributions in April and July 2015. The average yearly dose in 2014 was 0.7 mSv, which increased by 0.2 mSv from 0.5 mSv in 2012 and 2013. However, no cumulative dose from 2012-2014 exceeded 20 mSv, which was far below than the dose limits (100 mSv/5 years and 50 mSv/year). Although current dose distributions of decontamination workers were within appropriate levels, careful monitoring of dose distribution is necessary for preserving the proper

Natural soil gamma radioactivity levels and resultant population dose in the cities of Zacatecas and Guadalupe, Zacatecas, Mexico.

PubMed

Mireles, F; Dávila, J I; Quirino, L L; Lugo, J F; Pinedo, J L; Ríos, C

2003-03-01

The study of natural gamma radioactivity was made to determine the concentrations of natural radionuclides in soil. Twenty soil samples collected in the cities of Zacatecas and Guadalupe and their suburban areas in the Mexican state of Zacatecas were analyzed by gamma-ray spectrometry to determine the activity concentrations of 226Ra, 232Th, and 40K. Gamma-spectrometry measurements were made using a hyperpure germanium detector surrounded with shielding material to reduce the background counting rate. The GammaVision-32 MCA emulation software was used for gamma-ray spectrum analysis and the TRUMP card of 2k as a MCA emulator. Conversion factors were used to calculate the dose to the population from outdoor exposure to terrestrial gamma rays. The measured activity concentration of 226Ra varies from 11 to 38 Bq kg(-1), the activity concentration of 232Th varies from 8 to 38 Bq kg(-1). The activity concentration of 40K is in the range 309-1,049 Bq kg(-1). The overall population mean outdoor terrestrial gamma dose rate is 44.94 nGy h(-1).

SU-E-T-750: Three Dimensional in Silico Study of Brachytherapy Application with In-Situ Dose-Painting Administered Via Gold-Nanoparticle Eluters

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

Sinha, N; Cifter, G; Ngwa, W

Purpose: Brachytherapy Application with in-situ Dose-painting Administered via Gold-Nanoparticle Eluters (BANDAGE) has been proposed as a new therapeutic strategy for radiation boosting of high-risk prostate tumor subvolume while minimizing dose to neighboring organs-at-risk. In a previous study the one-dimensional dose-painting with gold nanoparticles (GNP) released from GNP-loaded brachytherapy spacers was investigated. The current study investigates BANDAGE in three-dimensions. Methods: To simulate GNPs transport in prostrate tumors, a three dimensional, cylindrically symmetric transport model was generated using a finite element method (FEM). A mathematical model of Gold nanoparticle (GNPs) transport provides a useful strategy to optimize potential treatment planning for BANDAGE.more » Here, treatment of tumors with a radius of 2.5 cm was simulated in 3-D. This simulation phase considered one gold based cylindrical spacer (GBS of size 5mm × 0.8 mm) introduced at the center of the spherical tumor with initial concentration of 100 mg/g or 508 mol/m3 of GNP. Finite element mesh is used to stimulate the GNP transport. Gold concentrations within the tumor were obtained using a 3-D FEM solution implemented by COMSOL. Results: The analysis shows the spread of the GNPs through-out the tumor with the increase of concentration towards the periphery with time. The analysis also shows the concentration profiles and corresponding dose enhancement factors (dose boost factor) as a function of GNP size. Conclusion: This study demonstrates the use of computational modeling and optimal parameter estimation to predict local GNPs from central implant as a function of x, y and z axis . Such a study provides a useful reference for ongoing translational studies for the BANDAGE approach.« less

Even 'safe' medications need to be administered with care.

PubMed

Lutwak, Nancy; Howland, Mary Ann; Gambetta, Rosemarie; Dill, Curt

2013-01-02

A 60-year-old man with a history of hepatic cirrhosis and cardiomyopathy underwent transoesophageal echocardiogram. He received mild sedation and topical lidocaine. During the recovery period the patient developed ataxia and diplopia for about 30 mins, a result of lidocaine toxicity. The patient was administered a commonly used local anaesthetic, a combination of 2% viscous lidocaine, 4% lidocaine gargle and 5% lidocaine ointment topically to the oropharnyx. The total dose was at least 280 mg. Oral lidocaine undergoes extensive first pass metabolism and its clearance is quite dependent on rates of liver blood flow as well as other factors. The patient's central nervous system symptoms were mild and transient but remind us that to avoid adverse side effects, orally administered drugs with fairly high hepatic extraction ratio given to patients with chronic liver disease need to be given in reduced dosages. Even 'Safe' medications need to be carefully administered.

In vitro Dosimetric Study of Biliary Stent Loaded with Radioactive 125I Seeds

PubMed Central

Yao, Li-Hong; Wang, Jun-Jie; Shang, Charles; Jiang, Ping; Lin, Lei; Sun, Hai-Tao; Liu, Lu; Liu, Hao; He, Di; Yang, Rui-Jie

2017-01-01

Background: A novel radioactive 125I seed-loaded biliary stent has been used for patients with malignant biliary obstruction. However, the dosimetric characteristics of the stents remain unclear. Therefore, we aimed to describe the dosimetry of the stents of different lengths — with different number as well as activities of 125I seeds. Methods: The radiation dosimetry of three representative radioactive stent models was evaluated using a treatment planning system (TPS), thermoluminescent dosimeter (TLD) measurements, and Monte Carlo (MC) simulations. In the process of TPS calculation and TLD measurement, two different water-equivalent phantoms were designed to obtain cumulative radial dose distribution. Calibration procedures using TLD in the designed phantom were also conducted. MC simulations were performed using the Monte Carlo N-Particle eXtended version 2.5 general purpose code to calculate the radioactive stent's three-dimensional dose rate distribution in liquid water. Analysis of covariance was used to examine the factors influencing radial dose distribution of the radioactive stent. Results: The maximum reduction in cumulative radial dose was 26% when the seed activity changed from 0.5 mCi to 0.4 mCi for the same length of radioactive stents. The TLD's dose response in the range of 0–10 mGy irradiation by 137Cs γ-ray was linear: y = 182225x − 6651.9 (R2= 0.99152; y is the irradiation dose in mGy, x is the TLDs’ reading in nC). When TLDs were irradiated by different energy radiation sources to a dose of 1 mGy, reading of TLDs was different. Doses at a distance of 0.1 cm from the three stents’ surface simulated by MC were 79, 93, and 97 Gy. Conclusions: TPS calculation, TLD measurement, and MC simulation were performed and were found to be in good agreement. Although the whole experiment was conducted in water-equivalent phantom, data in our evaluation may provide a theoretical basis for dosimetry for the clinical application. PMID:28469106

Safety of DTaP-IPV/Hib vaccine administered routinely to infants and toddlers.

PubMed

Hansen, John; Timbol, Julius; Lewis, Ned; Pool, Vitali; Decker, Michael D; Greenberg, David P; Klein, Nicola P

2016-07-29

The combination DTaP-IPV/Hib vaccine was licensed in the United States in 2008 for children ages 6weeks through 4years with doses administered at 2, 4, 6, and 15-18months of age. The aim of this study was to assess the safety of DTaP-IPV/Hib vaccine routinely administered as part of clinical care to infants at Kaiser Permanente Northern California. This was an observational, retrospective study that included all 2-month-old infants vaccinated with either DTaP-IPV/Hib or another DTaP-containing vaccine. We monitored all subjects for non-elective hospitalizations, emergency department visits and selected outpatient outcomes (seizures, Guillain-Barré Syndrome, encephalopathy, encephalitis, alteration of consciousness, meningitis, hypersensitivity reactions, immune thrombocytopenic purpura, hemolytic anemia, type 1 diabetes, and Kawasaki disease) beginning with their first dose through 6months after a 4th dose or until 24months of age. We calculated incidence rate ratios (IRRs) in the primary analysis by comparing rates of outcomes during the post-vaccination risk interval with rates during a comparison interval more remote from vaccination. Secondary analyses compared outcomes after DTaP-IPV/Hib with those after other DTaP-containing vaccines. We reviewed the medical records of selected outcomes. From October 1, 2008 through July 31, 2010, 14,042 subjects received a first dose of DTaP-IPV/Hib, 13,194 received 2 doses, 12,548 received 3 doses and 6702 received 4 doses. Overall, there were 166 comparisons with significantly elevated IRRs and 165 comparisons with significantly reduced IRRs. Medical record review of outcomes with significantly elevated IRRs in both the primary and secondary analyses did not suggest any relationship with DTaP-IPV/Hib. This study did not detect any safety concerns following DTaP-IPV/Hib and provides reassurance that DTaP-IPV/Hib administered as part of routine care was not associated with unexpected safety risks. Clinical

SU-E-T-13: Comparison of Dose Rates with and without Gold Backing of USC #9 Radioactive Eye Plaque Using MCNP5.

PubMed

Aryal, P; Molloy, J

2012-06-01

To show the effect of gold backing on dose rates for the USC #9 radioactive eye plaque. An I125 source (IsoAid model IAI-125A) and gold backing was modeled using MCNP5 Monte Carlo code. A single iodine seed was simulated with and without gold backing. Dose rates were calculated in two orthogonal planes. Dose calculation points were structured in two orthogonal planes that bisect the center of the source. A 2×2 cm matrix of spherical points of radius 0.2 mm was created in a water phantom of 10 cm radius. 0.2 billion particle histories were tracked. Dose differences with and without the gold backing were analyzed using Matlab. The gold backing produced a 3% increase in the dose rate near the source surface (<1mm) relative to that without the backing. This was presumably caused by fluorescent photons from the gold. At distances between 1 and 2 cm, the gold backing reduced the dose rate by up to 12%, which we attribute to a lack of scatter resulting from the attenuation from the gold. Dose differences were most pronounced in the radial direction near the source center but off axis. The dose decreased by 25%, 65% and 81% at 1, 2, and 3 mm off axis at a distance of 1 mm from the source surface. These effects were less pronounced in the perpendicular dimension near the source tip, where maximum dose decreases of 2% were noted. I 125 sources embedded directly into gold troughs display dose differences of 2 - 90%, relative to doses without the gold backing. This is relevant for certain types of plaques used in treatment of ocular melanoma. Large dose reductions can be observed and may have implications for scleral dose reduction. © 2012 American Association of Physicists in Medicine.

Imaging plant leaves to determine changes in radioactive contamination status in Fukushima, Japan.

PubMed

Nakajima, Hiroo; Fujiwara, Mamoru; Tanihata, Isao; Saito, Tadashi; Matsuda, Norihiro; Todo, Takeshi

2014-05-01

The chemical composition of plant leaves often reflects environmental contamination. The authors analyzed images of plant leaves to investigate the regional radioactivity ecology resulting from the 2011 accident at the Fukushima No. 1 nuclear power plant, Japan. The present study is not an evaluation of the macro radiation dose per weight, which has been performed previously, but rather an image analysis of the radioactive dose per leaf, allowing the capture of various gradual changes in radioactive contamination as a function of elapsed time. In addition, the leaf analysis method has potential applications in the decontamination of food plants or other materials.

Radioactive Iodine Treatment for Hyperthyroidism

MedlinePlus

... other parts of the body. RAI, also called iodine 131 (I-131), is given as a single-dose capsule or liquid. Most often, you will not need a hospital stay. It can take 6 to ... Know? Radioactive iodine is a generally safe treatment that can cure ...

A lifetime cancer bioassay of quinacrine administered into the uterine horns of female rats.

PubMed

Cancel, Aida M; Dillberger, John E; Kelly, Catherine M; Bolte, Henry F; Creasy, Dianne M; Sokal, David C

2010-03-01

This study investigated if quinacrine can induce a tumorigenic response in rats when administered in a manner similar to the intended human use for female non-surgical sterilization. Young sexually mature female rats received two doses of quinacrine (or 1% methylcellulose control) into each uterine horn approximately 21 days apart, and were observed for 23 months after the second dose administration. Dose levels were 0/0, 0/0, 10/10, 70/70, and 70/250-350 mg/kg (first dose/second dose), which represent local doses in the uterus at approximate multiples of 1x, 8x and 40x the human dose (mg quinacrine/g uterine weight) used for female non-surgical sterilization. Rats were observed for viability, clinical signs of toxicity, and changes in body weight and food consumption. At necropsy, selected organs were weighed, macroscopic observations were recorded, and tissues were collected, fixed, processed, and examined for microscopic pathologic findings. Acute quinacrine toxicity was evident during the dosing period but did not affect long-term survival. Non-neoplastic findings were more common in treated animals than controls, providing evidence of the appropriateness of the bioassay. The incidence of uncommon tumors of the reproductive tract was similar to controls at doses of 10/10mg/kg but increased with dose level and was significantly greater than controls at >or=70/70 mg/kg. We conclude that two doses of quinacrine administered approximately 21 days apart into the uterus of young sexually mature rats at a local dose approximately 8 times the human dose used for non-surgical female sterilization increased the lifetime risk of tumor development in the reproductive tract. (c) 2009 Elsevier Inc. All rights reserved.

Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels

PubMed Central

Perez, Ana Paula; Mundiña-Weilenmann, Cecilia; Romero, Eder Lilia; Morilla, Maria Jose

2012-01-01

Background Molecules taken up by olfactory and trigeminal nerve neurons directly access the brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels would increase the residence time of intranasal material, favoring the nose-to-brain delivery. In this first approach, brain radioactivity after intranasal administration of 32P-small interference RNA (siRNA) complexed with poly(amidoamine) G7 dendrimers (siRNA dendriplexes) within in situ-forming mucoadhesive gels, was determined. Materials 32P-siRNA dendriplexes were incorporated into in situ-forming mucoadhesive gels prepared by blending thermosensitive poloxamer (23% w/w) with mucoadhesive chitosan (1% w/w, PxChi) or carbopol (0.25% w/w, PxBCP). Rheological properties, radiolabel release profile, and local toxicity in rat nasal mucosa were determined. The best-suited formulation was intranasally administered to rats, and blood absorption and brain distribution of radioactivity were measured. Results The gelation temperature of both formulations was 23°C. The PxChi liquid showed non-Newtonian pseudoplastic behavior of high consistency and difficult manipulation, and the gel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a Newtonian behavior of low viscosity and easy manipulation, while in the gel phase showed apparent viscosity similar to that of the mucus but higher than that of aqueous solution. The gel released 35% of radiolabel and the released material showed silencing activity in vitro. Three intranasal doses of dendriplexes in PxCBP gel did not damage the rat nasal mucosa. A combination of 32P-siRNA complexation with dendrimers, incorporation of the dendriplexes into PxCBP gel, and administration of two intranasal doses was necessary to achieve higher brain radioactivity than that achieved by intravenous dendriplexes or intranasal naked siRNA. Conclusion The increased radioactivity within the olfactory bulb suggested that the combination above mentioned favored the

Mannan adjuvants intranasally administered inactivated influenza virus in mice rendering low doses inductive of strong serum IgG and IgA in the lung.

PubMed

Proudfoot, Owen; Esparon, Sandra; Tang, Choon-Kit; Laurie, Karen; Barr, Ian; Pietersz, Geoffrey

2015-02-26

H1N1 influenza viruses mutate rapidly, rendering vaccines developed in any given year relatively ineffective in subsequent years. Thus it is necessary to generate new vaccines every year, but this is time-consuming and resource-intensive. Should a highly virulent influenza strain capable of human-to-human transmission emerge, these factors will severely limit the number of people that can be effectively immunised against that strain in time to prevent a pandemic. An adjuvant and mode of administration capable of rendering ordinarily unprotective vaccine doses protective would thus be highly advantageous. The carbohydrate mannan was conjugated to whole inactivated H1N1 influenza virus at a range of ratios, and mixed with it at a range of ratios, and various doses of the resulting preparations were administered to mice via the intranasal (IN) route. Serum immunity was assessed via antigen-specific IgG ELISA and the haemagglutination-inhibition (HI) assay, and mucosal immunity was assessed via IgA ELISA of bronchio-alveolar lavages. IN-administered inactivated H1N1 mixed with mannan induced higher serum IgG and respiratory-tract IgA than inactivated H1N1 conjugated to mannan, and HIN1 alone. Adjuvantation was mannan-dose-dependent, with 100 μg of mannan adjuvanting 1 μg of H1N1 more effectively than 10 or 50 μg of mannan. Serum samples from mice immunised with 1 μg H1N1 adjuvanted with 10 μg mannan did not inhibit agglutination of red blood cells (RBCs) at a dilution factor of 10 in the HI assay, but samples resulting from adjuvantation with 50 and 100 μg mannan inhibited agglutination at dilution factors of ≥ 40. Both serum IgG1 and IgG2a were induced by IN mannan-adjuvanted H1N1 vaccination, suggesting the induction of humoral and cellular immunity. Mixing 100 μg of mannan with 1 μg of inactivated H1N1 adjuvanted the vaccine in mice, such that IN immunisation induced higher serum IgG and respiratory tract IgA than immunisation with virus alone. The

Radiation doses to critical groups since the early 1950s due to discharges of liquid radioactive waste from Sellafield.

PubMed

Hunt, G J

1997-04-01

First, some of the early work is reviewed on exposure pathways in connection with proposed and early liquid radioactive waste discharges from Sellafield. The main historical features of these discharges, affected by relevant plant operations, are then briefly described. The important radiological exposure pathways resulting from the discharges and people's consumption and occupancy habits are considered. To place the changing scenario onto a consistent basis using present-day methodology, a reconstruction of exposures has been carried out using environmental monitoring data and models. The three major pathways are examined of Porphyra/laverbread consumption in South Wales, fish and shellfish consumption near Sellafield, and external exposure over local and more distant sediments. The results show that over the period 1952 to about 1970 the laverbread pathway was probably critical, taking a cautious approach. Effective dose rates fluctuated at around 1 mSv y(-1) from about 1956 to 1971. From about 1970 to 1985, the fish and shellfish pathway was likely to have been critical, with effective dose rates peaking at about 2 mSv y(-1) in 1975-1976. External exposure was likely to have been of lesser importance than the other two pathways until about 1985, when with the retention of previously-released radiocesium on sediments it has become dominant. This phenomenon applies particularly further afield where radiocesium concentrations have been slower to decline; in the Ribble estuary, houseboat dwellers have been the critical group from about 1985. Effective doses have been at about 0.3 mSv y(-1) and declining; they are due to the effects of radiocesium discharges in earlier years. Dose rates have remained within contemporary ICRP dose limits.

Radioactivity of spent TRIGA fuel

NASA Astrophysics Data System (ADS)

Usang, M. D.; Nabil, A. R. A.; Alfred, S. L.; Hamzah, N. S.; Abi, M. J. B.; Rawi, M. Z. M.; Abu, M. P.

2015-04-01

Some of the oldest TRIGA fuel in the Malaysian Reaktor TRIGA PUSPATI (RTP) is approaching the limit of its end of life with burn-up of around 20%. Hence it is prudent for us to start planning on the replacement of the fuel in the reactor and other derivative activities associated with it. In this regard, we need to understand all of the risk associated with such operation and one of them is to predict the radioactivity of the fuel, so as to estimate the safety of our working conditions. The radioactivity of several fuels are measured and compared with simulation results to confirm the burnup levels of the selected fuels. The radioactivity measurement are conducted inside the water tank to reduce the risk of exposure and in this case the detector wrapped in plastics are lowered under water. In nuclear power plant, the general practice was to continuously burn the fuel. In research reactor, most operations are based on the immediate needs of the reactor and our RTP for example operate periodically. By integrating the burnup contribution for each core configuration, we simplify the simulation of burn up for each core configuration. Our results for two (2) fuel however indicates that the dose from simulation underestimate the actual dose from our measurements. Several postulates are investigated but the underlying reason remain inconclusive.

Four-year antibody persistence and response to a booster dose of a pentavalent MenABCWY vaccine administered to healthy adolescents and young adults

PubMed Central

Sáez-Llorens, Xavier; Beltran-Rodriguez, Johnny; Novoa Pizarro, Jose M.; Mensi, Ilhem; Keshavan, Pavitra; Toneatto, Daniela

2018-01-01

ABSTRACT This open-label, multicenter extension study (NCT02451514) assessed persistence of Neisseria meningitidis serogroups ABCWY antibodies 4 years after primary vaccination. Adolescents and young adults who previously received 2 doses of MenABCWY+OMV (Group III), 1 dose of MenACWY-CRM (Group VI), or newly-recruited vaccine-naïve participants (Group VII) were administered 1 (Group III) or 2 doses (Groups VI and VII) of MenABCWY+OMV, 1 month apart. Immunogenicity was assessed by human serum bactericidal assay (hSBA). Safety and reactogenicity were also evaluated. Percentages of participants with hSBA titers ≥8 (serogroups ACWY), ≥5 (serogroup B) and hSBA geometric mean titers (GMTs) were evaluated in all 129 enrolled participants (Group III: 33; Group VI: 46; Group VII: 50). Anti-ACWY antibody concentrations waned over 4 years post-vaccination, but remained above pre-vaccination concentrations. Similarly, levels of antibodies against serogroup B test strains also waned over 4 years post-vaccination, but remained above pre-vaccination concentrations for some strains. MenABCWY+OMV booster induced a robust anamnestic anti-ACWY response in Group III and VI and a good response against serogroup B test strains (≥82%) in Group III. In serogroup B-naïve participants (Groups VI and VII), anti-B responses to 2 doses of MenABCWY+OMV were less homogenous and lower than in Group III. MenABCWY+OMV was reactogenic, but well-tolerated. No safety concerns were identified. These findings indicate that although antibodies against N. meningitidis serogroups ABCWY waned over 4 years post-vaccination, exposure to a MenABCWY+OMV booster dose elicits an anamnestic response in adolescents previously exposed to the same or another multivalent meningococcal vaccine. PMID:29601256

Issues of natural radioactivity in phosphates

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

Schnug, E.; Haneklaus, S.; Schnier, C.

1996-12-31

The fertilization of phosphorus (P) fertilizers is essential in agricultural production, but phosphates contain in dependence on their origin different amounts of trace elements. The problem of cadmium (Cd) loads and other heavy metals is well known. However, only a limited number of investigations examined the contamination of phosphates with the two heaviest metals, uranium (U) and thorium (Th), which are radioactive. Also potassium (K) is lightly radioactive. Measurements are done n the radioactivity content of phosphates, P fertilizers and soils. The radiation doses to workers and public as well as possible contamination of soils from phosphate rock or fertilizermore » caused by these elements or their daughter products is of interest with regard to radiation protection. The use of P fertilizers is necessary for a sustainable agriculture, but it involves radioactive contamination of soils. The consequences of the use of P fertilizers is discussed, also with regard to existing and proposed legislation. 11 refs., 2 figs., 7 tabs.« less

Radioactive excretion in human milk following administration of /sup 99m/Tc macroaggregated albumin

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

Pittard, W.B.; Merkatz, R.; Fletcher, B.D.

Albumin-tagged sodium pertechnetate (technetium) is routinely used in nuclear medicine for scanning procedures of the lung. The rate of excretion of this radionuclide into breast milk and the resultant potential radiation hazard to the nursing infant have received little attention. Therefore the milk from a nursing mother who required a lung scan because of suspected pulmonary emboli using an intravenous injection of 4 mCi of /sup 99m/Tc macroaggregated human serum albumin was monitored. Albumin tagging severely limited the entrance of technetium into her milk and the radioactivity of the milk returned to base line by 24 hours. A total ofmore » 2.02 muCi of technetium was measured in the 24-hour milk collection after technetium injection and 94% of this amount was excreted by 15.5 hours. This amount of technetium administered orally to a newborn would deliver a total body radiation dose of .3 mrad. Therefore, an infant would receive trivial doses of radiation if breast-feeding were resumed 15.5 hours after administration of the radionuclide to the mother and nursing can clearly be resumed safely 24 hours after injection.« less

Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

2005-07-01

We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.

Phase I dose-escalation study of vinflunine hard capsules administered twice a day for 2 consecutive days every week in patients with advanced/metastatic solid tumors.

PubMed

Calvo, E; Vermorken, J B; Hiret, S; Rodon, J; Cortes, J; Senellart, H; Van den Brande, J; Dyck, J; Pétain, A; Ferre, P; Bennouna, J

2012-06-01

Vinflunine is a new microtubule inhibitor of the vinca-alkaloid family. It is marketed in transitional cell carcinoma of urothelial tract as a 20 min infusion given every 3 weeks in Europe. In this phase I study, vinflunine was administered to patients with advanced malignancies as hard capsules given twice a day on days 1-2 every week, with 3 weeks cycles. Serial blood samples were collected during the first cycle for pharmacokinetic investigations. Thirty-six patients (pts) were treated at 6 dose levels 150 (3 pts), 190 (3 pts), 230 (8 pts), 300 mg/day (6 pts) and then 250 (3 pts) and 270 mg/day (13 pts). The Maximal Tolerated Dose (MTD) was reached at 300 mg/day where 2 patients out of 6 experienced a dose limiting toxicity (febrile neutropenia with diarrhea). The lower dose level of 270 mg/day was the recommended dose (RD), the toxicity profile being mainly anaemia, neutropenia, fatigue and constipation. The pharmacokinetic analysis demonstrated the adequacy of the flat-fixed dosing regimen, as no correlation between clearance of vinflunine and body surface area was evidenced. Blood concentrations and exposure increased with dose, and a pharmacokinetic accumulation was observed, which is consistent with the terminal half-life of the compounds. The inter-individual exposure variability at the RD was 35%. Repeated weekly administration of oral vinflunine is feasible and exhibits a moderate inter-individual PK variability. The MTD was achieved at 300 mg/day given for 2 consecutive days. According to the protocol rules, the RD was established at 270 mg/day.

Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

PubMed

Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

2017-08-01

The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright �

Correlation-study about the ambient dose rate and the weather conditions

NASA Astrophysics Data System (ADS)

Furuya, Masato; Hatano, Yuko; Aoyama, Tomoo; Igarashi, Yasuhito; Kita, Kazuyuki; Ishizuka, Masahide

2016-04-01

The long-term radiation risks are believed to be heavily affected by the resuspension process. We therefore focus on the surface-atmosphere exchange process of released radioactive materials in this study. Radioactive materials were deposited on the soil and float in the air, and such complicated process are influenced by the weather conditions deeply. We need to reveal the correlation between the weather conditions and the ambient dose rate. In this study, we study the correlation between the weather conditions and the ambient dose rate with the correction of the decrease due to the radioactive decay. We found that there is a negative correlation between the ambient dose rate and the soil water content by the correlation coefficient. Using this result, we reconstruct the ambient dose rate from the weather conditions by the multiple regression analysis and found that the reconstructed data agree with the observation very well. Using Kalman filter, which can be sequentially updates the state estimate, we obtained such a good agreement.

Radioactivity concentrations in soils in the Qingdao area, China.

PubMed

Qu, Limei; Yao, De; Cong, Pifu; Xia, Ning

2008-10-01

The specific activity concentrations of radionuclides (238)U, (232)Th, and (40)K of 2300 sampling points in the Qingdao area were measured by an FD-3022 gamma-ray spectrometer. The radioactivity concentrations of (238)U, (232)Th, and (40)K ranged from 3.3 to 185.3, from 6.9 to 157.2, and from 115.8 to 7834.4 Bq kg(-1), respectively. The air-absorbed dose at 1 meter above ground, effective annual dose, external hazard index, and radium equivalent activity were also calculated to systematically evaluate the radiological hazards of the natural radioactivity in Qingdao. The air-absorbed dose, effective annual dose, external hazard index, and radium equivalent activity in the study area were 98.6 nGy h(-1), 0.12 mSv, 0.56, 197 Bq kg(-1), respectively. Compared with the worldwide value, the air-absorbed dose is slightly high, but the other factors are all lower than the recommended value. The natural external exposure will not pose significant radiological threat to the population. In conclusion, the Qingdao area is safe with regard to the radiological level and suitable for living.

Systemic Absorption of Rifamycin SV MMX Administered as Modified-Release Tablets in Healthy Volunteers▿

PubMed Central

Di Stefano, A. F. D.; Rusca, A.; Loprete, L.; Dröge, M. J.; Moro, L.; Assandri, A.

2011-01-01

The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single- and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single- and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (ΣXu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410 ± 0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed. PMID:21402860

Multidose pharmacokineetecs of orally administered florfenicol in channel catfish Ictalurus punctatus

USDA-ARS?s Scientific Manuscript database

Plasma disposition of florfenicol in channel catfish was investigated after an oral dose (10mg/kg for 10 days) administered in freshwater at water temperatures ranging from 24.7 to 25.9°C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. Af...

Phase I study of adenovirus p53 administered by bronchoalveolar lavage in patients with bronchioloalveolar cell lung carcinoma: ECOG 6597.

PubMed

Keedy, Vicki; Wang, Wei; Schiller, Joan; Chada, Sunil; Slovis, Bonnie; Coffee, Keith; Worrell, John; Thet, Lyn A; Johnson, David H; Carbone, David P

2008-09-01

This pilot phase I trial evaluated the safety and maximum-tolerated dose of p53 gene transfer using an adenovirus vector (Ad-p53) delivered via bronchoalveolar lavage (BAL) to patients with bronchioloalveolar lung carcinoma (BAC). Patients were initially administered two treatments of Ad-p53 to a single involved lobe, beginning at 2 x 10(9) viral particles (vp) per dose and escalated to a maximum of 2 x 10(12) vp. If a clinical benefit was seen and the treatment was well tolerated, additional doses could be administered to additional lobes. Twenty-five patients were treated at doses between 2 x 10(9) and 2 x 10(12) vp. At 2 x 10(12) vp, one patient experienced grade 4 pulmonary toxicity, and one patient died 25 days after his second cycle; therefore, a cohort of 10 patients was treated at the recommended phase II dose of 5 x 10(11) vp, with no grade 4 toxicity observed. The most frequent toxicities included low-grade fever, hypoxia, and dyspnea. Of the 23 assessable patients, 16 had stable disease as their best response. Subjective improvement in breathing was noted in eight patients. Limited distribution of vector was observed, with transient detection in patient sputum for 1 to 2 days after administration. Ad-p53 can be administered safely by BAL at 5 x 10(11) vp with repeated dosing. Stabilization of disease and symptomatic improvement may warrant further studies of Ad-p53 or other adenoviruses administered by BAL in patients with BAC.

Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation

PubMed Central

McCaffrey, Katherine A.; Jones, Brian; Mabrey, Natalie; Weiss, Bernard; Swan, Shanna H.; Patisaul, Heather B.

2013-01-01

Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000 mg/kg bw/day BPA through daily, noninvasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50 mg/kg/day can alter sex specific hypothalamic morphology in the rat. PMID:23500335

Natural radioactivity measurements in building materials used in Samsun, Turkey.

PubMed

Tufan, M Çagatay; Disci, Tugba

2013-01-01

In this study, radioactivity levels of 35 different samples of 11 commonly used building materials in Samsun were measured by using a gamma spectrometry system. The analysis carried out with the high purity Germanium gamma spectrometry system. Radioactivity concentrations of (226)Ra, (232)Th and (40)K range from 6 to 54 Bq kg(-1), 5 to 88 Bq kg(-1) and 6 to 1070 Bq kg(-1), respectively. From these results, radium equivalent activities, gamma indexes, absorbed dose rates and annual effective doses were calculated for all samples. Obtained results were compared with the available data, and it was concluded that all the investigated materials did not have radiological risk.

An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

NASA Astrophysics Data System (ADS)

Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

2015-04-01

Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

Evolution of radioactive dose rates in fresh sediment deposits along coastal rivers draining Fukushima contamination plume

PubMed Central

Evrard, Olivier; Chartin, Caroline; Onda, Yuichi; Patin, Jeremy; Lepage, Hugo; Lefèvre, Irène; Ayrault, Sophie; Ottlé, Catherine; Bonté, Philippe

2013-01-01

Measurement of radioactive dose rates in fine sediment that has recently deposited on channel bed-sand provides a solution to address the lack of continuous river monitoring in Fukushima Prefecture after Fukushima Dai-ichi nuclear power plant (FDNPP) accident. We show that coastal rivers of Eastern Fukushima Prefecture were rapidly supplied with sediment contaminated by radionuclides originating from inland mountain ranges, and that this contaminated material was partly exported by typhoons to the coastal plains as soon as by November 2011. This export was amplified during snowmelt and typhoons in 2012. In 2013, contamination levels measured in sediment found in the upper parts of the catchments were almost systematically lower than the ones measured in nearby soils, whereas their contamination was higher in the coastal plains. We thereby suggest that storage of contaminated sediment in reservoirs and in coastal sections of the river channels now represents the most crucial issue. PMID:24165695

Preclinical safety evaluation of intravenously administered mixed micelles.

PubMed

Teelmann, K; Schläppi, B; Schüpbach, M; Kistler, A

1984-01-01

Mixed micelles, with their main constituents lecithin and glycocholic acid, form a new principle for the parenteral administration of compounds which are poorly water-soluble. Their composition of mainly physiological substances as well as their comparatively good stability substantiate their attractivity in comparison to existing solvents. A decomposition due to physical influences such as heat or storage for several years will almost exclusively affect the lecithin component in the form of hydrolysis into free fatty acids and lysolecithin. Their toxicity was examined experimentally in various studies using both undecomposed and artificially decomposed mixed micelles. In these studies the mixed micelles were locally and systemically well tolerated and proved to be neither embryotoxic, teratogenic nor mutagenic. Only when comparatively high doses of the undecomposed mixed micelles were administered, corresponding to approximately 30 to 50 times the anticipated clinical injection volume (of e.g. diazepam mixed micelles), did some vomitus (dogs), slight liver enzyme elevation (rats and dogs), and slightly increased liver weights (dogs) occur. After repeated injections of the artificially decomposed formulation (approximately 25% of lecithin hydrolyzed to free fatty acids and lysolecithin) effects such as intravascular haemolysis, liver enzyme elevations and intrahepatic cholestasis (dogs only) were observed but only when doses exceeding a threshold of approximately 40 to 60 mg lysolecithin/kg body weight were administered. All alterations were reversible after cessation of treatment.

Disposition, metabolism and mass balance of delafloxacin in healthy human volunteers following intravenous administration.

PubMed

McEwen, Andrew; Lawrence, Laura; Hoover, Randy; Stevens, Lloyd; Mair, Stuart; Ford, Gill; Williams, Dylan; Wood, Stuart

2015-01-01

1. The pharmacokinetics and disposition of delafloxacin was investigated following a single intravenous (300 mg, 100 µCi) dose to healthy male subjects. 2. Mean Cmax, AUC0-∞, Tmax and t1/2 values for delafloxacin were 8.98 µg/mL, 21.31 µg h/mL, 1 h and 2.35 h, respectively, after intravenous dosing. 3. Radioactivity was predominantly excreted via the kidney with 66% of the radioactive dose recovered in the urine. Approximately 29% of the radioactivity was recovered in the faeces, giving an overall mean recovery of 94% administered radioactivity. 4. The predominant circulating components were identified as delafloxacin and a direct glucuronide conjugate of delafloxacin.

In vivo dose verification method in catheter based high dose rate brachytherapy.

PubMed

Jaselskė, Evelina; Adlienė, Diana; Rudžianskas, Viktoras; Urbonavičius, Benas Gabrielis; Inčiūra, Arturas

2017-12-01

In vivo dosimetry is a powerful tool for dose verification in radiotherapy. Its application in high dose rate (HDR) brachytherapy is usually limited to the estimation of gross errors, due to inability of the dosimetry system/ method to record non-uniform dose distribution in steep dose gradient fields close to the radioactive source. In vivo dose verification in interstitial catheter based HDR brachytherapy is crucial since the treatment is performed inserting radioactive source at the certain positions within the catheters that are pre-implanted into the tumour. We propose in vivo dose verification method for this type of brachytherapy treatment which is based on the comparison between experimentally measured and theoretical dose values calculated at well-defined locations corresponding dosemeter positions in the catheter. Dose measurements were performed using TLD 100-H rods (6 mm long, 1 mm diameter) inserted in a certain sequences into additionally pre-implanted dosimetry catheter. The adjustment of dosemeter positioning in the catheter was performed using reconstructed CT scans of patient with pre-implanted catheters. Doses to three Head&Neck and one Breast cancer patient have been measured during several randomly selected treatment fractions. It was found that the average experimental dose error varied from 4.02% to 12.93% during independent in vivo dosimetry control measurements for selected Head&Neck cancer patients and from 7.17% to 8.63% - for Breast cancer patient. Average experimental dose error was below the AAPM recommended margin of 20% and did not exceed the measurement uncertainty of 17.87% estimated for this type of dosemeters. Tendency of slightly increasing average dose error was observed in every following treatment fraction of the same patient. It was linked to the changes of theoretically estimated dosemeter positions due to the possible patient's organ movement between different treatment fractions, since catheter reconstruction was

Propofol dose and incidence of dreaming during sedation.

PubMed

Eer, Audrey Singyi; Padmanabhan, Usha; Leslie, Kate

2009-10-01

Dreaming is commonly reported after propofol-based sedation. We measured the incidence of dreaming and bispectral index (BIS) values in colonoscopy patients sedated with combinations of propofol, midazolam and fentanyl. Two hundred patients presenting for elective outpatient colonoscopy were sedated with combinations of propofol, midazolam and fentanyl. BIS was monitored throughout the procedure. Patients were interviewed immediately after they emerged from sedation. The primary end point was a report of dreaming during sedation. Ninety-seven patients were administered propofol alone, 44 were administered propofol and fentanyl, 16 were administered propofol and midazolam and 43 were administered propofol, midazolam and fentanyl. Dreaming was reported by 19% of patients. Dreamers received higher doses of propofol and had lower BIS values during sedation. Age of 50 years or less, preoperative quality of recovery score of less than 14, higher home dream recall, propofol dose of more than 300 mg and time to Observers' Assessment of Alertness/Sedation score equalling 5 of 8 min or less were independent predictors of dreaming. Dreaming during sedation is associated with higher propofol dose and lower BIS values.

Fast radioactive seed localization in intraoperative cone beam CT for low-dose-rate prostate brachytherapy

NASA Astrophysics Data System (ADS)

Hu, Yu-chi; Xiong, Jian-ping; Cohan, Gilad; Zaider, Marco; Mageras, Gig; Zelefsky, Michael

2013-03-01

A fast knowledge-based radioactive seed localization method for brachytherapy was developed to automatically localize radioactive seeds in an intraoperative volumetric cone beam CT (CBCT) so that corrections, if needed, can be made during prostate implant surgery. A transrectal ultrasound (TRUS) scan is acquired for intraoperative treatment planning. Planned seed positions are transferred to intraoperative CBCT following TRUS-to-CBCT registration using a reference CBCT scan of the TRUS probe as a template, in which the probe and its external fiducial markers are pre-segmented and their positions in TRUS are known. The transferred planned seeds and probe serve as an atlas to reduce the search space in CBCT. Candidate seed voxels are identified based on image intensity. Regions are grown from candidate voxels and overlay regions are merged. Region volume and intensity variance is checked against known seed volume and intensity profile. Regions meeting the above criteria are flagged as detected seeds; otherwise they are flagged as likely seeds and sorted by a score that is based on volume, intensity profile and distance to the closest planned seed. A graphical interface allows users to review and accept or reject likely seeds. Likely seeds with approximately twice the seed volume are automatically split. Five clinical cases are tested. Without any manual correction in seed detection, the method performed the localization in 5 seconds (excluding registration time) for a CBCT scan with 512×512×192 voxels. The average precision rate per case is 99% and the recall rate is 96% for a total of 416 seeds. All false negative seeds are found with 15 in likely seeds and 1 included in a detected seed. With the new method, updating of calculations of dose distribution during the procedure is possible and thus facilitating evaluation and improvement of treatment quality.

Even ‘safe’ medications need to be administered with care

PubMed Central

Lutwak, Nancy; Howland, Mary Ann; Gambetta, Rosemarie; Dill, Curt

2013-01-01

A 60-year-old man with a history of hepatic cirrhosis and cardiomyopathy underwent transoesophageal echocardiogram. He received mild sedation and topical lidocaine. During the recovery period the patient developed ataxia and diplopia for about 30 mins, a result of lidocaine toxicity. The patient was administered a commonly used local anaesthetic, a combination of 2% viscous lidocaine, 4% lidocaine gargle and 5% lidocaine ointment topically to the oropharnyx. The total dose was at least 280 mg. Oral lidocaine undergoes extensive first pass metabolism and its clearance is quite dependent on rates of liver blood flow as well as other factors. The patient's central nervous system symptoms were mild and transient but remind us that to avoid adverse side effects, orally administered drugs with fairly high hepatic extraction ratio given to patients with chronic liver disease need to be given in reduced dosages. Even ‘Safe’ medications need to be carefully administered. PMID:23283606

Safe Handling of Radioactive Materials. Recommendations of the National Committee on Radiation Protection. Handbook 92.

ERIC Educational Resources Information Center

National Bureau of Standards (DOC), Washington, DC.

This handbook is designed to help users of radioactive materials to handle the radioactive material without exposing themselves or others to radiation doses in excess of maximum permissible limits. The discussion of radiation levels is in terms of readings from dosimeters and survey instruments. Safety in the handling of radioactive materials in…

In vivo TLD dose measurements in catheter-based high-dose-rate brachytherapy.

PubMed

Adlienė, Diana; Jakštas, Karolis; Urbonavičius, Benas Gabrielis

2015-07-01

Routine in vivo dosimetry is well established in external beam radiotherapy; however, it is restricted mainly to detection of gross errors in high-dose-rate (HDR) brachytherapy due to complicated measurements in the field of steep dose gradients in the vicinity of radioactive source and high uncertainties. The results of in vivo dose measurements using TLD 100 mini rods and TLD 'pin worms' in catheter-based HDR brachytherapy are provided in this paper alongside with their comparison with corresponding dose values obtained using calculation algorithm of the treatment planning system. Possibility to perform independent verification of treatment delivery in HDR brachytherapy using TLDs is discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Safety of an ED High-Dose Opioid Protocol for Sickle Cell Disease Pain.

PubMed

Tanabe, Paula; Martinovich, Zoran; Buckley, Barbara; Schmelzer, Annie; Paice, Judith A

2015-05-01

A nurse-initiated high dose, opioid protocol for vaso-occlusive crisis (VOC) was implemented. Total intravenous morphine sulfate equivalents (IVMSE) in mgs] and safety was evaluated. A medical record review was conducted for all ED visits in adult patients with VOC post protocol implementation. Opioids doses and routes administered during the ED stay, and six hours into the hospital admission were abstracted and total IVMSE administered calculated. Oxygen saturation (SPO2), respiratory rate (RR), administration of naloxone or vasoactive medications, evidence of respiratory arrest, or any other types of resuscitation effort were abstracted. A RR of <10 or SPO2 <92% were coded as abnormal. Descriptive statistics report the total dose. Logistic regression was used to predict abnormal events. Predictors were age, gender, ED dose (10 mg increments) administered, and time from 1st dose to discharge from ED. 72 patients, 603 visits, 276 admitted. The total (ED & hospital dose) mean (95% CI) mg IVMSE administered for all visits was 93 mg (CI 86, 100), ED visit 63 mg (CI 59, 67) and hospital 66 mg (CI 59, 72). The mean (SD) time from administration of 1st analgesic dose to discharge from the ED was 203 (143) minutes, (range = 30-1396 minutes). During two visits, patients experienced a RR <10; while 61 visits were associated with a SPO2 <92%. No medications were administered, or resuscitative measures required. Controlling for demographics and evaluated at the average total ED dose, the longer patients were in the ED, patients were 1.359 times more likely to experience an abnormal vital sign. Controlling for demographics and evaluated at the average total time in the ED, for every 10 mg increase in IVMSE, patients were 1.057 times more likely to experience an abnormal vital sign. The effect of ED dose on the odds of experiencing an abnormal vital sign decreased by a multiplicative factor of 0.0970 for every 1 hour increase in time until discharge. The larger the dose

Studies of Inhibition of Intestinal Absorption of Radioactive Strontium

PubMed Central

Skoryna, Stanley C.; Paul, T. M.; Waldron-Edward, Deirdre

1965-01-01

A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, allowing calcium to be available to the body. Studies were carried out on the inhibitory effect of various amounts of sodium alginate and the dose-response relationship of Sr89 and bone uptake. The results obtained indicated that under laboratory conditions sodium alginate effectively reduces Sr89 uptake in a constant proportion. This effect was observed at the three levels of administration of 1.4%, 12% and 24% of sodium alginate. The linear relationship between the dosage of the radioisotope and the bone uptake in the presence of sodium alginate suggests that the same proportion is maintained at the lower levels of intake of radioactive strontium. Previous studies with small constant doses of sodium alginate were extended in rats to a period corresponding approximately to three years of human life span. Low doses were sufficient to reduce appreciably bone uptake of radiostrontium. PMID:14341649

Serum thyroxine concentrations after radioactive iodine therapy in cats with hyperthyroidism

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

Meric, S.M.; Hawkins, E.C.; Washabau, R.J.

Thirty-one cats with hyperthyroidism were given one dose of radioactive iodine (131I) IV. Serum thyroxine (T4) concentrations were measured before treatment in all cats, at 12-hour intervals after treatment in 10 cats, and at 48-hour intervals after treatment in 21 cats. Serum T4 concentrations also were measured one month after /sup 131/I therapy in 29 cats. Activity of 131I administered was 1.5 to 6.13 mCi, resulting in a dose of 20,000 rads to the thyroid. Serum T4 concentrations before /sup 131/I administration were 5.3 to 51.0 micrograms/dl, with a median T4 concentration of 11.0 micrograms/dl. Serum T4 decreased most rapidlymore » during the first 3 to 6 days after treatment. Sixteen cats (55%) had normal serum thyroxine concentrations by day 4 after 131I administration, and 23 cats (74%) were euthyroxinemic by day 8 after treatment. One month after administration of 131I, the 29 cats evaluated were clinically improved, and 24 (83%) of the 29 cats evaluated had normal serum T4 concentrations, 3 cats (10%) remained hyperthyroxinemic, and 2 cats (7%) were hypothyroxinemic. Therefore, administration of 131I was a safe and effective method to quickly decrease serum T4 concentrations in hyperthyroid cats.« less

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

PubMed

Cosgrave, David; Galligan, Marie; Soukhin, Era; McMullan, Victoria; McGuinness, Siobhan; Puttappa, Anand; Conlon, Niamh; Boylan, John; Hussain, Rabia; Doran, Peter; Nichol, Alistair

2017-12-29

Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety

Combination Effects of Forty Carcinogens Administered at Low Doses to Male Rats

PubMed Central

Takayama, Shozo; Hasegawa, Hirokazu; Ohgaki, Hiroko

1989-01-01

An investigation was conducted to determine whether a mixture of low doses of forty carcinogens that target different organs, including the liver, intestine, thyroid, urinary bladder, and skin, is effective for tumor induction in F344/DuCrj rats. The dose of each carcinogen in the diet was 1/50 of the TD50 value, treatment being continued for 102 weeks. Significant numbers of neoplastic nodules of the liver and follicular cell tumors of the thyroid developed in the animals exposed to the carcinogen mixture, although the question of whether the observed carcinogenic effects were synergistic or additive could not be answered. The results serve to evaluate carcinogenic risk in the search for causes of human cancer. PMID:2511179

21 CFR 361.1 - Radioactive drugs for certain research uses.

Code of Federal Regulations, 2014 CFR

2014-04-01

... following: Whole body, active blood-forming organs, lens of the eye, and gonads: Rems Single dose 3 Annual... body, active blood-forming organs, lens of the eye, gonads, and other organ doses from the administered... set forth in paragraph (d) of this section, that: (i) The pharmacological dose is within the limits...

21 CFR 361.1 - Radioactive drugs for certain research uses.

Code of Federal Regulations, 2013 CFR

2013-04-01

... following: Whole body, active blood-forming organs, lens of the eye, and gonads: Rems Single dose 3 Annual... body, active blood-forming organs, lens of the eye, gonads, and other organ doses from the administered... set forth in paragraph (d) of this section, that: (i) The pharmacological dose is within the limits...

21 CFR 361.1 - Radioactive drugs for certain research uses.

Code of Federal Regulations, 2012 CFR

2012-04-01

... following: Whole body, active blood-forming organs, lens of the eye, and gonads: Rems Single dose 3 Annual... body, active blood-forming organs, lens of the eye, gonads, and other organ doses from the administered... set forth in paragraph (d) of this section, that: (i) The pharmacological dose is within the limits...

Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation.

PubMed

McCaffrey, Katherine A; Jones, Brian; Mabrey, Natalie; Weiss, Bernard; Swan, Shanna H; Patisaul, Heather B

2013-05-01

Bisphenol A (BPA) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products. The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear. Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anterioventral periventricular (AVPV) nucleus. Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior. Long Evans rats were prenatally exposed to 10, 100, 1000, 10,000μg/kg bw/day BPA through daily, non-invasive oral administration of dosed-cookies to the dams. Offspring were reared to adulthood. Their brains were collected and immunolabeled for tyrosine hydroxylase (TH) in the AVPV and calbindin (CALB) in the SDN-POA. We observed decreased TH-ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization. In males, AVPV TH-ir cell numbers were significantly reduced in only the BPA 10 and BPA 10,000 groups. SDN-POA endpoints were unaltered in females but in males SDN-POA volume was significantly lower in all BPA exposure groups. CALB-ir was significantly lower in all but the BPA 1000 group. These effects are consistent with demasculinization. Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level (NOAEL) of 50mg/kg/day can alter sex specific hypothalamic morphology in the rat. Copyright © 2013 Elsevier Inc. All rights reserved.

Carcinogenicity of benzotrichloride administered to mice by gastric intubation.

PubMed

Fukuda, K; Matsushita, H; Takemoto, K; Toya, T

1993-01-01

Epidemiological studies suggest that benzotrichloride (BTC) is a human carcinogen. In the present study, BTC was tested to evaluate its ability to induce lung tumors as a result of systemic exposure. Administration of BTC by gastric intubation, 2.0-0.0315 microliters/mouse (4 doses), twice a week for 25 weeks, in female ICR mice, produced forestomach tumors (squamous cell carcinoma and papilloma), lung tumors (adenocarcinoma and adenoma) and tumors of the hematopoietic system (thymic lymphosarcoma and lymphatic leukemia) with dose-related response by 18 months. The present and previous studies indicate that the target organs of BTC carcinogenesis in mice are the local tissue which is primarily exposed, and the lung and hematopoietic tissue when BTC is administered systematically.

RADIATION DOSES AND CANCER RISKS IN THE MARSHALL ISLANDS ASSOCIATED WITH EXPOSURE TO RADIOACTIVE FALLOUT FROM BIKINI AND ENEWETAK NUCLEAR WEAPONS TESTS: SUMMARY

PubMed Central

Simon, Steven L.; Bouville, André; Land, Charles E.; Beck, Harold L.

2014-01-01

Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946–1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. From our analysis, we concluded that 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall Islands. In this work, we estimated deposition densities (kBq m−2) of all important dose-contributing radionuclides at each of the 32 atolls and separate reef islands of the Marshall Islands. Quantitative deposition estimates were made for 63 radionuclides from each test at each atoll. Those estimates along with reported measurements of exposure rates at various times after fallout were used to estimate radiation absorbed doses to the red bone marrow, thyroid gland, stomach wall, and colon wall of atoll residents from both external and internal exposure. Annual doses were estimated for six age groups ranging from newborns to adults. We found that the total deposition of 137Cs, external dose, internal organ doses, and cancer risks followed the same geographic pattern with the large population of the southern atolls receiving the lowest doses. Permanent residents of the southern atolls who were of adult age at the beginning of the testing period received external doses ranging from 5 to 12 mGy on average; the external doses to adults at the mid-latitude atolls ranged from 22 to 59 mGy on average, while the residents of the northern atolls received external doses in the hundreds to over 1,000 mGy. Internal doses varied significantly by age at exposure, location, and organ. Except

Radiation doses and cancer risks in the Marshall Islands associated with exposure to radioactive fallout from Bikini and Enewetak nuclear weapons tests: summary.

PubMed

Simon, Steven L; Bouville, André; Land, Charles E; Beck, Harold L

2010-08-01

Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946-1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. From our analysis, we concluded that 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall Islands. In this work, we estimated deposition densities (kBq m(-2)) of all important dose-contributing radionuclides at each of the 32 atolls and separate reef islands of the Marshall Islands. Quantitative deposition estimates were made for 63 radionuclides from each test at each atoll. Those estimates along with reported measurements of exposure rates at various times after fallout were used to estimate radiation absorbed doses to the red bone marrow, thyroid gland, stomach wall, and colon wall of atoll residents from both external and internal exposure. Annual doses were estimated for six age groups ranging from newborns to adults. We found that the total deposition of 137Cs, external dose, internal organ doses, and cancer risks followed the same geographic pattern with the large population of the southern atolls receiving the lowest doses. Permanent residents of the southern atolls who were of adult age at the beginning of the testing period received external doses ranging from 5 to 12 mGy on average; the external doses to adults at the mid-latitude atolls ranged from 22 to 59 mGy on average, while the residents of the northern atolls received external doses in the hundreds to over 1,000 mGy. Internal doses varied significantly by age at exposure, location, and organ. Except

Gut vagal afferents are necessary for the eating-suppressive effect of intraperitoneally administered ginsenoside Rb1 in rats.

PubMed

Shen, Ling; Wang, David Q-H; Lo, Chunmin C; Arnold, Myrtha; Tso, Patrick; Woods, Stephen C; Liu, Min

2015-12-01

Ginsenoside Rb1 (Rb1) reduces food intake in both lean and high-fat diet induced-obese rats; however, the sites and/or mediation of the eating-suppressive effect of Rb1 have not previously been identified. We hypothesized that intraperitoneally (ip) administered Rb1 exerts its anorectic action by enhancing sensitivity to satiation signals, such as cholecystokinin (CCK), and/or that it acts through vagal afferent nerves that relay the satiating signaling to the hindbrain. To test these hypotheses, we gave ip bolus doses of Rb1 (2.5-10.0mg/kg) and CCK-8 (0.125-4.0μg/kg) alone or in combination and assessed food intake in rats. Low doses of Rb1 (2.5mg/kg) or CCK-8 (0.125μg/kg) alone had no effect on food intake whereas higher doses did. When these subthreshold doses of Rb1 and CCK-8 were co-administered, the combination significantly reduced food intake relative to saline controls, and this effect was attenuated by lorglumide, a selective CCK1-receptor antagonist. Interestingly, lorglumide blocked food intake induced by an effective dose of CCK-8 alone, but not by Rb1 alone, suggesting that Rb1's anorectic effect is independent of the CCK1 receptor. To determine whether peripherally administered Rb1 suppresses feeding via abdominal vagal nerves, we evaluated the effect of ip Rb1 injection in subdiaphragmatic vagal deafferentation (SDA) and control rats. Rb1's effect on food intake was significantly attenuated in SDA rats, compared with that in SHAM controls. These data indicate that the vagal afferent system is the major pathway conveying peripherally administered Rb1's satiation signal. Copyright © 2015 Elsevier Inc. All rights reserved.

Age and gender patterns of thyroid cancer incidence in Ukraine depending on thyroid radiation doses from radioactive iodine exposure after the Chornobyl NPP accident.

PubMed

Fuzik, M M; Prysyazhnyuk, A Y; Shibata, Y; Romanenko, A Y; Fedorenko, Z P; Gudzenko, N A; Gulak, L O; Trotsyuk, N K; Goroh, Y L; Khukhrianska, O M; Sumkina, O V; Saenko, V A; Yamashita, S

2013-01-01

The objective of this study was to investigate the thyroid cancer incidence in a whole territory of Ukraine and to clear up its age and gender patterns depending on average regional (oblast) thyroid doses from radioactive iodine due to the Chornobyl accident. MATERIALS AND METHODS. On the basis of average accumulated thyroid doses from radioactive iodine the geographical regions of Ukraine with low and high average thyroid doses were identified for a comparative analysis performance. Methods of descriptive epidemiology were used. The level and dynamics of thyroid cancer incidence were analyzed in different gender and age groups (both for attained age and age at the moment of the Chornobyl accident). Results of this study confirmed the radiation excess of thyroid cancer in individuals who were children and adolescents in 1986. Some excess was observed in elder age groups too. Especial situation was observed in female age group 40-49 at the moment of the Chornobyl accident i.e. the age-specific thyroid cancer incidence rates were significantly higher in "high exposure" regions comparing with "low exposure" ones during all years of observation within 1989-2009. A probable radiation excess of thyroid cancer was suggested not only in children and adolescents but also in adult age groups. In elder age groups this excess was less expressed and manifested after a longer period of time. The origin of the phenomenon in female age group of 40-49 is unclear now. Hypothesis of combined effect of radiation and natural changing of hormonal status in this age should be checked in the future studies. Fuzik M. M, Prysyazhnyuk A. Ye, Shibata Y., Romanenko A. Yu., Fedorenko Z. P., Gudzenko N. A., Gulak L. O., Trotsyuk N. K., Goroh Ye. L., Khukhrianska O. M., Sumkina O. V., Saenko V. A., Yamashita Sh., 2013.

New Fetal Dose Estimates from 18F-FDG Administered During Pregnancy: Standardization of Dose Calculations and Estimations with Voxel-Based Anthropomorphic Phantoms.

PubMed

Zanotti-Fregonara, Paolo; Chastan, Mathieu; Edet-Sanson, Agathe; Ekmekcioglu, Ozgul; Erdogan, Ezgi Basak; Hapdey, Sebastien; Hindie, Elif; Stabin, Michael G

2016-11-01

Data from the literature show that the fetal absorbed dose from 18 F-FDG administration to the pregnant mother ranges from 0.5E-2 to 4E-2 mGy/MBq. These figures were, however, obtained using different quantification techniques and with basic geometric anthropomorphic phantoms. The aim of this study was to refine the fetal dose estimates of published as well as new cases using realistic voxel-based phantoms. The 18 F-FDG doses to the fetus (n = 19; 5-34 wk of pregnancy) were calculated with new voxel-based anthropomorphic phantoms of the pregnant woman. The image-derived fetal time-integrated activity values were combined with those of the mothers' organs from the International Commission on Radiological Protection publication 106 and the dynamic bladder model with a 1-h bladder-voiding interval. The dose to the uterus was used as a proxy for early pregnancy (up to 10 wk). The time-integrated activities were entered into OLINDA/EXM 1.1 to derive the dose with the classic anthropomorphic phantoms of pregnant women, then into OLINDA/EXM 2.0 to assess the dose using new voxel-based phantoms. The average fetal doses (mGy/MBq) with OLINDA/EXM 2.0 were 2.5E-02 in early pregnancy, 1.3E-02 in the late part of the first trimester, 8.5E-03 in the second trimester, and 5.1E-03 in the third trimester. The differences compared with the doses calculated with OLINDA/EXM 1.1 were +7%, +70%, +35%, and -8%, respectively. Except in late pregnancy, the doses estimated with realistic voxelwise anthropomorphic phantoms are higher than the doses derived from old geometric phantoms. The doses remain, however, well below the threshold for any deterministic effects. Thus, pregnancy is not an absolute contraindication of a clinically justified 18 F-FDG PET scan. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.

PubMed

Dubinsky, Marla C; Phan, Becky L; Singh, Namita; Rabizadeh, Shervin; Mould, Diane R

2017-01-01

Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.

Environmental radioactivity levels, Browns Ferry Nuclear Plant. Annual report, 1983

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

Not Available

1984-04-01

This report describes the environmental radiological monitoring of the Browns Ferry Nuclear Plant (BFN), located in Limestone County, Alabama, conducted in 1983. Dose estimates were calculated from concentrations of radioactivity found in samples of air, milk, meat, vegetation, drinking water, and fish. Estimated doses were essentially identical to those determined at control locations. 12 figures, 29 tables.

Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity

PubMed Central

Ciarlet, Max; Crawford, Sue E.; Barone, Christopher; Bertolotti-Ciarlet, Andrea; Ramig, Robert F.; Estes, Mary K.; Conner, Margaret E.

1998-01-01

Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund’s adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 103 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson’s correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund’s adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund’s adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund’s adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine. PMID:9765471

The pharmacology of chymotrypsin administered by inhalation

PubMed Central

Golberg, L.; Martin, L. E.; Sheard, P.; Harrison, C.

1960-01-01

The ability of chymotrypsin to reach the limits of the bronchial tree has been studied in cats receiving the enzyme by inhalation as a very fine powder. For this purpose derivatives of chymotrypsin were used which had been labelled with a fluorescent molecule or with [131I]. Quantitative measurements of the absorption and distribution of inhaled chymotrypsin- [131I] revealed a rapid removal of radioactivity from the lungs over the first 24 hr. and corresponding excretion of labelled inorganic iodide in the urine. High levels of activity were not attained in the blood or thyroid. Subcutaneous administration of labelled enzyme led to more rapid accumulation of radioactivity in the blood and thyroid. Consideration of these and other results leads to the conclusion that, while some enzyme ascends the respiratory tract by ciliary movement of mucus, a substantial part is absorbed into the lungs and the [131I] subsequently detached from it. The changes in tidal air accompanying inhalation of labelled trypsin and chymotrypsin were followed in anaesthetized cats. Trypsin brings about a decrease in tidal air in distinctly lower doses than does chymotrypsin. Prior administration of mepyramine had an antagonistic effect, and it is suggested that the change in tidal air is essentially the result of bronchial spasm. ImagesFIG. 2FIG. 3 PMID:13850540

Investigation of radioactivity concentration in spent technetium generators

NASA Astrophysics Data System (ADS)

Idriss, Hajo; Salih, Isam; Alaamer, Abdulaziz S.; Eisa, M. H.; Sam, A. K.

2014-04-01

This study was carried out to survey and measure radioactivity concentration and estimate radiation dose level at the surface of spent technetium generator columns for the safe final disposal of radioactive waste. High resolution γ-spectrometry with the aid of handheld radiation survey meters has been used. The radioactivity measurements has shown that 238U, 40K and 137Cs were only measurable in one sample whereas 125Sb was found in 14 samples out of total of 20 samples with an activity concentration which ranged from 21 to 7404 with an average value of 1095 Bq/kg. The activity concentration of 125Sb is highly variable indicating that the spent 99mTc generator columns are of different origin. This investigation highlighted the importance of radiation monitoring of spent technetium generators in the country in order to protect workers, and the public from the dangers posed by radioactive waste.

A phase 1, randomized, controlled dose-escalation study of EP-1300 polyepitope DNA vaccine against Plasmodium falciparum malaria administered via electroporation.

PubMed

Spearman, Paul; Mulligan, Mark; Anderson, Evan J; Shane, Andi L; Stephens, Kathy; Gibson, Theda; Hartwell, Brooke; Hannaman, Drew; Watson, Nora L; Singh, Karnail

2016-11-04

Plasmodium falciparum malaria is one of the leading infectious causes of childhood mortality in Africa. EP-1300 is a polyepitope plasmid DNA vaccine expressing 38 cytotoxic T cell epitopes and 16 helper T cell epitopes derived from P. falciparum antigens expressed predominantly in the liver phase of the parasite's life cycle. We performed a phase 1 randomized, placebo-controlled, dose escalation clinical trial of the EP-1300 DNA vaccine administered via electroporation using the TriGrid Delivery System device (Ichor Medical Systems). Although the delivery of the EP-1300 DNA vaccine via electroporation was safe, tolerability was less than that usually observed with standard needle and syringe intramuscular administration. This was primarily due to acute local discomfort at the administration site during electroporation. Despite the use of electroporation, the vaccine was poorly immunogenic. The reasons for the poor immunogenicity of this polyepitope DNA vaccine remain uncertain. ClinicalTrials.gov NCT01169077. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reduced administered activity, reduced acquisition time, and preserved image quality for the new CZT camera.

PubMed

Oddstig, Jenny; Hedeer, Fredrik; Jögi, Jonas; Carlsson, Marcus; Hindorf, Cecilia; Engblom, Henrik

2013-02-01

For a 1-day myocardial perfusion SPECT (MPS) the recommendations for administered activity stated in the EANM guidelines results in an effective dose of up to 16 mSv per patient. Recently, a gamma camera system, based on cadmium zinc telluride (CZT) technology, was introduced. This technique has the potential to reduce the effective dose and scan time compared to the conventional NaI gamma camera. The aim of this study was to investigate if the effective dose can be reduced with a preserved image quality using CZT technology in MPS. In total, 150 patients were included in the study. All underwent a 1-day (99m)Tc-tetrofosmin stress-rest protocol and were divided into three subgroups (n = 50 in each group) with 4, 3, and 2.5 MBq/kg body weight of administered activity in the stress examination, respectively. The acquisition time was increased in proportion to the decrease in administered activity. All examinations were analyzed for image quality by visual grading on a 4-point scale (1 = poor, 2 = adequate, 3 = good, 4 = excellent), by two expert readers. The total effective dose (stress + rest) decreased from 9.3 to 5.8 mSv comparing 4 to 2.5 MBq/kg body weight. For the patients undergoing stress examination only (35%) the effective dose, administrating 2.5 MBq/kg, was 1.4 mSv. The image acquisition times for 2.5 MBq/kg body weight were 475 and 300 seconds (stress and rest) compared to 900 seconds for each when using conventional MPS. The average image quality was 3.7 ± 0.5, 3.8 ± 0.5, and 3.8 ± 0.4 for the stress images and 3.5 ± 0.6, 3.6 ± 0.6, and 3.5 ± 0.6 for the rest images and showed no statistically significant difference (P = .62) among the 4, 3, and 2.5 MBq/kg groups. The new CZT technology can be used to considerably decrease the effective dose and acquisition time for MPS with preserved high image quality.

The pharmacokinetics of a single oral or rectal dose of concurrently administered isoniazid, rifampin, pyrazinamide, and ethambutol in Asian elephants (Elephas maximus).

PubMed

P Brock, A; Isaza, R; Egelund, E F; Hunter, R P; Peloquin, C A

2014-10-01

Tuberculosis, caused by Mycobacterium tuberculosis, is a disease of concern in captive Asian elephants (Elephas maximus). Treatment for tuberculosis in elephants utilizes multidrug protocols combining isoniazid, rifampin, pyrazinamide, and/or ethambutol. In this study, a single, coformulated dose of isoniazid 5 mg/kg, rifampin 10 mg/kg, pyrazinamide 30 mg/kg, and ethambutol 30 mg/kg was administered orally to six Asian elephants, and rectally to five elephants using a cross-over design. Blood samples were collected serially over 24 h. Pyrazinamide and ethambutol concentrations were determined using validated gas chromatography assays. Isoniazid and rifampin concentrations were determined using validated high-performance liquid chromatography assays. Rectal isoniazid produced an earlier Tmax compared with oral administration. Oral isoniazid resulted in a comparatively lower Cmax , but higher AUC values compared with rectal isoniazid. Oral rifampin and oral ethambutol were well absorbed while rectal rifampin was not. Oral pyrazinamide produced comparatively higher Cmax and AUC values compared with rectal pyrazinamide. Results of this study indicate that currently recommended therapeutic monitoring sample collection times for rectal isoniazid and oral rifampin do not provide an accurate assessment of exposure for these drugs. This study demonstrates notable individual variability, indicating that dosing of these medications requires individual monitoring and provides additional information to guide the clinician when treating elephants. © 2014 John Wiley & Sons Ltd.

Recovery of cholinesterase activity in mallard ducklings administered organophosphorus pesticides

USGS Publications Warehouse

Fleming, W.J.; Bradbury, S.P.

1981-01-01

Oral doses of the organophosphorus pesticides acephate, dicrotophos, fensulfothion, fonofos, malathion, and parathion were administered to mallard ducklings (Anas platyrhynchos), and brain and plasma cholinesterase (ChE) activities were determined for up to 77 d after dosing. In vivo recovery of brain ChE activity to within 2 standard deviations of the mean activity of undosed birds occurred within 8 d, after being depressed an average of 25-58% at 24 h after dosing. In vivo recovery of plasma ChE appeared as fast as or faster than that of brain, but the pattern of recovery was more erratic and therefore statistical comparison with brain ChE recovery was not attempted. In vitro tests indicated that the potential for dephosphorylation to contribute to in vivo recovery of inhibited brain ChE differed among chemical treatments. Some ducklings died as a result of organophosphate dosing. In an experiment in which ducklings within each treatment group received the same dose (mg/kg), the brain ChE activity in birds that died was less than that in birds that survived. Brain ChE activities in ducklings that died were significantly different among pesticide treatments: fensulfothion > parathion> acephate > malathion (p < 0.05).

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

PubMed

Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W

2017-07-01

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy

PubMed Central

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-01-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their 24Na and 38Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to 24Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive 24Na is mainly generated from 23Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood 24Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood 24Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood 24Na was determined using a germanium counter. The activity of 24Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood 24Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible. PMID:23392825

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy.

PubMed

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-07-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their (24)Na and (38)Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to (24)Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive (24)Na is mainly generated from (23)Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood (24)Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood (24)Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood (24)Na was determined using a germanium counter. The activity of (24)Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood (24)Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible.

A Subanalgesic Dose of Morphine Eliminates Nalbuphine Anti-analgesia in Postoperative Pain

PubMed Central

Gear, Robert W.; Gordon, Newton C.; Hossaini-Zadeh, Mehran; Lee, Janice S.; Miaskowski, Christine; Paul, Steven M.; Levine, Jon D.

2008-01-01

The agonist-antagonist kappa-opioid nalbuphine administered for postoperative pain produces greater analgesia in females than in males. In fact, males administered nalbuphine (5 mg) experience pain greater than those receiving placebo, suggesting the existence of an anti-analgesic effect. These sexually dimorphic effects on postoperative pain can be eliminated by co-administration of a fixed ratio of the prototypical opioid receptor antagonist naloxone with nalbuphine, implying a role for opioid receptors in the anti-analgesic as well as analgesic effects of nalbuphine. In the present study, we further evaluated the role of opioid receptors in the sex-specific effects on pain produced by nalbuphine by co-administering a dose of morphine low enough that it does not produce analgesia. Following extraction of bony impacted third molar teeth, nalbuphine (5 mg) was administered alone or in combination with either of two low doses of morphine (2 mg or 4 mg). Both doses of morphine reversed nalbuphine-induced anti-analgesia in males, but only the lower dose (2 mg) reached statistical significance. Neither dose affected nalbuphine-induced analgesia in females, and when administered alone in either males or females, morphine (2 mg) had no analgesic effect. Though not observed in females, the effect of morphine in males argues that, like naloxone, low dose morphine may act as an anti-analgesia opioid receptor antagonist. Perspective Previously we reported that the nalbuphine produces both analgesic and anti-analgesic effects, and that the opioid antagonist naloxone can enhance nalbuphine analgesia by selectively antagonizing the anti-analgesic effect. Here we show that morphine, given in a subanalgesic dose, reverses nalbuphine-induced anti-analgesia in males, perhaps by a similar mechanism. PMID:18201935

Radioactivity of Nevada hot-spring systems

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

Wollenberg, H.A.

1974-01-01

Field gamma radiometry and laboratory gamma spectrometry of waters and spring deposits were accomplished for some hot-sprin systems in northern Nevada. Gamma dose rates measured on-site range from 2 to 500 mu rphr, and depend msinly on the amounts of the natural radioelements in the spring deposits. At several locations /sup 222/Rn, emanating from the water, casuses recognizable ganna anomalies. High radioactivities, primarily from /sup 226/Ra, are associated with hot-spring systems dominated by CaCO/sub 3/, while silica-dominated systems sre relatively low in radioactivity. Gamma spectrometry disclosed the enrichment of / sup 226/Ra with respect to its parent U in CaCO/submore » 3/-dominated systems. /sup 226/Ra preferentially associates with Ca; therefore, where tufa and siliceous sinter are present in a deposit, the calcareous material is highest in radioacnvity. Spring deposits at fast-flowing CaCO/sub 3/-dominated systems are generally less radioactive than calcareous deposits at slower flowing springs. (auth)« less

Radioactive waste management complex low-level waste radiological composite analysis

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

McCarthy, J.M.; Becker, B.H.; Magnuson, S.O.

1998-05-01

The composite analysis estimates the projected cumulative impacts to future members of the public from the disposal of low-level radioactive waste (LLW) at the Idaho National Engineering and Environmental Laboratory (INEEL) Radioactive Waste Management Complex (RWMC) and all other sources of radioactive contamination at the INEEL that could interact with the LLW disposal facility to affect the radiological dose. Based upon the composite analysis evaluation, waste buried in the Subsurface Disposal Area (SDA) at the RWMC is the only source at the INEEL that will significantly interact with the LLW facility. The source term used in the composite analysis consistsmore » of all historical SDA subsurface disposals of radionuclides as well as the authorized LLW subsurface disposal inventory and projected LLW subsurface disposal inventory. Exposure scenarios evaluated in the composite analysis include all the all-pathways and groundwater protection scenarios. The projected dose of 58 mrem/yr exceeds the composite analysis guidance dose constraint of 30 mrem/yr; therefore, an options analysis was conducted to determine the feasibility of reducing the projected annual dose. Three options for creating such a reduction were considered: (1) lowering infiltration of precipitation through the waste by providing a better cover, (2) maintaining control over the RWMC and portions of the INEEL indefinitely, and (3) extending the period of institutional control beyond the 100 years assumed in the composite analysis. Of the three options investigated, maintaining control over the RWMC and a small part of the present INEEL appears to be feasible and cost effective.« less

Immunogenicity of quadrivalent HPV and combined hepatitis A and B vaccine when co-administered or administered one month apart to 9-10 year-old girls according to 0-6 month schedule.

PubMed

Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gaston; Couillard, Michel; Krajden, Mel; Ouakki, Manale; Murphy, Donald; Trevisan, Andrea; Dionne, Marc

2014-01-01

No immunogenicity data has been reported after a single dose of the quadrivalent HPV vaccine (qHPV-Gardasil®) and no data are available on co-administration of this vaccine with the HAV/HBV vaccine (Twinrix-Junior®). Two pre-licensure studies reported similar anti-HPV but lower anti-HBs titers when co-administering HPV and HBV vaccines. To assess the immunogenicity of the qHPV and HAV/HBV vaccine when co-administered (Group-Co-adm) or given one month apart (Group-Sep) and to measure the persistence of HPV antibodies three years post-second dose of qHPV vaccine in both study groups. 416 9-10 year-old girls were enrolled. Vaccination schedule was 0-6 months. Anti-HAV and anti-HBs were measured in all subjects 6 months post-first dose and 1 month post-second dose. Anti-HPV were measured 6 months post-first dose in Group-Co-adm and in all subjects 1 and 36 months post-second dose. Six months post-first dose: 100% of subjects had detectable anti-HAV and 56% and 73% had detectable anti-HBs in Group-Co-Adm and Group-Sep, respectively. In Group-Co-adm 94, 100, 99 and 96% had detectable antibodies to HPV 6, 11, 16 and 18, respectively. One month post-second dose of qHPV and HAV/HBV vaccine, in both study groups 99.5-100% of subjects had an anti-HAV titer ≥ 20IU/L, 97.5-97.6% an anti-HBs level ≥ 10IU/L, and 100% had an anti-HPV titer ≥ 3LU. Thirty-six months post-second dose of qHPV all but four subjects (99%) had antibodies to HPV18 and 100% had antibodies to HPV6, 11 and 16. The great majority (97-100%) had an anti-HPV titer ≥ 3 LU. Post-second dose administration of qHPV and HAV/HBV, no meaningful difference was observed in the immune response in the two study groups to any component of vaccines. The results indicate that qHPV and HAV/HBV can be given during the same vaccination session. Two doses of of qHPV and HAV/HBV vaccines induce a strong immune response. Three years post-second dose of qHPV, the great majority of subjects had antibodies to HPV types

Benefits of adopting good radiation practices in reducing the whole body radiation dose to the nuclear medicine personnel during (18)F-fluorodeoxyglucose positron emission tomography/computed tomography imaging.

PubMed

Verma, Shashwat; Kheruka, Subhash Chand; Maurya, Anil Kumar; Kumar, Narvesh; Gambhir, Sanjay; Kumari, Sarita

2016-01-01

Positron emission tomography has been established as an important imaging modality in the management of patients, especially in oncology. The higher gamma radiation energy of positron-emitting isotopes poses an additional radiation safety problem. Those working with this modality may likely to receive higher whole body doses than those working only in conventional nuclear medicine. The radiation exposure to the personnel occurs in dispensing the dose, administration of activity, patient positioning, and while removing the intravenous (i.v.) cannula. The estimation of radiation dose to Nuclear Medicine Physician (NMP) involved during administration of activity to the patient and technical staff assisting in these procedures in a positron emission tomography/computed tomography (PET/CT) facility was carried out. An i.v access was secured for the patient by putting the cannula and blood sugar was monitored. The activity was then dispensed and measured in the dose calibrator and administered to the patient by NMP. Personnel doses received by NMP and technical staff were measured using electronic pocket dosimeter. The radiation exposure levels at various working locations were assessed with the help of gamma survey meter. The radiation level at working distance while administering the radioactivity was found to be 106-170 μSv/h with a mean value of 126.5 ± 14.88 μSv/h which was reduced to 4.2-14.2 μSv/h with a mean value of 7.16 ± 2.29 μSv/h with introduction of L-bench for administration of radioactivity. This shows a mean exposure level reduction of 94.45 ± 1.03%. The radiation level at working distance, while removing the i.v. cannula postscanning was found to be 25-70 μSv/h with a mean value of 37.4 ± 13.16 μSv/h which was reduced to 1.0-5.0 μSv/h with a mean value of 2.77 ± 1.3 μSv/h with introduction of L-bench for removal of i.v cannula. This shows a mean exposure level reduction of 92.85 ± 1.78%. This study shows that good radiation practices are

Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956)- An Assessment of Quantities released, Off-Site Radiation Doses, and Potential Excess Risks of Thyroid Cancer, Volume 1

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

Apostoaei, A.I.; Burns, R.E.; Hoffman, F.O.

1999-07-01

In the early 1990s, concern about the Oak Ridge Reservation's past releases of contaminants to the environment prompted Tennessee's public health officials to pursue an in-depth study of potential off-site health effects at Oak Ridge. This study, the Oak Ridge dose reconstruction, was supported by an agreement between the U.S. Department of Energy (DOE) and the State of Tennessee, and was overseen by a 12-member panel appointed by Tennessee's Commissioner of Health. One of the major contaminants studied in the dose reconstruction was radioactive iodine, which was released to the air by X-10 (now called Oak Ridge National Laboratory) asmore » it processed spent nuclear reactor fuel from 1944 through 1956. The process recovered radioactive lanthanum for use in weapons development. Iodine concentrates in the thyroid gland so health concerns include various diseases of the thyroid, such as thyroid cancer. The large report, ''Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956) - An Assessment of Quantities Released, Off-site Radiation Doses, and Potential Excess Risks of Thyroid Cancer,'' is in two volumes. Volume 1 is the main body of the report, and Volume 1A, which has the same title, consists of 22 supporting appendices. Together, these reports serve the following purposes: (1) describe the methodologies used to estimate the amount of iodine-131 (I-131) released; (2) evaluate I-131's pathway from air to vegetation to food to humans; (3) estimate doses received by human thyroids; (4) estimate excess risk of acquiring a thyroid cancer during ones lifetime; and (5) provide equations, examples of historical documents used, and tables of calculated values. Results indicate that females born in 1952 who consumed milk from a goat pastured a few miles east of X-10 received the highest doses from I-131 and would have had the highest risks of contracting thyroid cancer. Doses from cow's milk are considerably less

Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis.

PubMed

Subramanian, Raju; Zhu, Xiaochun; Hock, M Benjamin; Sloey, Bethlyn J; Wu, Benjamin; Wilson, Sarah F; Egbuna, Ogo; Slatter, J Greg; Xiao, Jim; Skiles, Gary L

2017-02-01

Etelcalcetide (AMG 416) is a novel synthetic peptide calcium-sensing receptor activator in clinical development as an intravenous calcimimetic for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. Etelcalcetide is composed of seven D-aminoacids with an L-cysteine linked to a D-cysteine by a disulfide bond. A single intravenous dose of [ 14 C]etelcalcetide (10 mg; 26.3 kBq; 710 nCi) was administered to patients with CKD on hemodialysis to elucidate the pharmacokinetics, biotransformation, and excretion of etelcalcetide in this setting. Blood, dialysate, urine, and feces were collected to characterize the pharmacokinetics, biotransformation product profiles, mass balance, and formation of anti-etelcalcetide antibodies. Accelerator mass spectrometry was necessary to measure the microtracer quantities of C-14 excreted in the large volumes of dialysate and other biomatrices. An estimated 67 % of the [ 14 C]etelcalcetide dose was recovered in dialysate, urine, and feces 176 days after dose administration. Etelcalcetide was primarily cleared by hemodialysis, with approximately 60 % of the administered dose eliminated in dialysate. Minor excretion was observed in urine and feces. Biotransformation resulted from disulfide exchange with endogenous thiols, and preserved the etelcalcetide D-amino acid backbone. Drug-related radioactivity circulated primarily as serum albumin peptide conjugate (SAPC). Following removal of plasma etelcalcetide by hemodialysis, re-equilibration occurred between SAPC and L-cysteine present in blood to partially restore the etelcalcetide plasma concentrations between dialysis sessions. No unanticipated safety signals or anti-etelcalcetide or anti-SAPC antibodies were detected.

Estimation of annual effective dose due to natural radioactive elements in ingestion of foodstuffs in tin mining area of Jos-Plateau, Nigeria.

PubMed

Jibiri, N N; Farai, I P; Alausa, S K

2007-01-01

Soils and food crops from a former tin mining location in a high background radiation area on the Jos-Plateau, Nigeria were collected and analyzed by gamma spectrometry to measure their contents of 40K, 238U and 232Th. As well as collecting samples, in situ dose rates on farms were measured using a precalibrated survey meter. Activity concentrations determined in food crops were compared with the local food derivatives or diets to investigate the possible removal or addition of radionuclides during food preparation by cooking or other means. Potassium-40 was found to contribute the highest activity in all the food products. The activity concentration of 40K, 238U and 232Th in local prepared diets ranged between 60 and 494 Bq kg-1, between BDL and 48 Bq kg-1 and between BDL and 17 Bq kg-1, respectively. The internal effective dose to individuals from the consumption of the food types was estimated on the basis of the measured radionuclide contents in the food crops. It ranged between 0.2 microSv y-1 (beans) and 2164 microSv y-1 (yam) while the annual external gamma effective dose in the farms due to soil radioactivity ranged between 228 microSv and 4065 microSv.

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.

Biomedical aspects of natural and manufactured environmental radioactivity

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

Hodge, V.

1996-12-31

While weapons testing has altered natural radioactivity background, manufactured radioactivity in most parts of the world constitutes but a very small fraction of the total alpha, beta, and gamma radioactivity in soil, air, water, and the biota. For example, in the early 1970s, we found what appeared to be the highest natural concentration of radioactivity ever reported in fish while attempting to measure the manufactured plutonium ({sup 239}Pu and {sup 240}Pu) in organs of oceanic tuna. The natural alpha emitter polonium ({sup 210}Po) was discovered in the same organs at orders of magnitude higher concentrations. In particular, the caecum, whichmore » is a digestive organ composed of many small closed-ended sacs, contained concentrations of polonium as high as 79 pCi/g of wet tissue and lesser amounts of two manufactured isotopes: 0.0001 pCi/g of plutonium and 0.01 pCi/g of radiocesium ({sup 137}Cs). This equates to {approximately}80 rem/yr of radiation dose to this organ, overwhelmingly from the natural polonium, or {approximately}5000 times higher than is found in the human liver, the highest polonium concentration in man. The average background radiation for humans, for comparison, is {approximately}0.2 rem/yr, but the dose for Japanese, whose diet is high in seafood, is {approximately}15 rem/yr. The question arose: {open_quotes}Are these high concentrations of natural polonium limited to oceanic fish?{close_quotes} To answer this question, polonium was determined in the organs of striped bass and catfish from Lake Mead. In a related study, the plutonium and radiocesium ({sup 137}Cs) distributions in soils were determined to ascertain the impact of weapons testing on the natural background radioactivity of soils.« less

InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps

PubMed Central

Pratt, Brenda E.; Chittenden, Sarah J.; Murray, Iain S.; Causer, Louise; Grey, Matthew J.; Gear, Jonathan I.; Du, Yong; Flux, Glenn D.

2017-01-01

The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an 131I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration. PMID:28187040

Chylothorax Associated with Substernal Goiter in Graves' Disease Treated with Radioactive Iodine.

PubMed

Young Oh, Seo; Hyun Kim, Bo; Young Kim, Do; Min Lee, Kyu; Jin Lee, Min; Su Kim, Sung; Ho Kim, Jong; Kyung Jeon, Yun; Soo Kim, Sang; Ki Kim, Yong; Joo Kim, In

2017-04-01

We present a rare case of chylothorax associated with an intrathoracic goiter in Graves' disease that was treated with radioactive iodine. A 23-year-old woman with Graves' disease was referred to our clinic with a pleural effusion, dyspnea, characteristic bilateral proptosis, and a diffuse goiter. The pleural fluid biochemistry was consistent with chylothorax. However, the chylothorax did not decrease with conservative therapy. Therefore, RAI was administered. Subsequently, the chylothorax and goiter improved more quickly than expected. This case illustrates that chylothorax associated with a substernal goiter in Graves' disease can be treated successfully with radioactive iodine instead of surgery.

INTERNAL RADIATION DOSE MEASUREMENTS IN LIVE EXPERIMENTAL ANIMALS. PART II

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

Nold, M.M.; Hayes, R.L.; Comar, C.L.

1960-12-01

Silver phosphate glass dosimeter rods were implanted in various portions of the digestive tract and the radiation dose was measured after ingestion of a known amount of Y/sup 90/. It was found that a state of diarrhea reduced the average radiation dose by a factor of from 2 to 4. In the constipated animal the dose was increased by a factor of from 3 to 7. Investigation was made to determine the role of various processes governing the radiation dose delivered to gastrointestinal mucosa. The total dose to a particular site along the intestinal tract was obtained by determination ofmore » the time integral of the radioactive concentration. Serial sacrifices were made at specific times after administration of the radioactivity. Calculations in this manner agreed exceptionally well with the doses that were measured by the glass dosimeter method. It is estimated that 4 and 17 - c of Y/sup 90/ for the dog and goat, respectively, will deliver a 300mrad dose to the critical organ, the lower large intestine. The twelve-fold average difference in dose between the diarrhea and constipation groups of dogs emphasizes the importance of the physical state of bowel passages upon the dose delivered to the critical organ. (auth)« less

Correlation between measles vaccine doses: implications for the maintenance of elimination.

PubMed

McKee, A; Ferrari, M J; Shea, K

2018-03-01

Measles eradication efforts have been successful at achieving elimination in many countries worldwide. Such countries actively work to maintain this elimination by continuing to improve coverage of two routine doses of measles vaccine following measles elimination. While improving measles vaccine coverage is always beneficial, we show, using a steady-state analysis of a dynamical model, that the correlation between populations receiving the first and second routine dose also has a significant impact on the population immunity achieved by a specified combination of first and second dose coverage. If the second dose is administered to people independently of whether they had the first dose, high second-dose coverage improves the proportion of the population receiving at least one dose, and will have a large effect on population immunity. If the second dose is administered only to people who have had the first dose, high second-dose coverage reduces the rate of primary vaccine failure, but does not reach people who missed the first dose; this will therefore have a relatively small effect on population immunity. When doses are administered dependently, and assuming the first dose has higher coverage, increasing the coverage of the first dose has a larger impact on population immunity than does increasing the coverage of the second. Correlation between vaccine doses has a significant impact on the level of population immunity maintained by current vaccination coverage, potentially outweighing the effects of age structure and, in some cases, recent improvements in vaccine coverage. It is therefore important to understand the correlation between vaccine doses as such correlation may have a large impact on the effectiveness of measles vaccination strategies.

Monte Carlo simulations of radioactive waste encapsulated by bisphenol-A polycarbonate and effect of bismuth-III oxide filler material

NASA Astrophysics Data System (ADS)

Özdemir, Tonguç

2017-06-01

Radioactive waste generated from the nuclear industry and non-power applications should carefully be treated, conditioned and disposed according to the regulations set by the competent authority(ies). Bisphenol-a polycarbonate (BPA-PC), a very widely used polymer, might be considered as a potential candidate material for low level radioactive waste encapsulation. In this work, the dose rate distribution in the radioactive waste drum (containing radioactive waste and the BPA-PC polymer matrix) was determined using Monte Carlo simulations. Moreover, the change of mechanical properties of BPA-PC was estimated and their variation within the waste drum was determined for the periods of 15, 30 and 300 years after disposal to the final disposal site. The change of the dose rate within the waste drum with different contents of bismuth-III oxide were also simulated. It was concluded that addition of bismuth-III oxide filler decreases the dose delivered to the polymeric matrix due to photoelectric effect.

Disposition and metabolism of [14C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats

PubMed Central

Brunner, Valérie; Maynadier, Bernadette; Chen, Laishun; Roques, Louise; Hude, Isabelle; Séguier, Sébastien; Barthe, Laurence; Hermann, Philippe

2015-01-01

Levomilnacipran is approved in the US for the treatment of major depressive disorder in adults. We characterized the metabolic profile of levomilnacipran in humans, monkeys, and rats after oral administration of [14C]-levomilnacipran. In vitro binding of levomilnacipran to human plasma proteins was also studied. Unchanged levomilnacipran was the major circulating compound after dosing in all species. Within 12 hours of dosing in humans, levomilnacipran accounted for 52.9% of total plasma radioactivity; the circulating metabolites N-desethyl levomilnacipran N-carbamoyl glucuronide, N-desethyl levomilnacipran, and levomilnacipran N-carbamoyl glucuronide accounted for 11.3%, 7.5%, and 5.6%, respectively. Similar results were seen in monkeys. N-Desethyl levomilnacipran and p-hydroxy levomilnacipran were the main circulating metabolites in rats. Mass balance results indicated that renal excretion was the major route of elimination with 58.4%, 35.5%, and 40.2% of total radioactivity being excreted as unchanged levomilnacipran in humans, monkeys, and rats, respectively. N-Desethyl levomilnacipran was detected in human, monkey, and rat urine (18.2%, 12.4%, and 7.9% of administered dose, respectively). Human and monkey urine contained measurable quantities of levomilnacipran glucuronide (3.8% and 4.1% of administered dose, respectively) and N-desethyl levomilnacipran glucuronide (3.2% and 2.3% of administered dose, respectively); these metabolites were not detected in rat urine. The metabolites p-hydroxy levomilnacipran and p-hydroxy levomilnacipran glucuronide were detected in human urine (≤1.2% of administered dose), and p-hydroxy levomilnacipran glucuronide was found in rat urine (4% of administered dose). None of the metabolites were pharmacologically active. Levomilnacipran was widely distributed with low plasma protein binding (22%). PMID:26150694

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

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

Rapid measurement of 89,90Sr radioactivity in rinse water.

PubMed

Masashi, Takada; Hiroko, Enomoto; Toshikazu, Suzuki

2013-03-01

Rapid measurement of radioactivity from Sr in aqueous solutions is performed using a technique combining a strontium rad disk and a picobeta spectrometer. Identification of Sr radionuclides is accomplished in as little as 90 min in a radiation-tainted solution that contains more highly radioactive cesium. It is possible to perform triage by assessing skin exposure doses in this short time. This simple technique could be used in mobile laboratories. Sr having 1 Bq radioactivities are measured in 10 kBq Cs in aqueous solution. The radioactivity contained in rinse water used to decontaminate the feet of workers who stepped into highly contaminated water in the basement of the turbine building of Unit 3 at the Fukushima Daiichi nuclear power station was measured. The amount of Sr radioactivity in rinse water using the authors' rapid measurement technique (0.29 Bq mL) and a traditional method agree well, with 3.6% difference. Based on this agreement, this technique is confirmed to be useful for rapid measurement of Sr radioactivities.

Effect of oral dosing vehicles on the developmental toxicity of flubendazole in rats.

PubMed

Yoshimura, Haruo

2003-01-01

Flubendazole was suspended in deionized water or olive oil and administered by gavage once daily to pregnant rats on Days 8-15 of pregnancy to examine if the embryolethal and teratogenic doses were affected by the vehicles used. Flubendazole in olive oil caused a statistically significant increase in embryolethality at doses of 7.83 mg/kg per day and higher, with complete resorption in all dams at 31.33 mg/kg per day. When flubendazole was suspended in deionized water, a significant increase in embryolethality occurred only at a maternal dose of 125.32 mg/kg per day. The proportion of litters with anomalous fetuses was significantly increased at doses of 31.33 mg/kg per day and above when flubendazole was administered in deionized water, but increased at doses at four times lower when flubendazole was administered as in olive oil. Administered as a single dose in olive oil on any one of Days 6-12 of pregnancy, a flubendazole dose of 31.33 mg/kg caused significant increases in embryolethality and decreased fetal body weights on Days 7-9, with an 82.7% incidence of embryolethality on Day 8, with complete resorption in 5 of the 8 dams. The critical periods for teratogenic effects were between Days 8 and 11 of pregnancy, with Day 9 being the most critical. Fetuses with gross, skeletal, or internal anomalies were seen in dams given a single dose of as low as 7.83 mg/kg.

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

PubMed

Bryan, J P; MacArthy, P; Rudock, A; Fogarty, J P; Dowd, H; Legters, L J; Perine, P L

1997-06-01

The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice

PubMed Central

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

2010-01-01

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7–9, 10–12 or 13–15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13–15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug. PMID:23961116

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

PubMed

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

2011-04-01

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with {sup 131}I-metaiodobenzylguanidine with implications for the activity to administer

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

Mínguez, Pablo, E-mail: pablo.minguezgabina@osakidetza.net; Flux, Glenn; Genollá, José

2015-07-15

Purpose: The aim was to investigate whole-body and red marrow absorbed doses in treatments of neuroblastoma (NB) and adult neuroendocrine tumors (NETs) with {sup 131}I-metaiodobenzylguanidine and to propose a simple method for determining the activity to administer when dosimetric data for the individual patient are not available. Methods: Nine NB patients and six NET patients were included, giving in total 19 treatments as four patients were treated twice. Whole-body absorbed doses were determined from dose-rate measurements and planar gamma-camera imaging. For six NB and five NET treatments, red marrow absorbed doses were also determined using the blood-based method. Results: Dosimetricmore » data from repeated administrations in the same patient were consistent. In groups of NB and NET patients, similar whole-body residence times were obtained, implying that whole-body absorbed dose per unit of administered activity could be reasonably well described as a power function of the patient mass. For NB, this functional form was found to be consistent with dosimetric data from previously published studies. The whole-body to red marrow absorbed dose ratio was similar among patients, with values of 1.4 ± 0.6–1.7 ± 0.7 (1 standard deviation) in NB treatments and between 1.5 ± 0.6 and 1.7 ± 0.7 (1 standard deviation) in NET treatments. Conclusions: The consistency of dosimetric results between administrations for the same patient supports prescription of the activity based on dosimetry performed in pretreatment studies, or during the first administration in a fractionated schedule. The expressions obtained for whole-body absorbed doses per unit of administered activity as a function of patient mass for NB and NET treatments are believed to be a useful tool to estimate the activity to administer at the stage when the individual patient biokinetics has not yet been measured.« less

Occupational exposure to natural radioactivity in a zircon sand milling plant.

PubMed

Ballesteros, Luisa; Zarza, Isidoro; Ortiz, Josefina; Serradell, Vicente

2008-10-01

Raw zirconium sand is one of the substances (naturally occurring radioactive material, NORM) which is widely used in the ceramic industry. This sand contains varying concentrations of natural radionuclides: mostly U-238 but also Th-232 and U-235, together with their daughters, and therefore may need to be regulated by Directive 96/29/EURATOM. This paper describes the method used to perform the radiological study on a zircon sand milling plant and presents the results obtained. Internal and external doses were evaluated using radioactivity readings from sand, airborne dust, intermediate materials and end products. The results on total effective dose show the need for this type of industry to be carefully controlled, since values near to 1 mSv were obtained.

Effects of radioactive contamination on Scots pines in the remote period after the Chernobyl accident.

PubMed

Geras'kin, Stanislav; Oudalova, Alla; Dikareva, Nina; Spiridonov, Sergey; Hinton, Thomas; Chernonog, Elena; Garnier-Laplace, Jacqueline

2011-08-01

A 6 year study of Scots pine populations inhabiting sites in the Bryansk region of Russia radioactively contaminated as a result of the Chernobyl accident is presented. In six study sites, (137)Cs activity concentrations and heavy metal content in soils, as well as (137)Cs, (90)Sr and heavy metal concentrations in cones were measured. Doses absorbed in reproduction organs of pine trees were calculated using a dosimetric model. The maximum annual dose absorbed at the most contaminated site was about 130 mGy. Occurrence of aberrant cells scored in the root meristem of germinated seeds collected from pine trees growing on radioactively contaminated territories for over 20 years significantly exceeded the reference levels during all 6 years of the study. The data suggest that cytogenetic effects occur in Scots pine populations due to the radioactive contamination. However, no consistent differences in reproductive ability were detected between the impacted and reference populations as measured by the frequency of abortive seeds. Even though the Scots pine populations have occupied radioactively contaminated territories for two decades, there were no clear indications of adaptation to the radiation, when measured by the number of aberrant cells in root meristems of seeds exposed to an additional acute dose of radiation.

Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years.

PubMed

Black, Steven; Friedland, Leonard R; Schuind, Anne; Howe, Barbara

2006-08-28

Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.

ISCORS ASSESSMENT OF RADIOACTIVITY IN SEWAGE SLUDGE: MODELING TO ASSESS RADIATION DOSES

EPA Science Inventory

The Interagency Steering Committee on Radiation Standards (ISCORS) has recently completed a study of the occurrence within the United States of radioactive materials in sewage sludge and sewage incineration ash. One component of that effort was an examination of the possible tran...

Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics.

PubMed

Rocha, José-Francisco; Sicard, Éric; Fauchoux, Nicolas; Falcão, Amílcar; Santos, Ana; Loureiro, Ana I; Pinto, Roberto; Bonifácio, Maria João; Nunes, Teresa; Almeida, Luís; Soares-da-Silva, Patrício

2017-03-01

To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. Two randomized, double blind, sex-balanced, placebo-controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once-daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LB was administered. All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose-dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (E max ) and extent (AUEC) of the catechol-O-methyltransferase activity in relation to placebo. The tolerability profile was favourable. Opicapone, as once-daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long-lasting and sustained catechol-O-methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo. © 2016 The British Pharmacological Society.

Estimation of internal radiation dose from both immediate releases and continued exposures to contaminated materials.

PubMed

Napier, Bruce

2012-03-01

A brief description is provided of the basic concepts related to 'internal dose' and how it differs from doses that result from radioactive materials and direct radiation outside of the body. The principles of radiation dose reconstruction, as applied to both internal and external doses, are discussed on the basis of a recent publication prepared by the US National Council on Radiation Protection and Measurements. Finally, ideas are introduced related to residual radioactive contamination in the environment that has resulted from the releases from damaged reactors and also to the management of wastes that may be generated in both regional cleanup and decommissioning of the Fukushima nuclear power plant.

Effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients with type 2 diabetes mellitus.

PubMed

Kanto, Kousei; Ito, Hiroyuki; Noso, Shinsuke; Babaya, Naru; Hiromine, Yoshihisa; Taketomo, Yasunori; Toma, Junko; Niwano, Fumimaru; Yasutake, Sara; Kawabata, Yumiko; Ikegami, Hiroshi

2017-09-30

Differences in the efficacy and safety of antidiabetic drugs among different ethnic groups are well documented. Metformin is widely used in the treatment of type 2 diabetes in Western countries, but high doses of metformin have been approved only recently for clinical use in Japan. The aim of the present study was to investigate the effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients. A total of 71 Japanese patients with type 2 diabetes were prospectively studied for the effects of dosage and dosing frequency on the efficacy and safety of metformin during hospitalization. Dose effects were studied in 27 patients treated with 0, 500, 1,000, 1,500 and 2,250 mg/day of metformin. The effect of dosing frequency was compared in 56 patients with 1,500 mg/day of metformin administered either two or three times per day. Significant dose-dependent improvement in daily profiles of blood glucose was observed with metformin dosages up to 1,500 mg/day, with a trend towards further improvement observed at 2,250 mg/day. The efficacy of 1,500 mg of metformin was comparable when the drug was administered either two or three times per day. The most frequently reported side-effects were gastrointestinal symptoms, which were not affected by the dosage or dosing frequency of metformin. These results show that the efficacy of high-dose metformin is dose-dependent in Japanese patients. The efficacy and safety of metformin were similar when the drug was administered either two or three times per day. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Radioactive body burden measurements in (131)iodine therapy for differentiated thyroid cancer: effect of recombinant thyroid stimulating hormone in whole body (131)iodine clearance.

PubMed

Ravichandran, Ramamoorthy; Al Saadi, Amal; Al Balushi, Naima

2014-01-01

Protocols in the management of differentiated thyroid cancer, recommend adequate thyroid stimulating hormone (TSH) stimulation for radioactive (131)I administrations, both for imaging and subsequent ablations. Commonly followed method is to achieve this by endogenous TSH stimulation by withdrawal of thyroxine. Numerous studies worldwide have reported comparable results with recombinant human thyroid stimulating hormone (rhTSH) intervention as conventional thyroxine hormone withdrawal. Radiation safety applications call for the need to understand radioactive (131)I (RA(131)I) clearance pattern to estimate whole body doses when this new methodology is used in our institution. A study of radiation body burden estimation was undertaken in two groups of patients treated with RA(131)I; (a) one group of patients having thyroxine medication suspended for 5 weeks prior to therapy and (b) in the other group retaining thyroxine support with two rhTSH injections prior to therapy with RA(131)I. Sequential exposure rates at 1 m in the air were measured in these patients using a digital auto-ranging beta gamma survey instrument calibrated for measurement of exposure rates. The mean measured exposure rates at 1 m in μSv/h immediately after administration and at 24 h intervals until 3 days are used for calculating of effective ½ time of clearance of administered activity in both groups of patients, 81 patients in conventionally treated group (stop thyroxine) and 22 patients with rhTSH administration. The (131)I activities ranged from 2.6 to 7.9 GBq. The mean administered (131)I activities were 4.24 ± 0.95 GBq (n = 81) in "stop hormone" group and 5.11 ± 1.40 GBq (n = 22) in rhTSH group. The fall of radioactive body burden showed two clearance patterns within observed 72 h. Calculated T½eff values were 16.45 h (stop hormone group) 12.35 h (rhTSH group) for elapsed period of 48 h. Beyond 48 h post administration, clearance of RA(131)I takes place with T½eff> 20 h in both groups

Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants.

PubMed

Undre, Nasrullah; Dickinson, James

2017-04-04

Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants. A phase 1, open-label, single-dose, cross-over study. A single clinical research unit. In total, 20 male participants, 18-55 years old, entered and completed the study. All participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration-time profile over 144 hours was used to estimate pharmacokinetic parameters. Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration-time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC 0-∞ ); AUC measured until the last quantifiable concentration (AUC 0-tz ); maximum observed concentration (C max ); time to C max (T max )). Tolerability was assessed throughout the study. Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC 0-tz and AUC 0-∞ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). C max was higher for oral and nasogastric suspension (30% and 28%, respectively), and median T max was shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10�

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise.

PubMed

Hubbell, J A E; Sams, R A; Schmall, L M; Robertson, J T; Hinchcliff, K W; Muir, W W

2009-05-01

Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.

Macroscopic and microscopic biodistribution of intravenously administered iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Misra, Adwiteeya; Petryk, Alicia A.; Strawbridge, Rendall R.; Hoopes, P. Jack

2015-03-01

Iron oxide nanoparticles (IONP) are being developed for use as a cancer treatment. They have demonstrated efficacy when used either as a monotherapy or in conjunction with conventional chemotherapy and radiation. The success of IONP as a therapeutic tool depends on the delivery of a safe and controlled cytotoxic thermal dose to tumor tissue following activation with an alternating magnetic field (AMF). Prior to clinical approval, knowledge of IONP toxicity, biodistribution and physiological clearance is essential. This preliminary time-course study determines the acute toxicity and biodistribution of 110 nm dextran-coated IONP (iron) in mice, 7 days post systemic, at doses of 0.4, 0.6, and 1.0 mg Fe/ g mouse bodyweight. Acute toxicity, manifested as changes in the behavior of mice, was only observed temporarily at 1.0 mg Fe/ g mouse bodyweight, the highest dose administered. Regardless of dose, mass spectrometry and histological analysis demonstrated over 3 mg Fe/g tissue in organs within the reticuloendotheilial system (i.e. liver, spleen, and lymph nodes). Other organs (brain, heart, lungs, and kidney) had less than 0.5 mg Fe/g tissue with iron predominantly confined to the organ vasculature.

Mobile-Dose: A Dose-Meter Designed for Use in Automatic Machineries for Dose Manipulation in Nuclear Medicine

NASA Astrophysics Data System (ADS)

de Asmundis, Riccardo; Boiano, Alfonso; Ramaglia, Antonio

2008-06-01

Mobile-Dose has been designed for a very innovative use: the integration in a robotic machinery for automatic preparation of radioactive doses, to be injected to patients in Nuclear Medicine Departments, with real time measurement of the activity under preparation. Mobile-Dose gives a constant measurement of the dose during the filling of vials or syringes, triggering the end of the filling process based on a predefined dose limit. Several applications of Mobile-Dose have been delivered worldwide, from Italian hospitals and clinics to European and Japanese ones. The design of such an instrument and its integration in robotic machineries, was required by an Italian company specialised in radiation protection tools for nuclear applications, in the period 2001-2003. At the time of its design, apparently no commercial instruments with a suitable interfacing capability to the external world existed: we designed it in order to satisfy all the strict requirements coming from the medical aspects (precision within 10%, repeatability, stability, time response) and from the industrial conceiving principles that are mandatory to ensure a good reliability in such a complicated environment. The instrument is suitable to be used in standalone mode too, thanks to its portability and compactness and to the intelligent operator panel programmed for this purpose.

Cancer risk in relation to radioactivity in tobacco.

PubMed

Kilthau, G F

1996-01-01

Leaf tobacco contains minute amounts of lead 210 (210Pb) and polonium 210 (210Po), both of which are radioactive carcinogens and both of which can be found in smoke from burning tobacco. Tobacco smoke also contains carcinogens that are nonradioactive. People who inhale tobacco smoke are exposed to higher concentrations of radioactivity than nonsmokers. Deposits of 210Pb and alpha particle-emitting 210Po form in the lungs of smokers, generating localized radiation doses far greater than the radiation exposures humans experience from natural sources. This radiation exposure, delivered to sensitive tissues for long periods of time, may induce cancer both alone and synergistically with nonradioactive carcinogens. This article explores the relationship between the radioactive and nonradioactive carcinogens in leaf tobacco and tobacco smoke and the risk of cancer in those who inhale tobacco smoke.

Analytics of Radioactive Materials Released in the Fukushima Daiichi Nuclear Accident

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

Egarievwe, Stephen U.; Nuclear Engineering Department, University of Tennessee, Knoxville, TN; Coble, Jamie B.

The 2011 Fukushima Daiichi nuclear accident in Japan resulted in the release of radioactive materials into the atmosphere, the nearby sea, and the surrounding land. Following the accident, several meteorological models were used to predict the transport of the radioactive materials to other continents such as North America and Europe. Also of high importance is the dispersion of radioactive materials locally and within Japan. Based on the International Atomic Energy Agency (IAEA) Convention on Early Notification of a nuclear accident, several radiological data sets were collected on the accident by the Japanese authorities. Among the radioactive materials monitored, are I-131more » and Cs-137 which form the major contributions to the contamination of drinking water. The radiation dose in the atmosphere was also measured. It is impractical to measure contamination and radiation dose in every place of interest. Therefore, modeling helps to predict contamination and radiation dose. Some modeling studies that have been reported in the literature include the simulation of transport and deposition of I-131 and Cs-137 from the accident, Cs-137 deposition and contamination of Japanese soils, and preliminary estimates of I-131 and Cs-137 discharged from the plant into the atmosphere. In this paper, we present statistical analytics of I-131 and Cs-137 with the goal of predicting gamma dose from the Fukushima Daiichi nuclear accident. The data sets used in our study were collected from the IAEA Fukushima Monitoring Database. As part of this study, we investigated several regression models to find the best algorithm for modeling the gamma dose. The modeling techniques used in our study include linear regression, principal component regression (PCR), partial least square (PLS) regression, and ridge regression. Our preliminary results on the first set of data showed that the linear regression model with one variable was the best with a root mean square error of 0.0133 �

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

PubMed Central

Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2016-01-01

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

Location Modification Factors for Potential Dose Estimation

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

Snyder, Sandra F.; Barnett, J. Matthew

2017-01-01

A Department of Energy facility must comply with the National Emission Standard for Hazardous Air Pollutants for radioactive air emissions. The standard is an effective dose of less than 0.1 mSv yr-1 to the maximum public receptor. Additionally, a lower dose level may be assigned to a specific emission point in a State issued permit. A method to efficiently estimate the expected dose for future emissions is described. This method is most appropriately applied to a research facility with several emission points with generally low emission levels of numerous isotopes.

Pharmacokinetics of Dolutegravir When Administered With Mineral Supplements in Healthy Adult Subjects

PubMed Central

Song, Ivy; Borland, Julie; Arya, Niki; Wynne, Brian; Piscitelli, Stephen

2015-01-01

All commercially available integrase inhibitors are 2-metal binders and may be affected by co-administration with metal cations. The purpose of this study was to evaluate the effect of calcium and iron supplements on dolutegravir pharmacokinetics and strategies (dose separation and food) to attenuate the effects if significant reductions in dolutegravir exposure were observed. This was an open-label, crossover study that randomized 24 healthy subjects into 1 of 2 cohorts to receive 4 treatments: (1) dolutegravir alone, fasting; (2) dolutegravir with calcium carbonate or ferrous fumarate, fasting; (3) dolutegravir with calcium carbonate or ferrous fumarate with a moderate-fat meal; (4) dolutegravir administered 2 hours before calcium carbonate or ferrous fumarate, fasting. Plasma dolutegravir AUC(0–∞), Cmax, and C24 were reduced by 39%, 37%, and 39%, respectively, when co-administered with calcium carbonate while fasting and were reduced by 54%, 57%, and 56%, respectively, when co-administered with ferrous fumarate while fasting. Dolutegravir administration 2 hours before calcium or iron supplement administration (fasted), as well as administration with a meal, counteracted the effect. Dolutegravir and calcium or iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium or iron supplements. PMID:25449994

Radioactivity of buildings materials available in Slovakia

NASA Astrophysics Data System (ADS)

Singovszka, E.; Estokova, A.; Mitterpach, J.

2017-10-01

In the last decades building materials, both of natural origin and containing industrial by-products, have been shown to significantly contribute to the exposure of the population to natural radioactivity. As a matter of fact, neither the absorbed dose rate in air due to gamma radiation nor the radon activity concentration are negligible in closed environments. The soil and rocks of the earth contains substances which are naturally radioactive and provide natural radiation exposures. The most important radioactive elements which occur in the soil and in rocks are the long lived primordial isotopes of potassium (40K), uranium (238U) and thorium (232Th). Therefore, additional exposures have to be measured and compared with respect to the natural radiation exposure. Further, it is important to estimate the potential risk from radiation from the environment. The paper presents the results of mass activities of 226Ra, 232Th a 40K radionuclides in cement mortars with addition of silica fume. The gamma index was calculated as well.

Practical applications of internal dose calculations

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

Carbaugh, E.H.

1994-06-01

Accurate estimates of intake magnitude and internal dose are the goal for any assessment of an actual intake of radioactivity. When only one datum is available on which to base estimates, the choices for internal dose assessment become straight-forward: apply the appropriate retention or excretion function, calculate the intake, and calculate the dose. The difficulty comes when multiple data and different types of data become available. Then practical decisions must be made on how to interpret conflicting data, or how to adjust the assumptions and techniques underlying internal dose assessments to give results consistent with the data. This article describesmore » nine types of adjustments which can be incorporated into calculations of intake and internal dose, and then offers several practical insights to dealing with some real-world internal dose puzzles.« less

Route and Type of Formulation Administered Influences the Absorption and Disposition of Vitamin B12 Levels in Serum

PubMed Central

Zhou, Joyce; Manuel, Rachel; Dal Forno, Serena; Rutolo, David

2018-01-01

The administration of biological compounds that optimize health benefits is an ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological compounds have been administered via many different routes in order to produce a systemic pharmacological effect. The article summarizes the findings from an Australian comparative study in adults administered vitamin B12 through different oral delivery platforms. A total of 16 subjects (9 males, 7 females) voluntarily partook in a comparative clinical study of five different vitamin B12 formulations across a six-month period, completing 474 person-hours of cumulative contribution, that was equivalent to an n = 60 participation. A nanoparticle delivered vitamin B12 through a NanoCelle platform was observed to be significantly (p < 0.05) better absorbed than all other dose equivalent platforms (i.e., tablets, emulsions, or liposomes) from baseline to 1, 3, and 6 h of the study period. The nanoparticle platform delivered vitamin B12 demonstrated an enhanced and significant absorption profile as exemplified by rapid systemic detection (i.e., 1 h from baseline) when administered to the oro-buccal mucosa with no reports of any adverse events of toxicity. The nanoparticle formulation of methylcobalamin (1000 µg/dose in 0.3 mL volume) showed bioequivalence only with a chewable-dissolvable tablet that administered a five times higher dose of methylcobalamin (5000 µg) per tablet. This study has demonstrated that an active metabolite embedded in a functional biomaterial (NanoCelle) may constitute a drug delivery method that can better access the circulatory system. PMID:29361736

A biosphere modeling methodology for dose assessments of the potential Yucca Mountain deep geological high level radioactive waste repository.

PubMed

Watkins, B M; Smith, G M; Little, R H; Kessler, J

1999-04-01

Recent developments in performance standards for proposed high level radioactive waste disposal at Yucca Mountain suggest that health risk or dose rate limits will likely be part of future standards. Approaches to the development of biosphere modeling and dose assessments for Yucca Mountain have been relatively lacking in previous performance assessments due to the absence of such a requirement. This paper describes a practical methodology used to develop a biosphere model appropriate for calculating doses from use of well water by hypothetical individuals due to discharges of contaminated groundwater into a deep well. The biosphere model methodology, developed in parallel with the BIOMOVS II international study, allows a transparent recording of the decisions at each step, from the specification of the biosphere assessment context through to model development and analysis of results. A list of features, events, and processes relevant to Yucca Mountain was recorded and an interaction matrix developed to help identify relationships between them. Special consideration was given to critical/potential exposure group issues and approaches. The conceptual model of the biosphere system was then developed, based on the interaction matrix, to show how radionuclides migrate and accumulate in the biosphere media and result in potential exposure pathways. A mathematical dose assessment model was specified using the flexible AMBER software application, which allows users to construct their own compartment models. The starting point for the biosphere calculations was a unit flux of each radionuclide from the groundwater in the geosphere into the drinking water in the well. For each of the 26 radionuclides considered, the most significant exposure pathways for hypothetical individuals were identified. For 14 of the radionuclides, the primary exposure pathways were identified as consumption of various crops and animal products following assumed agricultural use of the contaminated

Effect of opicapone multiple‐dose regimens on levodopa pharmacokinetics

PubMed Central

Rocha, José‐Francisco; Sicard, Éric; Fauchoux, Nicolas; Falcão, Amílcar; Santos, Ana; Loureiro, Ana I.; Pinto, Roberto; Bonifácio, Maria João; Nunes, Teresa; Almeida, Luís

2016-01-01

Aims To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. Methods Two randomized, double blind, sex‐balanced, placebo‐controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once‐daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate‐release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate‐release 100/25 mg LB was administered. Results All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose‐dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (Emax) and extent (AUEC) of the catechol‐O‐methyltransferase activity in relation to placebo. The tolerability profile was favourable. Conclusion Opicapone, as once‐daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long‐lasting and sustained catechol‐O‐methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo. PMID:27763682

Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses.

PubMed

Barton, Christopher; Kouokam, J Calvin; Hurst, Harrell; Palmer, Kenneth E

2016-12-17

Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome-Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses.

Administering Eye Medications.

ERIC Educational Resources Information Center

Morris, Sara; Michael, Nancy, Ed.

This module on administering eye medications is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. A brief discussion follows of…

Defining the rectal dose constraint for permanent radioactive seed implantation of the prostate.

PubMed

Albert, Michele; Song, Jun S; Schultz, Delray; Cormack, Robert A; Tempany, Clare M; Haker, Steve; Devlin, Phillip M; Beard, Clair; Hurwitz, Mark D; Suh, Wonsuk W; Jolesz, Ferenc; D'Amico, Anthony V

2008-01-01

This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy. Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test. There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment. Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Pharmacokinetics of theophylline: a dose-range study.

PubMed Central

Rovei, V; Chanoine, F; Strolin Benedetti, M

1982-01-01

1 Pharmacokinetics of theophylline were investigated in a group of healthy adult volunteers (non smokers and on xanthine-free diet) following single oral administration of 125, 250, 375 and 500 mg doses as tablets (Theodel). 2 Absorption of theophylline was rapid and followed first-order kinetics. Plasma curves were fitted according to a one compartment open model. 3 There was a linear relationship (P less than 0.001) between plasma Cmax or AUCx values and the administered dose. The analysis of variance showed that the pharmacokinetic parameters of theophylline (t1/2 abs, tmax, t1/2 beta, CL, CLR, Vd and F) were not modified at any dose. 4 Absorption of the drug was complete since the recovery in urine of theophylline (13.7 to 16.8% of the dose) and its major metabolites, 1,3-dimethyluric acid (35 to 42%), 1-methyluric acid (21.3 to 26.7%) and 3-methylxanthine (11.5 to 13.7%), accounted for the administered dose. Some impairment of demethylation to 3-methylxanthine was observed in two subjects, however the percentage of theophylline and its major metabolites excreted in urine was constant for all the four doses. 5 On the basis of these results, after single oral administration, elimination of theophylline followed first-order kinetics in the range of doses investigated (1.62 to 10.42 mg/kg). PMID:7150456

Natural radioactivity and radiation hazards in some building materials used in Isparta, Turkey

NASA Astrophysics Data System (ADS)

Mavi, B.; Akkurt, I.

2010-09-01

The activity concentrations of uranium, thorium and potassium can vary from material to material and it should be measured as the radiation is hazardous for human health. Thus first studies have been planned to obtain radioactivity of building material used in the Isparta region of Turkey. The radioactivity of some building materials used in this region has been measured using a γ-ray spectrometry, which contains a NaI(Tl) detector connected to MCA. The specific activity for 226Ra, 232Th and 40K, from the selected building materials, were in the range 17.91-58.88, 6.77-19.49 and 65.72-248.76 Bq/kg, respectively. Absorbed dose rate in air ( D), annual effective dose (AED), radium equivalent activities (Ra eq), and external hazard index ( Hex) associated with the natural radionuclide are calculated to assess the radiation hazard of the natural radioactivity in the building materials. It was found that none of the results exceeds the recommended limit value.

Effect of reactor coolant radioactivity upon configuration feasibility for a nuclear electric propulsion vehicle

NASA Technical Reports Server (NTRS)

Soffer, L.; Wright, G. N.

1973-01-01

A preliminary shielding analysis was carried out for a conceptual nuclear electric propulsion vehicle designed to transport payloads from low earth orbit to synchronous orbit. The vehicle employed a thermionic nuclear reactor operating at 1575 kilowatts and generated 120 kilowatts of electricity for a round-trip mission time of 2000 hours. Propulsion was via axially directed ion engines employing 3300 pounds of mercury as a propellant. The vehicle configuration permitted a reactor shadow shield geometry using LiH and the mercury propellant for shielding. However, much of the radioactive NaK reactor coolant was unshielded and in close proximity to the power conditioning electronics. An estimate of the radioactivity of the NaK coolant was made and its unshielded dose rate to the power conditioning equipment calculated. It was found that the activated NaK contributed about three-fourths of the gamma dose constraint. The NaK dose was considered a sufficiently high fraction of the allowable gamma dose to necessitate modifications in configuration.

Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent.

PubMed

Ormsby, Rebecca J; Lawrence, Mark D; Blyth, Benjamin J; Bexis, Katrina; Bezak, Eva; Murley, Jeffrey S; Grdina, David J; Sykes, Pamela J

2014-02-01

The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.

Disposition of styrene-acrylonitrile (SAN) trimer in female rats: single dose intravenous and gavage studies.

PubMed

Gargas, Michael L; Collins, Brad; Fennell, Timothy R; Gaudette, Norman F; Sweeney, Lisa M

2008-04-21

Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile polymer. Disposition studies in female rats were conducted to evaluate the pharmacokinetic behavior of [3H]SAN Trimer following a single intravenous administration (26 mg/kg) to nonpregnant rats; a single gavage administration (nominal doses of 25 mg/kg, 75 mg/kg, or 200 mg/kg in corn oil) to nonpregnant rats; and a single gavage administration (nominal dose of 200 mg/kg in corn oil) to pregnant and lactating rats. SAN Trimer was rapidly eliminated from blood (T1/2 approximately 1h) following a single intravenous dose and following single oral doses (T1/2 approximately 3-4h). SAN Trimer was also rapidly excreted in the urine and feces following single oral doses, while total radioactivity was cleared more slowly. In pregnant rats, the concentrations of both radioactivity and SAN Trimer 2h after dosing were highest in the blood, followed by the placenta, with the lowest levels in the fetus. In lactating rats, the concentrations of both radioactivity and SAN Trimer were higher in milk than in maternal blood. Total radioactivity and SAN Trimer blood concentrations in nonpregnant, pregnant, and lactating rats were both higher in lactating rats compared to nonpregnant and pregnant rats.

Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats.

PubMed

Griffenhagen, Gregg M; Rezende, Marlis L; Gustafson, Daniel L; Hansen, Ryan J; Lunghofer, Paul J; Mama, Khursheed R

2015-09-01

To compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats. Prospective experimental study. Six healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg. Cats received 8 mg kg(-1) IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05). Plasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg(-1)  minute(-1) in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration. The addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats. © 2014 Association of Veterinary Anaesthetists and the

[Dose-effect relationship of orally administered Pyritinol in the chronic organic brain syndrome (author's transl)].

PubMed

Glatzel, J

1978-08-04

161 patients with the chronic organic brain syndrome (average age 64 years) were treated with various oral doses of Pyritinol for various periods of time. Statistical analysis of the data by means of "Konfigurationsfrequenzanalyse" showed that the success rate of treatment increases significantly with increasing dose and duration of the treatment. This means that the recommended daily dose should be exceeded if - for example at the start of treatment and in severe cases or in hospitalized patients - there is no immediate clear improvement in the condition. From the point of view of method this study shows that a retrospective analysis of a group of patients treated in a clinic can also provide interesting results and appropriately supplement controlled studies.

Assessment of natural radioactivity levels in soil samples from some areas in Assiut, Egypt.

PubMed

El-Gamal, Hany; Farid, M El-Azab; Abdel Mageed, A I; Hasabelnaby, M; Hassanien, Hassanien M

2013-12-01

The natural radioactivity of soil samples from Assiut city, Egypt, was studied. The activity concentrations of 28 samples were measured with a NaI(Tl) detector. The radioactivity concentrations of (226)Ra, (232)Th, and (40)K showed large variations, so the results were classified into two groups (A and B) to facilitate the interpretation of the results. Group A represents samples collected from different locations in Assiut and characterized by low activity concentrations with average values of 46.15 ± 9.69, 30.57 ± 4.90, and 553.14 ± 23.19 for (226)Ra, (232)Th, and (40)K, respectively. Group B represents samples mainly collected from the area around Assiut Thermal Power Plant and characterized by very high activity concentrations with average values of 3,803 ± 145, 1,782 ± 98, and 1,377 ± 78 for (226)Ra, (232)Th, and (40)K, respectively. In order to evaluate the radiological hazard of the natural radioactivity, the radium equivalent activity (Raeq), the absorbed dose rate (D), the annual effective dose rate (E), the external hazard index (H ex), and the annual gonadal dose equivalent (AGDE) have been calculated and compared with the internationally approved values. For group A, the calculated averages of these parameters are in good agreement with the international recommended values except for the absorbed dose rate and the AGDE values which are slightly higher than the international recommended values. However, for group B, all obtained averages of these parameters are much higher by several orders of magnitude than the international recommended values. The present work provides a background of radioactivity concentrations in the soil of Assiut.

[Investigation of actual condition of management and disposal of medical radioactive waste in Korea].

PubMed

Watanabe, Hiroshi; Nagaoka, Hiroaki; Yamaguchi, Ichiro; Horiuchi, Shoji; Imoto, Atsushi

2009-07-20

In order to realize the rational management and disposal of radioactive waste like DIS or its clearance as performed in Europe, North America, and Japan, we investigated the situation of medical radioactive waste in Korea and its enforcement. We visited three major Korean facilities in May 2008 and confirmed details of the procedure being used by administering a questionnaire after our visit. From the results, we were able to verify that the governmental agency had established regulations for the clearance of radioactive waste as self-disposal based on the clearance level of IAEA in Korea and that the medical facilities performed suitable management and disposal of radioactive waste based on the regulations and superintendence of a radiation safety officer. The type of nuclear medicine was almost the same as that in Japan, and the half-life of all radiopharmaceuticals was 60 days or less. While performing regulatory adjustment concerning the rational management and disposal of radioactive waste in Korea for reference also in this country, it is important to provide an enforcement procedure with quality assurance in the regulations.

Cocaine self-administration under variable-dose schedules in squirrel monkeys.

PubMed

Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W

2006-06-01

Squirrel monkeys self-administered cocaine under a variable-dose schedule, with the dose varied from injection to injection. As in earlier studies with rats, post-injection pauses varied as a monotonic function of dose, allowing a cocaine dose-effect curve to be obtained during each session. These curves were shifted by pretreatment with dopamine antagonists, demonstrating that this procedure may provide an efficient means of evaluating treatments that affect drug self-administration. However, drug intake eventually became "dysregulated" after extensive training (100-300 sessions), with relatively short pauses following all doses. Dose-sensitivity was restored by adding a 60-s timeout period after each injection, suggesting that dysregulation occurred because the monkeys developed a tendency to self-administer another injection before the previous injection had been adequately distributed. Finally, when the response requirement under the variable-dose schedule was increased from 1 to 10, both the post-injection pause and the rate of responding following the pause ("run rates") were found to vary with dose. The dose-dependency of run rates suggests that post-injection pauses reflect not only motivational factors, such as satiety, but also the direct effects of cocaine on leverpressing.

Single oral dose safety of D-allulose in dogs.

PubMed

Nishii, Naohito; Nomizo, Toru; Takashima, Satoshi; Matsubara, Tatsuya; Tokuda, Masaaki; Kitagawa, Hitoshi

2016-07-01

Healthy dogs were administered acute oral doses of D-allulose (also called D-psicose) to evaluate its toxicity. Six dogs received oral doses of either a placebo or D-allulose solution (1 and 4 g/kg) on three different study days. One dog experienced vomiting, and five dogs showed transient diarrhea when 4 g/kg of D-allulose was administered. All dogs were active and had a good appetite throughout the study period. Blood glucose concentration slightly decreased without a rise in plasma insulin concentration 2 hr after D-allulose administration. Plasma alkaline phosphatase activities showed a mild increase between 12 and 48 hr after D-allulose administration. These data suggested that a single oral dose of D-allulose does not show severe toxicity in dogs.

Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

PubMed

Halasa, Natasha B; Gerber, Michael A; Berry, Andrea A; Anderson, Edwin L; Winokur, Patricia; Keyserling, Harry; Eckard, Allison Ross; Hill, Heather; Wolff, Mark C; McNeal, Monica M; Edwards, Kathryn M; Bernstein, David I

2015-09-01

Children 6 through 35 months of age are recommended to receive half the dose of influenza vaccine compared with older children and adults. This was a 6-site, randomized 2:1, double-blind study comparing full-dose (0.5 mL) trivalent inactivated influenza vaccine (TIV) with half-dose (0.25 mL) TIV in children 6 through 35 months of age. Children previously immunized with influenza vaccine (primed cohort) received 1 dose, and those with no previous influenza immunizations (naive cohort) received 2 doses of TIV. Local and systemic adverse events were recorded. Sera were collected before immunization and 1 month after last dose of TIV. Hemagglutination inhibition antibody testing was performed. Of the 243 subjects enrolled (32 primed, 211 naive), data for 232 were available for complete analysis. No significant differences in local or systemic reactions were observed. Few significant differences in immunogenicity to the 3 vaccine antigens were noted. The immune response to H1N1 was significantly higher in the full-dose group among primed subjects. In the naive cohort, the geometric mean titer for all 3 antigens after 2 doses of TIV were significantly higher in the 12 through 35 months compared with the 6 through 11 months age group. Our study confirms the safety of full-dose TIV given to children 6 through 35 months of age. An increase in antibody responses after full- versus half-dose TIV was not observed, except for H1N1 in the primed group. Larger studies are needed to clarify the potential for improved immunogenicity with higher vaccine doses. Recommending the same dose could simplify the production, storage, and administration of influenza vaccines.

EMP Attachment 3 DOE-SC PNNL Site Dose Assessment Guidance

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

Snyder, Sandra F.

2011-12-21

This Dose Assessment Guidance (DAG) describes methods to use to determine the Maximally-Exposed Individual (MEI) location and to estimate dose impact to that individual under the U.S. Department of Energy Office of Science (DOE-SC) Pacific Northwest National Laboratory (PNNL) Site Environmental Monitoring Plan (EMP). This guidance applies to public dose from radioactive material releases to the air from PNNL Site operations. This document is an attachment to the Pacific Northwest National Laboratory (PNNL) Environmental Monitoring Plan (EMP) and describes dose assessment guidance for radiological air emissions. The impact of radiological air emissions from the U.S. Department of Energy Office ofmore » Science (DOE-SC) PNNL Site is indicated by dose estimates to a maximally exposed member of the public, referred to as the maximally exposed individual (MEI). Reporting requirements associated with dose to members of the public from radiological air emissions are in 40 CFR Part 61.94, WAC 246-247-080, and DOE Order 458.1. The DOE Order and state standards for dose from radioactive air emissions are consistent with U.S. Environmental Protection Agency (EPA) dose standards in 40 CFR 61.92 (i.e., 10 mrem/yr to a MEI). Despite the fact that the current Contract Requirements Document (CRD) for the DOE-SC PNNL Site operations does not include the requirement to meet DOE CRD 458.1, paragraph 2.b, public dose limits, the DOE dose limits would be met when EPA limits are met.« less

Effective dose in the manufacturing process of rutile covered welding electrodes.

PubMed

Herranz, M; Rozas, S; Pérez, C; Idoeta, R; Núñez-Lagos, R; Legarda, F

2013-03-01

Shielded metal arc welding using covered electrodes is the most common welding process. Sometimes the covering contains naturally occurring radioactive materials (NORMs). In Spain the most used electrodes are those covered with rutile mixed with other materials. Rutile contains some detectable natural radionuclides, so it can be considered a NORM. This paper mainly focuses on the use of MCNP (Monte Carlo N-Particle Transport Code) as a predictive tool to obtain doses in a factory which produces this type of electrode and assess the radiological impact in a specific facility after estimating the internal dose.To do this, in the facility, areas of highest radiation and positions of workers were identified, radioactive content of rutile and rutile covered electrodes was measured, and, considering a worst possible scenario, external dose at working points has been calculated using MCNP. This procedure has been validated comparing the results obtained with those from a pressurised ionisation chamber and TLD dosimeters. The internal dose has been calculated using DCAL (dose and risk calculation). The doses range between 8.8 and 394 μSv yr(-1), always lower than the effective dose limit for the public, 1 mSv yr(-1). The highest dose corresponds to the mixing area.

Simulating the venting of radioactivity from a soviet nuclear test

NASA Astrophysics Data System (ADS)

Rodriguez, Daniel J.; Peterson, Kendall R.

Fresh fission products were found in several routine air samples in Europe during the second and third weeks of March 1987. Initially, it was suspected that the radionuclides, principally 133Xe and 131I, had been accidentally released from a European facility handling nuclear materials. However, the announcement of an underground nuclear test at Semipalatinsk, U.S.S.R. on 26 February 1987 suggested that the elevated amounts of radioactivity may, instead, have been caused by a venting episode. Upon learning of these events, we simulated the transport and diffusion of 133Xe with our Hemispheric MEDIC and ADPIC models, assuming Semipalatinsk to be the source of the radioactive emissions. The correspondence between the calculated concentrations and the daily average 133Xe measurements made by the Federal Office for Civil Protection in F.R.G. was excellent. While this agreement does not, in itself, prove that an atmospheric venting of radioactive material occurred at Semipalatinsk, a body of circumstantial evidence exists which, when added together, strongly supports this conclusion. Our calculations suggested a total fission yield of about 40 kt, which is within the 20-150 kt range of tests acknowledged by the U.S.S.R. Finally, dose calculations indicated that no health or environmental impact occurred outside of the U.S.S.R. due to the suspected venting of 133Xe. However, the inhalation dose resulting from 133I, an unmodeled component of the radioactive cloud, represented a greater potential risk to public health.

The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome.

PubMed

Mao, Qixing; Manservisi, Fabiana; Panzacchi, Simona; Mandrioli, Daniele; Menghetti, Ilaria; Vornoli, Andrea; Bua, Luciano; Falcioni, Laura; Lesseur, Corina; Chen, Jia; Belpoggi, Fiorella; Hu, Jianzhong

2018-05-29

Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats. Glyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis. Microbiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls. This study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood.

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

PubMed

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

Effects of low doses of americium 241 on animals

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

Rudnitskaya, E.I.; Moskalev, Yu.I.

1979-10-01

The long term effects of low doses of americium 241 on dogs and rats were investigated. Americium chloride was administered intravenously to dogs and intraperitoneally to rats in varying doses. The biological radiation effects were determined at autopsy. Survival times were reported.

Reference levels of background radioactivity for beach sands and soils in İnebolu/Kastamonu-Turkey

NASA Astrophysics Data System (ADS)

Kurnaz, Aslı; Türkdoǧan, Savaş; Hançerlioǧulları, Aybaba; ćetiner, M. Atıf

2016-03-01

This paper presents the measurement results of environmental radioactivity levels for İnebolu district (tourist area), Kastamonu-Turkey. The radioactivity concentrations of 238U, 232Th, 40K and the fission product 137Cs in soil samples collected from 13 region surroundings of study area and in 12 beach sand samples collected from along the coast of İnebolu were determined. To evaluate the radiological hazard of the natural radioactivity, based on the measured concentrations of these radionuclides, the mean absorbed gamma dose and the annual effective dose were evaluated separately, and found to be 112.90 nGy h-1 and 138.46 µSv y-1 for soil samples and 75.19 nGy h-1 and 92.22 µSv y-1 for beach sand samples, respectively. The results show that İnebolu does not have high background.

Radioactive impacts on nekton species in the Northwest Pacific and humans more than one year after the Fukushima nuclear accident.

PubMed

Men, Wu; Deng, Fangfang; He, Jianhua; Yu, Wen; Wang, Fenfen; Li, Yiliang; Lin, Feng; Lin, Jing; Lin, Longshan; Zhang, Yusheng; Yu, Xingguang

2017-10-01

This study investigated the radioactive impacts on 10 nekton species in the Northwest Pacific more than one year after the Fukushima Nuclear Accident (FNA) from the two perspectives of contamination and harm. Squids were especially used for the spatial and temporal comparisons to demonstrate the impacts from the FNA. The radiation doses to nekton species and humans were assessed to link this radioactivity contamination to possible harm. The total dose rates to nektons were lower than the ERICA ecosystem screening benchmark of 10μGy/h. Further dose-contribution analysis showed that the internal doses from the naturally occurring nuclide 210 Po were the main dose contributor. The dose rates from 134 Cs, 137 Cs, 90 Sr and 110m Ag were approximately three or four orders of magnitude lower than those from naturally occurring radionuclides. The 210 Po-derived dose was also the main contributor of the total human dose from immersion in the seawater and the ingestion of nekton species. The human doses from anthropogenic radionuclides were ~ 100 to ~ 10,000 times lower than the doses from naturally occurring radionuclides. A morbidity assessment was performed based on the Linear No Threshold assumptions of exposure and showed 7 additional cancer cases per 100,000,000 similarly exposed people. Taken together, there is no need for concern regarding the radioactive harm in the open ocean area of the Northwest Pacific. Copyright © 2017 Elsevier Inc. All rights reserved.

Induced radioactivity in the forward shielding and semiconductor tracker of the ATLAS detector.

PubMed

Bĕdajánek, I; Linhart, V; Stekl, I; Pospísil, S; Kolros, A; Kovalenko, V

2005-01-01

The radioactivity induced in the forward shielding, copper collimator and semiconductor tracker modules of the ATLAS detector has been studied. The ATLAS detector is a long-term experiment which, during operation, will require to have service and access to all of its parts and components. The radioactivity induced in the forward shielding was calculated by Monte Carlo methods based on GEANT3 software tool. The results show that the equivalent dose rates on the outer surface of the forward shielding are very low (at most 0.038 microSv h(-1)). On the other hand, the equivalent dose rates are significantly higher on the inner surface of the forward shielding (up to 661 microSv h(-1)) and, especially, at the copper collimator close to the beampipe (up to 60 mSv h(-1)). The radioactivity induced in the semiconductor tracker modules was studied experimentally. The module was activated by neutrons in a training nuclear reactor and the delayed gamma ray spectra were measured. From these measurements, the equivalent dose rate on the surface of the semiconductor tracker module was estimated to be < 100 microSv h(-1) after 100 d of Large Hadron Collider (LHC) operation and 10 d of cooling.

Automatic optimisation of gamma dose rate sensor networks: The DETECT Optimisation Tool

NASA Astrophysics Data System (ADS)

Helle, K. B.; Müller, T. O.; Astrup, P.; Dyve, J. E.

2014-05-01

Fast delivery of comprehensive information on the radiological situation is essential for decision-making in nuclear emergencies. Most national radiological agencies in Europe employ gamma dose rate sensor networks to monitor radioactive pollution of the atmosphere. Sensor locations were often chosen using regular grids or according to administrative constraints. Nowadays, however, the choice can be based on more realistic risk assessment, as it is possible to simulate potential radioactive plumes. To support sensor planning, we developed the DETECT Optimisation Tool (DOT) within the scope of the EU FP 7 project DETECT. It evaluates the gamma dose rates that a proposed set of sensors might measure in an emergency and uses this information to optimise the sensor locations. The gamma dose rates are taken from a comprehensive library of simulations of atmospheric radioactive plumes from 64 source locations. These simulations cover the whole European Union, so the DOT allows evaluation and optimisation of sensor networks for all EU countries, as well as evaluation of fencing sensors around possible sources. Users can choose from seven cost functions to evaluate the capability of a given monitoring network for early detection of radioactive plumes or for the creation of dose maps. The DOT is implemented as a stand-alone easy-to-use JAVA-based application with a graphical user interface and an R backend. Users can run evaluations and optimisations, and display, store and download the results. The DOT runs on a server and can be accessed via common web browsers; it can also be installed locally.

Discussions about safety criteria and guidelines for radioactive waste management.

PubMed

Yamamoto, Masafumi

2011-07-01

In Japan, the clearance levels for uranium-bearing waste have been established by the Nuclear Safety Commission (NSC). The criteria for uranium-bearing waste disposal are also necessary; however, the NSC has not concluded the discussion on this subject. Meanwhile, the General Administrative Group of the Radiation Council has concluded the revision of its former recommendation 'Regulatory exemption dose for radioactive solid waste disposal', the dose criteria after the institutional control period for a repository. The Standardization Committee on Radiation Protection in the Japan Health Physics Society (The Committee) also has developed the relevant safety criteria and guidelines for existing exposure situations, which are potentially applicable to uranium-bearing waste disposal. A new working group established by The Committee was initially aimed at developing criteria and guidelines specifically for uranium-bearing waste disposal; however, the aim has been shifted to broader criteria applicable to any radioactive wastes.

Radioactive Waste Management Complex low-level waste radiological performance assessment

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

Maheras, S.J.; Rood, A.S.; Magnuson, S.O.

This report documents the projected radiological dose impacts associated with the disposal of radioactive low-level waste at the Radioactive Waste Management Complex at the Idaho National Engineering Laboratory. This radiological performance assessment was conducted to evaluate compliance with applicable radiological criteria of the US Department of Energy and the US Environmental Protection Agency for protection of the public and the environment. The calculations involved modeling the transport of radionuclides from buried waste, to surface soil and subsurface media, and eventually to members of the public via air, groundwater, and food chain pathways. Projections of doses were made for both offsitemore » receptors and individuals inadvertently intruding onto the site after closure. In addition, uncertainty and sensitivity analyses were performed. The results of the analyses indicate compliance with established radiological criteria and provide reasonable assurance that public health and safety will be protected.« less

Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.

PubMed

Tyl, Benoît; Kabbaj, Meriam; Azzam, Sara; Sologuren, Ander; Valiente, Román; Reinbolt, Elizabeth; Roupe, Kathryn; Blanco, Nathalie; Wheeler, William

2012-06-01

The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

Rivaroxaban crushed tablet suspension characteristics and relative bioavailability in healthy adults when administered orally or via nasogastric tube.

PubMed

Moore, Kenneth T; Krook, Mark A; Vaidyanathan, Seema; Sarich, Troy C; Damaraju, C V; Fields, Larry E

2014-07-01

Because some patients have difficulty swallowing a whole tablet, we investigated the relative bioavailability of a crushed 20 mg rivaroxaban tablet and of 2 alternative crushed tablet dosing strategies. Stability and nasogastric (NG) tube adsorption characteristics of a crushed rivaroxaban tablet were assessed. Then, in 55 healthy adults, relative bioavailability of rivaroxaban administered orally as a whole tablet (Reference [Whole-Oral]), crushed tablet in applesauce suspension (Crushed-Oral), or crushed tablet in water suspension via NG tube (Crushed-NG) were determined. There were no significant changes in mean percent of non-degraded rivaroxaban recovered over 4 hours from crushed tablet suspensions (>98.4% recovery across all suspensions and time points) or after NG tube exposure (recovery: 99.1% for silicone and 98.9% for polyvinyl chloride NG tubes). Relative bioavailability was similar between Crushed-Oral and Reference dosing (Cmax and AUC∞ were within the 80-125% bioequivalence limits). Relative bioavailability was also similar between the Crushed-NG and Reference dosing (AUC∞ was within bioequivalence limits; Cmax [90% CI range: 78.5-85.8%] was only slightly below the 80% lower bioequivalence limit). A crushed rivaroxaban tablet was stable and when administered orally or via NG tube, displayed similar relative bioavailability compared to a whole tablet administered orally. © 2014, The American College of Clinical Pharmacology.

ASSESSMENT OF RADIOACTIVE AND NON-RADIOACTIVE CONTAMINANTS FOUND IN LOW LEVEL RADIOACTIVE WASTE STREAMS

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

R.H. Little, P.R. Maul, J.S.S. Penfoldag

2003-02-27

This paper describes and presents the findings from two studies undertaken for the European Commission to assess the long-term impact upon the environment and human health of non-radioactive contaminants found in various low level radioactive waste streams. The initial study investigated the application of safety assessment approaches developed for radioactive contaminants to the assessment of nonradioactive contaminants in low level radioactive waste. It demonstrated how disposal limits could be derived for a range of non-radioactive contaminants and generic disposal facilities. The follow-up study used the same approach but undertook more detailed, disposal system specific calculations, assessing the impacts of bothmore » the non-radioactive and radioactive contaminants. The calculations undertaken indicated that it is prudent to consider non-radioactive, as well as radioactive contaminants, when assessing the impacts of low level radioactive waste disposal. For some waste streams with relatively low concentrations of radionuclides, the potential post-closure disposal impacts from non-radioactive contaminants can be comparable with the potential radiological impacts. For such waste streams there is therefore an added incentive to explore options for recycling the materials involved wherever possible.« less

A study of folate absorption and metabolism in man utilizing carbon-14—labeled polyglutamates synthesized by the solid phase method

PubMed Central

Butterworth, C. E.; Baugh, C. M.; Krumdieck, Carlos

1969-01-01

The absorption and metabolism of synthetic polyglutamates of folic acid have been compared with free pteroylglutamic acid in four subjects having chronic lymphatic leukemia and one with Hodgkin's granuloma. Pteroylpolyglutamates containing either three or seven glutamate residues were prepared by the solid-phase method permitting placement of carbon-14 labels in either the pteridine ring or in a selected glutamate unit of the gamma peptide chain. Complete dissociation was observed between biological folate activity and radioactivity of plasma after ingestion of pteroyltriglutamate labeled in the middle glutamate. This indicates cleavage to the monoglutamate form at the time of absorption from the intestine or very soon thereafter. A large portion of radioactivity liberated from the middle glutamate is recoverable as carbon dioxide in the exhaled air. Fecal losses of folate tended to be greater with increasing length of the poly-γ-glutamyl chain. Higher blood levels and greater urinary losses of folate tended to occur after ingestion of mono- and triglutamates than with the heptaglutamate. Calculations based on radioactivity determinations in feces plus urinary folate losses, judged by either radioactivity or microbiological assays, indicated net retention of 37-67% of the dose irrespective of chain length ingested and major avenue of loss. During the peak of absorption the folate circulating in plasma was active for both Streptococcus fecalis and Lactobacillus casei and carried specific radioactivity which was virtually identical with that of the administered dose. This suggests that neither methylation, conjugation, nor displacement of nonradioactive folate occurred to any significant extent during the 1st 2 hr. The specific radioactivity of 24-hr urine specimens as measured with L. casei corresponded closely with that of the administered dose. Evidence exists that methylation of the radioactive folate may occur, but significant displacement of nonradioactive

Understanding the Radioactive Ingrowth and Decay of Naturally Occurring Radioactive Materials in the Environment: An Analysis of Produced Fluids from the Marcellus Shale.

PubMed

Nelson, Andrew W; Eitrheim, Eric S; Knight, Andrew W; May, Dustin; Mehrhoff, Marinea A; Shannon, Robert; Litman, Robert; Burnett, William C; Forbes, Tori Z; Schultz, Michael K

2015-07-01

The economic value of unconventional natural gas resources has stimulated rapid globalization of horizontal drilling and hydraulic fracturing. However, natural radioactivity found in the large volumes of "produced fluids" generated by these technologies is emerging as an international environmental health concern. Current assessments of the radioactivity concentration in liquid wastes focus on a single element-radium. However, the use of radium alone to predict radioactivity concentrations can greatly underestimate total levels. We investigated the contribution to radioactivity concentrations from naturally occurring radioactive materials (NORM), including uranium, thorium, actinium, radium, lead, bismuth, and polonium isotopes, to the total radioactivity of hydraulic fracturing wastes. For this study we used established methods and developed new methods designed to quantitate NORM of public health concern that may be enriched in complex brines from hydraulic fracturing wastes. Specifically, we examined the use of high-purity germanium gamma spectrometry and isotope dilution alpha spectrometry to quantitate NORM. We observed that radium decay products were initially absent from produced fluids due to differences in solubility. However, in systems closed to the release of gaseous radon, our model predicted that decay products will begin to ingrow immediately and (under these closed-system conditions) can contribute to an increase in the total radioactivity for more than 100 years. Accurate predictions of radioactivity concentrations are critical for estimating doses to potentially exposed individuals and the surrounding environment. These predictions must include an understanding of the geochemistry, decay properties, and ingrowth kinetics of radium and its decay product radionuclides.

Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

PubMed

Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

2016-12-01

Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

Radiological protection from radioactive waste management in existing exposure situations resulting from a nuclear accident.

PubMed

Sugiyama, Daisuke; Hattori, Takatoshi

2013-01-01

In environmental remediation after nuclear accidents, radioactive wastes have to be appropriately managed in existing exposure situations with contamination resulting from the emission of radionuclides by such accidents. In this paper, a framework of radiation protection from radioactive waste management in existing exposure situations for application to the practical and reasonable waste management in contaminated areas, referring to related ICRP recommendations was proposed. In the proposed concept, intermediate reference levels for waste management are adopted gradually according to the progress of the reduction in the existing ambient dose in the environment on the basis of the principles of justification and optimisation by taking into account the practicability of the management of radioactive waste and environmental remediation. It is essential to include the participation of relevant stakeholders living in existing exposure situations in the selection of reference levels for the existing ambient dose and waste management.

Radiological protection from radioactive waste management in existing exposure situations resulting from a nuclear accident

PubMed Central

Sugiyama, Daisuke; Hattori, Takatoshi

2013-01-01

In environmental remediation after nuclear accidents, radioactive wastes have to be appropriately managed in existing exposure situations with contamination resulting from the emission of radionuclides by such accidents. In this paper, a framework of radiation protection from radioactive waste management in existing exposure situations for application to the practical and reasonable waste management in contaminated areas, referring to related ICRP recommendations was proposed. In the proposed concept, intermediate reference levels for waste management are adopted gradually according to the progress of the reduction in the existing ambient dose in the environment on the basis of the principles of justification and optimisation by taking into account the practicability of the management of radioactive waste and environmental remediation. It is essential to include the participation of relevant stakeholders living in existing exposure situations in the selection of reference levels for the existing ambient dose and waste management. PMID:22719047

Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets.

PubMed

Christrup, L L; Angelo, H R; Bonde, J; Kristensen, F; Rasmussen, S N

1990-01-01

Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum and tablets (p greater than 0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts.

Analysis on the influence of forest soil characteristics on radioactive Cs infiltration and evaluation of residual radioactive Cs on surfaces.

PubMed

Mori, Yoshitomo; Yoneda, Minoru; Shimada, Yoko; Fukutani, Satoshi; Ikegami, Maiko; Shimomura, Ryohei

2018-03-29

We investigated the depth profiles of radioactive Cs, ignition loss, and cation exchange capacity (CEC) in five types of forest soils sampled using scraper plates. We then simulated the monitored depth profiles in a compartment model, taking ignition loss as a parameter based on experimental results showing a positive correlation between ignition loss and the CEC. The calculated values were comparable with the monitored values, though some discrepancy was observed in the middle of the soil layer. Based on decontamination data on the surface dose rate and surface contamination concentration, we newly defined a surface residual index (SRI) to evaluate the residual radioactive Cs on surfaces. The SRI value tended to gradually decrease in forests and unpaved roads and was much smaller in forests and on unpaved roads than on paved roads. The radioactive Cs was assumed to have already infiltrated underground 18 months after the nuclear power plant accident, and the sinking was assumed to be ongoing. The SRI values measured on paved roads suggested that radioactive Cs remained on the surfaces, though a gradual infiltration was observed towards the end of the monitoring term. The SRI value is thought to be effective in grasping the rough condition of residual radioactive Cs quickly at sites of decontamination activity in the field. The SRI value may be serviceable for actual contamination works after further research is done to elucidate points such as the relation between the SRI and the infiltration of radioactive Cs in various types of objects.

Bioequivalence among three methods of administering pantoprazole granules in healthy subjects.

PubMed

Tammara, Brinda; Weisel, Kathy; Katz, Arie; Meng, Xu

2009-11-01

The bioequivalence among three methods of administering pantoprazole granules was studied in healthy subjects. In this randomized, open-label, three-period, crossover study, 25 healthy adults received a single 40-mg dose of pantoprazole granules with applesauce orally, with apple juice orally, and with apple juice administered via a nasogastric tube. Subjects were randomly assigned to one of six treatment sequences. Blood samples were collected within 2 hours before treatment administration on study day 1 and at 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours after treatment administration. Plasma pantoprazole concentrations were analyzed by a validated liquid chromatography-tandem mass spectrometry method. The plasma pantoprazole concentration-time data for each subject were analyzed using noncompartmental methods. The 90% confidence intervals (CIs) for the test:reference geometric mean ratio were calculated for the peak pantoprazole concentration (C(max) ) and area under the concentration-time curve (AUC). Of the 25 subjects enrolled, 100% completed the study. The mean C(max) and AUC values were similar for the three administration methods. The 90% CIs for the ratios of the geometric means of the granules in apple juice orally (92.4-112.5%) and in apple juice administered through a nasogastric tube (102.7-125.2%), relative to the granules administered with applesauce orally, were essentially within the bioequivalent limits of 80-125%. No serious adverse events or study discontinuations occurred. Three methods of administering pantoprazole delayed-release granules for oral suspension-with apple juice orally, with applesauce orally, and with apple juice through a nasogastric tube--were bioequivalent in healthy subjects.

The clinical pharmacology of alkylating agents in high-dose chemotherapy.

PubMed

Huitema, A D; Smits, K D; Mathôt, R A; Schellens, J H; Rodenhuis, S; Beijnen, J H

2000-08-01

Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is to summarize the clinical pharmacology of the alkylating agents (including the platinum compounds) in high-dose chemotherapy. Differences between conventional and high doses will be discussed.

Radiometric assessment of natural radioactivity levels of agricultural soil samples collected in Dakahlia, Egypt.

PubMed

Issa, Shams A M

2013-01-01

Determination of the natural radioactivity has been carried out, by using a gamma-ray spectrometry [NaI (Tl) 3″ × 3″] system, in surface soil samples collected from various locations in Dakahlia governorate, Egypt. These locations form the agriculturally important regions of Egypt. The study area has many industries such as chemical, paper, organic fertilisers and construction materials, and the soils of the study region are used as a construction material. Therefore, it becomes necessary to study the natural radioactivity levels in soil to assess the dose for the population in order to know the health risks. The activity concentrations of (226)Ra, (232)Th and (40)K in the soil ranged from 5.7 ± 0.3 to 140 ± 7, from 9.0 ± 0.4 to 139 ± 7 and from 22 ± 1 to 319 ± 16 Bq kg(-1), respectively. The absorbed dose rate, annual effective dose rate, radium equivalent (Req), excess lifetime cancer risk, hazard indices (Hex and Hin) and annual gonadal dose equivalent, which resulted from the natural radionuclides in the soil were calculated.

A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma.

PubMed

Dunphy, F R; Boyd, J H; Kim, H J; Dunphy, C H; Harrison, B R; Dunleavy, T L; Rodriguez, J J; McDonough, E M; Minster, J R; Hilton, J G

1997-05-15

Standard therapy for advanced head and neck carcinoma is surgery and radiation, and the subsequent 5-year survival with this treatment has been less than 50%. New combined modality treatment strategies are being tested to improve survival. New chemotherapy combinations are being developed and administered simultaneously with, or sequenced with, radiation and surgery. This article reports the Phase I results of administering paclitaxel and carboplatin preoperatively. The authors' objective was to develop an outpatient chemotherapy that would downstage tumors and allow organ preservation with equal or improved survival as compared with standard therapy. Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. All patients had lesions that were measurable in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days with escalating doses of paclitaxel (150-265 mg/m2) given as a 3-hour infusion immediately preceding carboplatin. Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was administered intravenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5). The dose-limiting toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of 250-265 mg/m2. Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting. Toxicity was acceptable. The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this combination are warranted in the treatment of these carcinomas.

Optimising drug dosing in patients receiving extracorporeal membrane oxygenation.

PubMed

Cheng, Vesa; Abdul-Aziz, Mohd-Hafiz; Roberts, Jason A; Shekar, Kiran

2018-03-01

Optimal pharmacological management during extracorporeal membrane oxygenation (ECMO) involves more than administering drugs to reverse underlying disease. ECMO is a complex therapy that should be administered in a goal-directed manner to achieve therapeutic endpoints that allow reversal of disease and ECMO wean, minimisation of complications (treatment of complications when they do occur), early interruption of sedation and rehabilitation, maximising patient comfort and minimising risks of delirium. ECMO can alter both the pharmacokinetics (PK) and pharmacodynamics (PD) of administered drugs and our understanding of these alterations is still evolving. Based on available data it appears that modern ECMO circuitry probably has a less significant impact on PK when compared with critical illness itself. However, these findings need further confirmation in clinical population PK studies and such studies are underway. The altered PD associated with ECMO is less understood and more research is indicated. Until robust dosing guidelines become available, clinicians will have to rely on the principles of drug dosing in critically ill and known PK alterations induced by ECMO itself. This article summarises the PK alterations and makes preliminary recommendations on possible dosing approaches.

Effective dose evaluation of NORM-added consumer products using Monte Carlo simulations and the ICRP computational human phantoms.

PubMed

Lee, Hyun Cheol; Yoo, Do Hyeon; Testa, Mauro; Shin, Wook-Geun; Choi, Hyun Joon; Ha, Wi-Ho; Yoo, Jaeryong; Yoon, Seokwon; Min, Chul Hee

2016-04-01

The aim of this study is to evaluate the potential hazard of naturally occurring radioactive material (NORM) added consumer products. Using the Monte Carlo method, the radioactive products were simulated with ICRP reference phantom and the organ doses were calculated with the usage scenario. Finally, the annual effective doses were evaluated as lower than the public dose limit of 1mSv y(-1) for 44 products. It was demonstrated that NORM-added consumer products could be quantitatively assessed for the safety regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative Analgesic Efficacy of Pregabalin Administered According to Either a Prevention Protocol or an Intervention Protocol in Rats with Cisplatin-induced Peripheral Neuropathy.

PubMed

Han, F Y; Kuo, A; Nicholson, J R; Corradinni, L; Smith, M T

2018-05-21

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of peripheral neuropathic pain that may be dose-limiting in patients administered potentially curative cancer chemotherapy dosing regimens. In cancer survivors, persistent CIPN adversely affects patient quality of life and so adjuvant drugs (anticonvulsants e.g. pregabalin or antidepressants e.g. amitriptyline) are recommended for the relief of CIPN. However, most studies in rodent models of CIPN involve administration of single bolus doses of adjuvant drugs to assess pain-relieving efficacy. Hence this study was designed to assess the efficacy of pregabalin administered to CIPN-rats according to either a prevention or an intervention protocol. Groups of male Sprague-Dawley rats received four single intraperitoneal bolus doses of cisplatin at 3 mg/kg at once-weekly intervals to induce CIPN. For the prevention protocol, oral pregabalin (or vehicle) was administered to CIPN-rats once-daily for 21 consecutive days from day 0 to day 20 inclusive. For the intervention protocol, oral pregabalin was administered once-daily for 21 consecutive days from day 28 to day 48 inclusive. Mechanical allodynia and mechanical hyperalgesia in the bilateral hindpaws were assessed just prior to each dose of cisplatin and at least once-weekly until study completion (day 27, prevention protocol; or day 48, intervention protocol). Mechanical allodynia and mechanical hyperalgesia were also determined at the time of peak effect at ~2 h post- pregabalin/vehicle administration once-weekly until study completion. For the prevention protocol in CIPN-rats, pregabalin alleviated mechanical hyperalgesia but not mechanical allodynia. For the intervention protocol, pregabalin alleviated both mechanical allodynia and mechanical hyperalgesia in the hindpaws. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Determination of spatial dose distribution in UCC treatments with LDR brachytherapy using Monte Carlo methods.

PubMed

Benites-Rengifo, Jorge Luis; Vega-Carrillo, Hector Rene

2018-05-19

Using Monte Carlos methods, with the MCNP5 code, a gynecological phantom and a vaginal cylinder were modeled. The spatial distribution of absorbed dose rates in Uterine Cervical Cancer treatment through low dose rate brachytherapy was determined. A liquid water gynecology computational phantom, including a vaginal cylinder applicator made of Lucite, was designed. The applicator has a linear array of four radioactive sources of Cesium 137. Around the vaginal cylinder, 13 water spherical cells of 0.5 cm-diameter were modeled to calculate absorbed dose emulating the procedure made by the treatment planning system. The gamma-ray fluence distribution was estimated, as well as the absorbed doses resulting approximately symmetrical for cells located at upper and lower of vaginal cylinder. Obtained results allow the use of the radioactive decay law to determine dose rate for Uterine Cervical Cancer using low dose rate brachytherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Emergency department management of patients internally contaminated with radioactive material

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

Kazzi, Ziad; Buzzell, Jennifer; Bertelli, Luiz

After a radiation emergency that involves the dispersal of radioactive material, patients can become externally and internally contaminated with one or more radionuclides. Internal contamination can lead to the delivery of harmful ionizing radiation doses to various organs and tissues or the whole body. The clinical consequences can range from acute radiation syndrome (ARS) to the long term development of cancer. Estimating the amount of radioactive material absorbed into the body can guide the management of patients. Treatment includes, in addition to supportive care and long term monitoring, certain medical countermeasures like Prussian blue, Calcium DTPA and Zinc DTPA.

Emergency department management of patients internally contaminated with radioactive material

DOE PAGES

Kazzi, Ziad; Buzzell, Jennifer; Bertelli, Luiz; ...

2014-11-15

After a radiation emergency that involves the dispersal of radioactive material, patients can become externally and internally contaminated with one or more radionuclides. Internal contamination can lead to the delivery of harmful ionizing radiation doses to various organs and tissues or the whole body. The clinical consequences can range from acute radiation syndrome (ARS) to the long term development of cancer. Estimating the amount of radioactive material absorbed into the body can guide the management of patients. Treatment includes, in addition to supportive care and long term monitoring, certain medical countermeasures like Prussian blue, Calcium DTPA and Zinc DTPA.

Emergency Department Management of Patients Internally Contaminated with Radioactive Material

PubMed Central

Kazzi, Ziad; Buzzell, Jennifer; Bertelli, Luiz; Christensen, Doran

2017-01-01

SUMMARY Internal contamination with radioactive material can expose patients to radiation leading to short- and long-term clinical consequences. After the patient’s emergency conditions are addressed and the skin is decontaminated, the treating physicians assess the amount of radioactive material that has been internalized. This evaluation allows the estimation of the radiation dose that is delivered the specific radionuclide inside the body and supports the need for additional therapies and monitoring. These complex assessments warrant the reliance on a multidisciplinary approach that incorporates local, regional, and national experts in radiation medicine and emergencies. PMID:25455668

Radioactive plume from the Three Mile Island accident: xenon-133 in air at a distance of 375 kilometers.

PubMed

Wahlen, M; Kunz, C O; Matuszek, J M; Mahoney, W E; Thompson, R C

1980-02-08

The transit of an air mass containing radioactive gas released from the Three Mile Island reactor was recorded in Albany, New York, by measuring xenon-133. These measurements provide an evaluation of Three Mile Island effluents to distances greater than 100 kilometers. Two independent techniques identified xenon-133 in ambient air at concentrations as high as 3900 picocuries per cubic meter. The local gamma-ray whole-body dose from the passing radioactivity amounted to 0.004 millirem, or 0.004 percent of the annual dose from natural sources.

Radiological risk assessment and biosphere modelling for radioactive waste disposal in Switzerland.

PubMed

Brennwald, M S; van Dorp, F

2009-12-01

Long-term safety assessments for geological disposal of radioactive waste in Switzerland involve the demonstration that the annual radiation dose to humans due to the potential release of radionuclides from the waste repository into the biosphere will not exceed the regulatory limit of 0.1 mSv. Here, we describe the simple but robust approach used by Nagra (Swiss National Cooperative for the Disposal of Radioactive Waste) to quantify the dose to humans as a result to time-dependent release of radionuclides from the geosphere into the biosphere. The model calculates the concentrations of radionuclides in different terrestrial and aquatic compartments of the surface environment. The fluxes of water and solids within the environment are the drivers for the exchange of radionuclides between these compartments. The calculated radionuclide concentrations in the biosphere are then used to estimate the radiation doses to humans due to various exposure paths (e.g. ingestion of radionuclides via drinking water and food, inhalation of radionuclides, external irradiation from radionuclides in soils). In this paper we also discuss recent new achievements and planned future work.

The Effect of Ongoing Exposure Dynamics in Dose Response Relationships

PubMed Central

Pujol, Josep M.; Eisenberg, Joseph E.; Haas, Charles N.; Koopman, James S.

2009-01-01

Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, is a sequence of discrete events where concurrent or prior pathogen arrival affects the capacity of immune effectors to engage and kill newly arriving pathogens. We model immune effector and pathogen interactions during the period before infection becomes established in order to capture the dynamics generating dose timing effects. Model analysis reveals an inverse relationship between the time over which exposures accumulate and the risk of infection. Data from one time dose experiments will thus overestimate per pathogen infection risks of real world exposures. For instance, fitting our model to one time dosing data reveals a risk of 0.66 from 313 Cryptosporidium parvum pathogens. When the temporal exposure window is increased 100-fold using the same parameters fitted by our model to the one time dose data, the risk of infection is reduced to 0.09. Confirmation of this risk prediction requires data from experiments administering doses with different timings. Our model demonstrates that dose timing could markedly alter the risks generated by airborne versus fomite transmitted pathogens. PMID:19503605

Characteristics and Dose Levels for Spent Reactor Fuels

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

Coates, Cameron W

2007-01-01

Current guidance considers highly radioactive special nuclear materials to be those materials that, unshielded, emit a radiation dose [rate] measured at 1 m which exceeds 100 rem/h. Smaller, less massive fuel assemblies from research reactors can present a challenge from the point of view of self protection because of their size (lower dose, easier to handle) and the desirability of higher enrichments; however, a follow-on study to cross-compare dose trends of research reactors and power reactors was deemed useful to confirm/verify these trends. This paper summarizes the characteristics and dose levels of spent reactor fuels for both research reactors andmore » power reactors and extends previous studies aimed at quantifying expected dose rates from research reactor fuels worldwide.« less

Effective dose in SMAW and FCAW welding processes using rutile consumables.

PubMed

Herranz, M; Rozas, S; Idoeta, R; Alegría, N

2014-03-01

The shielded metal arc welding (SMAW) and flux cored arc welding (FCAW) processes use covered electrodes and flux cored wire as consumables. Among these consumables, ones containing rutile are the most widely used, and since they have a considerable natural radioactive content, they can be considered as NORM (naturally occurring radioactive material). To calculate the effective dose on workers during their use in a conservative situation, samples of slag and aerosols and particles emitted or deposited during welding were taken and measured by gamma, alpha and beta spectrometry. An analytical method was also developed for estimating the activity concentration of radionuclides in the inhaled air. (222)Rn activity concentration was also assessed. With all these data, internal and external doses were calculated. The results show that external doses are negligible in comparison with internal ones, which do not exceed 1 mSv yr(-1), either in this conservative situation or in any other more favourable one. Radionuclides after Rn in the radioactive natural series are emitted at the same activity concentration to the atmosphere, this being around 17 times higher than that corresponding to radionuclides before Rn. Taking into account these conclusions and the analytical method developed, it can be concluded that one way to assess the activity concentration of natural radionuclides in inhaled air and hence effective doses could be the early gamma-ray spectrometry of aerosols and particles sampled during the welding process.

Reference levels of background radioactivity for beach sands and soils in İnebolu/Kastamonu-Turkey

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

Kurnaz, Aslı, E-mail: akurnaz@kastamonu.edu.tr; Türkdoğan, Savaş, E-mail: savas-turk-dogan@hotmail.com; Hançerlioğulları, Aybaba, E-mail: aybaba@kastamonu.edu.tr

This paper presents the measurement results of environmental radioactivity levels for İnebolu district (tourist area), Kastamonu-Turkey. The radioactivity concentrations of {sup 238}U, {sup 232}Th, {sup 40}K and the fission product {sup 137}Cs in soil samples collected from 13 region surroundings of study area and in 12 beach sand samples collected from along the coast of İnebolu were determined. To evaluate the radiological hazard of the natural radioactivity, based on the measured concentrations of these radionuclides, the mean absorbed gamma dose and the annual effective dose were evaluated separately, and found to be 112.90 nGy h-1 and 138.46 µSv y-1 for soilmore » samples and 75.19 nGy h-1 and 92.22 µSv y-1 for beach sand samples, respectively. The results show that İnebolu does not have high background.« less

Establishment of the low-level radwaste classification using the dose-to-curie technique at the Lan-Yu Temporary Storage Site, Taiwan

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

King, J.Y.; Lang, T.C.; Wei, H.J.

2007-07-01

The Fuel Cycle and Materials Administration (FCMA) in Taiwan announced a Supplementary Regulation for Classification of Low Radioactive Wastes, as well as the Regulation for Disposing of Low Radioactive Wastes and its Facility Safety Management in July 17, 1997, and September 10, 2003, respectively. The latter regulation states that in the future, before delivering low-level radioactive waste to a final land disposal site, each waste drum must specify the nuclide activity and be classified as class A, B, C or greater than C. The nuclide activity data for approximately 100,000 drums of low-level radwaste at the Lan-Yu temporary storage sitemore » accumulated in 1982-1995, therefore, must be established according to the above regulations. The original waste database at the Lan-Yu site indicates that the data were absent for about 9% and 72% of Co-60 and Cs-137 key nuclide activities, respectively. One of the principal tasks in this project was to perform whole drum gamma radioactivity analysis and contact dose rate counting to establish the relationship of dose-to-curie (D-to-C) of specific waste stream to derive gamma radioactivity of counting drums for 2 trenches repackaged at the Lan-Yu site. Utilizing regression function of Microsoft Excel and collected gamma data, a dose-to-curie relationship for the whole-drum radwaste is estimated in this study. Based on the relationship between radioactivity of various nuclides and the surface dose rate, an empirical function of the dose rate (Dose) associated with product of nuclide activity (Curie) and energy (Energy), CE is set up. Statistical data demonstrated that 838 whole drums were counted employing D-to-C approach to classify other 3,279 drums, and only the contact dose rate was detected for roughly 75% of the drums to estimate gamma radioactivity of whole drums, which can save considerable cost, time, and manpower. The 4,508 drums were classified as A and 7 drums as C after repackaging was complete. The estimation

The display of sexual behaviors by female rats administered ICI 182,780.

PubMed

Clark, Ann S; Guarraci, Fay A; Megroz, Alison B; Porter, Donna M; Henderson, Leslie P

2003-04-01

ICI 182,780 (ICI) is a pure antiestrogen that when administered systemically does not cross the blood-brain barrier, thus its actions are limited to the periphery. Four experiments were conducted to test the effects of ICI on the display of sexual behaviors in ovariectomized rats. Experiment 1 examined the effects of three doses of ICI (250, 500, and 750 micro g/rat) on sexual receptivity and paced mating behavior in rats primed with estradiol benzoate (EB) in combination with progesterone (P). Experiments 2 and 3 compared the display of sexual behaviors in rats primed with EB+P or EB alone and administered either 250 micro g ICI (Experiment 2) or 500 micro g ICI (Experiment 3). Experiment 4 tested the effects of ICI (250 and 500 micro g) on the expression of estrogen-induced progestin receptors in the uterus. ICI did not affect the display of sexual receptivity in any experiment. In rats primed with EB+P, paced mating behavior was altered by the 500 and 750 micro g, but not the 250 micro g, doses of ICI. The lowest (250 micro g) dose of ICI did alter paced mating behavior in rats primed with EB alone. The effects of ICI on paced mating behavior were manifested by a substantial lengthening of contact-return latencies following intromissions and ejaculations. The percentage of exits were not affected by ICI. Estrogen stimulation of uterine weight and induction of uterine progestin receptors was suppressed by ICI (250 and 500 micro g). ICI effects on paced mating behavior in hormone-primed female rats are likely to reflect antiestrogenic actions in the periphery, including interference with the estrogen induction of progestin receptors.

Nonclinical Safety Assessment of SYN-004: An Oral β-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics.

PubMed

Kokai-Kun, John F; Bristol, J Andrew; Setser, John; Schlosser, Michael

2016-05-01

SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials. © The Author(s) 2015.

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2012 CFR

2012-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2013 CFR

2013-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

10 CFR 20.1502 - Conditions requiring individual monitoring of external and internal occupational dose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... internal occupational dose. 20.1502 Section 20.1502 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Surveys and Monitoring § 20.1502 Conditions requiring individual monitoring of external and internal occupational dose. Each licensee shall monitor exposures to radiation and radioactive...

Radioactivity of cigarettes and the importance of (210)Po and thorium isotopes for radiation dose assessment due to smoking.

PubMed

Kubalek, Davor; Serša, Gregor; Štrok, Marko; Benedik, Ljudmila; Jeran, Zvonka

2016-05-01

Tobacco and tobacco smoke are very complex mixtures. In addition to various chemical and organic compounds they also contain natural radioactive elements (radionuclides). In this work, the natural radionuclide activity concentrations ((234)U, (238)U, (228)Th, (230)Th, (232)Th, (226)Ra, (210)Pb and (210)Po) of nine different cigarette samples available on the Slovenian market are reported. In addition to (210)Po, the transfer of thorium isotopes from a cigarette to a smoker's body and lungs have been determined for the first time. Cigarette smoke and exhaled air from smokers' lungs were collected from volunteer smokers (C-4 brand) to determinate what quantity of (210)Po and thorium isotopes is transferred from the tobacco to the smoker's lungs. Cigarette ash and smoked filters were also collected and analysed. Among the determined isotopes, (210)Pb and (210)Po showed the highest activity concentrations. During the smoking of one cigarette approximately 22% of (210)Po (and presumably its predecessor (210)Pb), 0.6% of (228)Th, 24% of (230)Th, and 31% of (232)Th are transferred from the cigarette and retained in the smoker's body. The estimated annual effective dose for smokers is 61 μSv/year from (210)Po; 9 μSv/year from (210)Pb; 6 μSv/year from (228)Th; 47 μSv/year from (230)Th, and 37 μSv/year from (232)Th. These results show the importance of thorium isotopes in contributing to the annual effective dose for smoking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral desensitization to milk: how to choose the starting dose!

PubMed Central

Mori, Francesca; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Azzari, Chiara; Novembre, Elio

2010-01-01

Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. PMID:19624618

Radiation Dose Assessments for Fleet-Based Individuals in Operation Tomodachi, Revision 1

DTIC Science & Technology

2014-04-01

U.S. agencies were also deployed to the area. DOD took actions to ensure that radioactively contaminated food and bottled water did not reach the...material from contaminated surfaces of ships or aircraft or in water, food , or soil and dust each day while on shore. These doses were calculated for...Exposure below Deck on Ships .......................................................... 22 2.4.4. Exposure related to Radioactive Surface Contamination

Understanding the Radioactive Ingrowth and Decay of Naturally Occurring Radioactive Materials in the Environment: An Analysis of Produced Fluids from the Marcellus Shale

PubMed Central

Nelson, Andrew W.; Eitrheim, Eric S.; Knight, Andrew W.; May, Dustin; Mehrhoff, Marinea A.; Shannon, Robert; Litman, Robert; Burnett, William C.; Forbes, Tori Z.

2015-01-01

Background The economic value of unconventional natural gas resources has stimulated rapid globalization of horizontal drilling and hydraulic fracturing. However, natural radioactivity found in the large volumes of “produced fluids” generated by these technologies is emerging as an international environmental health concern. Current assessments of the radioactivity concentration in liquid wastes focus on a single element—radium. However, the use of radium alone to predict radioactivity concentrations can greatly underestimate total levels. Objective We investigated the contribution to radioactivity concentrations from naturally occurring radioactive materials (NORM), including uranium, thorium, actinium, radium, lead, bismuth, and polonium isotopes, to the total radioactivity of hydraulic fracturing wastes. Methods For this study we used established methods and developed new methods designed to quantitate NORM of public health concern that may be enriched in complex brines from hydraulic fracturing wastes. Specifically, we examined the use of high-purity germanium gamma spectrometry and isotope dilution alpha spectrometry to quantitate NORM. Results We observed that radium decay products were initially absent from produced fluids due to differences in solubility. However, in systems closed to the release of gaseous radon, our model predicted that decay products will begin to ingrow immediately and (under these closed-system conditions) can contribute to an increase in the total radioactivity for more than 100 years. Conclusions Accurate predictions of radioactivity concentrations are critical for estimating doses to potentially exposed individuals and the surrounding environment. These predictions must include an understanding of the geochemistry, decay properties, and ingrowth kinetics of radium and its decay product radionuclides. Citation Nelson AW, Eitrheim ES, Knight AW, May D, Mehrhoff MA, Shannon R, Litman R, Burnett WC, Forbes TZ, Schultz MK. 2015

High-dose-rate prostate brachytherapy inverse planning on dose-volume criteria by simulated annealing.

PubMed

Deist, T M; Gorissen, B L

2016-02-07

High-dose-rate brachytherapy is a tumor treatment method where a highly radioactive source is brought in close proximity to the tumor. In this paper we develop a simulated annealing algorithm to optimize the dwell times at preselected dwell positions to maximize tumor coverage under dose-volume constraints on the organs at risk. Compared to existing algorithms, our algorithm has advantages in terms of speed and objective value and does not require an expensive general purpose solver. Its success mainly depends on exploiting the efficiency of matrix multiplication and a careful selection of the neighboring states. In this paper we outline its details and make an in-depth comparison with existing methods using real patient data.

Efficacy, immunogenicity, and safety of two doses of a tetravalent rotavirus vaccine RRV-TV in Ghana with the first dose administered during the neonatal period.

PubMed

Armah, George E; Kapikian, Albert Z; Vesikari, Timo; Cunliffe, Nigel; Jacobson, Robert M; Burlington, D Bruce; Ruiz, Leonard P

2013-08-01

Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

PubMed

Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

2018-06-01

There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial.

PubMed

Mayer, Kenneth H; Seaton, Kelly E; Huang, Yunda; Grunenberg, Nicole; Isaacs, Abby; Allen, Mary; Ledgerwood, Julie E; Frank, Ian; Sobieszczyk, Magdalena E; Baden, Lindsey R; Rodriguez, Benigno; Van Tieu, Hong; Tomaras, Georgia D; Deal, Aaron; Goodman, Derrick; Bailer, Robert T; Ferrari, Guido; Jensen, Ryan; Hural, John; Graham, Barney S; Mascola, John R; Corey, Lawrence; Montefiori, David C

2017-11-01

VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18-50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities

Pharmacokinetics of pregabalin controlled-release in healthy volunteers: effect of food in five single-dose, randomized, clinical pharmacology studies.

PubMed

Chew, Marci L; Plotka, Anna; Alvey, Christine W; Pitman, Verne W; Alebic-Kolbah, Tanja; Scavone, Joseph M; Bockbrader, Howard N

2014-09-01

The pharmacokinetic properties of the immediate-release (IR) and the recently developed controlled-release (CR) formulation of pregabalin are dose proportional. Pregabalin IR can be taken with or without food. This analysis characterizes the effect of food on pregabalin CR. The objectives of this analysis were: (1) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR (330 mg) relative to a single dose of pregabalin IR (300 mg); (2) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food; and (3) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food. The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I, open-label, single-dose, crossover studies (24-28 participants/study). Caloric and fat content of meals were varied and treatments were administered in the morning, at midday, or in the evening. Blood samples were collected up to 48 h post-dose. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout all studies. One hundred and twenty-eight healthy participants (19-54 years of age) received pregabalin. Peak plasma concentrations (C max) were lower for CR than the respective pregabalin IR doses, and time to C max occurred later. When pregabalin CR was administered with food at midday or in the evening, total exposures [area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC∞)] were equivalent for pregabalin CR and IR formulations regardless of fat or caloric content. When pregabalin CR was administered with an 800-1,000 calorie medium-fat breakfast, AUC∞ was equivalent for

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2013 CFR

2013-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2014 CFR

2014-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2012 CFR

2012-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2011 CFR

2011-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2010 CFR

2010-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

Dose commitments due to radioactive releases from nuclear power plant sites in 1989

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

Baker, D.A.

Population and individual radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1989. Fifty-year dose commitments for a one-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 72 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for each of the sites is an estimate of individual doses which are compared with 10 CFR Partmore » 50, Appendix I design objectives. The total collective dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 14 person-rem to a low of 0.005 person-rem for the sites with plants in operation and producing power during the year. The arithmetic mean was 1.2 person-rem. The total population dose for all sites was estimated at 84 person-rem for the 140 million people considered at risk. The individual dose commitments estimated for all sites were below the Appendix I design objectives.« less

DELAYED PREPUTIAL SEPARATION (PPS) AND SP22 MEASUREMENT IN RATS ADMINISTERED BROMOCHLOROACETIC ACID (BCA) IN DRINKING WATER

EPA Science Inventory

Reproductive effects of BCA were determined in a dose range finding study (DRFS) and definitive two-generational study. Adult male and female CD� (SD) rats were administered BCA in drinking water for two weeks in the DRFS (10/sex/group) and ten weeks in the definitive study (25/s...

Severe neuropathy after high dose carboplatin in three patients receiving multidrug chemotherapy

PubMed Central

Heinzlef, O.; Lotz, J.; Roullet, E.

1998-01-01

Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation. 

 PMID:9598687

RADIOACTIVE IODINE IN THE LYMPH LEAVING THE THYROID GLAND

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

Daniel, R.M.; Gale, M.M.; Pratt, O.E.

1963-04-01

Very high levels of I/sup 131/ were found in lymph of vessels draining the thyroid gland of animals injected with the isotope. The lymph was collected from the draining lymphatics 2-6 days after subcutaneous injection of 50-100 mu C in rabbits and cats and 200 mu C in sheep. Thyroid lymph contained a concentration of radioactivity considerably higher than that in either thyroid venous plasma or systemic blood plasma. This was found in all three species both before and after giving thyroid-stimulating hormone (TSH). Almost all the radioactivity in the lymph was due to organic I/sup 131/. When tie thyroidmore » gland was excised postmortem, a count showed that the proportion of I/sup 131/ which had been injected and which rernained in the gland at the end of the experiment varied considerably. Estimates of the radiation dose varied between 30 and 200 rad. There was no obvious relation between this dose the lymph/plasma I/sup 131/ ratio, which indicates that the radiation dose was not so high as to produce damage to the gland. The radiation dose to the thyroid in these experiments was not greater than is customarily given in studies of hormone release from the thyroid and the dosage used gives a lower level of radiation than that thought to cause radiation damage to the gland. Since, therefore, damage to the thyroid can be discounted as a cause for the release of iodinated protein, it seems likely that a significart proportion of organic iodine leaves the gland under normal conditions via the lymphatic pathway both before and after the administration of TSH and that this pathway should be taken into account in all studies of thyroid secretion. Gentle massage of the gland, which increases the flow of lymph, did not lead to an increase in the output of radioactivity. Movement of lymph in the thyroid vessels is relatively rapid and since the concentration of I/sup 131/ in thyroid lymph is high, the amount of thyroid hormones leaving the gland by this pathway must be

Design of a portable dose rate detector based on a double Geiger-Mueller counter

NASA Astrophysics Data System (ADS)

Wang, Peng; Tang, Xiao-Bin; Gong, Pin; Huang, Xi; Wen, Liang-Sheng; Han, Zhen-Yang; He, Jian-Ping

2018-01-01

A portable dose rate detector was designed to monitor radioactive pollution and radioactive environments. The portable dose detector can measure background radiation levels (0.1 μSv/h) to nuclear accident radiation levels (>10 Sv/h). Both automatic switch technology of a double Geiger-Mueller counter and time-to-count technology were adopted to broaden the measurement range of the instrument. Global positioning systems and the 3G telecommunication protocol were installed to prevent radiation damage to the human body. In addition, the Monte Carlo N-Particle code was used to design the thin layer of metal for energy compensation, which was used to flatten energy response The portable dose rate detector has been calibrated by the standard radiation field method, and it can be used alone or in combination with additional radiation detectors.

Pavlovian conditioning between co-administered drugs: elicitation of an apomorphine-induced antiparkinsonian response by scopolamine.

PubMed

Carey, R J

1991-01-01

Sprague-Dawley rats with unilateral 6-OHDA substantia nigra lesions were given combined scopolamine (0.5 mg/kg IP) and apomorphine (0.05 mg/kg SC) treatments. In this animal model, scopolamine, when administered separately, induces ipsilateral rotation and apomorphine, contralateral rotation. When these drugs are co-administered at 0.5 mg/kg and 0.05 mg/kg dose levels, respectively, animals rotate in the contralateral direction, creating the opportunity for the stimulus effect of scopolamine to become associated with the response effect of apomorphine. In tests with scopolamine (0.5 mg/kg), animals that previously had scopolamine and apomorphine co-administered rotated contralaterally in the test chamber, thereby behaving as if they had received apomorphine. Thus, scopolamine exhibited a functionally acquired conditioned stimulus (CS) property by eliciting the apomorphine response of contralateral rotation as a conditioned response. This acquired CS property was extinguished with separate scopolamine trials and reacquired following one scopolamine-apomorphine co-administration trial.

Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

PubMed

Goldberg, J; Freund, E; Beckers, B; Hinzmann, R

2001-02-01

Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler.

Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report.

PubMed

Stevens, R Brian; Mercer, David F; Grant, Wendy J; Freifeld, Alison G; Lane, James T; Groggel, Gerald C; Rigley, Theodore H; Nielsen, Kathleen J; Henning, Megan E; Skorupa, Jill Y; Skorupa, Anna J; Christensen, Kecia A; Sandoz, John P; Kellogg, Anna M; Langnas, Alan N; Wrenshall, Lucile E

2008-05-27

The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months). There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

Understanding the toxicity of buried radioactive waste and its impacts.

PubMed

Cohen, Bernard L

2005-10-01

The oral ingestion toxicities of buried high level radioactive waste from nuclear power plants and of the natural radioactivity in the ground are calculated and expressed as cancer doses, the number of fatal cancers predicted by the linear no-threshold theory if all of the material were fed to people. Unless the size of the U.S. nuclear power industry is greatly expanded, there will probably never be more than 2 trillion cancer doses (CD) in U.S. repositories, as compared with 31 trillion CD in the ground above them. Measurements of the uranium, thorium, and radium in human bodies indicate that the latter cause 500 deaths per year in U.S. The great majority of this material is derived from the top few meters of soil that are penetrated by plant roots. It is concluded that the annual number of U.S. deaths from buried nuclear wastes will be about 1.0 (or less), orders of magnitude less than the number from coal burning electricity generation, the principal competitor of nuclear power.

Predicting induced radioactivity for the accelerator operations at the Taiwan Photon Source.

PubMed

Sheu, R J; Jiang, S H

2010-12-01

This study investigates the characteristics of induced radioactivity due to the operations of a 3-GeV electron accelerator at the Taiwan Photon Source (TPS). According to the beam loss analysis, the authors set two representative irradiation conditions for the activation analysis. The FLUKA Monte Carlo code has been used to predict the isotope inventories, residual activities, and remanent dose rates as a function of time. The calculation model itself is simple but conservative for the evaluation of induced radioactivity in a light source facility. This study highlights the importance of beam loss scenarios and demonstrates the great advantage of using FLUKA in comparing the predicted radioactivity with corresponding regulatory limits. The calculated results lead to the conclusion that, due to fairly low electron consumption, the radioactivity induced in the accelerator components and surrounding concrete walls of the TPS is rather moderate and manageable, while the possible activation of air and cooling water in the tunnel and their environmental releases are negligible.

Radiation Doses from the Norwegian Diet.

PubMed

Komperød, Mari; Skuterud, Lavrans

2018-06-13

Ingestion doses between and within countries are expected to vary significantly due to differences in dietary habits and geographical variations in radionuclide concentrations. This paper presents the most comprehensive assessment to date of the effective radiation dose from the Norwegian diet, from natural as well as anthropogenic radionuclides. Ingestion doses to the Norwegian public are calculated using national dietary statistics and the most relevant radionuclide concentration data for the various food products. The age-weighted average effective dose received by the Norwegian population from the diet is estimated at 0.41 mSv y from naturally occurring radionuclides and 0.010 mSv y from anthropogenic radionuclides. This is approximately 50% higher than the estimated world average. Fish and shellfish is the food group that provides the largest dose contribution from the average Norwegian diet. Although the average dose from anthropogenic radionuclides today is low, the exposure may still be significant for certain critical groups-especially persons who consume large amounts of reindeer meat from the regions that received significant radioactive fallout after the Chernobyl accident. Furthermore, persons with high Rn concentrations in their drinking water are among those receiving the highest ingestion doses in Norway.

Absorption, distribution, metabolism and excretion (ADME) of the ALK inhibitor alectinib: results from an absolute bioavailability and mass balance study in healthy subjects.

PubMed

Morcos, Peter N; Yu, Li; Bogman, Katrijn; Sato, Mika; Katsuki, Hisakazu; Kawashima, Kosuke; Moore, David J; Whayman, Matt; Nieforth, Keith; Heinig, Katja; Guerini, Elena; Muri, Dieter; Martin-Facklam, Meret; Phipps, Alex

2017-03-01

1. Alectinib is a highly selective, central nervous system-active small molecule anaplastic lymphoma kinase inhibitor. 2. The absolute bioavailability, metabolism, excretion and pharmacokinetics of alectinib were studied in a two-period single-sequence crossover study. A 50 μg radiolabelled intravenous microdose of alectinib was co-administered with a single 600 mg oral dose of alectinib in the first period, and a single 600 mg/67 μCi oral dose of radiolabelled alectinib was administered in the second period to six healthy male subjects. 3. The absolute bioavailability of alectinib was moderate at 36.9%. Geometric mean clearance was 34.5 L/h, volume of distribution was 475 L and the hepatic extraction ratio was low (0.14). 4. Near-complete recovery of administered radioactivity was achieved within 168 h post-dose (98.2%) with excretion predominantly in faeces (97.8%) and negligible excretion in urine (0.456%). Alectinib and its major active metabolite, M4, were the main components in plasma, accounting for 76% of total plasma radioactivity. In faeces, 84% of dose was excreted as unchanged alectinib with metabolites M4, M1a/b and M6 contributing to 5.8%, 7.2% and 0.2% of dose, respectively. 5. This novel study design characterised the full absorption, distribution, metabolism and excretion properties in each subject, providing insight into alectinib absorption and disposition in humans.

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.

The radioactivity estimation of 14C and 3H in graphite waste samples of the KRR-2.

PubMed

Reyoung Kim, Hee

2013-09-01

The radioactivity of (14)C and (3)H in graphite samples from the dismantled Korea Research Reactor-2 (the KRR-2) site was analyzed by high-temperature oxidation and liquid scintillation counting, and the graphite waste was suggested to be disposed of as a low-level radioactive waste. The graphite samples were oxidized at a high temperature of 800 °C, and their counting rates were measured by using a liquid scintillation counter (LSC). The combustion ratio of the graphite was about 99% on the sample with a maximum weight of 1g. The recoveries from the combustion furnace were around 100% and 90% in (14)C and (3)H, respectively. The minimum detectable activity was 0.04-0.05 Bq/g for the (14)C and 0.13-0.15 Bq/g for the (3)H at the same background counting time. The activity of (14)C was higher than that of (3)H over all samples with the activity ratios of the (14)C to (3)H, (14)C/(3)H, being between 2.8 and 25. The dose calculation was carried out from its radioactivity analysis results. The dose estimation gave a higher annual dose than the domestic legal limit for a clearance. It was thought that the sampled graphite waste from the dismantled research reactor was not available for reuse or recycling and should be monitored as low-level radioactive waste. Copyright © 2013 Elsevier Ltd. All rights reserved.

Developmental toxic effects of N-ethyl-2-pyrrolidone administered orally to rats.

PubMed

Saillenfait, A M; Gallissot, F; Sabaté, J P

2007-01-01

The developmental toxicity of N-ethyl-2-pyrrolidone (NEP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given NEP at doses of 0 (distilled water), 50, 250, 500 and 750 mg kg(-1) day(-1), by gavage (5 ml kg(-1)), on gestational days (GD) 6-20. Maternal toxicity, as evidenced by reduction in body weight gain and food consumption, was observed in all NEP groups at the beginning of treatment (GD 6-9). The incidence of resorptions was significantly increased at 500 mg kg(-1) day(-1), and reached 83% at 750 mg kg(-1) day(-1). There was a dose-related decrease in fetal weight, which was significantly lower than control at 250 mg kg(-1) day(-1) and higher doses. The incidence of malformed fetuses per litter and the number of litters with malformed fetuses were significantly increased at 500 and 750 mg kg(-1) day(-1). Malformations mainly consisted of edema, anal atresia with absent tail, cardiovascular defects and fused cervical arches. Ossification of skull bones and sternebrae was significantly reduced at 500 and 750 mg kg(-1) day(-1). The incidence of supernumerary ribs was significantly elevated at 250 mg kg(-1) day(-1) and higher doses. In conclusion, NEP administered by gavage is embryotoxic and teratogenic at maternal toxic doses. (c) 2007 John Wiley & Sons, Ltd.

In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

PubMed

Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

2018-04-15

The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

Enterohepatic disposition of rosuvastatin in pigs and the impact of concomitant dosing with cyclosporine and gemfibrozil.

PubMed

Bergman, Ebba; Lundahl, Anna; Fridblom, Patrik; Hedeland, Mikael; Bondesson, Ulf; Knutson, Lars; Lennernäs, Hans

2009-12-01

The hepatobiliary transport and local disposition of rosuvastatin in pig were investigated, along with the impact of concomitant dosing with two known multiple transport inhibitors; cyclosporine and gemfibrozil. Rosuvastatin (80 mg) was administered as an intrajejunal bolus dose in treatments I, II, and III (TI, TII, and TIII, respectively; n = 6 per treatment). Cyclosporine (300 mg) and gemfibrozil (600 mg) were administered in addition to the rosuvastatin dose in TII and TIII, respectively. Cyclosporine was administered as a 2-h intravenous infusion and gemfibrozil as an intrajejunal bolus dose. In treatment IV (TIV, n = 4) 5.9 mg of rosuvastatin was administered as an intravenous bolus dose. The study was conducted using a pig model, which enabled plasma sampling from the portal (VP), hepatic (VH), and femoral veins and bile from the common hepatic duct. The biliary recoveries of the administered rosuvastatin dose were 9.0 +/- 3.5 and 35.7 +/- 15.6% in TI and TIV, respectively. Rosuvastatin was highly transported into bile as shown by the median AUC(bile)/AUC(VH) ratio in TI of 1770 (1640-11,300). Gemfibrozil did not have an effect on the plasma pharmacokinetics of rosuvastatin, most likely because the unbound inhibitor concentrations did not exceed the reported IC(50) values. However, cyclosporine significantly reduced the hepatic extraction of rosuvastatin (TI, 0.89 +/- 0.06; TII, 0.46 +/- 0.13) and increased the AUC(VP) and AUC(VH) by 1.6- and 9.1-fold, respectively. In addition, the biliary exposure and f(e, bile) were reduced by approximately 50%. The strong effect of cyclosporine was in accordance with inhibition of sinusoidal uptake transporters, such as members of the organic anion-transporting polypeptide family, rather than canalicular transporters.

Efficacy of alternate day versus daily dosing of rosuvastatin

PubMed Central

Dulay, Daisy; LaHaye, Stephen A; Lahey, Karen A; Day, Andrew G

2009-01-01

BACKGROUND: Compared with other statins, rosuvastatin has a relatively long half-life, which may allow for the administration of this medication on an alternate day basis. OBJECTIVE: To compare the efficacy of administering rosuvastatin on a daily basis versus on an alternate day basis for the treatment of dyslipidemia. METHODS: In the present crossover study, 45 patients with documented hypercholesterolemia requiring pharmacotherapy were administered either 20 mg of rosuvastatin on alternate days or 10 mg of rosuvastatin daily for six weeks. After a four-week washout period, patients were then switched to the other regimen for another six weeks. The primary end point was the percentage reduction of low-density lipoprotein cholesterol (LDL-C). RESULTS: LDL-C decreased by 48.5% versus 40.9% with daily and alternate day dosing, respectively. This represented an additional absolute reduction of LDL-C of 7.6% (95% CI 1.8% to 13.4%, P=0.012) with the daily dosing regimen. Both dosing regimens provided similar improvements in high-density lipoprotein cholesterol and triglycerides. CONCLUSIONS: Compared with alternate day dosing, daily dosing of rosuvastatin provides a statistically significant advantage in LDL-C reduction. However, the alternate day regimen may be a viable option for those patients in whom cost is a limitation to compliance. PMID:19214297

Bioavailability of dexmedetomidine after extravascular doses in healthy subjects

PubMed Central

Anttila, Markku; Penttilä, Jani; Helminen, Antti; Vuorilehto, Lauri; Scheinin, Harry

2003-01-01

Aim To determine the absolute bioavailability of extravascularly administered dexmedetomidine, a novel a2-adrenoceptor agonist, in healthy subjects. Methods Single 2 µg kg−1 doses of dexmedetomidine were given intravenously, intramuscularly, perorally and buccally (where the solution is not swallowed) to 12 healthy male subjects. The drug concentration-time data were analysed using linear one-compartment (buccal and peroral data), or two-compartment modelling (intravenous data), or noncompartmental methods (intramuscular data). Results Mean (95% CI) absolute bioavailability after peroral, buccal and intramuscular administration was 16% (12–20%), 82% (73–92%) and 104% (96–112%), respectively. Conclusion Dexmedetomidine is well absorbed systemically through the oral mucosa, and therefore buccal dosing may provide an effective, noninvasive route to administer the drug. PMID:14616431

Natural radioactivity in granite stones used as building materials in Iran.

PubMed

Asgharizadeh, F; Abbasi, A; Hochaghani, O; Gooya, E S

2012-04-01

Due to increasing concern about environmental radiological protection, specific radioactivity concentrations of (226)Ra, (232)Th and (40)K in different types of commonly used granite stone samples collected from the Tehran city of Iran have been determined by means of a high-resolution HPGe gamma-spectroscopy system. The activity concentrations of (232)Th, (226)Ra and (40)K in the selected granite samples ranged from 18 to 178, 6 to 160 and 556 to 1539 Bq kg(-1), respectively. The radium equivalent activities (Ra(eq)) are lower than the limit of 370 Bq kg(-1) set by NEA-OECD [Nuclear Energy Agency. Exposure to radiation from natural radioactivity in building materials. Report by NEA Group of Experts. OECD (1979)], except in two samples. The internal hazard indexes have been found well below the acceptable limit in most of the samples. Five samples of investigated commercial granite stones do not satisfy the safety criterion illustrated by UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation. Exposure from natural sources of radiation. Report to the General Assembly (1993). Applying dose criteria recently recommended by the EC [European Commission Report on Radiological Protection Principles Concerning the Natural Radioactivity of Building Materials. Radiation Protection 112 (1999)] for superficial materials, all investigated samples meet the exemption dose limit of 0.3 mSv y(-1).

Low dose orally administered arginine is able to enhance both basal and growth hormone-releasing hormone-induced growth hormone secretion in normal short children.

PubMed

Bellone, J; Bartolotta, E; Cardinale, G; Arvat, E; Cherubini, V; Aimaretti, G; Maccario, M; Mucci, M; Camanni, F; Ghigo, E

1993-01-01

Aim of this study was to verify whether arginine (ARG), which likely inhibits hypothalamic somatostatin release, has an enhancing effect on the GHRH-induced GH rise, even when administered orally at low dose. To this goal we studied the effects of 4 g orally administered ARG, either hydrochloride (ARG-H) or aspartate (ARG-A), on both basal and GHRH (1 microgram/Kg i.v.)-stimulated GH secretion in 31 children with familial short stature (11 males and 20 females, aged 5.5-13.8 yr, pubertal stage I-III, and compared the results with those of i.v. infusion of 0.5 g/kg ARG-H. Oral ARG-H (Group A, n = 11) induced a significant increase of basal GH levels (4.2 +/- 1.3 vs 1.0 +/- 0.4 micrograms/L, p < 0.02) and enhanced the GH response to GHRH (41.1 +/- 8.6 vs 25.3 +/- 6.7 micrograms/L, p < 0.02). Oral ARG-A (Group B, n = 10) induced a slight, but not statistically significant increase in serum GH levels (3.4 +/- 1.5 vs 1.0 +/- 0.3 micrograms/L) and enhanced the GHRH-induced GH rise (49.7 +/- 9.8 vs 26.1 +/- 8.4 micrograms/L, p < 0.05). Intravenous ARG-H (Group C, n = 10) stimulated basal GH levels (6.2 +/- 1.2 vs 1.2 +/- 0.3 micrograms/L, p < 0.005) and increased the GHRH-induced GH rise (46.7 +/- 5.0 vs 17.1 +/- 2.3 micrograms/L, p < 0.005). This response was similar to those after oral ARG-H or ARG-A plus GHRH. No variation was observed in PRL levels after oral ARG (either ARG-H or ARG-A) and/or GHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel method for estimation of the indoor-to-outdoor airborne radioactivity ratio following the Fukushima Daiichi Nuclear Power Plant accident.

PubMed

Tan, Yanliang; Ishikawa, Tetsuo; Janik, Miroslaw; Tokonami, Shinji; Hosoda, Masahiro; Sorimachi, Atsuyuki; Kearfott, Kimberlee

2015-12-01

The accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP) in Japan resulted in significant releases of fission products. While substantial data exist concerning outdoor air radioactivity following the accident, the resulting indoor radioactivity remains pure speculation without a proper method for estimating the ratio of the indoor to outdoor airborne radioactivity, termed the airborne sheltering factor (ASF). Lacking a meaningful value of the ASF, it is difficult to assess the inhalation doses to residents and evacuees even when outdoor radionuclide concentrations are available. A simple model was developed and the key parameters needed to estimate the ASF were obtained through data fitting of selected indoor and outdoor airborne radioactivity measurement data obtained following the accident at a single location. Using the new model with values of the air exchange rate, interior air volume, and the inner surface area of the dwellings, the ASF can be estimated for a variety of dwelling types. Assessment of the inhalation dose to individuals readily follows from the value of the ASF, the person's indoor occupancy factor, and the measured outdoor radioactivity concentration. Copyright © 2015 Elsevier B.V. All rights reserved.

Radiation protection considerations along a radioactive ion beam transport line

NASA Astrophysics Data System (ADS)

Sarchiapone, Lucia; Zafiropoulos, Demetre

2016-09-01

The goal of the SPES project is to produce accelerated radioactive ion beams for Physics studies at “Laboratori Nazionali di Legnaro” (INFN, Italy). This accelerator complex is scheduled to be built by 2016 for an effective operation in 2017. Radioactive species are produced in a uranium carbide target, by the interaction of 200 μA of protons at 40 MeV. All of the ionized species in the 1+ state come out of the target (ISOL method), and pass through a Wien filter for a first selection and an HMRS (high mass resolution spectrometer). Then they are transported by an electrostatic beam line toward a charge state breeder (where the 1+ to n+ multi-ionization takes place) before selection and reacceleration at the already existing superconducting linac. The work concerning dose evaluations, activation calculation, and radiation protection constraints related to the transport of the radioactive ion beam (RIB) from the target to the mass separator will be described in this paper. The FLUKA code has been used as tool for those calculations needing Monte Carlo simulations, in particular for the evaluation of the dose rate due to the presence of the radioactive beam in the selection/interaction points. The time evolution of a radionuclide inventory can be computed online with FLUKA for arbitrary irradiation profiles and decay times. The activity evolution is analytically evaluated through the implementation of the Bateman equations. Furthermore, the generation and transport of decay radiation (limited to gamma, beta- and beta+ emissions) is possible, referring to a dedicated database of decay emissions using mostly information obtained from NNDC, sometimes supplemented with other data and checked for consistency. When the use of Monte Carlo simulations was not feasible, the Bateman equations, or possible simplifications, have been used directly.

16 CFR 1000.2 - Laws administered.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act (Pub...

16 CFR 1000.2 - Laws administered.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act (Pub...

16 CFR 1000.2 - Laws administered.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act (Pub...

16 CFR 1000.2 - Laws administered.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Laws administered. 1000.2 Section 1000.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL COMMISSION ORGANIZATION AND FUNCTIONS § 1000.2 Laws administered. The Commission administers five acts: (a) The Consumer Product Safety Act (Pub...

22 CFR 196.4 - Administering office.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4... AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of State's Bureau of Human Resources, Office of Recruitment is responsible for administering the Thomas R...

Pharmacokinetics of ketamine and its metabolite norketamine administered at a sub-anesthetic dose together with xylazine to calves prior to castration.

PubMed

Gehring, R; Coetzee, J F; Tarus-Sang, J; Apley, M D

2009-04-01

The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two-compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time-concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time-concentration profiles observed in this study were volume of the central compartment (V(c) = 132.82 +/- 68.23 mL/kg), distribution clearance (CL(D) = 15.49 +/- 2.56 mL/min/kg), volume of the peripheral compartment (V(T) = 257.05 +/- 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL(2M) = 8.56 +/- 7.37 mL/kg/min) and ketamine clearance by other routes (CL(o) = 16.41 +/- 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one-third of the parent drug. An understanding of the time-concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.

Dose comparison of ultrasonic transdermal insulin delivery to subcutaneous insulin injection

NASA Astrophysics Data System (ADS)

Park, Eun-Joo; Dodds, Jeff; Barrie Smith, Nadine

2010-03-01

Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array. In this study the physiologic response to ultrasound mediated transdermal insulin delivery is compared to that of subcutaneously administered insulin. Anesthetized rats (350-550 g) were divided into four groups of four animals; one group representing ultrasound mediated insulin delivery and three representing subcutaneously administered insulin (0.15, 0.20, and 0.25 U/kg). The cymbal array was operated for 60 minutes at 20 kHz with 100 mW/cm2 spatial-peak temporal-peak intensity and a 20% duty cycle. The blood glucose level was determined at the beginning of the experiment and, following insulin administration, every 15 minutes for 90 minutes for both the ultrasound and injection groups. The change in blood glucose from baseline was compared between groups. When administered by subcutaneous injection at insulin doses of 0.15 and 0.20 U/kg, there was little change in the blood glucose levels over the 90 minute experiment. Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190±96 mg/dl (mean±SD) at 90 minutes. The change in blood glucose following ultrasound mediated insulin delivery was -262±40 mg/dl at 90 minutes. As expected, the magnitude of change in blood glucose between the three injection groups was dependant on the dose of insulin administered. The change in blood glucose in the ultrasound group was greater than that observed in the injection groups suggesting that a higher effective dose of insulin was delivered.

Gestational age and dose influence on placental transfer of 63Ni in rats.

PubMed

Wang, X-W; Gu, J-Y; Li, Z; Song, Y-F; Wu, W-S; Hou, Y-P

2010-04-01

The effects of gestational age and dose of nickel exposure on regulating and influencing placental transfer were investigated. Pregnant rats on gestational day (GD) 12, 15 or 20 were injected intraperitoneally with saline, 64,320 or 640 kBq/kg body weight of (63)Ni. Twenty-four hours after administration, samples were harvested from each for measurement of radioactivity by liquid scintillation counting and for autoradiography. In placenta, amniotic fluid and fetal membrane, (63)Ni concentrations increased with increasing doses and gestational age. In fetus, (63)Ni concentrations reached a maximum on GD 15 and then declined on GD 20 although they maintained a dose-dependency for each GD group. In fetal blood on GD 20, (63)Ni concentration increased dose-dependently and was higher than in maternal blood. The autoradiographs demonstrated that (63)Ni radioactivity was located within placental basal lamina, fetal bones and most organs. These findings suggest that the nickel uptake, retention and transport in placenta increase dose- and gestation age-dependently, and nickel transfer through placental barrier is primarily from mother into the fetus, but hardly from fetus to mother. Copyright 2010 Elsevier Ltd. All rights reserved.

Radioactive Decay

EPA Pesticide Factsheets

Radioactive decay is the emission of energy in the form of ionizing radiation. Example decay chains illustrate how radioactive atoms can go through many transformations as they become stable and no longer radioactive.

Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients

PubMed Central

Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

2014-01-01

Objectives To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. Methods A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. Results There were 47 181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Discussion Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. Conclusions The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. PMID:24496386

Self-Administered Computer Therapy for Apraxia of Speech: Two-Period Randomized Control Trial With Crossover.

PubMed

Varley, Rosemary; Cowell, Patricia E; Dyson, Lucy; Inglis, Lesley; Roper, Abigail; Whiteside, Sandra P

2016-03-01

There is currently little evidence on effective interventions for poststroke apraxia of speech. We report outcomes of a trial of self-administered computer therapy for apraxia of speech. Effects of speech intervention on naming and repetition of treated and untreated words were compared with those of a visuospatial sham program. The study used a parallel-group, 2-period, crossover design, with participants receiving 2 interventions. Fifty participants with chronic and stable apraxia of speech were randomly allocated to 1 of 2 order conditions: speech-first condition versus sham-first condition. Period 1 design was equivalent to a randomized controlled trial. We report results for this period and profile the effect of the period 2 crossover. Period 1 results revealed significant improvement in naming and repetition only in the speech-first group. The sham-first group displayed improvement in speech production after speech intervention in period 2. Significant improvement of treated words was found in both naming and repetition, with little generalization to structurally similar and dissimilar untreated words. Speech gains were largely maintained after withdrawal of intervention. There was a significant relationship between treatment dose and response. However, average self-administered dose was modest for both groups. Future software design would benefit from incorporation of social and gaming components to boost motivation. Single-word production can be improved in chronic apraxia of speech with behavioral intervention. Self-administered computerized therapy is a promising method for delivering high-intensity speech/language rehabilitation. URL: http://orcid.org/0000-0002-1278-0601. Unique identifier: ISRCTN88245643. © 2016 American Heart Association, Inc.

Eye doses to staff in a nuclear medicine department.

PubMed

Summers, Elizabeth C; Brown, Janis L E; Bownes, Peter J; Anderson, Shona E

2012-05-01

Occupational radiation doses to the Nuclear Medicine Department staff at Mount Vernon Hospital are routinely measured using optically stimulated luminescence dosemeters for whole-body effective dose and ring thermoluminescence dosemeters (TLDs) for finger dose. In 2002, a project was carried out using LiF:Mg,Cu,P Chinese TLDs to measure the dose to the lens of the eye received by staff during normal working procedures. Separate pairs of TLDs were worn by staff on their forehead between their eyes while dispensing and releasing in the radiopharmacy, injecting, and when administering I-131 capsules to patients. The dose received was calculated using calibration data from identical TLDs irradiated with Tc-99m, I-131, and the Ir-192 source of a Gammamed High Dose Rate (HDR) treatment unit. Data were collected over a 5-month period and the mean dose to the eye was calculated for each procedure. Using a typical yearly workload, the annual dose to the eye for a single member of staff was calculated and found to be 4.5 mSv. The occupational eye dose limit was, at the time, 150 mSv; therefore, staff were well below the level (3/10th of this limit) that would have required them to be classified. However, there have been large increases in radiopharmacy production and I-131 therapies administered at Mount Vernon in subsequent years. It is therefore expected that the eye dose received by staff will have increased to be significantly higher than 4.5 mSv and will in fact be greater than 6 mSv, which is 3/10th of the proposed new dose limit and would require these staff to become classified workers.

Reactogenicity of tetanus, diphtheria, 5-component acellular pertussis vaccine administered as a sixth consecutive acellular pertussis vaccine dose to adolescents.

PubMed

Liese, Johannes G; Rieber, Nikolaus; Malzer, Thomas; Ocak, Marion; Johnson, David R; Decker, Michael D

2010-12-01

Safety of a sixth consecutive dose of acellular pertussis vaccine in adolescents was assessed in a 2-armed, randomized study. Adolescents who had received 5 doses of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (6-dose group) received 1 dose of reduced 5-component acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid (Tdap). Adolescents who had received a primary series of 3 doses of whole-cell pertussis and 1 acellular or whole-cell pertussis booster received 1 dose of Tdap vaccine (5-dose group). Of 214 participants, 176 (82%) reported an injection-site reaction with pain (80%), erythema (22%), and swelling (19%) most frequently reported. A systemic reaction was reported by 169 of 214 (79%) with myalgia (66%), headache (42%), malaise (39%), and fever (9%) most frequently reported. The overall rate of solicited reactions was lower in the 6-dose group than in the 5-dose group (for injection-site reactions: 76.1% vs. 89.7%; for systemic reactions 72.6% vs. 86.6%). Significant differences were observed for injection-site pain, erythema, and for grade 1 or grade 2 increases in arm circumference. Fever, myalgia, and headache were reported at a significantly lower rate in the 6-dose group. Swelling >10 cm was observed in 5 patients (2%), 4 in the 5-dose group. Tdap vaccine was safe when given to adolescents who had received 5 prior doses of acellular pertussis vaccine.

Detailed deposition density maps constructed by large-scale soil sampling for gamma-ray emitting radioactive nuclides from the Fukushima Dai-ichi Nuclear Power Plant accident.

PubMed

Saito, Kimiaki; Tanihata, Isao; Fujiwara, Mamoru; Saito, Takashi; Shimoura, Susumu; Otsuka, Takaharu; Onda, Yuichi; Hoshi, Masaharu; Ikeuchi, Yoshihiro; Takahashi, Fumiaki; Kinouchi, Nobuyuki; Saegusa, Jun; Seki, Akiyuki; Takemiya, Hiroshi; Shibata, Tokushi

2015-01-01

Soil deposition density maps of gamma-ray emitting radioactive nuclides from the Fukushima Dai-ichi Nuclear Power Plant (NPP) accident were constructed on the basis of results from large-scale soil sampling. In total 10,915 soil samples were collected at 2168 locations. Gamma rays emitted from the samples were measured by Ge detectors and analyzed using a reliable unified method. The determined radioactivity was corrected to that of June 14, 2011 by considering the intrinsic decay constant of each nuclide. Finally the deposition maps were created for (134)Cs, (137)Cs, (131)I, (129m)Te and (110m)Ag. The radioactivity ratio of (134)Cs-(137)Cs was almost constant at 0.91 regardless of the locations of soil sampling. The radioactivity ratios of (131)I and (129m)Te-(137)Cs were relatively high in the regions south of the Fukushima NPP site. Effective doses for 50 y after the accident were evaluated for external and inhalation exposures due to the observed radioactive nuclides. The radiation doses from radioactive cesium were found to be much higher than those from the other radioactive nuclides. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of the image-derived radioactivity and blood-sample radioactivity for estimating the clinical indicators of the efficacy of boron neutron capture therapy (BNCT): 4-borono-2-18F-fluoro-phenylalanine (FBPA) PET study.

PubMed

Isohashi, Kayako; Shimosegawa, Eku; Naka, Sadahiro; Kanai, Yasukazu; Horitsugi, Genki; Mochida, Ikuko; Matsunaga, Keiko; Watabe, Tadashi; Kato, Hiroki; Tatsumi, Mitsuaki; Hatazawa, Jun

2016-12-01

In boron neutron capture therapy (BNCT), positron emission tomography (PET) with 4-borono-2- 18 F-fluoro-phenylalanine (FBPA) is the only method to estimate an accumulation of 10 B to target tumor and surrounding normal tissue after administering 10 B carrier of L-paraboronophenylalanine and to search the indication of BNCT for individual patient. Absolute concentration of 10 B in tumor has been estimated by multiplying 10 B concentration in blood during BNCT by tumor to blood radioactivity (T/B) ratio derived from FBPA PET. However, the method to measure blood radioactivity either by blood sampling or image data has not been standardized. We compared image-derived blood radioactivity of FBPA with blood sampling data and studied appropriate timing and location for measuring image-derived blood counts. We obtained 7 repeated whole-body PET scans in five healthy subjects. Arterialized venous blood samples were obtained from the antecubital vein, heated in a heating blanket. Time-activity curves (TACs) of image-derived blood radioactivity were obtained using volumes of interest (VOIs) over ascending aorta, aortic arch, pulmonary artery, left and right ventricles, inferior vena cava, and abdominal aorta. Image-derived blood radioactivity was compared with those measured by blood sampling data in each location. Both the TACs of blood sampling radioactivity in each subject, and the TACs of image-derived blood radioactivity showed a peak within 5 min after the tracer injection, and promptly decreased soon thereafter. Linear relationship was found between blood sampling radioactivity and image-derived blood radioactivity in all the VOIs at any timing of data sampling (p < 0.001). Image-derived radioactivity measured in the left and right ventricles 30 min after injection showed high correlation with blood radioactivity. Image-derived blood radioactivity was lower than blood sampling radioactivity data by 20 %. Reduction of blood radioactivity of FBPA in left

Development of a sedation protocol using orally administered tiletamine-zolazepam-acepromazine in free-roaming dogs.

PubMed

Huang, Hsiao-Chun; Huang, Shih-Wei; Yu, Kuan-Hua; Wang, Jiann-Hsiung; Wu, Jui-Te

2017-09-01

To investigate the sedative effects in dogs of tiletamine-zolazepam-acepromazine (TZA) or ketamine-flunitrazepam (KF) administered orally and to evaluate the effectiveness of encapsulated TZA for capturing free-roaming dogs. Experimental study followed by a field trial. Six research dogs and 27 free-roaming dogs. In a pilot study, six research dogs were administered liquid TZA (20 mg kg -1 tiletamine-zolazepam and 2 mg kg -1 acepromazine) or liquid KF (50 mg kg -1 ketamine and 2 mg kg -1 flunitrazepam) orally: treatment 1, forcefully squirting liquid medication into the mouth; treatment 2, encapsulating liquid medication for administration in canned food; treatment 3, administering liquid medication mixed with gravy. Sedation was scored. A follow-up field trial attempted capture of 27 free-roaming dogs. In the pilot study, the median time (range) to lateral recumbency (% dogs) after TZA administration was: treatment 1, 47.5 (35-80) minutes (67%); treatment 2, 30 (15-65) minutes (83%); and treatment 3, 75 (45-110) minutes (100%). No dogs in KF treatment 2 or 3 achieved lateral recumbency. Based on these results, 20 free-roaming dogs were offered encapsulated TZA in canned food: TZ (20 mg kg -1 ) and acepromazine (2 mg kg -1 ). Of these, no further drugs to four dogs (one dog captured), 10 dogs were administered a second dose within 30 minutes (five dogs captured) and six dogs were administered TZ (5 mg kg -1 ) and xylazine (1.1-2.2 mg kg -1 ) intramuscularly by blow dart (six dogs captured). Seven dogs were initially offered twice the TZA dose (five dogs captured). In total, 63% free-roaming dogs were captured after administration of encapsulated TZA in canned food. Oral administration of encapsulated TZA in canned dog food can aid in the capture of free-roaming dogs, but additional drugs may be required. The sedation onset time and medication palatability influenced the capture rate. Copyright © 2017 Association of Veterinary Anaesthetists and

Radioactivity of natural medicinal preparations contained extracts from peat mud available in retail trade used externally.

PubMed

Karpińska, Maria; Kapała, Jacek; Raciborska, Agnieszka; Kulesza, Grzegorz; Milewska, Anna; Mnich, Stanisław

2017-08-01

In this work were identified and measured the activity of radioactive isotopes present in medicinal preparations from peat mud and estimated the doses obtained from them during therapy. Radioactivity of 22 preparations from peat mud and 20 water samples from water of the North-East region of Poland was studied. The median of the total activity was 24.8 Bq kg -1 . Total maximal isotope activity was observed in the Iwonicka Cube 146 Bq kg -1 while considerable amounts of isotopes were found in the Kolobrzeska Peat Mud Paste 112 Bq kg -1 . The doses obtained during therapy were within the range of 11 nSv-13 μSv depending on extracts of medicinal preparations from peat mud. The probability that such a small dose would stimulate biological effects is low. However, some clinicians believe that one of the possible therapeutic mechanisms in the treatment of rheumatoid disorders is the induction of immune response by ionising radiation.

Population dose commitments due to radioactive releases from nuclear power plant sites in 1987

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1987. Fifty-year dose commitments for a one-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 70 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for reach of the sites is a histogram showing the fraction of the total population within 2 to 80 kmmore » around each site receiving various average dose commitments from the airborne pathways. The site average individual dose commitment from all pathways ranged from a low of 2 {times} 10{sup {minus}6} mrem to a high of 0.009 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites. However, licensee calculation of doses to the maximally exposed individual at some sites indicated values of up to approximately 100 times average individual doses (on the order of a few millirem per year). 2 refs., 2 figs., 7 tabs.« less

WE-G-BRE-06: New Potential for Enhancing External Beam Radiotherapy for Lung Cancer Using FDA-Approved Concentrations of Cisplatin Or Carboplatin Nanoparticles Administered Via Inhalation

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

Hao, Y; Altundal, Y; Sajo, E

Purpose: This study investigates, for the first time, the dose enhancement to lung tumors due to cisplatin nanoparticles (CNPs) and carboplatin nanoparticles (CBNPs) administered via inhalation route (IR) during external beam radiotherapy. Methods: Using Monte Carlo generated 6 MV energy fluence spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumor due to radiation-induced photoelectrons from CNPs administered via IR in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung tumor via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of CNPs canmore » reach the lung tumors by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the dose with and without CNPs was calculated for field size of 10 cm × 10 cm (sweeping gap), for a range of tumor depths and tumor sizes. Similar calculations were done for CBNPs. Results: For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of 1.19–1.30 were obtained for CNPs at 3–10 cm depth, respectively, in comparison to 1.06–1.09 for IV. For CBNPs, DEF values of 1.26–1.41 were obtained in comparison to 1.07–1.12 for IV. For IR with 14.6 times higher concentrations, higher DEF values were obtained e.g. 1.81–2.27 for CNPs. DEF increased with increasing field size or decreasing tumor size. Conclusions: Our preliminary results indicate that major dose enhancement to lung tumors can be achieved using CNPs/CBNPs administered via IR, in contrast to IV administration during external beam radiotherapy. These findings highlight a potential new approach for radiation boosting to lung tumors using CNPs/CBNPs administered via IR. This would, especially, be applicable during concomitant chemoradiotherapy, potentially allowing for dose enhancement while

Radiation Dose-Response Relationships and Risk Assessment

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

Strom, Daniel J.

The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is alsomore » the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is

Effectiveness of Haemophilus influenzae type b vaccines administered according to various schedules: systematic review and meta-analysis of observational data.

PubMed

Jackson, Charlotte; Mann, Andrea; Mangtani, Punam; Fine, Paul

2013-11-01

Conjugate vaccines against Haemophilus influenzae type b (Hib) are widely used. The full implications of Hib vaccination schedule for vaccine effectiveness (VE) are unclear. We searched the literature for observational studies reporting the effectiveness of conjugate Hib vaccines administered according to different schedules. We summarized dose-specific VE estimates, where appropriate, using random effects meta-analysis. Thirty-one eligible articles (reporting 30 studies conducted in 17 countries) were identified. Meta-analysis of case-control studies using community controls produced VE estimates against Hib meningitis of 55% (95% confidence interval: 2-80%, based on 3 studies), 96% (86-99%, 3 studies) and 96% (86-99%, 4 studies) after 1, 2 and 3 doses of vaccines other than the polyribosyl ribitol phosphate outer membrane protein vaccine. Estimates were similar using hospital controls. VE against invasive Hib disease in case-control studies was estimated as 59% (30-76%, 3 studies) and 97% (87-99%, 3 studies) for 1 and 3 doses (insufficient data were identified to estimate 2-dose VE). Point estimates from 2 studies suggested VE>90% after 1 dose of the polyribosyl ribitol phosphate outer membrane protein vaccine, but meta-analysis was not possible. Using data from 4 cohort studies, 3-dose VE was estimated as 94% (88-97%). There was some evidence that Hib vaccine was less effective when administered with acellular (rather than whole cell) pertussis vaccine. Weak evidence from 2 studies suggested that a booster confers some additional protection following full primary vaccination and may compensate for an incomplete primary series. Observational data suggest that ≥2 doses of Hib vaccine are required for high effectiveness, but do not strongly favor any particular schedule.

An FDA oncology analysis of immune activating products and first-in-human dose selection.

PubMed

Saber, Haleh; Gudi, Ramadevi; Manning, Michael; Wearne, Emily; Leighton, John K

2016-11-01

As sub-therapeutic doses are not medically justifiable in patients with cancer, we retrospectively analyzed data on immune activating products, to assess approaches used in first-in-human (FIH) dose selection, the utility of animal toxicology studies in dose selection, and the length of time to complete FIH trials. The information collected included pharmacology and toxicology data, FIH dose and rationale, and dose-finding trial design. We used the principles of the Hill equation to estimate the FIH doses for antibodies and compared them to the doses administered to patients with acceptable toxicities. For approximately half the antibodies (44%) examined, the FIH doses were at least a hundred-fold lower than the doses safely administered to patients, indicating optimization of FIH dose selection and/or optimization of dose-finding trial design is needed to minimize patient exposure to sub-therapeutic doses. However, selection of the FIH dose for antibodies based on animal toxicology studies using 1/6th the HNSTD or 1/10th the NOAEL resulted in human doses that were unsafe for several antibodies examined. We also concluded that antibodies with Fc-modifications for increased effector function may be less tolerated, resulting in toxicities at lower doses than those without such modifications. There was insufficient information to evaluate CD3 bispecific products. Published by Elsevier Inc.

Regulation of Motivation to Self-Administer Ethanol by mGluR5 in Alcohol-Preferring (P) Rats

PubMed Central

Besheer, Joyce; Faccidomo, Sara; Grondin, Julie J. M.; Hodge, Clyde W.

2008-01-01

Background Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self-administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement. Methods Alcohol-preferring (P) rats were trained to self-administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self-administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance. Results The mGluR1 antagonist, 3,4-dihydro-2H-pyrano[2,3]b quinolin-7-yl (cis-4-methoxy-cyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6-methyl-2-(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose-dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity. Conclusions Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self-administer ethanol. PMID:18162077

Natural Radioactivity of Boron Added Clay Samples

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

Akkurt, I.; Guenoglu, K.; Canakcii, H.

2011-12-26

Clay, consisting fine-grained minerals, is an interesting materials and can be used in a variety of different fields especially in dermatology application. Using clay such a field it is important to measure its natural radioactivity. Thus the purpose of this study is to measure {sup 226}Ra, {sup 232}Th and {sup 40}K concentration in clay samples enriched with boron. Three different types of clay samples were prepared where boron is used in different rate. The measurements have been determined using a gamma-ray spectrometry consists of a 3''x3'' NaI(Tl) detector. From the measured activity the radium equivalent activities (Ra{sub eq}), external hazardmore » index (H{sub ex}), absorbed dose rate in air (D) and annual effective dose (AED) have also been obtained.« less

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

PubMed

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

2014-01-01

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

Evaluation of the radiological risks associated with the routine transport of radioactive material within Michigan

NASA Astrophysics Data System (ADS)

Steinman, Rebecca Lee

Radioactive materials play an important role in modern society. In addition to providing electrical power and supporting national defense, radioisotopes play significant roles in the fields of medicine, research, manufacturing, and industry. Since most of these materials are not manufactured or disposed of at the site where they are used, they must be transported between various processing, use, storage, and disposal facilities. This dissertation examines the mathematical model used to predict the collective dose to the population that resides along a potential transport route, commonly called the off-link dose. The currently accepted RADTRAN and RISKIND transient dose models are reviewed. Then three new individual transient dose models are derived by assuming that a point, line, or surface cylinder can approximate the actual transport package. Groundscatter effects were investigated using a Monte Carlo simulation of the surface cylinder model and found to contribute no more than 12% to the total individual dose from a passing shipment of radioactive material, thus not warranting explicit inclusion in the newly derived transient dose models. All five of the individual transient dose models were evaluated for representative shipments of spent nuclear fuel and low-level waste within the State of Michigan and compared to experimentally measured doses. The individual dose for the Michigan shipment scenarios was found to be on the order of 1 murem. Comparison to the experimental measurements revealed that RISKIND consistently predicts the best estimate of the measured dose, followed closely by the surface cylinder model. RADTRAN consistently over predicted the measured dose by at least a factor of two. Finally, the line dose model is integrated over strips of uniform population along the transport route to arrive at the collective off-link population dose. This off-link dose model was incorporated into an ArcView application using the Avenue scripting language. Then

Single-center, single-dose, open-label, randomized, two-period crossover study on the bioavailability of methotrexate administered using a novel prefilled, needle-free delivery system.

PubMed

Bienvenu, Boris; Aouba, Achille; Gottenberg, Jacques-Eric; Verstuyft, Celine

2017-04-01

Zeneo 1 is a needle-free injection device. We performed a pharmacokinetic study to investigate the bioequivalence of methotrexate administered subcutaneously using either the needle-free injection device or a conventional needle and syringe. This was a single-dose, open-label, laboratory-blind, randomized crossover study performed in adult healthy volunteers. Each participant received two methotrexate injections (each 25 mg), one via needle-free injection device and one via conventional injection, with a 21-28 day wash-out interval between dosing. For each participant, the administration site for both injections was either the abdomen or the thigh. The primary pharmacokinetic outcome parameters were AUC (0- t ) and C max . Bioequivalence was assessed by standard criteria: whether 90% confidence intervals of geometric mean ratios for the two administration methods were within 80-125%. Fifty-two individuals completed the study. Bioequivalence criteria were met for AUC (0- t ) , for the overall analysis (both injection sites: 90% confidence interval: 99.4-103.1%), and for each injection site separately. Bioequivalence was similarly demonstrated with AUC (0-∞) . Bioequivalence criteria for C max were fulfilled for abdominal administration but not for the overall analysis. Injection via the needle-free injection device was well tolerated. Limitations include conducting the study in healthy volunteers and the relatively small subject number (albeit satisfactory for bioequivalence). This study shows that methotrexate injection via needle-free injection device is bioequivalent to a conventional needle and syringe in relation to AUC (0- t ) and AUC (0-∞) . Studies of needle-free injection device use in patients requiring methotrexate therapy are planned.

The Somatostatin Analog Rhenium Re-188-P2045 Inhibits the Growth of AR42J Pancreatic Tumor-xenografts

PubMed Central

Nelson, Carol A.; Azure, Michael T.; Adams, Christopher T.; Zinn, Kurt R.

2015-01-01

P2045 is a peptide analog of somatostatin with picomolar affinity for the somatostatin receptor subtype 2 (SSTR2) upregulated in some pancreatic tumors. Studies were conducted in rat AR42J pancreatic tumor-xenograft mice to determine if Re-188-P2045 could inhibit the growth of pancreatic cancer in an animal model. Methods Re-188-P2045 was intravenously administered every 3 days for 16 days to nude mice with AR42J tumor-xenografts that were ≈ 20 mm3 at study initiation. Tumor volumes were recorded throughout the dosing period. At necropsy all tissues were assessed for levels of radioactivity and evaluated for histological abnormalities. Clinical chemistry and hematology parameters were determined from terminal blood samples. The affinity of non-radioactive Re-185/187-P2045 for somatostatin receptors was compared in human NCI-H69 and rat AR42J tumor-cell membranes expressing predominantly SSTR2. Results In the 1.85 and 5.55 mBq groups tumor growth was inhibited in a dose-dependent fashion. In the 11.1 mBq group tumor growth was completely inhibited throughout the dosing period and for 12 days after the last administered dose. The radioactivity level in tumors 4 hours post-injection was 10%ID/g, which was 2-fold higher than in the kidneys. Re-188-P2045 was well tolerated in all dose-groups with no adverse clinical, histological, or hematological findings. The non-radioactive Re-185/187-P2045 bound more avidly (0.2 nM) to SSTR2 in human than rat tumor membranes suggesting that these studies are relevant to human studies. Conclusion Re-188-P2045 is a promising therapeutic candidate for patients with somatostatin-receptor-positive cancer. PMID:25359879

[DIURETIC ACTIVITY OF 4-O-CARBOXYPHENYL-D-GLUCOPYRANOSIDE SODIUM SALT ADMINISTERED VIA DIFFERENT ROUTES].

PubMed

Smirnov, I V; Murashko, T O; Ivanov, A A; Nemtsev, A O; Postnikov, P S; Bondarev, A A; Udut, V V

2016-01-01

It was compared the diuretic activity of the sodium salt of 4-(O-β-D-glucopyranosyloxy)benzoic acid for enteral (intragastric) and parenteral ways of administration. The test substance was administered enterally and parenterally (subcutaneously in the region of the withers) in a daily dose of 18 µmol/kg for the first seven days and in a dose of 54 mmol/kg for the next seven days. Diuretic activity of the sodium salt of 4-(O-β-D-glucopyranosyloxy)benzoic acid was evaluated in terms of urine volume. Urine was analyzed for creatinine and the concentration of sodium, potassium and chloride ions. Experiments showed that the sodium salt of 4-(O-β-D-glucopyranosyloxy)benzoic acid produced a diuretic effect only for the enteral administration route.

Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children: Booster dose and 2-dose catch-up regimens in the second year of life.

PubMed

Odusanya, Olumuyiwa O; Kuyinu, Yetunde A; Kehinde, Omolara A; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Dobbelaere, Kurt; Rüggeberg, Jens U; Borys, Dorota; Schuerman, Lode

2014-01-01

In a previous study, 3-dose primary vaccination of Nigerian infants with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with comparable tolerability between PHiD-CV and control groups. In an open-label study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa) booster dose at 15-21 months and 36 children unprimed for pneumococcal vaccination received two PHiD-CV catch-up doses (first dose co-administered with DTPa booster dose) at 15-21 and 17-23 months. Adverse events were recorded and immune responses were measured before and one month after vaccination. In both groups, pain was the most frequent solicited local symptom and fever was the most frequent solicited general symptom after the booster dose and each catch-up dose. Few grade 3 solicited symptoms and no vaccine-related serious adverse events were reported. After booster vaccination, for each vaccine serotype, at least 98.5% of children had an antibody concentration ≥ 0.2 µg/ml and at least 94.0% had an opsonophagocytic activity (OPA) titer ≥ 8. After 2-dose catch-up, for each vaccine serotype, at least 97.1% had an antibody concentration ≥ 0.2 µg/ml, except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA titer ≥8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced antibody responses against protein D in both groups. In conclusion, PHiD-CV administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well tolerated and immunogenic for vaccine pneumococcal serotypes and protein D.

Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

PubMed

Strange, P; Schwartz, S L; Graf, R J; Polvino, W; Weston, I; Marbury, T C; Huang, W C; Goldberg, R B

1999-01-01

The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

Population dose commitments due to radioactive releases from nuclear-power-plant sites in 1978

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

Peloquin, R.A.; Schwab, J.D.; Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1978. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each site. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each site is a histogram showing the fraction of the total population within 2 to 80 km around each site receiving variousmore » average dose commitments from the airborne pathways. The total dose commitment from both liquid and airborne pathways ranged from a high of 200 person-rem to a low of 0.0004 person-rem with an arithmetic mean of 14 person-rem. The total population dose for allsites was estimated at 660 person-rem for the 93 million people considered at risk. The average individual dose commitment from all pathways on a site basis ranged from a low of 3 x 10/sup -6/ mrem to a high of 0.08 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population dose commitments due to radioactive releases from Nuclear-Power-Plant Sites in 1979

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

Baker, D.A.; Peloquin, R.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1979. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each site. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each site is a histogram showing the fraction of the total population within 2 to 80 km around each site receiving variousmore » average dose commitments from the airborne pathways. The total dose commitment from both liquid and airborne pathways ranged from a high of 1300 person-rem to a low of 0.0002 person-rem with an arithmetic mean of 38 person-rem. The total population dose for all sites was estimated at 1800 person-rem for the 94 million people considered at risk. The average individual dose commitment from all pathways on a site basis ranged from a low of 2 x 10/sup -6/ mrem to a high of 0.7 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population Dose Commitments Due to Radioactive Releases from Nuclear Power Plant Sites in 1977

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

Baker, D. A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1977. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each site. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ, Also included for each site is a histogram showing the fraction of the total population within 2 to 80 km around each site receiving variousmore » average dose commitments from the airborne pathways. The total dose commitment from both liquid and airborne pathways ranged from a high of 220 person-rem to a low of 0.003 person-rem with an arithmetic mean of 16 person-rem. The total population dose for all sites was estimated at 700 person-rem for the 92 million people considered at risk. The average individual dose commitment from all pathways on a site basis ranged from a low of 2 x 10{sup -5} mrem to a high of 0.1 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1980

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

Baker, D.A.; Peloquin, R.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1980. In addition doses derived from the shutdown reactors at the Three Mile Island site were included. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each site. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each site is a histogram showingmore » the fraction of the total population within 2 to 80 km around each site receiving various average dose commitments from the airborne pathways. The total dose commitment from both liquid and airborne pathways ranged from a high of 40 person-rem to a low of 0.02 person-rem with an arithmetic mean of 4 person-rem. The total population dose for all sites was estimated at 180 person-rem for the 96 million people considered at risk.« less

Buccally Administered Intranasal Desmopressin Acetate for the Treatment of Neurogenic Diabetes Insipidus in Infancy.

PubMed

Smego, Allison R; Backeljauw, Philippe; Gutmark-Little, Iris

2016-05-01

The treatment of neurogenic diabetes insipidus (DI) in infancy is challenging and complicated by fluid overload and dehydration. Therapy with subcutaneous (SC), intranasal (IN), or oral tablet desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) remains difficult to titrate in infants. Assess the efficacy and safety of buccally administered IN DDAVP for the management of infants with neurogenic DI. Retrospective review of clinical and laboratory data of 15 infants (mean age, 4.5 mo) with neurogenic DI treated at a tertiary care center. Treatment was with diluted IN DDAVP formulation (10 mcg/mL) administered buccally via a tuberculin syringe to the buccal mucosa. After initial DDAVP titration of 2-3 days, IN DDAVP doses ranged from 1 to 5 mcg twice daily given buccally. Mean serum sodium concentration at DI diagnosis was 159 ± 6.6 mmol/L (range, 151-178) and improved to 142 ± 3.5 mmol/L (range, 137-147) with the buccally administered IN DDAVP. Normal sodium concentrations were established without major fluctuations. Serum sodium was then maintained in the outpatient setting at a mean of 145.7 ± 4.8 mmol/L (mean duration of follow-up, 11 mo). Buccally administered IN formulation of DDAVP provides a practical and safe treatment alternative for neurogenic DI in infancy. Our approach avoided severe hypo- and hypernatremia during DDAVP titration and ongoing outpatient management of DI. The possibility for smaller dosage increments and ease of administration make IN DDAVP administered buccally preferable over other DDAVP treatment options in infants.

Behavior of autologous indium-114m-labeled lymphocytes in patients with lymphoid cell malignancy

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

Hamilton, D.; Cowan, R.A.; Sharma, H.L.

1988-04-01

It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that /sup 114m/In deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples,more » and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1988

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1988. Fifty-year commitments for a one-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 71 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for each of the sites is a histogram showing the fraction of the total population within 2 to 80 km aroundmore » each site receiving various average dose commitments from the airborne pathways. The total collective dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 16 person-rem to a low of 0.0011 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 1.1 person-rem. The total population dose for all sites was estimated at 75 person-rem for the 150 million people considered at risk. The site average individual dose commitment from all pathways ranged from a low of 3 {times} 10{sup {minus}7} mrem to a high of 0.02 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites. However, licensee calculation of doses to the maximally exposed individual at some sites indicated values of up to approximately 100 times average individual doses (on the order of a few millirem per year).« less

Cigarette smoke radioactivity and lung cancer risk.

PubMed

Karagueuzian, Hrayr S; White, Celia; Sayre, James; Norman, Amos

2012-01-01

To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers. Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998. The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential "cancerous growth" in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant "nicotine kick" sensation. The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

PubMed

Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna

2018-03-01

Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

Gamma-ray dose from an overhead plume

DOE PAGES

McNaughton, Michael W.; Gillis, Jessica McDonnel; Ruedig, Elizabeth; ...

2017-05-01

Standard plume models can underestimate the gamma-ray dose when most of the radioactive material is above the heads of the receptors. Typically, a model is used to calculate the air concentration at the height of the receptor, and the dose is calculated by multiplying the air concentration by a concentration-to-dose conversion factor. Models indicate that if the plume is emitted from a stack during stable atmospheric conditions, the lower edges of the plume may not reach the ground, in which case both the ground-level concentration and the dose are usually reported as zero. However, in such cases, the dose frommore » overhead gamma-emitting radionuclides may be substantial. Such underestimates could impact decision making in emergency situations. The Monte Carlo N-Particle code, MCNP, was used to calculate the overhead shine dose and to compare with standard plume models. At long distances and during unstable atmospheric conditions, the MCNP results agree with the standard models. As a result, at short distances, where many models calculate zero, the true dose (as modeled by MCNP) can be estimated with simple equations.« less

Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

PubMed

Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

2010-04-16

The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone

Population dose commitments due to radioactive releases from nuclear power plant sites in 1985

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commericial power reactors operating during 1985. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 61 sites. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each of the sites is a histogram showing the fraction of the total population within 2 to 80 km aroundmore » each site receiving various average dose commitments from the airborne pathways. The total dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 73 person-rem to a low of 0.011 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 3 person-rem. The total population dose for all sites was estimated at 200 person-rem for the 110 million people considered at risk. The site average individual dose commitment from all pathways ranged from a low of 5 /times/ 10/sup /minus/6/ mrem to a high of 0.02 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1984

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1984. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 56 sites. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each of the sites is a histogram showing the fraction of the total population within 2 to 80 km aroundmore » each site receiving various average dose commitments from the airborne pathways. The total dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 110 person-rem to a low of 0.002 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 5 person-rem. The total population dose for all sites was estimated at 280 person-rem for the 100 million people considered at risk. The site average individual dose commitment from all pathways ranged from a low of 6 x 10/sup -6/ mrem to a high of 0.04 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1986

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1986. Fifty-year dose commitments for a one-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 66 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for each of the sites is a histogram showing the fraction of the total population within 2 to 80 kmmore » around each site receiving various average dose commitments from the airborne pathways. The total dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 31 person-rem to a low of 0.0007 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 1.7 person-rem. The total population dose for all sites was estimated at 110 person-rem for the 140 million people considered at risk. The site average individual dose commitment from all pathways ranged from a low of 2 {times} 10{sup -6} mrem to a high of 0.02 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites. 12 refs.« less

Potential hazard due to induced radioactivity secondary to radiotherapy: the report of task group 136 of the American Association of Physicists in Medicine.

PubMed

Thomadsen, Bruce; Nath, Ravinder; Bateman, Fred B; Farr, Jonathan; Glisson, Cal; Islam, Mohammad K; LaFrance, Terry; Moore, Mary E; George Xu, X; Yudelev, Mark

2014-11-01

External-beam radiation therapy mostly uses high-energy photons (x-rays) produced by medical accelerators, but many facilities now use proton beams, and a few use fast-neutron beams. High-energy photons offer several advantages over lower-energy photons in terms of better dose distributions for deep-seated tumors, lower skin dose, less sensitivity to tissue heterogeneities, etc. However, for beams operating at or above 10 MV, some of the materials in the accelerator room and the radiotherapy patient become radioactive due primarily to photonuclear reactions and neutron capture, exposing therapy staff and patients to unwanted radiation dose. Some recent advances in radiotherapy technology require treatments using a higher number of monitor units and monitor-unit rates for the same delivered dose, and compared to the conventional treatment techniques and fractionation schemes, the activation dose to personnel can be substantially higher. Radiotherapy treatments with proton and neutron beams all result in activated materials in the treatment room. In this report, the authors review critically the published literature on radiation exposures from induced radioactivity in radiotherapy. They conclude that the additional exposure to the patient due to induced radioactivity is negligible compared to the overall radiation exposure as a part of the treatment. The additional exposure to the staff due to induced activity from photon beams is small at an estimated level of about 1 to 2 mSv y. This is well below the allowed occupational exposure limits. Therefore, the potential hazard to staff from induced radioactivity in the use of high-energy x-rays is considered to be low, and no specific actions are considered necessary or mandatory. However, in the spirit of the "As Low as Reasonably Achievable (ALARA)" program, some reasonable steps are recommended that can be taken to reduce this small exposure to an even lower level. The dose reduction strategies suggested should be

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans

PubMed Central

Manini, Alex F.; Yiannoulos, Georgia; Bergamaschi, Mateus M.; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J.; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A.; Hurd, Yasmin L.

2015-01-01

Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse. PMID:25748562

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

RADIO-ACTIVE TRANSDUCER

DOEpatents

Wanetick, S.

1962-03-01

ABS>ure the change in velocity of a moving object. The transducer includes a radioactive source having a collimated beam of radioactive particles, a shield which can block the passage of the radioactive beam, and a scintillation detector to measure the number of radioactive particles in the beam which are not blocked by the shield. The shield is operatively placed across the radioactive beam so that any motion normal to the beam will cause the shield to move in the opposite direction thereby allowing more radioactive particles to reach the detector. The number of particles detected indicates the acceleration. (AEC)

Effective Dose in Nuclear Medicine Studies and SPECT/CT: Dosimetry Survey Across Quebec Province.

PubMed

Charest, Mathieu; Asselin, Chantal

2018-06-01

The aims of the current study were to draw a portrait of the delivered dose in selected nuclear medicine studies in Québec province and to assess the degree of change between an earlier survey performed in 2010 and a later survey performed in 2014. Methods: Each surveyed nuclear medicine department had to complete 2 forms: the first, about the administered activity in selected nuclear medicine studies, and the second, about the CT parameters used in SPECT/CT imaging, if available. The administered activities were converted into effective doses using the most recent conversion factors. Diagnostic reference levels were computed for each imaging procedure to obtain a benchmark for comparison. Results: The distributions of administered activity in various nuclear medicine studies, along with the corresponding distribution of the effective doses, were determined. Excluding 131 I for thyroid studies, 67 Ga-citrate for infectious workups, and combined stress and rest myocardial perfusion studies, the remainder of the 99m Tc-based studies delivered average effective doses clustered below 10 mSv. Between the 2010 survey and the 2014 survey, there was a statistically significant decrease in delivered dose from 18.3 to 14.5 mSv. 67 Ga-citrate studies for infectious workups also showed a significant decrease in delivered dose from 31.0 to 26.2 mSv. The standardized CT portion of SPECT/CT studies yielded a mean effective dose 14 times lower than the radiopharmaceutical portion of the study. Conclusion: Between 2010 and 2014, there was a significant decrease in the delivered effective dose in myocardial perfusion and 67 Ga-citrate studies. The CT portions of the surveyed SPECT/CT studies contributed a relatively small fraction of the total delivered effective dose. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Orally administered DTPA penta-ethyl ester for the decorporation of inhaled 241Am

PubMed Central

Sueda, Katsuhiko; Sadgrove, Matthew P.; Huckle, James E.; Leed, Marina G. D.; Weber, Waylon M.; Doyle-Eisele, Melanie; Guilmette, Raymond A.; Jay, Michael

2014-01-01

Diethylenetriaminepentaacetic acid (DTPA) is an effective decorporation agent to facilitate the elimination of radionuclides from the body, but its permeability-limited oral bioavailability limits its utility in mass-casualty emergencies. To overcome this limitation, a prodrug strategy using the penta-ethyl ester form of DTPA is under investigation. Pharmacokinetic and biodistribution studies were conducted in rats by orally administering [14C]DTPA penta-ethyl ester, and this prodrug and its hydrolysis products were analyzed as a single entity. Compared to a previous reporting of intravenously administered DTPA, the oral administration of this prodrug resulted in a sustained plasma concentration profile with higher plasma exposure and lower clearance. An assessment of the urine composition revealed that the bioactivation was extensive but incomplete, with no detectable levels of the penta- or tetra-ester forms. Tissue distribution at 12 h was limited, with approximately 73% of the administered dose being associated with the gastrointestinal tract. In the efficacy study, rats were exposed to aerosols of 241Am nitrate before receiving a single oral treatment of the prodrug. The urinary excretion of 241Am was found to be 19% higher than with the control. Consistent with prior reports of DTPA, the prodrug was most effective when the treatment delays were minimized. PMID:24619514

Effect of artichoke extract (Cynara scolymus L.) on palmitic-1-14C acid oxidation in rats.

PubMed

Juzyszyn, Zygmunt; Czerny, Boguslaw; Pawlik, Andrzej; Drozdzik, Marek

2008-05-01

Studies on the effect of the artichoke extract (AE) on oxidation of palmitic-1-14C acid administered intravenously to rats at a dose 25 and 50 mg/kg bw demonstrated marked enhancement of both 14CO2 expiration rate and 14CO2 recovery in the expired air. The extract suppressed accumulation of palmitic-1-14C acid in serum lipids and epididymal fat pad tissue as well. The effects of the extract on 14CO2 expiration rate, 14CO2 recovery, as well as accumulation of palmitic-1-14C acid were dose dependent. Total14CO2 recovery in expired air during 60 min was elevated by 17.3% (p < 0.05) and 52.1% (p < 0.001) in rats administered the extract at a dose of 25 and 50 mg/kg, respectively. The rats supplemented with the AE at a dose of 25 and 50 mg/kg bw were characterized by 10.0% (not significant) and 19% (p < 0.05) decrease in( 14)C radioactivity of serum lipids as well as reduction of epididymal fat tissue 14C radioactivity by 8.7 and 17.5% (p < 0.05), respectively, in comparison with the control rats. Thus, the results demonstrate that the AE possess stimulatory properties with respect to oxidation of palmitic acid administered to rats, and provide new information on the mechanism of antilipemic activity of the extract associated with activation of lipid oxidation in the organism.

Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™.

PubMed

Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Baccarini, Carmen; Miller, Jacqueline M

2015-02-11

Co-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP) at age 15-18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers. Infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15-18 months (Coad group); or HibMenCY-TT at 12-15 months and DTaP at 15-18 months (HibMenCY-TT group). Controls received DTaP at 15-18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination. Pre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone. Routine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

PubMed Central

Bull, Cecilia; Freitas, Kelen CC; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

2014-01-01

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with

Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.

PubMed

Bull, Cecilia; Freitas, Kelen C C; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

2014-11-01

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with

Uptake, metabolism and excretion of orally and intravenously administered, 14C- and 3H-labeled N-acetylneuraminic acid mixture in the mouse and rat.