Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol.

PubMed

Rönn, O; Bengtsson, B; Edgar, B; Raner, S

1985-01-01

In a single-blind randomised study in 9 healthy men we compared the acute haemodynamic effects of the calcium antagonists felodipine and verapamil, singly and in combination with metoprolol. Three different cumulative intravenous doses of 0.25, 0.75 and 1.5 mg felodipine and of 2.0, 4.0 and 8.0 mg verapamil or placebo were given as constant infusions over 5 minutes on 3 occasions and were followed by intravenous metoprolol (15 mg). Felodipine caused a significant and dose-dependent decrease in the total peripheral resistance, and an increase in the forearm blood flow by 8, 48 and 163% with progressively increasing doses showing that the drug is a potent arteriolar vasodilator. A significant and dose-dependent increase in heart rate and a decrease in the pre-ejection period/left ventricular ejection time (PEP/LVET) ratio of up to 15% was also recorded, mainly reflecting a reflexogenic increase in the sympathetic tone. Total peripheral resistance, forearm blood flow, heart rate and the systolic time intervals were mainly unchanged after verapamil, whereas the PQ interval was prolonged. Metoprolol given after the 2 calcium antagonists caused a decrease in heart rate and blood flow and an increase in the total peripheral resistance and PEP/LVET ratio. The tolerability was good to all infusions.

Relationship between high daily erythemal UV doses, total ozone, surface albedo and cloudiness: An analysis of 30 years of data from Switzerland and Austria

NASA Astrophysics Data System (ADS)

Rieder, H. E.; Staehelin, J.; Weihs, P.; Vuilleumier, L.; Maeder, J. A.; Holawe, F.; Blumthaler, M.; Lindfors, A.; Peter, T.; Simic, S.; Spichtinger, P.; Wagner, J. E.; Walker, D.; Ribatet, M.

2010-10-01

This work investigates the occurrence frequency of days with high erythemal UV doses at three stations in Switzerland and Austria (Davos, Hoher Sonnblick and Vienna) for the time period 1974-2003. While several earlier studies have reported on increases in erythemal UV dose up to 10% during the last decades, this study focuses on days with high erythemal UV dose, which is defined as a daily dose at least 15% higher than for 1950s clear-sky conditions (which represent preindustrial conditions with respect to anthropogenic chlorine). Furthermore, the influence of low column ozone, clear-sky/partly cloudy conditions and surface albedo on UV irradiance has been analyzed on annual and seasonal basis. The results of this study show that in the Central Alpine Region the number of days with high UV dose increased strongly in the early 1990s. A large fraction of all days with high UV dose occurring in the period 1974-2003 was found especially during the years 1994-2003, namely 40% at Davos, 54% at Hoher Sonnblick and 65% at Vienna. The importance of total ozone, clear-sky/partly cloudy conditions and surface albedo (e.g. in dependence of snow cover) varies strongly among the seasons. However, overall the interplay of low total ozone and clear-sky/partly cloudy conditions led to the largest fraction of days showing high erythemal UV dose. Furthermore, an analysis of the synoptic weather situation showed that days with high erythemal UV dose, low total ozone and high relative sunshine duration occur at all three stations more frequently during situations with low pressure gradients or southerly advection.

Diagnostic radiation exposure in pediatric trauma patients.

PubMed

Brunetti, Marissa A; Mahesh, Mahadevappa; Nabaweesi, Rosemary; Locke, Paul; Ziegfeld, Susan; Brown, Robert

2011-02-01

The amount of imaging studies performed for disease diagnosis has been rapidly increasing. We examined the amount of radiation exposure that pediatric trauma patients receive because they are an at-risk population. Our hypothesis was that pediatric trauma patients are exposed to high levels of radiation during a single hospital visit. Retrospective review of children who presented to Johns Hopkins Pediatric Trauma Center from July 1, 2004, to June 30, 2005. Radiographic studies were recorded for each patient and doses were calculated to give a total effective dose of radiation. All radiographic studies that each child received during evaluation, including any associated hospital admission, were included. A total of 945 children were evaluated during the study year. A total of 719 children were included in the analysis. Mean age was 7.8 (±4.6) years. Four thousand six hundred three radiographic studies were performed; 1,457 were computed tomography (CT) studies (31.7%). Average radiation dose was 12.8 (±12) mSv. We found that while CT accounted for only 31.7% of the radiologic studies performed, it accounted for 91% of the total radiation dose. Mean dose for admitted children was 17.9 (±13.8) mSv. Mean dose for discharged children was 8.4 (±7.8) mSv (p<0.0001). Burn injuries had the lowest radiation dose [1.2 (±2.6) mSv], whereas motor vehicle collision victims had the highest dose [18.8 (±14.7) mSv]. When the use of radiologic imaging is considered essential, cumulative radiation exposure can be high. In young children with relatively long life spans, the benefit of each imaging study and the cumulative radiation dose should be weighed against the long-term risks of increased exposure.

Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors

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

Parsons, J.T.; Bova, F.J.; Million, R.R.

1994-11-15

To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 andmore » 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.« less

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 administered in less time, the more likely patients experienced an abnormal vital sign. High opioid doses were safely administered to patients with sickle cell disease. Copyright © 2015 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

PubMed

Wheldon, T E; O'Donoghue, J A; Hilditch, T E; Barrett, A

1988-02-01

A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to the limitations of the theoretical analysis.

Radiometric and Radiation Response of Visible FPAs

NASA Technical Reports Server (NTRS)

Hubbs, John

2007-01-01

The readout integrated circuit (ROIC) used in these devices was originally developed for use in space based infrared systems operating at deep cryogenic temperatures and was selected because of its proven tolerance to total ionizing radiation? The detectors are a 128 x 128 array of 60 pm x 60 pm pixel elements that have been anti-reflection (AR) coated to improve the response at very short wavelengths. These visible focal plane arrays were operated at -40 C (233 K). Two focal planes were characterized using cobalt-60 radiation to produce ionizing total dose damage in the VFPAs. Both operational and performance data were obtained as functions of total dose. The first device tested showed no appreciable change in responsivity or noise up to 300 krad(Si). However, at the next dose level of 600 krad(Si), the readout was non-operational due to failure in the digital circuitry. The second device was characterized to a total dose of 750 krad(Si) with no observed change in responsivity. An increase dark current was observed in both devices, and in the second device, the dark current caused an increase in noise at low irradiance at 400 krad(Si) and above. The increase in dark current was somewhat un-expected for visible PIN detectors. The median dark current increased more than two orders of magnitude at 300 krad(Si) for the first device and a factor of 350 at 750 krad(Si) for pixels near the edge for the second device. The dark current was found to be a strong function of detector bias, with pixels near the edge of the array showing a greater increase in dark current with bias than those near the center. Since the optical response was not a function of bias, it is hypothesized that the dark current is a surface effect and that the variation in dark current with location is due to a variation in pixel bias, caused by a voltage drop across the pixel common lead. As the total dose increased, the dark current and the voltage drop increased

The radiation dosimeter on-board the FY-4 Satellite

NASA Astrophysics Data System (ADS)

Zhang, B.; Sun, Y.; Zhang, S.; Zhang, X.; Sun, Y.; Jing, T.

2017-12-01

The total radiation dose effect can lead to a decrease in the performance of satellite devices or materials. Accurately obtaining the total radiation dose during satellite operation could help to analyze the abnormality of payloads in orbit and optimize the design of radiation shielding. The radiation dosimeter is one of the space environmental monitoring devices on the "FY-4" satellite, which is a new generation of geostationary meteorological satellite. The dosimeter consists of 8 detectors, which are installed in different locations of the satellite, to obtain the total radiation dose with different shielding thickness and different orientations. To measure a total radiation dose up to 2000krad(Si), 100nm ion implantation RADFET was used. To improve the sensitivity of the dosimeter, the bias voltage of RADFET is set to 15V, and a 10V, 15-bit A/D is adopted to digitalize the RADFET's threshold voltage, which is increased as the total radiation dose grows. In addition, the temperature effect of RADFET is corrected from the measured temperature on orbit. The preliminary monitoring results show that the radiation dose is less than 35rad (Si) per day at 0.87 mm shielding thickness of equivalent aluminum in the geostationary orbit, and the dose in Y direction of the satellite is less than those in the X and Z directions. The radiation dose at the thickness of 3.87 mm equivalent aluminum is less than 1rad(Si)/day. It is found that the daily total dose measured by the dosimeter has a strong correlation with the flux of high energy electrons.

INSECTICIDAL AND OXIDATIVE EFFECTS OF AZADIRACHTIN ON THE MODEL ORGANISM Galleria mellonella L. (LEPIDOPTERA: PYRALIDAE).

PubMed

Dere, Beyza; Altuntaş, Hülya; Nurullahoğlu, Z Ulya

2015-07-01

The insecticidal effects, specifically, changes in hemolymph total protein and malondialdehyde (MDA) levels, and antioxidant enzyme activities of azadirachtin (AZA) given to the wax moth, Galleria mellonella L. (Lepidoptera: Pyralidae) larvae via force feeding were investigated. Bioassays showed that the LD50 and LD99 (lethal dose) values of AZA were 2.1 and 4.6 μg/larva, respectively. Experimental analyses were performed with five doses of AZA (0.5, 1, 1.5, 2, and 3 μg/larva). Total protein level in larval hemolymph increased at all AZA doses at 24 h whereas a considerable decrease was observed at 2 and 3 μg/larva doses, and only an increase displayed at 1.5 μg/larva at 72 h. The level of MDA increased at 2 and 3 μg/larva doses at 24 h compared with controls. This trend was also observed at 1.5, 2, and 3 μg/larva doses at 72 h and MDA levels were lower when compared with those of 24 h at all doses except for 1.5 μg/larva dose. Catalase activity decreased at 1, 1.5, and 2 μg/larva doses at 24 h whereas increased at all doses except for 0.5 μg/larva at 72 h compared with controls. AZA led to a decline in superoxide dismutase activity at all experimental doses at 24 and 72 h except for 3 μg/larva doses at 72 h. An increase in glutathione-S-transferase (GST) activity was evident at all AZA doses at 24 h. AZA displayed 68% decline in GST activity at 72 h post treatments when compared to 24 h. Consequently, We infer that the toxicity of AZA extends beyond its known actions in molting processes to redox homeostasis. © 2015 Wiley Periodicals, Inc.

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology.

PubMed

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C; Morelli, John N

2017-01-01

We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms "interventional/computed tomography" and "radiation dose/radiation dose reduction." A PubMed query using the above-mentioned search terms for the years of 2005-2015 was performed. Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6-27) and 246±105 diagnostic radiology abstracts (range, 112-389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79-187) and 1205±307 publications (range, 829-1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted.

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology

PubMed Central

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C.; Morelli, John N.

2017-01-01

PURPOSE We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. METHODS Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms “interventional/computed tomography” and “radiation dose/radiation dose reduction.” A PubMed query using the above-mentioned search terms for the years of 2005–2015 was performed. RESULTS Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6–27) and 246±105 diagnostic radiology abstracts (range, 112–389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79–187) and 1205±307 publications (range, 829–1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). CONCLUSION The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted. PMID:28287072

Wastewater disinfection alternatives: chlorine, ozone, peracetic acid, and UV light.

PubMed

Mezzanotte, V; Antonelli, M; Citterio, S; Nurizzo, C

2007-11-01

Disinfection tests were carried out at pilot scale to compare the disinfection efficiency of ozone, sodium hypochlorite (NaOCl), peracetic acid (PAA), and UV irradiation. Total coliforms, fecal coliforms, and Escherichia coli were monitored as reference microorganisms. Total heterotrophic bacteria (THB) were also enumerated by cytometry. At similar doses, NaOCl was more effective than PAA, and its action was less affected by contact time. The results obtained by ozonation were comparable for total coliforms, fecal coliforms, and E. coli. On the contrary, some differences among the three indicators were observed for NaOCl, PAA, and UV. Differences increased with increasing values of the disinfectant concentration times contact time (C x t) and were probably the result of different initial counts, as total coliforms include fecal coliforms, which include E. coli. The UV irradiation lead to complete E. coli removals, even at low doses (10 to 20 mJ/cm2). Total heterotrophic bacteria appeared to be too wide a group to be a good disinfection indicator; no correlation was found among THB inactivation, dose, and contact time.

Design of spray dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose.

PubMed

Ung, Keith T; Rao, Nagaraja; Weers, Jeffry G; Huang, Daniel; Chan, Hak-Kim

2016-09-25

Inhaled drugs all too often deliver only a fraction of the emitted dose to the target lung site due to deposition in the extrathoracic region (i.e., mouth and throat), which can lead to increased variation in lung exposure, and in some instances increases in local and systemic side effects. For aerosol medications, improved targeting to the lungs may be achieved by tailoring the micromeritic properties of the particles (e.g., size, density, rugosity) to minimize deposition in the mouth-throat and maximize the total lung dose. This study evaluated a co-solvent spray drying approach to modulate particle morphology and dose delivery characteristics of engineered powder formulations of insulin microparticles. The binary co-solvent system studied included water as the primary solvent mixed with an organic co-solvent, e.g., ethanol. Factors such as the relative rate of evaporation of each component of a binary co-solvent mixture, and insulin solubility in each component were considered in selecting feedstock compositions. A water-ethanol co-solvent mixture with a composition range considered suitable for modulating particle shell formation during drying was selected for experimental investigation. An Alberta Idealized Throat model was used to evaluate the in vitro total lung dose of a series of spray dried insulin formulations engineered with different bulk powder properties and delivered with two prototype inhalers that fluidize and disperse powder using different principles. The in vitro total lung dose of insulin microparticles was improved and favored for powders with low bulk density and small primary particle size, with reduction of deposition in the extrathoracic region. The results demonstrated that a total lung dose >95% of the delivered dose can be achieved with engineered particles, indicating a high degree of lung targeting, almost completely bypassing deposition in the mouth-throat. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of gamma-irradiation on the occurrence of pathogenic microorganisms and nutritive value of four principal cereal grains.

PubMed

Aziz, N H; Souzan, R M; Shahin Azza, A

2006-12-01

The effects of (60)Co gamma-photon-irradiation on the natural occurrence of pathogenic microorganisms in four principal cereal grains and on amino acids and vitamins in these cereals were investigated. The total numbers of aerobic bacteria were reduced by three logarithmic decades when grains were given a dose of 10kGy. Coliforms and "coagulase- positive" staphylococci were inhibited by a dose of 1kGy, whereas fungi were inhibited by a dose of 5kGy. The 15kGy dose eliminated viable microorganisms in cereal grains, and about 10-30 colony-forming units of Clostridium sp. per gram of grain survived after this dose. The dose of 10kGy did not cause any measurable destruction of total amino acids. Thiamin was reduced by 22-33% and riboflavin by 10-16% after a dose of 10kGy. Irradiation did not increase the acid values significantly, but did increase the peroxide values, which was not accompanied by the off-odors of cereals. We conclude that the overall dose of 10kGy is very effective for microbial decontamination of cereal grains, and does not adversely affect the nutritional quality of cereal grains.

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

PubMed

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

2007-03-01

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

Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men.

PubMed

Gårevik, N; Börjesson, A; Choong, E; Ekström, L; Lehtihet, M

2016-06-01

The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29-46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol®, Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone-binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)-cholesterol and plasma (P)-apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S-cholesterol and (3) P-ApoB level. The long-term consequences on cardiovascular risk that may appear in users remain to be elucidated. © 2015 Blackwell Verlag GmbH.

The dependence of the growth rate and meat content of young boars on semen parameters and conception rate.

PubMed

Knecht, D; Jankowska-Mąkosa, A; Duziński, K

2017-05-01

Boars have a decisive impact on the progress in pig production, however, there is no recent information about the optimal growth parameters during the rearing period for modern breed later used in artificial insemination (AI) stations. Therefore, the objective of the research was to conduct semen parameter and conception rate analyses on the basis of growth rate and meat content assessments made during the rearing of AI boars of different genotypes. The study was carried out between 2010 and 2014 and included 184 boars in five breed combinations: 46 Polish Large White, 50 Polish Landrace, 27 Pietrain, 36 Duroc×Pietrain and 25 Hampshire×Pietrain. Boars were qualified by daily gains and meat content assessment (between 170 and 210 days of life). A total number of 38 272 ejaculates were examined (semen volume (ml), spermatozoa concentration (×106 ml-1), total number of spermatozoa (×109) and number of insemination doses from one ejaculate (n)). The fertility was determined by the conception rate (%). Semen volume, spermatozoa concentration and conception rate (P<0.01), followed by the total number of spermatozoa and insemination doses (P<0.05) were characterized by the highest variability in relation to breed of boars. The effect of daily gains was reported for spermatozoa concentration, number of insemination doses, conception rate (all P<0.01) and total number of spermatozoa (P<0.05). The peak of growth for spermatozoa concentration, total number of spermatozoa, insemination doses and conception rate was achieved for 800 to 850 g gains. Meat content affected semen volume, number of insemination doses and conception rate (P<0.05). Rearing boars while maintaining daily gains at the 800 to 850 g level and 62.5% to 65% meat content helps AI stations to increase the efficiency and economic profitability, and the number of insemination doses to increase by up to 300 doses/boar within a year. The analyses of growth parameters may help increase the efficiency and economic viability of AI stations.

Evaluation of a total scalp electron irradiation technique.

PubMed

Able, C M; Mills, M D; McNeese, M D; Hogstrom, K R

1991-09-01

A dosimetric evaluation of a total scalp electron-beam irradiation technique that uses six stationary fields was performed. The initial treatment plan specified a) that there be a 3-mm gap between abutted fields and b) that the field junctions be shifted 1 cm after 50% of the prescribed dose had been delivered. Dosimetric measurements were made at the scalp surface, scalp-skull interface, and the skull-brain interface in an anthropomorphic head phantom using both film and thermoluminescent dosimeters (TLD-100). The measurements showed that the initial technique yields areas of increased and decreased dose ranging from -50% to +70% in the region of the field junctions. To reduce regions of nonuniform dose, the treatment protocol was changed by eliminating the gap between the coronal borders of abutted fields and by increasing the field shift from 1 cm to 2 cm for all borders. Subsequent measurements showed that these changes in treatment protocol resulted in a significantly more uniform dose to the scalp and decreased variation of doses near field junctions (-10% to +50%).

The radiation environment on the Moon from galactic cosmic rays in a lunar habitat.

PubMed

Jia, Y; Lin, Z W

2010-02-01

We calculated how the radiation environment in a habitat on the surface of the Moon would have depended on the thickness of the habitat in the 1977 galactic cosmic-ray environment. The Geant4 Monte Carlo transport code was used, and a hemispherical dome made of lunar regolith was used to simulate the lunar habitat. We investigated the effective dose from primary and secondary particles including nuclei from protons up to nickel, neutrons, charged pions, photons, electrons and positrons. The total effective dose showed a strong decrease with the thickness of the habitat dome. However, the effective dose values from secondary neutrons, charged pions, photons, electrons and positrons all showed a strong increase followed by a gradual decrease with the habitat thickness. The fraction of the summed effective dose from these secondary particles in the total effective dose increased with the habitat thickness, from approximately 5% for the no-habitat case to about 47% for the habitat with an areal thickness of 100 g/cm(2).

Evaluation of Total Daily Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the Hospital

DTIC Science & Technology

2016-05-20

regular insulin has significantly increased in recent years. These patients are severely insulin resistant requiring high doses of insulin to achieve...on U-500 Insulin Admitted to the Hospital presented at SURF Conference, San Antonio, TX 20 May 201 6 with MDWI 41-108, and has been assigned local...59th CSPG/SGVU) C.201 4 . I 52d PROTOCOL TITLE Evaluation of Total Dai ly Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the

Total Dose Effects on Error Rates in Linear Bipolar Systems

NASA Technical Reports Server (NTRS)

Buchner, Stephen; McMorrow, Dale; Bernard, Muriel; Roche, Nicholas; Dusseau, Laurent

2007-01-01

The shapes of single event transients in linear bipolar circuits are distorted by exposure to total ionizing dose radiation. Some transients become broader and others become narrower. Such distortions may affect SET system error rates in a radiation environment. If the transients are broadened by TID, the error rate could increase during the course of a mission, a possibility that has implications for hardness assurance.

Long-term erythemal UV doses at Sodankylä estimated using total ozone, sunshine duration and snow depth

NASA Astrophysics Data System (ADS)

Lindfors, A. V.; Arola, A.; Kaurola, J.; Taalas, P.; Svenøe, T.

2003-04-01

A method for estimating daily erythemal UV doses using total ozone, sunshine duration and snow depth has been developed. The method consists of three steps: (1) daily clear-sky UV doses were simulated using the UVSPEC radiative transfer program, with daily values of total ozone as input data, (2) an empirical relationship was sought between the simulated clear-sky UV doses, the measured UV doses and the duration of bright sunshine, (3) daily erythemal UV doses were estimated using this relationship. The method accounts for the varying surface albedo by dividing the period of interest into winter and summer days, depending on the snow depth. Using this method, the daily erythemal UV doses at Sodankylä were estimated for the period 1950--99. This was done using Tromsø's total ozone together with Sodankylä's own sunshine duration and snow depth as input data. Although the method is fairly simple, the results are in good agreement, even on the daily scale, with the UV radiation measured with the Brewer spectrophotometer at Sodankylä. Statistically significant increasing trends in erythemal UV doses of a few percents per decade over the period 1950--99 were found for March and April, suggesting a connection to the stratospheric ozone depletion. For July, on the other hand, a significant decreasing trend of about 3% per decade, supported by the changes in both total ozone and sunshine duration, was found. The produced data set of erythemal UV doses is the longest time series of estimated UV known to the authors.

The Impact of Dose Rate on the Accuracy of Step-and-Shoot Intensity-modulated Radiation Therapy Quality Assurance Using Varian 2300CD.

PubMed

Njeh, Christopher F; Salmon, Howard W; Schiller, Claire

2017-01-01

Intensity-modulated radiation therapy (IMRT) delivery using "step-and-shoot" technique on Varian C-Series linear accelerator (linac) is influenced by the communication frequency between the multileaf collimator and linac controllers. Hence, the dose delivery accuracy is affected by the dose rate. Our aim was to quantify the impact of using two dose rates on plan quality assurance (QA). Twenty IMRT patients were selected for this study. The plan QA was measured at two different dose rates. A gamma analysis was performed, and the degree of plan modulation on the QA pass rate was also evaluated in terms of average monitor unit per segment (MU/segment) and the total number of segments. The mean percentage gamma pass rate of 94.9% and 93.5% for 300 MU/min and 600 MU/min dose rate, respectively, was observed. There was a significant ( P = 0.001) decrease in percentage gamma pass rate when the dose rate was increased from 300 MU/min to 600 MU/min. There was a weak, but significant association between the percentage pass rate at both dose rate and total number of segments. The total number of MU was significantly correlated to the total number of segments ( r = 0.59). We found a positive correlation between the percentage pass rate and mean MU/segment, r = 0.52 and r = 0.57 for 300 MU/min and 600 MU/min, respectively. IMRT delivery using step-and-shoot technique on Varian 2300CD is impacted by the dose rate and the total amount of segments.

Dose-dependent consumption of farmed Atlantic salmon (Salmo salar) increases plasma phospholipid n-3 fatty acids differentially

PubMed Central

Raatz, Susan K.; Rosenberger, Thad A.; Johnson, LuAnn K.; Wolters, William W.; Burr, Gary S; Picklo, Matthew J.

2013-01-01

Enhanced omega-3 fatty acid (n-3) intake benefits cardiovascular disease (CVD) risk reduction. Increasing consumption at a population level may be better addressed by diet than through supplementation. However, limited data are available on the effect of the dose response to fish intake on plasma levels of n-3 fatty acids. To compare the effects of different doses of farmed Atlantic salmon on plasma phospholipid fatty acid (PLFA) proportions and CVD risk biomarkers (glucose, insulin, HOMAIR, hsCRP, and IL-6) in healthy subjects we performed a randomized 3-period cross-over designed trial (4 wk treatment, 4-8 wk washout) to compare the effects of twice/wk consumption of farmed Atlantic salmon at doses of 90, 180, and 270 g in 19 apparently healthy men and women with a mean age of aged 40-65 years and a BMI between 25-34.9 kg/m2. All study visits were conducted at the USDA, ARS Grand Forks Human Nutrition Research Center. EPA and total n-3 were increased (p<0.05) by all treatments in a dose response manner, with total n-3 of 8.03 ± 0.26 and 9.21 ± 0.26 % for 180 and 270 g doses, respectively. Linoleic acid did not change in response to treatment while arachidonic acid (P<0.05) and total omega-6 fatty acids (n-6) decreased dose dependently (<0.0001). The addition of farmed Atlantic salmon to the diet twice/wk for 4 wk at portions of 180g and 270g modifies PLFA proportions of n-3 and n-6 in a level associated with decreased risk for CVD. PMID:23351633

Rejoining and misrejoining of radiation-induced chromatin breaks. I. experiments with human lymphocytes

NASA Technical Reports Server (NTRS)

Durante, M.; George, K.; Wu, H.; Yang, T. C.

1996-01-01

Fluorescence in situ hybridization with a composite probe for human chromosome 4 and a probe that stained all centromeres was used to study gamma-ray induced breakage, rejoining and misrejoining in prematurely condensed chromosomes in human lymphocytes. Dose-response curves for the induction of all types of aberrations in prematurely condensed human chromosomes 4 were determined immediately after irradiation and after 8 h postirradiation incubation. In addition, aberrations were measured after various incubation times from 0 to 18 h after a dose of 7 Gy. Unrejoined chromosome breaks were the most frequent type of aberration observed immediately after irradiation. Approximately 15% of total aberrations observed were chromosome exchanges. After 8 h postirradiation incubation, the frequency of breaks in prematurely condensed chromosomes declined to about 20% of the initial value, and chromosomal exchanges became the most frequent aberration. Results of metaphase analysis were similar to those for prematurely condensed chromosomes after 8 h incubation with the exception that a significantly lower frequency of fragments was observed. Symmetrical and asymmetrical interchanges were found at similar frequencies at all doses. No complex exchanges were observed in lymphocyte chromosomes immediately after exposure. They accounted for about 1% of total exchanges in metaphase chromosomes at doses <3 Gy and about 14% at 7 Gy. Incomplete exchanges amounted to approximately 15% of total exchanges at all doses. The kinetics of break rejoining was exponential, and the frequency of exchanges increased with kinetics similar to that observed for the rejoining of the breaks. This increase in the total exchanges as a function of the time between irradiation and fusion was due to a rapid increase in reciprocal interchanges, and a slower increase in complex exchanges; the frequency of incomplete exchanges increased initially, then decreased with prolonged incubation to the level observed in metaphase. It is concluded that the formation of each kind of chromosome aberrations follows different kinetics.

Determination of fatty acid composition of γ-irradiated hazelnuts, walnuts, almonds, and pistachios

NASA Astrophysics Data System (ADS)

Gecgel, Umit; Gumus, Tuncay; Tasan, Murat; Daglioglu, Orhan; Arici, Muhammet

2011-04-01

Hazelnut, walnut, almonds, and pistachio nuts were treated with 1, 3, 5, and 7 kGy of gamma irradiation, respectively. Oil content, free fatty acid, peroxide value, and fatty acid composition of the nuts were investigated immediately after irradiation. The data obtained from the experiments indicated that gamma irradiation did not cause any significant change in the oil content of nuts. In contrast, free fatty acid and peroxide value of the nuts increased proportionally to the dose (p<0.05). Among the fatty acids determined, the concentration of total saturated fatty acids increased while total monounsaturated and total polyunsaturated fatty acids decreased with the irradiation dose (p<0.05 and <0.01).

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

NASA Technical Reports Server (NTRS)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

The financial impact of increasing home-based high dose haemodialysis and peritoneal dialysis.

PubMed

Liu, Frank Xiaoqing; Treharne, Catrin; Culleton, Bruce; Crowe, Lydia; Arici, Murat

2014-10-02

Evidence suggests that high dose haemodialysis (HD) may be associated with better health outcomes and even cost savings (if conducted at home) versus conventional in-centre HD (ICHD). Home-based regimens such as peritoneal dialysis (PD) are also associated with significant cost reductions and are more convenient for patients. However, the financial impact of increasing the use of high dose HD at home with an increased tariff is uncertain. A budget impact analysis was performed to investigate the financial impact of increasing the proportion of patients receiving home-based dialysis modalities from the perspective of the England National Health Service (NHS) payer. A Markov model was constructed to investigate the 5 year budget impact of increasing the proportion of dialysis patients receiving home-based dialysis, including both high dose HD at home and PD, under the current reimbursement tariff and a hypothetically increased tariff for home HD (£575/week). Five scenarios were compared with the current England dialysis modality distribution (prevalent patients, 14.1% PD, 82.0% ICHD, 3.9% conventional home HD; incident patients, 22.9% PD, 77.1% ICHD) with all increases coming from the ICHD population. Under the current tariff of £456/week, increasing the proportion of dialysis patients receiving high dose HD at home resulted in a saving of £19.6 million. Conducting high dose HD at home under a hypothetical tariff of £575/week was associated with a budget increase (£19.9 million). The costs of high dose HD at home were totally offset by increasing the usage of PD to 20-25%, generating savings of £40.0 million - £94.5 million over 5 years under the increased tariff. Conversely, having all patients treated in-centre resulted in a £172.6 million increase in dialysis costs over 5 years. This analysis shows that performing high dose HD at home could allow the UK healthcare system to capture the clinical and humanistic benefits associated with this therapy while limiting the impact on the dialysis budget. Increasing the usage of PD to 20-25%, the levels observed in 2005-2008, will totally offset the additional costs and generate further savings.

Pharmacokinetic and Genomic Effects of Arsenite in Drinking Water on Mouse Lung in a 30-Day Exposure

PubMed Central

Chilakapati, Jaya; Wallace, Kathleen; Hernandez-Zavala, Araceli; Moore, Tanya; Ren, Hongzu

2015-01-01

The 2 objectives of this subchronic study were to determine the arsenite drinking water exposure dependent increases in female C3H mouse liver and lung tissue arsenicals and to characterize the dose response (to 0, 0.05, 0.25, 1, 10, and 85 ppm arsenite in drinking water for 30 days and a purified AIN-93M diet) for genomic mouse lung expression patterns. Mouse lungs were analyzed for inorganic arsenic, monomethylated, and dimethylated arsenicals by hydride generation atomic absorption spectroscopy. The total lung mean arsenical levels were 1.4, 22.5, 30.1, 50.9, 105.3, and 316.4 ng/g lung tissue after 0, 0.05, 0.25, 1, 10, and 85 ppm, respectively. At 85 ppm, the total mean lung arsenical levels increased 14-fold and 131-fold when compared to either the lowest noncontrol dose (0.05 ppm) or the control dose, respectively. We found that arsenic exposure elicited minimal numbers of differentially expressed genes (DEGs; 77, 38, 90, 87, and 87 DEGs) after 0.05, 0.25, 1, 10, and 85 ppm, respectively, which were associated with cardiovascular disease, development, differentiation, apoptosis, proliferation, and stress response. After 30 days of arsenite exposure, this study showed monotonic increases in mouse lung arsenical (total arsenic and dimethylarsinic acid) concentrations but no clear dose-related increases in DEG numbers. PMID:26674514

Pharmacokinetic and Genomic Effects of Arsenite in Drinking Water on Mouse Lung in a 30-Day Exposure.

PubMed

Chilakapati, Jaya; Wallace, Kathleen; Hernandez-Zavala, Araceli; Moore, Tanya; Ren, Hongzu; Kitchin, Kirk T

2015-01-01

The 2 objectives of this subchronic study were to determine the arsenite drinking water exposure dependent increases in female C3H mouse liver and lung tissue arsenicals and to characterize the dose response (to 0, 0.05, 0.25, 1, 10, and 85 ppm arsenite in drinking water for 30 days and a purified AIN-93M diet) for genomic mouse lung expression patterns. Mouse lungs were analyzed for inorganic arsenic, monomethylated, and dimethylated arsenicals by hydride generation atomic absorption spectroscopy. The total lung mean arsenical levels were 1.4, 22.5, 30.1, 50.9, 105.3, and 316.4 ng/g lung tissue after 0, 0.05, 0.25, 1, 10, and 85 ppm, respectively. At 85 ppm, the total mean lung arsenical levels increased 14-fold and 131-fold when compared to either the lowest noncontrol dose (0.05 ppm) or the control dose, respectively. We found that arsenic exposure elicited minimal numbers of differentially expressed genes (DEGs; 77, 38, 90, 87, and 87 DEGs) after 0.05, 0.25, 1, 10, and 85 ppm, respectively, which were associated with cardiovascular disease, development, differentiation, apoptosis, proliferation, and stress response. After 30 days of arsenite exposure, this study showed monotonic increases in mouse lung arsenical (total arsenic and dimethylarsinic acid) concentrations but no clear dose-related increases in DEG numbers.

Fault handling schemes in electronic systems with specific application to radiation tolerance and VLSI design

NASA Technical Reports Server (NTRS)

Attia, John Okyere

1993-01-01

Naturally occurring space radiation particles can produce transient and permanent changes in the electrical properties of electronic devices and systems. In this work, the transient radiation effects on DRAM and CMOS SRAM were considered. In addition, the effect of total ionizing dose radiation of the switching times of CMOS logic gates were investigated. Effects of transient radiation on the column and cell of MOS dynamic memory cell was simulated using SPICE. It was found that the critical charge of the bitline was higher than that of the cell. In addition, the critical charge of the combined cell-bitline was found to be dependent on the gate voltage of the access transistor. In addition, the effect of total ionizing dose radiation on the switching times of CMOS logic gate was obtained. The results of this work indicate that, the rise time of CMOS logic gates increases, while the fall time decreases with an increase in total ionizing dose radiation. Also, by increasing the size of the P-channel transistor with respect to that of the N-channel transistor, the propagation delay of CMOS logic gate can be made to decrease with, or be independent of an increase in total ionizing dose radiation. Furthermore, a method was developed for replacing polysilicon feedback resistance of SRAMs with a switched capacitor network. A switched capacitor SRAM was implemented using MOS Technology. The critical change of the switched capacitor SRAM has a very large critical charge. The results of this work indicate that switched capacitor SRAM is a viable alternative to SRAM with polysilicon feedback resistance.

Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

PubMed

Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

2014-01-01

Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning.

PubMed

Abugideiri, Mustafa; Nanda, Ronica H; Butker, Charlotte; Zhang, Chao; Kim, Sungjin; Chiang, Kuang-Yueh; Butker, Elizabeth; Khan, Mohammad K; Haight, Ann E; Chen, Zhengjia; Esiashvili, Natia

2016-02-01

This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS. Copyright © 2016 Elsevier Inc. All rights reserved.

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning

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

Abugideiri, Mustafa, E-mail: Mabugid@emory.edu; Nanda, Ronica H.; Butker, Charlotte

Purpose: This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). Methods and Materials: The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified usingmore » clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. Results: PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. Conclusions: A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS.« less

Calculated organ doses from selected prostate treatment plans using Monte Carlo simulations and an anatomically realistic computational phantom

PubMed Central

Bednarz, Bryan; Hancox, Cindy; Xu, X George

2012-01-01

There is growing concern about radiation-induced second cancers associated with radiation treatments. Particular attention has been focused on the risk to patients treated with intensity-modulated radiation therapy (IMRT) due primarily to increased monitor units. To address this concern we have combined a detailed medical linear accelerator model of the Varian Clinac 2100 C with anatomically realistic computational phantoms to calculate organ doses from selected treatment plans. This paper describes the application to calculate organ-averaged equivalent doses using a computational phantom for three different treatments of prostate cancer: a 4-field box treatment, the same box treatment plus a 6-field 3D-CRT boost treatment and a 7-field IMRT treatment. The equivalent doses per MU to those organs that have shown a predilection for second cancers were compared between the different treatment techniques. In addition, the dependence of photon and neutron equivalent doses on gantry angle and energy was investigated. The results indicate that the box treatment plus 6-field boost delivered the highest intermediate- and low-level photon doses per treatment MU to the patient primarily due to the elevated patient scatter contribution as a result of an increase in integral dose delivered by this treatment. In most organs the contribution of neutron dose to the total equivalent dose for the 3D-CRT treatments was less than the contribution of photon dose, except for the lung, esophagus, thyroid and brain. The total equivalent dose per MU to each organ was calculated by summing the photon and neutron dose contributions. For all organs non-adjacent to the primary beam, the equivalent doses per MU from the IMRT treatment were less than the doses from the 3D-CRT treatments. This is due to the increase in the integral dose and the added neutron dose to these organs from the 18 MV treatments. However, depending on the application technique and optimization used, the required MU values for IMRT treatments can be two to three times greater than 3D CRT. Therefore, the total equivalent dose in most organs would be higher from the IMRT treatment compared to the box treatment and comparable to the organ doses from the box treatment plus the 6-field boost. This is the first time when organ dose data for an adult male patient of the ICRP reference anatomy have been calculated and documented. The tools presented in this paper can be used to estimate the second cancer risk to patients undergoing radiation treatment. PMID:19671968

Calculated organ doses from selected prostate treatment plans using Monte Carlo simulations and an anatomically realistic computational phantom

NASA Astrophysics Data System (ADS)

Bednarz, Bryan; Hancox, Cindy; Xu, X. George

2009-09-01

There is growing concern about radiation-induced second cancers associated with radiation treatments. Particular attention has been focused on the risk to patients treated with intensity-modulated radiation therapy (IMRT) due primarily to increased monitor units. To address this concern we have combined a detailed medical linear accelerator model of the Varian Clinac 2100 C with anatomically realistic computational phantoms to calculate organ doses from selected treatment plans. This paper describes the application to calculate organ-averaged equivalent doses using a computational phantom for three different treatments of prostate cancer: a 4-field box treatment, the same box treatment plus a 6-field 3D-CRT boost treatment and a 7-field IMRT treatment. The equivalent doses per MU to those organs that have shown a predilection for second cancers were compared between the different treatment techniques. In addition, the dependence of photon and neutron equivalent doses on gantry angle and energy was investigated. The results indicate that the box treatment plus 6-field boost delivered the highest intermediate- and low-level photon doses per treatment MU to the patient primarily due to the elevated patient scatter contribution as a result of an increase in integral dose delivered by this treatment. In most organs the contribution of neutron dose to the total equivalent dose for the 3D-CRT treatments was less than the contribution of photon dose, except for the lung, esophagus, thyroid and brain. The total equivalent dose per MU to each organ was calculated by summing the photon and neutron dose contributions. For all organs non-adjacent to the primary beam, the equivalent doses per MU from the IMRT treatment were less than the doses from the 3D-CRT treatments. This is due to the increase in the integral dose and the added neutron dose to these organs from the 18 MV treatments. However, depending on the application technique and optimization used, the required MU values for IMRT treatments can be two to three times greater than 3D CRT. Therefore, the total equivalent dose in most organs would be higher from the IMRT treatment compared to the box treatment and comparable to the organ doses from the box treatment plus the 6-field boost. This is the first time when organ dose data for an adult male patient of the ICRP reference anatomy have been calculated and documented. The tools presented in this paper can be used to estimate the second cancer risk to patients undergoing radiation treatment.

Advanced p-MOSFET Ionizing-Radiation Dosimeter

NASA Technical Reports Server (NTRS)

Buehler, Martin G.; Blaes, Brent R.

1994-01-01

Circuit measures total dose of ionizing radiation in terms of shift in threshold gate voltage of doped-channel metal oxide/semiconductor field-effect transistor (p-MOSFET). Drain current set at temperature-independent point to increase accuracy in determination of radiation dose.

Effect of gamma irradiation on some physicochemical properties and bioactive compounds of jujube (Ziziphus jujuba var vulgaris) fruit

NASA Astrophysics Data System (ADS)

Najafabadi, Najmeh Shams; Sahari, Mohammad Ali; Barzegar, Mohsen; Esfahani, Zohreh Hamidi

2017-01-01

Interest in the protection of bioactive compounds and a safe alternative method for preservation of processed fruits and fruit juices has recently increased significantly throughout the world. There is a distinct lack of information on the profile of bioactive compounds in jujube fruit (e.g. organic acids, anthocyanins, and water-soluble vitamins) and their changes during processing (e.g. gamma irradiation). Therefore, in this study, the effect of gamma irradiation at different doses (0.0, 0.5, 1.0, 2.5 and 5.0 kGy) on some physicochemical properties and the bioactive compounds of jujube fruit was investigated. The total soluble solids (TSSs) values remained unaffected at various doses, while the level of total acidity (TA) showed a slight increase at doses ≥ 2.5 kGy (p ≤ 0.05). Irradiation up to 2.5 kGy caused a significant increase in the total monomeric anthocyanin and the total phenolic content (about 12% and 6%, respectively), but a significant decrease was observed in both parameters immediately after irradiation at 5 kGy. Moreover, irradiation treatment caused a significant decrease in L* value and a significant increase in a* and b* values (P ≤ 0.05); however, changes of color were slight until the dose of 5 kGy. Gamma irradiation up to 2.5 kGy had no significant effect on the concentration of malic, citric and succinic acids, while the level of ascorbic acid decreased significantly at all irradiation doses (0-5 kGy). Cyanidin-3, 5-diglucoside was determined as the major anthocyanin in the jujube fruit studied (about 68%), which was reduced significantly when 5 kGy of irradiation was applied (degradation percentage: 27%). The results demonstrated that vitamins C, B2 and B1 are the most water-soluble vitamins in jujube fruit, respectively. Vitamins C and B1 content significantly decreased at all applied doses (0-5 kGy), whereas B2 content at doses ≤ 2.5 kGy was not significantly affected. The results of this study indicate that gamma irradiation at doses below 2.5 kGy can be successfully used for improving the quality the jujube fruit.

Acute respiratory toxicity following inhalation exposure to soman in guinea pigs.

PubMed

Perkins, Michael W; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Kabra, Kareem; Chanda, Soma; Oguntayo, Samuel; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2010-06-01

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m(3) concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m(3) soman survived, while animals exposed to 841, and 1121 mg/m(3) resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt(50) for soman determined by probit analysis was 827.2mg/m(3). A majority of the animals that died at 1121 mg/m(3) developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs. (c) 2010 Elsevier Inc. All rights reserved.

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

Perkins, Michael W.; Pierre, Zdenka; Rezk, Peter

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m{sup 3} concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m{sup 3} soman survived, while animals exposed to 841, and 1121 mg/m{sup 3} resulted in 38% and 13% survival,more » respectively. The microinstillation inhalation exposure LCt{sub 50} for soman determined by probit analysis was 827.2 mg/m{sup 3}. A majority of the animals that died at 1121 mg/m{sup 3} developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.« less

Water-soluble quercetin modulates the choleresis and bile lipid ratio in rats.

PubMed

Vovkun, Tatiana; Yanchuk, Petro; Shtanova, Lidiya; Veselskiy, Stanislav; Filimonova, Natalia; Shalamay, Anatoly; Vedmid, Volodymyr

2018-01-01

Water-soluble analogue of quercetin, corvitin is used in patients with myocardial infarction as blocker of 5-lipoxygenase. However, its effects on secretion, lipid content and physico-chemical properties of bile have not been understood yet. We investigated the effect of corvitin, applied in different doses, on the level of bile flow, the content of bile free and esterified cholesterol, phospholipids, triacylglycerols, and free fatty acids. In order to determine stability of the bile colloidal system, we examined the relationship between different lipid components. The rats were injected intraportally with a bolus of corvitin. At doses of 2.5, 5, and 10 mg/kg, the latter increased bile flow and concentration of total cholates, as well as free fatty acids. Corvitin (5 mg/kg) elevated phospholipids and cholesterol content, but at a dose of 10 mg/kg it increased the concentration of bile cholesterol esters and triacylglycerols. Corvitin applied at doses of 2.5 and 10 mg/kg increased total cholates/cholesterol ratio, but at a dose of 10 mg/kg, the drug reduced cholesterol / esterified cholesterol ratio. The results suggest that corvitin exerts choleretic effect and improves stability of bile colloidal system.

Reconstruction and analysis of erythemal UV radiation time series from Hradec Králové (Czech Republic) over the past 50 years

NASA Astrophysics Data System (ADS)

Čížková, Klára; Láska, Kamil; Metelka, Ladislav; Staněk, Martin

2018-02-01

This paper evaluates the variability of erythemal ultraviolet (EUV) radiation from Hradec Králové (Czech Republic) in the period 1964-2013. The EUV radiation time series was reconstructed using a radiative transfer model and additional empirical relationships, with the final root mean square error of 9.9 %. The reconstructed time series documented the increase in EUV radiation doses in the 1980s and the 1990s (up to 15 % per decade), which was linked to the steep decline in total ozone (10 % per decade). The changes in cloud cover were the major factor affecting the EUV radiation doses especially in the 1960s, 1970s, and at the beginning of the new millennium. The mean annual EUV radiation doses in the decade 2004-2013 declined by 5 %. The factors affecting the EUV radiation doses differed also according to the chosen integration period (daily, monthly, and annually): solar zenith angle was the most important for daily doses, cloud cover, and surface UV albedo for their monthly means, and the annual means of EUV radiation doses were most influenced by total ozone column. The number of days with very high EUV radiation doses increased by 22 % per decade, the increase was statistically significant in all seasons except autumn. The occurrence of the days with very high EUV doses was influenced mostly by low total ozone column (82 % of days), clear-sky or partly cloudy conditions (74 % of days) and by increased surface albedo (19 % of days). The principal component analysis documented that the occurrence of days with very high EUV radiation doses was much affected by the positive phase of North Atlantic Oscillation with an Azores High promontory reaching over central Europe. In the stratosphere, a strong Arctic circumpolar vortex and the meridional inflow of ozone-poor air from the southwest were favorable for the occurrence of days with very high EUV radiation doses. This is the first analysis of the relationship between the high EUV radiation doses and macroscale circulation patterns, and therefore more attention should be given also to other dynamical variables that may affect the solar UV radiation on the Earth surface.

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

PubMed

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

2008-04-15

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

TU-EF-204-09: A Preliminary Method of Risk-Informed Optimization of Tube Current Modulation for Dose Reduction in CT

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

Gao, Y; Liu, B; Kalra, M

Purpose: X-rays from CT scans can increase cancer risk to patients. Lifetime Attributable Risk of Cancer Incidence for adult patients has been investigated and shown to decrease as patient age. However, a new risk model shows an increasing risk trend for several radiosensitive organs for middle age patients. This study investigates the feasibility of a general method for optimizing tube current modulation (TCM) functions to minimize risk by reducing radiation dose to radiosensitive organs of patients. Methods: Organ-based TCM has been investigated in literature for eye lens dose and breast dose. Adopting the concept in organ-based TCM, this study seeksmore » to find an optimized tube current for minimal total risk to breasts and lungs by reducing dose to these organs. The contributions of each CT view to organ dose are determined through simulations of CT scan view-by-view using a GPU-based fast Monte Carlo code, ARCHER. A Linear Programming problem is established for tube current optimization, with Monte Carlo results as weighting factors at each view. A pre-determined dose is used as upper dose boundary, and tube current of each view is optimized to minimize the total risk. Results: An optimized tube current is found to minimize the total risk of lungs and breasts: compared to fixed current, the risk is reduced by 13%, with breast dose reduced by 38% and lung dose reduced by 7%. The average tube current is maintained during optimization to maintain image quality. In addition, dose to other organs in chest region is slightly affected, with relative change in dose smaller than 10%. Conclusion: Optimized tube current plans can be generated to minimize cancer risk to lungs and breasts while maintaining image quality. In the future, various risk models and greater number of projections per rotation will be simulated on phantoms of different gender and age. National Institutes of Health R01EB015478.« less

Long-term erythemal UV doses at Sodankylä estimated using total ozone, sunshine duration, and snow depth

NASA Astrophysics Data System (ADS)

Lindfors, A. V.; Arola, A.; Kaurola, J.; Taalas, P.; SvenøE, T.

2003-08-01

A method for estimating daily erythemal UV doses using total ozone, sunshine duration, and snow depth has been developed. The method consists of three steps: (1) daily clear-sky UV doses were simulated using the UVSPEC radiative transfer program, with daily values of total ozone as input data, (2) an empirical relationship was sought between the simulated clear-sky UV doses, the measured UV doses, and the duration of bright sunshine, and (3) daily erythemal UV doses were estimated using this relationship. The method accounts for the varying surface albedo by dividing the period of interest into winter and summer days, depending on the snow depth. Using this method, the daily erythemal UV doses at Sodankylä were estimated for the period 1950-1999. This was done using Tromsø's total ozone together with Sodankylä's own sunshine duration and snow depth as input data. Although the method is fairly simple, the results are in good agreement, even on the daily scale, with the UV radiation measured with the Brewer spectrophotometer at Sodankylä. Over the period 1950-1999 a statistically significant increasing trend of 3.9% per decade in erythemal UV doses was found for March. The fact that this trend is much more pronounced during the latter part of the period, which is also the case for April, suggests a connection to the stratospheric ozone depletion. For July, on the other hand, a significant decreasing trend of 3.3% per decade, supported by the changes in both total ozone and sunshine duration, was found.

Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy.

PubMed

Ferris, Matthew J; Zhong, Jim; Switchenko, Jeffrey M; Higgins, Kristin A; Cassidy, Richard J; McDonald, Mark W; Eaton, Bree R; Patel, Kirtesh R; Steuer, Conor E; Baddour, H Michael; Miller, Andrew H; Bruner, Deborah W; Xiao, Canhua; Beitler, Jonathan J

2018-01-01

Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients. At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose-volume histograms, and associations with MFI-20 scores were analyzed. Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p<0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores. In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue. Copyright © 2017 Elsevier B.V. All rights reserved.

An investigation of voxel geometries for MCNP-based radiation dose calculations.

PubMed

Zhang, Juying; Bednarz, Bryan; Xu, X George

2006-11-01

Voxelized geometry such as those obtained from medical images is increasingly used in Monte Carlo calculations of absorbed doses. One useful application of calculated absorbed dose is the determination of fluence-to-dose conversion factors for different organs. However, confusion still exists about how such a geometry is defined and how the energy deposition is best computed, especially involving a popular code, MCNP5. This study investigated two different types of geometries in the MCNP5 code, cell and lattice definitions. A 10 cm x 10 cm x 10 cm test phantom, which contained an embedded 2 cm x 2 cm x 2 cm target at its center, was considered. A planar source emitting parallel photons was also considered in the study. The results revealed that MCNP5 does not calculate total target volume for multi-voxel geometries. Therefore, tallies which involve total target volume must be divided by the user by the total number of voxels to obtain a correct dose result. Also, using planar source areas greater than the phantom size results in the same fluence-to-dose conversion factor.

Changes in Neuropsychiatric Inventory Associated with Semagacestat Treatment of Alzheimer's Disease.

PubMed

Rosenberg, Paul B; Lanctôt, Krista L; Herrmann, Nathan; Mintzer, Jacobo E; Porsteinsson, Anton P; Sun, Xiaoying; Raman, Rema

2016-08-10

In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD). We sought to examine the effect of semagacestat treatment on neuropsychiatric symptoms (NPS). 1,537 participants with mild to moderate AD were randomized to 76 weeks' treatment with placebo versus two doses of semagacestat. NPS were assessed with the Neuropsychiatric Inventory (NPI-Total and subdomains). Cognition was assessed with the Alzheimer's Disease Assessment Scale-Cognitive (first 11 items, ADAS11). Mixed-Model Repeated Measures was used to compare the effects of treatment assignment on change in NPI-total and subdomains over time. Survival analysis was used to assess the treatment effect on time to first worsening of NPS (NPI-Total ≥10 or NPI subdomain ≥4) for subjects with no or minor NPS at baseline. Participants on high dose semagecestat (140 mg) had greater increase in NPI-Total and greater risk of incident first worsening in NPI-Total and in subdomains of aberrant motor behavior, appetite, depression/dysphoria, and sleep. ADAS11 increased more in participants whose NPI-Total increased. In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. Increased NPS was associated with cognitive decline regardless of treatment assignment. These findings suggest that greater NPS may be the result of gamma-secretase treatment and emphasize the importance of monitoring NPS as potential adverse events in trials of novel treatments for AD.

Effects of whole-body, ionizing radiation on the semen in beagle dogs

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

Day, P.A.

1988-01-01

Six beagle dogs were exposed to a total dose of 183 R of gamma radiation at a dose rate of 1 R/day, while three other dogs were exposed to a single dose of 100 R. Weekly semen analysis was performed on all irradiated dogs plus four nonirradiated dogs. Semen volume, sperm concentration, total sperm count, sperm motility and sperm head morphometry were examined. Dogs exposed to chronic radiation showed a severe decline in sperm numbers, detected after seven weeks of exposure. Sperm concentration and total sperm count were the first parameters affected and were the only parameters consistently affected. Themore » dogs exposed to 100 R as a single dose, did not show a significant decline in sperm numbers. During a 36 week recovery period, the chronically irradiated dogs did show a slight increase in sperm numbers, but they never approached pre-exposure levels.« less

High Dose Hyperfractionated Radiotherapy for Adults with Glioblastomas

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

Koukourakis, Michael; Scarlatos, John; Yiannakakis, Dimitrios

2015-01-15

From 1989 to 1991, 27 patients with glioblastoma multiforme or anaplastic astrocytoma of the brain were treated with radiotherapy. Fifteen of twenty-seven patients were treated through limited volume fields, with a thrice-a-day (1.1 Gy/f) or twice-a-day (1.4 Gy/f) hyperfractionated regimen to a total physical dose of 62–92 Gy (median dose 76 Gy). The remaining 12 were treated with whole brain irradiation (40 Gy of total conventionally fractionated dose) and a localised boost to a total dose of 60 Gy. The hyperfractionated regimen was well tolerated and there was no sign of increased brain oedema to indicate the insertion of amore » split. Of six patients who received a NTD10 (normalised total dose for α/β =10) higher than 71 Gy, five showed CR (83% CR rate) versus three of 21 patients who received a lower NTD10 (14% CR rate). For 13 patients who received a NTD10 higher than 66 Gy, the 18-months survival was 61% (8/13) versus 28% (4/14) for 14 patients who received a NTD10 less than 66 Gy. As far as the late morbidity is concerned, of six patients treated with 76-92 Gy of physical dose, none died because of radiation-induced brain necrosis within 18-42 months of follow-up, and three of them are without evidence of disease 18-31 months after the end of radiation treatment. None of our 15 patients who received less than whole brain irradiation relapsed outside the radiation portals. The present study strongly suggests the use of limited volume hyperfractionated radiotherapy schemes, so as to increase the local tumor dose (NTD10) to values higher than 79 Gy, at the same time keeping the NTD2 (NTD for α/β = 2) below 68 Gy.« less

Nitrogen split dose fertilization, plant age and frost effects on phytochemical content and sensory properties of curly kale (Brassica oleracea L. var. sabellica).

PubMed

Groenbaek, Marie; Jensen, Sidsel; Neugart, Susanne; Schreiner, Monika; Kidmose, Ulla; Kristensen, Hanne L

2016-04-15

We investigated how concentrations of sensory relevant compounds: glucosinolates (GLSs), flavonoid glycosides, hydroxycinnamic acid derivatives and sugars in kale responded to split dose and reduced nitrogen (N) fertilization, plant age and controlled frost exposure. In addition, frost effects on sensory properties combined with N supply were assessed. Seventeen week old kale plants showed decreased aliphatic GLSs at split dose N fertilization; whereas reduced N increased aliphatic and total GLSs. Ontogenetic effects were demonstrated for all compounds: sugars, aliphatic and total GLSs increased throughout plant development, whereas kaempferol and total flavonoid glycosides showed higher concentrations in 13 week old plants. Controlled frost exposure altered sugar composition slightly, but not GLSs or flavonoid glycosides. Reduced N supply resulted in less bitterness, astringency and pungent aroma, whereas frost exposure mainly influenced aroma and texture. N treatment explained most of the sensory variation. Producers should not rely on frost only to obtain altered sensory properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2007-01-01

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

High dose psilocybin is associated with positive subjective effects in healthy volunteers.

PubMed

Nicholas, Christopher R; Henriquez, Kelsey M; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Hetzel, Scott; Brown, Randall T; Cozzi, Nicholas V; Thomas, Chantelle; Hutson, Paul R

2018-06-01

The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire. There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience. High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.

Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

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

Edmondson, Elijah F., E-mail: elijah.edmondson@colostate.edu; Hunter, Nancy R.; Weil, Michael M.

2015-07-15

Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. Results: A total of 210 tumors were induced within the radiation field in 788 mice. Anmore » overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor susceptibility among stromal cell populations.« less

Patient-specific radiation dose and cancer risk for pediatric chest CT.

PubMed

Li, Xiang; Samei, Ehsan; Segars, W Paul; Sturgeon, Gregory M; Colsher, James G; Frush, Donald P

2011-06-01

To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0-16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDI(vol)) or dose-length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Organ dose normalized by tube current-time product or CTDI(vol) decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current-time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current-time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1. RSNA, 2011

Accelerating an Ordered-Subset Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction with a Power Factor and Total Variation Minimization.

PubMed

Huang, Hsuan-Ming; Hsiao, Ing-Tsung

2016-01-01

In recent years, there has been increased interest in low-dose X-ray cone beam computed tomography (CBCT) in many fields, including dentistry, guided radiotherapy and small animal imaging. Despite reducing the radiation dose, low-dose CBCT has not gained widespread acceptance in routine clinical practice. In addition to performing more evaluation studies, developing a fast and high-quality reconstruction algorithm is required. In this work, we propose an iterative reconstruction method that accelerates ordered-subsets (OS) reconstruction using a power factor. Furthermore, we combine it with the total-variation (TV) minimization method. Both simulation and phantom studies were conducted to evaluate the performance of the proposed method. Results show that the proposed method can accelerate conventional OS methods, greatly increase the convergence speed in early iterations. Moreover, applying the TV minimization to the power acceleration scheme can further improve the image quality while preserving the fast convergence rate.

Studies of soy sauce sterilization and its special flavour improvement by gamma-ray irradiation

NASA Astrophysics Data System (ADS)

Jingtian, Yang; Xinhua, Jin; Guoxing, Gu; Guichun, Yun

Experimental studies for sterilizing 12 kinds of soy sauce with gamma-ray irradiation showed that both of effects for sterilization and improving flavour and quality of soy sauce were obtained simultaneously. All colibacillus in soy sauce were sterilized using 1 kGy radiation dose and total bacteria count in soy sauce can be reduced to below national standard at 5 kGy dose ( 5x10 4count/ml ). But above 10 kGy dose is needed to kill all bacteria in soy sauce. The significant changes on chemical components in soy sauce irradiated at 5-7 kGy dose took place: raduceing-sugar increased by 1-10%, total amount of 18 kinds of free amino acid raised between 3.5-28 %, emerging-sweet smell substances which have low boiling point, such as alchols, aldehydes and esters obviously increased. The taste-specialists from some soy sauce factories concluded that flavour and quality of soy sauce irradiated are better than non-irradiated.

Accelerating an Ordered-Subset Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction with a Power Factor and Total Variation Minimization

PubMed Central

Huang, Hsuan-Ming; Hsiao, Ing-Tsung

2016-01-01

In recent years, there has been increased interest in low-dose X-ray cone beam computed tomography (CBCT) in many fields, including dentistry, guided radiotherapy and small animal imaging. Despite reducing the radiation dose, low-dose CBCT has not gained widespread acceptance in routine clinical practice. In addition to performing more evaluation studies, developing a fast and high-quality reconstruction algorithm is required. In this work, we propose an iterative reconstruction method that accelerates ordered-subsets (OS) reconstruction using a power factor. Furthermore, we combine it with the total-variation (TV) minimization method. Both simulation and phantom studies were conducted to evaluate the performance of the proposed method. Results show that the proposed method can accelerate conventional OS methods, greatly increase the convergence speed in early iterations. Moreover, applying the TV minimization to the power acceleration scheme can further improve the image quality while preserving the fast convergence rate. PMID:27073853

Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice.

PubMed

Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Takemura, Motohiko

2014-04-01

We investigated whether pretreatment with the neurotransmitter/neuromodulator agmatine (decarboxylated L-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing. By contrast, agmatine did not affect the total incidence of stereotypy induced by a higher dose of METH (10 mg/kg). However, the nature of stereotypy induced by this dose of METH was substantially altered; agmatine pretreatment significantly reduced stereotyped biting but significantly increased stereotyped sniffing and persistent locomotion. Agmatine pretreatment therefore appears to produce a rightward shift in the dose-response curve for METH. Pretreatment of mice with piperazine-1-carboxamidine (a putative agmatinase inhibitor) had no effect on locomotion or stereotypy induced by a low dose of METH, suggesting that endogenous agmatine may not regulate the METH action.

Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

PubMed Central

Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

2015-01-01

Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

Clinical outcomes and cost minimization with an alternative dosing regimen for meropenem in a community hospital.

PubMed

Patel, Gita Wasan; Duquaine, Susan M; McKinnon, Peggy S

2007-12-01

To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. Retrospective cohort study with a cost-minimization analysis. A 417-bed, privately owned community hospital. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

Effect of Direct-Fed Microbial Dosage on the Fecal Concentrations of Enterohemorrhagic Escherichia coli in Feedlot Cattle.

PubMed

Luedtke, Brandon E; Bosilevac, Joseph M; Harhay, Dayna M; Arthur, Terrance M

2016-04-01

Contamination of beef products by Shiga toxin-producing Escherichia coli is a concern for food safety with a particular subset, the enterohemorrhagic E. coli (EHEC), being the most relevant to human disease. To mitigate food safety risks, preharvest intervention strategies have been implemented with the aim to reduce EHEC in cattle. One class of interventions that has been widely used in feedlots is direct-fed microbials (DFMs), which can contain various dosing rates of probiotic bacteria. Here we compare the use of two different doses of a commercially available DFM on total EHEC load in a commercial feedlot setting. The DFMs used were the standard 10(9) Propionibacterium freudenreichii and 10(6) Lactobacillus acidophilus colony forming units (CFUs)/head/day dose of Bovamine(®) (Nutrition Physiology Company, Guymon, OK) and the higher dose, Bovamine Defend™ (Nutrition Physiology Company), which is dosed at 10(9) P. freudenreichii and 10(9) Lactobacillus acidophilus CFUs/head/day. To analyze the total EHEC fecal concentration, 2200 head of cattle were assigned a DFM feed regimen lasting approximately 5 months. At harvest, 480 head of cattle were sampled using rectoanal mucosal swabs. A quantitative polymerase chain reaction assay targeting ecf1 was used to enumerate the total EHEC fecal concentration for 240 head fed the low-dose DFM and 240 head fed the high-dose DFM. No significant difference (p > 0.05) in the fecal concentration of total EHEC was observed between the two doses. This suggests that using an increased dosage provides no additional reduction in the total EHEC fecal concentration of feedlot cattle compared to the standard dosage.

Patient-specific Radiation Dose and Cancer Risk for Pediatric Chest CT

PubMed Central

Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2011-01-01

Purpose: To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. Materials and Methods: The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0–16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDIvol) or dose–length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Results: Organ dose normalized by tube current–time product or CTDIvol decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current–time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current–time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). Conclusion: The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1 PMID:21467251

Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.

PubMed

Zahnreich, Sebastian; Ebersberger, Anne; Kaina, Bernd; Schmidberger, Heinz

2015-04-01

The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter but proportionality to the equivalent whole-body dose was maintained. Conversely, the frequency of radiation-induced cytogenetic damage increased from 0.5 h to 1 day after the first partial-body exposure with a linear dependence on the administered equivalent whole-body dose, for prostate cancer patients only. Only γ-H2AX foci assessment immediately after partial-body radiotherapy was a reliable measure of the expected equivalent whole-body dose. Local tumor doses could be approximated with both assays after one day. After total-body radiotherapy satisfactory dose estimates were achieved with both assays up to 8 h after exposure. In conclusion, the quantification of radiation-induced γ-H2AX foci, but not cytogenetic damage in peripheral leukocytes was a sensitive and rapid biodosimeter after acute heterogeneous irradiation of partial body volumes that was able to primarily assess the absorbed equivalent whole-body dose.

Impact of Long-Term Serum Platinum Concentrations on Neuro- and Ototoxicity in Cisplatin-Treated Survivors of Testicular Cancer

PubMed Central

Sprauten, Mette; Darrah, Thomas H.; Peterson, Derick R.; Campbell, M. Ellen; Hannigan, Robyn E.; Cvancarova, Milada; Beard, Clair; Haugnes, Hege S.; Fosså, Sophie D.; Oldenburg, Jan; Travis, Lois B.

2012-01-01

Purpose Cisplatin-induced neurotoxicity and ototoxicity (NTX) are important adverse effects after chemotherapy for testicular cancer (TC). Although serum platinum is measurable years after therapy, its impact on NTX has not been evaluated. Patients and Methods In all, 169 cisplatin-treated survivors of TC provided blood samples at Survey I and reported NTX during Survey I (1998-2002) and Survey II (2007-2008). Serum platinum was quantified by inductively coupled plasma mass spectrometry. Patient-reported outcomes were evaluated with the Scale for Chemotherapy-Induced Neurotoxicity (SCIN), regarding the extent of symptom bother as 0, “not at all”; 1, “a little”; 2, “quite a bit”; or 3, “very much.” Summing the six symptom scores yielded a total SCIN score of 0 to 18. Categorizing total SCIN scores into quartiles yielded similar-sized groups with increasing symptoms. Multivariate ordinal logistic regression analyses evaluated associations between NTX and long-term serum platinum levels, adjusting for cisplatin dose, dosing schedule, and age. Results At Survey I, a significant four- to five-fold association with total SCIN score emerged for the highest serum platinum quartile (odds ratio [OR], 4.69; 95% CI, 1.82 to 12.08). Paresthesias and Raynaud's syndrome (hands and feet) showed significant two- to four-fold increased risks with the highest platinum quartile. At Survey II, total SCIN score remained significantly associated with the highest platinum quartile (OR, 4.28; 95% CI, 1.36 to 13.48). Paresthesias (hands and feet) and tinnitus showed significant three- to four-fold increased risks for the highest platinum quartile. Cumulative cisplatin dose was not associated with total SCIN score or individual SCIN symptoms in multivariate analyses. Conclusion Here we document a significant relationship between increasing levels of residual serum platinum and NTX severity after adjusting for initial cisplatin dose. PMID:22184390

[Usefulness of Bolus Administration Using the FLEX Mode(Bolus Infusion Mode)for Baclofen Tolerance].

PubMed

Tanaka, Kazunori

2017-02-01

Intrathecal baclofen(ITB)is used to treat intractable spasticity of various etiologies and can provide better control of spasticity through the adjustment of the dose administered through the pump. However, in patients who develop tolerance to baclofen with the standard simple continuous mode, a sharp increase in dose becomes necessary, and spasticity can become harder to control. We investigated whether switching from the simple continuous mode to the bolus infusion mode was effective in controlling spasticity in patients with baclofen tolerance. We reported four patients undergoing ITB therapy at our facility who were considered to have developed baclofen tolerance. We observed the number of bolus infusions and total dose suitable for maintaining spasticity control after switching from the simple continuous mode to the bolus infusion mode. After switching to the bolus infusion mode, the total dose could be reduced in the short term; however, in the long term, the frequency of bolus infusions had to be increased to maintain spasticity control. Two years after changing to bolus infusion six times a day, the total dose was higher than that in the simple continuous mode for two of the four patients, and was the same level in the other two patients. Our four cases suggest that bolus infusion is effective in patients with baclofen tolerance during ITB therapy. Therefore, the conditions of bolus infusion should be further investigated.

Simulation and measurement of total ionizing dose radiation induced image lag increase in pinned photodiode CMOS image sensors

NASA Astrophysics Data System (ADS)

Liu, Jing; Chen, Wei; Wang, Zujun; Xue, Yuanyuan; Yao, Zhibin; He, Baoping; Ma, Wuying; Jin, Junshan; Sheng, Jiangkun; Dong, Guantao

2017-06-01

This paper presents an investigation of total ionizing dose (TID) induced image lag sources in pinned photodiodes (PPD) CMOS image sensors based on radiation experiments and TCAD simulation. The radiation experiments have been carried out at the Cobalt -60 gamma-ray source. The experimental results show the image lag degradation is more and more serious with increasing TID. Combining with the TCAD simulation results, we can confirm that the junction of PPD and transfer gate (TG) is an important region forming image lag during irradiation. These simulations demonstrate that TID can generate a potential pocket leading to incomplete transfer.

Ischaemic heart disease incidence and mortality in an extended cohort of Mayak workers first employed in 1948–1982

PubMed Central

Grigoryeva, Evgeniya S; Haylock, Richard G E; Pikulina, Maria V; Moseeva, Maria B

2015-01-01

Objective: Incidence and mortality from ischaemic heart disease (IHD) was studied in an extended cohort of 22,377 workers first employed at the Mayak Production Association during 1948–82 and followed up to the end of 2008. Methods: Relative risks and excess relative risks per unit dose (ERR/Gy) were calculated based on the maximum likelihood using Epicure software (Hirosoft International Corporation, Seattle, WA). Dose estimates used in analyses were provided by an updated “Mayak Worker Dosimetry System—2008”. Results: A significant increasing linear trend in IHD incidence with total dose from external γ-rays was observed after having adjusted for non-radiation factors and dose from internal radiation {ERR/Gy = 0.10 [95% confidence interval (CI): 0.04 to 0.17]}. The pure quadratic model provided a better fit of the data than did the linear one. No significant association of IHD mortality with total dose from external γ-rays after having adjusted for non-radiation factors and dose from internal alpha radiation was observed in the study cohort [ERR/Gy = 0.06 (95% CI: <0 to 0.15)]. A significant increasing linear trend was observed in IHD mortality with total absorbed dose from internal alpha radiation to the liver after having adjusted for non-radiation factors and dose from external γ-rays in both the whole cohort [ERR/Gy = 0.21 (95% CI: 0.01 to 0.58)] and the subcohort of workers exposed at alpha dose <1.00 Gy [ERR/Gy = 1.08 (95% CI: 0.34 to 2.15)]. No association of IHD incidence with total dose from internal alpha radiation to the liver was found in the whole cohort after having adjusted for non-radiation factors and external gamma dose [ERR/Gy = 0.02 (95% CI: not available to 0.10)]. Statistically significant dose effect was revealed in the subcohort of workers exposed to internal alpha radiation at dose to the liver <1.00 Gy [ERR/Gy = 0.44 (95% CI: 0.09 to 0.85)]. Conclusion: This study provides strong evidence of IHD incidence and mortality association with external γ-ray exposure and some evidence of IHD incidence and mortality association with internal alpha-radiation exposure. Advances in knowledge: It is the first time the validity of internal radiation dose estimates has been shown to affect the risk of IHD incidence. PMID:26224431

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

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Effect of amphetamine on human macronutrient intake.

PubMed

Foltin, R W; Kelly, T H; Fischman, M W

1995-11-01

Six male subjects participated in a 15-day residential study examining the effects of amphetamine on macronutrient intake. During the first 11 days, carbohydrate intake was manipulated by providing lunch meals high (155 g) or low (25 g) in carbohydrate. Subjects received oral d-amphetamine (5, 10 mg/70 kg, BID) or placebo. Total daily caloric intake was similar under both lunch conditions (approximately 3400/Kcal), but carbohydrate contributed more energy under the high-carbohydrate condition. Both doses of amphetamine decreased total caloric intake to approximately 2600 Kcal, by decreasing the number of eating bouts, without affecting macronutrient selection. During the last four days subjects received a higher daily dose of amphetamine (30 mg/70 kg in four doses) or placebo, and were allowed to self-select lunch. Although 30 mg amphetamine decreased intake of all macronutrients, the relative contribution of carbohydrate to total caloric intake was increased from 54% to 62%, while the contribution of fat was decreased from 32% to 26% and the contribution of protein was decreased from 14% to 12%. Thus, at a high dose, amphetamine altered the relative contribution of specific macronutrients to total caloric intake.

Ferromagnetism in proton irradiated 4H-SiC single crystal

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

Zhou, Ren-Wei; Wang, Hua-Jie; Chen, Wei-Bin

Room-temperature ferromagnetism is observed in proton irradiated 4H-SiC single crystal. An initial increase in proton dose leads to pronounced ferromagnetism, accompanying with obvious increase in vacancy concentration. Further increase in irradiation dose lowers the saturation magnetization with the decrease in total vacancy defects due to the defects recombination. It is found that divacancies are the mainly defects in proton irradiated 4H-SiC and responsible for the observed ferromagnetism.

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

The relationship of body mass index and abdominal fat on the radiation dose received during routine computed tomographic imaging of the abdomen and pelvis.

PubMed

Chan, Victoria O; McDermott, Shaunagh; Buckley, Orla; Allen, Sonya; Casey, Michael; O'Laoide, Risteard; Torreggiani, William C

2012-11-01

To determine the relationship of increasing body mass index (BMI) and abdominal fat on the effective dose acquired from computed tomography (CT) abdomen and pelvis scans. Over 6 months, dose-length product and total milliamp-seconds (mAs) from routine CT abdomen and pelvis scans of 100 patients were recorded. The scans were performed on a 64-slice CT scanner by using an automatic exposure control system. Effective dose (mSv) based on dose-length product, BMI, periumbilical fat thickness, and intra-abdominal fat were documented for each patient. BMI, periumbilical fat thickness, and intra-abdominal fat were compared with effective dose. Thirty-nine men and 61 women were included in the study (mean age, 56.3 years). The mean BMI was 26.2 kg/m(2). The mean effective dose was 10.3 mSv. The mean periumbilical fat thickness was 2.4 cm. Sixty-five patients had a small amount of intra-abdominal fat, and 35 had a large amount of intra-abdominal fat. The effective dose increased with increasing BMI (P < .001) and increasing amounts of intra-abdominal fat (P < .001). For every kilogram of weight, there is a 0.13 mSv increase in effective dose, which is equal to 6.5 chest radiographs per CT examination. For an increase in BMI by 5 kg/m(2), there is a 1.95 mSv increase in effective dose, which is equal to 97.5 chest radiographs per CT examination. Increasing BMI and abdominal fat significantly increases the effective dose received from CT abdomen and pelvis scans. Copyright © 2012 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Thermoluminescent dosimetry in electron beams: energy dependence.

PubMed

Robar, V; Zankowski, C; Olivares Pla, M; Podgorsak, E B

1996-05-01

The response of thermoluminescent dosimeters to electron irradiations depends on the radiation dose, mean electron energy at the position of the dosimeter in phantom, and the size of the dosimeter. In this paper the semi-empirical expression proposed by Holt et al. [Phys. Med. Biol. 20, 559-570 (1975)] is combined with the calculated electron dose fraction to determine the thermoluminescent dosimetry (TLD) response as a function of the mean electron energy and the dosimeter size. The electron and photon dose fractions, defined as the relative contributions of electrons and bremsstrahlung photons to the total dose for a clinical electron beam, are calculated with Monte Carlo techniques using EGS4. Agreement between the calculated and measured TLD response is very good. We show that the considerable reduction in TLD response per unit dose at low electron energies, i.e., at large depths in phantom, is offset by an ever-increasing relative contribution of bremsstrahlung photons to the total dose of clinical electron beams. This renders the TLD sufficiently reliable for dose measurements over the entire electron depth dose distribution despite the dependence of the TLD response on electron beam energy.

Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing.

PubMed

Edelman, Alison B; Cherala, Ganesh; Blue, Steven W; Erikson, David W; Jensen, Jeffrey T

2016-07-01

To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. Healthy, reproductive-age women with obese and normal BMIs received 1.5mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5h. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. A total of 10 women enrolled and completed the study (normal BMI=5, median 22.8kg/m(2), range 20.8-23.7; obese BMI=5, 39.5kg/m(2), range 35.9-46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1990-03-01

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.

Reconstruction of erythemal UV irradiance at Hohenpeissenberg (1968-2001) considering trends of total ozone, cloudiness, and turbidity

NASA Astrophysics Data System (ADS)

Trepte, S.; Winkler, P.

2003-04-01

The global mean total column ozone amount for the period 1997-2001 was approximately 3% below the 1964-1980 average. The largest ozone decreases in the northern hemisphere midlatitudes are observed during winter-spring (˜4%), with summer-autumn decreases approximately half as large. Total ozone measured at Hohenpeissenberg, Germany (48^oN, 11^oE) shows a strong decrease by about 10% since 1968, representing the long-term downward trend over Central Europe. The main consequence of this phenomenon is the expected increase of solar ultraviolet irradiation (UV-B) reaching the Earth's surface with the known harmful effects on the biosphere. Global data records of reliable routine observations of UV irradiance are still too short for accurate estimation of long-term UV variations and trends. While direct UV mesaurements at Hohenpeissenberg are available only since 1990, the long-term development of UV-B have to be reconstructed. Besides on the amount of total ozone the UV irradiation at the ground depends also on atmospheric turbidity and cloudiness. The reconstruction method is based on statistical correlations of measured UV-B data with the influencing parameters total ozone, turbidity and cloud modification factors derived from eye-observations in connection with total solar irradiance data. These observed data allow a realistic reconstruction of the UV-B time series, since no assumption on these influencing data have to be made. A model is presented, using hourly observed spectral UV-B irradiance (1990-1998), total solar irradiance, total ozone amount (daily mean) and clouds to derive erythemal UV irradiance and daily doses at Hohenpeissenberg in the period 1968-2001. A comparison with recorded UV data shows good agreement. Due to long-term total ozone loss, peak values of erythemal UV irradiance in spring and summer at clear-sky conditions have strongly increased (+4.2%/decade in June). Mean daily doses have also increased in this season (+5.4%/decade in May) but meteorological changes like reduced sunshine duration and increased cloudiness lead to a partly compensation of the ozone-loss effect in spring and to an overcompensation in autumn, where we found a long-term decrease of the daily dose (-3.0%/decade in September). Model calculations also demonstrate large year-to-year fluctuations of UV doses induced by meteorological variability, which exceed the long-term trend of the various months significantly. Nevertheless, this investigation has shown that on a long-term time scale the daily doses develop in a different way as compared to the peak values because the reasons for ozone decline (anthropogenic CFC's) and the cloud cover (hydrological cycle changes due to greenhouse effect) are caused by different phenomena.

Protein Binding of Lopinavir and Ritonavir During Four Phases of Pregnancy: Implications for Treatment Guidelines

PubMed Central

Patterson, Kristine B.; Dumond, Julie B.; Prince, Heather A.; Jenkins, Amanda J.; Scarsi, Kimberly K.; Wang, Ruili; Malone, Stephanie; Hudgens, Michael G.; Kashuba, Angela DM.

2013-01-01

Objective To investigate the intraindividual pharmacokinetics of total (protein bound + unbound) and unbound lopinavir/ritonavir (LPV/RTV) and to assess whether the pediatric formulation (100mg/25mg) can overcome any pregnancy-associated changes. Design Prospective longitudinal pharmacokinetic (PK) study Methods HIV-infected pregnant antiretroviral therapy-naïve and experienced women receiving LPV/RTV 400mg/100mg tablets twice daily. Intensive PK evaluations were performed at 20–24 weeks (PK1), 30 weeks (PK2) followed by empiric dose increase using the pediatric formulation (100mg/25mg twice daily), 32 weeks (PK3), and 8 weeks postpartum (PK4). Results Twelve women completed pre-specified PK evaluations. Median (range) age was 28 (1–35) years and baseline BMI was 32 (19–41) kg/m2. During pregnancy, total area under the time concentration (AUC0–12hr) for LPV was significantly lower than postpartum [PK1, PK2 or PK3 vs. PK4, p= 0.005]. Protein unbound LPV AUC0–12hr remained unchanged during pregnancy [PK1: 1.6 (1.3–1.9) vs. PK2: 1.6 (1.3–1.9) µg*hr/mL, p=0.4] despite a 25% dose increase [PK2 vs. PK3: 1.8 (1.3–2.1) µg*hr/mL, p=0.5]. Protein unbound LPV predose concentrations (C12h) did not significantly change despite dose increase [PK2: 0.10 (0.08–0.15) vs. PK3: 0.12 (0.10–0.15) µg/mL, p=0.09]. Albumin and LPV AUC0–12h fraction unbound were correlated (rs=0.3, p=0.03). Conclusions Total LPV exposure was significantly decreased throughout pregnancy despite the increased dose. However, the exposure of unbound LPV did not change significantly regardless of trimester or dose. Predose concentrations of unbound LPV were not affected by the additional dose and were 70-fold greater than the minimum efficacy concentration. These findings suggest dose adjustments may not be necessary in all HIV-infected pregnant women. PMID:23221983

The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model

PubMed Central

Sanzari, Jenine K.; Wan, X. Steven; Krigsfeld, Gabriel S.; Wroe, Andrew J.; Gridley, Daila S.; Kennedy, Ann R.

2014-01-01

Exposure to total-body radiation induces hematological changes, which can detriment one's immune response to wounds and infection. Here, the decreases in blood cell counts after acute radiation doses of γ-ray or proton radiation exposure, at the doses and dose-rates expected during a solar particle event (SPE), are reported in the ferret model system. Following the exposure to γ-ray or proton radiation, the ferret peripheral total white blood cell (WBC) and lymphocyte counts decreased whereas neutrophil count increased within 3 hours. At 48 hours after irradiation, the WBC, neutrophil, and lymphocyte counts decreased in a dose-dependent manner but were not significantly affected by the radiation type (γ-rays verses protons) or dose rate (0.5 Gy/minute verses 0.5 Gy/hour). The loss of these blood cells could accompany and contribute to the physiological symptoms of the acute radiation syndrome (ARS). PMID:25356435

Effects of gamma radiation on total phenolics, trypsin and tannin inhibitors in soybean grains

NASA Astrophysics Data System (ADS)

de Toledo, T. C. F.; Canniatti-Brazaca, S. G.; Arthur, V.; Piedade, S. M. S.

2007-10-01

The objective was determining possible radiation-induced alterations (with doses of 2, 4 and 8 kGy) in raw or cooked grains from five soybean cultivars through the analysis of some antinutrient. Total phenolic ranged from 2.46 to 10.83 mg/g, the trypsin inhibited from 18.19 to 71.64 UTI/g and tannins from 0.01 to 0.39 mg/g. All the antinutrient studied underwent reduction with increases in the doses and cooking process was effective too.

Indoor Air Quality Management for Operations and Maintenance Personnel

DTIC Science & Technology

1991-09-01

short-lived radioisotopes collectively referred to as radon " daughters ." The first four of these daughters-polonium- 218, lead-214, bismuth-214, and...that can damage cells, increasing the risk of lung cancer. The radiation dose from inhaled radon daughters makes up about half the total dose from

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

PubMed

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

2011-11-03

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

[Effectiveness of various dopamine doses in acute myocardial ischemia complicated by cardiogenic shock (an experimental study)].

PubMed

Kipshidze, N N; Korotkov, A A; Marsagishvili, L A; Prigolashvili, T Sh; Bokhua, M R

1981-06-01

The effect of various doses of dopamine on the values of cardiac contractile and hemodynamic function under conditions of acute two-hour ischemia complicated by cardiogenic shock was studied in 27 experiments on dogs. In a dose of 5 microgram/kg/min dopamine caused an optimum increase in cardiac productive capacity, reduction of peripheral resistance, adequate increase in coronary circulation and decrease in ST segment depression on the ECG. Infusion of 10 microgram/kg/min dopamine usually caused myocardial hyperfunction with an increase in total peripheral resistance and cardiac performance. Maximum dopamine doses (10 microgram/kg/min and more) were effective in the areactive form of cardiogenic shock. In longterm dopamine infusion it is necessary to establish continuous control over the hemodynamic parameters and the ECG to prevent aggravation of ischemia and for stage-by-stage reduction of the drug concentration and determination of the minimum maintenance dose.

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

PubMed

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

2017-09-23

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

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.

PubMed

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

2017-03-01

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

Long-term antipsychotic and benzodiazepine use and brain volume changes in schizophrenia: The Northern Finland Birth Cohort 1966 study.

PubMed

Huhtaniska, Sanna; Jääskeläinen, Erika; Heikka, Tuomas; Moilanen, Jani S; Lehtiniemi, Heli; Tohka, Jussi; Manjón, José V; Coupé, Pierrick; Björnholm, Lassi; Koponen, Hannu; Veijola, Juha; Isohanni, Matti; Kiviniemi, Vesa; Murray, Graham K; Miettunen, Jouko

2017-08-30

High doses of antipsychotics have been associated with loss in cortical and total gray matter in schizophrenia. However, previous imaging studies have not taken benzodiazepine use into account, in spite of evidence suggesting adverse effects such as cognitive impairment and increased mortality. In this Northern Finland Birth Cohort 1966 study, 69 controls and 38 individuals with schizophrenia underwent brain MRI at the ages of 34 and 43 years. At baseline, the average illness duration was over 10 years. Brain structures were delineated using an automated volumetry system, volBrain, and medication data on cumulative antipsychotic and benzodiazepine doses were collected using medical records and interviews. We used linear regression with intracranial volume and sex as covariates; illness severity was also taken into account. Though both medication doses associated to volumetric changes in subcortical structures, after adjusting for each other and the average PANSS total score, higher scan-interval antipsychotic dose associated only to volume increase in lateral ventricles and higher benzodiazepine dose associated with volume decrease in the caudate nucleus. To our knowledge, there are no previous studies reporting associations between benzodiazepine dose and brain structural changes. Further studies should focus on how these observations correspond to cognition and functioning. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Fractionated irradiation of carbon beam and the isoeffect dose on acute reaction of skin

PubMed Central

Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Koda, Kana; Koike, Sachiko; Ando, Koichi; Furusawa, Yoshiya

2014-01-01

Purpose: The aim of this study was to clear any specific LETs cause change in skin reaction. We irradiated mice feet with mono-energetic and SOBP carbon ions, to obtain dose–response of early skin reaction at different LETs. Materials and methods: Mice: C3H/HeMsNrsf female mice aged 4 months old were used for this study. The animals were produced and maintained in specific pathogen-free (SPF) facilities. Irradiation: The mice right hind legs received daily fractionated irradiation ranged from single to six fractions. Carbon ions (12C6+) were accelerated by the HIMAC synchrotron to 290 MeV/u. Irradiation was conducted using horizontal carbon-ion beams with a dose rate of ∼3 Gy/min. We chose the LETs at entrance of plateau (20keV/μm) and the SOBP (proximal: 40 keV/μm, middle: 45 keV/μm, distal: 60 keV/μm, distal-end: 80 keV/μm). The reference beam was 137Cs gamma rays with a dose rate of 1.2 Gy/min. Skin reaction: Skin reaction of the irradiated legs was scored every other day, between the14th and 35th post-irradiation days. Our scoring scale consisted of seven steps, ranging from 0.5 to 3.5 [ 1]. The skin score analyzed a result by the method that described by Ando et al. [ 2]. The Fe-plot proposed by Douglas and Fowler was used as a multifraction linear quadratic model. A plot between the reciprocal of the isoeffect dose and the dose per fraction resulted in a straight line. Results: Required isoeffect total dose increased linearly with the fraction numbers on a semi-logarithmic chart at LET 20–60 keV/µm SOBP beam. The isoeffect total dose decreased with the increase in the LET. However, no increases in isoeffect total dose were observed at few fractionations at 80 keV/µm. (data not shown) Using an Fe-plot, we analyzed the isoeffect total dose to evaluate the dependence on Carbon beam, or gamma ray. When I irradiate it by gamma ray, an Fe-plot shows linearly. But, irradiated by Carbon beam, an Fe-plot bent at low fractions (Fig. 1). Conclusion: The LQ-model-based Fe-plot could not fit skin reaction at few fractions at high-LET. Clinical Trial Registration number if required: No.Fig. 1.The reciprocal of the isoeffect dose is plotted against the dose per fraction. (i) Gamma ray: Fe-plot was linear. (ii) C-ions: Fe-plot bent at low fractions.

BOOK REVIEW: NCRP Report No. 160: Ionizing Radiation Exposure of the Population of the United States NCRP Report No. 160: Ionizing Radiation Exposure of the Population of the United States

NASA Astrophysics Data System (ADS)

Thurston, Jim

2010-10-01

This report by Committee 6 of the Council is an extensive update of a previous report on the exposure of the US population to ionizing radiation sources from data gathered in the 1980s (published as Report 93 in 1987). It is combined with an update on the more in-depth assessment of data on medical exposures previously reported in 1989 (Report 100). Individual chapters in this new report are dedicated to specific sources of exposure to the US population—both from natural and artificial radiation—and the level of detail in each chapter is intended to reflect the significance of the contribution of each source to the total collective dose of the population. The first chapter is on the most significant contributor: background radiation. It expands on the concept of natural background radiation in Report 93, renaming it 'ubiquitous background', and describing in detail the contributions from both extra-terrestrial and terrestrial sources. The data demonstrates that the average dose from such exposure has varied little since the previous report (a slight increase from 3.0 mSv to 3.1 mSv). The next chapter is on medical radiation, i.e. the exposure to the population when attending as patients, not including occupational exposure to hospital workers. The most striking data published in the entire report is the increase in the contribution to the total US population dose attributed to such medical exposures. It is now as significant as that from background radiation: medical exposures now account for an average effective dose to the US citizen of 3.00 mSv, up from 0.53 mSv in 1992 (Report 100). The most important contribution to this increase is the 1.46 mSv from CT scanning alone. The nuclear medicine (including PET) contribution is up from 0.14 mSv to 0.77mSv. This evidently must be due to significant changes in medical radiological practice in the US tied to the increase in the availability of CT and PET imaging facilities. These increasing contributions have driven the overall average effective dose to a US citizen from approximately 3.6 mSv reported in 1987 to 6.2 mSv per annum, with medical exposures now responsible for 48% of the total (up from 15% in 1992). It is interesting to note that over roughly the same period of time, the total dose to the UK population has been revised upwards from 2.6 mSv to 2.7mSv to reflect (amongst other factors) the increase in CT scanning in the UK—obviously a much smaller change. However, one has to consider whether medical radiological practices in the UK might similarly change in the coming years, and UK population doses subsequently follow the US trend reported here. There is now a more detailed chapter on exposure to the population from consumer products and activities. Of the contributing factors in this category, the radiation dose received from radioactivity in tobacco smoke is the most significant, followed by building materials and air travel. There has been no significant change in the total dose received from these sources when compared to the earlier Report 93, at 0.13 mSv. The report also gives significant detail on exposure to the public from industrial sources (not just nuclear power), and discusses occupational exposure. Both these categories of exposure, averaged out of the whole population, give very small contributions to the total dose (0.003 mSv and 0.005 mSv, respectively). There are two final points to make about this report. Firstly, it continues the NCRP policy introduced for Report 93 of using SI units rather than the radiation units more commonly used within the US, hence making this report more readily accessible to an international audience. Secondly, in all the descriptions of the exposures and radiation doses received, no attempt is made to convert the doses into risk. The view of the Council, as stated in the forward to the report, is that attempting to quantify the risks associated with such levels of radiation exposure falls outside the remit of the Committee that prepared the report.

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

PubMed

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

2017-12-01

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

Electrically-inactive phosphorus re-distribution during low temperature annealing

NASA Astrophysics Data System (ADS)

Peral, Ana; Youssef, Amanda; Dastgheib-Shirazi, Amir; Akey, Austin; Peters, Ian Marius; Hahn, Giso; Buonassisi, Tonio; del Cañizo, Carlos

2018-04-01

An increased total dose of phosphorus (P dose) in the first 40 nm of a phosphorus diffused emitter has been measured after Low Temperature Annealing (LTA) at 700 °C using the Glow Discharge Optical Emission Spectrometry technique. This evidence has been observed in three versions of the same emitter containing different amounts of initial phosphorus. A stepwise chemical etching of a diffused phosphorus emitter has been carried out to prepare the three types of samples. The total P dose in the first 40 nm increases during annealing by 1.4 × 1015 cm-2 for the sample with the highly doped emitter, by 0.8 × 1015 cm-2 in the middle-doped emitter, and by 0.5 × 1015 cm-2 in the lowest-doped emitter. The presence of surface dislocations in the first few nanometers of the phosphorus emitter might play a role as preferential sites of local phosphorus gettering in phosphorus re-distribution, because the phosphorus gettering to the first 40 nm is lower when this region is etched stepwise. This total increase in phosphorus takes place even though the calculated electrically active phosphorus concentration shows a reduction, and the measured sheet resistance shows an increase after annealing at a low temperature. The reduced electrically active P dose is around 0.6 × 1015 cm-2 for all the emitters. This can be explained with phosphorus-atoms diffusing towards the surface during annealing, occupying electrically inactive configurations. An atomic-scale visual local analysis is carried out with needle-shaped samples of tens of nm in diameter containing a region of the highly doped emitter before and after LTA using Atom Probe Tomography, showing phosphorus precipitates of 10 nm and less before annealing and an increased density of larger precipitates after annealing (25 nm and less).

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

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

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

2006-10-01

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

Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.

PubMed

Bell, Guinevere H; Griffin, William C; Patrick, Kennerly S

2011-12-01

Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal DL-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral DL-methylphenidate (7.5 mg/kg) or transdermal DL-methylphenidate (Daytrana®;1/4 of a 12.5 cm(2) patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. An otherwise depressive dose of ethanol significantly potentiated oral DL-methylphenidate induced increases in total distance traveled for the first 100 min (p<0.05). Transdermal DL-methylphenidate increased total distance traveled after a latency of 80 min, though this effect was not potentiated by concomitant ethanol. Mean 3 h brain D-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding L-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of DL-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of DL-methylphenidate when combined with ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

PubMed

Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

2011-05-01

The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.

High Doses of Bone Morphogenetic Protein 2 Induce Structurally Abnormal Bone and Inflammation In Vivo

PubMed Central

Zara, Janette N.; Siu, Ronald K.; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M.; Ting, Kang

2011-01-01

The major Food and Drug Association–approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL. PMID:21247344

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce;

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi;

In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor

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

Cohen, A.M.; Zsebo, K.M.; Inoue, H.

1987-04-01

Osmotic pumps containing Escherichia coli-derived recombinant human granulocyte colony-stimulating factor (rhG-CSF) were attached to indwelling jugular vein catheters and implanted subcutaneously into Golden Syrian hamsters. Within 3 days, peripheral granulocyte counts had increased > 10-fold with a concomitant 4-fold increase in total leukocytes. Microscopic examination of Wright-Giemsa-stained blood smears from rhG-CSF hamsters showed that only the neutrophil subpopulation of granulocytes had increased. After subcutaneous injection at /sup 35/S-labeled rhG-CSF doses of up to 10 ..mu..g x kg/sup -1/ x day/sup -1/ only granulocyte counts were affected. However, at higher dose levels, a transient thrombocytopenia was noted. Erythrocyte and lymphocyte/monocyte countsmore » remained unaffected by rhG-CSF over the entire dose range studied. Total leukocyte counts increased 3-fold within 12 hr after a single s.c. injection of rhG-CSF. This early effect was associated with an increase in the total number of colony-forming cells and the percent of active cycling cells in the marrow. A sustained elevation of peripheral leukocyte and marrow progenitor counts was observed following seven daily s.c. injections of rhG-CSF. The ability of rhG-CSF to increase the production and release of granulocytes from the marrow may underlie the beneficial effect it produced on the restoration of peripheral leukocyte counts in hamsters made leukopenic by treatment with 5-fluorouracil.« less

Estimation of effective dose and lifetime attributable risk from multiple head CT scans in ventriculoperitoneal shunted children.

PubMed

Aw-Zoretic, J; Seth, D; Katzman, G; Sammet, S

2014-10-01

The purpose of this review is to determine the averaged effective dose and lifetime attributable risk factor from multiple head computed tomography (CT) dose data on children with ventriculoperitoneal shunts (VPS). A total of 422 paediatric head CT exams were found between October 2008 and January 2011 and retrospectively reviewed. The CT dose data was weighted with the latest IRCP 103 conversion factor to obtain the effective dose per study and the averaged effective dose was calculated. Estimates of the lifetime attributable risk were also calculated from the averaged effective dose using a conversion factor from the latest BEIR VII report. Our study found the highest effective doses in neonates and the lowest effective doses were observed in the 10-18 years age group. We estimated a 0.007% potential increase risk in neonates and 0.001% potential increased risk in teenagers over the base risk. Multiple head CTs in children equates to a slight potential increase risk in lifetime attributable risk over the baseline risk for cancer, slightly higher in neonates relative to teenagers. The potential risks versus clinical benefit must be assessed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Radiation exposure from work-related medical X-rays at the Portsmouth Naval Shipyard.

PubMed

Daniels, Robert D; Kubale, Travis L; Spitz, Henry B

2005-03-01

Previous analyses suggest that worker radiation dose may be significantly increased by routine occupational X-ray examinations. Medical exposures are investigated for 570 civilian workers employed at the Portsmouth Naval Shipyard (PNS) at Kittery, Maine. The research objective was to determine the radiation exposure contribution of work-related chest X-rays (WRX) relative to conventional workplace radiation sources. Methods were developed to estimate absorbed doses to the active (hematopoietic) bone marrow from X-ray examinations and workplace exposures using data extracted from worker dosimetry records (8,468) and health records (2,453). Dose distributions were examined for radiation and non-radiation workers. Photofluorographic chest examinations resulted in 82% of the dose from medical sources. Radiation workers received 26% of their collective dose from WRX and received 66% more WRX exposure than non-radiation workers. WRX can result in a significant fraction of the total dose, especially for radiation workers who were more likely to be subjected to routine medical monitoring. Omission of WRX from the total dose is a likely source of bias that can lead to dose category misclassification and may skew the epidemiologic dose-response assessment for cancers induced by the workplace.

Gamma irradiation to improve plant vigour, grain development, and yield attributes of wheat

NASA Astrophysics Data System (ADS)

Singh, Bhupinder; Datta, P. S.

2010-02-01

Utilizing low dose gamma radiation holds promise for physiological crop improvement. Seed treatment of low dose gamma radiation 0.01-0.10 kGy reduced plant height, improved plant vigour, flag leaf area, total and number of EBT. Gamma irradiation increased grain yield due to an increase in number of EBT and grain number while 1000 grain weight was negatively affected. Further uniformity in low dose radiation response in wheat in the field suggests that the affect is essentially at physiological than at genetic level and that role of growth hormones could be crucial.

A randomized controlled clinical trial investigating the effect of calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress and insulin resistance in pregnant women at risk for pre-eclampsia.

PubMed

Asemi, Z; Samimi, M; Heidarzadeh, Z; Khorrammian, H; Tabassi, Z

2012-05-15

Increased levels of pro-inflammatory factors, markers of oxidative stress and insulin resistance during pregnancy have been associated with the development of pre-eclampsia. There is some evidence to suggest that calcium supplement and aspirin can reduce the risk of the disorder. To our knowledge, no reports are available indicating the effects of consumed calcium supplement plus aspirin on high sensitivity C-reactive protein (hs-CRP), oxidative stress parameters and insulin resistance in pregnant women at risk for pre-eclampsia. This study was designed to investigate the effects of consumed calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress parameters and insulin resistance among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was carried out among 42 pregnant women at risk for pre-eclampsia, primigravida, aged 18-40 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to received either the placebo (n = 22) or calcium supplement plus low-dose aspirin (n = 20) for 9 weeks. Calcium supplement plus low-dose aspirin were containing 500 mg carbonate calcium plus 80 mg aspirin. Fasting blood samples were taken at baseline and after 9 weeks intervention to measure serum hs-CRP, oxidative stress parameters including plasma Total Antioxidant Capacity (TAC) and Total Glutathione (GSH), Fasting Plasma Glucose (FPG), serum insulin and HOMA-IR score. Consumption of calcium supplement plus low-dose aspirin resulted in a significant difference serum hs-CRP levels as compared to the placebo (102.87 vs. 3227.75 ng mL(-1), p = 0.01). Also, mean changes for plasma TAC (68.96 vs. -74.46 mmol L(-1), p = 0.04) and total GSH levels (304.33 vs. -39.33 micromol L(-1), p = 0.03) were significantly different between the two groups. No significant differences were found comparing calcium supplement plus low-dose aspirin and placebo in terms of their effects on FPG, serum insulin levels and HOMA-IR. Within-group differences in the placebo group revealed a significant increase in serum hs-CRP levels (3227.75 ng mL(-1), p = 0.008) and marginally significant increase in plasma total GSH levels (304.33 micromol L(-1), p = 0.07). In conclusion, consumption calcium supplement plus low-dose aspirin during pregnancy for 9 weeks in pregnant women at risk for pre-eclampsia resulted in a significant difference serum hs-CRP and increased levels of plasma TAC and total GSH as compared to the placebo group, but could not affect serum insulin levels and HOMA-IR score.

Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells.

PubMed

Hajiani, Maliheh; Razi, Farideh; Golestani, Aboualfazl; Frouzandeh, Mehdi; Owji, Ali Akbar; Khaghani, Shahnaz; Ghannadian, Naghmeh; Shariftabrizi, Ahmad; Pasalar, Parvin

2012-01-01

Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as a gene regulator, and its gene modulation effects have been observed at different levels of gene expression and cell signaling. This study was performed to investigate the effects of vitamin E on the activity and expression of the most important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma. Twenty-eight male Sprauge-Dawley rats were divided into four groups: control group and three dosing groups. The control group received the vehicle (liquid paraffin), and the dosing groups received twice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) for 6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and enzyme assays were used to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells at 0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidant capacity were also assessed in plasma at the same time intervals. Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 and 6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was not significantly changed in response to vitamin E administration at any time points, whereas Cu/Zn-SOD mRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) of vitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin E treatment in 30 and 100 mg/kg dosing groups. Total antioxidant status was significantly increased after 4 and 6 weeks in the 100 mg/kg dosing group. Only the chronic administration of higher doses of alpha-tocopherol is associated with the increased activity and expression of Mn-SOD in rats. Cu/Zn-SOD activity and expression does not dramatically change in response to vitamin E.

Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice.

PubMed

Onaolapo, J Olakunle; Onaolapo, Y Adejoke; Akanmu, A Moses; Olayiwola, Gbola

2016-01-01

Effects of daily caffeine consumption on open-field behaviours, serum corticosterone and brain antioxidant levels were investigated after six hours of total sleep-deprivation in prepubertal mice. We tested the hypothesis that daily caffeine consumption may significantly alter behaviour, stress and antioxidative response of prepubertal mice to an acute episode of total sleep-deprivation. Prepubertal Swiss mice of both sexes were assigned to two main groups of 120 each (subdivided into 6 groups of 10 each, based on sex), and administered vehicle or graded oral doses of caffeine (10, 20, 40, 80 and 120 mg/kg/day) for 14 days. On day 14, a main group was subjected to 6 h of total sleep-deprivation by 'gentle-handling'. Open-field behaviours were then assessed in both groups, after which animals were euthanized, and levels of corticosterone, superoxide dismutase and glutathione peroxidase assayed. Horizontal locomotion, rearing and grooming increased significantly, compared to control, with sleep-deprived (SD) mice showing stronger caffeine-driven responses at higher doses; and SD female mice showing sustained response to caffeine, compared to respective males. Plasma corticosterone increased with increasing doses of caffeine in both non sleep-deprived (NSD) and SD mice; although SD mice had higher corticosterone levels. Sleep-deprivation and/or higher doses of caffeine were associated with derangements in brain antioxidant levels. Repeated caffeine consumption and/or acute sleep-deprivation led to significant changes in pattern of open-field behaviour and stress/antioxidant response in mice. Responses seen in the study are probably due to modulatory effects of caffeine on the total body response to stressful stimuli.

Clinical application of the OneDose Patient Dosimetry System for total body irradiation.

PubMed

Best, S; Ralston, A; Suchowerska, N

2005-12-21

The OneDose Patient Dosimetry System (Sicel Technologies) is a new dosimeter based on metal oxide semiconductor field-effect transistor technology and designed for the in vivo measurement of patient dose during radiotherapy. In vivo dosimetry for total body irradiation (TBI) is challenging due to the extended treatment distance, low dose rates and beam spoilers. Phantom results confirm the suitability of the dosimeter for TBI in terms of inherent build-up, post-irradiation fading, accuracy, reproducibility, linearity and temperature dependence. Directional dependence is significant and should be taken into account. The OneDose dosimeters were also trialed in vivo for two TBI patients and the dose measured compared to conventional dosimeter measurements using an ionization chamber and thermoluminescent dosimeters (TLD), with agreement to within 2.2% and 3.9%, respectively. Phantom and patient results confirm that the OneDose patient dosimetry system is a practical and convenient alternative to TLDs for TBI in vivo dosimetry. For increased confidence in results with this dosimeter, we recommend that two dosimeters be used for each site of interest.

Bile acid changes after high-dose ursodeoxycholic acid treatment in primary sclerosing cholangitis: relation to disease progression

PubMed Central

Sinakos, Emmanouil; Marschall, Hanns-Ulrich; Kowdley, Kris V.; Befeler, Alex; Keach, Jill; Lindor, Keith

2010-01-01

High-dose (28-30mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), due to limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high dose UDCA versus placebo. Samples for analysis were obtained at baseline and at the end of treatment. The mean changes in UDCA (16.86 vs 0.05 μmol/L) and total bile acid (17.21 vs −0.55 μmol/L) levels were significantly higher in the UDCA group (n=29) compared to placebo (n=27) when pretreatment levels were compared (p<0.0001). LCA was also markedly increased (0.22 vs 0.01 μmol/L) in the UDCA group compared to placebo (p=0.001). No significant changes were detected for cholic acid (CA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). Patients (n=9) in the UDCA group who reached clinical endpoints of disease progression (development of cirrhosis, varices, liver transplantation or death) tend to have greater increase in their post-treatment total bile acid levels (34.99 vs 9.21 μmol/L) (p<0.08) compared to those who did not. Conclusion High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool including lithocholic acid. PMID:20564380

Effects of gamma irradiation on physicochemical properties, antioxidant and microbial activities of sour cherry juice

NASA Astrophysics Data System (ADS)

Arjeh, Edris; Barzegar, Mohsen; Ali Sahari, Mohammad

2015-09-01

Recently, due to the beneficial effects of bioactive compounds, demand for minimally processed fruits and fruit juices has increased rapidly in the world. In this study, sour cherry juice (SCJ) was exposed to gamma irradiation at 0.0, 0.5, 1.5, 3.0, 4.5, and 6.0 kGy and then stored at 4 °C for 60 days. Total soluble solids (TSS), total acidity (TA), color, total phenolic content (TPC), total monomeric anthocyanin content (TMC), antioxidant activity, organic acid profile, and microbial analysis were evaluated at regular intervals during the storage. Results indicated that irradiation did not have any significant effect on TSS, while level of TA increased significantly at the dose of 6 kGy (p<0.05). Furthermore, irradiation treatment and storage time led to a significant increase in L* and b* values and a decrease in a* values. Total monomeric anthocyanin content of the irradiated SCJ was lower than that of the non-irradiated one (24% at 3.0 kGy) and also changed toward a more negative direction during the storage (63% at 3.0 kGy for 60 days). There was a significant decrease in the antioxidant activity (DPPH radical scavenging and FRAP assay) in both irradiated and stored SCJs. After irradiation (0-6 kGy), the results showed that the concentration of malic and oxalic acid significantly increased; but, the concentration of ascorbic, citric, fumaric, and succinic acids significantly decreased. Gamma irradiation with doses of ≥3 kGy resulted in overall reduction in microbial loads. Based on the results obtained from the changes of physicochemical properties, antioxidant activity, and microbial analysis, irradiation of SCJ at doses of higher than 3.0 kGy is not recommended.

Structural Features and Potent Antidepressant Effects of Total Sterols and β-sitosterol Extracted from Sargassum horneri

PubMed Central

Zhao, Donghai; Zheng, Lianwen; Qi, Ling; Wang, Shuran; Guan, Liping; Xia, Yanan; Cai, Jianhui

2016-01-01

The purified total sterols and β-sitosterol extracted from Sargassum horneri were evaluated for their antidepressant-like activity using the forced swim test (FST) and tail suspension test (TST) in mice. Total sterols and β-sitosterol significantly reduced the immobility time in the FST and TST. Total sterols were administered orally for 7 days at doses of 50, 100, and 200 mg/kg, and β-sitosterol was administered intraperitoneally at doses of 10, 20, and 30 mg/kg. β-sitosterol had no effect on locomotor activity in the open field test. In addition, total sterols and β-sitosterol significantly increased NE, 5-HT, and the metabolite 5-HIAA in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters. PMID:27367705

Structural Features and Potent Antidepressant Effects of Total Sterols and β-sitosterol Extracted from Sargassum horneri.

PubMed

Zhao, Donghai; Zheng, Lianwen; Qi, Ling; Wang, Shuran; Guan, Liping; Xia, Yanan; Cai, Jianhui

2016-06-28

The purified total sterols and β-sitosterol extracted from Sargassum horneri were evaluated for their antidepressant-like activity using the forced swim test (FST) and tail suspension test (TST) in mice. Total sterols and β-sitosterol significantly reduced the immobility time in the FST and TST. Total sterols were administered orally for 7 days at doses of 50, 100, and 200 mg/kg, and β-sitosterol was administered intraperitoneally at doses of 10, 20, and 30 mg/kg. β-sitosterol had no effect on locomotor activity in the open field test. In addition, total sterols and β-sitosterol significantly increased NE, 5-HT, and the metabolite 5-HIAA in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters.

High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II-III esophageal cancer.

PubMed

Suh, Yang-Gun; Lee, Ik Jae; Koom, Wong Sub; Cha, Jihye; Lee, Jong Young; Kim, Soo Kon; Lee, Chang Geol

2014-06-01

In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects.

PubMed

Tonstad, Serena; Smerud, Knut; Høie, Lars

2002-07-01

Studies have shown that soy protein reduces some atherogenic lipid and lipoprotein concentrations, although lipoprotein(a) concentrations may be increased. The dose response of soy protein has not been established; neither has its effect on plasma total homocysteine. Our objective was to evaluate the effect of 2 doses of soy protein on lipid, lipoprotein, and homocysteine concentrations. Four to 24 wk after being instructed to consume a lipid-lowering diet, 130 men and women with LDL-cholesterol concentrations > or = 4 mmol/L were studied during a parallel group trial in which 4 interventions were assigned randomly. Thirty grams isolated soy protein (ISP) and 10 g cotyledon fiber or 50 g ISP and 16.6 g cotyledon fiber or equivalent doses of casein and cellulose were consumed daily as a beverage for 16 wk. When the 2 groups who consumed ISP were compared with the 2 groups who consumed casein, the differences in the net changes from baseline to week 16 in the concentrations of LDL cholesterol and plasma total homocysteine were -0.26 mmol/L (95% CI: -0.43, -0.09 mmol/L; P = 0.01) and -0.8 micromol/L (-1.4, -0.2 micromol/L; P = 0.005), respectively. The effect of the ISP dose was not significant. There were no significant differences between the 2 ISP and the 2 casein groups in changes in lipoprotein(a), HDL-cholesterol, or triacylglycerol concentrations. Adding 30-50 g soy protein/d to a lipid-lowering diet significantly reduced LDL-cholesterol concentrations without increasing lipoprotein(a) concentrations. Plasma total homocysteine concentrations also decreased, suggesting a novel, possibly antiatherosclerotic effect.

Safety, Tolerability, and Pharmacokinetic Properties of Intravenous Delafloxacin After Single and Multiple Doses in Healthy Volunteers.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report was to determine the pharmacokinetic properties, safety, and tolerability of single and multiple doses of intravenous delafloxacin. In addition, the absolute bioavailability (BA) of the 450-mg tablet formulation of delafloxacin was determined. Three clinical trials are summarized. The first study was a randomized, double-blind, placebo-controlled, single- (300, 450, 600, 750, 900, and 1200 mg) ascending-dose study of IV delafloxacin in 62 (52 active, 10 placebo) healthy volunteers. The second study was a randomized, double-blind, placebo-controlled study of IV delafloxacin (300 mg) given as a single dose on day 1, followed by twice-daily dosing on days 2 through 14; 12 (8 active, 4 placebo) healthy volunteers were enrolled. The third study was an open-label, randomized, 2-period, 2-sequence crossover study in which 56 healthy volunteers were randomly assigned to 1 of 2 sequences of a single oral dose of delafloxacin (450-mg tablet) or IV delafloxacin (300 mg). Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were calculated. Delafloxacin Cmax values increased proportionally with increasing single IV dose for the dose range of 300 to 1200 mg, whereas the AUC values increased more than proportionally to dose for the same dose range. The mean terminal half-life of delafloxacin was approximately 12 hours (ranging from 8 to 17 hours). The volume of distribution (Vd) at steady state was approximately 35 L, which is similar to the volume of total body water. There was minimal accumulation of delafloxacin after twice-daily IV administration of 300 mg with an accumulation ratio of 1.09. The delafloxacin total exposure after a single 1-hour IV infusion of 300 mg and a single oral dose of a 450-mg tablet were equivalent with geometric least square mean ratio (90% CI) of 0.8768 (0.8356-0.9200) for AUC0-∞ and 0.8445 (0.8090-0.8815) for AUC0-t, respectively. The Cmax values of delafloxacin were not equivalent for the 2 formulations with a ratio (90% CI) of 0.5516 (0.5150-0.5908), respectively. The mean absolute bioavailability of delafloxacin was 58.8%. Delafloxacin was well tolerated in healthy volunteers after single and multiple IV doses. The total systemic exposure to IV (300 mg) and oral (450 mg) delafloxacin is comparable, supporting that a switch between the 2 formulations is appropriate. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

PubMed

Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

2014-04-01

Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

SU-E-T-585: Optically-Stimulated Luminescent Dosimeters for Monitoring Pacemaker Dose in Radiation Therapy

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

Apicello, L; Riegel, A; Jamshidi, A

2015-06-15

Purpose: A sufficient amount of ionizing radiation can cause failure to components of pacemakers. Studies have shown that permanent damage can occur after a dose of 10 Gy and minor damage to functionality occurs at doses as low as 2 Gy. Optically stimulated thermoluminescent dosimeters (OSLDs) can be used as in vivo dosimeters to predict dose to be deposited throughout the treatment. The purpose of this work is to determine the effectiveness of using OSLDs for in vivo dosimetry of pacemaker dose. Methods: As part of a clinical in vivo dosimetry experience, OSLDs were placed at the site of themore » pacemaker by the therapist for one fraction of the radiation treatment. OSLD measurements were extrapolated to the total dose to be received by the pacemaker during treatment. A total of 79 measurements were collected from November 2011 to December 2013 on six linacs. Sixty-six (66) patients treated in various anatomical sites had the dose of their pacemakers monitored. Results: Of the 79 measurements recorded, 76 measurements (96 %) were below 2 Gy. The mean and standard deviation were 50.12 ± 76.41 cGy. Of the 3 measurements that exceeded 2 Gy, 2 measurements matched the dose predicted in the treatment plan and 1 was repeated after an unexpectedly high Result. The repeated measurement yielded a total dose less than 2 Gy. Conclusion: This analysis suggests OSLDs may be used for in vivo monitoring of pacemaker dose. Further research should be performed to assess the effect of increased backscatter from the pacemaker device.« less

Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

DOE PAGES

Stark, Karolina; Scott, David E.; Tsyusko, Olga; ...

2015-04-30

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad ( Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments didmore » not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less

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

PubMed

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

2017-12-14

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

Helical irradiation of the total skin with dose painting to replace total skin electron beam therapy for therapy-refractory cutaneous CD4+ T-cell lymphoma.

PubMed

Hsieh, Chen-Hsi; Shueng, Pei-Wei; Lin, Shih-Chiang; Tien, Hui-Ju; Shiau, An-Cheng; Chou, Yueh-Hung; Wu, Meng-Hao; Wang, Jen-Yu; Chen, Chi-Kuan; Chen, Yu-Jen

2013-01-01

A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS) and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB) technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

The total ozone and UV solar radiation over Stara Zagora, Bulgaria

NASA Astrophysics Data System (ADS)

Mendeva, B. D.; Gogosheva, Ts. N.; Petkov, B. H.; Krastev, D. G.

The results from direct ground-based solar UV irradiance measurements and the total ozone content (TOC) over Stara Zagora (42° 25'N, 25° 37'E), Bulgaria are presented. During the period 1999-2003 the TOC data show seasonal variations, typical for the middle latitudes - maximum in the spring and minimum in the autumn. The comparison between TOC ground-based data and Global Ozone Monitoring Experiment (GOME) satellite-borne ones shows a seasonal dependence of the differences between them. A strong negative relationship between the total ozone and the 305 nm wavelength irradiance was found. The dependence between the two variables is significant ( r = -0.62 ± 0.18) at 98% confidence level. The direct sun UV doses for some specific biological effects (erythema and eyes) are obtained. The estimation of the radiation amplification factor RAF shows that the ozone reduction by 1% increases the erythemal dose by 2.3%. The eye-damaging doses are more influenced by the TOC changes and in this case RAF = -2.7%. The amount of these biological doses depended on the solar altitude over the horizon. This dependence was not so strong when the total ozone content in the atmosphere was lower.

Effect of black cumin seeds on growth performance, nutrient utilization, immunity, gut health and nitrogen excretion in broiler chickens.

PubMed

Kumar, Pawan; Patra, Amlan Kumar; Mandal, Guru Prasad; Samanta, Indranil; Pradhan, Saktipada

2017-08-01

Use of antibiotic growth promoters (AB) as feed additives in broiler chickens poses risks due to cross-resistance amongst pathogens and residues in tissues. The aim of this study was to evaluate the effect of dietary supplementation of black cumin seeds (BCS) as a natural growth promoter in chickens on nutrient utilization, intestinal microbiota and morphology, immunity, antioxidant status, protein deposition in muscles and nitrogen excretion. Broiler chickens were fed BCS at 0, 5, 10 and 20 g kg -1 diet. Body weight gain tended to increase (P = 0.10) and daily feed intake increased quadratically with increasing concentrations of BCS in the diets. Supplementation of BCS resulted in a tendency to decrease feed conversion efficiency on days 28-42. Metabolizability of nutrients increased linearly with increasing doses of BCS. Protein deposition in thigh and breast muscles was increased and nitrogen excretion was reduced by BCS and AB compared with the control (CON). Intestinal morphology in the duodenum, jejunum and ileum was not generally affected by BCS. Counts of total bacteria, Escherichia coli, Lactobacillus spp. and Clostridium spp. were not affected by BCS and AB compared with CON, but Salmonella spp. decreased linearly (P = 0.05) with increasing doses of BCS. Antibody titers against Newcastle disease virus on day 35 increased quadratically (P < 0.001) with increasing doses of BCS. Concentrations of glucose and triglyceride in blood were not affected by BCS. Concentrations of cholesterol decreased linearly while the concentration of total protein increased linearly with increasing doses of BCS. The use of dietary BCS may improve growth performance, immunity and nutrient utilization in broiler chickens. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

LDEF: Dosimetric measurement results (AO 138-7 experiment)

NASA Technical Reports Server (NTRS)

Bourrieau, J.

1992-01-01

One of the objectives of the AO 138-7 experiment on board the LDEF was a total dose measurement with Thermo Luminescent Detectors (TLD 100). Two identical cases, both including 5 TLDs inside various aluminum shields, are exposed to the space environment in order to obtain the absorbed dose profile induced. Radiation fluence received during the total mission length was computed, taking into account the trapped particles (solar maximum and solar minimum periods) and the cosmic rays; due to the magnetospheric shielding, the solar proton fluences are negligible on the LDEF orbit. The total dose induced by these radiations inside a semi-infinite plane shield of Al are computed with radiation transport codes. TLD reading are performed after flight; due to the mission duration increase, a post-flight calibration was necessary in order to cover the range of the flight induced dose. The results obtained, similar (+ or - 30 pct.) in both cases, are compared with the dose profile computation. In practice, these LDEF results, with less than a factor 1.4 between measurements and forecasts, reinforce the validity of the computation methods and models used for the long term evaluation of space radiation intensity on low inclination Earth orbits.

Implementation and application of an interactive user-friendly validation software for RADIANCE

NASA Astrophysics Data System (ADS)

Sundaram, Anand; Boonn, William W.; Kim, Woojin; Cook, Tessa S.

2012-02-01

RADIANCE extracts CT dose parameters from dose sheets using optical character recognition and stores the data in a relational database. To facilitate validation of RADIANCE's performance, a simple user interface was initially implemented and about 300 records were evaluated. Here, we extend this interface to achieve a wider variety of functions and perform a larger-scale validation. The validator uses some data from the RADIANCE database to prepopulate quality-testing fields, such as correspondence between calculated and reported total dose-length product. The interface also displays relevant parameters from the DICOM headers. A total of 5,098 dose sheets were used to test the performance accuracy of RADIANCE in dose data extraction. Several search criteria were implemented. All records were searchable by accession number, study date, or dose parameters beyond chosen thresholds. Validated records were searchable according to additional criteria from validation inputs. An error rate of 0.303% was demonstrated in the validation. Dose monitoring is increasingly important and RADIANCE provides an open-source solution with a high level of accuracy. The RADIANCE validator has been updated to enable users to test the integrity of their installation and verify that their dose monitoring is accurate and effective.

Dose-dependent effects of vitamin 1,25(OH)2D3 on oxidative stress and apoptosis.

PubMed

Cakici, Cagri; Yigitbasi, Turkan; Ayla, Sule; Karimkhani, Hadi; Bayramoglu, Feyza; Yigit, Pakize; Kilic, Ertugrul; Emekli, Nesrin

2018-02-08

Background The purpose of this study is to examine the dose-dependent effects of vitamin 1,25(OH)2D3 on apoptosis and oxidative stress. Methods In this study, 50 male Balb/c mice were used as control and experiment groups. The mice were divided into 5 groups each consisting of 10 mice. Calcitriol was intraperitoneally administered as low dose, medium dose, medium-high dose and high dose vitamin D groups (at 0.5, 1, 5 and 10 μg/kg, respectively), for three times a week during 14 days. At the end of the study, annexin V was measured by enzyme-linked immunosorbent assay method, and total antioxidant capacity and total oxidant status values were measured by colorimetric method in serum. Hematoxylin eosin staining was performed in liver tissues and periodic acid schiff staining was performed in kidney tissues. Results While comparing the results of medium-high dose (5 μg/kg) and high dose (10 μg/kg) vitamin D administration to that of the control group, it was observed that serum antioxidant status and annexin V levels decreased and glomerular mesenchial matrix ratio increased in kidney (p<0.05). In addition to these findings, in the group receiving high dose vitamin D (10 μg/kg), it was observed that the damage to the liver increased together with the the oxidative stress index values (p<0.05). Conclusions As a result, this study was the first in the literature to report that use of high-dose vitamin D (10 μg/kg) results in oxidant effect, rather than being an antioxidant, and causes severe histopathological toxicity in the liver and kidney.

Increasing the Vegetable Intake Dose Is Associated with a Rise in Plasma Carotenoids without Modifying Oxidative Stress or Inflammation in Overweight or Obese Postmenopausal Women123

PubMed Central

Crane, Tracy E.; Kubota, Chieri; West, Julie L.; Kroggel, Mark A.; Wertheim, Betsy C.; Thomson, Cynthia A.

2011-01-01

The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women. PMID:21865569

Metabolic changes in humans following total body irradiation. Report for February 1960-October 1961

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

Not Available

These studies are designed to obtain new information about the metabolic effects of total body and partial body irradiation so as to have a better understanding of the acute and subacute effects of irradiation in the human. The initial studies are pointed toward the elucidation of biological indicators of radiation effects in humans. The major parameters being investigated at present are urinary amino aciduria and alterations in immunological patterns. Certain other parameters such as creatine and creatinine excretion and hematological effects are also being followed. The long-term program envisions carrying out the various observations at dose levels of 100 radmore » and gradually increasing the dose to 150, 200, 250 and 300 rad. Eventually doses up to 600 rad are anticipated. Also comparison of effects of radiomimetic drugs with total body radiation will be studied.« less

Improved solubilization of activated sludge by ozonation in pressure cycles.

PubMed

Cheng, Chia-Jung; Hong, P K Andy; Lin, Cheng-Fang

2012-05-01

The generation of a large volume of activated sludge (AS) from wastewater treatment has increasingly become a great burden on the environment. Anaerobic digestion is routinely practiced for excess waste sludge; however, the process retention time is long because of kinetic limitation in the hydrolysis step. We tested the feasibility of applying ozone in pressure cycles to enhance the disintegration and solubilization of AS with the goal to prepare them for digestion using reduced ozone dose and contact time. The AS was subjected to repetitive pressure cycles in a closed vessel in which an ozone gas mixture was compressed into the slurry to reach 1040 kPa in the headspace to be followed by rapid venting. For a returned AS with total COD (tCOD) of 8200 mg L(-1), a dose of 0.01 gO(3)g(-1) total suspended solids (TSS) delivered via 20 pressure cycles within 16 min resulted in a 37-fold increase of the sCOD/tCOD ratio (due to increased soluble COD, i.e. sCOD) and a 25% reduction of TSS, in comparison to a dose of 0.08 gO(3)g(-1) TSS via bubbling contact over 15 min that resulted in a 15-fold increase of the sCOD/tCOD ratio and a 12% reduction of TSS. Sludge solubilization was evidenced by increased dissolved contents of total phosphorous (from 10 to 64 mg L(-1)), total nitrogen (from 14 to 120 mg L(-1)), and protein (from <15 to 39 mg L(-1)) in the sludge suspension after treatment, indicating significant solubilization of AS. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Dose Response Relationship for Radiation Carcinogenesis

NASA Astrophysics Data System (ADS)

Hall, Eric

2008-03-01

Recent surveys show that the collective population radiation dose from medical procedures in the U.S. has increased by 750% in the past two decades. It would be impossible to imagine the practice of medicine today without diagnostic and therapeutic radiology, but nevertheless the widespread and rapidly increasing use of a modality which is a known human carcinogen is a cause for concern. To assess the magnitude of the problem it is necessary to establish the shape of the dose response relationship for radiation carcinogenesis. Information on radiation carcinogenesis comes from the A-bomb survivors, from occupationally exposed individuals and from radiotherapy patients. The A-bomb survivor data indicates a linear relationship between dose and the risk of solid cancers up to a dose of about 2.5 Sv. The lowest dose at which there is a significant excess cancer risk is debatable, but it would appear to be between 40 and 100 mSv. Data from the occupation exposure of nuclear workers shows an excess cancer risk at an average dose of 19.4 mSv. At the other end of the dose scale, data on second cancers in radiotherapy patients indicates that cancer risk does not continue to rise as a linear function of dose, but tends towards a plateau of 40 to 60 Gy, delivered in a fractionated regime. These data can be used to estimate the impact of diagnostic radiology at the low dose end of the dose response relationship, and the impact of new radiotherapy modalities at the high end of the dose response relationship. In the case of diagnostic radiology about 90% of the collective population dose comes from procedures (principally CT scans) which involve doses at which there is credible evidence of an excess cancer incidence. While the risk to the individual is small and justified in a symptomatic patient, the same is not true of some screening procedures is asymptomatic individuals, and in any case the huge number of procedures must add up to a potential public health problem. In the case of radiation oncology, modern innovations such as Intensity Modulated Radiation Oncology or Proton Therapy both result in a substantial total-body dose to the patient, which must result in an increased incidence of second cancers. The technology exists to reduce these total body doses and the problem needs to be addressed.

[Protective effect of emodin pretreatment in young rats with intrahepatic cholestasis].

PubMed

Xiong, Xiao-Li; Yan, Su-Qi; Qin, Huan; Zhou, Li-Shan; Zhang, Ling-Ling; Jiang, Zhi-Xia; Ding, Yan

2016-02-01

To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups. Emodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect.

Acute Biological Effects of Simulating the Whole-Body Radiation Dose Distribution from a Solar Particle Event Using a Porcine Model

PubMed Central

Wilson, Jolaine M.; Sanzari, Jenine K.; Diffenderfer, Eric S.; Yee, Stephanie S.; Seykora, John T.; Maks, Casey; Ware, Jeffrey H.; Litt, Harold I.; Reetz, Jennifer A.; McDonough, James; Weissman, Drew; Kennedy, Ann R.; Cengel, Keith A.

2011-01-01

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses. PMID:21859326

Vaginal dose de-escalation in image guided adaptive brachytherapy for locally advanced cervical cancer.

PubMed

Mohamed, Sandy; Lindegaard, Jacob Christian; de Leeuw, Astrid A C; Jürgenliemk-Schulz, Ina; Kirchheiner, Kathrin; Kirisits, Christian; Pötter, Richard; Tanderup, Kari

2016-09-01

Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de-escalation (VDD). Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV⩾85Gy EQD2) while reducing the dose to the surface of the vagina to <140% of the physical fractional brachytherapy dose corresponding to a total EQD2 of 85Gy. The mean vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points (p<0.001) without compromising the target dose. The dose to the ICRU recto-vaginal point was reduced by a mean of 4±4Gy EQD2 (p<0.001), while doses to bladder and rectum (D 2cm 3 ) were reduced by 2±2Gy and 3±2Gy, respectively (p<0.001). VDD significantly reduces dose to the upper vagina which is expected to result in reduction of vaginal stenosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effective doses to patients undergoing thoracic computed tomography examinations.

PubMed

Huda, W; Scalzetti, E M; Roskopf, M

2000-05-01

The purpose of this study was to investigate how x-ray technique factors and effective doses vary with patient size in chest CT examinations. Technique factors (kVp, mAs, section thickness, and number of sections) were recorded for 44 patients who underwent a routine chest CT examination. Patient weights were recorded together with dimensions and mean Hounsfield unit values obtained from representative axial CT images. The total mass of directly irradiated patient was modeled as a cylinder of water to permit the computation of the mean patient dose and total energy imparted for each chest CT examination. Computed values of energy imparted during the chest CT examination were converted into effective doses taking into account the patient weight. Patient weights ranged from 4.5 to 127 kg, and half the patients in this study were children under 18 years of age. All scans were performed at 120 kVp with a 1 s scan time. The selected tube current showed no correlation with patient weight (r2=0.06), indicating that chest CT examination protocols do not take into account for the size of the patient. Energy imparted increased with increasing patient weight, with values of energy imparted for 10 and 70 kg patients being 85 and 310 mJ, respectively. The effective dose showed an inverse correlation with increasing patient weight, however, with values of effective dose for 10 and 70 kg patients being 9.6 and 5.4 mSv, respectively. Current CT technique factors (kVp/mAs) used to perform chest CT examinations result in relatively high patient doses, which could be reduced by adjusting technique factors based on patient size.

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

PubMed

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

2015-11-01

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

Developmental and genetic toxicity of stannous chloride in mouse dams and fetuses.

PubMed

El-Makawy, Aida I; Girgis, Shenouda M; Khalil, Wagdy K B

2008-12-08

Humans are exposed to stannous chloride (SnCl2) present in packaged food, soft drinks, biocides, dentifrices, etc. Health effects in children exposed to tin and tin compounds have not been investigated yet. Therefore, we evaluated the possible teratogenic and genotoxic effects of SnCl2 in pregnant female mice and their fetuses. Teratogenic effects including morphological malformation of the fetus and its skeleton were observed. Exposures to environmental stressors including toxic chemicals that have the potential of modulating the immune system can often be linked to ecologically relevant endpoints, such as reduced resistance to disease. Therefore, the semi-quantitative reverse-transcription PCR (RT-PCR) assay was used to evaluate the expression of immune-response genes in the liver of SnCl2-treated dams and their fetuses. Bone-marrow cells of dams and fetuses were investigated for the presence of aberrant chromosomes. Three oral doses of SnCl2 (2, 10 and 20 mg/kg bw) were tested. The results of the teratological study show that SnCl2 induced a significant decrease in the number of living fetuses and a significant increase in the number of post-implantation losses. The high dose of SnCl2 induced complete post-implantation loss. Furthermore, SnCl2 caused reduction in the ossification of the fetal skeleton. The RT-PCR assay showed that the immune-response genes GARP and SIMP were not expressed in the liver of dams and fetuses in the controls or in the group treated with SnCl2 at 2 mg/kg bw. However, the expression of these genes was up-regulated in the groups treated with the other doses of SnCl2. Regarding the chromosome analysis, SnCl2 induced a dose-dependent increase in the frequency of individual and total chromosomal aberrations (P

Green Tea Increases the Concentration of Total Mercury in the Blood of Rats following an Oral Fish Tissue Bolus

PubMed Central

Freiser, Helene; Manganais, Christopher; Santerre, Charles R.

2015-01-01

Fish has many health benefits but is also the most common source of methylmercury. The bioavailability of methylmercury in fish may be affected by other meal components. In this study, the effect of green tea on the bioavailability of methylmercury from an oral bolus of fish muscle tissue was studied in rats and compared to a water treated control group and a group treated with meso-2,3-dimercaptosuccinic acid (DMSA), a compound used medically to chelate mercury. Rats were given a single oral dose of fish tissue via gavage and one of the treatments. Rats were given access to food for 3 h at 12 h intervals. They were dosed with each of the treatments with each meal. Blood samples were collected for 95 hours. Green tea significantly increased the concentration of total mercury in blood relative to the control, whereas DMSA significantly decreased it. In addition, feeding caused a slight increase in blood mercury for several meals following the initial dose. PMID:26301246

Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.

PubMed

DeBo, Ryne J; Register, Thomas C; Caudell, David L; Sempowski, Gregory D; Dugan, Gregory; Gray, Shauna; Owzar, Kouros; Jiang, Chen; Bourland, J Daniel; Chao, Nelson J; Cline, J Mark

2015-06-01

The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomolgus macaques. Animals received a single total-body irradiation (TBI) exposure at doses of 0, 2 or 5 Gy with scheduled necropsies at 5 days, 8 weeks and 24 weeks post-exposure. Blood and lymphoid tissues were evaluated for morphologic, cellular, and molecular responses. Irradiated animals developed symptoms of acute hematopoietic syndrome, and reductions in thymus weight, thymopoiesis, and bone marrow cellularity. Acute, transient increases in plasma monocyte chemoattractant protein 1 (MCP-1) were observed in 5 Gy animals along with dose-dependent alterations in messenger ribonucleic acid (mRNA) signatures in thymus, spleen, and lymph node. Expression of T cell markers was lower in thymus and spleen, while expression of macrophage marker CD68 (cluster of differentiation 68) was relatively elevated in lymphoid tissues from irradiated animals. Ovariectomized female macaques exposed to moderate doses of radiation experienced increased morbidity, including acute, dose-dependent alterations in systemic and tissue-specific biomarkers, and increased macrophage/T cell ratios. The effects on mortality exceeded expectations based on previous studies in males, warranting further investigation.

Dose-dependent cytotoxicity evaluation of graphite nanoparticles for diamond-like carbon film application on artificial joints.

PubMed

Liao, T T; Deng, Q Y; Wu, B J; Li, S S; Li, X; Wu, J; Leng, Y X; Guo, Y B; Huang, N

2017-01-24

While a diamond-like carbon (DLC)-coated joint prosthesis represents the implant of choice for total hip replacement in patients, it also leads to concern due to the cytotoxicity of wear debris in the form of graphite nanoparticles (GNs), ultimately limiting its clinical use. In this study, the cytotoxicity of various GN doses was evaluated. Mouse macrophages and osteoblasts were incubated with GNs (<30 nm diameter), followed by evaluation of cytotoxicity by means of assessing inflammatory cytokines, results of alkaline phosphatase assays, and related signaling protein expression. Cytotoxicity evaluation showed that cell viability decreased in a dose-dependent manner (10-100 μg ml -1 ), and steeply declined at GNs concentrations greater than 30 μg ml -1 . Noticeable cytotoxicity was observed as the GN dose exceeded this threshold due to upregulated receptor of activator of nuclear factor kB-ligand expression and downregulated osteoprotegerin expression. Meanwhile, activated macrophage morphology was observed as a result of the intense inflammatory response caused by the high doses of GNs (>30 μg ml -1 ), as observed by the increased release of TNF-α and IL-6. The results suggest that GNs had a significant dose-dependent cytotoxicity in vitro, with a lethal dose of 30 μg ml -1 leading to dramatic increases in cytotoxicity. Our GN cytotoxicity evaluation indicates a safe level for wear debris-related arthropathy and could propel the clinical application of DLC-coated total hip prostheses.

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

Comparison of effect of 5 MeV proton and Co-60 gamma irradiation on silicon NPN rf power transistors and N-channel depletion MOSFETs

NASA Astrophysics Data System (ADS)

Gnana Prakash, A. P.; Pradeep, T. M.; Hegde, Vinayakprasanna N.; Pushpa, N.; Bajpai, P. K.; Patel, S. P.; Trivedi, Tarkeshwar; Bhushan, K. G.

2017-12-01

NPN transistors and N-channel depletion metal oxide semiconductor field effect transistors (MOSFETs) were irradiated with 5 MeV protons and 60Co gamma radiation in the dose ranging from 1 Mrad(Si) to 100 Mrad(Si). The different electrical characteristics of the NPN transistor such as Gummel characteristics, excess base current (ΔIB), dc current gain (hFE), transconductance (gm), displacement damage factor (K) and output characteristics were studied as a function of total dose. The different electrical characteristics of N-channel MOSFETs such as threshold voltage (Vth), density of interface trapped charges (ΔNit), density of oxide trapped charges (ΔNot), transconductance (gm), mobility (µ) and drain saturation current (IDSat) were studied systematically before and after irradiation in the same dose ranges. A considerable increase in the base current (IB) and decrease in the hFE, gm and collector saturation current (ICSat) were observed after irradiation in the case of the NPN transistor. In the N-channel MOSFETs, the ΔNit and ΔNot were found to increase and Vth, gm, µ and IDSat were found to decrease with increase in the radiation dose. The 5 MeV proton irradiation results of both the NPN transistor and N-channel MOSFETs were compared with 60Co gamma-irradiated devices in the same dose ranges. It was observed that the degradation in 5 MeV proton-irradiated devices is more when compared with the 60Co gamma-irradiated devices at higher total doses.

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

NASA Astrophysics Data System (ADS)

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

2015-06-01

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

Fate of return activated sludge after ozonation: an optimization study for sludge disintegration.

PubMed

Demir, Ozlem; Filibeli, Ayse

2012-09-01

The effects of ozonation on sludge disintegration should be investigated before the application of ozone during biological treatment, in order to minimize excess sludge production. In this study, changes in sludge and supernatant after ozonation of return activated sludge were investigated for seven different ozone doses. The optimum ozone dose to avoid inhibition of ozonation and high ozone cost was determined in terms of disintegration degree as 0.05 g O3/gTS. Suspended solid and volatile suspended solid concentrations of sludge decreased by 77.8% and 71.6%, respectively, at the optimum ozone dose. Ozonation significantly decomposed sludge flocs. The release of cell contents was proved by the increase of supernatant total nitrogen (TN) and phosphorus (TP). While TN increased from 7 mg/L to 151 mg/L, TP increased from 8.8 to 33 mg/L at the optimum ozone dose. The dewaterability and filterability characteristics of the ozonated sludge were also examined. Capillary suction time increased with increasing ozone dosage, but specific resistance to filtration increased to a specific value and then decreased dramatically. The particle size distribution changed significantly as a result of floc disruption at an optimum dose of 0.05 gO3/gTS.

Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign-Haiti, 2013.

PubMed

Routh, Janell A; Sreenivasan, Nandini; Adhikari, Bishwa B; Andrecy, Lesly L; Bernateau, Margarette; Abimbola, Taiwo; Njau, Joseph; Jackson, Ernsley; Juin, Stanley; Francois, Jeannot; Tohme, Rania A; Meltzer, Martin I; Katz, Mark A; Mintz, Eric D

2017-10-01

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

Study of the dose rate effect of 180 nm nMOSFETs

NASA Astrophysics Data System (ADS)

He, Bao-Ping; Yao, Zhi-Bin; Sheng, Jiang-Kun; Wang, Zu-Jun; Huang, Shao-Yan; Liu, Min-Bo; Xiao, Zhi-Gang

2015-01-01

Radiation induced offstate leakage in the shallow trench isolation regions of SIMC 0.18 μm nMOSFETs is studied as a function of dose rate. A “true” dose rate effect (TDRE) is observed. Increased damage is observed at low dose rate (LDR) than at high dose rate (HDR) when annealing is taken into account. A new method of simulating radiation induced degradation in shallow trench isolation (STI) is presented. A comparison of radiation induced offstate leakage current in test nMOSFETs between total dose irradiation experiments and simulation results exhibits excellent agreement. The investigation results imply that the enhancement of the leakage current may be worse for the dose rate encountered in the environment of space.

Treatment and therapeutic monitoring of canine hypothyroidism.

PubMed

Dixon, R M; Reid, S W J; Mooney, C T

2002-08-01

Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.

Leukocyte and platelet changes following low-dose lipopolysaccharide administration in five dogs.

PubMed

Flatland, B; Fry, M M; LeBlanc, C J; Rohrbach, B W

2011-02-01

Effects of low-dose LPS (0.1 μg/kg i.v.) on leukocyte and platelet parameters measured using an Advia 120 hematology analyzer were investigated. Five dogs received a saline sham treatment prior to LPS, and blood was collected before and 3, 6, and 24 h post-treatment. LPS-treated dogs had mild neutrophil toxic change and increased neutrophil bands at 3 and 6 h. Compared to saline-treated controls, total leukocyte, neutrophil, and monocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Compared to baseline, total leukocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Mean platelet volume was significantly increased and mean platelet component concentration was decreased at 3 h compared to baseline. Platelet count was significantly decreased at 3 and 6 h; plateletcrit did not change significantly. High dosage is not required in order to detect LPS-mediated hematologic effects in dogs. Low-dose LPS administration causes significant changes in leukocyte and platelet indices in dogs without causing severe clinical signs or death. Copyright © 2010 Elsevier Ltd. All rights reserved.

The contribution of interventional cardiology procedures to the population radiation dose in a ‘health-care level I’ representative region

PubMed Central

Peruzzo Cornetto, Andrea; Aimonetto, Stefania; Pisano, Francesco; Giudice, Marcello; Sicuro, Marco; Meloni, Teodoro; Tofani, Santi

2016-01-01

This study evaluates per-procedure, collective and per capita effective dose to the population by interventional cardiology (IC) procedures performed during 2002–11 at the main hospital of Aosta Valley Region that can be considered as representative of the health-care level I countries, as defined by the UNSCEAR, based on its socio-demographic characteristics. IC procedures investigated were often multiple procedures in patients older than 60 y. The median extreme dose-area product values of 300 and 22 908 cGycm2 were found for standard pacemaker implantation and coronary angioplasty, respectively, while the relative mean per-procedure effective dose ranged from 0.7 to 47 mSv. A 3-fold increase in frequency has been observed together with a correlated increase in the delivered per capita dose (0.05–0.27 mSv y−1) and the collective dose (5.8–35 man Sv y−1). Doses increased particularly from 2008 onwards mainly because of the introduction of coronary angioplasty procedures in the authors’ institution. IC practice contributed remarkably in terms of effective dose to the population, delivering ∼10 % of the total dose by medical ionising radiation examination categories. PMID:26012484

Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?

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

Harriss-Phillips, Wendy M., E-mail: wharrphil@gmail.com; School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia; Bezak, Eva

Purpose: To simulate stereotactic ablative radiation therapy on hypoxic and well-oxygenated in silico tumors, incorporating probabilistic parameter distributions and linear-quadratic versus linear-quadratic-cubic methodology and the evaluation of optimal fractionation schemes using biological effective dose (BED{sub α/β=10} {sub or} {sub 3}) comparisons. Methods and Materials: A temporal tumor growth and radiation therapy algorithm simulated high-dose external beam radiation therapy using stochastic methods. Realistic biological proliferative cellular hierarchy and pO{sub 2} histograms were incorporated into the 10{sup 8}-cell tumor model, with randomized radiation therapy applied during continual cell proliferation and volume-based gradual tumor reoxygenation. Dose fractions ranged from 6-35 Gy, with predictive outcomes presentedmore » in terms of the total doses (converted to BED) required to eliminate all cells that could potentially regenerate the tumor. Results: Well-oxygenated tumor control BED{sub 10} outcomes were not significantly different for high-dose versus conventional radiation therapy (BED{sub 10}: 79-84 Gy; Equivalent Dose in 2 Gy fractions with α/β of 10: 66-70 Gy); however, total treatment times decreased from 7 down to 1-3 weeks. For hypoxic tumors, an additional 28 Gy (51 Gy BED{sub 10}) was required, with BED{sub 10} increasing with dose per fraction due to wasted dose in the final fraction. Fractions of 9 Gy compromised well for total treatment time and BED, with BED{sub 10}:BED{sub 3} of 84:176 Gy for oxic and 132:278 Gy for non-reoxygenating hypoxic tumors. Initial doses of 12 Gy followed by 6 Gy further increased the therapeutic ratio. When delivering ≥9 Gy per fraction, applying reoxygenation and/or linear-quadratic-cubic cell survival both affected tumor control doses by a significant 1-2 fractions. Conclusions: The complex temporal dynamics of tumor oxygenation combined with probabilistic cell kinetics in the modeling of radiation therapy requires sophisticated stochastic modeling to predict tumor cell kill. For stereotactic ablative radiation therapy, high doses in the first week followed by doses that are more moderate may be beneficial because a high percentage of hypoxic cells could be eradicated early while keeping the required BED{sub 10} relatively low and BED{sub 3} toxicity to tolerable levels.« less

Caffeinated and decaffeinated coffee consumption and melanoma risk: a dose-response meta-analysis of prospective cohort studies.

PubMed

Micek, Agnieszka; Godos, Justyna; Lafranconi, Alessandra; Marranzano, Marina; Pajak, Andrzej

2018-06-01

To determine the association between total, caffeinated and decaffeinated coffee consumption and melanoma risk a dose-response meta-analysis on prospective cohort studies were performed. Eligible studies were identified searching PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by random-effects meta-analysis and the shape of the exposure-outcome curve was modelled linearly and using restricted cubic splines. A total of seven studies eligible for meta-analysis were identified that comprised 1,418,779 participants and 9211 melanoma cases. A linear dose-response meta-analysis showed a significant association between total coffee consumption and melanoma risk. An increase in coffee consumption of one cup per day was associated with a 3% reduction in melanoma risk (RR 0.97; 95% CI 0.95-0.99). Our findings suggest that coffee intake may be inversely associated with incidence of melanoma. Nevertheless, further studies exploring also the role of confounding factors are needed to explain the heterogeneity among studies.

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

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

Yu, V; Nguyen, D; Pajonk, F

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

Renal dysfunction after total body irradiation: Dose-effect relationship

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

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

2006-07-15

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

Shorter Exposures to Harder X-Rays Trigger Early Apoptotic Events in Xenopus laevis Embryos

PubMed Central

Dong, JiaJia; Mury, Sean P.; Drahos, Karen E.; Moscovitch, Marko

2010-01-01

Background A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. Methodology/Principal Findings We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. Conclusions/Significance Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes. PMID:20126466

Low but inducible contribution of renal elimination to clearance of propylene glycol in preterm and term neonates.

PubMed

De Cock, Roosmarijn F W; Allegaert, Karel; Vanhaesebrouck, Sophie; de Hoon, Jan; Verbesselt, Rene; Danhof, Meindert; Knibbe, Catherijne A J

2014-06-01

Despite limited information being available on the pharmacokinetics of excipients, propylene glycol (PG) is often used as an excipient in both adults and children. The aim of this study is to characterize the renal and hepatic elimination of PG in preterm and term neonates. The pharmacokinetic analysis of PG was performed in NONMEM 6.2. on the basis of PG concentrations in plasma and/or urine samples for a total of 69 (pre)term neonates (birth weight 630-3980 g, gestational age 24-41 weeks, postnatal age 1-29 days) who received PG coadministered with intravenous paracetamol (5-10 mg/kg per 6 hours), phenobarbital (5 mg·kg(-1)·d(-1)), or both. To capture the time-dependent trend in the renal excretion of PG, different models based on time after the first dose, urine volume, and creatinine amount in urine were tested. A one-compartment model parameterized in terms of renal clearance, hepatic clearance, and volume of distribution was found to adequately describe the observations in both plasma and urine. After the first dose was administered, the renal elimination of PG was 15% of total clearance, which increased over time to 25% at 24 hours after the first dose of PG. This increase was best described using a hyperbolic function based on time after the first dose. Renal elimination of PG in (pre)term neonates is low, particularly compared with the reported percentage of 45% in adults, but it may increase with time after the first dose of PG. To study whether this increase is caused by an autoinduced increase in the renal secretion or a reduction of tubular reabsorption of PG, further research is needed.

Alfalfa seed germination and yield ratio and alfalfa sprout microbial keeping quality following irradiation of seeds and sprouts.

PubMed

Rajkowski, K T; Thayer, D W

2001-12-01

Foods can be treated with gamma radiation, a nonthermal food process, to inactivate foodborne pathogens and fungi, to kill insects on or in fruits and vegetables, and to increase shelf life. Gamma irradiation is especially well suited for these treatments because of its ability to penetrate commercial pallets of foods. Irradiated fruits, vegetables, poultry, and hamburger have been received favorably by the public and are now available in supermarkets. The use of irradiation on fresh alfalfa sprouts was studied to determine its effect on keeping quality as related to aerobic microbial load. After an irradiation dose of 2 kGy, the total aerobic count decreased from 10(5-8) to 10(3-5) CFU/g, and the total coliform counts decreased from 10(5-8) to 10(3-0) CFU/g. The results showed that the sprouts maintained their structure after irradiation, and the keeping quality was extended to 21 days, which is an increase of 10 days from the usual shelf life. The effect of various doses of irradiation on alfalfa seeds as measured by percent germination and yield ratio (wt/wt) of sprouts was determined. There was little effect on the percent germination, but as the dose increased, the yield ratio of alfalfa sprouts decreased. As the length of growing time increased, so did the yield ratio of the lower dose irradiated seeds (1 to 2 kGy). The irradiation process can be used to increase the shelf life of alfalfa sprouts, and irradiating alfalfa seeds at doses up to 2 kGy does not unacceptably decrease the yield ratio for production of alfalfa sprouts.

Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing

PubMed Central

Edelman, Alison B; Cherala, Ganesh; Blue, Steven W; Erikson, David W; Jensen, Jeffrey T

2016-01-01

Objective To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. Study design Healthy, reproductive-age women with obese and normal BMIs received 1.5 mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5 hours. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. Results A total of 10 women enrolled and completed the study (normal BMI = 5, median 22.8 kg/m2, range 20.8–23.7; obese BMI = 5, 39.5 kg/m2, range 35.9–46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48 ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=0.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=0.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. Conclusion Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. Implications This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. PMID:27000996

Dose-per-fraction escalation of accelerated hypofractionated three-dimensional conformal radiotherapy in locally advanced non-small cell lung cancer.

PubMed

Kepka, Lucyna; Tyc-Szczepaniak, Dobromira; Bujko, Krzysztof

2009-07-01

To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 through 2.8 Gy (level 1 escalation) to 2.9 Gy (level 2 escalation); the total dose increased, respectively, from 56.7 Gy through 58.8 Gy to 60.9 Gy. The dose to the elective area and the overall treatment time remained unchanged. Fit patients received two to three courses of chemotherapy before radiotherapy. The 2- and 3-year overall survival rates were 32 and 19%, respectively (median survival = 17 months). Of the patients, 7% had grade III acute esophageal toxicity and 6% had grade III or greater late pulmonary toxicity. Two of the nine patients who received the level 2 escalation (60.9 Gy) died of pulmonary toxicity. The study was terminated at a dose of 58.8 Gy and this schema was adopted as the institutional policy for treatment of stage III NSCLC. Although dose escalation with accelerated hypofractionated 3D-CRT was limited, the results and toxicity profiles obtained using this technique are promising.

Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin

PubMed Central

Popovich, Irina G; Anisimov, Vladimir N; Zabezhinski, Mark A; Semenchenko, Anna V; Tyndyk, Margarita L; Yurova, Maria N; Blagosklonny, Mikhail V

2014-01-01

Target of Rapamycin (TOR) is involved in cellular and organismal aging. Rapamycin extends lifespan and delays cancer in mice. It is important to determine the minimum effective dose and frequency of its administration that still extends lifespan and prevents cancer. Previously we tested 1.5 mg/kg of rapamycin given subcutaneously 6 times per two weeks followed by a two-week break (1.5 × 6/bi-weekly schedule: total of 6 injections during a 4-week period). This intermittent treatment prolonged lifespan and delayed cancer in cancer-prone female FVB/N HER-2/neu mice. Here, the dose was decreased from 1.5 mg/kg to 0.45 mg/kg per injection. This treatment was started at the age of 2 months (group Rap-2), 4 months (Rap-4), and 5 months (Rap-5). Three control groups received the solvent from the same ages. Rapamycin significantly delayed cancer and decreased tumor burden in Rap-2 and Rap-5 groups, increased mean lifespan in Rap-4 and Rap-5 groups, and increased maximal lifespan in Rap-2 and Rap-5 groups. In Rap-4 group, mean lifespan extension was achieved without significant cancer prevention. The complex relationship between life-extension and cancer-prevention depends on both the direct effect of rapamycin on cancer cells and its anti-aging effect on the organism, which in turn prevents cancer indirectly. We conclude that total doses of rapamycin that are an order of magnitude lower than standard total doses can detectably extend life span in cancer-prone mice. PMID:24556924

Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin.

PubMed

Popovich, Irina G; Anisimov, Vladimir N; Zabezhinski, Mark A; Semenchenko, Anna V; Tyndyk, Margarita L; Yurova, Maria N; Blagosklonny, Mikhail V

2014-05-01

Target of Rapamycin (TOR) is involved in cellular and organismal aging. Rapamycin extends lifespan and delays cancer in mice. It is important to determine the minimum effective dose and frequency of its administration that still extends lifespan and prevents cancer. Previously we tested 1.5 mg/kg of rapamycin given subcutaneously 6 times per two weeks followed by a two-week break (1.5 × 6/bi-weekly schedule: total of 6 injections during a 4-week period). This intermittent treatment prolonged lifespan and delayed cancer in cancer-prone female FVB/N HER-2/neu mice. Here, the dose was decreased from 1.5 mg/kg to 0.45 mg/kg per injection. This treatment was started at the age of 2 months (group Rap-2), 4 months (Rap-4), and 5 months (Rap-5). Three control groups received the solvent from the same ages. Rapamycin significantly delayed cancer and decreased tumor burden in Rap-2 and Rap-5 groups, increased mean lifespan in Rap-4 and Rap-5 groups, and increased maximal lifespan in Rap-2 and Rap-5 groups. In Rap-4 group, mean lifespan extension was achieved without significant cancer prevention. The complex relationship between life-extension and cancer-prevention depends on both the direct effect of rapamycin on cancer cells and its anti-aging effect on the organism, which in turn prevents cancer indirectly. We conclude that total doses of rapamycin that are an order of magnitude lower than standard total doses can detectably extend life span in cancer-prone mice.

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

PubMed

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

2009-09-01

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

Radiation exposure in transcatheter patent ductus arteriosus closure: time to tune?

PubMed

Villemain, Olivier; Malekzadeh-Milani, Sophie; Sitefane, Fidelio; Mostefa-Kara, Meriem; Boudjemline, Younes

2018-05-01

The aims of this study were to describe radiation level at our institution during transcatheter patent ductus arteriosus occlusion and to evaluate the components contributing to radiation exposure. Transcatheter occlusion relying on X-ray imaging has become the treatment of choice for patients with patent ductus arteriosus. Interventionists now work hard to minimise radiation exposure in order to reduce risk of induced cancers. We retrospectively reviewed all consecutive children who underwent transcatheter closure of patent ductus arteriosus from January 2012 to January 2016. Clinical data, anatomical characteristics, and catheterisation procedure parameters were reported. Radiation doses were analysed for the following variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per body weight, Gy.cm2/kg; and total fluoroscopic time. A total of 324 patients were included (median age=1.51 [Q1-Q3: 0.62-4.23] years; weight=10.3 [6.7-17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median radiation doses were as follows: total air kerma: 26 (14.5-49.3) mGy; dose area product: 1.01 (0.56-2.24) Gy.cm2; dose area product/kg: 0.106 (0.061-0.185) Gy.cm2/kg; and fluoroscopic time: 2.8 (2-4) min. In multivariate analysis, a weight >10 kg, a ductus arteriosus width <2 mm, complications during the procedure, and a high frame rate (15 frames/second) were risk factors for an increased exposure. Lower doses of radiation can be achieved with subsequent recommendations: technical improvement, frame rate reduction, avoidance of biplane cineangiograms, use of stored fluoroscopy as much as possible, and limitation of fluoroscopic time. A greater use of echocardiography might even lessen the exposure.

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

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

Storb, R.; Raff, R.F.; Graham, T.

1993-03-20

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionatedmore » total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.« less

Effect of ractopamine hydrochloride (Optaflexx) dose and duration on growth performance and carcass characteristics of finishing steers.

PubMed

Bittner, C J; Crawford, G I; Berger, L L; Holt, S; Pritchard, R R; Platter, W J; Van Koevering, M T; Pyatt, N A; Erickson, G E

2016-12-01

Three experiments evaluated the effects of ractopamine hydrochloride (RAC) dose and duration on growth performance and carcass characteristics of feedlot steers. In total, 1,509 crossbred steers (530 kg initial BW [SD 22]) were used in a randomized complete block design using a 3 × 3 factorial treatment structure. Treatments consisted of RAC dose (0, 100, or 200 mg/steer daily) and duration (28, 35, or 42 d) of RAC feeding prior to harvest. Initiation of RAC dose was staggered (7 d apart) based on RAC duration, which resulted in common days on feed among treatments. Data from the 3 experiments were combined for statistical analyses. There were no RAC dose × duration interactions ( ≥ 0.85) for growth performance. Live final BW was not different ( ≥ 0.24) as RAC dose increased. Dry matter intake linearly decreased ( < 0.01) as RAC dose increased. Live ADG and G:F linearly increased ( ≤ 0.01) as RAC dose increased. Carcass-adjusted ADG and G:F linearly increased ( ≤ 0.02) as RAC dose increased. Compared with steers fed 0 mg RAC/steer daily, G:F was improved by 5.0 and 13.0% when steers were fed 100 ( = 0.31) and 200 ( = 0.01) mg RAC/steer daily, respectively. Hot carcass weight tended ( = 0.10) to linearly increase as RAC dose increased, with carcasses from steers fed 100 ( = 0.38) and 200 ( = 0.10) mg RAC/steer daily being 2.2 and 4.1 kg heavier, respectively, than carcasses from steers fed 0 mg RAC/steer daily. Increasing RAC dose linearly ( < 0.01) increased LM area and linearly ( = 0.02) decreased marbling score. Live final BW was not different ( ≥ 0.60) among RAC durations. Carcass-adjusted final BW, ADG, and G:F were not different ( ≥ 0.41) as RAC duration increased. Carcass traits did not differ ( ≥ 0.18) among RAC duration. Feeding 200 mg RAC/steer daily improved ADG, feed efficiency, and HCW. Increasing the feeding duration of RAC had no effect of growth performance or carcass characteristics. These data indicate that feeding 200 mg RAC/steer daily for 28 d improves steer growth performance.

Pretreatment with scutellaria baicalensis stem-leaf total flavonoid prevents cerebral ischemia-reperfusion injury

PubMed Central

Zhao, Shumin; Kong, Wei; Zhang, Shufeng; Chen, Meng; Zheng, Xiaoying; Kong, Xiangyu

2013-01-01

Pretreatment with scutellaria baicalensis stem-leaf total flavonoid has protective effects against ischemia and attenuates myocardial ischemia-reperfusion injury. In this study, rats were given scutellaria baicalensis stem-leaf total flavonoid intragastrically at 50, 100, and 200 mg/kg per day for 7 days before focal cerebral ischemia-reperfusion injury models were established using the suture method. We then determined the protective effects of scutellaria baicalensis stem-leaf total flavonoid pretreatment on focal cerebral ischemia-reperfusion injury. Results showed that neurological deficit scores increased, infarct volumes enlarged, apoptosis increased and Bcl-2 and Bax protein expression were upregulated at 24 hours after reperfusion. Pretreatment with scutellaria baicalensis stem-leaf total flavonoid at any dose lowered the neurological deficit scores, reduced the infarct volume, prevented apoptosis in hippocampal cells, attenuated neuronal and blood-brain barrier damage and upregulated Bcl-2 protein expression but inhibited Bax protein expression. Doses of 100 and 200 mg/kg were the most efficacious. Our findings indicate that pretreatment with scutellaria baicalensis stem-leaf total flavonoid at 100 and 200 mg/kg can improve the neurological functions and have preventive and protective roles after focal cerebral ischemia-reperfusion injury. PMID:25206639

Hepatic glutathione metabolism and lipid peroxidation in response to excess dietary selenomethionine and selenite in mallard ducklings

USGS Publications Warehouse

Hoffman, D.J.; Heinz, G.H.; Krynitsky, A.J.

1989-01-01

Selenium from selenomethionine accumulated in a dose-dependent manner in the liver, resulting in a decrease in hepatic-reduced glutathione with a corresponding decrease in total hepatic thiols. There was a dose-dependent increase in the oxidized to reduced glutathione ratio, and an increase in lipid peroxidation. These findings indicate that Se in the diet at 10 ppm and higher causes significant sublethal alterations in mallard ducklings, and 20-40 ppm causes significant hepatotoxicity.

Pharmacokinetic/pharmacodynamic modeling and simulation of neutropenia during phase I development of liposome-entrapped paclitaxel.

PubMed

Fetterly, Gerald J; Grasela, Thaddeus H; Sherman, Jeffrey W; Dul, Jeanne L; Grahn, Amy; Lecomte, Diane; Fiedler-Kelly, Jill; Damjanov, Nevena; Fishman, Mayer; Kane, Michael P; Rubin, Eric H; Tan, Antoinette R

2008-09-15

To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of liposome-entrapped paclitaxel easy-to-use (LEP-ETU) and to characterize the relationship between LEP-ETU concentrations and the time course of neutropenia in cancer patients. LEP-ETU was administered to 88 patients and 63 were evaluable for pharmacokinetic/pharmacodynamic (PK/PD) analysis following 1.5- and 3-h infusions every 3 weeks (q3w; dose range, 135-375 mg/m(2)). MTD was identified using a 3 + 3, up-and-down dose-finding algorithm. PK/PD modeling was done to describe the temporal relationship between paclitaxel concentrations and neutrophil count. Simulations assessed the influence of dose and schedule on neutropenia severity to help guide dose selection. The MTD of LEP-ETU was identified as 325 mg/m(2). DLTs occurring at 375 mg/m(2) consisted of febrile neutropenia and neuropathy. The C(max) and area under the plasma concentration-time curve of LEP-ETU were less than proportional with increasing dose. The PK/PD model showed that LEP-ETU inhibition of neutrophil proliferation was 9.1% per 10 mug/mL of total paclitaxel concentration. The incidence of grade 4 neutropenia increased from 33% to 42% across the dose range of 275 to 325 mg/m(2) q3w. For a dose of 110 mg/m(2) given weekly, grade 4 neutropenia was estimated to be 16% compared with 42% for the same total dose administered q3w. LEP-ETU can be administered safely at higher doses than Taxol. Modeling and simulation studies predict that 325 mg/m(2) LEP-ETU q3w provides acceptable neutropenic events relative to those observed at 175 mg/m(2) Taxol q3w. A 275 mg/m(2) dose may offer an improved therapeutic index.

Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

PubMed

Ivannikov, A I; Zhumadilov, Zh; Gusev, B I; Miyazawa, Ch; Jiao, L; Skvortsov, V G; Stepanenko, V F; Takada, J; Hoshi, M

2002-08-01

Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

[Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].

PubMed

Qin, Lu-shan; Zhao, Hai-ping; Zhao, Yan-ling; Ma, Zhi-jiel; Zeng, Ling-na; Zhang, Ya-ming; Zhang, Ping; Yan, Dan; Bai, Zhao-fang; Li, Yue; Hao, Qing-xiu; Zhao, Kui-jun; Wang, Jia-bo; Xiao, Xiao-he

2014-06-01

To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver. One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis. Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT. Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

PubMed

Cortes-Briones, Jose A; Cahill, John D; Skosnik, Patrick D; Mathalon, Daniel H; Williams, Ashley; Sewell, R Andrew; Roach, Brian J; Ford, Judith M; Ranganathan, Mohini; D'Souza, Deepak Cyril

2015-12-01

Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

SU-E-T-515: Field-In-Field Compensation Technique Using Multi-Leaf Collimator to Deliver Total Body Irradiation (TBI) Dose

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

Lakeman, T; Wang, IZ; Roswell Park Cancer Institute, Buffalo, NY

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been used conventionally to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern field-in-field (FIF) technique with the multi-leaf collimator (MLC) to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the FIF technique to deliver a total body dose were createdmore » retrospectively for patients for whom CT data had been previously acquired. Treatment fields include one pair of opposed open large fields (collimator=45°) with a specific weighting and a succession of smaller fields (collimator=90°) each with their own weighting. The smaller fields are shaped by moving MLC to block the sections of the patient which have already received close to 100% of the prescribed dose. The weighting factors for each of these fields were calculated using the attenuation coefficient of the initial lead compensators and the separation of the patient in different positions in the axial plane. Results: Dose-volume histograms (DVH) were calculated for evaluating the FIF compensation technique. The maximum body doses calculated from the DVH were reduced from the non-compensated 179.3% to 148.2% in the FIF plans, indicating a more uniform dose with the FIF compensation. All calculated monitor units were well within clinically acceptable limits and exceeded those of the original lead compensation plan by less than 50 MU (only ~1.1% increase). Conclusion: MLC FIF technique for TBI will not significantly increase the beam on time while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.« less

UV controlling factors and trends derived from the ground-based measurements taken at Belsk, Poland, 1976-1994

NASA Astrophysics Data System (ADS)

KrzyśCin, Janusz W.

1996-07-01

Monthly means of UV erythemal dose at ground level from the Robertson-Berger (RB) sunburn meter (1976-1992) and the UV-Biometer model 501 MED meter (1993-1994) located at Belsk (21°E, 52°N), Poland, are examined. The monthly means are calculated from all-sky daily means of UV erythemal dose. Ancillary measurements of column ozone (by Dobson spectrophotometer), sunshine duration (by Campbell-Stokes heliograph), and total (sun and sky) radiation (by a pyranometer) are considered to explain variations in the UV data. A multiple regression model is proposed to study trends in the UV data. The model accounts for the UV erythemal dose changes induced by total ozone, sunshine duration (surrogate for cloud cover variations), or total solar radiation (surrogate for combined cloud cover and atmospheric turbidity impact on the UV radiation), trends due to instrument drift, step changes in the data, and serial correlations. A strong relationship between monthly all-sky UV erythemal dose changes and total ozone (and total solar radiation) is found. Calculations show that an erythemal radiative amplification factor (RAF) due to ozone under all skies is close to its clear-sky value (about 1). However, the model gives evidence that the RAF due to ozone is smaller for cloudier (and/or more turbid) atmospheres than long-term reference. Total solar radiation change of 1% is associated with a change of 0.7% in the UV erythemal dose. Modeled trends in the Belsk's UV data, inferred from the model using ozone and total solar radiation as the UV forcing factors, are 2.3% ± 0.4% (1σ) per decade in the period 1976-1994. The large increase in the UV erythemal dose, of the order of 4% per decade due to ozone depletion (-3.2% per decade), is partially compensated by a decreasing tendency (-2.8% per decade) in total solar radiation. The model estimates the trend in the UV data of the order of 0.1% per decade (not statistically significant) due to superposition of the instrument drift and long-term effects related to other UV influencing factors (not parameterized by the model).

A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

NASA Astrophysics Data System (ADS)

Osman, N. D.; Shamsuri, S. B. M.; Tan, Y. W.; Razali, M. A. S. M.; Isa, S. M.

2017-05-01

Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDIvol and CTDIw) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDIw ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients.

Importance of 6-mercaptopurine dose in lymphoblastic leukaemia.

PubMed Central

Hale, J P; Lilleyman, J S

1991-01-01

To explore the possibility that higher total dosage of 'maintenance' treatment may have contributed to the recent improvement in outlook of children in the United Kingdom with lymphoblastic leukaemia, details of the amount of 6-mercaptopurine prescribed during the first two years of treatment were studied in an unselected cohort of children diagnosed between 1973 and 1987. Eighty five patients were studied, 30 diagnosed before and 55 after 1980. The group diagnosed after 1980 showed an 18% improvement in relapse free survival at five years. Their median total dose of 6-mercaptopurine had increased by 22%, whereas according to the protocol it should have risen by an average of only 9%. After 1980 boys were prescribed significantly more 6-mercaptopurine than girls, and had fewer dose reductions because of myelosuppression. These findings support the clinical impression that after 1980 an important therapeutic difference resulting from the new United Kingdom acute lymphoblastic leukaemia protocols was an increase in the amount of 6-mercaptopurine that children actually received as a result of changes in prescribing guidelines rather than dose. They also provide further evidence that boys tolerate 6-mercaptopurine better than girls, which may be related to the still unexplained difference in prognosis between the sexes. PMID:2031601

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

PubMed

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

2015-11-01

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

Improving treatment geometries in total skin electron therapy: Experimental investigation of linac angles and floor scatter dose contributions using Cherenkov imaging.

PubMed

Andreozzi, Jacqueline M; Brůža, Petr; Tendler, Irwin I; Mooney, Karen E; Jarvis, Lesley A; Cammin, Jochen; Li, Harold; Pogue, Brian W; Gladstone, David J

2018-06-01

The purpose of this study was to identify the optimal treatment geometry for total skin electron therapy (TSET) using a new optimization metric from Cherenkov image analysis, and to investigate the sensitivity of the Cherenkov imaging method to floor scatter effects in this unique treatment setup. Cherenkov imaging using an intensified charge coupled device (ICCD) was employed to measure the relative surface dose distribution as a 2D image in the total skin electron treatment plane. A 1.2 m × 2.2 m × 1 cm white polyethylene sheet was placed vertically at a source to surface distance (SSD) of 300 cm, and irradiated with 6 MeV high dose rate TSET beams. The linear accelerator coordinate system used stipulates 0° is the bottom of the gantry arc, and progresses counterclockwise so that gantry angle 270° produces a horizontal beam orthogonal to the treatment plane. First, all unique pairs of treatment beams were analyzed to determine the performance of the currently recommended symmetric treatment angles (±20° from the horizontal), compared to treatment geometries unconstrained to upholding gantry angle symmetry. This was performed on two medical linear accelerators (linacs). Second, the extent of the floor scatter contributions to measured surface dose at the extended SSD required for TSET were imaged using three gantry angles of incidence: 270° (horizontal), 253° (-17°), and 240° (-30°). Images of the surface dose profile at each angle were compared to the standard concrete floor when steel plates, polyvinyl chloride (PVC), and solid water were placed on the ground at the base of the treatment plane. Postprocessing of these images allowed for comparison of floor material-based scatter profiles with previously published simulation results. Analysis of the symmetric treatment geometry (270 ± 20°) and the identified optimal treatment geometry (270 + 23° and 270 - 17°) showed a 16% increase in the 90% isodose area for the latter field pair on the first linac. The optimal asymmetric pair for the second linac (270 + 25° and 270 - 17°) provided a 52% increase in the 90% isodose area when compared to the symmetric geometry. Difference images between Cherenkov images captured with test materials (steel, PVC, and solid water) and the control (concrete floor) demonstrated relative changes in the two-dimensional (2D) dose profile over a 1 × 1.9 m region of interest (ROI) that were consistent with published simulation data. Qualitative observation of the residual images demonstrates localized increases and decreases with respect to the change in floor material and gantry angle. The most significant changes occurred when the beam was most directly impinging the floor (gantry angle 240°, horizontal -30°), where the PVC floor material decreased scatter dose by 1-3% in 7.2% of the total ROI area, and the steel plate increased scatter dose by 1-3% in 7.0% of the total ROI area. An updated Cherenkov imaging method identified asymmetric, machine-dependent TSET field angle pairs that provided much larger 90% isodose areas than the commonly adopted symmetric geometry suggested by Task Group 30 Report 23. A novel demonstration of scatter dose Cherenkov imaging in the TSET field was established. © 2018 American Association of Physicists in Medicine.

The dose-dependent effects of chronic iron overload on the production of oxygen free radicals and vitamin E concentrations in the liver of a murine model.

PubMed

McCullough, Karey D; Bartfay, Wally J

2007-04-01

Genetic disorders of iron metabolism such as primary and secondary hemochromatosis affect thousands of individuals worldwide and are major causes of liver dysfunction, morbidity, and mortality. Although the exact mechanism of hepatic injury associated with these genetic disorders is not fully understood, the propagation of excess concentrations of iron-catalyzed oxygen free radicals (OFRs) may play a role. The authors hypothesized that chronic iron burden would result in dose-dependent (a) increases in hepatic iron stores, (b) increases in hepatic OFR-mediated hepatic cellular injury as quantified by the cytotoxic aldehydes malondialdehyde (MDA) and hexanal, and (c) decreases in protective antioxidant reserve status as quantified by plasma vitamin E (alpha-tocopherol) levels in a murine model. Twenty B(6)D(2)F1 male mice were randomized to the (a) saline control (0.05 mL intraperiotoneal [i.p.]/mouse/day, n = 5), (b) 100 mg total iron burden (n = 5), (c) 200 mg total iron burden (n = 5), or (d) 400 mg total iron burden (n = 5) group. Iron burden was achieved by daily injections of iron dextran (Imferon, 0.05 mL i.p./mouse/day). In comparison to control mice and in support of the hypothesis, the authors observed significant dose-dependent increases in total hepatic iron burden (p < .001) with corresponding increases in MDA and hexanal concentrations (p < .001) and decreases in the protective plasma antioxidant vitamin E (p < .001). These findings suggest that iron-catalyzed OFR-mediated damage may play a role in damaging the liver in chronic states of iron burden.

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

Jeong, K; Basavatia, A; Mynampati, D

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

Dosimetric evaluation of the effect of dental implants in head and neck radiotherapy.

PubMed

Ozen, Julide; Dirican, Bahar; Oysul, Kaan; Beyzadeoglu, Murat; Ucok, Ozlem; Beydemir, Bedri

2005-06-01

The aim of the study was to examine the dose enhancement from scattered radiation at bone-dental implant interfaces during simulated head and neck radiotherapy. Four cylindrical titanium dental implants with 3 different sizes and lengths were implanted into a human mandible in 4 different positions. Ionization measurements for 6 MV X, 25 MV X, and Co-60 gamma rays were done. Thermoluminescent dosimeter (TLD 100 ) chips were used to measure radiation dose enhancement due to the scattered electrons from titanium and electronic disequilibrium at the tissue-metal interface. The results showed that for Co-60, there is a 21% maximum increase in dose to alveolar mandibular bone at the close proximity to the titanium. For 6-MV x-rays the dose enhancement increase was almost the same or slightly lower than for Co-60, while for 25-MV high-energy x-rays, dose enhancement was lower than that of others. This increase in dose enhancement fell off rapidly and became insignificant at 2 mm from the interface. Total dose that may lead to osteoradionecrosis risk of the mandible is slightly but not significantly affected by the scattered dose of the dental implants of lower jaw in the radiation field exposed to 3 different radiation beams.

Evaluation of contralateral breast skin doses by thermoluminescent dosimeters of patients receiving adjuvant radiotherapy for breast cancer.

PubMed

Gorken, I B; Kentli, S; Alanyali, H; Karagüler, Z; Kinay, M

2002-01-01

It is reported that low dose radiation received by the contralateral breast (CLB) during adjuvant radiotherapy (RT) is carcinogenic. This trial was planned to evaluate the CLB skin doses received during adjuvant RT of breast carcinoma. Twenty-four breast carcinoma patients treated locally or locoregionally with adjuvant RT were included. RT was performed with only tangential fields (TA) in 6 patients whereas 9 patients had an extra internal mammary (IM) field (TAIM). The remaining 9 patients received 5-field locoregional RT (5FLR). All patients were treated with wedge filters except for 3 TA patients. Of 9 5FLR patients IM fields were treated with Co60 in 5 and with electrons in the remaining 4 patients. LiF(2)-based Ribbon type thermoluminescent dosimeters (TLD) were used for dose evaluation. An average of 10 TLD's, placed with 1 cm gaps beginning from the medial border of the treatment field along the central axis were used to obtain dose measurements. Median measure of TLD's between 2-8 cm and maximum dose point (MDP) values in the same range were used to evaluate the CLB dose. In TA patients the CLB skin received 6.3% of the total dose in patients treated with wedge filters and 7.13% with half-beam blocks. For 6 TAIM patients with IM fields treated with Co60, the CLB dose was 7.24%. In 5 of 9 5FLR patients, whose IM fields were treated with Co60 the CLB skin received 8.8% of the total dose, while for electron beam therapy the CLB dose was 5.44%. CLB median MDP values were as follows: 12.76% in TA patients treated with wedge filters and 11.45% with half-beam blocking; 11.89% in TAIM patients with IM fields treated with Co60 and 7.83% with electron beams; 12.29% in 5FLR patients of whose IM fields were treated with Co60 and 8.94% with electron beams. When compared to wedge filters, halfbeam blocks caused 13% increase in CLB doses. If IM fields were added, 27.5% and 62% increases at CLB doses were established with Co60 when compared to electron beam RT in 3-field and 5-field treatments, respectively. CLB doses increased by 15-40% with the increased number of treatment fields. MDP values were also found to be higher with IM fields treated with Co60, but the number of treatment fields and accessories used seemed to have no effect on MDP doses. We conclude that by using wedge filters instead of half-beam blocks and by increasing the number of fractions treated with electron energies for IM fields, apparent decreases in CLB doses can be obtained. Large number of cases is needed to statistically establish the significant differences between subgroups.

Pharmacokinetics of oral hydrocortisone - Results and implications from a randomized controlled trial.

PubMed

Werumeus Buning, Jorien; Touw, Daan J; Brummelman, Pauline; Dullaart, Robin P F; van den Berg, Gerrit; van der Klauw, Melanie M; Kamp, Jasper; Wolffenbuttel, Bruce H R; van Beek, André P

2017-06-01

This study aimed at comparing pharmacokinetics of two different doses of hydrocortisone (HC) in patients with secondary adrenal insufficiency (SAI). Forty-six patients with SAI participated in this randomized double-blind crossover study. Patients received two different doses of HC (0.2-0.3mg HC/kg body weight/day and 0.4-0.6mg HC/kg body weight/day). One- and two-compartment population models for plasma free cortisol, plasma total cortisol and salivary cortisol were parameterized. The individual pharmacokinetic parameters clearance (CL), volume of distribution (V d ), elimination half-life (t 1/2 ), maximum concentration (C max ), and area under the curve (AUC) were calculated. The one-compartment models gave a better description of the data compared to the two-compartment models. Weight-adjusted dosing reduced variability in cortisol exposure with comparable AUCs between weight groups. However, there was large inter-individual variation in CL and V d of plasma free cortisol, plasma total cortisol and salivary cortisol. As a consequence, AUC 24h varied more than 10 fold. Cortisol exposure was increased with the higher dose, but this was dose proportional only for free cortisol concentrations and not for total cortisol. Cortisol concentrations after a doubling of the dose were only dose proportional for free cortisol. HC pharmacokinetics can differ up to 10-fold inter-individually and individual adjustment of treatment doses may be necessary. Doubling of the HC dose in fast metabolizers (patients that showed relative low AUC and thus high clearance compared to other patients), does not result in significantly enhanced exposure during large parts of the day and these patients may need other management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide.

PubMed

Schmitz, Ole; Lund, Sten; Andersen, Per Heden; Jønler, Morten; Pørksen, Nils

2002-02-01

Repaglinide, a novel antidiabetic agent that has a rapid onset and short duration of action, was developed for mealtime dosing. The purpose of this pharmacodynamic study was to validate a prandial regimen of repaglinide by comparing meal-related dosing with a regimen in which the same total daily dose was divided into only two doses at morning and evening meals. The study was a double-blind, randomized, parallel-group trial in 19 antidiabetic agent-naive subjects with type 2 diabetes (mean age 58 years, known duration of diabetes 3.5 years, HbA(1c) 7.3%, and BMI 32 kg/m(2)). Patients were randomly assigned to receive repaglinide either before each of the three main meals or before breakfast and before the evening meal. Patients in both groups received the same total daily dose of repaglinide. Twenty-four hour profiles of blood glucose, plasma insulin, and plasma C-peptide concentrations were measured at baseline and after 4 weeks of treatment. Repaglinide increased postprandial insulin levels and markedly reduced postprandial glucose levels relative to baseline in both groups. Significant reductions were also recorded in fasting blood glucose and HbA(1c) levels. The repaglinide regimen, in which a dose was taken before each main meal, was more effective in improving glycemic control (including postprandial glucose and HbA(1c) levels) than the same total dose of repaglinide divided into morning and evening mealtime doses. These data support the strategy of mealtime dosing with repaglinide. The improvements in glycemic control observed in these patients are encouraging. In addition to classic parameters of glycemic control, improvements in postprandial glucose excursions may prove to be important because postprandial hyperglycemia has been suggested to be an independent risk factor for cardiovascular disease in diabetes.

SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

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

Han, C; Schultheiss, T

Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) weremore » used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.« less

Prediction of obliteration after gamma knife surgery for cerebral arteriovenous malformations.

PubMed

Karlsson, B; Lindquist, C; Steiner, L

1997-03-01

To define the factors of importance for the obliteration of cerebral arteriovenous malformations (AVMs), thus making a prediction of the probability for obliteration possible. In 945 AVMs of a series of 1319 patients treated with the gamma knife during 1970 to 1990, the relationship between patient, AVMs, and treatment parameters on the one hand and the obliteration of the nidus on the other was analyzed. The obliteration rate increased both with increased minimum (lowest periphery) and average dose and decreased with increased AVM volume. The minimum dose to the AVMs was the decisive dose factor for the treatment result. The higher the minimum dose, the higher the chance for total obliteration. The curve illustrating this relation increased logarithmically to a value of 87%. A higher average dose shortened the latency to AVM obliteration. For the obliterated cases, the larger the malformation, the lower the minimum dose used. This prompted us to relate the obliteration rate to the product minimum dose (AVM volume)1/3 (K index). The obliteration rate increased linearly with the K index up to a value of approximately 27, and for higher K values, the obliteration rate had a constant value of approximately 80%. For the group of 273 cases treated with a minimum dose of at least 25 Gy, the obliteration rate at the study end point (defined as 2-yr latency) was 80% (95% confidence interval = 75-85%). If obliterations that occurred beyond the end point are included, the obliteration rate increased to 85% (81-89%). The probability of obliteration of AVMs after gamma knife surgery is related both to the lowest dose to the AVMs and the AVM volume, and it can be predicted using the K index.

SU-F-T-322: A Comparison of Two Si Detectors for in Vivo Dosimetry

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

Talarico, O; Krylova, T; Lebedenko, I

Purpose: To compare two types of semiconductor detectors for in vivo dosimetry by their dependence from various parameters in different conditions. Methods: QED yellow (Sun Nuclear) and EDP (Scanditronix) Si detectors were radiated by a Varian Clinac 2300 ix with 6 and 18 MV energies. 10 cm thickness water equivalent phantom consisted of 30×30 cm{sup 2} squared plates was used for experiments. Dose dependencies for different beam angles (0 – 180°), field size (3–40 cm), dose (50 – 300 MU), and dose rates (50 – 300 MU/min) were obtained and calibrated with Standard Farmer chamber (PTW). Results: Reproducibility, linearity, dosemore » rate, angular dependence, and field size dependence were obtained for QED and EDP. They show no dose-rate dependence in available clinical dose rate range (100–600 MU/min). Both diodes have linear dependence with increasing the dose. Therefore even in case of high radiation therapy (including total body irradiation) it is not necessary to apply an additional correction during in vivo dosimetry. The diodes have different behavior for angular and field size dependencies. QED diode showed that dose value is stable for beam angles from 0 to 60°, for 60–180° correction factor has to be applied for each beam angle during in vivo measurements. For EDP diode dose value is sensitive to beam angle in whole range of angles. Conclusion: The study shows that QED diode is more suitable for in vivo dosimetry due to dose value independence from incident beam angle in the range 0–60°. There is no need in correction factors for increasing of dose and dose rate for both diodes. The next step will be to carry out measurements in non-standard conditions of total body irradiation. After this modeling of these experiments with Monte Carlo simulation for comparison calculated and obtained data is planned.« less

Evaluation of Aqueous Leaf Extract of Cardiospermum halicacabum (L.) on Fertility of Male Rats.

PubMed

Peiris, L Dinithi C; Dhanushka, M A T; Jayathilake, T A H D G

2015-01-01

Treatment with 100 mg/kg and 200 mg/kg body weight of aqueous leaf extract (ALE) of Cardiospermum halicacabum for 30 days produced a significant dose dependent increase in the sperm counts and sperm motility in both caput and cauda regions. Further, significant increase in serum testosterone level was evident at all applied doses. However, no significant changes in the weight of sex organs were observed. Aqueous leaf extract also increased the number of females impregnated, number of implantations, and number of viable fetuses while decreasing the total number of resorption sites in the pregnant females. However, the total cholesterol level in the serum remained unchanged and there were no records on renotoxicity; nevertheless ALE exhibited a hepatoprotective effect. It was concluded that aqueous leaf extract of Cardiospermum halicacabum enhanced sperm concentration, motility, and testosterone, leading to positive results in fertility.

Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax®) in individuals aged ≥ 70 years: a randomized study of a single dose vs. two different two-dose schedules.

PubMed

Vesikari, Timo; Hardt, Roland; Rümke, Hans C; Icardi, Giancarlo; Montero, Jordi; Thomas, Stéphane; Sadorge, Christine; Fiquet, Anne

2013-04-01

Disease protection provided by herpes zoster (HZ) vaccination tends to reduce as age increases. This study was designed to ascertain whether a second dose of the HZ vaccine, Zostavax(®), would increase varicella zoster virus (VZV)-specific immune response among individuals aged ≥ 70 y. Individuals aged ≥ 70 y were randomized to receive HZ vaccine in one of three schedules: a single dose (0.65 mL), two doses at 0 and 1 mo, or two doses at 0 and 3 mo. VZV antibody titers were measured at baseline, 4 weeks after each vaccine dose, and 12 mo after the last dose. In total, 759 participants (mean age 76.1 y) were randomized to receive vaccination. Antibody responses were similar after a single dose or two doses of HZ vaccine [post-dose 2/post-dose 1 geometric mean titer (GMT) ratios for the 1-mo or 3-mo schedules were 1.11, 95% confidence interval (CI) 1.02-1.22 and 0.78, 95% CI 0.73-0.85], respectively). The 12-mo post-dose 2/12-mo post-dose 1 GMT ratio was similar for the 1-mo schedule and for the 3-mo schedule (1.06, 95% CI 0.96-1.17 and 1.08, 95% CI 0.98-1.19, respectively). Similar immune responses were observed in participants aged 70-79 y and those aged ≥ 80 y. HZ vaccine was generally well tolerated, with no evidence of increased adverse event incidence after the second dose with either schedule. Compared with a single-dose regimen, two-dose vaccination did not increase VZV antibody responses among individuals aged ≥ 70 y. Antibody persistence after 12 mo was similar with all three schedules.

Comparative study on skin dose measurement using MOSFET and TLD for pediatric patients with acute lymphatic leukemia.

PubMed

Al-Mohammed, Huda I; Mahyoub, Fareed H; Moftah, Belal A

2010-07-01

The object of this study was to compare the difference of skin dose measured in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using metal oxide semiconductor field-effect transistors (mobile MOSFET dose verification system (TN-RD-70-W) and thermoluminescent dosimeters (TLD-100 chips, Harshaw/ Bicron, OH, USA). Because TLD has been the most-commonly used technique in the skin dose measurement of TBI, the aim of the present study is to prove the benefit of using the mobile MOSFET (metal oxide semiconductor field effect transistor) dosimeter, for entrance dose measurements during the total body irradiation (TBI) over thermoluminescent dosimeters (TLD). The measurements involved 10 pediatric patients ages between 3 and 14 years. Thermoluminescent dosimeters and MOSFET dosimetry were performed at 9 different anatomic sites on each patient. The present results show there is a variation between skin dose measured with MOSFET and TLD in all patients, and for every anatomic site selected, there is no significant difference in the dose delivered using MOSFET as compared to the prescribed dose. However, there is a significant difference for every anatomic site using TLD compared with either the prescribed dose or MOSFET. The results indicate that the dosimeter measurements using the MOSFET gave precise measurements of prescribed dose. However, TLD measurement showed significant increased skin dose of cGy as compared to either prescribed dose or MOSFET group. MOSFET dosimeters provide superior dose accuracy for skin dose measurement in TBI as compared with TLD.

The effects of UV radiation during the vegetative period on antioxidant compounds and postharvest quality of broccoli (Brassica oleracea L.).

PubMed

Topcu, Yasin; Dogan, Adem; Kasimoglu, Zehra; Sahin-Nadeem, Hilal; Polat, Ersin; Erkan, Mustafa

2015-08-01

In this study, the effects of supplementary UV radiation during the vegetative period on antioxidant compounds, antioxidant activity and postharvest quality of broccoli heads during long term storage was studied. The broccolis were grown under three different doses of supplementary UV radiation (2.2, 8.8 and 16.4 kJ/m(2)/day) in a soilless system in a glasshouse. Harvested broccoli heads were stored at 0 °C in modified atmosphere packaging for 60 days. The supplementary UV radiation (280-315 nm) during the vegetative period significantly decreased total carotenoid, the chlorophyll a and chlorophyll b content but increased the ascorbic acid, total phenolic and flavonoid contents of broccolis. All supplementary UV treatments slightly reduced the antioxidant activity of the broccolis, however, no remarkable change was observed between 2.2 and 8.8 kJ/m(2) radiation levels. The sinigrin and glucotropaeolin contents of the broccolis were substantially increased by UV treatments. The prolonged storage period resulted in decreased ascorbic acid, total phenolic and flavonoid contents, as well as antioxidant activity. Discoloration of the heads, due to decreased chlorophyll and carotenoid contents, was also observed with prolonged storage duration. Glucosinolates levels showed an increasing tendency till the 45th day of storage, and then their levels started to decline. The weight loss of broccoli heads during storage progressively increased with storage time in all treatments. Total soluble solids, solids content and titratable acidity decreased continuously during storage. Titratable acidity was not affected by UV radiation doses during the storage time whereas soluble solids and solids content (dry matter) were significantly affected by UV doses. Supplementary UV radiation increased the lightness (L*) and chroma (C*) values of the broccoli heads. Pre-harvest UV radiation during vegetative period seems to be a promising tool for increasing the beneficial health components of broccolis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Methodological variations and their effects on reported medication administration error rates.

PubMed

McLeod, Monsey Chan; Barber, Nick; Franklin, Bryony Dean

2013-04-01

Medication administration errors (MAEs) are a problem, yet methodological variation between studies presents a potential barrier to understanding how best to increase safety. Using the UK as a case-study, we systematically summarised methodological variations in MAE studies, and their effects on reported MAE rates. Nine healthcare databases were searched for quantitative observational MAE studies in UK hospitals. Methodological variations were analysed and meta-analysis of MAE rates performed using studies that used the same definitions. Odds ratios (OR) were calculated to compare MAE rates between intravenous (IV) and non-IV doses, and between paediatric and adult doses. We identified 16 unique studies reporting three MAE definitions, 44 MAE subcategories and four different denominators. Overall adult MAE rates were 5.6% of a total of 21 533 non-IV opportunities for error (OE) (95% CI 4.6% to 6.7%) and 35% of a total of 154 IV OEs (95% CI 2% to 68%). MAEs were five times more likely in IV than non-IV doses (pooled OR 5.1; 95% CI 3.5 to 7.5). Including timing errors of ±30 min increased the MAE rate from 27% to 69% of 320 IV doses in one study. Five studies were unclear as to whether the denominator included dose omissions; omissions accounted for 0%-13% of IV doses and 1.8%-5.1% of non-IV doses. Wide methodological variations exist even within one country, some with significant effects on reported MAE rates. We have made recommendations for future MAE studies; these may be applied both within and outside the UK.

Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose

PubMed Central

Marciani, L; Garsed, K C; Hoad, C L; Fields, A; Fordham, I; Pritchard, S E; Placidi, E; Murray, K; Chaddock, G; Costigan, C; Lam, C; Jalanka-Tuovinen, J; De Vos, W M; Gowland, P A; Spiller, R C

2014-01-01

Background Most methods of assessing colonic motility are poorly acceptable to patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility and fluid distributions. We predicted that a dose of oral polyethylene glycol (PEG) and electrolyte solution would increase ileo-colonic inflow and stimulate colonic motility. We aimed to investigate the colonic response to distension by oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of single 2 L vs split (2 × 1 L) dosing. Methods Twelve HVs received a split dose (1 L the evening before and 1 L on the study day) and another 12 HVs a single dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans, completed symptom questionnaires, and provided stool samples. Outcomes included small bowel water content, ascending colon motility index, and regional colonic volumes. Key Results Small bowel water content increased fourfold from baseline after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total colonic volume increase from baseline was smaller for the split dose at 35 ± 8% than for the single dose at 102 ± 27%, p = 0.0332. The ascending colon motility index after treatment was twofold higher for the single dose group (p = 0.0103). Conclusions & Inferences Ingestion of 1 and 2 L PEG electrolyte solution caused a rapid increase in the small bowel and colonic volumes and a robust rise in colonic motility. The increase in both volumes and motility was dose dependent. Such a challenge, being well-tolerated, could be a useful way of assessing colonic motility in future studies. PMID:25060551

The lateral plane delivers higher dose than the frontal plane in biplane cardiac catheterization systems.

PubMed

Aldoss, Osamah; Patel, Sonali; Harris, Kyle; Divekar, Abhay

2015-06-01

The objective of the study is to compare radiation dose between the frontal and lateral planes in a biplane cardiac catheterization laboratory. Tube angulation progressively increases patient and operator radiation dose in single-plane cardiac catheterization laboratories. This retrospective study captured biplane radiation dose in a pediatric cardiac catheterization laboratory between April 2010 and January 2014. Raw and time-indexed fluoroscopic, cineangiographic and total (fluoroscopic + cineangiographic) air kerma (AK, mGy) and kerma area product (PKA, µGym(2)/Kg) for each plane were compared. Data for 716 patients were analyzed: 408 (56.98 %) were male, the median age was 4.86 years, and the median weight was 17.35 kg. Although median beam-on time (minutes) was 4.2 times greater in the frontal plane, there was no difference in raw median total PKA between the two planes. However, when indexed to beam-on time, the lateral plane had a higher median-indexed fluoroscopic (0.75 vs. 1.70), cineangiographic (16.03 vs. 24.92), and total (1.43 vs. 5.15) PKA (p < 0.0001). The median time-indexed total PKA in the lateral plane is 3.6 times the frontal plane. This is the first report showing that the lateral plane delivers a higher dose than the frontal plane per unit time. Operators should consciously reduce the lateral plane beam-on time and incorporate this practice in radiation reduction protocols.

Response of Intestinal Bacterial Flora to the Long-term Feeding of Aflatoxin B1 (AFB1) in Mice.

PubMed

Yang, Xiai; Liu, Liangliang; Chen, Jing; Xiao, Aiping

2017-10-12

In order to investigate the influence of aflatoxin B1 (AFB1) on intestinal bacterial flora, 24 Kunming mice (KM mice) were randomly placed into four groups, which were labeled as control, low-dose, medium-dose, and high-dose groups. They were fed intragastrically with 0.4 mL of 0 mg/L, 2.5 mg/L, 4 mg/L, or 10 mg/L of AFB1 solutions, twice a day for 2 months. The hypervariable region V3 + V4 on 16S rDNA of intestinal bacterial flora was sequenced by the use of a high-flux sequencing system on a Miseq Illumina platform; then, the obtained sequences were analyzed. The results showed that, when compared with the control group, both genera and phyla of intestinal bacteria in the three treatment groups decreased. About one third of the total genera and one half of the total phyla remained in the high-dose group. The dominant flora were Lactobacillus and Bacteroides in all groups. There were significant differences in the relative abundance of intestinal bacterial flora among groups. Most bacteria decreased as a whole from the control to the high-dose groups, but several beneficial and pathogenic bacterial species increased significantly with increasing dose of AFB1. Thus, the conclusion was that intragastric feeding with 2.5~10 mg/mL AFB1 for 2 months could decrease the majority of intestinal bacterial flora and induce the proliferation of some intestinal bacteria flora.

Low-molecular-weight heparin use in the obese, elderly, and in renal insufficiency.

PubMed

Clark, N P

2008-01-01

Superior bioavailability and simple weight-based dosing have made low-molecular-weight heparins (LMWH) the preferred agents for treatment and prevention of venous thromboembolism (VTE) for most indications. Despite improved pharmacokinetics, there remain populations where appropriate LMWH dose intensity and frequency are open to question. Obese patients have a lower proportion of lean body mass as a percentage of total body weight. As a result, LMWH dosing based on total body weight could cause supra-therapeutic anticoagulation. Elderly patients also have less lean body mass in addition to a higher incidence of age-related renal disease and increased risk of bleeding. Renal insufficiency presents a risk of LMWH accumulation as well as increased risk of bleeding. Among LMWH products, only dalteparin labeling recommends a maximum dose. Prospective data call into question the validity of this dose limitation. Additionally, because obese patients are already at higher risk of VTE recurrence, they may be particularly sensitive to subtherapeutic anticoagulation. Prospective data evaluating LMWH use in elderly patients have been limited to in-patient treatment. Few recommendations can be made in this population other than close monitoring. Renal insufficiency is a risk for bleeding during LMWH use. Available evidence supports the potential for enoxaparin accumulation, but not tinzaparin. Enoxaparin dose adjustment, either empiric or based on anti-Xa monitoring, has insufficient data to support widespread implementation. Unfractionated heparin is not reliant on renal elimination and is a sensible option for VTE treatment in patients with a creatinine clearance<30 ml/min.

A comparative analysis of 3D conformal deep inspiratory–breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer

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

Reardon, Kelli A.; Read, Paul W.; Morris, Monica M.

2013-07-01

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory–breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumesmore » of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.« less

Selected heavy metals speciation in chemically stabilised sewage sludge

NASA Astrophysics Data System (ADS)

Wiśniowska, Ewa; Włodarczyk-Makuła, Marła

2017-11-01

Selected heavy metals (Pb, Ni, Cd) were analysed in soil, digested sewage sludge as well as in the sludge stabilised with CaO or Fenton's reagent. The dose of Fenton's reagent was as follows: Fe2+ = 1g.L-1, Fe2+/H2O2=1:100; stabilisation lasted for 2 h. Dose of CaO was equal to 1 g CaO.g d.m.-1 Total concentration of all metals in the digested sewage sludge was higher than in the soil. Chemical stabilisation of sludge with Fenton's reagent increased total metal content in the sludge as a result of total solids removal. Opposite effect was stated when the sludge was mixed with CaO. Also chemical fractions of heavy metals were identified (exchangeable, carbonate bound, iron oxides bound, organic and residual). The results indicate that stabilisation of the sludge with Fenton's reagent increased mobility of heavy metals compared to the digested sludge. Amendment of CaO increased percent share of examined metals in residual fraction, thus immobilised them and decreased their bioavailability.

Assessment of the anticancer compounds Se-methylselenocysteine and glucosinolates in Se-biofortified broccoli (Brassica oleracea L. var. italica) sprouts and florets.

PubMed

Ávila, Fabricio William; Faquin, Valdemar; Yang, Yong; Ramos, Silvio Junio; Guilherme, Luiz Roberto G; Thannhauser, Theodore W; Li, Li

2013-07-03

Broccoli (Brassica oleracea L. var. italica) is a rich source of chemopreventive compounds. Here, we evaluated and compared the effect of selenium (Se) treatment on the accumulation of anticancer compounds Se-methylselenocysteine (SeMSCys) and glucosinolates in broccoli sprouts and florets. Total Se and SeMSCys content in sprouts increased concomitantly with increasing Se doses. Selenate was superior to selenite in inducing total Se accumulation, but selenite is equally effective as selenate in promoting SeMSCys synthesis in sprouts. Increasing sulfur doses reduced total Se and SeMSCys content in sprouts treated with selenate, but not in those with selenite. Examination of five broccoli cultivars reveals that sprouts generally have better fractional ability than florets to convert inorganic Se into SeMSCys. Distinctive glucosinolate profiles between sprouts and florets were observed, and sprouts contained approximately 6-fold more glucoraphanin than florets. In contrast to florets, glucosinolate content was not affected by Se treatment in sprouts. Thus, Se-enriched broccoli sprouts are excellent for simultaneous accumulation of chemopreventive compounds SeMSCys and glucoraphanin.

Primary Analysis of a Phase II Randomized Trial Radiation Therapy Oncology Group (RTOG) 0212: Impact of Different Total Doses and Schedules of Prophylactic Cranial Irradiation on Chronic Neurotoxicity and Quality of Life for Patients With Limited-Disease Small-Cell Lung Cancer

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

Wolfson, Aaron H., E-mail: awolfson@med.miami.edu; Bae, Kyounghwa; Komaki, Ritsuko

2011-09-01

Purpose: To determine the effect of dose and fractionation schedule of prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity (CNt) and changes in quality of life for selected patients with limited-disease small-cell lung cancer (LD SCLC). Methods and Materials: Patients with LD SCLC who achieved a complete response after chemotherapy and thoracic irradiation were eligible for randomization to undergo PCI to a total dose of 25 Gy in 10 daily fractions (Arm 1) vs. the experimental cohort of 36 Gy. Those receiving 36 Gy underwent a secondary randomization between daily 18 fractions (Arm 2) and twice-daily 24 fractionsmore » (Arm 3). Enrolled patients participated in baseline and follow-up neuropsychological test batteries along with quality-of-life assessments. Results: A total of 265 patients were accrued, with 131 in Arm 1, 67 in Arm 2, and 66 in Arm 3 being eligible. There are 112 patients (42.2%) alive with 25.3 months of median follow-up. There were no significant baseline differences among groups regarding quality-of-life measures and one of the neuropsychological tests, namely the Hopkins Verbal Learning Test. However, at 12 months after PCI there was a significant increase in the occurrence of CNt in the 36-Gy cohort (p = 0.02). Logistic regression analysis revealed increasing age to be the most significant predictor of CNt (p = 0.005). Conclusions: Because of the increased risk of developing CNt in study patients with 36 Gy, a total PCI dose of 25 Gy remains the standard of care for patients with LD SCLC attaining a complete response to initial chemoradiation.« less

Partially hydrolyzed guar gum supplement reduces high-fat diet increased blood lipids and oxidative stress and ameliorates FeCl3-induced acute arterial injury in hamsters

PubMed Central

Kuo, Dar-Chih; Hsu, Shih-Ping; Chien, Chiang-Ting

2009-01-01

Increased reactive oxygen species (ROS) and hyperlipidemia can promote arterial thrombus. We evaluated the potential of a partially hydrolyzed guar gum (PHGG) as dietary fiber on lipid profiles and FeCl3-induced arterial thrombosis in the high fat-diet fed hamsters. Our in vitro results found that PHGG is efficient to scavenge O2-•, H2O2, and HOCl. High fat-diet increased plasma triglyceride, total cholesterol, LDL, VLDL, methylguanidine and dityrosine level and accelerated FeCl3-induced arterial thrombosis formation (from 463 ± 51 to 303 ± 45 sec). Low dose PHGG supplement significantly decreased the total cholesterol, LDL, methylguanidine and dityrosine level and delayed the time for arterial thrombosis formation (528 ± 75 sec). High dose PHGG supplement decreased the level in triglyceride, total cholesterol, LDL and VLDL and further delayed the time for arterial thrombus (671 ± 36 sec). The increased Bax protein and decreased Bcl-2 and HSP-70 protein expression was found in the carotid and femoral arteries of high fat-diet hamsters. Low and high dose of PHGG supplement decreased Bax expression and increased Bcl-2 and HSP-70 protein expression. We found that FeCl3 significantly enhanced intercellular adhesion molecule-1 and 4-hydroxynonenal expression in the endothelial site of damaged artery after 150-sec FeCl3 stimulation. PHGG supplement decreased the endothelial ICAM-1 and 4-hydroxynonenal expression after 150-sec FeCl3 stimulation. Based on these results, we conclude that PHGG supplement can increase antioxidant protein expression and thus decrease oxidative stress induced arterial injury. PMID:19272178

Calculation of Glucose Dose for Intraperitoneal Glucose Tolerance Tests in Lean and Obese Mice.

PubMed

Jørgensen, Mikkel S; Tornqvist, Kristina S; Hvid, Henning

2017-01-01

Glucose tolerance tests are used frequently in nonclinical research with laboratory animals, for example during characterization of obese phenotypes. Despite published standard operating procedures for glucose tolerance tests in rodents, how glucose doses should be calculated when obese and lean animals are compared is not well documented. Typically the glucose dose is calculated as 2 g/kg body weight, regardless of body composition. With this approach, obese mice receive larger glucose doses than do lean animals, potentially leading to overestimation of glucose intolerance in obese animals. In this study, we performed intraperitoneal glucose tolerance tests in mice with diet-induced obesity and their lean controls, with glucose doses based on either the total body weight or the lean body mass of the animals. To determine glucose tolerance, we determined the blood glucose AUC during the glucose tolerance test. We found that the blood glucose AUC was increased significantly in obese mice compared with lean mice by 75% on average when glucose was dosed according to the lean body mass and by 87% when the glucose dose was calculated according to total body weight. Therefore, mice with diet-induced obesity were approximately equally glucose intolerant between the 2 dose-calculation protocols. However, we recommend calculating the glucose dose according to the lean body mass of the mice, because doing so eliminates the concern regarding overdosing of obese animals.

Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium with Neonatal Outcomes

PubMed Central

Kacinko, SL; Jones, HE; Johnson, RE; Choo, RE; Huestis, MA

2009-01-01

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS ) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. PMID:18701886

Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels.

PubMed

Schver, Giovanna C R M; Lee, Ping I

2018-05-07

Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates sufficiently rapid initial supersaturation buildup above the critical supersaturation, resulting in more rapid precipitation. Above this smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of drug release gets slower, which results in a more modest rate of supersaturation buildup, leading to a maximum supersaturation below the critical-supersaturation level without appreciable precipitation. The area-under-the-curve (AUC) values of the in vitro kinetic-solubility concentration-time profiles were used to correlate the corresponding trends in dissolution enhancement. There are observed monotonic increases in AUC values with increasing particle sizes for high-dose ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously reported AUC maxima at some intermediate supersaturation rates or doses in soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the critical dose levels), crystallization would be negligible, leading to sustained supersaturation with all particle sizes (i.e., eventually reaching the same maximum supersaturation) and the smallest particle size reaching the maximum supersaturation the fastest. As a result, the smallest particle sizes yield the largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel matrixes. In addition to probing the interplay between the supersaturation-generation rates and total doses in ASDs based on insoluble hydrogel carriers, our results further support the fact that through either increasing the hydrogel-particle size or lowering the total dose to achieve maximum supersaturation still below the critical-supersaturation level, it is possible to avoid drug precipitation so as to maintain sustained supersaturation.

Clinical radiobiology of stage T2-T3 bladder cancer.

PubMed

Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

2004-09-01

To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival (p = 0.087), and OTT did not reach statistical significance. The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.

A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy

PubMed Central

Richards, Cynthia; Iosifescu, Dan V; Mago, Rajnish; Sarkis, Elias; Reynolds, James; Geibel, Brooke; Dauphin, Matthew

2017-01-01

Background: This randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy. Methods: Eligible adults (18–65 years) were assigned to antidepressant monotherapy (escitalopram or venlafaxine extended-release) plus lisdexamfetamine dimesylate-matching placebo during an eight-week single-blind lead-in phase. Participants meeting randomization criteria were randomized (1:1:1:1:1) to eight weeks of lisdexamfetamine dimesylate (10, 30, 50, or 70 mg) or placebo while maintaining antidepressant therapy. Dose-responses for changes from augmentation baseline to week 16/early termination for Montgomery-Åsberg Depression Rating Scale total score (primary efficacy endpoint) and vital signs (systolic and diastolic blood pressure and pulse) were assessed using multiple comparisons procedures with modeling. Results: For Montgomery-Åsberg Depression Rating Scale total score change, no significant dose-responses were observed for any candidate dose-response curve (all p>0.10). In the dose-response evaluable population, least squares mean (90% confidence interval) treatment differences versus placebo for Montgomery-Åsberg Depression Rating Scale total score change at week 16 were −1.4 (−3.9, 1.2), 0.1 (−2.5, 2.7), −0.7 (−3.4, 2.0), and −0.9 (−3.5, 1.6) with 10, 30, 50, and 70 mg lisdexamfetamine dimesylate, respectively. For all vital sign parameters, lisdexamfetamine dimesylate exhibited significant dose-responses for all candidate dose-response curves (all p<0.10), with increases observed as lisdexamfetamine dimesylate dose increased; a linear relationship provided the best fit. Mean±standard deviation changes from augmentation baseline for systolic and diastolic blood pressure and pulse at week 16/early termination were −0.7±9.90 and −0.3±7.24 mm Hg and 0.2±10.57 bpm with placebo and were 1.9±9.47 and 0.8±7.40 mm Hg and 3.6±9.74 bpm with lisdexamfetamine dimesylate (all doses combined). The safety and tolerability profile of lisdexamfetamine dimesylate was consistent with previous studies. Conclusions: Lisdexamfetamine dimesylate augmentation did not provide benefit over placebo in adults with inadequate responses to antidepressant monotherapy based on the assessed efficacy measures. PMID:28857719

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

PubMed

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

2017-01-01

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

Inactivation, reactivation and regrowth of indigenous bacteria in reclaimed water after chlorine disinfection of a municipal wastewater treatment plant.

PubMed

Li, Dan; Zeng, Siyu; Gu, April Z; He, Miao; Shi, Hanchang

2013-07-01

Disinfection of reclaimed water prior to reuse is important to prevent the transmission of pathogens. Chlorine is a widely utilized disinfectant and as such is a leading contender for disinfection of reclaimed water. To understand the risks of chlorination resulting from the potential selection of pathogenic bacteria, the inactivation, reactivation and regrowth rates of indigenous bacteria were investigated in reclaimed water after chlorine disinfection. Inactivation of total coliforms, Enterococcus and Salmonella showed linear correlations, with constants of 0.1384, 0.1624 and 0.057 L/(mg.min) and R2 of 0.7617, 0.8316 and 0.845, respectively. However, inactivation of total viable cells by measurement of metabolic activity typically showed a linear correlation at lower chlorine dose (0-22 (mg-min)/L), and a trailing region with chlorine dose increasing from 22 to 69 (mg.min)/L. Reactivation and regrowth of bacteria were most likely to occur after exposure to lower chlorine doses, and extents of reactivation decreased gradually with increasing chlorine dose. In contrast to total coliforms and Enterococcus, Salmonella had a high level of regrowth and reactivation, and still had 2% regrowth even after chlorination of 69 (mg.min)/L and 24 hr storage. The bacterial compositions were also significantly altered by chlorination and storage of reclaimed water, and the ratio of Salmonella was significantly increased from 0.001% to 0.045% after chlorination of 69 (mg.min)/L and 24 hr storage. These trends indicated that chlorination contributes to the selection of chlorine-resistant pathogenic bacteria, and regrowth of pathogenic bacteria after chlorination in reclaimed water with a long retention time could threaten public health security during wastewater reuse.

The Effect of Intra-articular Corticosteroids on Articular Cartilage

PubMed Central

Wernecke, Chloe; Braun, Hillary J.; Dragoo, Jason L.

2015-01-01

Background: Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s. Purpose: To review the current literature on the effects of IA corticosteroids on articular cartilage. Study Design: Systematic review. Methods: A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies. Results: Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds. Conclusion: Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used. PMID:26674652

On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males.

PubMed

Badr, F M; Rabouh, S A; Badr, R S

1979-11-01

The mutagenicity of methadone hydrochloride was tested in male mice using the dominant lethal mutation technique and the spermatocyte test of treated mice. Male mice of C3H inbred strain received one of the following doses, 1, 2, 4 or 6 mg/kg body weight once a day for 3 consecutive days. Another group of mice served as control and received saline instead. Treated males were then mated to virgin females at 3-day intervals for a period of 45 days. Pregnant females were dissected at mid-term and the corpora lutea and intrauterine contents were recorded. The spermatocytes of treated males were examined 45-50 d after treatments with methadone and abnormal pairing configurations were scored. The methadone treatment was found to increase the rate of preimplantation deaths consistently in all post-meiotic stages with all doses used. In addition, the higher doses, 4 and 6 mg, affected spermatogonia stages. Quantitatively, the dose-response relationship cannot be demonstrated though the spectrum of effect increased with higher doses as more spermatogenesis stages became more sensitive to the treatment. In many cases the frequency of live implants showed a positive correlation with preimplantation deaths in contrast with the frequency of early deaths which showed only sporadic variation. The mutation indices based on total embryonic death indicate that methadone hydrochloride affected several stages of germ-cell maturation namely, spermatozoa (M.I. 14-35), late spermatids (M.I. 15-48), early spermatids (M.I. 14-50), late spermatocytes (M.I. 15-43) and spermatogonial stages (M.I. 12-63). Chromosome analysis at diakinesis-metaphase 1 revealed significant increase in the frequency of sex chromosome and autosome univalents with different doses of methadone. The smallest dose applied was quite effective and the data represent direct dose-response relationship. Of the multivalent configuration, the most frequent type was chain quadrivalents. The frequencies of total translocations per cell were estimated as 0.1, 0.16 and 0.2 for the 4 applied doses illustrating a dose-response relationship for the doses: 1, 2 and 4 mg, whereas with the higher dose, 6 mg, an abrupt decrease was apparent (0.05). This study calls for concern regarding the possible genetic hazards this drug may impose upon human populations.

Use of a hybrid iterative reconstruction technique to reduce image noise and improve image quality in obese patients undergoing computed tomographic pulmonary angiography.

PubMed

Kligerman, Seth; Mehta, Dhruv; Farnadesh, Mahmmoudreza; Jeudy, Jean; Olsen, Kathryn; White, Charles

2013-01-01

To determine whether an iterative reconstruction (IR) technique (iDose, Philips Healthcare) can reduce image noise and improve image quality in obese patients undergoing computed tomographic pulmonary angiography (CTPA). The study was Health Insurance Portability and Accountability Act compliant and approved by our institutional review board. A total of 33 obese patients (average body mass index: 42.7) underwent CTPA studies following standard departmental protocols. The data were reconstructed with filtered back projection (FBP) and 3 iDose strengths (iDoseL1, iDoseL3, and iDoseL5) for a total of 132 studies. FBP data were collected from 33 controls (average body mass index: 22) undergoing CTPA. Regions of interest were drawn at 6 identical levels in the pulmonary artery (PA), from the main PA to a subsegmental branch, in both the control group and study groups using each algorithm. Noise and attenuation were measured at all PA levels. Three thoracic radiologists graded each study on a scale of 1 (very poor) to 5 (ideal) by 4 categories: image quality, noise, PA enhancement, and "plastic" appearance. Statistical analysis was performed using an unpaired t test, 1-way analysis of variance, and linear weighted κ. Compared with the control group, there was significantly higher noise with FBP, iDoseL1, and iDoseL3 algorithms (P<0.001) in the study group. There was no significant difference between the noise in the control group and iDoseL5 algorithm in the study group. Analysis within the study group showed a significant and progressive decrease in noise and increase in the contrast-to-noise ratio as the level of IR was increased (P<0.001). Compared with FBP, readers graded overall image quality as being higher using iDoseL1 (P=0.0018), iDoseL3 (P<0.001), and iDoseL5 (P<0.001). Compared with FBP, there was subjective improvement in image noise and PA enhancement with increasing levels of iDose. The use of an IR technique leads to qualitative and quantitative improvements in image noise and image quality in obese patients undergoing CTPA.

Association Between Media Dose, Ad Tagging, and Changes in Web Traffic for a National Tobacco Education Campaign: A Market-Level Longitudinal Study.

PubMed

Shafer, Paul R; Davis, Kevin C; Patel, Deesha; Rodes, Robert; Beistle, Diane

2016-02-17

In 2012, the US Centers for Disease Control and Prevention (CDC) launched Tips From Former Smokers (Tips), the first federally funded national tobacco education campaign. In 2013, a follow-up Tips campaign aired on national cable television networks, radio, and other channels, with supporting digital advertising to drive traffic to the Tips campaign website. The objective of this study was to use geographic and temporal variability in 2013 Tips campaign television media doses and ad tagging to evaluate changes in traffic to the campaign website in response to specific doses of campaign media. Linear regression models were used to estimate the dose-response relationship between weekly market-level television gross rating points (GRPs) and weekly Web traffic to the Tips campaign website. This relationship was measured using unique visitors, total visits, and page views as outcomes. Ad GRP effects were estimated separately for ads tagged with the Tips campaign website URL and 1-800-QUIT-NOW. In the average media market, an increase of 100 television GRPs per week for ads tagged with the Tips campaign website URL was associated with an increase of 650 unique visitors (P<.001), 769 total visits (P<.001), and 1255 total page views (P<.001) per week. The associations between GRPs for ads tagged with 1-800-QUIT-NOW and each Web traffic measure were also statistically significant (P<.001), but smaller in magnitude. Based on these findings, we estimate that the 16-week 2013 Tips television campaign generated approximately 660,000 unique visitors, 900,000 total visits, and 1,390,000 page views for the Tips campaign website. These findings can help campaign planners forecast the likely impact of targeted advertising efforts on consumers' use of campaign-specific websites.

Enrichment increases hippocampal neurogenesis independent of blood monocyte-derived microglia presence following high-dose total body irradiation.

PubMed

Ruitenberg, Marc J; Wells, Julia; Bartlett, Perry F; Harvey, Alan R; Vukovic, Jana

2017-06-01

Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche. This depressive effect of total body irradiation on adult neurogenesis was partially alleviated by exposure to enriched environment but not voluntary exercise, where mice were single-housed with unlimited access to a running wheel. Exposure to voluntary exercise, but not enriched environment, did lead to significant increases in microglia density in the granule cell layer of the hippocampus; our study shows that these changes result from local microglia proliferation rather than recruitment and infiltration of circulating Cx 3 cr1 +/gfp blood monocytes that subsequently differentiate into microglia-like cells. In summary, latent neural precursor cells remain present in the neurogenic niche of the adult hippocampus up to 8 weeks following high-dose total body irradiation. Environmental enrichment can partially restore the adult neurogenic process in this part of the brain following high-dose irradiation, and this was found to be independent of blood monocyte-derived microglia presence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Longitudinal trends of total white blood cell and differential white blood cell counts of atomic bomb survivors.

PubMed

Hsu, Wan-Ling; Tatsukawa, Yoshimi; Neriishi, Kazuo; Yamada, Michiko; Cologne, John; Fujiwara, Saeko

2010-01-01

In studying the late health effects of atomic-bomb (A-bomb) survivors, earlier findings were that white blood cell (WBC) count increased with radiation dose in cross-sectional studies. However, a persistent effect of radiation on WBC count and other risk factors has yet to be confirmed. The objectives of the present study were 1) to examine the longitudinal relationship between A-bomb radiation dose and WBC and differential WBC counts among A-bomb survivors and 2) to investigate the potential confounding risk factors (such as age at exposure and smoking status) as well as modification of the radiation dose-response. A total of 7,562 A-bomb survivors in Hiroshima and Nagasaki were included in this study from 1964-2004. A linear mixed model was applied using the repeated WBC measurements. During the study period, a secular downward trend of WBC count was observed. Radiation exposure was a significant risk factor for elevated WBC and differential WBC counts over time. A significant increase of WBC counts among survivors with high radiation dose (> 2 Gy) was detected in men exposed below the age of 20 and in women regardless of age at exposure. Effects on WBC of low dose radiation remain unclear, however. Cigarette smoking produced the most pronounced effect on WBC counts and its impact was much larger than that of radiation exposure.

Negative Impact of Total Body Irradiation on the Antitumor Activity of Rhenium-(I)-diselenoether.

PubMed

Collery, Philippe; Santoni, Francois; Mohsen, Ahmed; Mignard, Caroline; Desmaele, Didier

2016-11-01

It has been shown that a rhenium-(I)-diselenoether complex had significant antitumor activity in MDA-MB231 tumor-bearing mice after repeated oral or intraperitoneal administrations for 4 weeks at safe doses of 10 mg/kg/day. It has also been suggested that lower doses could be as effective as this dose. We, thus, tested two doses (5 and 10 mg/kg). The drug was orally administered daily by gavage for 4 weeks and for a further 2 weeks with or without 15 mg/kg paclitaxel treatment (intravenously, once a week). This experiment was performed in MDA-MB 231 tumor-bearing mice, as a model of resistant breast tumor. However, in contrast to previous studies, the mice were pretreated with total body irradiation to increase the tumor growth. These two doses were safe, even in combination with paclitaxel. The expected tumor regression was not observed with the rhenium-(I)-diselenoether complex, and there was even a significant increase of the tumor volume in mice treated with 10 mg/kg versus controls. No synergism was observed with paclitaxel. We comment on the possible negative impact of radiotherapy on the antitumor activity of the drug. Plasma and tumor rhenium and selenium concentrations are also reported. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Thermoluminescent response of LiF:Mg, Ti to low energy electrons

NASA Astrophysics Data System (ADS)

Mercado-Uribe, H.; Brandan, M. E.

2000-10-01

The dose response curve of LiF:Mg, Ti (TLD-100) exposed to 20 keV electrons from a scanning electron microscope has been measured. The total TL signal shows linear-supralinear behavior. The preliminary results indicate the onset of supralinearity at doses close to 70 Gy. The supralinear response is due to the increasingly important contribution of the high temperature peaks.

Changes in some physicochemical properties and fatty acid composition of irradiated meatballs during storage.

PubMed

Gecgel, Umit

2013-06-01

Meatball samples were irradiated using a (60)Co irradiation source (with the dose of 1, 3, 5 and 7 kGy) and stored (1, 2 and 3 weeks at 4°C) to appraise some physicochemical properties and the fatty acid composition. The physicochemical results showed no significant differences in moisture, protein, fat and ash content of meatballs because of irradiation. However, total acidity, peroxide and thiobarbituric acid (TBA) values increased significantly as a result of irradiation doses and storage period. The fatty acid profile in meatball samples changed with irradiation. While saturated fatty acids (C16:0, C17:0, C18:0, and C20:0) increased with irradiation, monounsaturated (C14:1, C15:1, C18:1, and C20:1) and polyunsaturated (C18:2, C18:3, and C22:2) fatty acids decreased with irradiation. Trans fatty acids (C16:1trans, C18:1trans, C18:2trans, C18:3trans) increased with increasing irradiation doses. Meatball samples irradiated at 7 kGy had the highest total trans fatty acid content. This research shows that some physicochemical properties and fatty acid composition of meatballs can be changed by gamma irradiation.

Effect of total body irradiation on late lung effects: hidden dangers.

PubMed

Johnston, Carl J; Manning, Casey; Hernady, Eric; Reed, Christina; Thurston, Sally W; Finkelstein, Jacob N; Williams, Jacqueline P

2011-08-01

In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge. C57BL/6J mice received total body irradiation (0.5-10 Gy) and were followed for 6-18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]). Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL]6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls. We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.

Enhanced coagulation for turbidity and Total Organic Carbon (TOC) removal from river Kansawati water.

PubMed

Narayan, Sumit; Goel, Sudha

2011-01-01

The objective of this study was to determine optimum coagulant doses for turbidity and Total Organic Carbon (TOC) removal and evaluate the extent to which TOC can be removed by enhanced coagulation. Jar tests were conducted in the laboratory to determine optimum doses of alum for the removal of turbidity and Natural Organic Matter (NOM) from river water. Various other water quality parameters were measured before and after thejar tests and included: UV Absorbance (UVA) at 254 nm, microbial concentrations, TDS, conductivity, hardness, alkalinity, and pH. The optimum alum dose for removal of turbidity and TOC was 20 mg/L for the sample collected in November 2009 and 100 mg/L for the sample collected in March 2010. In both cases, the dose for enhanced coagulation was significantly higher than that for conventional coagulation. The gain in TOC removal was insignificant compared to the increase in coagulant dose required. This is usual for low TOC (< 2 mg/L)--high alkalinity water. Other water samples with higher TOC need to be tested to demonstrate the effectiveness of enhanced coagulation.

Safe extensive tumescent liposuction with segmental infiltration of lower concentration lidocaine under monitored anesthesia care.

PubMed

Wang, Gang; Cao, Wei-Gang; Li, Sheng-Li; Liu, Li-Na; Jiang, Zhao-Hua

2015-01-01

Tumescent anesthesia makes it feasible to perform liposuction in an office setting. There are often patients who desire extensive liposuction on approximately 30% of total body surface area, which means the lidocaine total dose might be over the dosing recommendation. So the segmental infiltration is applied, although the concentration of lidocaine in tumescent fluid is gradually reduced to 0.0252%. Moreover, supplemental intravenous (IV) sedation using monitored anesthesia care is usually applied concurrently to help alleviate discomfort and pain of the patients during tumescent anesthetic infusion and fat extraction which in turn increases the risks of potential lidocaine toxicity due to possible drug interactions. This study was to demonstrate the safety of segmental infiltration of tumescent fluid with lower lidocaine concentration combined with IV sedation in extensive liposuction and determine whether the risk of lidocaine toxicity is increased in this protocol. Ten female patients who requested the extensive liposuction participated in the study. The targeted areas were divided into 2 segments and treated in turn in 1 session. Lidocaine (1600 mg) was infiltrated into the first segment, and approximately 928 mg lidocaine was subsequently infiltrated after accomplishment of the first segment operation. Serum levels of lidocaine were taken every 4 hours during the first 24 hours after the second infiltration. The average time of the procedure is 222 (33) minutes. The dose and total amount of lidocaine injected are 40.7 (5.8) mg/kg and 2528.2 (155.2) mg, respectively. The total volume of the infusates and aspirates are 9918.1 (494) and 6325 (1461.6) mL, respectively, the ratio of total infusates to total aspirates is 1.66 (0.45). The total aspirated fat and fluids are 3280 (1051.8) and 3045 (824.1) mL, respectively. The peak lidocaine levels [2.18 (0.63) μg/mL] occurred after 12 to 20 hours [16.4 (2.27) hours]. No significant correlation between dose per kilogram body weight or total dose of lidocaine infiltrated and its peak levels or time existed. The extensive liposuction covering the 30% total body surface areas was well tolerated by the patients under tumescent anesthesia in combination with the supplemental IV sedation. Our previous study on the fluid management has demonstrated the risk of hypovolemia or fluid overload is very low with this technique, although the patients who received only maintenance fluid (500 mL) in the operating room and could discharge and resume oral intake after 6 hours of recovery room stay. The adequate anesthesia support is available in our office-based setting with adequate recovery facilities in place. It has a high margin of safety, without increasing of lidocaine toxicity or adverse cardiopulmonary sequelae while using a segmental tumescent infiltration with lower concentration of lidocaine.

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

PubMed

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

2015-10-13

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

Dose-volume effects in pathologic lymph nodes in locally advanced cervical cancer.

PubMed

Bacorro, Warren; Dumas, Isabelle; Escande, Alexandre; Gouy, Sebastien; Bentivegna, Enrica; Morice, Philippe; Haie-Meder, Christine; Chargari, Cyrus

2018-03-01

In cervical cancer patients, dose-volume relationships have been demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The nodal control probability (NCP) according to dose/volume parameters was investigated. Patients with node-positive cervical cancer treated curatively with external beam radiotherapy (EBRT) and image-guided brachytherapy (IGABT) were identified. Nodal doses during EBRT, IGABT and boost were converted to 2-Gy equivalent (α/β = 10 Gy) and summed. Pathologic nodes were followed individually from diagnosis to relapse. Statistical analyses comprised log-rank tests (univariate analyses), Cox proportional model (factors with p ≤ 0.1 in univariate) and Probit analyses. A total of 108 patients with 254 unresected pathological nodes were identified. The mean nodal volume at diagnosis was 3.4 ± 5.8 cm 3 . The mean total nodal EQD2 doses were 55.3 ± 5.6 Gy. Concurrent chemotherapy was given in 96%. With a median follow-up of 33.5 months, 20 patients (18.5%) experienced relapse in nodes considered pathologic at diagnosis. Overall nodal recurrence rate was 9.1% (23/254). On univariate analyses, nodal volume (threshold: 3 cm 3 , p < .0001) and lymph node dose (≥57.5 Gy α/β10 , p = .039) were significant for nodal control. The use of simultaneous boost was borderline for significance (p = .07). On multivariate analysis, volume (HR = 8.2, 4.0-16.6, p < .0001) and dose (HR = 2, 1.05-3.9, p = .034) remained independent factors. Probit analysis combining dose and volume showed significant relationships with NCP, with increasing gap between the curves with higher nodal volumes. A nodal dose-volume effect on NCP is demonstrated for the first time, with increasing NCP benefit of additional doses to higher-volume nodes. Copyright © 2018 Elsevier Inc. All rights reserved.

Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy.

PubMed

Ruben, Jeremy D; Dally, Michael; Bailey, Michael; Smith, Robin; McLean, Catriona A; Fedele, Pasqual

2006-06-01

To investigate radiation necrosis in patients treated for glioma in terms of incidence, outcomes, predictive and prognostic factors. Records were reviewed for 426 patients followed up until death or for at least 3 years. Logistic regression analysis was performed to identify predictive and prognostic factors. Multivariate survival analysis was conducted using Cox proportional hazards regression. Separate analyses were performed for the subset of 352 patients who received a biologically effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who were at highest risk for radionecrosis. Twenty-one patients developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after 3 years. In the high-risk subset, radiation parameters confirmed as risk factors included total dose (p < 0.001), BED (p < 0.005), neuret (p < 0.001), fraction size (p = 0.028), and the product of total dose and fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed radionecrosis. Subsequent chemotherapy significantly increased the risk of cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR], 5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR, 5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the onset of necrosis (p = 0.013). The development of radionecrosis did not affect survival (p = 0.09). Cerebral necrosis is unlikely at doses below 50 Gy in 25 fractions. The risk increases significantly with increasing radiation dose, fraction size, and the subsequent administration of chemotherapy.

Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

PubMed

Park, Jung Duck; Chung, Yong Hyun; Kim, Choong Yong; Ha, Chang Soo; Yang, Seoung Oh; Khang, Hyun Soo; Yu, In Kyu; Cheong, Hae Kwan; Lee, Jong Seong; Song, Chang-Woo; Kwon, Il Hoon; Han, Jeong Hee; Sung, Jae Hyuck; Heo, Jeong Doo; Choi, Byung Sun; Im, Ruth; Jeong, Jayoung; Yu, Il Je

2007-09-01

Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

[Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

PubMed

Kojima, Shuji

2006-10-01

We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

HIV-1 Expression Within Resting CD4+ T Cells After Multiple Doses of Vorinostat

PubMed Central

Archin, Nancy M.; Bateson, Rosalie; Tripathy, Manoj K.; Crooks, Amanda M.; Yang, Kuo-Hsiung; Dahl, Noelle P.; Kearney, Mary F.; Anderson, Elizabeth M.; Coffin, John M.; Strain, Matthew C.; Richman, Douglas D.; Robertson, Kevin R.; Kashuba, Angela D.; Bosch, Ronald J.; Hazuda, Daria J.; Kuruc, Joann D.; Eron, Joseph J.; Margolis, David M.

2014-01-01

Background. A single dose of the histone deacetylase inhibitor vorinostat (VOR) up-regulates HIV RNA expression within resting CD4+ T cells of treated, aviremic human immunodeficiency virus (HIV)–positive participants. The ability of multiple exposures to VOR to repeatedly disrupt latency has not been directly measured, to our knowledge. Methods. Five participants in whom resting CD4+ T-cell–associated HIV RNA (rc-RNA) increased after a single dose of VOR agreed to receive daily VOR Monday through Wednesday for 8 weekly cycles. VOR serum levels, peripheral blood mononuclear cell histone acetylation, plasma HIV RNA single-copy assays, rc-RNA, total cellular HIV DNA, and quantitative viral outgrowth assays from resting CD4+ T cells were assayed. Results. VOR was well tolerated, with exposures within expected parameters. However, rc-RNA measured after dose 11 (second dose of cycle 4) or dose 22 (second dose of cycle 8) increased significantly in only 3 of the 5 participants, and the magnitude of the rc-RNA increase was much reduced compared with that after a single dose. Changes in histone acetylation were blunted. Results of quantitative viral outgrowth and other assays were unchanged. Conclusions. Although HIV latency is disrupted by an initial VOR dose, the effect of subsequent doses in this protocol was much reduced. We hypothesize that the global effect of VOR results in a refractory period of ≥24 hours. The optimal schedule for VOR administration is still to be defined. PMID:24620025

Engineering cord blood to improve engraftment after cord blood transplant

PubMed Central

Dave, Hema; Bollard, Catherine M.; Shpall, Elizabeth J.

2017-01-01

Umbilical cord blood transplant (CBT) has traditionally been associated with slower engraftment of neutrophils, delayed immune reconstitution and consequently higher risk of infections as compared with peripheral blood progenitor cell (PBPC) or bone marrow (BM) transplants. This is primarily due to low numbers of total nucleated cells (TNCs) and the naive nature of CB immune cells. The use of double unit CB transplant (DCBT) increases the total cell dose in the graft, but it still does not produce as rapid engraftment as seen with PBPC or even BM transplants. Herein, we discuss strategies to improve engraftment after CBT. We describe methods of (I) expansion of CB graft ex vivo to increase the total cell dose; and (II) enhancement of BM homing capability of CB progenitor cells; (III) ex vivo expansion of CB derived T cells for improving T cell function against viruses, tumors and protection from graft versus host disease (GVHD). With these novel approaches, engraftment after CBT is now reaching levels comparable to that of other graft types. PMID:28607915

Accurate low-dose iterative CT reconstruction from few projections by Generalized Anisotropic Total Variation minimization for industrial CT.

PubMed

Debatin, Maurice; Hesser, Jürgen

2015-01-01

Reducing the amount of time for data acquisition and reconstruction in industrial CT decreases the operation time of the X-ray machine and therefore increases the sales. This can be achieved by reducing both, the dose and the pulse length of the CT system and the number of projections for the reconstruction, respectively. In this paper, a novel generalized Anisotropic Total Variation regularization for under-sampled, low-dose iterative CT reconstruction is discussed and compared to the standard methods, Total Variation, Adaptive weighted Total Variation and Filtered Backprojection. The novel regularization function uses a priori information about the Gradient Magnitude Distribution of the scanned object for the reconstruction. We provide a general parameterization scheme and evaluate the efficiency of our new algorithm for different noise levels and different number of projection views. When noise is not present, error-free reconstructions are achievable for AwTV and GATV from 40 projections. In cases where noise is simulated, our strategy achieves a Relative Root Mean Square Error that is up to 11 times lower than Total Variation-based and up to 4 times lower than AwTV-based iterative statistical reconstruction (e.g. for a SNR of 223 and 40 projections). To obtain the same reconstruction quality as achieved by Total Variation, the projection number and the pulse length, and the acquisition time and the dose respectively can be reduced by a factor of approximately 3.5, when AwTV is used and a factor of approximately 6.7, when our proposed algorithm is used.

Effect of low dose, short-term creatine supplementation on muscle power output in elite youth soccer players.

PubMed

Yáñez-Silva, Aquiles; Buzzachera, Cosme F; Piçarro, Ivan Da C; Januario, Renata S B; Ferreira, Luis H B; McAnulty, Steven R; Utter, Alan C; Souza-Junior, Tacito P

2017-01-01

To determine the effects of a low dose, short-term Creatine monohydrate (Cr) supplementation (0.03 g.kg.d -1 during 14 d) on muscle power output in elite youth soccer players. Using a two-group matched, double blind, placebo-controlled design, nineteen male soccer players (mean age = 17.0 ± 0.5 years) were randomly assigned to either Cr ( N  = 9) or placebo ( N  = 10) group. Before and after supplementation, participants performed a 30s Wingate Anaerobic Test (WAnT) to assess peak power output (PPO), mean power output (MPO), fatigue index (FI), and total work. There were significant increases in both PPO and MPO after the Cr supplementation period ( P  ≤ 0.05) but not the placebo period. There were also significant increases in total work, but not FI, after the Cr supplementation and placebo periods ( P  ≤ 0.05). Notably, there were differences in total work between the Cr and placebo groups after ( P  ≤ 0.05) but not before the 14 d supplementation period. There is substantial evidence to indicate that a low-dose, short-term oral Cr supplementation beneficially affected muscle power output in elite youth soccer players.

Study design and early result of a phase I study of SABR for early-stage glottic cancer.

PubMed

Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

2018-05-14

Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Life threatening acute pneumonitis during low dose methotrexate treatment for rheumatoid arthritis: a case report and review of the literature.

PubMed Central

Ridley, M G; Wolfe, C S; Mathews, J A

1988-01-01

A patient is described with definite rheumatoid arthritis (RA) who developed life threatening acute pneumonitis after receiving a total dose of only 12.5 mg methotrexate (MTX). This complication has been previously described, but this is probably the lowest reported dose before development of pneumonitis in a patient with RA. The possible significance of this case is discussed in the light of recent reports suggesting an increased susceptibility of patients with RA to the pulmonary toxicity of MTX. Images PMID:3052323

Switching to instant black coffee modulates sodium selenite-induced cataract in rats.

PubMed

El Okda, E A; Mohamed, M M; Shaheed, E B; Abdel-Moemin, A R

2016-01-01

The influence of daily consumption of some common beverages on the development of cataract in rats was investigated. Total phenol content was determined in the beverages and an oral standardized dose of total phenols from each beverage was given to the treated rats. Weaned male albino rats were used and divided into five groups (n=7). Rats were fed Ain 93G and administered the standardized dose of instant coffee, black tea and hibiscus beverages for 30 days. On day 14 all rats were injected with a single dose of sodium selenite (Na2SeO3) 15 µmol/kg bodyweight, except the control groups NC (negative control, did not receive Na2SeO3) and PC (positive control, was already injected on day 1 of the study). The rats were continued on Ain 93G and the standardized dose for another 16 days. Positive control rats were used. Total phenols were 210, 40, and 44 mg/g dry weight gallic acid equivalent in black coffee, black tea, and hibiscus, respectively. Decreased levels (statistically significant P<0.05) of malondialdehyde, total nitric oxide, Ca-ATPase, tumor necrosis factor-α, interleukin-1β, superoxide dismutase, and conversely, increased levels (statistically significant P<0.05) of total protein, reduced glutathione, catalase were found in the lenses of the coffee group compared to PC. There are co-phenol substances in the instant black coffee that promoted coffee to be the most effective beverage.

Switching to instant black coffee modulates sodium selenite-induced cataract in rats

PubMed Central

El Okda, E. A.; Mohamed, M. M.; Shaheed, E. B.; Abdel-Moemin, A. R.

2016-01-01

The influence of daily consumption of some common beverages on the development of cataract in rats was investigated. Total phenol content was determined in the beverages and an oral standardized dose of total phenols from each beverage was given to the treated rats. Weaned male albino rats were used and divided into five groups (n=7). Rats were fed Ain 93G and administered the standardized dose of instant coffee, black tea and hibiscus beverages for 30 days. On day 14 all rats were injected with a single dose of sodium selenite (Na2SeO3) 15 µmol/kg bodyweight, except the control groups NC (negative control, did not receive Na2SeO3) and PC (positive control, was already injected on day 1 of the study). The rats were continued on Ain 93G and the standardized dose for another 16 days. Positive control rats were used. Total phenols were 210, 40, and 44 mg/g dry weight gallic acid equivalent in black coffee, black tea, and hibiscus, respectively. Decreased levels (statistically significant P<0.05) of malondialdehyde, total nitric oxide, Ca-ATPase, tumor necrosis factor-α, interleukin-1β, superoxide dismutase, and conversely, increased levels (statistically significant P<0.05) of total protein, reduced glutathione, catalase were found in the lenses of the coffee group compared to PC. There are co-phenol substances in the instant black coffee that promoted coffee to be the most effective beverage. PMID:27158251

Biodosimetry estimate for high-LET irradiation.

PubMed

Wang, Z Z; Li, W J; Zhi, D J; Jing, X G; Wei, W; Gao, Q X; Liu, B

2007-08-01

The purpose of this paper is to prepare for an easy and reliable biodosimeter protocol for radiation accidents involving high-linear energy transfer (LET) exposure. Human peripheral blood lymphocytes were irradiated using carbon ions (LET: 34.6 keV microm(-1)), and the chromosome aberrations induced were analyzed using both a conventional colcemid block method and a calyculin A induced premature chromosome condensation (PCC) method. At a lower dose range (0-4 Gy), the measured dicentric (dics) and centric ring chromosomes (cRings) provided reasonable dose information. At higher doses (8 Gy), however, the frequency of dics and cRings was not suitable for dose estimation. Instead, we found that the number of Giemsa-stained drug-induced G2 prematurely condensed chromosomes (G2-PCC) can be used for dose estimation, since the total chromosome number (including fragments) was linearly correlated with radiation dose (r = 0.99). The ratio of the longest and the shortest chromosome length of the drug-induced G2-PCCs increased with radiation dose in a linear-quadratic manner (r = 0.96), which indicates that this ratio can also be used to estimate radiation doses. Obviously, it is easier to establish the dose response curve using the PCC technique than using the conventional metaphase chromosome method. It is assumed that combining the ratio of the longest and the shortest chromosome length with analysis of the total chromosome number might be a valuable tool for rapid and precise dose estimation for victims of radiation accidents.

Influence of exposure and geometric parameters on absorbed doses associated with common neuro-interventional procedures.

PubMed

Safari, Mohammad Javad; Wong, Jeannie Hsiu Ding; Jong, Wei Loong; Thorpe, Nathan; Cutajar, Dean; Rosenfeld, Anatoly; Ng, Kwan Hoong

2017-03-01

The purpose of this study was to investigate the effects of routine exposure parameters on patient's dose during neuro-interventional radiology procedures. We scrutinized the routine radiological exposure parameters during 58 clinical neuro-interventional procedures such as, exposure direction, magnification, frame rate, and distance between image receptor to patient's body and evaluate their effects on patient's dose using an anthropomorphic phantom. Radiation dose received by the occipital region, ears and eyes of the phantom were measured using MOSkin detectors. DSA imaging technique is a major contributor to patient's dose (80.9%) even though they are used sparingly (5.3% of total frame number). The occipital region of the brain received high dose largely from the frontal tube constantly placed under couch (73.7% of the total KAP). When rotating the frontal tube away from under the couch, the radiation dose to the occipital reduced by 40%. The use of magnification modes could increase radiation dose by 94%. Changing the image receptor to the phantom surface distance from 10 to 40cm doubled the radiation dose received by the patient's skin at the occipital region. Our findings provided important insights into the contribution of selected fluoroscopic exposure parameters and their impact on patient's dose during neuro-interventional radiology procedures. This study showed that the DSA imaging technique contributed to the highest patient's dose and judicial use of exposure parameters might assist interventional radiologists in effective skin and eye lens dose reduction for patients undergoing neuro-interventional procedures. Copyright © 2017 Associazione Italiana di Fisica Medica. All rights reserved.

The predictive factors of α1-D/A adrenoceptor antagonist, naftopidil, dose increase therapy for male lower urinary tract symptoms caused by benign prostatic hyperplasia: INFORM study.

PubMed

Tanuma, Yasushi; Tanaka, Yoshinori; Takeyama, Ko; Okamoto, Tomoshi

2017-01-01

We evaluated the predictive factors which affect the efficacy of naftopidil 50 mg/day therapy and dose increase therapy to administration of 75 mg/day after an initial dose of 50 mg/day. A total of 92 patients with male lower urinary tract symptoms/benign prostatic hyperplasia were administrated naftopidil 50 mg/day for 4 weeks (50 mg therapy). At week 4, the patients were divided into an effective and an ineffective group (Group E and Group I, respectively). For further 4 weeks, the dosage of naftopidil was increased to 75 mg/day in all patients. At week 8, the patients of Group E and Group I were divided into an effective and an ineffective group (Group EE, Group EI, Group IE, and Group II, respectively). Postvoid residual (PVR) urine volume at baseline was a predictive factor for efficacy of 50 mg therapy. In Group E, change in International Prostate Symptom Score storage symptoms subscore from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. In Group I, change in maximum flow rate from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. The short term of naftopidil 50 mg therapy was ineffective for the patients who had large PVR. The predictive factor of this dose increase therapy might be a dynamic variable in 50 mg/day of dose period, but not a baseline variable at the time of 75 mg/day dosage starts.

Over-scanning in chest CT: Comparison of practice among six hospitals and its impact on radiation dose.

PubMed

Schwartz, Fides; Stieltjes, Bram; Szucs-Farkas, Zsolt; Euler, André

2018-05-01

Compare incidence of over-scanning in chest CT among six hospitals and impact on effective and organ effective radiation dose. Scout images of 600 chest CTs from six hospitals (A-F) were retrospectively reviewed using a radiation dose tracking software (RTS). Optimal scan range was determined and compared to the actual scan range. Incidence of cranial and caudal over-scanning was assessed and changes in total and organ effective dose were calculated. Descriptive statistics, Tukey- and Wilcoxon matched pairs test were applied. Simultaneous cranial and caudal over-scanning occurred in 29 of 600 scans (A = 0%, B = 1%, C = 12%, D = 3%, E = 11%, F = 2%). Effective radiation dose increased on average by 0.29 mSv (P < 0.001). Cranial over-scanning was observed in 45 of 600 scans (A = 0%, B = 8%, C = 2%, D = 15%, E = 17%, F = 3%) and increased organ effective dose by 0.35 mSv in the thyroid gland (P < 0.001). Caudal over-scanning occurred in 147 of 600 scans (A = 7%, B = 9%, C = 35%, D = 4%, E = 32%, F = 60%) and increased organ effective doses in the upper abdomen by up to 14% (P < 0.001 for all organs). Substantial differences in the incidence of over-scanning in chest CT exist among different hospitals. These differences result in excessive effective radiation dose and increased individual organ effective doses in patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Chronic toxicity of a mixture of chlorinated alkanes and alkenes in ICR mice.

PubMed

Wang, Fun-In; Kuo, Min-Liang; Shun, Chia-Tung; Ma, Yee-Chung; Wang, Jung-Der; Ueng, Tzuu-Huei

2002-02-01

The aim of this study was to determine the chronic toxicity of a mixture of chlorinated alkanes and alkenes (CA) consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene. These chlorinated organic solvents were present in the underground water near an electronic appliances manufactory in Taoyuan, Taiwan. Male and female weanling ICR mice were treated with low-, medium-, and high-dose CA mixtures in drinking water for 16 and 18 mo, respectively. A significant number of male mice treated with the high-dose CA mixture developed tail alopecia and deformation, which was not prominent in CA-treated female mice. Medium- and high-dose CA mixtures induced marginal increases of liver and lung weights, blood urea nitrogen, and serum creatinine levels in male mice. In female mice, the high-dose CA mixture increased liver, kidney, and uterus and ovary total weights, without affecting serum biochemistry parameters. CA mixtures had no effects on the total glutathione content or the level of glutathione S-transferase activity in the livers and kid- neys of male and female mice. Treatments with CA mixtures produced a trend of increasing frequency of hepatocelluar neoplasms in male mice, compared to male and female controls and CA-treated female mice. The high-dose CA mixture induced a significantly higher incidence of mammary adenocarcinoma in female mice. The calculated odds ratios of mammary adenocarcinoma in female mice induced by low-, medium-, and high-dose CA mixtures were 1.14, 1.37, and 3.53 times that of the controls, respectively. The low-dose CA mixture induced a higher incidence of cysts and inflammation in and around the ovaries. This study has demonstrated that the CA mixture is a potential carcinogen to male and female mice. These animal toxicology data may be important in assessing the health effects of individuals exposed to the CA mixture.

Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in human lymphocytes in vitro.

PubMed

Yilmaz, Dilek; Teksoy, Ozgun; Bilaloglu, Rahmi; Çinkilic, Nilufer

2016-01-01

Naringin is a flavonoid found in grapefruit and other citrus fruits that shows antioxidant activity. The aim of the present study was to determine the anti-genotoxic and protective effects of naringin on the chemotherapeutic/radiomimetic agent bleomycin (BLM) in human blood lymphocyte cultures in vitro using micronucleus test and chromosomal aberrations (CA) assay. We tested the three doses of naringin (1, 2, 3 µg/mL) and a single dose of BLM (20 µg/mL). BLM significantly increased the total CAs and micronucleus frequency at a concentration of 20 µg/mL. Naringin did not show any toxicity in doses of 1, 2, and 3 µg/mL. Combined treatments of BLM and naringin (2 and 3 µg/mL) significantly reduced micronucleus formation. Naringin dose-dependently decreased the total chromosome aberrations frequency induced by BLM. These results indicate that naringin could prevent BLM (20 µg/mL)-induced genotoxicity.

Evaluation of the mutagenicity of alkylating agents, methylnitrosourea and temozolomide, using the rat Pig-a assay with total red blood cells or reticulocytes.

PubMed

Muto, Shigeharu; Yamada, Katsuya; Kato, Tatsuya; Ando, Masamitsu; Inoue, Yoshimi; Iwase, Yumiko; Uno, Yoshifumi

2016-11-15

A collaborative study of the endogenous phosphatidylinositol glycan class A (Pig-a) gene mutation assay was conducted by the Japanese Environmental Mutagen Society/Mammalian Mutagenicity Study Group with a single-dosing regimen of test chemicals administered to male rats. As a part of the study, two DNA alkylating agents, methylnitrosourea (MNU) and temozolomide (TMZ), were dosed by single oral gavage at 25, 50, and 100mg/kg body weight. Pig-a mutant analysis of total red blood cells (RBCs; RBC Pig-a assay) and reticulocytes (RETs; PIGRET assay) was performed on Days 8, 15 and 29 after the administration. Both chemicals increased Pig-a mutants among RBCs and RETs with dose dependency on all days examined. The mutant frequencies were higher among RETs compared with RBCs, indicating that the PIGRET assay could detect mutagenicity more sensitively than the RBC Pig-a assay after a single dose of test chemicals. Copyright © 2016 Elsevier B.V. All rights reserved.

Electron beam initiated modification of acrylic elastomer in presence of polyfunctional monomers

NASA Astrophysics Data System (ADS)

Vijayabaskar, V.; Bhattacharya, S.; Tikku, V. K.; Bhowmick, Anil K.

2004-12-01

The structural changes of an acrylic rubber (ACM) in presence and absence of polyfunctional monomers like trimethylolpropane triacrylate, tripropyleneglycol diacrylate, trimethylolmethane tetraacrylate and trimethylolpropane trimethacrylate at different doses of electron beam (EB) irradiations were investigated with the help of FTIR spectroscopy (in the attenuated total reflectance mode) and sol-gel analysis. As the radiation dose increases, the concentration of carbonyl group increases in the ACM rubber due to aerial oxidation. This is corroborated from the increase in the absorbance values at 1734 and 1160 cm -1, which are due to carbonyl and C-O-C stretching frequencies, respectively. The increase in crosslinking is revealed by the increase in percentage gel content with radiation dose. The lifetime of spurs formed and the critical dose, an important criterion for overlapping of spurs have been determined for both grafted and ungrafted ACM rubber using a mathematical model. The predominance of crosslinking by electronic stopping with energetic EB projectile and the increase in effective radius of crosslinking have also been verified by this model. The doses at which the synergistic occurrence of both dislinking and endlinking steps originate have been calculated using linear energy transfer of EB. The ratio of scissioning to crosslinking for ACM rubber has been determined by using Charlesby-Pinner equation. The mechanical properties have been studied for different modified and unmodified systems and the tensile strength is found to increase with grafting of polyfunctional monomers.

Nandrolone androgenic hormone presents genotoxic effects in different cells of mice.

PubMed

do Carmo, Carolina Almeida; Gonçalves, Álvaro Luiz Martini; Salvadori, Daisy Maria Fávero; Maistro, Edson Luis

2012-10-01

Nandrolone is an androgenic-anabolic steroid (AAS) with diverse medical applications but taken indiscriminately by some to rapidly increase muscle mass. The aim of this study was to evaluate the genotoxic and clastogenic potential of nandrolone (deca-durabolin®) in vivo in different cells of mice, using the comet assay and micronucleus test, respectively. The animals received subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg⁻¹ body weight). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE-NCE ratio). The results showed a significant dose-related increase in the frequency of DNA damage in leukocytes, liver, bone marrow, brain and testicle cells at the three tested doses and a significant increase of the micronucleated polychromatic erythrocytes at all tested doses. Under our experimental conditions, the nandrolone steroid hormone showed genotoxic and clastogenic effects when administered subcutaneously to mice. Copyright © 2011 John Wiley & Sons, Ltd.

Heavy-ion-induced sucrose radicals investigated using EPR and UV spectroscopy

PubMed Central

Nakagawa, Kouichi; Karakirova, Yordanka; Yordanov, Nicola D.

2015-01-01

The potential use of a sucrose dosimeter for estimating both linear energy transfer (LET) and the absorbed dose of heavy ion and X-ray radiation was investigated. The stable free radicals were produced when sucrose was irradiated with heavy ions, such as helium, carbon, silicon and neon ions, and when the X-ray radiation was similar to the obtained electron paramagnetic resonance (EPR) spectra, which were ∼7 mT wide and composed of several hyperfine structures. In addition, the total spin concentration resulting from heavy-ion irradiation increased linearly as the absorbed dose increased, and decreased logarithmically as the LET increased. These empirical relations imply that the LET at a certain dose can be determined from the spin concentration. For sucrose and alanine, both cross-sections following C-ion irradiation with a 50 Gy dose were ∼1.3 × 10−12 [μm2], taking into account the molecular size of the samples. The values of these cross-sections imply that multiple ionizing particles were involved in the production of stable radicals. Furthermore, UV absorbance at 267 nm of an aqueous solution of irradiated sucrose was found to linearly increase with increasing absorbed dose. Therefore, the EPR and UV results suggest that sucrose can be a useful dosimeter for heavy-ion irradiation. PMID:25480828

The total ozone and UV solar radiation over Stara Zagora, Bulgaria

NASA Astrophysics Data System (ADS)

Mendeva, B.; Gogosheva, Ts.; Petkov, B.; Krastev, D.

Direct ground-based UV measurements and the total ozone content (TOC) over Stara Zagora, Bulgaria are presented. The observations are conducted by a scanning spectrophotometer, which measures the direct solar radiation in the range 290 - 360 nm with 1 nm resolution. For the time period 1998 -- 2003 the TOC data show seasonal variations, typical for the middle latitudes -- maximum in the spring and minimum in the autumn. The comparison of these TOC ground-based data to TOC satellite-borne data from the Global Ozone Monitoring Experiment (GOME) shows a seasonal dependence of the differences between the ground-based and satellite data. The relation between the UV radiation and TOC is investigated. Clear negative relationship is recognized between the total ozone and the irradiance of the wavelength 305 nm. The opposition of the two variables is significant ( r = - 0,62 ± 0,18) at 98 % confidence level. Yet, for 325 nm it is almost independent with the total ozone. The dependence of the UV-B radiation on the solar zenith angle at given TOC is also analyzed. A decrease of all wavelengths intensities with increase of the solar zenith angle is obtained but with different rate for each of them. The direct sun UV doses for some specific biological effects (erythema and eyes) are obtained as the integral in the wavelength interval 290-330 nm of the measured UV solar spectrum, weighted with an action spectrum, typical for each effect. The estimation of the radiation amplification factor RAF shows that the ozone reduction by 1% increases the erythemal dose by 2,3 %.The eye-damaging doses are more influenced by the TOC changes and in this case RAF=-2,7%. The amount of these biological doses is in a direct ratio with the solar altitude over the horizon. This dependence is more markedly expressed at lower total ozone content in the atmosphere.

Maximizing Tumor Immunity With Fractionated Radiation

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

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

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

Use of neuromuscular blockers and neostigmine for general anesthesia and its association with neuraxial blockade

PubMed Central

Santos, Filipe Nadir Caparica; Braga, Angélica de Fátima de Assunção; Junqueira, Fernando Eduardo Feres; Bezerra, Rafaela Menezes; de Almeida, Felipe Ferreira; Braga, Franklin Sarmento da Silva; Carvalho, Vanessa Henriques

2017-01-01

Abstract This research aimed to assess the use of neuromuscular blockers (NMB) and its reversal, associated or not with neuraxial blockade, after general anesthesia. This retrospective study analyzed 1295 patients that underwent surgery with general anesthesia at Prof. Dr. José Aristodemo Pinotti Hospital in 2013. The study included patients aged >1 year, with complete, readable medical charts and anesthetic records. Rocuronium (ROC) was the most used NMB (96.7%), with an initial dose of 0.60 (0.52–0.74) mg/kg and total dose of 0.38 (0.27–0.53) mg/kg/h. In 24.3% of the cases, neuraxial blockade was associated with a significantly longer anesthesia (P < .001) than in cases without neuraxial block, regardless of technique (total intravenous (TIV) vs intravenous and inhalational (IV+IN)). In 71.9% of the cases, a single dose of NMB was used. Patients under TIV general anesthesia associated with neuraxial blockade had a lower total dose of ROC (mg/kg/h) in comparison with TIV GA alone (0.30 (0.23–0.39) and 0.42 (0.30–0.56) mg/kg/h, respectively, P < .001). The same was observed for patients under IV+IN GA (0.32 (0.23–0.41) and 0.43 (0.31–0.56) mg/kg/h, respectively, P < .001). The duration of anesthesia was longer according to increasing number of additional NMB doses (P < .001). Dose of neostigmine was 2.00 (2.00–2.00) mg or 29.41 (25.31–33.89) μg/kg. The interval between neostigmine and extubation was >30 minutes in 10.9% of cases. The most widely used NMB was ROC. Neuroaxial blockade (spinal or epidural) was significantly associated with reduced total dose of ROC (mg/kg/h) during general anesthesia, even in the absence of neuromuscular monitoring and regardless of general anesthetic technique chosen. In most cases, neostigmine was used to reverse neuromuscular block. The prolonged interval between neostigmine and extubation (>30 minutes) was neither associated with total doses of ROC or neostigmine, nor with the time of NMB administration. This study corroborates the important role of quantitative neuromuscular monitors and demonstrates that neuraxial blockade is associated with reduced total ROC dose. Further studies are needed to evaluate the possible role of neuraxial blockade in reducing the incidence of postoperative residual curarization. PMID:28658142

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

Pharmacokinetics of paracetamol and its metabolites in women at delivery and post‐partum

PubMed Central

Kulo, Aida; Peeters, Mariska Y.; Allegaert, Karel; Smits, Anne; de Hoon, Jan; Verbesselt, Rene; Lewi, Liesbeth; van de Velde, Marc; Knibbe, Catherijne A. J.

2013-01-01

Aim A recent report on intravenous (i.v.) paracetamol pharmacokinetics (PK) showed a higher total clearance in women at delivery compared with non‐pregnant women. To describe the paracetamol metabolic and elimination routes involved in this increase in clearance, we performed a population PK analysis in women at delivery and post‐partum in which the different pathways were considered. Methods Population PK parameters using non‐linear mixed effect modelling were estimated in a two‐period PK study in women to whom i.v. paracetamol (2 g loading dose followed by 1 g every 6 h up to 24 h) was administered immediately following Caesarean delivery and in a subgroup of the same women to whom single 2 g i.v.loading dose was administered 10–15 weeks post‐partum. Results Population PK analysis was performed based on 255 plasma and 71 urine samples collected in 39 women at delivery and in eight of these 39 women 12 weeks post‐partum. Total clearance was higher in women at delivery compared with 12th post‐partum week (21.1 vs. 11.7 l h−1) due to higher clearances to paracetamol glucuronide (11.6 vs. 4.76 l h−1), to oxidative metabolites (4.95 vs. 2.77 l h−1) and of unchanged paracetamol (1.15 vs. 0.75 l h−1). In contrast, there was no difference in clearance to paracetamol sulphate. Conclusion The increased total paracetamol clearance at delivery is caused by a disproportional increase in glucuronidation clearance and a proportional increase in clearance of unchanged paracetamol and in oxidation clearance, of which the latter may potentially limit further dose increase in this patient group. PMID:22845052

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation.

PubMed

Sanzari, Jenine K; Cengel, Keith A; Wan, X Steven; Rusek, Adam; Kennedy, Ann R

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure.

Acute hematological effects in mice exposed to the expected doses, dose-rates, and energies of solar particle event-like proton radiation

NASA Astrophysics Data System (ADS)

Sanzari, Jenine K.; Cengel, Keith A.; Steven Wan, X.; Rusek, Adam; Kennedy, Ann R.

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during an SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hours post-radiation exposure.

Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

PubMed

Wang, Linlin; Wang, Tingting; Li, Haobo; Liu, Qing; Zhang, Zhongjun; Xie, Wanli; Feng, Yinglu; Socorburam, Tumenjavkhlan; Wu, Gui; Xia, Zhengyuan; Wu, Qingping

2016-01-01

Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP), mixed lineage kinase domain-like protein (MLKL), total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI) staining. Levels of TNF-a, Interleukin (IL)-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO) activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg) -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg) -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose LPS- induced severe ARDS in mice.

Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice

PubMed Central

Li, Haobo; Liu, Qing; Zhang, Zhongjun; Xie, Wanli; Feng, Yinglu; Socorburam, Tumenjavkhlan; Wu, Gui; Xia, Zhengyuan; Wu, Qingping

2016-01-01

Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP), mixed lineage kinase domain-like protein (MLKL), total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI) staining. Levels of TNF-a, Interleukin (IL)-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO) activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg) -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg) -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose LPS- induced severe ARDS in mice. PMID:27195494

Red marrow and blood dosimetry in 131I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results

NASA Astrophysics Data System (ADS)

Giostra, A.; Richetta, E.; Pasquino, M.; Miranti, A.; Cutaia, C.; Brusasco, G.; Pellerito, R. E.; Stasi, M.

2016-06-01

Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher 131I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from 131I activity in the blood and the dose from 131I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher 131I activities to be safely used in-treatment.

Enhancing the biological degradability of sulfamethoxazole by ionizing radiation treatment in aqueous solution

NASA Astrophysics Data System (ADS)

Sági, Gyuri; Kovács, Krisztina; Bezsenyi, Anikó; Csay, Tamás; Takács, Erzsébet; Wojnárovits, László

2016-07-01

Changes of biodegradability and toxicity were followed up on aqueous solutions of sulfamethoxazole (SMX), during ionizing radiation treatment. The biodegradability of SMX (0.1 mmol dm-3) was specified by five-day biological oxygen demand (BOD5), using municipal activated sludge, and the results showed an improvement with applying only 0.4 kGy dose. BOD5 further increased with prolonged irradiation, indicating a conversion of SMX, a non-biodegradable compound, to biologically treatable substances. At 2.5 kGy dose, the BOD5/COD ratio increased from 0 to 0.16. The total organic carbon (TOC) content showed a decrease of only 15% at this point, thus high degree of mineralization is not necessary to make SMX digestible for the low concentrations of microorganisms used during BOD5 measurements. Increment in respiration inhibition of municipal activated sludge was observed with increasing the dose. The EC50 values showed a decrease of one order of magnitude when changing the dose from 0.4 kGy to 2.5 kGy. The increase of inhibition and formation of H2O2 showed a strong correlation.

Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice.

PubMed

Henry, Scott P; Levin, Arthur A; White, Kimber; Mennear, John H

2006-12-01

ISIS 2302 is a phosphorothioate oligonucleotide designed to inhibit human ICAM-1 and is intended for treatment of inflammatory diseases. Molecules of this class are known to elicit pro-inflammatory effects, and immunotoxicity studies were performed in mice to elucidate the nature of effects of ISIS 2302 on mammalian immune function. ISIS 2302 (1, 5, 20, or 50 mg/kg/dose) was administered intravenously every other day for 27 days. The pro-inflammatory properties of the drug were observed at doses > or = 20 mg/kg. A dose-dependent increase in spleen weight was associated with increased absolute splenocyte and B-lymphocyte counts after the 50 mg/kg/dose regimen. The mitogenic response of B-lymphocytes to bacterial lipopolysaccharide was increased after the 20 and 50 mg/kg/doses but antibody-forming cell activities remained unchanged. Total serum IgG concentration was decreased after the 20 and 50 mg/kg/dose regimens but IgM titers were unchanged. Increases in IL-6, IL-12, and MCP-1 as well as NK cell activity were observed after administration of 20 and 50 mg/kg/dose. Cytotoxic T-lymphocyte activity was decreased by the 50 mg/kg/dose regimen. Other changes in immune function were not observed in ISIS 2302-dosed mice. ISIS 3082, a murine active ICAM-1 inhibitor, was used to demonstrate the anti-inflammatory activity of ICAM-1 inhibition in the 2,4-dinitrofluorobenzene-induced contact sensitization model. Intravenous administration of 1 mg/kg of ISIS 3082 every other day for 27 days was unequivocally anti-inflammatory in the contact sensitization test. The results of these experiments support the conclusion that the prophlogistic effects of ISIS 2302 in mice are observed only at suprapharmacologic doses.

Main Sources and Doses of Space Radiation during Mars Missions and Total Radiation Risk for Cosmonauts

NASA Astrophysics Data System (ADS)

Mitrikas, Victor; Aleksandr, Shafirkin; Shurshakov, Vyacheslav

This work contains calculation data of generalized doses and dose equivalents in critical organs and tissues of cosmonauts produces by galactic cosmic rays (GCR), solar cosmic rays (SCR) and the Earth’s radiation belts (ERB) that will impact crewmembers during a flight to Mars, while staying in the landing module and on the Martian surface, and during the return to Earth. Also calculated total radiation risk values during whole life of cosmonauts after the flight are presented. Radiation risk (RR) calculations are performed on the basis of a radiobiological model of radiation damage to living organisms, while taking into account reparation processes acting during continuous long-term exposure at various dose rates and under acute recurrent radiation impact. The calculations of RR are performed for crewmembers of various ages implementing a flight to Mars over 2 - 3 years in maximum and minimum of the solar cycle. The total carcinogenic and non-carcinogenic RR and possible life-span shortening are estimated on the basis of a model of the radiation death probability for mammals. This model takes into account the decrease in compensatory reserve of an organism as well as the increase in mortality rate and descent of the subsequent lifetime of the cosmonaut. The analyzed dose distributions in the shielding and body areas are applied to making model calculations of tissue equivalent spherical and anthropomorphic phantoms.

Comparison of U.S. Environmental Protection Agency's CAP88 PC Versions 3.0 and 4.0.

PubMed

Jannik, Tim; Farfan, Eduardo B; Dixon, Ken; Newton, Joseph; Sailors, Christopher; Johnson, Levi; Moore, Kelsey; Stahman, Richard

2015-08-01

The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (U.S. EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with U.S. EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within its corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective dose. A detailed summary for select radionuclides of concern at the Savannah River Site (60Co, 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes U.S. EPA made in the external ground shine calculations.

Treatment of traumatic infra orbital nerve paresthesia

PubMed Central

Lone, Parveen Akhter; Singh, R. K.; Pal, U. S.

2012-01-01

This study was done to find out the role of topiramate therapy in infraorbital nerve paresthesia after miniplate fixation in zygomatic complxex fractures. A total 2 cases of unilateral zygomatic complex fracture, 2-3 weeks old with infra orbital nerve paresthesia were slected. Open reduction and plating was done in frontozygomaticregion. Antiepileptic drug tab topiramate was given in therapeutic doses and dose was increased slowly until functional recovery was noticed. PMID:23833503

Outreach hepatitis B vaccination of female sex workers in central-west Brazil: immunization status, compliance, and immune response.

PubMed

Carneiro, Luciene Moraes; Mousquer, Gina Jonasson; Pinheiro, Raquel Silva; Castro, Ana Rita Coimbra Motta; França, Divânia Dias Da Silva; Caetano, Karlla Antonieta Amorim; Carneiro, Megmar Aparecida dos Santos; Martins, Regina Maria Bringel; Matos, Marcos André de; Castro, Lisie; Rezende, Grazielli; Teles, Sheila Araujo

2014-01-01

To evaluate the hepatitis B immunization status of female sex workers (FSWs) in Central-West Brazil and to evaluate their compliance with and immune response to hepatitis B vaccination delivered using outreach strategies. A total of 721 FSWs recruited in 2 large cities in Central-West Brazil were interviewed and screened for the presence of hepatitis B virus (HBV) markers. Hepatitis B vaccine was offered to all women susceptible to HBV, using outreach strategies. The immune response of FSWs who received a full course of vaccine was assessed following the final vaccine dose. We found that 27.6% of FSWs, the majority of whom were aged 18 to 25 years, had serological evidence of previous hepatitis B vaccination. A total of 434 FSWs were eligible for vaccination, 389 (89.6%) of whom accepted the first hepatitis B vaccine dose. Of those, 64% received a second dose and 37.5% received all three doses. Through the outreach strategy, there was a 52.2% increase in the number of women who received the second dose and a 67% increase in the number who received the third dose. Of the 146 women who received a full course of vaccine, 105 accepted testing for quantitative anti-HBs (hepatitis B surface antibody) following the final vaccine dose, and 92.4% of those tested had developed protective levels of anti-HBs. Lower education level, workplace, and length of prostitution were predictors of full-vaccine acceptance. The present findings illustrate the benefits of using outreach strategies to overcome the difficulties of vaccinating hard-to-reach populations such as FSWs.

Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials.

PubMed

Kiernan, Michael S; Stevens, Susanna R; Tang, W H Wilson; Butler, Javed; Anstrom, Kevin J; Birati, Edo Y; Grodin, Justin L; Gupta, Divya; Margulies, Kenneth B; LaRue, Shane; Dávila-Román, Victor G; Hernandez, Adrian F; de Las Fuentes, Lisa

2018-03-01

Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240-11775) with median furosemide dose of 320 mg (220-480) compared with 8030 ml (6300-9915) and 840 mg (600-1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24-0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population. Copyright © 2018 Elsevier Inc. All rights reserved.

Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

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

Swisher-McClure, Samuel, E-mail: Swisher-Mcclure@uphs.upenn.edu; Leonard Davis Institute of Health Economics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Mitra, Nandita

Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Usingmore » multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.« less

Real-time colour pictorial radiation monitoring during coronary angiography: effect on patient peak skin and total dose during coronary angiography.

PubMed

Wilson, Sharon M; Prasan, Ananth M; Virdi, Amy; Lassere, Marissa; Ison, Glenn; Ramsay, David R; Weaver, James C

2016-10-10

The aim of this study was to evaluate whether a real-time (RT) colour pictorial radiation dose monitoring system reduces patient skin and total radiation dose during coronary angiography and intervention. Patient demographics, procedural variables and radiation parameters were recorded before and after institution of the RT skin dose recording system. Peak skin dose as well as traditionally available measures of procedural radiation dose were compared. A total of 1,077 consecutive patients underwent coronary angiography, of whom 460 also had PCI. Institution of the RT skin dose recording system resulted in a 22% reduction in peak skin dose after accounting for confounding variables. Radiation dose reduction was most pronounced in those having PCI but was also seen over a range of subgroups including those with prior coronary artery bypass surgery, high BMI, and with radial arterial access. This was associated with a significant reduction in the number of patients placed at risk of skin damage. Similar reductions in parameters reflective of total radiation dose were also demonstrated after institution of RT radiation monitoring. Institution of an RT skin dose recording reduced patient peak skin and total radiation dose during coronary angiography and intervention. Consideration should be given to widespread adoption of this technology.

Bayesian dose selection design for a binary outcome using restricted response adaptive randomization.

PubMed

Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I

2017-09-08

In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy within the context of limited resources. While the design is general enough to apply to many situations, future work is needed to address interim analyses and the incorporation of models for dose response.

Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

PubMed

Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

2018-01-05

In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of butaphosphan and cyanocobalamin on postpartum metabolism and milk production in dairy cows.

PubMed

Pereira, R A; Silveira, P A S; Montagner, P; Schneider, A; Schmitt, E; Rabassa, V R; Pfeifer, L F M; Del Pino, F A B; Pulga, M E; Corrêa, M N

2013-07-01

The aim of this study was to determine the effect of butaphosphan and cyanocobalamin (BTPC) supplementation on plasma metabolites and milk production in postpartum dairy cows. A total of fifty-two Holstein cows were randomly assigned to receive either: (1) 10 ml of saline (NaCl 0.9%, control group); (2) 1000 mg of butaphosphan and 0.5 mg of cyanocobalamin (BTPC1 group); and (3) 2000 mg of butaphosphan and 1.0 mg of cyanocobalamin (BTPC2 group). All cows received injections every 5 days from calving to 20 days in milk (DIM). Blood samples were collected every 15 days from calving until 75 DIM to determine serum concentration of glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), cholesterol, urea, calcium (Ca), phosphorus (P), magnesium (Mg), aminotransferase aspartate (AST) and γ-glutamyltransferase (GGT). The body condition score (BCS) and milk production were evaluated from calving until 90 DIM. Increasing doses of BTPC caused a linear reduction in plasma concentrations of NEFA and cholesterol. Supplementation of BTPC also reduced concentrations of BHB but it did not differ between the two treatment doses. Milk yield and milk protein had a linear increase with increasing doses of BTPC. A quadratic effect was detected for milk fat and total milk solids according to treatment dose, and BTPC1 had the lowest mean values. Concentrations of glucose, urea, P, Mg, AST, GGT, milk lactose and BCS were not affected by treatment. These results indicate that injections of BTPC during the early postpartum period can reduce NEFA and BHB concentrations and increase milk production in Holstein cows.

Morphine decreases social interaction of adult male rats, while THC does not affect it.

PubMed

Šlamberová, R; Mikulecká, A; Macúchová, E; Hrebíčková, I; Ševčíková, M; Nohejlová, K; Pometlová, M

2016-12-22

The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.

Effects of medetomidine on serum glucose in cattle calves.

PubMed

Tariq, Muhammad; Kalhoro, Amir Bukhsh; Sarwar, Mian Saeed; Khan, Hamayun; Ahmad, Shakoor; Hassan, Sayed Mubashir; Zahoor, Arshad

2016-05-01

An experimental study was carried out to compare physiological effects (serum glucose level) of medetomidine in Red Sindhi cattle calves at three different doses i.e. 8, 10 and 12µg/kg body weight intravenously. Medetomidine produced a dose dependent significant (P<0.01) increase in serum glucose level with a maximum increase observed at 30 minutes with 8µg/kg, 10μg/kg and 12μg/kg body weight respectively. Start of sedation, degree of sedation and total duration of sedation were all dose dependent and the values obtained were significantly (P<0.01) different from each other. It was observed that the sedation was rapid, deep and longer with the higher doses of medetomidine i.e. 12μg/kg. The results of the present study shows that medetomidine is a very effective and safest drug use as sedative for calves which in lower doses (8μg/kg) can be used as a pre-anesthetic and for restraining of the animal, while higher calculated doses (10μg/kg, 12μg/kg) can be used to execute the minor surgical procedures.

Improving the performance of membrane bioreactors by powdered activated carbon dosing with cost considerations.

PubMed

Yang, W; Paetkau, M; Cicek, N

2010-01-01

Effects of powdered activated carbon (PAC) dosing on the overall performance of membrane bioreactors (MBR) were investigated in two bench-scale submerged MBRs. Positive impacts of PAC dosing on membrane fouling and the removal of 17beta-estradiol (E2) and 17alpha-ethyinylestradiol (EE2) were demonstrated over a six-month stable operational period. PAC dosing in the MBR increased the removal rates of E2 and EE2 by 3.4% and 15.8%, respectively. The average soluble extracellular polymeric substances (EPS) and colloidal total organic carbon (TOC) concentrations in the PAC-MBR sludge was 60.1% and 61.8% lower than the control MBR sludge, respectively. Lower soluble EPS and colloidal TOC concentrations in the PAC-MBR sludge resulted in a slower rate of trans-membrane pressure (TMP) increase during MBRs operation, which could prolong the lifespan of membranes. Cost assessment showed that PAC dosing could reduce the operating cost for membrane cleaning and/or membrane replacement by about 25%. The operating cost for PAC dosing could be offset by the benefit from its reducing the cost for membrane maintenance.

Evaluation of ameliorative potential of supranutritional selenium on enrofloxacin-induced testicular toxicity.

PubMed

Rungsung, Soya; Khan, Adil Mehraj; Sood, Naresh Kumar; Rampal, Satyavan; Singh Saini, Simrat Pal

2016-05-25

The study was designed to assess the ameliorative potential of selenium (Se) on enrofloxacin-induced testicular toxicity in rats. There was a significant decrease in body weight and non-significant decrease in mean testicular weight of enrofloxacin treated rats. In enrofloxacin treated rats, total sperm count and viability decreased where as sperm abnormalities increased. Testicular histopathology revealed dose dependent dysregulation of spermatogenesis and presence of necrotic debris in seminiferous tubules which was marginally improved with Se. Enrofloxacin also produced a dose dependent decrease in testosterone level. The activity of testicular antioxidant enzymes decreased where as lipid peroxidation increased in a dose-dependent manner. Se supplementation partially restored oxidative stress and sperm damage and did not affect the plasma concentrations of enrofloxacin or ciprofloxacain. The results indicate that enrofloxacin produces a dose-dependent testicular toxicity in rats that is moderately ameliorated with supranutritional Se. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Feasibility study on an integrated AEC-grid device for the optimization of image quality and exposure dose in mammography

NASA Astrophysics Data System (ADS)

Kim, Kyo-Tae; Yun, Ryang-Young; Han, Moo-Jae; Heo, Ye-Ji; Song, Yong-Keun; Heo, Sung-Wook; Oh, Kyeong-Min; Park, Sung-Kwang

2017-10-01

Currently, in the radiation diagnosis field, mammography is used for the early detection of breast cancer. In addition, studies are being conducted on a grid to produce high-quality images. Although the grid ratio of the grid, which affects the scattering removal rate, must be increased to improve image quality, it increases the total exposure dose. While the use of automatic exposure control is recommended to minimize this problem, existing mammography equipment, unlike general radiography equipment, is mounted on the back of a detector. Therefore, the device is greatly affected by the detector and supporting device, and it is difficult to control the exposure dose. Accordingly, in this research, an integrated AEC-grid device that simultaneously performs AEC and grid functions was used to minimize the unnecessary exposure dose while removing scattering, thereby realizing superior image quality.

Influence of Al³⁺ addition on the flocculation and sedimentation of activated sludge: comparison of single and multiple dosing patterns.

PubMed

Wen, Yue; Zheng, Wanlin; Yang, Yundi; Cao, Asheng; Zhou, Qi

2015-05-15

In this study, the flocculation and sedimentation performance of activated sludge (AS) with single and multiple dosing of trivalent aluminum (Al(3+)) were studied. The AS samples were cultivated in sequencing batch reactors at 22 °C. The dosages of Al(3+) were 0.00, 0.125, 0.5, 1.0, and 1.5 meq/L for single dosing, and 0.1 meq/L for multiple dosing. Under single dosing conditions, as Al(3+) dosage increased, the zeta potential, total interaction energy, and effluent turbidity decreased, whereas the sludge volume index (SVI) increased, indicating that single Al(3+) dosing could enhance sludge flocculation, but deteriorate sedimentation. By comparison, adding an equal amount of Al(3+) through multiple dosing achieved a similar reduction in turbidity, but the zeta potential was higher, while the loosely bound extracellular polymeric substances (LB-EPS) content and SVI remarkably declined. Although the difference in the flocculation performances between the two dosing patterns was not significant, the underlying mechanisms were quite distinct: the interaction energy played a more important role under single dosing conditions, whereas multiple dosing was more effective in reducing the EPS content. Multiple dosing, which allows sufficient time for sludge restructuring and floc aggregation, could simultaneously optimize sludge flocculation and sedimentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

PubMed

Ye, Jian; Zhu, Rui; He, Xiaosheng; Feng, Yingying; Yang, Liangle; Zhu, Xiaoyan; Deng, Qifei; Wu, Tangchun; Zhang, Xiaomin

2014-01-01

Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with reduced heart rate variability (HRV), a strong predictor of cardiovascular diseases, but the mechanism is not well understood. We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function. HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6) and heat shock protein 70 (Hsp70) were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs) were measured by gas chromatography-mass spectrometry. We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05); and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP) and low frequency (LF) (Ptrend = 0.014 and 0.006, respectively). In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05), but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN), TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05). We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV. In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.

Association of Plasma IL-6 and Hsp70 with HRV at Different Levels of PAHs Metabolites

PubMed Central

He, Xiaosheng; Feng, Yingying; Yang, Liangle; Zhu, Xiaoyan; Deng, Qifei; Wu, Tangchun; Zhang, Xiaomin

2014-01-01

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with reduced heart rate variability (HRV), a strong predictor of cardiovascular diseases, but the mechanism is not well understood. Objectives We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function. Methods HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6) and heat shock protein 70 (Hsp70) were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs) were measured by gas chromatography-mass spectrometry. Results We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all P trend<0.05); and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP) and low frequency (LF) (P trend = 0.014 and 0.006, respectively). In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all P trend<0.05), but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN), TP and LF in the low-PAHs metabolites groups (all P trend<0.05). We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV. Conclusions In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups. PMID:24722336

Quantification of rat retinal growth and vascular population changes after single and split doses of proton irradiation: translational study using stereology methods

NASA Technical Reports Server (NTRS)

Mao, Xiao W.; Archambeau, John O.; Kubinova, Lucie; Boyle, Soames; Petersen, Georgia; Grove, Roger; Nelson, G. A. (Principal Investigator)

2003-01-01

This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (P<0.01) after 28 Gy given in single and split doses and after 20 Gy given as a split dose (P<0.05). Total vessel length in microvessel was significantly shortened at 20 and 28 Gy compared to that of controls (P<0.05). No evident dose recovery was observed in the endothelial populations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.

Oxidative stress in a model of toxic demyelination in rat brain: the effect of piracetam and vinpocetine.

PubMed

Abdel-Salam, Omar M E; Khadrawy, Yasser A; Salem, Neveen A; Sleem, Amany A

2011-06-01

We studied the role of oxidative stress and the effect of vinpocetine (1.5, 3 or 6 mg/kg) and piracetam (150 or 300 mg/kg) in acute demyelination of the rat brain following intracerebral injection of ethidium bromide (10 μl of 0.1%). ethidium bromide caused (1) increased malondialdehyde (MDA) in cortex, hippocampus and striatum; (2) decreased total antioxidant capacity (TAC) in cortex, hippocampus and striatum; (3) decreased reduced glutathione (GSH) in cortex and hippocampus (4); increased serum nitric oxide and (5) increased striatal (but not cortical or hippocampal) acetylcholinesterase (AChE) activity. MDA decreased in striatum and cortex by the lower doses of vinpocetine or piracetam but increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC. GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide. Vinpocetine and piracetam displayed variable effects on regional AChE activity.

Coffee component 3-caffeoylquinic acid increases antioxidant capacity but not polyphenol content in experimental cerebral infarction.

PubMed

Ruiz-Crespo, Silvia; Trejo-Gabriel-Galan, Jose M; Cavia-Saiz, Monica; Muñiz, Pilar

2012-05-01

Although coffee has antioxidant capacity, it is not known which of its bioactive compounds is responsible for it, nor has it been analyzed in experimental cerebral infarction. We studied the effect one of its compounds, 3-caffeoylquinic acid (3-CQA), at doses of 4, 25 and 100 μg on plasma antioxidant capacity and plasma polyphenol content, measuring the differences before and after inducing a cerebral infarction in an experimental rat model. We compared them with 3-caffeoylquinic-free controls. The increase in total antioxidant capacity was only higher than in controls in 3-CQA treated animals with the highest dose. This increase in antioxidant capacity was not due to an increase in polyphenols. No differences between the experimental and control group were found regarding polyphenol content and cerebral infarction volume. In conclusion, this increase in antioxidant capacity in the group that received the highest dose of 3-CQA was not able to reduce experimental cerebral infarction.

Nutrient digestibility and milk production responses to increasing levels of palmitic acid supplementation vary in cows receiving diets with or without whole cottonseed.

PubMed

Rico, J E; de Souza, J; Allen, M S; Lock, A L

2017-01-01

Our study evaluated the dose-dependent effects of a palmitic acid-enriched supplement in basal diets with or without the inclusion of whole cottonseed on nutrient digestibility and production responses of dairy cows. Sixteen Holstein cows (149 ± 56 days in milk) were used in a split plot Latin square design experiment. Cows were blocked by 3.5% fat-corrected milk (FCM) and allocated to a main plot receiving either a basal diet with soyhulls (SH, = 8) or a basal diet with whole cottonseed (CS, = 8) that was fed throughout the experiment. A palmitic acid-enriched supplement (PA 88.5% C16:0) was fed at 0, 0.75, 1.50, or 2.25% of ration DM in a replicated 4 × 4 Latin Square design within each basal diet group. Periods were 14 d with the final 4 d used for data collection. PA dose increased milk fat content linearly, and cubically affected yields of milk fat and 3.5% FCM. The PA dose did not affect milk protein and lactose contents, BW, and BCS, but tended to increase yields of milk, milk protein, and milk lactose. Also, PA dose reduced DMI and 16-carbon fatty acid digestibility quadratically, and increased 18-carbon fatty acid digestibility quadratically. There were no effects of basal diet on the yield of milk or milk components, but DMI tended to decrease in CS compared with SH, increasing feed efficiency (3.5% FCM/DMI). Compared with SH, CS diets increased yield of preformed milk fatty acids and 16-carbon fatty acid digestibility, and tended to decrease 18-carbon fatty acid digestibility. We observed basal diet × PA dose interactions for yields of milk and milk protein and for 16-carbon and total fatty acid digestibility, as well as tendency for yields of milk fat and 3.5% FCM. Also, there was a tendency for an interaction between basal diet and PA dose for NDF digestibility, which increased more for CS with increasing PA than for SH. PA dose linearly decreased digestibility of total fatty acids in SH diets but did not affect it in CS diets Results demonstrate that responses to PA dose are affected by the dietary basal diet. Additionally, the decrease in fatty acid digestibility only in the SH diets suggests that digestibility is impacted mainly by the profile of 16- and 18-carbon fatty acids reaching the duodenum. Under the dietary conditions evaluated, the yield of 3.5% FCM and milk fat were optimal when PA was fed at 1.5% of ration DM.

Immediate effects of 33 to 180 rad/min (60)Co exposure on performance and blood pressure in monkeys. Topical report

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

Bruner, A.

1976-09-01

Four groups of monkeys received 1000 rads (60)Co at 33, 50, 75, or 180 rad/min wholebody irradiation while performing a delayed matching-to-sample task. Systematic dose rate effects were observed on performance and blood pressure within the initial 20 min postirradiation. The incidence and severity of performance decrement (PD) increased with higher dose rate. The appearance of postirradiation hypotension was systematically delayed and its rate of fall prolonged as dose rate was lower. The hypotension likewise appeared less deep with lower dose rate exposure. Based on the calculated cumulative dose absorbed at the time of symptom appearance two coactive thresholds weremore » proposed to exist: a total dose threshold of approximately 300 rads (midbody measurement), and a dose rate threshold of about 25 rad/min.« less

The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child.

PubMed

Orr, J M; Farrell, K; Abbott, F S; Ferguson, S; Godolphin, W J

1983-01-01

The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.

Burosumab Therapy in Children with X-Linked Hypophosphatemia.

PubMed

Carpenter, Thomas O; Whyte, Michael P; Imel, Erik A; Boot, Annemieke M; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; Van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A

2018-05-24

X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).

Radhard optical patchcords and packaging for satellites using liquid crystal polymers

NASA Astrophysics Data System (ADS)

O'Riorden, S.; Mahapatra, A.

2017-11-01

There are many advantages to employing fiber optics for high capacity satellite communication. However, optical cables can be susceptible to high radiation, temperature extremes and vacuum environment. Any hardware used in these systems must be rugged, durable and immune to the detrimental effects of the aforementioned conditions. Standard COTS optical fiber will darken when exposed to high levels of radiation limiting the effectiveness of the communications system. Of particular concern to satellites in GEO are energetic electrons, bursts of heavy particles due to solar storms which can cause total dose and single event effects (SEE). Conventional fiber optic cables have several issues performing in high radiation environments. Linden has patented and developed a novel cable using an extruded layer of Liquid Crystal Polymer (LCP) applied to commercially available fiber. Total dose effects are minimized by shielding with Liquid Crystal Polymer jacketing. It is a simple, inexpensive way to increase the radiation shielding and mechanical performance of cables in satellites while concomitantly providing hermeticity and thus increased fatigue factor for optical glass. • LCPs exposed to 5000 Mrad dose of gamma rays retain in excess of 90% of their mechanical properties. • LCPs exposed to 1 Mrad radiation dose with energetic protons retain almost 100% of their mechanical strength. Tensile modulus increases with exposure to the radiation. • Weight for weight the proton absorbing power of LCP is 25% better than that of aluminum. We will present experimental data on radhard optical patchcords.

Lean methodology in i.v. medication processes in a children's hospital.

PubMed

L'Hommedieu, Timothy; Kappeler, Karl

2010-12-15

The impact of lean methodology in i.v. medication processes in a children's hospital was studied. Medication orders at a children's hospital were analyzed for 30 days to identify the specific times when most medications were changed or discontinued. Value-stream mapping was used to define the current state of preparation and identify non-value-added tasks in the i.v. medication preparation and dispensing processes. An optimization model was created using specific measurements to establish the optimal number of batches and batch preparation times of batches. Returned i.v. medications were collected for 7 days before and after implementation of the lean process to determine the impact of the lean process changes. Patient-days increased from 1,836 during the first collection period to 2,017 during the second, and the total number of i.v. doses dispensed increased from 8,054 to 9,907. Wasted i.v. doses decreased from 1,339 (16.6% of the total doses dispensed) to 853 (8.6%). With the new process, Nationwide Children's Hospital was projected to realize a weekly savings of $8,197 ($426,244 annually), resulting in a 2.6% reduction in annual drug expenditure. The annual savings is a conservative estimate, due to the 10% increase in patient-days after the lean collection period compared with baseline. The differences in wasted doses and their costs were significant (p < 0.05). Implementing lean concepts in the i.v. medication preparation process had a positive effect on efficiency and drug cost.

Varicella routine vaccination and the effects on varicella epidemiology – results from the Bavarian Varicella Surveillance Project (BaVariPro), 2006-2011

PubMed Central

2013-01-01

Background In 2004, routine varicella vaccination was recommended in Germany for children 11-14 months of age with one dose, and since 2009, with a second dose at 15-23 months of age. The effects on varicella epidemiology were investigated. Methods Data on varicella vaccinations, cases and complications were collected from annual parent surveys (2006-2011), monthly paediatric practice surveillance (Oct 2006 - Sep 2011; five varicella seasons) and paediatric hospital databases (2005-2009) in the area of Munich (about 238,000 paediatric inhabitants); annual incidences of cases and hospitalisations were estimated. Results Varicella vaccination coverage (1st dose) in children 18-36 months of age increased in two steps (38%, 51%, 53%, 53%, 66% and 68%); second-dose coverage reached 59% in the 2011 survey. A monthly mean of 82 (62%) practices participated; they applied a total of 50,059 first-dose and 40,541 second-dose varicella vaccinations, with preferential use of combined MMR-varicella vaccine after recommendation of two doses, and reported a total of 16,054 varicella cases <17 years of age. The mean number of cases decreased by 67% in two steps, from 6.6 (95%CI 6.1-7.0) per 1,000 patient contacts in season 2006/07 to 4.2 (95%CI 3.9-4.6) in 2007/08 and 4.0 (95%CI 3.6-4.3) in 2008/09, and further to 2.3 (95%CI 2.0-2.6) in 2009/10 and 2.2 (95%CI 1.9-2.5) in 2010/11. The decrease occurred in all paediatric age groups, indicating herd protection effects. Incidence of varicella was estimated as 78/1,000 children <17 years of age in 2006/07, and 19/1,000 in 2010/11. Vaccinated cases increased from 0.3 (95%0.2-0.3) per 1,000 patient contacts in 2006/07 to 0.4 (95%CI 0.3-0.5) until 2008/09 and decreased to 0.2 (95%CI 0.2-0.3) until 2010/11. The practices treated a total of 134 complicated cases, mainly with skin complications. The paediatric hospitals recorded a total of 178 varicella patients, including 40 (22.5%) with neurological complications and one (0.6%) fatality due to varicella pneumonia. Incidence of hospitalisations decreased from 7.6 per 100,000 children <17 years of age in 2005 to 4.3 in 2009, and from 21.0 to 4.7 in children <5 years of age. Conclusions Overall, the results show increasing acceptance and a strong impact of the varicella vaccination program, even with still suboptimal vaccination coverage. PMID:23815523

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

NASA Technical Reports Server (NTRS)

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

1989-01-01

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

Relationship between plant growth and cytological effect in root apical meristem after exposure of wheat dry seeds to carbon ion beams

NASA Astrophysics Data System (ADS)

Liu, Qingfang; Wang, Zhuanzi; Zhou, Libin; Qu, Ying; Lu, Dong; Yu, Lixia; Du, Yan; Jin, Wenjie; Li, Wenjian

2013-06-01

In order to analyze the relationship between plant growth and cytological effects, wheat dry seeds were exposed to various doses of 12C6+ beams and the biological endpoints reflecting plant growth and root apical meristem (RAM) activities were investigated. The results showed that most of the seeds were able to germinate normally within all dose range, while the plant survival rate descended at higher doses. The seedling growth including root length and seedling height also decreased significantly at higher doses. Mitotic index (MI) in RAM had no changes at 10 and 20 Gy and decreased obviously at higher doses and the proportion of prophase cells had the same trend with MI. These data suggested that RAM cells experienced cell cycle arrest, which should be responsible for the inhibition of root growth after exposure to higher doses irradiation. Moreover, various types of chromosome aberrations (CAs) were observed in the mitotic cells. The frequencies of mitotic cells with lagging chromosomes and these with anaphase bridges peaked around 60 Gy, while the frequencies of these with fragments increased as the irradiation doses increased up to 200 Gy. The total frequencies of mitotic cells with CAs induced by irradiation increased significantly with the increasing doses. The serious damage of mitotic chromosomes maybe caused cell cycle arrest or cell death. These findings suggested that the influences of 12C6+ beams irradiation on plant growth were related to the alternation of mitotic activities and the chromosomal damages in RAM.

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

PubMed Central

Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p < 0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p = 0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p = 0.036) but not at 5 (p > 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

Serum biomarkers for acute hepatotoxicity of Echis pyramidum snake venom in rats.

PubMed

Asmari, Abdulrahman K Al; Khan, Haseeb A; Banah, Faisal A; Buraidi, Ahmed A Al; Manthiri, Rajamohammed A

2015-01-01

Echis pyramidum is a venomous viper responsible for most cases of envenomation in Arabian Peninsula. We determined the acute phase (3-6 h) changes in serum markers of liver function including alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and bilirubin in adult male Sprague Dawley rats injected with Echis pyramidum venom (EPV) in the doses of 0.00 (control), 0.25, 0.50 and 1.00 mg/kg bodyweight. We also analyzed markers of oxidative stress including superoxide dismutase (SOD), catalase (CAT), total thiols (T-SH) and thiobarbituric acids reactive substances (TBARS) in liver. The results showed significant and dose- and time-dependent increases in serum ALT, ALP and GGT activities after a single injection of EPV. Serum bilirubin was significantly increased by medium and high doses of EVP after 3 h post-injection and then decreased at 6 h. The low dose of EPV neither affected the activity of SOD nor altered the levels of liver T-SH and TBARS, however, it significantly decreased the activity of CAT at 6 h post-injection of EPV. The medium dose of EPV significantly reduced liver SOD activity after 6 h whereas the high dose significantly reduced the SOD activity at 3 h and 6 h post-dosing. Both medium and high doses of EPV caused significant as well as dose- and time-dependent reductions in liver CAT activities. The high dose significantly reduced T-SH and increased TBARS in rat liver. Further studies are warranted to test the pharmacological potential of early phase antioxidant therapy for neutralizing the toxic effects of EPV.

Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts.

PubMed Central

Yun, K L; Fann, J I; Sokoloff, M H; Fong, L G; Sarris, G E; Billingham, M E; Miller, D C

1991-01-01

With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7.9 +/- 1.9 microns versus 34.0 +/- 13.0 microns, analysis of variance: p = 0.054). Low-dose safflower oil also had a slight, but nonsignificant, beneficial effect on graft vessel disease when compared to control rabbits. The same trends were observed in the degree of histologic rejection (0 = none to 3 = severe) in fish oil- and safflower oil-treated animals. Rejection score correlated weakly but significantly (p = 0.0001) with mean luminal occlusion (r = 0.52) and intimal thickness (r = 0.46). Therefore allograft coronary disease in this model appeared to exhibit an unfavorable, direct-dose response to fish oil and safflower oil, independent of effects on plasma lipids.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 2. PMID:1867523

Nicotine replacement prescribing trends in a large psychiatric hospital, before and after implementation of a hospital-wide smoking ban.

PubMed

Scharf, Deborah; Fabian, Tanya; Fichter-DeSando, Cecilia; Douaihy, Antoine

2011-06-01

We examined prescribing patterns for nicotine replacement therapies (NRTs) in a large psychiatric hospital, before and after the implementation of a smoking ban. We extracted 5 years of NRT utilization data from hospital pharmacy records. The ban went into effect on January 1, 2007. Data reflect NRT prescriptions from 2 years before and 3 years after the ban, and N = 30,908 total inpatient hospital admissions. The monthly rate of total NRT prescriptions increased after the ban from M = 254.25 (SD = 126.60) doses per month to M = 4,467.52 (SD = 1,785.87) doses per month (>1,700% increase, p < .0001). After the smoking ban, clinicians prescribed higher doses of transdermal (but not oral) NRT (Tukey, p < .0001). Comparisons of NRT prescribing across hospital units tentatively suggested that patients being treated on the substance use disorders unit were prescribed more doses of NRT, as well as higher doses of NRT compared with patients on other units. Analysis of trends over time showed no apparent downward trend for NRT usage during the 3 years following the smoking ban, suggesting that clinicians continued to treat nicotine dependence after smoking was restricted. Clinicians are more likely to identify and treat symptoms of nicotine withdrawal when smoking is restricted. Hospitals should consider monitoring prescriptions for NRT as part of their ongoing quality assurance practices so that patients receive aggressive treatment of nicotine withdrawal symptoms--an essential component of high-quality patient care.

Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography.

PubMed

Kassamali, Rahil H; Kim, Daniel H; Patel, Hiten; Raichura, Nitin; Hoey, Edward T D; Hodson, James; Hussain, Shahid

2014-10-01

The purpose of this study was to assess the safety of heart rate optimization by use of β-adrenergic blockade solely by the i.v. route before coronary CT angiography. The records of 679 patients undergoing CT coronary angiography after receiving i.v. β-adrenergic blockade were retrospectively analyzed. Health screening was completed before scanning, and heart rate was optimized by administration of i.v. metoprolol titrated to a maximum of 70 mg to achieve a heart rate less than 65 beats/min. The median i.v. dose was 20 mg (range, 5-70 mg). The 679 patients analyzed had a total of 10 complications (1.47%). Major complications, defined as not resolving with observation and analgesia alone, occurred in only three patients (0.44%). These complications included a second-degree atrioventricular block. A total of 299 patients (44.0%) needed more than 20 mg of i.v. metoprolol to achieve target heart rate. Only three patients needed the maximum i.v. dose of 70 mg metoprolol. Target heart rate was reached successfully in 666 patients (98.1%) with doses of less than 70 mg. This study did not show a statistically significant association between increasing complication frequency and increasing dose. This study showed that high doses of i.v. metoprolol can be used effectively and with a low rate of major complications to control heart rate before coronary CT angiography in correctly screened patients.

TU-CD-304-04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

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

Yi, B; Xu, H; Mutaf, Y

2015-06-15

Purpose: Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI. Methods: Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speedmore » of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements. Results: Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity-oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min. Conclusion: This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC-based thickness compensation and partial lung blocking are also possible.« less

A randomized, double-blind, placebo-controlled clinical trial on the treatment of vitamin D insufficiency in postmenopausal women

PubMed Central

Hansen, Karen E.; Johnson, R. Erin; Chambers, Kaitlin R.; Johnson, Michael G.; Lemon, Christina C.; Thuy Vo, Tien Nguyen; Marvdashti, Sheeva

2015-01-01

Importance Experts debate optimal 25(OH)D levels for musculoskeletal health. Objective To compare effects of placebo, low-dose and high-dose vitamin D on one-year changes in total fractional calcium absorption, bone mineral density, Timed-Up-and-Go and 5-sit-to-stand tests and muscle mass in postmenopausal women with vitamin D insufficiency. Design Randomized, double-blind, placebo-controlled, clinical trial conducted from May 2010 to August 2014. Setting Single-center trial conducted in Madison, Wisconsin. Participants 230 postmenopausal women ≤75 years old with baseline 25(OH)D levels 14-27 ng/mL and no osteoporosis. Intervention Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=76), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels ≥30 ng/mL. Main Outcome Measures One year change in total fractional calcium absorption using two stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed-Up-and-Go and 5-Sit-to-Stand tests, functional status (Health Assessment Questionnaire) and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of p-values to control the false discovery rate. Results After controlling for baseline absorption, calcium absorption increased 1% (10 mg/day) in the high-dose arm, but decreased by 2% in low-dose (p=0.005 vs. high-dose) and by 1.3% placebo (p=0.03 vs. high-dose) arms. We found no between-arm changes in spine, mean total hip, mean femoral neck or total body bone mineral density, trabecular bone score, muscle mass, 5-sit-to-stand or Timed-Up-and-Go test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity or functional status. Conclusion and Relevance High-dose vitamin D therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone mineral density, muscle function, muscle mass or falls. We found no data to support experts’ recommendations to maintain serum 25(OH)D levels ≥30 ng/mL in postmenopausal women. Instead, we found that low and high-dose vitamin D were equivalent to placebo, in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels <30 ng/mL. ClinicalTrials.gov.Identifier:NCT00933244 PMID:26237520

SU-E-T-357: Electronic Compensation Technique to Deliver Total Body Dose

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

Lakeman, T; Wang, I; Podgorsak, M

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient’s immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has conventionally been used to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern electronic compensation technique to more accurately and efficiently deliver dose to patients in need of TBI. Methods: Treatment plans utilizing electronic compensation to deliver a total body dose were created retrospectively for patients for whom CTmore » data had been previously acquired. Each treatment plan includes two, specifically weighted, pair of opposed fields. One pair of open, large fields (collimator=45°), to encompass the patient’s entire anatomy, and one pair of smaller fields (collimator=0°) focused only on the thicker midsection of the patient. The optimal fluence for each one of the smaller fields was calculated at a patient specific penetration depth. Irregular surface compensators provide a more uniform dose distribution within the smaller opposed fields. Results: Dose-volume histograms (DVH) were calculated for the evaluating the electronic compensation technique. In one case, the maximum body doses calculated from the DVH were reduced from the non-compensated 195.8% to 165.3% in the electronically compensated plans, indicating a more uniform dose with the region of electronic compensation. The mean body doses calculated from the DVH were also reduced from the non-compensated 120.6% to 112.7% in the electronically compensated plans, indicating a more accurate delivery of the prescription dose. All calculated monitor units were well within clinically acceptable limits. Conclusion: Electronic compensation technique for TBI will not substantially increase the beam on time while it can significantly reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.« less

Electronic compensation technique to deliver a total body dose

NASA Astrophysics Data System (ADS)

Lakeman, Tara E.

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been conventionally used to compensate for the varying thickness throughout the body in large-field TBI. The goal of this study is to pursue utilizing the modern electronic compensation technique to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the electronic compensation to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Each treatment plan includes two pair of parallel opposed fields. One pair of large fields is used to encompass the majority of the patient's anatomy. The other pair are very small open fields focused only on the thin bottom portion of the patient's anatomy, which requires much less radiation than the rest of the body to reach 100% of the prescribed dose. A desirable fluence pattern was manually painted within each of the larger fields for each patient to provide a more uniform distribution. Results: Dose-volume histograms (DVH) were calculated for evaluating the electronic compensation technique. In the electronically compensated plans, the maximum body doses calculated from the DVH were reduced from the conventionally-compensated plans by an average of 15%, indicating a more uniform dose. The mean body doses calculated from the electronically compensated DVH remained comparable to that of the conventionally-compensated plans, indicating an accurate delivery of the prescription dose using electronic compensation. All calculated monitor units were within clinically acceptable limits. Conclusion: Electronic compensation technique for TBI will not increase the beam on time beyond clinically acceptable limits while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.

Multi-year double cropping biochar field trials in Nepal: Finding the optimal biochar dose through agronomic trials and cost-benefit analysis.

PubMed

Pandit, Naba Raj; Mulder, Jan; Hale, Sarah E; Zimmerman, Andrew R; Pandit, Bishnu Hari; Cornelissen, Gerard

2018-05-15

Poor water and nutrient retention are the major soil fertility limitations in the low productivity agricultural soils of Nepal. The addition of biochar to these soils is one way these hindrances can be overcome. In the present study, six different biochar doses (control, 5 t ha -1 , 10 t ha -1 , 15 t ha -1 , 25 t ha -1 and 40 t ha -1 ) were applied to a moderately acidic silty loam soil from Rasuwa, Nepal and the effects on soil physicochemical properties and maize and mustard yield over three years (i.e., six cropping seasons), were investigated. Biochar addition did not show significant effects on maize and mustard grain yield in the first year, however significant positive effects (p < 0.01) were observed during the second and third years. During the second year, maize grain yield significantly increased by 50%, 47% and 93% and mustard grain yield by 96%, 128% and 134% at 15 t ha -1 , 25 t ha -1 and 40 t ha -1 of biochar respectively. A similar significant increase in yield of both crops was observed in the third year. Yields for both maize and mustard correlated significantly (p < 0.001) with plant available P, K + , pH, total OC%, CEC, base saturation, and increased as a function of biochar addition. On the basis of the measured crop yields for the various biochar doses, a cost-benefit analysis was carried out, and gross margin was calculated to optimize biochar dose for local farming practice. Total costs included financial cost (farm input, labor and biochar production cost), health cost and methane emission cost during biochar production. Health costs were a minor factor (<2% of total biochar preparation cost), whereas methane emission costs were significant (up to 30% of biochar cost, depending on the C price). Total income comprised sale of crops and carbon sequestration credits. The cost-benefit analysis showed that the optimal biochar application dose was 15 t ha -1 for all C price scenarios, increasing gross margin by 21% and 53%, respectively, for 0 and 42 US$ per ton CO 2 price scenarios. In the current situation, only the 0 US$ price scenario is realistic for rural farmers in Nepal, but this still gives benefits of biochar amendment, which are capped at a 15 t ha -1 biochar addition. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of ethanol on cerebral blood flow (CBF) and metabolism (CMRO2) in conscious sheep

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

Krasney, J.A.; Zubkov, B.; Iwamoto, J.

1991-03-11

A moderate dose of ethanol severely depresses CBF and CMRO2 in the awake sheep fetus. However, the effects of ethanol on CBF and CMRO2 in the adult are unclear. The same dose of ethanol was infused for 2 hr in 5 ewes instrumented with aortic, left ventricular and sagittal sinus catheters. Ethanol caused ataxia accompanied by early modest and variable increases of total and regional CBF and CMRO2, followed by later modest and variable decreases of total and regional CBF (cerebellum) and CMRO2. Ethanol caused a cerebral transcapillary fluid shift as indicated by significant increases of the arterial-cerebral venous differencesmore » for hematocrit and hemoglobin. Brain wet-dry ratios increased by 10% above control levels. However, cerebral venous pressures were unchanged. The authors conclude that the adult cerebral response to ethanol differs quantitatively from that of the fetus. The functional significance of the cerebral fluid shift is unclear.« less

Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls.

PubMed

Mendenhall, William M; Amdur, Robert J; Palta, Jatinder R

2006-06-10

The purpose of this article is to review the role of intensity-modulated radiotherapy (IMRT) in the standard management of patients with head and neck cancer through a critical review of the pertinent literature. IMRT may result in a dose distribution that is more conformal than that achieved with three-dimensional conformal radiotherapy (3D CRT), allowing dose reduction to normal structures and thus decreasing toxicity and possibly enhancing locoregional control through dose escalation. Disadvantages associated with IMRT include increased risk of a marginal miss, decreased dose homogeneity, increased total body dose, and increased labor and expense. Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, depending on the location and extent of the tumor, late toxicity may be lower. Despite limited data on clinical outcomes, IMRT has been widely adopted as a standard technique in routine practice and clinical trials. The use of IMRT involves a learning curve for the practitioner and will continue to evolve, requiring continuing education and monitoring of outcomes from routine practice. Additional standards pertaining to a variety of issues, including target definitions and dose specification, need to be developed. Phase III trials will better define the role of IMRT in coming years.

Examining the Starting Dose of Glyburide in Gestational Diabetes

PubMed Central

GLOVER, Angelica V.; TITA, Alan; BIGGIO, Joseph R.; HARPER, Lorie M.

2016-01-01

OBJECTIVE The aim of this study was to determine the impact of initial glyburide dosing on pregnancy outcomes. STUDY DESIGN Retrospective cohort of singleton pregnancies complicated by gestational diabetes (GDM) from 2007-2013. Women who received glyburide were compared by initial dose: 2.5mg (n=170) versus 5mg (n=154) total daily dose. The primary maternal outcome was hypoglycemia, defined as a blood glucose <60 mg/dL. The primary neonatal outcome was birth weight. Secondary maternal outcomes included time to blood glucose control, preeclampsia, and cesarean delivery. Secondary neonatal outcomes included macrosomia (>4000g), hypoglycemia (<40 mg/dL), shoulder dystocia, and preterm delivery. RESULTS The 5 mg/day glyburide dose did not increase maternal hypoglycemia (26% in the 2.5 mg/day group versus 27% in the 5 mg/day group, AOR 0.67 (CI 0.30-1.49)). An increase in macrosomia in the 5 mg/day group was not significant after adjusting for maternal obesity (AOR 2.16 (CI 0.96-4.88)). Differences in preterm birth and large for gestational age were not significant after adjusting for prior preterm birth and maternal obesity, respectively. CONCLUSIONS A higher starting dose of glyburide for the management of GDM was not associated with increased maternal hypoglycemia or decreased adverse neonatal outcomes. PMID:26368915

Effects of multiple ascending doses of the glucagon receptor antagonist PF-06291874 in patients with type 2 diabetes mellitus.

PubMed

Kazierad, D J; Bergman, A; Tan, B; Erion, D M; Somayaji, V; Lee, D S; Rolph, T

2016-08-01

To assess the pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of the glucagon receptor antagonist PF-06291874 in patients with type 2 diabetes mellitus (T2DM). Patients were randomized to oral PF-06291874 or placebo on a background of either metformin (Part A, Cohorts 1-5: 5-150 mg once daily), or metformin and sulphonylurea (Part B, Cohorts 1-2: 15 or 30 mg once daily) for 14-28 days. A mixed-meal tolerance test (MMTT) was administered on days -1 (baseline), 14 and 28. Assessments were conducted with regard to pharmacokinetics, various pharmacodynamic variables, safety and tolerability. Circulating amino acid concentrations were also measured. PF-06291874 exposure was approximately dose-proportional with a half-life of ∼19.7-22.7 h. Day 14 fasting plasma glucose and mean daily glucose values were reduced from baseline in a dose-dependent manner, with placebo-corrected decreases of 34.3 and 42.4 mg/dl, respectively, at the 150 mg dose. After the MMTT, dose-dependent increases in glucagon and total glucagon-like peptide-1 (GLP-1) were observed, although no meaningful changes were noted in insulin, C-peptide or active GLP-1 levels. Small dose-dependent increases in LDL cholesterol were observed, along with reversible increases in serum aminotransferases that were largely within the laboratory reference range. An increase in circulating gluconeogenic amino acids was also observed on days 2 and 14. All dose levels of PF-06291874 were well tolerated. PF-06291874 was well tolerated, has a pharmacokinetic profile suitable for once-daily dosing, and results in reductions in glucose with minimal risk of hypoglycaemia. © 2016 John Wiley & Sons Ltd.

Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

PubMed

Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

2014-11-01

The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Comparison of different approaches of estimating effective dose from reported exposure data in 3D imaging with interventional fluoroscopy systems

NASA Astrophysics Data System (ADS)

Svalkvist, Angelica; Hansson, Jonny; Bâth, Magnus

2014-03-01

Three-dimensional (3D) imaging with interventional fluoroscopy systems is today a common examination. The examination includes acquisition of two-dimensional projection images, used to reconstruct section images of the patient. The aim of the present study was to investigate the difference in resulting effective dose obtained using different levels of complexity in calculations of effective doses from these examinations. In the study the Siemens Artis Zeego interventional fluoroscopy system (Siemens Medical Solutions, Erlangen, Germany) was used. Images of anthropomorphic chest and pelvis phantoms were acquired. The exposure values obtained were used to calculate the resulting effective doses from the examinations, using the computer software PCXMC (STUK, Helsinki, Finland). The dose calculations were performed using three different methods: 1. using individual exposure values for each projection image, 2. using the mean tube voltage and the total DAP value, evenly distributed over the projection images, and 3. using the mean kV and the total DAP value, evenly distributed over smaller selection of projection images. The results revealed that the difference in resulting effective dose between the first two methods was smaller than 5%. When only a selection of projection images were used in the dose calculations the difference increased to over 10%. Given the uncertainties associated with the effective dose concept, the results indicate that dose calculations based on average exposure values distributed over a smaller selection of projection angles can provide reasonably accurate estimations of the radiation doses from 3D imaging using interventional fluoroscopy systems.

Dose-response relationship between hand-transmitted vibration and hand-arm vibration syndrome in a tropical environment.

PubMed

Su, Anselm Ting; Maeda, Setsuo; Fukumoto, Jin; Darus, Azlan; Hoe, Victor C W; Miyai, Nobuyuki; Isahak, Marzuki; Takemura, Shigeki; Bulgiba, Awang; Yoshimasu, Kouichi; Miyashita, Kazuhisa

2013-07-01

The dose-response relationship for hand-transmitted vibration has been investigated extensively in temperate environments. Since the clinical features of hand-arm vibration syndrome (HAVS) differ between the temperate and tropical environment, we conducted this study to investigate the dose-response relationship of HAVS in a tropical environment. A total of 173 male construction, forestry and automobile manufacturing plant workers in Malaysia were recruited into this study between August 2011 and 2012. The participants were interviewed for history of vibration exposure and HAVS symptoms, followed by hand functions evaluation and vibration measurement. Three types of vibration doses-lifetime vibration dose (LVD), total operating time (TOT) and cumulative exposure index (CEI)-were calculated and its log values were regressed against the symptoms of HAVS. The correlation between each vibration exposure dose and the hand function evaluation results was obtained. The adjusted prevalence ratio for finger tingling and numbness was 3.34 (95% CI 1.27 to 8.98) for subjects with lnLVD≥20 ln m(2) s(-4) against those <16 ln m(2) s(-4). Similar dose-response pattern was found for CEI but not for TOT. No subject reported white finger. The prevalence of finger coldness did not increase with any of the vibration doses. Vibrotactile perception thresholds correlated moderately with lnLVD and lnCEI. The dose-response relationship of HAVS in a tropical environment is valid for finger tingling and numbness. The LVD and CEI are more useful than TOT when evaluating the dose-response pattern of a heterogeneous group of vibratory tools workers.

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

NASA Astrophysics Data System (ADS)

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

2011-03-01

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

Endophytic fungus Phomopsis liquidambari and different doses of N-fertilizer alter microbial community structure and function in rhizosphere of rice

PubMed Central

Siddikee, Md. Ashaduzzaman; Zereen, Mst Israt; Li, Cai-Feng; Dai, Chuan-Chao

2016-01-01

Microbial community structure and functions of rhizosphere soil of rice were investigated after applying low and high doses of nitrogenous fertilizer and Phomopsis liquidambari. Average well color development, substrate richness, catabolic diversity and soil enzymes activities varied after applying N-fertilizer and P. liquidambari and were greater in P. liquidambari treated soil than only N-fertilization. Multivariate analysis distinctly separated the catabolic and enzymes activity profile which statistically proved alteration of microbial functional diversity. Nitrogen fertilizer altered microbial community structure revealed by the increased content of total PLFAs, specific subgroup marker PLFAs except fungal PLFAs and by the decreased ratio of G+/G−, sat/monunsat, iso/anteiso, F/B except trans/cis while P. liquidambari inoculation enhanced N-fertilization effect except increased fungal PLFA and decreased trans/cis. PCA using identified marker PLFAs revealed definite discrimination among the treatments which further statistically confirmed structural changed of microbial community. Nitrogenase activity representative of N-fixing community decreased in N-fertilizer treatment while P. liquidambari inoculation increased. In short, application of P. liquidambari with low doses of N-fertilizer improved rice growth and reduced N-fertilizer requirement by increasing enzymes activities involved in C, N and P cycling, structural and functional diversity of microbes, nitrogenase activity involved in N2 fixation and accumulation of total-N. PMID:27596935

24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: implications for caffeine-induced depression.

PubMed

Haleem, D J; Yasmeen, A; Haleem, M A; Zafar, A

1995-01-01

Caffeine injected at doses of 20, 40 and 80 mg/kg increased brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in rat brain. In view of a possible role of 5-HT in caffeine-induced depression the effects of repeated administration of high doses of caffeine on brain 5-HT metabolism are investigated in rats. Caffeine was injected at doses of 80 mg/kg daily for five days. Control animals were injected with saline daily for five days. On the 6th day caffeine (80 mg/kg) injected to 5 day saline injected rats increased brain levels of tryptophan, 5-HT and 5-HIAA. Plasma total tryptophan levels were not affected and free tryptophan increased. Brain levels of 5-HT and 5-HIAA but not tryptophan decreased in 5 day caffeine injected rats injected with saline on the 6th day. Plasma total and free tryptophan were not altered in these rats. Caffeine-induced increases of brain tryptophan but not 5-HT and 5-HIAA were greater in 5 day caffeine than 5 day saline injected rats. The findings are discussed as repeated caffeine administration producing adaptive changes in the serotonergic neurons to decrease the conversion of tryptophan to 5-HT and this may precipitate depression particularly in conditions of caffeine withdrawal.

Increase in tiagabine serum concentration with coadministration of gemfibrozil.

PubMed

Burstein, Aaron H; Boudreau, Eilis A; Theodore, William H

2009-02-01

To report a case of possible acute tiagabine toxicity secondary to administration of gemfibrozil. A 39-year-old male was taking tiagabine 16 mg orally 3 times per day and carbamazepine 500 mg orally twice per day for complex partial seizures secondary to mesial temporal sclerosis. He was found to have type IV hypertriglyceridemia and was prescribed gemfibrozil. Because he reported severe confusion and altered consciousness shortly after a single 600-mg dose of gemfibrozil, he was admitted for controlled challenge with that drug. A single 300-mg dose of gemfibrozil resulted in lightheadedness and led to a 59% and 75% increase in total tiagabine serum concentrations at 2 and 5 hours, respectively, without significant change in baseline carbamazepine concentrations. This is the first report of an interaction between the widely used antihyperlipidemic drug gemfibrozil and tiagabine. Since tiagabine, which was originally developed as an antiepileptic medication, is now being used widely for a variety of other indications such as anxiety and depression, there is an increased risk for clinically significant interactions with gemfibrozil. Increased total and unbound tiagabine concentrations following a single 300-mg dose of gemfibrozil and reproduction of clinical symptoms with gemfibrozil rechallenge suggests the toxicity our patient experienced was due to a pharmacokinetic drug interaction. Use of the Horn Drug Interaction Probability Scale showed a probable interaction between gemfibrozil and tiagabine.

Morbidity and mortality reduction by supplemental vitamin A or beta-carotene in CBA mice given total-body gamma-radiation

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

Seifter, E.; Rettura, G.; Padawer, J.

Male CBA mice received graded doses (450-750 rad) of total-body gamma-radiation (TBR) from a dual-beam /sup 137/Cs irradiator. Commencing directly after TBR, 2 days later, or 6 days later, groups of mice received supplemental vitamin A (Vit A) or beta-carotene (beta-Car), compounds previously found to reduce radiation disease in mice subjected to partial-body X-irradiation. Given directly after TBR, supplemental Vit A decreased mortality, evidenced by increases in the radiation dose required to kill 50% of the mice within 30 days (LD50/30). In one experiment, Vit A increased the LD50/30 from 555 to 620 rad; in another experiment, Vit A increasedmore » the dose from 505 to 630 rad. Similarly, in a third experiment, supplemental beta-Car increased the LD50/30 from 510 to 645 rad. Additionally, each compound increased the survival times, even of those mice that died within 30 days. In addition to reduction of mortality and prolongation of survival time, supplemental Vit A moderated weight loss, adrenal gland hyperemia, thymus involution, and lymphopenia--all signs of radiation toxicity. Delaying the supplementation for 2 days after irradiation did not greatly reduce the efficacy of Vit A; however, delaying supplementation for 6 days decreased its effect almost completely.« less

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

PubMed

Zavgorodni, S

2004-12-07

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

Influence of gamma-irradiation and maize lipids on the production of aflatoxin B1 by Aspergillus flavus.

PubMed

Aziz, Nagy H; el-Zeany, Samia A; Moussa, Lotfy A A

2002-10-01

The effect of gamma-irradiation and maize lipids on aflatoxin B1 production by Aspergillus flavus artificially inoculated into sterilized maize at reduced water activity (aw 0.84) was investigated. By increasing the irradiation doses the total viable population of A. flavus decreased and the fungus was completely inhibited at 3.0 kGy. The amounts of aflatoxin B1 were enhanced at irradiation dose levels 1.0 and 1.5 kGy in both full-fat maize (FM) and defatted maize (DM) media and no aflatoxin B1 production at 3.0 kGy gamma-irradiation over 45 days of storage was observed. The level in free lipids of FM decreased gradually, whereas free fatty acid values and fungal lipase activity increased markedly by increasing the storage periods. The free fatty acid values decreased by increasing the irradiation dose levels and there was a significant enhancement of fungal lipase activity at doses of 1.0 and 1.50 kGy. The ability of A. flavus to grow at aw 0.84 and produce aflatoxin B1 is related to the lipid composition of maize. The enhancement of aflatoxin B1 at low doses was correlated to the enhancement of fungal lipase activity.

Fault Tolerant Characteristics of Artificial Neural Network Electronic Hardware

NASA Technical Reports Server (NTRS)

Zee, Frank

1995-01-01

The fault tolerant characteristics of analog-VLSI artificial neural network (with 32 neurons and 532 synapses) chips are studied by exposing them to high energy electrons, high energy protons, and gamma ionizing radiations under biased and unbiased conditions. The biased chips became nonfunctional after receiving a cumulative dose of less than 20 krads, while the unbiased chips only started to show degradation with a cumulative dose of over 100 krads. As the total radiation dose increased, all the components demonstrated graceful degradation. The analog sigmoidal function of the neuron became steeper (increase in gain), current leakage from the synapses progressively shifted the sigmoidal curve, and the digital memory of the synapses and the memory addressing circuits began to gradually fail. From these radiation experiments, we can learn how to modify certain designs of the neural network electronic hardware without using radiation-hardening techniques to increase its reliability and fault tolerance.

Comparison of U.S. Environmental Protection Agency’s CAP88 PC versions 3.0 and 4.0

DOE PAGES

Jannik, Tim; Farfan, Eduardo B.; Dixon, Ken; ...

2015-08-01

The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within itsmore » corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes EPA made in the external ground shine calculations.« less

Light dose versus rate of delivery: implications for macroalgal productivity.

PubMed

Desmond, Matthew J; Pritchard, Daniel W; Hepburn, Christopher D

2017-06-01

The role of how light is delivered over time is an area of macroalgal photosynthesis that has been overlooked but may play a significant role in controlling rates of productivity and the structure and persistence of communities. Here we present data that quantify the relative influence of total quantum dose and delivery rate on the photosynthetic productivity of five ecologically important Phaeophyceae species from southern New Zealand. Results suggested that greater net oxygen production occurs when light is delivered at a lower photon flux density (PFD) over a longer period compared to a greater PFD over a shorter period, given the same total dose. This was due to greater efficiency (α) at a lower PFD which, for some species, meant a compensatory effect can occur. This resulted in equal or greater productivity even when the total quantum dose of the lower PFD was significantly reduced. It was also shown that light limitation at Huriawa Peninsula, where macroaglae were sourced, may be restricting the acclimation potential of species at greater depths, and that even at shallow depth periods of significant light limitation are likely to occur. This research is of particular interest as the variability of light delivery to coastal reef systems increases as a result of anthropogenic disturbances, and as the value of in situ community primary productivity estimates is recognised.

Effect of Ayurvedic mercury preparation Makaradhwaja on geriatric canine--a preliminary study.

PubMed

Sinyorita, S; Ghosh, C K; Chakrabarti, A; Auddy, B; Ghosh, Runa; Debnath, P K

2011-07-01

Makaradhwaja, an alchemical Ayurvedic mercury preparation is used as stimulant and vitalizer. Towards veterinary practices, the acceptability, tolerability and toxicity studies were undertaken in geriatric pet dogs aged more than 10 years irrespective of breed and sex for future use. Makaradhwaja (2.5 mg/kg) was used with honey once daily for 30 days. Before and after treatment, blood was collected for hematological studies as well as liver, kidney function and anti-oxidant activity. In control group, honey itself showed no appreciable change whereas, Makaradhwaja lowered neutrophil and total leucocyte count. Serum cholesterol, urea, glucose, alanine amino transferase, aspartate amino transferase, sodium, phosphorus and calcium were decreased. Haemoglobin and serum creatinine were significantly increased. There was appreciable physical, behavioral and body weight change including quality of life. The dose was used in replication of human dose (125 mg/50 kg). Anti-oxidant study showed significant increase of lipid per oxidation in experimental group while the values of ABTS radical cation decolorisation assay although decreased but did not show any significant changes. Decrease of serum urea and increase of serum creatinine could not be explained on single dose response. Different dose study could only explain the optimum dose to be required in canine practices.

Experimental metolachlor toxicosis in Nubian goats in the Sudan.

PubMed

Mohamed, O S; Ahmed, K E; Adam, S E; Idris, O F

1994-01-01

Six out of 15 Nubian goats kids were given single oral doses of metolachlor (Dual 720 EC) at 2,000 or 500 mg/kg liveweight and died within 1 h of the dosing. Other 6 goats were given daily oral doses at 200 or 25 mg/kg and died or were slaughtered between days 8 and 25. In goats receiving single doses, the signs of poisoning were convulsive episodes, incoordination of movement, tremors, severe muscular spasms, stiffness, profuse salivation, respiratory distress, abnormal posture and recumbency. In goats receiving metolachlor at daily doses, the signs were similar, but developed slowly. Increases in the activities of serum AST and GGT and in the concentration of urea, and decreases in total protein concentration were correlated with clinical changes and lesions.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

PubMed Central

Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

2014-01-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

Evaluation of Myrtus communis Linn. berries (common myrtle) in experimental ulcer models in rats.

PubMed

Sumbul, Sabiha; Ahmad, Mohd Aftab; Asif, Mohd; Saud, Ibne; Akhtar, Mohd

2010-11-01

The present study was conducted to investigate the protective effect of the dried berries of Myrtus communis L. in gastric ulcer against ethanol, indomethacin and pyloric ligation induced models in Wistar rats. Two doses of aqueous extracts of M. communis (AE( 1) and AE(2)) at the dose 105 and 175 mg/kg, respectively, and methanolic extracts (ME(1) and ME(2)) at the dose of 93 and 154 mg/kg, respectively, were administered orally to animals prior to the exposure of ulcerogens. The parameters taken to assess anti-ulcer activity were ulcer index, gastric juice volume, gastric pH, total acidity, gastric wall mucus and histopathological studies. Oral administration of AE(1) and AE(2) significantly reduced the ulcer index in all models of ulcers. Low dose of aqueous extract and high dose of methanolic extract of M. communis exhibited more significant effect in comparison to omeprazole (standard drug) in ethanol-induced ulcer model. Both the doses of aqueous and methanolic extracts also reduced the gastric juice volume, total acidity and increased the gastric pH and gastric wall mucus content in all the models of ulcers used in the present study. Histopathological examinations of gastric tissues of rats treated with the aqueous and methanolic extracts in indomethacin-induced ulcer exhibited significant ulcer-protective effect at both the dose levels.

Hormetic Response by Silver Nanoparticles on In Vitro Multiplication of Sugarcane (Saccharum spp. Cv. Mex 69-290) Using a Temporary Immersion System.

PubMed

Bello-Bello, Jericó J; Chavez-Santoscoy, Rocío A; Lecona-Guzmán, Carlos A; Bogdanchikova, Nina; Salinas-Ruíz, Josafhat; Gómez-Merino, Fernando Carlos; Pestryakov, Alexey

2017-01-01

Hormesis is considered a dose-response phenomenon characterized by growth stimulation at low doses and inhibition at high doses. The hormetic response by silver nanoparticles (AgNPs) on in vitro multiplication of sugarcane was evaluated using a temporary immersion system. Sugarcane shoots were used as explants cultured in Murashige and Skoog medium with AgNPs at concentrations of 0, 25, 50, 100, and 200 mg/L. Shoot multiplication rate and length were used to determine hormetic response. Total content of phenolic compounds of sugarcane, mineral nutrition, and reactive oxygen species (ROS) was determined. Results were presented as a dose-response curve. Stimulation phase growth was observed at 50 mg/L AgNPs, whereas inhibition phase was detected at 200 mg/L AgNPs. Mineral nutrient analysis showed changes in macronutrient and micronutrient contents due to the effect of AgNPs. Moreover, AgNPs induced ROS production and increased total phenolic content, with a dose-dependent effect. Results suggested that the production of ROS and mineral nutrition are key mechanisms of AgNP-induced hormesis and that phenolic accumulation was obtained as a response of the plant to stress produced by high doses of AgNPs. Therefore, small doses of AgNPs in the culture medium could be an efficient strategy for commercial micropropagation.

Chemical and toxicological evaluation of methanol extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed on hematological parameters and hepatorenal functions in mice.

PubMed

Mazumder, Upal Kanti; Gupta, Malaya; Pal, Dilipkumar; Bhattacharya, Shiladitya

2003-01-01

Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%) and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75 mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and hematological parameters in mice were studied. No significant alteration of RBC count and hemoglobin content was observed in all dose level of treatment in MECR and MECO treated mice whereas significant increase of clotting time was seen in moderate and high doses in both case. MECR and MECO both caused significant increase in WBC count only in high dose level of treatment. Both the extracts in medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol significantly. Serum alkaline phosphatase and total bilirubin were also increased by both moderate and high dose level of treatments in MECR and MECO treated mice respectively. Low dose of both the extract did not exhibit any significant change of creatinine and serum protein level. But high dose level of MECR and MECO significantly increased creatinine level. Increase in plasma cholesterol may be due to decrease in cholesterol catabolism owing to liver dysfunction of due to the intake of MECO itself as it was found to be steroid in nature. Elevated level of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose level of weekly treated mice may be due to improper liver function following the treatment. Increased urea, non protein nitrogen and creatinine content in blood have been observed with impaired renal function. The slightly higher toxicity in case of MECO treated mice may be due to the presence of cardenolide glycosides in the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15 mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and kidney functions and hematological parameters.

Pharmacokinetic properties and tolerability of rotigotine transdermal patch after repeated-dose application in healthy korean volunteers.

PubMed

Kim, Bo-Hyung; Yu, Kyung-Sang; Jang, In-Jin; Soo Lim, Kyoung; Kim, Jung-Ryul; Elshoff, Jan-Peer; Andreas, Jens-Otto; Braun, Marina; Cawello, Willi

2015-04-01

Rotigotine, a nonergolinic dopamine receptor agonist, is a once-daily transdermal patch developed for the treatment of Parkinson's disease and restless legs syndrome. The objective of the present study was to determine the pharmacokinetic characteristics and tolerability of rotigotine transdermal patch after repeated-dose application in healthy male and female Korean subjects. In this randomized, double-blind, placebo-controlled, repeated-dose study, subjects were randomly assigned to receive either rotigotine or placebo (ratio, 20 rotigotine to 4 placebo, per sex). Rotigotine patches were applied once daily at a dose of 2 mg/24 h on days 1 to 3, followed by 4 mg/24 h on days 4 to 6. Serial blood and urine samples were collected on days 1 to 9 for the determination of the concentrations of rotigotine and its metabolites. Tolerability was evaluated by adverse events determined using physical examination, including vital signs with orthostatic measurements; ECG; and clinical laboratory testing. A total of 48 healthy Korean subjects were enrolled (24 men, 24 women; mean age, 24 years). Approximately 50% of the total drug content was delivered within 24 hours. The mean plasma concentration of unconjugated rotigotine increased proportionally with dose. At the 2 mg/24 h dose at steady state, the geometric mean AUC0-24h and Cmax values of unconjugated rotigotine were 5.88 ng·h/mL and 0.347 ng/mL, respectively; at the 4 mg/24 h dose, the corresponding values were 13.74 ng·h/mL and 0.838 ng/mL. The mean t½ of rotigotine was 4.96 hours. At the 2 mg/24 h dose at steady state, the geometric mean AUC0-24h and Cmax values of total rotigotine were 14.02 ng·h/mL and 0.776 ng/mL; at the 4-mg/24 h dose, 32.38 ng·h/mL and 1.867 ng/mL. Common adverse events reported in the rotigotine-treated subjects included nausea (17 subjects, 42.5%), headache (11, 27.5%), and dizziness (9, 22.5%). No clinically significant changes in blood pressure, ECG, or laboratory values were observed. The mean plasma exposures of unconjugated rotigotine increased proportionally with dose. Repeated daily application of the rotigotine patch was well tolerated in these healthy Korean volunteers. ClinicalTrials.gov identifier: NCT01964573. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Effects of irradiation source and dose level on quality characteristics of processed meat products

NASA Astrophysics Data System (ADS)

Ham, Youn-Kyung; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Kim, Yong-Jae; Choi, Yun-Sang; Song, Beom-Seok; Park, Jong-Heum; Kim, Cheon-Jei

2017-01-01

The effect of irradiation source (gamma-ray, electron-beam, and X-ray) and dose levels on the physicochemical, organoleptic and microbial properties of cooked beef patties and pork sausages was studied, during 10 days of storage at 30±1 °C. The processed meat products were irradiated at 0, 2.5, 5, 7.5, and 10 kGy by three different irradiation sources. The pH of cooked beef patties and pork sausages was unaffected by irradiation sources or their doses. The redness of beef patties linearly decreased with increasing dose level (P<0.05), obviously by e-beam irradiation compared to gamma-ray and X-ray (P<0.05). The redness of pork sausages was increased by gamma-ray irradiation, whereas it decreased by e-beam irradiation depending on absorbed dose level. No significant changes in overall acceptability were observed for pork sausages regardless of irradiation source (P>0.05), while gamma-ray irradiated beef patties showed significantly decreased overall acceptability in a dose-dependent manner (P<0.05). Lipid oxidation of samples was accelerated by irradiation depending on irradiation sources and dose levels during storage at 30 °C. E-beam reduced total aerobic bacteria of beef patties more effectively, while gamma-ray considerably decreased microbes in pork sausages as irradiation dose increased. The results of this study indicate that quality attributes of meat products, in particular color, lipid oxidation, and microbial properties are significantly influenced by the irradiation sources.

Effect of irradiated pork on physicochemical properties of meat emulsions

NASA Astrophysics Data System (ADS)

Choi, Yun-Sang; Sung, Jung-Min; Jeong, Tae-Jun; Hwang, Ko-Eun; Song, Dong-Heon; Ham, Youn-Kyung; Kim, Hyun-Wook; Kim, Young-Boong; Kim, Cheon-Jei

2016-02-01

The effect of pork irradiated with doses up to 10 kGy on meat emulsions formulated with carboxy methyl cellulose (CMC) was investigated. Raw pork was vacuums packaged at a thickness of 2.0 cm and irradiated by X-ray linear accelerator (15 kW, 5 MeV). The emulsion had higher lightness, myofibrillar protein solubility, total protein solubility, and apparent viscosity with increasing doses, whereas cooking loss, total expressible fluid separation, and hardness decreased. There were no significant differences in fat separation, sarcoplasmic protein solubility, springiness, and cohesiveness. Our results indicated that it is treatment by ionizing radiation which causes the effects the physicochemical properties of the final raw meat product.

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

PubMed Central

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

2013-01-01

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

Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

PubMed

Aziza, Samy Ali Hussein; Azab, Mohammed El-Said; El-Shall, Soheir Kamal

2014-08-01

Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT and SOD activities when compared with the control group. Rutin administration to iron-overloaded rats resulted in significant decrease in serum total iron, TIBC, Tf, TS%, ferritin levels and AST and ALT activities and liver total iron, L-MDA and NO levels with significant increases in serum UIBC, albumin, total protein and total cholesterol levels and in liver GSH, CAT and SOD activities compared with the IOL group. This study provides in vivo evidence that rutin administration can improve the antioxidant defense systems against IOL-induced hepatic oxidative stress in rats. This protective effect in liver of iron-loaded rats may be due to both antioxidant and metal chelation activities.

Effects of exposing ostrich eggs to doses of gamma radiation on hatchability, growth performance, and some blood biochemicals of hatched chicks.

PubMed

Mahrose, Khalid; Elsayed, Mohammed; Basuony, Hamdy; Gouda, Nour

2016-11-01

Effects of radiating ostrich eggs before incubation on hatchability, growth performance, and some blood components of ostrich chicks were studied. 72 ostrich eggs were randomly distributed into four groups. The first group was kept without exposure to gamma radiation (control). The 2nd, 3rd, and 4th groups were exposed to 0.8, 1.6, and 3.2 Gy, respectively, of 60 Co gamma rays just before incubation. Total bacterial counts (×10 3  CFU) were significantly increased with the increase in gamma radiation levels before incubation. Feed conversion was lower (P ≤ 0.01) in the control group than those irradiated. Embryonic mortality rate (%), hatchability (%) and chick weight at hatch, body weight, daily body weight gain, feed consumption, and all of hematology parameters studied were insignificantly fluctuated with the doses of gamma rays used. Serum concentrations of total protein, albumen, globulin, glucose, and triiodothyronin of the chicks from eggs of the control and the 1st group were significantly the highest. Chicks of the control group had significantly the lowest values of serum concentrations of uric acid, creatinine, triglyceride, total cholesterol, ALT, and AST when compared with the other groups. In conclusion, radiation of ostrich eggs before incubation with a dose of 0.8 Gy gamma has a stimulative effect upon the metabolism of hatched chicks.

Lead nitrate induced unallied expression of liver and kidney functions in male albino rats.

PubMed

Chougule, Priti; Patil, Bhagyashree; Kanase, Aruna

2005-06-01

To determine the effects of lead where lead accumulates maximum (liver followed by kidney), liver and kidney functions were studied using low oral dose of lead nitrate for prolonged duration. Dose of 20 mg lead nitrate/kg body wt/day was used in male albino rats. AST and ALT levels altered independently. When ALT remained unaltered after 7 and 21 days of treatment, it is decreased by 13.21% after 14 days treatment. AST was marginally lowered after 7 days, increased after 14 days and increased marginally after 21 days. Bilirubin (conjugated, unconjugated and total) decreased after 7 and 14 days and increased after 21 days. Urea increase was directly proportional to duration. Creatinine remained unaltered.

Safety and efficacy of stereotactic radiosurgery for tumors of the spine.

PubMed

Benzil, Deborah L; Saboori, Mehran; Mogilner, Alon Y; Rocchio, Ronald; Moorthy, Chitti R

2004-11-01

The extension of stereotactic radiosurgery treatment of tumors of the spine has the potential to benefit many patients. As in the early days of cranial stereotactic radiosurgery, however, dose-related efficacy and toxicity are not well understood. The authors report their initial experience with stereotactic radiosurgery of the spine with attention to dose, efficacy, and toxicity. All patients who underwent stereotactic radiosurgery of the spine were treated using the Novalis unit at Westchester Medical Center between December 2001 and January 2004 are included in a database consisting of demographics on disease, dose, outcome, and complications. A total of 31 patients (12 men, 19 women; mean age 61 years, median age 63 years) received treatment for 35 tumors. Tumor types included 26 metastases (12 lung, nine breast, five other) and nine primary tumors (four intradural, five extradural). Thoracic tumors were most common (17 metastases and four primary) followed by lumbar tumors (four metastases and four primary). Lesions were treated to the 85 to 90% isodose line with spinal cord doses being less than 50%. The dose per fraction and total dose were selected on the basis of previous treatment (particularly radiation exposure), size of lesion, and proximity to critical structures. Rapid and significant pain relief was achieved after stereotactic radiosurgery in 32 of 34 treated tumors. In patients treated for metastases, pain was relieved within 72 hours and remained reduced 3 months later. Pain relief was achieved with a single dose as low as 500 cGy. Spinal cord isodoses were less than 50% in all patients except those with intradural tumors (mean single dose to spinal cord 268 cGy and mean total dose to spinal cord 689 cGy). Two patients experienced transient radiculitis (both with a biological equivalent dose (BED) > 60 Gy). One patient who suffered multiple recurrences of a conus ependymoma had permanent neurological deterioration after initial improvement. Pathological evaluation of this lesion at surgery revealed radiation necrosis with some residual/recurrent tumor. No patient experienced other organ toxicity. Stereotactic radiosurgery of the spine is safe at the doses used and provides effective pain relief. In this study, BEDs greater than 60 Gy were associated with an increased risk of radiculitis.

The role of gamma irradiation on the extraction of phenolic compounds in onion (Allium cepa L.)

NASA Astrophysics Data System (ADS)

Yang, Eun In; Lee, Eun Mi; Kim, Young Soo; Chung, Byung Yeoup

2012-08-01

The effect of gamma irradiation on the content of total phenolic compounds, especially quercetin (Q), in onion (Allium cepa L.) skin was investigated. Onion skin extracts contained two predominant flavonoid compounds, Q and quercetin-4'-glucoside (Q4'G). After 10 kGy gamma irradiation, the yield of Q in the extracts increased significantly from 36.8 to 153.9 μg/ml of the extract, and the Q4'G content decreased slightly from 165.0 to 134.1 μg/ml. In addition, the total phenolic compound content also increased after irradiation at 10 kGy, from 228.0 μg/g of fresh weight to 346.6 μg/g; negligible changes (237.1-256.7 μg/g) occurred at doses of up to 5 kGy. As we expected, radical-scavenging activity was enhanced remarkably (by 88.8%) in the 10 kGy irradiated sample. A dose-dependent increase in the peak intensity of the electron paramagnetic resonance (EPR) spectra was observed in all irradiated samples, with a maximum increase at 10 kGy. The intensity relative to that of the control was 0.15, and it increased to 1.10 in 10 kGy irradiated samples. The optimum gamma irradiation dose, which is sufficient to break the chemical or physical bonds and release soluble phenols of low molecular weight in onion skin, is about 10 kGy.

Comparison of a new noncoplanar intensity-modulated radiation therapy technique for craniospinal irradiation with 3 coplanar techniques

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

Hansen, Anders T., E-mail: andehans@rm.dk; Lukacova, Slavka; Lassen-Ramshad, Yasmin

2015-01-01

When standard conformal x-ray technique for craniospinal irradiation is used, it is a challenge to achieve satisfactory dose coverage of the target including the area of the cribriform plate, while sparing organs at risk. We present a new intensity-modulated radiation therapy (IMRT), noncoplanar technique, for delivering irradiation to the cranial part and compare it with 3 other techniques and previously published results. A total of 13 patients who had previously received craniospinal irradiation with standard conformal x-ray technique were reviewed. New treatment plans were generated for each patient using the noncoplanar IMRT-based technique, a coplanar IMRT-based technique, and a coplanarmore » volumetric-modulated arch therapy (VMAT) technique. Dosimetry data for all patients were compared with the corresponding data from the conventional treatment plans. The new noncoplanar IMRT technique substantially reduced the mean dose to organs at risk compared with the standard radiation technique. The 2 other coplanar techniques also reduced the mean dose to some of the critical organs. However, this reduction was not as substantial as the reduction obtained by the noncoplanar technique. Furthermore, compared with the standard technique, the IMRT techniques reduced the total calculated radiation dose that was delivered to the normal tissue, whereas the VMAT technique increased this dose. Additionally, the coverage of the target was significantly improved by the noncoplanar IMRT technique. Compared with the standard technique, the coplanar IMRT and the VMAT technique did not improve the coverage of the target significantly. All the new planning techniques increased the number of monitor units (MU) used—the noncoplanar IMRT technique by 99%, the coplanar IMRT technique by 122%, and the VMAT technique by 26%—causing concern for leak radiation. The noncoplanar IMRT technique covered the target better and decreased doses to organs at risk compared with the other techniques. All the new techniques increased the number of MU compared with the standard technique.« less

Total body irradiation, toward optimal individual delivery: dose evaluation with metal oxide field effect transistors, thermoluminescence detectors, and a treatment planning system.

PubMed

Bloemen-van Gurp, Esther J; Mijnheer, Ben J; Verschueren, Tom A M; Lambin, Philippe

2007-11-15

To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

Comparison between in vivo dosimetry and barium contrast technique for prediction of rectal complications in high-dose-rate intracavitary radiotherapy in cervix cancer patients.

PubMed

Huh, Seung Jae; Lim, Do Hoon; Ahn, Yong Chan; Lee, Jeong Eun; Kang, Min Kyu; Shin, Seong Soo; Shin, Kyung Hwan; Kim, Bokyung; Park, Won; Han, Youngyih

2003-03-01

To investigate the correlation between late rectal complications and rectal dose in cervix cancer patients treated with high-dose-rate intracavitary radiotherapy (HDR ICR) and to analyze factors reducing rectal complications. A total of 136 patients with cervix cancer who were treated with external beam radiotherapy (EBRT) and HDR ICR from 1995 to 1999 were retrospectively analyzed. Radiotherapy (RT) consisted of EBRT plus HDR ICR. The median EBRT dose was 50.4 Gy, and midline block was done after 30-50 Gy of EBRT. A total of six fractions of HDR ICR with 4 Gy fraction size each were applied twice per week to the A point. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. In vivo measurement of the rectal dose was performed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 26 months (range 6-60 months). A total of 16 patients (12%) experienced rectal bleeding, which occurred 4-33 months (median 11 months) after the completion of RT. The calculated rectal doses did not differ in patients with rectal bleeding and those without, but the measured rectal doses were higher in affected patients. The differences of the measured ICR fractional rectal dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose exceeded 16 Gy, the ratio of the measured rectal dose to A point dose was > 70%; when the measured rectal BED exceeded 110 Gy(3), a high possibility of late rectal complications could be found. In vivo dosimetry using TLD during HDR ICR was a good predictor of late rectal complications. Hence, if data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.

Population approach to analyze the pharmacokinetics of free and total lopinavir in HIV-infected pregnant women and consequences for dose adjustment.

PubMed

Fauchet, Floris; Treluyer, Jean-Marc; Illamola, Silvia M; Pressiat, Claire; Lui, Gabrielle; Valade, Elodie; Mandelbrot, Laurent; Lechedanec, Jerome; Delmas, Sandrine; Blanche, Stéphane; Warszawski, Josiane; Urien, Saik; Tubiana, Roland; Hirt, Déborah

2015-09-01

The aims of this study were to describe the unbound and total lopinavir (LPV) pharmacokinetics in pregnant women in order to evaluate if a dosing adjustment is necessary during pregnancy. Lopinavir placental transfer is described, and several genetic covariates were tested to explain its variability. A total of 400 maternal, 79 cord blood, and 48 amniotic fluid samples were collected from 208 women for LPV concentration determinations and pharmacokinetics analysis. Among the maternal LPV concentrations, 79 samples were also used to measure the unbound LPV concentrations. Population pharmacokinetics models were developed by using NONMEM software. Two models were developed to describe (i) unbound and total LPV pharmacokinetics and (ii) LPV placental transfer. The pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. A pregnancy effect was found on maternal clearance (39% increase), whereas the treatment group (monotherapy versus triple therapy) or the genetic polymorphisms did not explain the pharmacokinetics or placental transfer of LPV. Efficient unbound LPV concentrations in nonpregnant women were similar to those measured during the third trimester of pregnancy. Our study showed a 39% increase of maternal total LPV clearance during pregnancy, whereas unbound LPV concentrations were similar to those simulated in nonpregnant women. The genetic polymorphisms selected did not influence the LPV pharmacokinetics or placental transfer. Thus, we suggest that the LPV dosage should not be increased during pregnancy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Population Approach To Analyze the Pharmacokinetics of Free and Total Lopinavir in HIV-Infected Pregnant Women and Consequences for Dose Adjustment

PubMed Central

Treluyer, Jean-Marc; Illamola, Silvia M.; Pressiat, Claire; Lui, Gabrielle; Valade, Elodie; Mandelbrot, Laurent; Lechedanec, Jerome; Delmas, Sandrine; Blanche, Stéphane; Warszawski, Josiane; Urien, Saik; Tubiana, Roland; Hirt, Déborah

2015-01-01

The aims of this study were to describe the unbound and total lopinavir (LPV) pharmacokinetics in pregnant women in order to evaluate if a dosing adjustment is necessary during pregnancy. Lopinavir placental transfer is described, and several genetic covariates were tested to explain its variability. A total of 400 maternal, 79 cord blood, and 48 amniotic fluid samples were collected from 208 women for LPV concentration determinations and pharmacokinetics analysis. Among the maternal LPV concentrations, 79 samples were also used to measure the unbound LPV concentrations. Population pharmacokinetics models were developed by using NONMEM software. Two models were developed to describe (i) unbound and total LPV pharmacokinetics and (ii) LPV placental transfer. The pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. A pregnancy effect was found on maternal clearance (39% increase), whereas the treatment group (monotherapy versus triple therapy) or the genetic polymorphisms did not explain the pharmacokinetics or placental transfer of LPV. Efficient unbound LPV concentrations in nonpregnant women were similar to those measured during the third trimester of pregnancy. Our study showed a 39% increase of maternal total LPV clearance during pregnancy, whereas unbound LPV concentrations were similar to those simulated in nonpregnant women. The genetic polymorphisms selected did not influence the LPV pharmacokinetics or placental transfer. Thus, we suggest that the LPV dosage should not be increased during pregnancy. PMID:26149996

Sensitivity of disease parameters to flexible budesonide/formoterol treatment in an allergic rat model.

PubMed

Brange, Charlotte; Smailagic, Amir; Jansson, Anne-Helene; Middleton, Brian; Miller-Larsson, Anna; Taylor, John D; Silberstein, David S; Lal, Harbans

2009-02-01

Clinical studies show that flexible dosing (maintenance and symptom-driven dose adjustments) of budesonide and formoterol (BUD/FORM) improves control of asthma exacerbations as compared to fixed maintenance dosing protocols (maintenance therapy) even when the latter utilize higher BUD/FORM doses. This suggests that dose-response relationships for certain pathobiologic mechanisms in asthma shift over time. Here, we have conducted animal studies to address this issue. (1) To test in an animal asthma-like model whether it is possible to achieve the same or greater pharmacological control over bronchoconstriction and airway/lung inflammation, and with less total drug used, by flexible BUD/FORM dosing (upward adjustment of doses) in association with allergen challenges. (2) To determine whether the benefit requires adjustment of both drug components. Rats sensitized on days 0 and 7 were challenged intratracheally with ovalbumin on days 14 and 21. On days 13-21, rats were treated intratracheally with fixed maintenance or flexible BUD/FORM combinations. On day 22, rats were challenged with methacholine and lungs were harvested for analysis. A flexible BUD/FORM dosing regimen (using 3.3 times less total drug than the fixed maintenance high dose regimen), delivered the same or greater reductions of excised lung gas volume (a measure of gas trapped in lung by bronchoconstriction) and lung weight (a measure of inflammatory oedema). When either BUD or FORM alone was increased on days of challenge, the benefit of the flexible dose upward adjustment was lost. Flexible dosing of the BUD/FORM combination improves the pharmacological inhibition of allergen-induced bronchoconstriction and an inflammatory oedema in an allergic asthma-like rat model.

Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves.

PubMed

Alam, Badrul; Akter, Fahima; Parvin, Nahida; Sharmin Pia, Rashna; Akter, Sharmin; Chowdhury, Jesmin; Sifath-E-Jahan, Kazi; Haque, Ekramul

2013-01-01

The present study was designed to evaluate the antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves (MPBL). MPBL was evaluated for anti-inflammatory activity using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was evaluated by hot plate, writhing, and formalin tests. Total phenolic and flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of total ROS generation, and assessment of reducing power were used to evaluate antioxidant potential of MPBL. The extract of MPBL, at the dose of 100 and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot plate method whereas significantly (p<0.05) reduced the writhing caused by acetic acid and the number of licks induced by formalin in a dose-dependent manner. The same ranges of doses of MPBL caused significant (p<0.05) inhibition of carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH, ONOO(-), and total ROS scavenging method, MPBL showed good antioxidant potentiality with the IC50 value of 16.33±1.02, 25.16±0.61 , and 41.72±0.48 µg/ml, respectively with a significant (p<0.05) good reducing power. The findings of the study suggested that MPBL has strong analgesic, anti-inflammatory, and antioxidant effects, conforming the traditional use of this plant for inflammatory pain alleviation to its antioxidant potentiality.

SU-F-P-55: Testicular Scatter Dose Determination During Prostate SBRT with and Without Pelvic Lymph Nodes

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

Venencia, C; Garrigo, E; Castro Pena, P

Purpose: The elective irradiation of pelvis lymph node for prostate cancer is still controversial. Including pelvic lymph node as part of the planning target volume could increase the testicular scatter dose, which could have a clinical impact. The objective of this work was to measure testicular scatter dose for prostate SBRT treatment with and without pelvic lymph nodes using TLD dosimetry. Methods: A 6MV beam (1000UM/min) produce by a Novalis TX (BrainLAB-VARIAN) equipped HDMLC was used. Treatment plan were done using iPlan v4.5.3 (BrainLAB) treatment planning system with sliding windows IMRT technique. Prostate SBRT plan (PLAN-1) uses 9 beams withmore » a dose prescription (D95%) of 4000cGy in 5 fractions. Prostate with lymph nodes SBRT plan (PLAN-2) uses 11 beams with a dose prescription (D95%) of 4000cGy to the prostate and 2500cGy to the lymph node in 5 fractions. An anthropomorphic pelvic phantom with a testicular volume was used. Phantom was positioned using ExacTrac IGRT system. Phosphor TLDs LiF:Mg, Ti (TLD700 Harshaw) were positioned in the anterior, posterior and inferior portion of the testicle. Two set of TLD measurements was done for each treatment plan. TLD in vivo dosimetry was done in one patient for each treatment plan. Results: The average phantom scatter doses per fraction for the PLAN-1 were 10.9±1cGy (anterior), 7.8±1cGy (inferior) and 10.7±1cGy (posterior) which represent an average total dose of 48±1cGy (1.2% of prostate dose prescription). The doses for PLAN-2 plan were 17.7±1cGy (anterior), 11±1cGy (inferior) and 13.3±1cGy (posterior) which represent an average total dose of 70.1±1cGy (1.8% of prostate dose prescription). The average dose for in vivo patient dosimetry was 60±1cGy for PLAN-1 and 85±1cGy for PLAN-2. Conclusion: Phantom and in vivo dosimetry shows that the pelvic lymph node irradiation with SBRT slightly increases the testicular scatter dose, which could have a clinical impact.« less

Melatonin for sleep disturbance in children with neurodevelopmental disorders: prospective observational naturalistic study.

PubMed

Ayyash, Hani F; Preece, Phillip; Morton, Richard; Cortese, Samuele

2015-06-01

Although melatonin is increasingly used for sleep disturbances in children with neurodevelopmental disorders, evidence on effective dose and impact on specific types of sleep disturbance is limited. We assessed 45 children (35 males, mean age: 6.3 ± 1.7 years) with neurodevelopmental disorders (n = 29: intellectual disability; n = 9: autism spectrum disorder; n = 7: attention-deficit/hyperactivity disorder) and sleep disturbances, treated with melatonin (mean duration: 326 days) with doses increased according to response. Thirty-eight percent of children responded to low (2.5-3 mg), 31% to medium (5-6 mg) and 9% to high doses (9-10 mg) of melatonin, with a significant increase in total hours of sleep/night, decreased sleep onset delay and decreased number of awakenings/night (all: p = 0.001), as measured with sleep diaries. No serious adverse events were reported. Melatonin is generally effective and safe in children with neurodevelopmental conditions. Increasing above 6 mg/night adds further benefit only in a small percentage of children.

SOME CHANGES IN THE CARBOHYDRATE METABOLISM AND THE ALBUMIN FRACTION OF THE BLOOD SERUM OF RABBITS IN CASE OF CHRONIC TREATMENT WITH IRON-59 (in Russian)

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

Orlyanskaya, R.L.

1962-01-01

A study was undertaken to determine the effect of chronic daily poisoning of rabbits with Fe/sup 59/on the sugar content of the blood, the albumin fraction, and the total albumin content after treatment with glucose. The results indicated that daily administration of 1 and 10 mu C/kg of body weight of Fe/sup 59/ for a total of 16 months causes only a slight change in the level of the blood sugar; only a chronic exposure to the higher dose resulted in a slight reduction in the sugar level. These animals also exhibited a tendency toward hypoglycemia. No changes were notedmore » in the total albumin content of the serum. Exposure to the higher dose for 6 months caused a reduction of the albumin fraction and a corresponding increase of the globulin content. The A/G ratio was found to decrease first, followed by an increase after a few months. (TTT)« less

[The influence of corvitin on secretory processes and blood flow in the rat gastric mucosa].

PubMed

Vovkun, T V; Ianchuk, P I; Shtanova, L Ia; Vesel'skyĭ, S P; Baranovs'kyĭ, V A

2013-01-01

We studied parameters of gastric secretion in pylorus-ligated rat and blood flow in the rat gastric mucosa under the influence of drug corvitin used intragastrically in doses of 2.5 and 5 mg/kg. Biochemical analysis of gastric juice was based on the determination of pH, total hydrochloric acid production and total protein, hexosamine and cysteine concentration. Gastric juice analysis in control rats found the presence of hexosamines-- a gastric mucus indicators and cysteine--free amino acid whith properties of a strong antioxidant. Concentration of these compounds in the gastric juice increased as a consequence of corvitin action. However, corvitin did not affect at these parameters of gastric secretion as the volume of gastric juice, pH, hydrochloric acid output rate, protein concentration. Additionally it was shown that corvitin in dose-dependent manner increased blood flow in the gastric mucosa. This results give reason to believe that corvitin can be considered as a tool that amplifies gastric mucosal defense mechanisms without affecting the secretion of gastric hydrochloric acid and total protein.

[Exposure to toxic dose of adrenaline on the functional state of the liver].

PubMed

Kopylova, S V; Vlasova, K M; Anashkina, A A

2017-01-01

The blood biochemical parameters characterizing the functional state of the liver, and the morphological profile of the body after a single exposure to a toxic dose of adrenaline were studied. Studies were conducted on 60 adult rats (female) weighing 0.15-0.2 kg, were divided into groups: intact animals; experience - animals, injected with epinephrine hydrochloride intraperitoneally in a dose of 0.5 mg/kg. All kinds of Biological material (blood, liver) were collected out through one and ten days after the start of the experiment. The degree of influence of high doses of epinephrine were evaluated in terms of lipid peroxidation (LPO) and protein (PSP) in liver homogenates, the concentration of average weight molecules (MSM), the activity of ALT, AST, alkaline phosphatase, LDH, total protein concentration, glucose and lactate in the blood plasma, as well as the determination of the prothrombin time (PTT) with the counting on the basis thereof of international normalized ration (INR). Histology of the liver was studied by light microscopy. It was found that throughout the experiment, there was an increased in the concentration of lipid peroxidation products and protein in liver homogenates, there was an increase in the concentration of MSM 1.7. Twenty-four hours after the administration of a toxic dose of adrenaline observed hyperenzymemia that manifested an increase in the activity of ALT and AST, was an increase in LDH. After 10-day five after the start of the experiment established the presence hyperenzymemia activity decreased ALT and AST, LDH activity remained elevated, total protein level was higher than in the group of animal in which investigations were conducted one day after the start of the experiment, PTV also continued to decline. In histological sections of the development of a pathological condition characterized by circulatory disturbance - plasmatization, both in central and in small vessels. From the hepatocytes both in the center and the periphery had changes granular dystrophy type, to some extent vacuolar.

Total Dose Survivability of Hubble Electronic Components

NASA Technical Reports Server (NTRS)

Xapsos, M. A.; Stauffer, C.; Jordan, T.; Poivey, C.; Haskins, D. N.; Lum, G.; Pergosky, A. M.; Smith, D. C.; LaBel, K. A.

2017-01-01

A total dose analysis for exposure of electronic parts at the box level is presented for the Hubble Space Telescope. This was done using solid angle sectoring/3-dimensional ray trace and Monte Carlo radiation transport simulations. Results are discussed in terms of parts that are potential total dose concerns.

New Approach to Total Dose Specification for Spacecraft Electronics

NASA Technical Reports Server (NTRS)

Xapsos, Michael

2017-01-01

Variability of the space radiation environment is investigated with regard to total dose specification for spacecraft electronics. It is shown to have a significant impact. A new approach is developed for total dose requirements that replaces the radiation design margin concept with failure probability during a mission.

LTC1877 High Efficiency Regulator Total Ionizing Dose Test Report

NASA Technical Reports Server (NTRS)

Oldham, Timothy; Pellish, Jonathan; Boutte, Alvin

2012-01-01

This report presents total ionizing dose evaluation data for the Linear Technology Corporation LTC1877 high efficiency monolithic synchronous step-down regulator. Data sheet parameters were tracked as a function of ionizing dose up to a total of 20 krad(SiO2). Control devices were also used.

SU-E-J-124: 18F-FDG PET Imaging to Improve RT Treatment Outcome for Locally Advanced Lung Cancer

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

Shusharina, N; Khan, F; Sharp, G

2015-06-15

Purpose: To investigate spatial correlation between high uptake regions of pre- and 10-days-post therapy{sup 1} {sup 8}F-FDG PET in recurrent lung cancer and to evaluate the feasibility of dose escalation boosting only regions with high FDG uptake identified on baseline PET. Methods: Nineteen patients with stages II– IV inoperable lung cancer were selected. Volumes of interest (VOI) on pre-therapy FDG-PET were defined using an isocontour at ≥50% of SUVmax. VOI of pre- and post-therapy PET images were correlated for the extent of overlap. A highly optimized IMRT plan to 60 Gy prescribed to PTV defined on the planning CT wasmore » designed using clinical dose constraints for the organs at risk. A boost of 18 Gy was prescribed to the VOI defined on baseline PET. A composite plan of the total 78 Gy was compared with the base 60 Gy plan. Increases in dose to the lungs, spinal cord and heart were evaluated. IMRT boost plan was compared with proton RT and SBRT boost plans. Results: Overlap fraction of baseline PET VOI with the VOI on 10 days-post therapy PET was 0.8 (95% CI: 0.7 – 0.9). Using baseline VOI as a boosting volume, dose could be escalated to 78 Gy for 15 patients without compromising the dose constraints. For 4 patients, the dose limiting factors were V20Gy and Dmean for the total lung, and Dmax for the spinal cord. An increase of the dose to OARs correlated significantly with the relative size of the boost volume. Conclusion: VOI defined on baseline 18F-FDG PET by the SUVmax-≥50% isocontour may be a biological target volume for escalated radiation dose. Dose escalation to this volume may provide improved tumor control without breaching predefined dose constraints for OARs. The best treatment outcome may be achieved with proton RT for large targets and with SBRT for small targets.« less

WE-EF-207-05: Monte Carlo Dosimetry for a Dedicated Cone-Beam CT Head Scanner

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

Sisniega, A; Zbijewski, W; Xu, J

Purpose: Cone-Beam CT (CBCT) is an attractive platform for point-of-care imaging of traumatic brain injury and intracranial hemorrhage. This work implements and evaluates a fast Monte-Carlo (MC) dose estimation engine for development of a dedicated head CBCT scanner, optimization of acquisition protocols, geometry, bowtie filter designs, and patient-specific dosimetry. Methods: Dose scoring with a GPU-based MC CBCT simulator was validated on an imaging bench using a modified 16 cm CTDI phantom with 7 ion chamber shafts along the central ray for 80–100 kVp (+2 mm Al, +0.2 mm Cu). Dose distributions were computed in a segmented CBCT reconstruction of anmore » anthropomorphic head phantom with 4×10{sup 5} tracked photons per scan (5 min runtime). Circular orbits with angular span ranging from short scan (180° + fan angle) to full rotation (360°) were considered for fixed total mAs per scan. Two aluminum filters were investigated: aggressive bowtie, and moderate bowtie (matched to 16 cm and 32 cm water cylinder, respectively). Results: MC dose estimates showed strong agreement with measurements (RMSE<0.001 mGy/mAs). A moderate (aggressive) bowtie reduced the dose, per total mAs, by 20% (30%) at the center of the head, by 40% (50%) at the eye lens, and by 70% (80%) at the posterior skin entrance. For the no bowtie configuration, a short scan reduced the eye lens dose by 62% (from 0.08 mGy/mAs to 0.03 mGy/mAs) compared to full scan, although the dose to spinal bone marrow increased by 40%. For both bowties, the short scan resulted in a similar 40% increase in bone marrow dose, but the reduction in the eye lens was more pronounced: 70% (90%) for the moderate (aggressive) bowtie. Conclusions: Dose maps obtained with validated MC simulation demonstrated dose reduction in sensitive structures (eye lens and bone marrow) through combination of short-scan trajectories and bowtie filters. Xiaohui Wang and David Foos are employees of Carestream Health.« less

Repeated sugammadex reversal of muscle relaxation during lumbar spine surgery with intraoperative neurophysiological multimodal monitoring.

PubMed

Errando, C L; Blanco, T; Díaz-Cambronero, Ó

2016-11-01

Intraoperative neurophysiological monitoring during spine surgery is usually acomplished avoiding muscle relaxants. A case of intraoperative sugammadex partial reversal of the neuromuscular blockade allowing adequate monitoring during spine surgery is presented. A 38 year-old man was scheduled for discectomy and vertebral arthrodesis throughout anterior and posterior approaches. Anesthesia consisted of total intravenous anesthesia plus rocuronium. Intraoperatively monitoring was needed, and the muscle relaxant reverted twice with low dose sugammadex in order to obtain adequate responses. The doses of sugammadex used were conservatively selected (0.1mg/kg boluses increases, total dose needed 0.4mg/kg). Both motor evoqued potentials, and electromyographic responses were deemed adequate by the neurophysiologist. If muscle relaxation was needed in the context described, this approach could be useful to prevent neurological sequelae. This is the first study using very low dose sugammadex to reverse rocuronium intraoperatively and to re-establish the neuromuscular blockade. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

A multicenter study of plasma use in the United States.

PubMed

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

2015-06-01

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

Acute liver failure in a term neonate after repeated paracetamol administration

PubMed Central

Bucaretchi, Fábio; Fernandes, Carla Borrasca; Branco, Maíra Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araújo; Porta, Gilda

2014-01-01

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) after receiving oral paracetamol (10mg/kg/dose every 4 hours) for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days. PMID:24676202

Effect of supplementation with flaxseed oil and different doses of fish oil for 2 weeks on plasma phosphatidylcholine fatty acids in young women.

PubMed

Hodson, Leanne; Crowe, Francesca L; McLachlan, Kirsten J; Skeaff, C Murray

2018-06-01

Although assumed, it remains unclear that fatty acid (FA) biomarkers of n-3 long-chain PUFA reflect wide ranges of intake. However, to be utilised as biomarkers, to predict dietary intake, dose-response curves that cover a spectrum of intakes are required. The aim of the study was to investigate whether the FA composition of plasma phosphatidylcholine (PC) is a sensitive biomarker of n-3 FAs from fish oil, across a range of supplementation doses, and alpha-linolenic acid (ALA) supplementation, in young, healthy women. A total of 303 young women were randomised to intakes ranging between 0.33 and 4.50 g EPA+DHA/day from fish oil (not all doses used in each year) or flaxseed oil (5.90-6.60 g/d) daily for 14 days in a series of trials, over 5 years. Fasting blood was collected at baseline (day 0) and day 14 and plasma PC FA composition, total and HDL-cholesterol and triglyceride concentrations measured. Fourteen days supplementation with fish oil significantly (P < 0.01) increased, in a dose-dependent fashion, plasma PC EPA, DPA and DHA at all doses except 1 and 3 mL/day. For the combined group of women who consumed any fish oil there was a 16% (P < 0.01) decrease in plasma triacylglycerol concentrations after 14 days supplementation. Flaxseed oil supplementation for 14 day resulted in significant (P < 0.01) increases in ALA, EPA and DPA, whilst DHA remained unchanged. Our data demonstrate plasma PC is a sensitive biomarker of n-3 FA intake and reflects changes within 14 days across a range of intakes.

A multicenter study of plasma use in the United States

PubMed Central

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

2016-01-01

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

Performance traits and metabolic responses in goats (Capra hircus) supplemented with inorganic trivalent chromium.

PubMed

Haldar, Sudipto; Mondal, Souvik; Samanta, Saikat; Ghosh, Tapan Kumar

2009-11-01

The effects of supplemental chromium (Cr) as chromic chloride hexahydrate in incremental dose levels (0, 0.5, 1.0, and 1.5 mg/day for 240 days) on metabolism of nutrients and trace elements were determined in dwarf Bengal goats (Capra hircus, castrated males, average age 3 months, n = 24, initial mean body weight 6.4 +/- 0.22 kg). Live weight increased linearly (p < 0.05) with the level of supplemental Cr. Organic matter and crude protein digestibility, intake of total digestible nutrients, and retention of N (g/g N intake) increased (p < 0.05) in a dose-dependent linear manner. Serum cholesterol and tryacylglycerol concentrations changed inversely with the dose of supplemental Cr (p < 0.01). Supplemental Cr positively influenced retention of copper and iron (p < 0.05) causing linear increase (p < 0.01) in their serum concentrations. It was concluded that Cr supplementation may improve utilization of nutrients including the trace elements and may also elicit a hypolidemic effect in goats. However, further study with regards to optimization of dose is warranted.

Chromosomal Aberrations in Wild Mice Captured in Areas Differentially Contaminated by the Fukushima Dai-Ichi Nuclear Power Plant Accident.

PubMed

Kubota, Yoshihisa; Tsuji, Hideo; Kawagoshi, Taiki; Shiomi, Naoko; Takahashi, Hiroyuki; Watanabe, Yoshito; Fuma, Shoichi; Doi, Kazutaka; Kawaguchi, Isao; Aoki, Masanari; Kubota, Masahide; Furuhata, Yoshiaki; Shigemura, Yusaku; Mizoguchi, Masahiko; Yamada, Fumio; Tomozawa, Morihiko; Sakamoto, Shinsuke H; Yoshida, Satoshi

2015-08-18

Following the Fukushima Dai-ichi Nuclear Power Plant accident, radiation effects on nonhuman biota in the contaminated areas have been a great concern. The induction of chromosomal aberrations in splenic lymphocytes of small Japanese field mice (Apodemus argenteus) and house mice (Mus musculus) inhabiting Fukushima Prefecture was investigated. In mice inhabiting the slightly contaminated area, the average frequency of dicentric chromosomes was similar to that seen in mice inhabiting a noncontaminated control area. In contrast, mice inhabiting the moderately and heavily contaminated areas showed a significant increase in the average frequencies of dicentric chromosomes. Total absorbed dose rate was estimated to be approximately 1 mGy d(-1) and 3 mGy d(-1) in the moderately and heavily contaminated areas, respectively. Chromosomal aberrations tended to roughly increase with dose rate. Although theoretically, the frequency of chromosomal aberrations was considered proportional to the absorbed dose, chromosomal aberrations in old mice (estimated median age 300 days) did not increase with radiation dose at the same rate as that observed in young mice (estimated median age 105 days).

Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions

NASA Technical Reports Server (NTRS)

Worgul, B. V.; Brenner, D. J.; Medvedovsky, C.; Merriam, G. R. Jr; Huang, Y.

1993-01-01

PURPOSE. To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS. Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS. In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS. The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

Interaction between physostigmine and soman on brain regional cholinesterase activity and /sup 3/H-physostigmine distribution

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

Hallak, M.E.; Woodruff, E.; Giacobini, E.

1986-03-05

Physostigmine (Phy) concentrations (as radioactivity) were studied in various brain areas after /sup 3/H-Phy administration as a function of time. Five min after 500 ..mu..g/kg i.m., cortex (CX) and total brain showed similar concentrations (370 ng/g) which were 50-90% higher than those of other brain regions (striatum, hippocampus, and medulla oblongata). Soman did not affect Phy levels in whole brain after pretreatment with Phy (100 or 500 ..mu..g/kg), however, the regional distribution of Phy was altered by soman as was ChE inhibition. A significant increase in Phy concentration was seen in HC (22 and 45% at 5 and 30 min,more » respectively) and CX (21% at 30 min). ChE activity in total brain was 12, 30, and 24% (5, 15 and 30 min after soman administration) lower than after Phy alone. If the pretreatment dose of Phy was increased to 500 ..mu..g/kg /sup 3/H-Phy, ChE activity was further reduced to 4, 13 and 19%. This might indicate that higher doses of Phy provide more protection of the enzyme from soman than lower doses. The protective role of Phy seen in total brain was not consistent for all brain regions. Soman alone produced a 95% ChE inhibition and there were no differences in its effect between total brain or brain areas. Pretreatment of the rat with Phy produced a protective effect upon ChE activity up to 30 min. However, no protective effect on survival was observed.« less

The effect of dosing regimens on the antimalarial efficacy of dihydroartemisinin-piperaquine: a pooled analysis of individual patient data.

PubMed

2013-12-01

Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy. A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI 96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%-96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%-21%) for every 5 mg/kg decrease in dose; p = 0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed. DP demonstrates excellent efficacy in a wide range of transmission settings; however, treatment failure is associated with a lower dose of piperaquine, particularly in young children, suggesting potential for further dose optimisation.

Atomoxetine Increased Effect over Time in Adults with Attention-Deficit/Hyperactivity Disorder Treated for up to 6 Months: Pooled Analysis of Two Double-Blind, Placebo-Controlled, Randomized Trials.

PubMed

Wietecha, Linda A; Clemow, David B; Buchanan, Andrew S; Young, Joel L; Sarkis, Elias H; Findling, Robert L

2016-07-01

Changes in the magnitude of efficacy throughout 26 weeks of atomoxetine treatment, along with impact of dosing, were evaluated in adults with ADHD from two randomized, double-blind, placebo-controlled studies. Pooled placebo (n = 485) and atomoxetine (n = 518) patients, dosed 25, 40, 60, 80 (target dose), or 100 mg daily, were assessed. Change from baseline in Conners' Adult ADHD Rating Scale-Investigator Rated Scale: Screening Version (CAARS) total ADHD symptoms score and Adult ADHD Investigator Symptom Rating Scale (AISRS) total score were analyzed using mixed-model repeated measures, with least squares mean change, effect size, and response rate calculated at 1, 2, 4, 8, 12, 16, 22, and 26 weeks. Decreases on CAARS for atomoxetine- versus placebo-treated patients were consistently statistically significantly greater at every time point beginning at one week (P ≤ 0.006, 0.28 effect size). By 4 weeks, comparison was -13.19 compared with -8.84 (P < 0.0001, 0.45 effect size). By 26 weeks, mean change was -15.42 versus -9.71 (0.52 effect size); increase in effect size over time was most pronounced in the 80 mg group (0.82 effect size). AISRS demonstrated similar results. Atomoxetine response rate (CAARS 50% decrease) continued to increase throughout 26 weeks. Atomoxetine treatment in adults with ADHD was associated with small effect sizes after 4 weeks and moderate effect sizes by 6 months of treatment. The data support increased effect size and response rate over time during longer-term treatment at target dose. © 2016 Eli Lilly and Company. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Total dose bias dependency and ELDRS effects in bipolar linear devices

NASA Technical Reports Server (NTRS)

Yui, C. C.; McClure, S. S.; Rex, B. G.; Lehman, J. M.; Minto, T. D.; Wiedeman, M.

2002-01-01

Total dose tests of several bipolar linear devices show sensitivity to both dose rate and bias during exposure. All devices exhibited Enhanced Low Dose Rate Sensitivity (ELDRS). An accelerated ELDRS test method for three different devices demonstrate results similar to tests at low dose rate. Behavior and critical parameters from these tests are compared and discussed.

Dose-Dependent Effects of Theta Burst rTMS on Cortical Excitability and Resting-State Connectivity of the Human Motor System

PubMed Central

Nettekoven, Charlotte; Volz, Lukas J.; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.

2014-01-01

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. PMID:24828639

Hepatoprotective and Antioxidant Activity of Dunaliella salina in Paracetamol-induced Acute Toxicity in Rats

PubMed Central

Madkour, Fedekar F.; Abdel-Daim, M. M.

2013-01-01

Paracetamol has a reasonable safety profile when taken in therapeutic doses. However, it could induce hepatotoxicity and even more severe fatal acute hepatic damage when taken in an overdose. The green alga, Dunaliella salina was investigated for hepatoprotective and antioxidant activity against paracetamol-induced liver damage in rats. Male albino Wistar rats overdosed with paracetamol showed liver damage and oxidative stress as indicated by significantly (P<0.05) increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide. At the same time, there were decreased activities of serum superoxide dismutase and total antioxidant capacity compared with the control group. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg body weight or silymarin could significantly (P<0.05) decrease the liver damage marker enzymes, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide levels and increase the activities of superoxide dismutase and total antioxidant capacity in serum when compared with paracetamol intoxicated group. Liver histopathology also showed that D. salina reduced the centrilobular necrosis, congestion and inflammatory cell infiltration evoked by paracetamol overdose. These results suggest that D. salina exhibits a potent hepatoprotective effect on paracetamol-induced liver damage in rats, which may be due to both the increase of antioxidant enzymes activity and inhibition of lipid peroxidation. PMID:24591738

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

NASA Astrophysics Data System (ADS)

Odonnell, F. R.; Etnier, E. L.; Holton, G. A.; Travis, C. C.

1981-10-01

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

Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation

PubMed Central

Williams, Benjamin B.; Dong, Ruhong; Nicolalde, Roberto J.; Matthews, Thomas P.; Gladstone, David J.; Demidenko, Eugene; Zaki, Bassem I.; Salikhov, Ildar K.; Lesniewski, Piotr N.; Swartz, Harold M.

2014-01-01

Purpose The ability to estimate individual exposures to radiation following a large attack or incident has been identified as a necessity for rational and effective emergency medical response. In vivo electron paramagnetic resonance (EPR) spectroscopy of tooth enamel has been developed to meet this need. Materials and methods A novel transportable EPR spectrometer, developed to facilitate tooth dosimetry in an emergency response setting, was used to measure upper incisors in a model system, in unirradiated subjects, and in patients who had received total body doses of 2 Gy. Results A linear dose response was observed in the model system. A statistically significant increase in the intensity of the radiation-induced EPR signal was observed in irradiated versus unirradiated subjects, with an estimated standard error of dose prediction of 0.9 + 0.3 Gy. Conclusions These results demonstrate the current ability of in vivo EPR tooth dosimetry to distinguish between subjects who have not been irradiated and those who have received exposures that place them at risk for acute radiation syndrome. Procedural and technical developments to further increase the precision of dose estimation and ensure reliable operation in the emergency setting are underway. With these developments EPR tooth dosimetry is likely to be a valuable resource for triage following potential radiation exposure of a large population. PMID:21696339

Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in a prospective cohort as remission maintenance in patients with rheumatoid arthritis.

PubMed

Kikuchi, Jun; Kondo, Tsuneo; Shibata, Akiko; Sakai, Ryota; Okada, Yusuke; Chino, Kentaro; Okuyama, Ayumi; Kurasawa, Takahiko; Takei, Hirofumi; Amano, Koichi

2018-05-01

To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission. Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 - erythrocyte sedimentation rate [ESR] ≤ 2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits. Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five. A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.

Genetic effects in children exposed in prenatal period to ionizing radiation after the Chornobyl nuclear power plant accident.

PubMed

Stepanova, Ye I; Vdovenko, V Yu; Misharina, Zh A; Kolos, V I; Mischenko, L P

2016-12-01

To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Incidence of minor developmental anomalies was studied in children exposed to radiation in utero (study group) and in the control group (1144 subjects surveyed in total). Cytogenetic tests using the method of differential G-banding of chromosomes were conducted in 60 children of both study and control groups (10-12-year-olds) and repeatedly in 39 adolescents (15-17-year-olds). A direct correlation was found between the number of minor developmental anomalies and fetal dose of radiation, and a reverse one with fetal gestational age at the time of radiation exposure. Incidence of chromosomal damage in somatic cells of 10-12-year-old children exposed prenatally was associated with radiation dose to the red bone marrow. The repeated testing has revealed that an increased level of chromosomal aberrations was preserved in a third of adolescents. The persons exposed to ionizing radiation at prenatal period should be attributed to the group of carcinogenic risk due to persisting increased levels of chromosome damage. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

[Foshouningshen decoction improves sleeping via the serotonergic system in a rat model of insomnia].

PubMed

Huang, Jie-Cong; Xie, Wei; Deng, Ning; Liang, Wen-Lin; Hu, Dong-Rong; Hong, Yu; Zhou, Yang

2017-08-20

To evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HT 1A R) in the hippocampus in a rat model of insomnia. Male KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HT 1A R protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively. In the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (P<0.05); in the test with a threshold dose of sodium pentobarbital, treatment with moderate- and high-dose FSNSD resulted in significantly prolonged sleeping time (P<0.01) and shortened sleep latency (P<0.05) in the mice. The rats in insomnia model group showed increased total distance in open field test (P<0.05) with significantly decreased content of 5-HT (P<0.01) and expressions of 5-HT 1A R protein and mRNA in the hippocampus (P<0.01). Treatment of the rats with estazolam or high-dose FSNSD obviously decreased the total distance in open field test (P<0.05) and increased the content of 5-HT (P<0.05) and expressions of 5-HT 1A R (P<0.01) in the hippocampus of rats with insomnia. FSNSD can produce therapeutic effects on insomnia possibly by increasing 5-HT content and expressions of 5-HT 1A R in the hippocampus.

Allogeneic Cardiospheres Delivered via Percutaneous Transendocardial Injection Increase Viable Myocardium, Decrease Scar Size, and Attenuate Cardiac Dilatation in Porcine Ischemic Cardiomyopathy

PubMed Central

Tseliou, Eleni; Cheng, Ke; Luthringer, Daniel J.; Ho, Chak-Sum; Takayama, Kentaro; Minamino, Naoto; Dawkins, James F.; Chowdhury, Supurna; Duong, Doan Trang; Seinfeld, Jeffrey; Middleton, Ryan C.; Dharmakumar, Rohan; Li, Debiao; Marbán, Linda; Makkar, Raj R.; Marbán, Eduardo

2014-01-01

Background Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy. Methods and Results We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled (“dose optimization”) study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled (“pivotal”) study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo. Conclusions Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration. PMID:25460005

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure.

PubMed

Sherlock, Mark; Behan, Lucy Ann; Hannon, Mark J; Alonso, Aurora Aragon; Thompson, Christopher J; Murray, Robert D; Crabtree, Nicola; Hughes, Beverly A; Arlt, Wiebke; Agha, Amar; Toogood, Andrew A; Stewart, Paul M

2015-11-01

Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy. To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition. We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE. Endocrine Centres within University Teaching Hospitals in the UK and Ireland. Urinary corticosteroid metabolite profile and body composition assessment. In study A, when patients were divided into three groups - patients not receiving HC and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls. In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype. © 2015 European Society of Endocrinology.

Association Between Media Dose, Ad Tagging, and Changes in Web Traffic for a National Tobacco Education Campaign: A Market-Level Longitudinal Study

PubMed Central

Davis, Kevin C; Patel, Deesha; Rodes, Robert; Beistle, Diane

2016-01-01

Background In 2012, the US Centers for Disease Control and Prevention (CDC) launched Tips From Former Smokers (Tips), the first federally funded national tobacco education campaign. In 2013, a follow-up Tips campaign aired on national cable television networks, radio, and other channels, with supporting digital advertising to drive traffic to the Tips campaign website. Objective The objective of this study was to use geographic and temporal variability in 2013 Tips campaign television media doses and ad tagging to evaluate changes in traffic to the campaign website in response to specific doses of campaign media. Methods Linear regression models were used to estimate the dose-response relationship between weekly market-level television gross rating points (GRPs) and weekly Web traffic to the Tips campaign website. This relationship was measured using unique visitors, total visits, and page views as outcomes. Ad GRP effects were estimated separately for ads tagged with the Tips campaign website URL and 1-800-QUIT-NOW. Results In the average media market, an increase of 100 television GRPs per week for ads tagged with the Tips campaign website URL was associated with an increase of 650 unique visitors (P<.001), 769 total visits (P<.001), and 1255 total page views (P<.001) per week. The associations between GRPs for ads tagged with 1-800-QUIT-NOW and each Web traffic measure were also statistically significant (P<.001), but smaller in magnitude. Conclusions Based on these findings, we estimate that the 16-week 2013 Tips television campaign generated approximately 660,000 unique visitors, 900,000 total visits, and 1,390,000 page views for the Tips campaign website. These findings can help campaign planners forecast the likely impact of targeted advertising efforts on consumers’ use of campaign-specific websites. PMID:26887959

Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test

PubMed Central

Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen

2013-01-01

Introduction Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Methods Forty male Wistar rats weighing 180–220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Results Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) Conclusion The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats. PMID:22970723

Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test.

PubMed

Yang, Chun; Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen; Yang, Jian-Jun

2013-03-01

Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Forty male Wistar rats weighing 180-220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats.

Promoting Abstinence from Cocaine and Heroin with a Methadone Dose Increase and a Novel Contingency

PubMed Central

Schmittner, John; Umbricht, Annie; Schroeder, Jennifer R.; Moolchan, Eric T.; Preston, Kenzie L.

2010-01-01

To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 X 3 (Dose X Contingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100 mg/day, double blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or “split”). The “split” contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was “split” between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The Split 100mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose Noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required. PMID:19101098

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

PubMed Central

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

2013-01-01

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

Comparison of patient specific dose metrics between chest radiography, tomosynthesis, and CT for adult patients of wide ranging body habitus

PubMed Central

Zhang, Yakun; Li, Xiang; Segars, W. Paul; Samei, Ehsan

2014-01-01

Purpose: Given the radiation concerns inherent to the x-ray modalities, accurately estimating the radiation doses that patients receive during different imaging modalities is crucial. This study estimated organ doses, effective doses, and risk indices for the three clinical chest x-ray imaging techniques (chest radiography, tomosynthesis, and CT) using 59 anatomically variable voxelized phantoms and Monte Carlo simulation methods. Methods: A total of 59 computational anthropomorphic male and female extended cardiac-torso (XCAT) adult phantoms were used in this study. Organ doses and effective doses were estimated for a clinical radiography system with the capability of conducting chest radiography and tomosynthesis (Definium 8000, VolumeRAD, GE Healthcare) and a clinical CT system (LightSpeed VCT, GE Healthcare). A Monte Carlo dose simulation program (PENELOPE, version 2006, Universitat de Barcelona, Spain) was used to mimic these two clinical systems. The Duke University (Durham, NC) technique charts were used to determine the clinical techniques for the radiographic modalities. An exponential relationship between CTDIvol and patient diameter was used to determine the absolute dose values for CT. The simulations of the two clinical systems compute organ and tissue doses, which were then used to calculate effective dose and risk index. The calculation of the two dose metrics used the tissue weighting factors from ICRP Publication 103 and BEIR VII report. Results: The average effective dose of the chest posteroanterior examination was found to be 0.04 mSv, which was 1.3% that of the chest CT examination. The average effective dose of the chest tomosynthesis examination was found to be about ten times that of the chest posteroanterior examination and about 12% that of the chest CT examination. With increasing patient average chest diameter, both the effective dose and risk index for CT increased considerably in an exponential fashion, while these two dose metrics only increased slightly for radiographic modalities and for chest tomosynthesis. Effective and organ doses normalized to mAs all illustrated an exponential decrease with increasing patient size. As a surface organ, breast doses had less correlation with body size than that of lungs or liver. Conclusions: Patient body size has a much greater impact on radiation dose of chest CT examinations than chest radiography and tomosynthesis. The size of a patient should be considered when choosing the best thoracic imaging modality. PMID:24506654

Monte Carlo investigation of backscatter point spread function for x-ray imaging examinations

NASA Astrophysics Data System (ADS)

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

2017-03-01

X-ray imaging examinations, especially complex interventions, may result in relatively high doses to the patient's skin inducing skin injuries. A method was developed to determine the skin-dose distribution for non-uniform x-ray beams by convolving the backscatter point-spread-function (PSF) with the primary-dose distribution to generate the backscatter distribution that, when added to the primary dose, gives the total-dose distribution. This technique was incorporated in the dose-tracking system (DTS), which provides a real-time color-coded 3D-mapping of skin dose during fluoroscopic procedures. The aim of this work is to investigate the variation of the backscatter PSF with different parameters. A backscatter PSF of a 1-mm x-ray beam was generated by EGSnrc Monte-Carlo code for different x-ray beam energies, different soft-tissue thickness above bone, different bone thickness and different entrance-beam angles, as well as for different locations on the SK-150 anthropomorphic head phantom. The results show a reduction of the peak scatter to primary dose ratio of 48% when X-ray beam voltage is increased from 40 keV to 120 keV. The backscatter dose was reduced when bone was beneath the soft tissue layer and this reduction increased with thinner soft tissue and thicker bone layers. The backscatter factor increased about 21% as the angle of incidence of the beam with the entrance surface decreased from 90° (perpendicular) to 30°. The backscatter PSF differed for different locations on the SK-150 phantom by up to 15%. The results of this study can be used to improve the accuracy of dose calculation when using PSF convolution in the DTS.

Comparison of Propofol, Propofol-Remifentanil, and Propofol-Fentanyl Administrations with Each Other Used for the Sedation of Patients to Undergo ERCP

PubMed Central

Haytural, Candan; Aydınlı, Bahar; Demir, Berna; Bozkurt, Elif; Parlak, Erkan; Dişibeyaz, Selçuk; Saraç, Ahmet; Özgök, Ayşegül; Kazancı, Dilek

2015-01-01

Introduction. Using single anesthetic agent in endoscopic retrograde cholangiopancreatography (ERCP) may lead to inadequate analgesia and sedation. To achieve the adequate analgesia and sedation the single anesthetic agent doses must be increased which causes undesirable side effects. For avoiding high doses of single anesthetic agent nowadays combination with sedative agents is mostly a choice for analgesia and sedation for ERCP. Aim. The aim of this study is to investigate the effects of propofol alone, propofol + remifentanil, and propofol + fentanyl combinations on the total dose of propofol to be administered during ERCP and on the pain scores after the process. Materials and Method. This randomized study was performed with 90 patients (ASA I-II-III) ranging between 18 and 70 years of age who underwent sedation/analgesia for elective ERCP. The patients were administered only propofol (1.5 mg/kg) in Group Ι, remifentanil (0.05 μg/kg) + propofol (1.5 mg/kg) combination in Group II, and fentanyl (1 μg/kg) + propofol (1.5 mg/kg) combination in Group III. All the patients' sedation levels were assessed with the Ramsey Sedation Scale (RSS). Their recovery was assessed with the Aldrete and Numerical Rating Scale Score (NRS) at 10 min intervals. Results. The total doses of propofol administered to the patients in the three groups in this study were as follows: 375 mg in Group I, 150 mg in Group II, and 245 mg in Group III. Conclusion. It was observed that, in the patients undergoing ERCP, administration of propofol in combination with an opioid provided effective and reliable sedation, reduced the total dose of propofol, increased the practitioner satisfaction, decreased the pain level, and provided hemodynamic stability compared to the administration of propofol alone. PMID:26576424

Comparative total and unbound pharmacokinetics of cefazolin administered by bolus versus continuous infusion in patients undergoing major surgery: a randomized controlled trial.

PubMed

Naik, B I; Roger, C; Ikeda, K; Todorovic, M S; Wallis, S C; Lipman, J; Roberts, J A

2017-06-01

Perioperative administration of cefazolin reduces the incidence of perioperative infections. Intraoperative re-dosing of cefazolin is commonly given between 2 and 5 h after the initial dose. This study was undertaken to determine whether intraoperative continuous infusions of cefazolin achieve better probability of target attainment (PTA) and fractional target attainment (FTA) than intermittent dosing. Patients undergoing major surgery received cefazolin 2 g before surgical incision. They were subsequently randomized to receive either an intermittent bolus (2 g every 4 h) or continuous infusion (500 mg h -1 ) of cefazolin until skin closure. Blood samples were analysed for total and unbound cefazolin concentrations using a validated chromatographic method. Population pharmacokinetic modelling was performed using Pmetrics ® software. Calculations of PTA and FTA were performed for common pathogens. Ten patients were enrolled in each arm. A two-compartment linear model best described the time course of the total plasma cefazolin concentrations. The covariates that improved the model were body weight and creatinine clearance. Protein binding varied with time [mean (range) 69 (44-80)%] with a fixed 21% unbound value of cefazolin used for the simulations (120 min post-initial dosing). Mean ( sd ) central volume of distribution was 5.73 (2.42) litres, and total cefazolin clearance was 4.72 (1.1) litres h -1 . Continuous infusions of cefazolin consistently achieved better drug exposures and FTA for different weight and creatinine clearances, particularly for less susceptible pathogens. Our study demonstrates that intraoperative continuous infusions of cefazolin increase the achievement of target plasma concentrations, even with lower infusion doses. Renal function and body weight are important when considering the need for alternative dosing regimens. NCT02058979. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Optimal clinical trial design based on a dichotomous Markov-chain mixed-effect sleep model.

PubMed

Steven Ernest, C; Nyberg, Joakim; Karlsson, Mats O; Hooker, Andrew C

2014-12-01

D-optimal designs for discrete-type responses have been derived using generalized linear mixed models, simulation based methods and analytical approximations for computing the fisher information matrix (FIM) of non-linear mixed effect models with homogeneous probabilities over time. In this work, D-optimal designs using an analytical approximation of the FIM for a dichotomous, non-homogeneous, Markov-chain phase advanced sleep non-linear mixed effect model was investigated. The non-linear mixed effect model consisted of transition probabilities of dichotomous sleep data estimated as logistic functions using piecewise linear functions. Theoretical linear and nonlinear dose effects were added to the transition probabilities to modify the probability of being in either sleep stage. D-optimal designs were computed by determining an analytical approximation the FIM for each Markov component (one where the previous state was awake and another where the previous state was asleep). Each Markov component FIM was weighted either equally or by the average probability of response being awake or asleep over the night and summed to derive the total FIM (FIM(total)). The reference designs were placebo, 0.1, 1-, 6-, 10- and 20-mg dosing for a 2- to 6-way crossover study in six dosing groups. Optimized design variables were dose and number of subjects in each dose group. The designs were validated using stochastic simulation/re-estimation (SSE). Contrary to expectations, the predicted parameter uncertainty obtained via FIM(total) was larger than the uncertainty in parameter estimates computed by SSE. Nevertheless, the D-optimal designs decreased the uncertainty of parameter estimates relative to the reference designs. Additionally, the improvement for the D-optimal designs were more pronounced using SSE than predicted via FIM(total). Through the use of an approximate analytic solution and weighting schemes, the FIM(total) for a non-homogeneous, dichotomous Markov-chain phase advanced sleep model was computed and provided more efficient trial designs and increased nonlinear mixed-effects modeling parameter precision.

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

PubMed

Santarmaki, Valentini; Kourkoutas, Yiannis; Zoumpopoulou, Georgia; Mavrogonatou, Eleni; Kiourtzidis, Mikis; Chorianopoulos, Nikos; Tassou, Chrysoula; Tsakalidou, Effie; Simopoulos, Constantinos; Ypsilantis, Petros

2017-09-01

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

Dosimetric aspects of breast radiotherapy with three-dimensional and intensity-modulated radiotherapy helical tomotherapy planning modules

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

Yadav, Poonam; Service of Radiation Therapy, University of Wisconsin Aspirus Cancer Center, Wisconsin Rapids, WI; Yan, Yue, E-mail: yyan5@mdanderson.org

In this work, we investigated the dosimetric differences between the intensity-modulated radiotherapy (IMRT) plans and the three-dimensional (3D) helical plans based on the TomoTherapy system. A total of 15 patients with supine setup were randomly selected from the data base. For patients with lumpectomy planning target volume (PTV), regional lymph nodes were also included as part of the target. For dose sparing, the significant differences between the helical IMRT and helical 3D were only found in the heart and contralateral breast. For the dose to the heart, helical IMRT reduced the maximum point dose by 6.98 Gy compared to themore » helical 3D plan (p = 0.01). For contralateral breast, the helical IMRT plans significantly reduced the maximum point dose by 5.6 Gy compared to the helical 3D plan. However, compared to the helical 3D plan, the helical IMRT plan increased the volume for lower dose (13.08% increase in V{sub 5} {sub Gy}, p = 0.01). In general, there are no significant differences in dose sparing between helical IMRT and helical 3D plans.« less

Effect of the dose of exogenous fibrolytic enzyme preparations on preingestive fiber hydrolysis, ruminal fermentation, and in vitro digestibility of bermudagrass haylage.

PubMed

Romero, J J; Zarate, M A; Adesogan, A T

2015-01-01

Our objectives were to evaluate the effects of the dose rates of 5 Trichoderma reesei and Aspergillus oryzae exogenous fibrolytic enzymes (EFE; 1A, 2A, 11C, 13D, and 15D) on in vitro digestibility, fermentation characteristics, and preingestive hydrolysis of bermudagrass haylage and to identify the optimal dose of each EFE for subsequent in vitro and in vivo studies. In experiment 1, EFE were diluted in citrate-phosphate buffer (pH 6) and applied in quadruplicate in each of 2 runs at 0× (control), 0.5×, 1×, 2×, and 3×; where 1× was the respective manufacturer-recommended dose (2.25, 2.25, 10, 15, and 15g of EFE/kg of dry matter). The suspension was incubated for 24h at 25°C and for a further 24h at 39°C after the addition of ruminal fluid. In experiment 2, a similar approach to that in experiment 1 was used to evaluate simulated preingestive effects, except that sodium azide (0.02% wt/vol) was added to the EFE solution. The suspension was incubated for 24h at 25°C and then 15mL of water was added before filtration to extract water-soluble compounds. For both experiments, data for each enzyme were analyzed separately as a completely randomized block design with a model that included effects of EFE dose, run, and their interaction. In experiment 1, increasing the EFE dose rate nonlinearly increased the DM digestibility of 1A, 2A, 11C, and 13D and the neutral detergent fiber digestibility (NDFD) of 1A, 2A, 11C, and 13D. Optimal doses of 1A, 2A, 11C, 13D, and 15D, as indicated by the greatest increases in NDFD at the lowest dose tested, were 2×, 2×, 1×, 0.5×, and 0.5×, respectively. Increasing the dose rate of 2A, 11C, and 13D nonlinearly increased concentrations of total volatile fatty acids and propionate (mM), decreased their acetate-to-propionate ratios and linearly decreased those of samples treated with 1A and 15D. In experiment 2, increasing the dose rate of each EFE nonlinearly decreased concentrations of netural detergent fiber; also, increasing the dose rate of 1A, 2A, 11C, and 1D nonlinearly increased concentrations of water-soluble carbohydrates and free ferulic acid (μg/g). Application of increasing doses of the EFE increased NDF hydrolysis, NDFD, and ruminal fluid fermentation of bermudagrass haylage, but the optimal dose varied with the EFE. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Propagation of an Avirulent Turkey Hemorrhagic Enteritis Virus Isolate in Chickens.

PubMed

Gerber, Priscilla F; Hossain, Mohammad F; Reynolds, Paul; Hoang, Phuong; Burgess, Susan K; Renz, Katrin; McMillan, Mary; Katz, Margaret E; Walkden-Brown, Stephen W

2018-03-01

A series of studies were undertaken to optimize the propagation of hemorrhagic enteritis virus (HEV) in specific-pathogen-free (SPF) chickens. A total of 562 SPF chickens were orally inoculated with an Australian avirulent HEV isolate of turkey origin at 9, 14, 21, or 28 days of age with 5, 6, 7, or 8 log  10 genomic copies (GC), while 102 chickens served as uninfected controls. No clinical signs were observed in infected chickens. There was an inoculum-dose-dependent increase in the relative spleen and liver weight ( P < 0.01). Relative spleen weight 7 days post-HEV inoculation was up to 85% higher in chickens that were inoculated with 6 to 7 GC compared with controls, with no further increase at higher doses. Relative liver weight increased up to 14% in chickens inoculated with 6 GC, with no further increase. Birds inoculated with a 7 GC dose had a higher frequency of HEV DNA-positive birds (77% to 86%) than birds inoculated with lower doses (33% to 59%; P < 0.01). The most efficient dose for live passage propagation was 7 GC inoculated in 9-to-14-day-old birds, yielding an infection rate of 81%. Livers and spleens from infected birds at all doses were processed to produce a putative vaccine with a final GC recovery in the vaccine material of 8.6 GC/bird. In summary, HEV of turkey origin can be readily propagated in SPF chickens, and conditions to maximize viral retrieval were established.

Effects of gibberellic acid on hemocytes of Galleria mellonella L. (Lepidoptera: Pyralidae).

PubMed

Altuntaş, H; Kılıç, A Y; Uçkan, F; Ergin, E

2012-06-01

The impacts of different doses of the plant growth regulator gibberellic acid (GA(3)) in diet on the number of total and differential hemocytes, frequency of apoptotic, and necrotic hemocytes, mitotic indices, encapsulation, and melanization responses were investigated using the greater wax moth Galleria mellonella L. (Lepidoptera: Pyralidae) larvae. Total hemocyte counts increased in G. mellonella larvae at all treatment doses whereas GA(3) application had no effect on the number of different hemocyte types. The occurrence of apoptosis, necrosis and mitotic indices in GA(3) treated and untreated last instars were detected by acridine orange or ethidium bromide double staining by fluorescence microscopy. While the ratio of necrotic hemocytes increased at all GA(3) treatments, that of late apoptotic cells was only higher at doses >200 ppm when compared with untreated larvae. The percentage of mitotic index also increased at 5,000 ppm. Positively charged DEAE Sephadex A-25 beads were used for analysis of the levels of encapsulation and melanization in GA(3) treated G. mellonella larvae. At four and 24 h posttreatments with Sephadex A-25 bead injection, insects were dissected under a stereomicroscope. Encapsulation rates of larval hemocytes were dependent on the extent of encapsulation and time but not treatment groups. While the extent of melanization of hemocytes showed differences related to time, in general, a decrease was observed at all doses of GA(3) treated larvae at 24 h. We suggest that GA(3) treatment negatively affects hemocyte physiology and cell immune responses inducing cells to die by necrosis and apoptosis in G. mellonella larvae.

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

PubMed

Nichols, Blake; Kubis, Sherri; Hewlett, Jennifer; Yehya, Nadir; Srinivasan, Vijay

2017-09-01

The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. Retrospective cohort study. Non-cardiac PICU. Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. None. The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 μg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 μg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 μg/dL (all p < 0.05). Children with stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p < 0.05). Mean random serum total cortisol levels were similar in children with and without stress dose hydrocortisone (21.1 vs 18.7 μg/dL; p = 0.69). In children with random serum total cortisol less than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p < 0.05). In children with random serum total cortisol greater than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU mortality and fewer ventilator-free days and vasopressor-free days (all p < 0.05). Stress dose hydrocortisone therapy in children with catecholamine-dependent septic shock correlated more with severity of illness than random serum total cortisol levels and was associated with worse outcomes, irrespective of random serum total cortisol levels.

The Relative Effects of Manual Versus Automatic Exposure Control on Radiation Dose to Vital Organs in Total Hip Arthroplasty.

PubMed

Harper, Katharine D; Li, Shidong; Jennings, Rachel; Amer, Kamil M; Haydel, Christopher; Ali, Sayed

2018-01-01

Technologic advances have reduced medical radiation exposure while maintaining image quality. The purpose of this study was to determine the effects of the presence of total hip arthroplasty implants, compared with native hips, on radiation exposure of the most radiosensitive organs when manual and automatic exposure control settings are used. Detection probes were placed at six locations (stomach, sigmoid colon, right pelvic wall, left pelvic wall, pubic symphysis, and anterior pubic skin) in a cadaver. Radiographs were obtained with the use of manual and automatic exposure control protocols, with exposures recorded. A total hip arthroplasty implant was placed in the cadaver, probe positioning was confirmed, and the radiographs were repeated, with exposure values recorded. The control probe placed at the stomach had values ranging from 0.00 mSv to 0.01 mSv in protocols with and without implants. With the manual protocol, exposures in the pelvis ranged from 0.36 mSv to 2.74 mSv in the native hip and from 0.33 mSv to 2.24 mSv after implant placement. The increases in exposure after implant placement, represented as relative risk, were as follows: stomach, 1.000; pubic symphysis, 0.818; left pelvic wall, 1.381; sigmoid colon, 1.550; right pelvic wall, 0.917; and anterior pubic skin, 1.015. With automatic exposure control, exposures in the pelvis ranged from 0.07 mSv to 0.89 mSv in the native hip and from 0.21 mSv to 1.15 mSv after implant placement. With automatic exposure control, the increases in exposure after implant placement, represented as relative risk, were as follows: stomach, 1.000; pubic symphysis, 1.292; left pelvic wall, 1.476; sigmoid colon, 2.182; right pelvic wall, 3.000; and anterior pubic skin, 1.378. The amount of radiation to which patients are exposed as a result of medical procedures or imaging, and whether exposure is associated with an increased risk of malignant transformation, are the subject of ongoing debate. We found that after insertion of a total hip arthroplasty implant, exposure values increased threefold at some anatomic locations and surpassed 1 mSv, the generally accepted threshold for concern. Radiation exposure to radiosensitive organs increased up to threefold after total hip implantation with automatic exposure control and up to approximately 1.5 times with the manual protocol. Doses were greater with manual exposures than with automatic exposure control (except at the control probe on the stomach, where exposure was negligible, as expected). However, after implant placement, doses increased more with automatic exposure control than with manual exposure. This difference can be attributed to increased scatter and the difficulty of dose modification because of the density of the implant. Current radiographic protocols should be reassessed to determine if the benefits of frequent radiographs outweigh the newly demonstrated risks.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer.

PubMed

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony; Bowen, Stephen R

2018-04-01

Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung V RX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. In this ten-patient sample, CTV V95 decreased significantly from 99-100% for PBopt to 77-94% for MCrecalc and recovered to 99-100% for MCopt (P<10 -5 ). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10 -3 ). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =-1%) compared to MCrecalc (ΔD95 =-6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., V RX ). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10 -3 ). MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer

PubMed Central

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony

2018-01-01

Background Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. Methods With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung VRX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. Results In this ten-patient sample, CTV V95 decreased significantly from 99–100% for PBopt to 77–94% for MCrecalc and recovered to 99–100% for MCopt (P<10−5). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10−3). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =−1%) compared to MCrecalc (ΔD95 =−6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., VRX). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10−3). Conclusions MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy. PMID:29876310

Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus.

PubMed

Sattler, F R; Jaque, S V; Schroeder, E T; Olson, C; Dube, M P; Martinez, C; Briggs, W; Horton, R; Azen, S

1999-04-01

This nonplacebo-controlled, open label, randomized study was conducted to test the hypotheses that pharmacological doses of nandrolone decanoate would increase lean body tissue, muscle mass, and strength in immunodeficient human immunodeficiency virus-infected men, and that these effects would be enhanced with progressive resistance training (PRT). Thirty human immunodeficiency virus-positive men with fewer than 400 CD4 lymphocytes/mm3 were randomly assigned to receive weekly injections of nandrolone alone or in combination with supervised PRT at 80% of the one-repetition maximum three times weekly for 12 weeks. Total body weight increased significantly in both groups (3.2 +/- 2.7 and 4.0 +/- 2.0 kg, respectively; P < 0.001), with increases due primarily to augmentation of lean tissue. Lean body mass determined by dual energy x-ray absorptiometry increased significantly more in the PRT group (3.9 +/- 2.3 vs. 5.2 +/- 5.7 kg, respectively; P = 0.03). Body cell mass by bioelectrical impedance analysis increased significantly (P < 0.001) in both groups (2.6 +/- 1.0 vs. 2.9 +/- 0.8 kg), but to a similar magnitude (P = NS). Significant increases in cross-sectional area by magnetic resonance imaging of total thigh muscles (1538 +/- 767 and 1480 +/- 532 mm2), quadriceps (705 +/- 365 and 717 +/- 288 mm2), and hamstrings (842 +/- 409 and 771 +/- 295 mm2) occurred with both treatment strategies (P < 0.001 for the three muscle areas); these increases were similar in both groups (P = NS). By the one-repetition method, strength increased in both upper and lower body exercises, with gains ranging from 10.3-31% in the nandrolone group and from 14.4-53.0% in the PRT group (P < 0.006 with one exception). Gains in strength were of significantly greater magnitude in the PRT group (P < or = 0.005 for all comparisons), even after correction for lean body mass. Thus, pharmacological doses of nandrolone decanoate yielded significant gains in total weight, lean body mass, body cell mass, muscle size, and strength. The increases in lean body mass and muscular strength were significantly augmented with PRT.

SU-G-BRB-14: Uncertainty of Radiochromic Film Based Relative Dose Measurements

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

Devic, S; Tomic, N; DeBlois, F

2016-06-15

Purpose: Due to inherently non-linear dose response, measurement of relative dose distribution with radiochromic film requires measurement of absolute dose using a calibration curve following previously established reference dosimetry protocol. On the other hand, a functional form that converts the inherently non-linear dose response curve of the radiochromic film dosimetry system into linear one has been proposed recently [Devic et al, Med. Phys. 39 4850–4857 (2012)]. However, there is a question what would be the uncertainty of such measured relative dose. Methods: If the relative dose distribution is determined going through the reference dosimetry system (conversion of the response bymore » using calibration curve into absolute dose) the total uncertainty of such determined relative dose will be calculated by summing in quadrature total uncertainties of doses measured at a given and at the reference point. On the other hand, if the relative dose is determined using linearization method, the new response variable is calculated as ζ=a(netOD)n/ln(netOD). In this case, the total uncertainty in relative dose will be calculated by summing in quadrature uncertainties for a new response function (σζ) for a given and the reference point. Results: Except at very low doses, where the measurement uncertainty dominates, the total relative dose uncertainty is less than 1% for the linear response method as compared to almost 2% uncertainty level for the reference dosimetry method. The result is not surprising having in mind that the total uncertainty of the reference dose method is dominated by the fitting uncertainty, which is mitigated in the case of linearization method. Conclusion: Linearization of the radiochromic film dose response provides a convenient and a more precise method for relative dose measurements as it does not require reference dosimetry and creation of calibration curve. However, the linearity of the newly introduced function must be verified. Dave Lewis is inventor and runs a consulting company for radiochromic films.« less

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

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

Richter, Daniel; TU Darmstadt, Darmstadt; Saito, Nami

2014-05-01

Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporalmore » correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V{sub 95}) and 107% (V{sub 107}) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V{sub 95} and V{sub 107} values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V{sub 95} > 87%, SD < 3%) and overdose (mean V{sub 107} < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.« less

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

Brock, K; Lee, C; Samuels, S

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

TU-EF-304-12: Proton Radiation Therapy for Left-Sided Breast Cancer: LET and RBE Considerations for Cardiac Toxicity

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

Giantsoudi, D; Jee, K; MacDonald, S

Purpose: Increased risk of coronary artery disease has been documented for patients treated with radiation for left-sided breast cancer. Proton therapy (PRT) has been shown to significantly decrease cardiac irradiation, however variations in relative biological effectiveness (RBE) have been ignored so far. In this study we evaluate the impact of accounting for RBE variations on sensitive structures located within high linear energy transfer (LET) areas (distal end) of the proton treatment fields, for this treatment site. Methods: Three patients treated in our institution with PRT for left-sided breast cancer were selected. All patients underwent reconstructive surgery after mastectomy and treatedmore » to a total dose of 50.4Gy with beam(s) vertical to the chest wall. Dose and LET distributions were calculated using Monte Carlo (MC-TOPAS - TOol for PArticle Simulation). The LET-based, variable-RBE-weighted dose was compared to the analytical calculation algorithm (ACA) and MC dose distributions for a constant RBE of 1.1, based on volume histograms and mean values for the target, heart and left anterior descending coronary artery (LAD). Results: Assuming a constant RBE and compared to the ACA dose, MC predicted lower mean target and heart doses by 0.5% to 2.7% of the prescription dose. For variable RBE, plan evaluation showed increased mean target dose by up to 5%. Mean variable-RBE-weighted doses for the LAD ranged from 2.7 to 5.9Gy(RBE) among patients increased by 41%–64.2% compared to constant RBE ACA calculation (absolute dose: 1.7–3.9Gy(RBE)). Smaller increase in mean heart doses was noticed. Conclusion: ACA overestimates the target mean dose by up to 2.7%. However, disregarding variations in RBE may lead to significant underestimation of the dose to sensitive structures at the distal end of the proton treatment field and could thus impact outcome modeling for cardiac toxicities after proton therapy. These results are subject to RBE model and parameter uncertainties.« less

Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

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

Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.

The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

DOE PAGES

Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; ...

2015-06-01

The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

PubMed

Lenarczyk, Marek; Su, Jidong; Haworth, Steven T; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q; Harmann, Leanne; Hopewell, John W; Kronenberg, Amy; Patel, Shailendra; Moulder, John E; Baker, John E

2015-06-01

The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

Calcium intake and colorectal adenoma risk: dose-response meta-analysis of prospective observational studies.

PubMed

Keum, NaNa; Lee, Dong Hoon; Greenwood, Darren C; Zhang, Xuehong; Giovannucci, Edward L

2015-04-01

Evidence from randomized controlled trials suggests that calcium may protect against recurrence of colorectal adenomas, which could lead to the subsequent prevention of cancer. Yet the trials used only a large single dose and were of small sizes, and thus, knowledge of the dose-response relationship and influence on high-risk adenomas is limited. To address these issues, we conducted linear and nonlinear dose-response meta-analyses primarily based on prospective observational studies published up to July 2014 identified from PubMed and Embase. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated for total and supplemental calcium intake, respectively, using a random-effects model. For total calcium intake, summary RR for each 300 mg/day increase was 0.95 (95% CI = 0.92-0.98; I(2)  = 45%; eight studies with 11,005 cases; range of intake = 333-2,229 mg/day). Evidence of nonlinearity was indicated: approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.92 (95% CI = 0.89-0.94) at 1,000 mg/day and 0.87 (95% CI = 0.84-0.90) at 1,450 mg/day (pnonlinearity  < 0.01). Associations were stronger for high-risk adenomas (≥1 cm in diameter, (tubulo)villous histology, dysplasia, or multiplicity): approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.77 (95% CI = 0.74-0.81) at 1,000 mg/day and reduced to 0.69 (95% CI = 0.66-0.73) at 1,450 mg/da (pnonlinearity  < 0.01). For supplemental calcium intake, summary RR of total adenoma risk for each 300 mg/day increase was 0.96 (95% CI = 0.93-0.99; I(2)  = 0%; three studies with 4,548 cases; range of supplementation = 0-1,366 mg/day). In conclusion, calcium intake may continue to decrease the risk of adenomas, particularly high-risk adenomas, over a wide range of calcium intake. © 2014 UICC.

Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-D3) dilution in rats.

PubMed

Stimpson, Stephen A; Turner, Scott M; Clifton, Lisa G; Poole, James C; Mohammed, Hussein A; Shearer, Todd W; Waitt, Greg M; Hagerty, Laura L; Remlinger, Katja S; Hellerstein, Marc K; Evans, William J

2012-06-01

There is currently no direct, facile method to determine total-body skeletal muscle mass for the diagnosis and treatment of skeletal muscle wasting conditions such as sarcopenia, cachexia, and disuse. We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d(3)) (D(3)-creatinine) in urine after a defined oral tracer dose of D(3)-creatine can be used to determine creatine pool size and skeletal muscle mass. We determined 1) an oral tracer dose of D(3)-creatine that was completely bioavailable with minimal urinary spillage and sufficient enrichment in the body creatine pool for detection of D(3)-creatine in muscle and D(3)-creatinine in urine, and 2) the time to isotopic steady state. We used cross-sectional studies to compare total creatine pool size determined by the D(3)-creatine dilution method to lean body mass determined by independent methods. The tracer dose of D(3)-creatine (<1 mg/rat) was >99% bioavailable with 0.2-1.2% urinary spillage. Isotopic steady state was achieved within 24-48 h. Creatine pool size calculated from urinary D(3)-creatinine enrichment at 72 h significantly increased with muscle accrual in rat growth, significantly decreased with dexamethasone-induced skeletal muscle atrophy, was correlated with lean body mass (r = 0.9590; P < 0.0001), and corresponded to predicted total muscle mass. Total-body creatine pool size and skeletal muscle mass can thus be accurately and precisely determined by an orally delivered dose of D(3)-creatine followed by the measurement of D(3)-creatinine enrichment in a single urine sample and is promising as a noninvasive tool for the clinical determination of skeletal muscle mass.

Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline.

PubMed Central

Crane, J; Burgess, C; Beasley, R

1989-01-01

The cardiovascular and hypokalaemic effects of equal doses of inhaled fenoterol, isoprenaline and salbutamol were compared in eight healthy male volunteers, in a double blind, placebo controlled study. Increasing doses of 400, 600, and 800 micrograms were given from a metered dose inhaler at 15 minute intervals, followed by measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, and plasma potassium concentration. After repeated inhalation, fenoterol resulted in significantly greater chronotropic, electrocardiographic, and hypokalaemic effects than either isoprenaline or salbutamol. The maximum inotropic effect of fenoterol was similar to that of isoprenaline. PMID:2928998

Effect of abomasal carbohydrates and live yeast on measures of postruminal fermentation.

PubMed

Gressley, T F; Davison, K A; Macies, J; Leonardi, C; McCarthy, M M; Nemec, L M; Rice, C A

2016-01-01

Two studies were conducted to evaluate the effects of abomasal carbohydrate infusion on nutrient digestibility and fecal measures. In Exp. 1, 5 Holstein steers were assigned to a Latin square with 1-wk periods and were abomasally infused on a single day at the end of each period with water alone, a single pulse dose of water with 1 g/kg BW oligofructose or cornstarch, or 4 pulse doses of water with 0.25 g/kg BW oligofructose or cornstarch administered every 6 h. Total tract nutrient digestibility was not affected by treatment except for a tendency for a decrease in starch digestibility in response to the 1 g/kg BW dose of cornstarch ( < 0.10). Compared with the control, both oligofructose and starch infusions caused similar decreases in fecal pH ( < 0.05) and increases in fecal short-chain fatty acids ( ≤ 0.01) measured 12 h after the first infusion, with the single 1 g/kg BW infusions causing a greater magnitude of pH change compared with the four 0.25-g/kg BW infusions ( < 0.01). All treatments increased concentration of fecal lipopolysaccharide compared with the control for at least 1 time point following the infusion ( < 0.05), with a greater increase observed for the 0.25 g/kg BW infusions of oligofructose compared with the other treatments ( < 0.05). Results of Exp. 1 indicate that both oligofructose and cornstarch infusions increased carbohydrate fermentation in the intestines and can be used as a method to evaluate the impact of excessive intestinal fermentation on intestinal health. In Exp. 2, 6 Holstein steers received abomasal pulse doses of 0 (control) or 10 g/d live var. (SB) according to a crossover design with 18-d periods. Abomasal infusions of 4 pulse doses of 0.25 g/kg BW oligofructose administered every 6 h were conducted on d 16 of each period. During the baseline period prior to the oligofructose challenge, there were no effects of SB on fecal measures except for an increase in apparent total tract NDF digestibility ( < 0.05), suggesting that SB increased intestinal fiber fermentation. During the oligofructose challenge, SB increased fecal score ( = 0.03) and tended to reduce fecal short-chain fatty acids ( = 0.10). Results of Exp. 2 suggest that abomasal SB modestly stabilized the intestinal environment during increased carbohydrate fermentation.

SU-E-T-193: FMEA Severity Scores - Do We Really Know?

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

Khan, A; Robertson, JD; Narra, V

2014-06-01

Purpose: Mycosis fungoides is a common form of cutaneous T-cell lymphoma which generally affects the skin. A typical course of treatment may include fractionated total skin electron beam therapy. Given the difficulties in uniformly irradiating some regions of the body and the need for frequent visits within the context of a fractionated protocol, this study investigated the feasibility of delivering the dose using form-fitting cloth which contained phosphorous-32 as a source for beta particle irradiation. Methods: A piece of fabric (0.97 g) consisting of a blend of spandex and flame retardant material impregnated with phosphorus-31 (2000 ppm) was bombarded withmore » neutrons to produce phosphorus-32. The cloth was then laid flat and a stack of radiochromic film placed on top. Sheets of film and tissue equivalent plastic were layered to form a stack measuring a total of 1 cm thickness and remained sandwiched for 77.3 hr. Results: The initial activity of the activated cloth was 44 μCi of P-32. The absorbed dose was uniform within planes parallel to the cloth and exponentially dependent on depth, delivering 560cGy at 0.3mm and falling to 20cGy at 3mm. Conclusion: The total dose prescribed for a typical course of TSET for mycosis fungoides is 36Gy delivered over 9 weeks and is expected to treat to at least 5mm depth. Therefore, the P-32 impregnated cloth may not be clinically indicated to treat this disease given the unfavorable depth-dose characteristics. However, a major advantage of using form-fitting cloth is the uniformity with which the dose could be delivered over the skin in areas which are not flat. Increasing the distance between cloth and skin could improve the depth-dose characteristics.« less

4D cone-beam CT imaging for guidance in radiation therapy: setup verification by use of implanted fiducial markers

NASA Astrophysics Data System (ADS)

Jin, Peng; van Wieringen, Niek; Hulshof, Maarten C. C. M.; Bel, Arjan; Alderliesten, Tanja

2016-03-01

The use of 4D cone-beam computed tomography (CBCT) and fiducial markers for guidance during radiation therapy of mobile tumors is challenging due to the trade-off between image quality, imaging dose, and scanning time. We aimed to investigate the visibility of markers and the feasibility of marker-based 4D registration and manual respiration-induced marker motion quantification for different CBCT acquisition settings. A dynamic thorax phantom and a patient with implanted gold markers were included. For both the phantom and patient, the peak-to-peak amplitude of marker motion in the cranial-caudal direction ranged from 5.3 to 14.0 mm, which did not affect the marker visibility and the associated marker-based registration feasibility. While using a medium field of view (FOV) and the same total imaging dose as is applied for 3D CBCT scanning in our clinic, it was feasible to attain an improved marker visibility by reducing the imaging dose per projection and increasing the number of projection images. For a small FOV with a shorter rotation arc but similar total imaging dose, streak artifacts were reduced due to using a smaller sampling angle. Additionally, the use of a small FOV allowed reducing total imaging dose and scanning time (~2.5 min) without losing the marker visibility. In conclusion, by using 4D CBCT with identical or lower imaging dose and a reduced gantry speed, it is feasible to attain sufficient marker visibility for marker-based 4D setup verification. Moreover, regardless of the settings, manual marker motion quantification can achieve a high accuracy with the error <1.2 mm.

Red and processed meat consumption and the risk of lung cancer: a dose-response meta-analysis of 33 published studies

PubMed Central

Xue, Xiu-Juan; Gao, Qing; Qiao, Jian-Hong; Zhang, Jie; Xu, Cui-Ping; Liu, Ju

2014-01-01

This meta-analysis was to summarize the published studies about the association between red/processed meat consumption and the risk of lung cancer. 5 databases were systematically reviewed, and random-effect model was used to pool the study results and to assess dose-response relationships. Results shown that six cohort studies and twenty eight case-control studies were included in this meat-analysis. The pooled Risk Radios (RR) for total red meat and processed meat were 1.44 (95% CI, 1.29-1.61) and 1.23 (95% CI, 1.10-1.37), respectively. Dose-response analysis revealed that for every increment of 120 grams red meat per day the risk of lung cancer increases 35% and for every increment of 50 grams red meat per day the risk of lung cancer increases 20%. The present dose-response meta-analysis suggested that both red and processed meat consumption showed a positive effect on lung cancer risk. PMID:25035778

Radiotherapy of soft tissue sarcomas in dogs.

PubMed

McChesney, S L; Withrow, S J; Gillette, E L; Powers, B E; Dewhirst, M W

1989-01-01

Megavoltage radiotherapy was administered to 42 dogs with soft tissue sarcoma. Acceptable local control of these aggressive tumors was achieved after one year of treatment. Control rates of 48 and 67% were obtained at doses of 45 and 50 gray (Gy), respectively. At 2 years, control rates decreased to 33% at the dose of 50 Gy. Serious complications developed in 4 of 42 dogs at doses of 40 to 50 Gy. The estimated dose with a 50% probability for causing serious complications was 54 Gy, given in 10 fractions. We believe that the large doses per fraction used in this study probably led to an increased probability for necrosis. Hemangiopericytomas seemed to be more responsive than fibrosarcomas. Only 2 of 11 recurrent tumors were controlled with surgery. Good local control was achieved with radiation alone for one year at doses with a low probability for serious complications; however, higher total radiation doses or combined modalities, such as surgery and radiation or radiation and hyperthermia, may be needed for longer-term control.

Phase I Design for Completely or Partially Ordered Treatment Schedules

PubMed Central

Wages, Nolan A.; O’Quigley, John; Conaway, Mark R.

2013-01-01

The majority of methods for the design of Phase I trials in oncology are based upon a single course of therapy, yet in actual practice it may be the case that there is more than one treatment schedule for any given dose. Therefore, the probability of observing a dose-limiting toxicity (DLT) may depend upon both the total amount of the dose given, as well as the frequency with which it is administered. The objective of the study then becomes to find an acceptable combination of both dose and schedule. Past literature on designing these trials has entailed the assumption that toxicity increases monotonically with both dose and schedule. In this article, we relax this assumption for schedules and present a dose-schedule finding design that can be generalized to situations in which we know the ordering between all schedules and those in which we do not. We present simulation results that compare our method to other suggested dose-schedule finding methodology. PMID:24114957

Inactivation of contaminated fungi and antioxidant effects of peach ( Prunus persica L. Batsch cv Dangeumdo) by 0.5-2 kGy gamma irradiation

NASA Astrophysics Data System (ADS)

Kim, Kyoung-Hee; Kim, Mi-Seon; Kim, Hong-Gi; Yook, Hong-Sun

2010-04-01

The effect of gamma irradiation (0.5-2 kGy) on the physicochemical properties of peaches was investigated during a 6-day storage at 20±3 °C. Gamma irradiation is able to inactivate the four pathogens, namely Botrytis cinerea, Penicillium expansum, Rhizopus stolonifer var. stolonifer and Monilinia fructicola in peaches. Hardness significantly decreased with the increment of irradiation dose level whereas soluble solid and total polyphenol contents increased with increment of irradiation dose level. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity of the irradiated peach was higher than that of control, and its activity increased with increment of irradiation dose level. These results suggest that gamma irradiation of peaches improved antioxidant activity, but dramatically affects the hardness throughout the entire storage time.

Gamma irradiation induced enhancement of phenylalanine ammonia-lyase (PAL) and antioxidant activity in peach ( Prunus persica Bausch, Cv. Elberta)

NASA Astrophysics Data System (ADS)

Hussain, Peerzada R.; Wani, Ali M.; Meena, Raghuveer S.; Dar, Mohd A.

2010-09-01

Effect of medium dose gamma irradiation on PAL and antioxidant activity of peach fruit was investigated. Peach fruit after harvest at commercial maturity was irradiated in the dose range 1.0-2.0 kGy, stored under refrigerated conditions (3±1 °C, RH 80%) and evaluated at intervals of 7 days. The antioxidant activity as determined by DPPH and FRAP methods revealed significant ( p≤0.05) increase particularly in the dose range 1.6-2.0 kGy. During storage, maximum increase in both PAL and antioxidant activity was observed after 21 days. Positive correlation ( r=0.75) existed between antioxidant activity and total phenols. EC 50 values as obtained from DPPH and FRAP experiments were significantly ( p≤0.05) lower in irradiated fruits compared to control.

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate.

PubMed

Cassell, S; Furst, D; Dromgoole, S; Paulus, H

1979-04-01

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.

Commentary: Ethical Issues of Current Health-Protection Policies on Low-Dose Ionizing Radiation

PubMed Central

Socol, Yehoshua; Dobrzyński, Ludwik; Doss, Mohan; Feinendegen, Ludwig E.; Janiak, Marek K.; Miller, Mark L.; Sanders, Charles L.; Scott, Bobby R.; Ulsh, Brant; Vaiserman, Alexander

2014-01-01

The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are “speculative, unproven, undetectable and ‘phantom’.” Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation. PMID:24910586

Examining the Starting Dose of Glyburide in Gestational Diabetes.

PubMed

Glover, Angelica V; Tita, Alan; Biggio, Joseph R; Harper, Lorie M

2016-01-01

The aim of this study was to determine the impact of initial glyburide dosing on pregnancy outcomes. STUDY DESign: Retrospective cohort of singleton pregnancies complicated by gestational diabetes mellitus (GDM) from 2007 to 2013. Women who received glyburide were compared by initial dose: 2.5 mg (n = 170) versus 5 mg (n = 154) total daily dose. The primary maternal outcome was hypoglycemia, defined as a blood glucose < 60 mg/dL. The primary neonatal outcome was birth weight. Secondary maternal outcomes included time to blood glucose control, preeclampsia, and cesarean delivery. Secondary neonatal outcomes included macrosomia (>4,000 g), hypoglycemia (<40 mg/dL), shoulder dystocia, and preterm delivery. The 5 mg/day glyburide dose did not increase maternal hypoglycemia (26% in the 2.5 mg/day group vs. 27% in the 5 mg/day group; adjusted odds ratio [AOR] 0.67; confidence interval [CI] 0.30-1.49). An increase in macrosomia in the 5 mg/day group was not significant after adjusting for maternal obesity (AOR 2.16; CI 0.96-4.88). Differences in preterm birth and large for gestational age were not significant after adjusting for prior preterm birth and maternal obesity, respectively. A higher starting dose of glyburide for the management of GDM was not associated with increased maternal hypoglycemia or decreased adverse neonatal outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose

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

Constine, Louis S.; Department of Pediatrics, James P. Wilmot Cancer Center at University of Rochester, Rochester, NY; Tarbell, Nancy

2008-09-01

Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). Results: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. Withmore » 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.« less

A moderate dose of red wine, but not de-alcoholized red wine increases coronary flow reserve.

PubMed

Kiviniemi, Tuomas O; Saraste, Antti; Toikka, Jyri O; Saraste, Markku; Raitakari, Olli T; Pärkkä, Jussi P; Lehtimäki, Terho; Hartiala, Jaakko J; Viikari, Jorma; Koskenvuo, Juha W

2007-12-01

Red wine consumption is associated with reduced cardiovascular disease mortality. Its cardioprotective properties may be partly related to its ability to improve endothelial function. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of red wine and de-alcoholized red wine improve coronary flow velocity reserve (CFR). Using transthoracic Doppler echocardiography, 176 CFR measurements were made in 22 healthy men before and after ingestion of a moderate (4.0+/-0.4 dl) and an escalating high dose (total amount 8.1+/-0.9 dl) of alcohol-containing red wine and de-alcoholized red wine, which contained similar amounts of phenolic substances. The difference in plasma antioxidant capacity was determined by colorimetric assay kit. Red wine increased CFR from 3.8+/-1.4 to 4.5+/-1.4 (p<0.01) and 4.0+/-1.2 (p=NS) after moderate and high doses, respectively; whereas de-alcoholized red wine had no significant effects on CFR (4.0+/-0.7, 4.3+/-1.3 and 4.5+/-1.4, respectively). Plasma antioxidant capacity increased significantly after high dose of red wine (27.5+/-14.7%, p<0.001), but not after de-alcoholized red wine (0.5+/-10.5%, p=NS) despite similar amounts of phenolic substances. Differences between CFR and plasma antioxidant capacities before and after drinking had no significant association. A moderate dose of red wine, but not de-alcoholized red wine increases CFR. The increase of CFR is probably mediated by other than direct antioxidant properties of polyphenols, because the simultaneous increase of CFR and plasma antioxidant capacity were not associated.

Subsequent malignancies in children treated for Hodgkin's disease: associations with gender and radiation dose.

PubMed

Constine, Louis S; Tarbell, Nancy; Hudson, Melissa M; Schwartz, Cindy; Fisher, Susan G; Muhs, Ann G; Basu, Swati K; Kun, Larry E; Ng, Andrea; Mauch, Peter; Sandhu, Ajay; Culakova, Eva; Lyman, Gary; Mendenhall, Nancy

2008-09-01

Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

Six months exposure to a real life mixture of 13 chemicals' below individual NOAELs induced non monotonic sex-dependent biochemical and redox status changes in rats.

PubMed

Docea, Anca Oana; Gofita, Eliza; Goumenou, Marina; Calina, Daniela; Rogoveanu, Otilia; Varut, Marius; Olaru, Cristian; Kerasioti, Efthalia; Fountoucidou, Polyxeni; Taitzoglou, Ioannis; Zlatian, Ovidiu; Rakitskii, Valerii N; Hernandez, Antonio F; Kouretas, Dimitrios; Tsatsakis, Aristidis

2018-05-01

This study assessed the potential adverse health effects of long-term low-dose exposure to chemical mixtures simulating complex real-life human exposures. Four groups of Sprague Dawley rats were administered mixtures containing carbaryl, dimethoate, glyphosate, methomyl, methyl parathion, triadimefon, aspartame, sodium benzoate, calcium disodium ethylene diamine tetra-acetate, ethylparaben, butylparaben, bisphenol A, and acacia gum at doses of 0, 0.25, 1 or 5 times the respective Toxicological Reference Values (TRV): acceptable daily intake (ADI) or tolerable daily intake (TDI) in a 24 weeks toxicity study. Body weight gain, feed and water consumption were evaluated weekly. At 24 weeks blood was collected and biochemistry parameters and redox status markers were assessed. Adverse effects were observed on body weight gain and in hepatotoxic parameters such as the total bilirubin, alanine aminotransferase (ALT) and alkaline phosphatase (ALP), especially in low dose and affecting mainly male rats. The low dose group showed increased catalase activity both in females and males, whereas the high dose group exhibited decreased protein carbonyl and total antioxidant capacity (TAC) levels in both sex groups. Non-monotonic effects and adaptive responses on liver function tests and redox status, leading to non-linear dose-responses curves, are probably produced by modulation of different mechanisms. Copyright © 2018. Published by Elsevier Ltd.

Doses to organs and tissues from concomitant imaging in radiotherapy: a suggested framework for clinical justification.

PubMed

Harrison, R M

2008-12-01

The increasing use of imaging for localization and verification in radiotherapy has raised issues concerning the justifiable doses to critical organs and tissues from concomitant exposures, particularly when extensive image-guided radiotherapy is indicated. Doses at positions remote from the target volume include components from high-energy leakage and scatter, as well as from concomitant imaging. In this paper, simulated prostate, breast and larynx treatments are used to compare doses from both high-energy and concomitant exposures as a function of distance from the target volume. It is suggested that the fraction, R, of the total dose at any point within the patient that is attributable to concomitant exposures may be a useful aid in their justification. R is small within the target volume and at large distances from it. However, there is a critical region immediately adjacent to the planning target volume where the dose from concomitant imaging combines with leakage and scatter to give values of R that approach 0.5 in the examples given here. This is noteworthy because the regions just outside the target volume will receive total doses in the order of 1 Gy, where commensurately high risk factors may not be substantially reduced because of cell kill. Other studies have identified these regions as sites of second cancers. The justification of an imaging regimen might therefore usefully take into account the maximum value of R encountered from the combination of imaging and radiotherapy for particular treatment sites.

Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

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

Neelis, Karen J.; Schimmel, Erik C.; Vermeer, Maarten H.

Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of themore » 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.« less

Detecting structural variances of Co 3O 4 catalysts by controlling beam-induced sample alterations in the vacuum of a transmission electron microscope

DOE PAGES

Kisielowski, C.; Frei, H.; Specht, P.; ...

2016-11-02

This article summarizes core aspects of beam-sample interactions in research that aims at exploiting the ability to detect single atoms at atomic resolution by mid-voltage transmission electron microscopy. Investigating the atomic structure of catalytic Co 3O 4 nanocrystals underscores how indispensable it is to rigorously control electron dose rates and total doses to understand native material properties on this scale. We apply in-line holography with variable dose rates to achieve this goal. Genuine object structures can be maintained if dose rates below ~100 e/Å 2s are used and the contrast required for detection of single atoms is generated by capturing largemore » image series. Threshold doses for the detection of single atoms are estimated. An increase of electron dose rates and total doses to common values for high resolution imaging of solids stimulates object excitations that restructure surfaces, interfaces, and defects and cause grain reorientation or growth. We observe a variety of previously unknown atom configurations in surface proximity of the Co 3O 4 spinel structure. These are hidden behind broadened diffraction patterns in reciprocal space but become visible in real space by solving the phase problem. Finallly, an exposure of the Co 3O 4 spinel structure to water vapor or other gases induces drastic structure alterations that can be captured in this manner.« less

The local and systemic side-effects of venom and inhaled-allergen subcutaneous immunotherapy.

PubMed

Adamic, Katja; Zidarn, Mihaela; Bajrovic, Nissera; Erzen, Renato; Kopac, Peter; Music, Ema

2009-01-01

Although immunotherapy is effective in allergic rhinitis, conjunctivitis, asthma and stinging insect hypersensitivity, it carries a risk of anaphylactic reactions. In a 4-year retrospective survey, we investigated 1257 adult patients who had received venom or inhaled-allergen subcutaneous immunotherapy. The dose-increase phase was performed as the 2-day rush protocol for venom immunotherapy and the 6-week protocol for inhaled-allergen immunotherapy. A total of 904 patients received venom immunotherapy and 353 patients inhaled-allergen immunotherapy. The prevalence of systemic reactions was 13.6%. The frequency of systemic reactions was higher during the maintenance phase than in the dose-increase phase (9.6% vs. 5.9%) and was highest in both phases of treatment with honeybee venom (P < 0.001). The majority of systemic reactions were mild. Five (0.4%) patients had reaction with a fall of blood pressure and were treated with adrenaline. There was no fatal outcome. The systemic side-effects during the dose-increase phase of venom immunotherapy occurred at a median dose of 46 microg (range 2-100 microg). Large local reactions occurred in 13.9% of patients without any significant difference between the allergens. We have shown that systemic reactions are not rare even during maintenance phase in patients with a well tolerated dose-increase phase of treatment. The most prominent risk factor for systemic reactions was immunotherapy with honeybee extract.

Organic and inorganic fertilizer effect on soil CO2 flux, microbial biomass, and growth of Nigella sativa L.

NASA Astrophysics Data System (ADS)

Salehi, Aliyeh; Fallah, Seyfollah; Sourki, Ali Abasi

2017-01-01

Cattle manure has a high carbon/nitrogen ratio and may not decompose; therefore, full-dose application of urea fertilizer might improve biological properties by increasing manure decomposition. This study aimed to investigate the effect of combining cattle manure and urea fertilizer on soil CO2 flux, microbial biomass carbon, and dry matter accumulation during Nigella sativa L. (black cumin) growth under field conditions. The treatments were control, cattle manure, urea, different levels of split and full-dose integrated fertilizer. The results showed that integrated application of cattle manure and chemical fertilizer significantly increased microbial biomass carbon by 10%, soil organic carbon by 2.45%, total N by 3.27%, mineral N at the flowering stage by 7.57%, and CO2 flux by 9% over solitary urea application. Integrated application increased microbial biomass carbon by 10% over the solitary application and the full-dose application by 5% over the split application. The soil properties and growth parameters of N. sativa L. benefited more from the full-dose application than the split application of urea. Cattle manure combined with chemical fertilizer and the full-dose application of urea increased fertilizer efficiency and improved biological soil parameters and plant growth. This method decreased the cost of top dressing urea fertilizer and proved beneficial for the environment and medicinal plant health.

Retrospective study evaluating dose standards for infliximab in patients with rheumatoid arthritis at Hospital Israelita Albert Einstein, São Paulo, Brazil.

PubMed

Scheinberg, Morton; Goldenberg, José; Feldman, Daniel P; Nóbrega, João Luiz

2008-08-01

We determined, in our surrounding environment, the proportion of patients being treated with infliximab who required a therapeutic scheme escalation (an infliximab dose increase surpassing the level of 3 mg/kg every 8 weeks and/or a decrease on the current between infusions' interval). This was a study of the retrospective analysis of data from the 41 rheumatoid arthritis (RA) patients receiving an infliximab therapy at the Albert Einstein Israelita Hospital, from January 2001 up to December 2005. A questionnaire was applied to these patients, assessing their clinical and laboratory data, adverse events, and individual information regarding the infliximab administration. Therapeutic dose information was available in 68% (28/41) of the RA patients, with 46% of these (13/28) receiving a dose increase, and 30% (8/27) experiencing a shortening of the between infusions' interval. The average final infliximab dose (4.21 mg/kg) was significantly greater than their average initial dose (3.29 mg/kg). The average time intervals between the initial and final infusions, though shortened, were not significantly different. A proportion of 73% (30/41) of these patients demonstrated improvement in at least one of the assessed clinical parameters, and 50% of these patients (15/30) experienced a dose increase, while 20% (6/30) experienced shortening of the between treatments' interval. A total of 20% (8/41) of the original patients experienced adverse events. Although infliximab is effective in the control of RA, dose adjustment and/or shortening of the between treatments' interval is frequently required.

Total Dose Effects on Single Event Transients in Digital CMOS and Linear Bipolar Circuits

NASA Technical Reports Server (NTRS)

Buchner, S.; McMorrow, D.; Sibley, M.; Eaton, P.; Mavis, D.; Dusseau, L.; Roche, N. J-H.; Bernard, M.

2009-01-01

This presentation discusses the effects of ionizing radiation on single event transients (SETs) in circuits. The exposure of integrated circuits to ionizing radiation changes electrical parameters. The total ionizing dose effect is observed in both complementary metal-oxide-semiconductor (CMOS) and bipolar circuits. In bipolar circuits, transistors exhibit grain degradation, while in CMOS circuits, transistors exhibit threshold voltage shifts. Changes in electrical parameters can cause changes in single event upset(SEU)/SET rates. Depending on the effect, the rates may increase or decrease. Therefore, measures taken for SEU/SET mitigation might work at the beginning of a mission but not at the end following TID exposure. The effect of TID on SET rates should be considered if SETs cannot be tolerated.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

Comparison of Biological Responses in Rats Under Various Cigarette Smoke Exposure Conditions

PubMed Central

Tsuji, Hiroyuki; Fujimoto, Hitoshi; Matsuura, Daiki; Nishino, Tomoki; Lee, K Monica; Yoshimura, Hiroyuki

2013-01-01

A variety of exposure regimens of cigarette smoke have been used in animal models of lung diseases. In this study, we compared biological responses of smoke exposure in rats, using different smoke concentrations (wet total particulate matter [WTPM]), daily exposure durations, and total days of exposure. As a range-finding acute study, we first compared pulmonary responses between SD and F344 strains after a single nose-only exposure to mainstream cigarette smoke or LPS. Secondly, F344 rats were exposed to cigarette smoke for 2 or 13 weeks under the comparable daily exposure dose (WTPM concentration x daily exposure duration; according to Haber’s rule) but at a different WTPM concentration or daily exposure duration. Blood carboxylhemoglobin was increased linearly to the WTPM concentration, while urinary nicotine plus cotinine value was higher for the longer daily exposure than the corresponding shorter exposure groups. Gamma glutamyl transferase activity in bronchoalveolar lavage fluid (BALF) was increased dose dependently after 2 and 13 weeks of cigarette smoke exposure, while the neutrophil content in BALF was not increased notably. Smoke-exposed groups showed reduced body weight gain and increased relative lung and heart weights. While BALF parameters and the relative lung weights suggest pulmonary responses, histopathological examination showed epithelial lesions mainly in the upper respiratory organs (nose and larynx). Collectively, the results indicate that, under the employed study design, the equivalent daily exposure dose (exposure concentration x duration) induces equivalent pulmonary responses in rats. PMID:23914058

Bisphenol S impairs blood functions and induces cardiovascular risks in rats.

PubMed

Pal, Sanghamitra; Sarkar, Kaushik; Nath, Partha Pratim; Mondal, Mukti; Khatun, Ashma; Paul, Goutam

2017-01-01

Bisphenol S (BPS) is an industrial chemical which is recently used to replace the potentially toxic Bisphenol A (BPA) in making polycarbonate plastics, epoxy resins and thermal receipt papers. The probable toxic effects of BPS on the functions of haemopoietic and cardiovascular systems have not been reported till to date. We report here that BPS depresses haematological functions and induces cardiovascular risks in rat. Adult male albino rats of Sprague-Dawley strain were given BPS at a dose level of 30, 60 and 120 mg/kg BW/day respectively for 30 days. Red blood cell (RBC) count, white blood cell (WBC) count, Hb concentration, and clotting time have been shown to be significantly (*P < 0.05) reduced in a dose dependent manner in all exposed groups of rats comparing to the control. It has also been shown that BPS increases total serum glucose and protein concentration in the exposed groups of rats. We have observed that BPS increases serum total cholesterol, triglyceride, glycerol free triglyceride, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) concentration, whereas high density lipoprotein (HDL) concentration has been found to be reduced in the exposed groups. BPS significantly increases serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities dose dependently. Moreover, serum calcium, bilirubin and urea concentration have been observed to be increased in all exposed groups. In conclusion, BPS probably impairs the functions of blood and promotes cardiovascular risks in rats.

Dietary Antioxidants Protect Hematopoietic Cells and Improve Animal Survival after Total-Body Irradiation

PubMed Central

Wambi, Chris; Sanzari, Jenine; Wan, X. Steven; Nuth, Manunya; Davis, James; Ko, Ying-Hui; Sayers, Carly M.; Baran, Matthew; Ware, Jeffrey H.; Kennedy, Ann R.

2009-01-01

The purpose of this study was to determine whether a dietary supplement consisting of L-selenomethionine, vitamin C, vitamin E succinate, α-lipoic acid and N-acetyl cysteine could improve the survival of mice after total-body irradiation. Antioxidants significantly increased the 30-day survival of mice after exposure to a potentially lethal dose of X rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 h after 1 Gy and 8 Gy. Antioxidants were effective in preventing peripheral lymphopenia only after low-dose irradiation. Antioxidant supplementation was also associated with increased bone marrow cell counts after irradiation. Supplementation with antioxidants was associated with increased Bcl2 and decreased Bax, caspase 9 and TGF-β1 mRNA expression in the bone marrow after irradiation. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow after sublethal or potentially lethal irradiation. Taken together, oral supplementation with antioxidants appears to be an effective approach for radioprotection of hematopoietic cells and improvement of animal survival, and modulation of apoptosis is implicated as a mechanism for the radioprotection of the hematopoietic system by antioxidants. PMID:18363433

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2018-05-17

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

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

PubMed

Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence

2016-11-01

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.

Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial.

PubMed

Isanaka, Sheila; Mugusi, Ferdinand; Hawkins, Claudia; Spiegelman, Donna; Okuma, James; Aboud, Said; Guerino, Chalamilla; Fawzi, Wafaie W

2012-10-17

Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART. To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART. A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance. The composite of HIV disease progression or death from any cause. The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels. Clinicaltrials.gov Identifier: NCT00383669.

Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

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

Dijk, Irma W.E.M. van, E-mail: i.w.vandijk@amc.uva.nl; Cardous-Ubbink, Mathilde C.; Pal, Helena J.H. van der

Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD{sub 2}). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 yearsmore » after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD{sub 2} in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD{sub 2}, we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD{sub 2} instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.« less

28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis

NASA Astrophysics Data System (ADS)

Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R.; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-05-01

Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including 28Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of 28Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of 28Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life-threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of 28Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6 J mice were exposed to 0.3, 0.6 and 0.9 Gy 28Si (600 MeV) total body irradiation (TBI). The effects of 28Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to 28Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of 28Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of 28Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to 28Si irradiation leads to acute HSC damage.

Differential effects of low and high dose folic acid on endothelial dysfunction in a murine model of mild hyperhomocysteinaemia.

PubMed

Clarke, Zoe L; Moat, Stuart J; Miller, Alastair L; Randall, Michael D; Lewis, Malcolm J; Lang, Derek

2006-12-03

The exact mechanism(s) by which hyperhomocysteinaemia promotes vascular disease remains unclear. Moreover, recent evidence suggests that the beneficial effect of folic acid on endothelial function is independent of homocysteine-lowering. In the present study the effect of a low (400 microg/70 kg/day) and high (5 mg/70 kg/day) dose folic acid supplement on endothelium-dependent relaxation in the isolated perfused mesenteric bed of heterozygous cystathionine beta-synthase deficient mice was investigated. Elevated total plasma homocysteine and impaired relaxation responses to methacholine were observed in heterozygous mice. In the presence of N(G)-nitro-L-arginine methyl ester relaxation responses in wild-type tissues were reduced, but in heterozygous tissues were abolished. Clotrimazole and 18alpha-glycyrrhetinic acid, both inhibitors of non-nitric oxide/non-prostanoid-induced endothelium-dependent relaxation, reduced responses to methacholine in wild-type but not heterozygous tissues. The combination of N(G)-nitro-L-arginine methyl ester and either clotrimazole or 18alpha-glycyrrhetinic acid completely inhibited relaxation responses in wild-type tissues. Both low and high dose folic acid increased plasma folate, reduced total plasma homocysteine and reversed endothelial dysfunction in heterozygous mice. A greater increase in plasma folate in the high dose group was accompanied by a more significant effect on endothelial function. In the presence of N(G)-nitro-L-arginine methyl ester, a significant residual relaxation response was evident in tissues from low and high dose folic acid treated heterozygous mice. These data suggest that the impaired mesenteric relaxation in heterozygous mice is largely due to loss of the non-nitric oxide/non-prostanoid component. While low dose folic acid may restore this response in a homocysteine-dependent manner, the higher dose has an additional effect on nitric oxide-mediated relaxation that would appear to be independent of homocysteine lowering.

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

PubMed Central

Lakshminrusimha, Satyan; Wedgwood, Stephen; Czech, Lyubov; Gugino, Sylvia F.; Russell, James A.; Farrow, Kathryn N.; Steinhorn, Robin H.

2012-01-01

In the pulmonary vasculature, cGMP levels are regulated by soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5). We previously reported that lambs with persistent pulmonary hypertension of the newborn (PPHN) demonstrate increased reactive oxygen species (ROS) and altered sGC and PDE5 activity, with resultant decreased cGMP. The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O2 for 24 h. Six lambs received 5 mg/kg hydrocortisone every 8 h times three doses (PPHN-hiHC), five lambs received 3 mg/kg hydrocortisone followed by 1 mg·kg−1·dose−1 times two doses (PPHN-loHC), and six lambs were ventilated with O2 alone (PPHN). All groups were compared with healthy 1-day spontaneously breathing lambs (1DSB). O2 ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved arterial-to-alveolar ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose hydrocortisone also increased sGC activity, decreased PDE5 expression, decreased ROS, and increased total vascular SOD activity vs. PPHN lambs. These data suggest that hydrocortisone treatment in clinically relevant doses improves oxygenation and decreases hyperoxia-induced changes in sGC and PDE5 activity, increasing cGMP levels. Hydrocortisone reduces ROS levels in part by increasing SOD activity in PPHN lambs ventilated with 100% O2. We speculate that hydrocortisone increases cGMP by direct effects on sGC and PDE5 expression and by attenuating abnormalities induced by oxidant stress. PMID:22198909

[Changes in gastric function in rats after intragastric introduction of corvitin at high doses].

PubMed

Vovkun, T V; Ianchuk, P I; Shtanova, L Ia; Vesel'skyĭ, S P; Baranovs'kyĭ, V A

2014-01-01

Intragastric administration of corvitin at doses of 10, 20 and 40 mg/kg dose-dependently increased the volume of gastric juice and the total production of hydrochloric acid (HA). Amplification of hexosamines and cysteine production was observed only when the study drug was administered at a dose of 10 mg/kg. When corvitin was used at 20 and 40 mg/kg, these parameters were at the level of control values. Protein production increased in response to 10 and 20 mg/kg corvitin, but fell below the control values after administration of 40 mg/kg of the drug. The level of blood flow in the gastric mucosa increased following administration of 10 mg/kg corvitin, was not different from the baseline after 20 mg/kg of the drug and significantly decreased in response to 40 mg/kg of flavonoid. Our results indicate that a single intragastric application of corvitin at dose of 10 mg/kg activates gastric defense mechanisms. At 20 and 40 mg/kg, corvitin does not affect them but gradually reduces blood flow in gastric mucosa, causes a disturbance of protein synthesis and hypersecretion of HA into the cavity of the stomach, which can lead to disruption of the digestive process and the integrity of gastric mucosa.

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

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

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

1981-10-01

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

Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial.

PubMed

El-Hajj Fuleihan, Ghada; Nabulsi, Mona; Tamim, Hala; Maalouf, Joyce; Salamoun, Mariana; Khalife, Hassan; Choucair, Mahmoud; Arabi, Asma; Vieth, Reinhold

2006-02-01

Despite the high prevalence of hypovitaminosis D in children and adolescents worldwide, the impact of vitamin D deficiency on skeletal health is unclear. One hundred seventy-nine girls, ages 10-17 yr, were randomly assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo-controlled, 1-yr protocol. Areal bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip, forearm, total body, and body composition were measured at baseline and 1 yr. Serum calcium, phosphorus, alkaline phosphatase, and vitamin D metabolites were measured during the study. In the overall group of girls, lean mass increased significantly in both treatment groups (P < or = 0.05); bone area and total hip BMC increased in the high-dose group (P < 0.02). In premenarcheal girls, lean mass increased significantly in both treatment groups, and there were consistent trends for increments in BMD and/or BMC at several skeletal sites, reaching significance at lumbar spine BMD in the low-dose group and at the trochanter BMC in both treatment groups. There was no significant change in lean mass, BMD, or BMC in postmenarcheal girls. Vitamin D replacement had a positive impact on musculoskeletal parameters in girls, especially during the premenarcheal period.

Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.

PubMed

Ren, Xiao-Cang; Wang, Quan-Yu; Zhang, Rui; Chen, Xue-Ji; Wang, Na; Liu, Yue-E; Zong, Jie; Guo, Zhi-Jun; Wang, Dong-Ying; Lin, Qiang

2016-04-23

Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC. Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied. After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%. For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols. NCT02720614, the date of registration: March 23, 2016.

Heavy-ion-induced sucrose radicals investigated using EPR and UV spectroscopy.

PubMed

Nakagawa, Kouichi; Karakirova, Yordanka; Yordanov, Nicola D

2015-05-01

The potential use of a sucrose dosimeter for estimating both linear energy transfer (LET) and the absorbed dose of heavy ion and X-ray radiation was investigated. The stable free radicals were produced when sucrose was irradiated with heavy ions, such as helium, carbon, silicon and neon ions, and when the X-ray radiation was similar to the obtained electron paramagnetic resonance (EPR) spectra, which were ∼7 mT wide and composed of several hyperfine structures. In addition, the total spin concentration resulting from heavy-ion irradiation increased linearly as the absorbed dose increased, and decreased logarithmically as the LET increased. These empirical relations imply that the LET at a certain dose can be determined from the spin concentration. For sucrose and alanine, both cross-sections following C-ion irradiation with a 50 Gy dose were ∼1.3 × 10(-12) [μm(2)], taking into account the molecular size of the samples. The values of these cross-sections imply that multiple ionizing particles were involved in the production of stable radicals. Furthermore, UV absorbance at 267 nm of an aqueous solution of irradiated sucrose was found to linearly increase with increasing absorbed dose. Therefore, the EPR and UV results suggest that sucrose can be a useful dosimeter for heavy-ion irradiation. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damages

NASA Technical Reports Server (NTRS)

George, K.; Cucinotta, F. A.

2006-01-01

Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from approximately 50 to 174 keV/micrometers and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation (PCC) technique. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 14 to 35. The RBE values increased with LET, reaching a maximum for the 1 GeV/n Fe ions with LET of 150 keV/micrometers, and decreased with further increases in LET. When LET of the primary beam was in the region of increasing RBE (i.e. below approximately 100 keV/micrometers), the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than 150 keV/micrometers.

A comparative analysis of warfarin and low-dose heparin as thromboembolism prophylaxis in total hip replacement patinets.

PubMed Central

Ritter, M A; HamiltonCW

1975-01-01

Warfarin, low-dose heparin, or a combination of low-dose heparin and hydrocortisone was administered to 300 patients undergoing total hip replacement. The lowest incidence of thromboembolic (5 per cent) was attained with Warfarin. Further investigation into the method of administration of low-dose heparin is necessary before it can be used effectively as thromboembolism prophylaxis in total hip replacement patients. The addition of hydrocortisone was not found useful. PMID:1138642

Imaging characteristics of different mammographic screens.

PubMed

Kuhn, H; Knüpfer, W

1992-01-01

A study of mammography systems with green-emitting screens was conducted to determine how the image quality parameters (apart from dose requirement), such as modulation transfer function (MTF) and Wiener spectrum (WS), depend on the dye content of the compound and coating weight of the screen. In addition, the contribution to total noise of the individual components, i.e., film, screen, and quantum noise, was studied. The quantities derived from MTF and WS, namely detective quantum efficiency (DQE) and noise equivalent quanta (NEQ), were also investigated in regard to their dose dependency. It can be demonstrated that the MTF of the screens becomes more favorable when the dye content is increased, while noise is not significantly affected. This suggests the use of a mammography screen capable of greater detail recognition, requiring at least double the dose of today's conventional systems with approximately 80 microGy system dose. On the other hand, the manufacture of a screen with about 60% of the dose of the conventional system is possible with very little loss in image quality. For the systems in common use today (80 microGy), quantum noise represents a considerable share of the total noise at low spatial frequencies, whereas in high spatial frequencies, the graininess of the film dominates quantum noise and screen structure.

Influence of eye size and beam entry angle on dose to non-targeted tissues of the eye during stereotactic x-ray radiosurgery of AMD

NASA Astrophysics Data System (ADS)

Cantley, Justin L.; Hanlon, Justin; Chell, Erik; Lee, Choonsik; Smith, W. Clay; Bolch, Wesley E.

2013-10-01

Age-related macular degeneration is a leading cause of vision loss for the elderly population of industrialized nations. The IRay® Radiotherapy System, developed by Oraya® Therapeutics, Inc., is a stereotactic low-voltage irradiation system designed to treat the wet form of the disease. The IRay System uses three robotically positioned 100 kVp collimated photon beams to deliver an absorbed dose of up to 24 Gy to the macula. The present study uses the Monte Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted tissues within the eye—total lens, radiosensitive tissues of the lens, optic nerve, distal tip of the central retinal artery, non-targeted portion of the retina, and the ciliary body--all as a function of eye size and beam entry angle. The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the polar entry angle of the delivery system varied from 18° to 34° in 2° increments. The resulting data showed insignificant variations in dose for all eye sizes. Slight variations in the dose to the optic nerve and the distal tip of the central retinal artery were noted as the polar beam angle changed. An increase in non-targeted retinal dose was noted as the entry angle increased, while the dose to the lens, sensitive volume of the lens, and ciliary body decreased as the treatment polar angle increased. Polar angles of 26° or greater resulted in no portion of the sensitive volume of the lens receiving an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures reported in this study were less than accepted thresholds for post-procedure complications.

Treatment with low-dose atorvastatin, losartan, and their combination increases expression of vasoactive-related genes in rat aortas.

PubMed

Lunder, Mojca; Drevenšek, Gorazd; Černe, Darko; Marc, Janja; Janić, Miodrag; Šabovič, Mišo

2013-03-01

Recently it has been shown that statins and angiotensin receptor blockers (ARBs) at low doses express beneficial pleiotropic vascular effects. We aimed to explore whether these drugs at low doses induce the expression of vasoactive-related genes. Sixty adult Wistar rats were treated with low-dose atorvastatin (2 mg/kg), low-dose losartan (5 mg/kg), their combination or saline daily for 4, 6, or 8 weeks. Expression of the vasoactive-related genes endothelin receptor type A (EDNRA), endothelial nitric oxide synthase 3 (NOS3), inducible nitric oxide synthase 2 (NOS2), and angiotensin II receptor type 1 (AGTRL1a) was measured in isolated thoracic aortas. Expression of EDNRA gradually decreased, the lowest values being obtained after 8 weeks (low-dose atorvastatin, losartan [1.6- and 1-7-fold vs controls, respectively; both P < .05], and the combination [2.3-fold vs control, P < .001]). The highest values of NOS3 were obtained after 6 weeks (low-dose atorvastatin, losartan, and their combination, 3.1-fold, P < .01; 3.4-fold, P < .001; and 3.6-fold, P < .001 vs controls, respectively) and then declined after 8 weeks. The combination was more effective in inducing total NOS3 expression when compared to the separate drugs (1.4-fold; P < .05). Importantly, expression of NOS3 was associated with increased plasma NO levels and positively correlated with thoracic aorta relaxation. No changes in expression of NOS2 and AGTRL1a were observed. We showed that low-dose atorvastatin or losartan and especially their combination increases the expression of NOS3 and decreases the expression of EDNRA. These findings are valuable in explaining the effectiveness of the "low-dose pharmacological approach" for improvement in arterial function.

Pharmacokinetics and pharmacodynamics of vildagliptin in healthy Chinese volunteers.

PubMed

Hu, Pei; Yin, Qi; Deckert, Fabienne; Jiang, Ji; Liu, Dongyang; Kjems, Lise; Dole, William P; He, Yan-Ling

2009-01-01

Vildagliptin is an orally effective, potent, and selective inhibitor of dipeptidyl peptidase IV (DPP-4) that improves glycemic control in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled, time-lagged, parallel-group study in a total of 60 healthy Chinese participants. Single- and multiple-dose pharmacokinetics and pharmacodynamics, and safety and tolerability of vildagliptin were assessed following administration of 25, 50, 100, or 200 mg qd, or 50 mg bid. Vildagliptin was rapidly absorbed (tmax 1.5-2.0 hours) across the dose range of 25 to 200 mg and was quickly eliminated with a terminal elimination half-life (t1/2) of approximately 2 hours. Consistent with the short t1/2, no accumulation of vildagliptin was observed following the administration of multiple doses (accumulation factors were 1.00-1.05 across the 25- to 200-mg dose range). Vildagliptin AUC and Cmax values increased in an approximately dose-proportional fashion (dose proportionality constant beta 1.00-1.16). Administration of vildagliptin 25 to 200 mg led to rapid and near-complete (>95%) inhibition of DPP-4 activity for at least 4 hours after dosing, which was associated with increases in plasma active glucagon-like peptide-1 of up to 2- to 3-fold compared with placebo. The duration of DPP-4 inhibition increased with dose. Glucose and insulin levels were not affected by vildagliptin in healthy participants, consistent with the fact that the glucose-lowering effects of vildagliptin occur in a glucose-dependent fashion. Vildagliptin was well tolerated at the highest tested dose of 200 mg qd. Vildagliptin 25 to 200 mg qd exhibits approximately dose-proportional pharmacokinetics with no evidence of accumulation after multiple dosing in healthy Chinese participants. Vildagliptin demonstrates potent inhibition of DPP-4 activity with excellent tolerability at doses of up to and including 200 mg qd.

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

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

Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.

2014-02-01

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analysesmore » were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.« less

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

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

Yaparpalvi, R; Mynampati, D; Kuo, H

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performedmore » using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates attributable to algorithm may very well be warranted.« less

SU-E-T-541: Bolus Effect of Thermoplastic Masks in IMRT and VMAT Head and Neck Treatments

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

Zhen, H; Nedzi, L; Chen, S

2014-06-01

Purpose: To quantitatively evaluate the bolus effect of thermoplalstic mask on patient skin dose during multi-field IMRT and VMAT treatment. Methods: The clinically approved target contours for five head and neck patients were deformably registered to an anthropomorphic Rando phantom. Two plans: Multifield IMRT plan with 7-9 beams and VMAT plan with 2-4 arcs were created for each patient following same dose constraints. 3mm skin was excluded from PTVs but not constrained during optimization. The prescription dose was 200-220 cGy/fraction. A thermoplastic head and shoulder mask was customized for the Rando phantom. Each plan was delivered to the phantom twicemore » with and without mask. During each delivery, two rectangular strips of EBT3 films (1cm x 6.8cm) were placed across the anterior upper and lower neck near PTVs to measure the surface dose. For consistency films were positioned at same locations for same patient. A total of 8 film strips were obtained for each patient. Film dose was calibrated in the range of 0-400cGy on the day of plan delivery. For dose comparison 3 regions of interests (ROIs) of 1×1 cm{sup 2} were selected at left, right and middle part of each film, resulting in 6 point doses at each plan delivery. Results: The films without mask show relatively uniform dose distribution while those with mask clearly show mesh pattern of mask, usually indicating an increase in skin dose. On average the increase in skin dose over all ROIs with mask was 31.9%(±14.8%) with a range of 11.4%- 58.4%. There is no statistically significant difference (p=0.44) between skin dose increase in VMAT (30.8%±15.3%) and IMRT delivery (33.0%±14.9%). Conclusion: Thermoplastic immobilization masks increase surface dose for HN patient by around 30%. The magnitude is comparable between multi-field IMRT and VMAT. Radiochromic EBT3 film serves as an effective tool to quantify bolus effect.« less

Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care.

PubMed

Jager, N G L; Rosing, H; Schellens, J H M; Linn, S C; Beijnen, J H

2014-02-01

A sensitive and selective HPLC-MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N-desmethyltamoxifen (E)-endoxifen, (Z)-endoxifen, N-desmethyl-4'-hydroxytamoxifen, 4-hydroxytamoxifen, and 4'-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the (Z)-endoxifen serum concentration was below the predefined therapeutic threshold concentration of 5.9 ng/mL, the clinician was advised to increase the tamoxifen dose and to collect another serum sample. Paired serum samples from patients at one dose level at different time points during the tamoxifen treatment were used to assess the intra-patient variability. A total of 251 serum samples were analyzed, obtained from 205 patients. Of these patients, 197 used 20 mg tamoxifen per day and 8 patients used 10 mg/day. There was wide variability in tamoxifen and metabolite concentrations within the dosing groups. The threshold concentration for (Z)-endoxifen was reached in one patient (12 %) in the 10 mg group, in 153 patients (78 %) in the 20 mg group, and in 26 (96 %) of the patients who received a dose increase to 30 or 40 mg/day. Dose increase from 20 to 30 or 40 mg per day resulted in a significant increase in the mean serum concentrations of all analytes (p < 0.001). The mean intra-patient variability was between 10 and 20 % for all analytes. These results support the suitability of TDM for optimizing the tamoxifen treatment. It is shown that tamoxifen dose is related to (Z)-endoxifen exposure and increasing this dose leads to a higher serum concentration of tamoxifen and its metabolites. The low intra-patient variability suggests that only one serum sample is needed for TDM, making this a relatively noninvasive way to optimize the patient's treatment.

Clinical consequences of initial duloxetine dosing strategies: Comparison of 30 and 60 mg QD starting doses

PubMed Central

Dunner, David L.; Wohlreich, Madelaine M.; Mallinckrodt, Craig H.; Watkin, John G.; Fava, Maurizio

2005-01-01

Background: To reduce the risk for treatment-emergent adverse events and increase patient compliance, clinicians frequently prescribe a suboptimal starting dose of antidepressants, with the goal of increasing the dose once the patient has demonstrated tolerability. Objective: The aim of this study was to examine the tolerability and effectiveness associated with an initial week of duloxetine hydrochloride treatment at 30 mg QD and subsequent dose increase to 60 mg QD, compared with a starting dose of 60 mg QD. Methods: In this open-label study, all patients met the criteria for major depressive disorder (MDD) described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Patients were required to wash out from previous antidepressant medications for 21 days, and were then randomized to receive duloxetine 30 or 60 mg QD for 1 week. After 1 week, patients receiving duloxetine 30 mg QD had their dose increased to 60 mg QD. Patients returned for assessments at weeks 2, 4, 6, 8, and 12. During the remainder of the 12-week study period, the duloxetine dose could be titrated based on the degree of response from 60 mg QD (minimum) to 120 mg QD (maximum), with 90 mg QD as an intermediate dose. Tolerability was assessed by means of discontinuation rates, spontaneously reported adverse events, changes in vital signs, and laboratory tests. Effectiveness measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 core and Maier subscales, individual HAMD17 items, the Hamilton Rating Scale for Anxiety total score, and the Clinical Global Impression of Severity. Results: One hundred thirty-seven patients were enrolled (82 women, 55 men; mean age, 42 years; duloxetine 30 mg QD, 67 patients; duloxetine 60 mg QD, 70 patients). The rate of discontinuation due to adverse events did not differ significantly between patients starting duloxetine at 30 mg QD and 60 mg QD (13.4% vs 18.6%). The most frequently reported adverse events across both treatment groups were nausea, headache, dry mouth, insomnia, and diarrhea. In the first week of treatment, patients receiving duloxetine 30 mg QD had a significantly lower rate of nausea compared with patients receiving 60 mg QD (16.4% vs 32.9%; P = 0.03). Over the 12-week acute-treatment phase, patients starting duloxetine treatment at 30 mg QD had a significantly lower rate of nausea compared with patients initiating treatment at 60 mg QD (P = 0.047). Although between-group differences in the HAMD17 total score were not statistically significant at any visit, patients starting at 30 mg QD experienced significantly less improvement in HAMD17 core and Maier subscales at week 1 compared with patients starting at 60 mg QD (core, P= 0.044; Maier, P = 0.047). After 2 weeks of treatment, the magnitude of improvement among patients starting at 30 mg QD did not differ significantly from that observed in patients who started treatment at 60 mg QD, and there were no significant between-group differences in effectiveness at any subsequent visit. Conclusions: Results from this open-label study in patients with MDD suggest that starting duloxetine treatment at 30 mg QD for 1 week, followed by escalation to 60 mg QD, might reduce the risk for treatment-emergent nausea in these patients while producing only a transitory impact on effectiveness compared with a starting dose of 60 mg QD. PMID:24678074

Reliability of gamma-irradiated n-channel ZnO thin-film transistors: electronic and interface properties

NASA Astrophysics Data System (ADS)

Lee, Kin Kiong; Wang, Danna; Shinobu, Onoda; Ohshima, Takeshi

2018-04-01

Radiation-induced charge trapping and interface traps in n-channel ZnO thin film transistors are characterised as a function of total dose and irradiation bias following exposure to gamma-rays. Devices were irradiated up to ∼60 kGy(SiO?) and the electrical characteristic exhibits two distinct regimes. In the first regime, up to a total dose of 40 kGy(SiO?), the threshold voltage increases positively. However, in the second regime with irradiation greater than 40 kGy(SiO?), the threshold voltage moves in the opposite direction. This reversal of threshold voltage is attributed to the influence of the radiation-induced interface and oxide- charge, in which both have opposite polarity, on the electrical performance of the transistors. In the first regime, the generation of the oxide- charge is initially greater than the density of interface traps and caused a positive shift. In the second regime, when the total doses were greater than 40 kGy(SiO?), the radiation-induced interface traps are greater than the density of oxide- charge and caused the threshold voltage to switch direction. Further, the generated interface traps contributed to the degradation of the effective channel mobility, whereas the density of traps at the grain-boundaries did not increase significantly upon irradiation. Isothermal annealing of the devices at 363 K results in a reduction in the trap density and an improvement of the effective channel mobility to ∼90% of its pre-irradiation value.

INCREASED DAMAGE TO THE TEETH BY DENTAL CARIES INDUCED BY IONIZING RADIATION (in Russian)

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

Fedorov, Yu.A.

A group of rats (60 days old) given a total x-ray dose of 300 r in fractions of 100 r showed caries in 57.6% of all molars compared to an incidence of caries of 66.6% in a group of rats given a total x-ray dose of 600 r in fractions of 200 r, and an incidence of l.3% in the control group. In another series of experiments the rats were put on a special carbohydrate diet which is used to produce dental caries in experimental animals. The animals were divided into three groups. Group A was fed 0.025 g ofmore » calcium glycerophosphate per day. Group B was given water containing 1 mg/l of sodium fluoride. Group C was given no special protection against the onset of dental caries. The three groups of rats were then given a total dose of 300 r in fractions of l00 r. Group C showed dental caries in 75% of all molars, Group B was 65.2% and Group C was 34.3%. The use of calcium glycerophosphate has a protective action on the formation of dental caries. (TTT)« less

Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves

PubMed Central

Alam, Badrul; Akter, Fahima; Parvin, Nahida; Sharmin Pia, Rashna; Akter, Sharmin; Chowdhury, Jesmin; Sifath-E-Jahan, Kazi; Haque, Ekramul

2013-01-01

Objective: The present study was designed to evaluate the antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves (MPBL). Materials and Methods: MPBL was evaluated for anti-inflammatory activity using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was evaluated by hot plate, writhing, and formalin tests. Total phenolic and flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of total ROS generation, and assessment of reducing power were used to evaluate antioxidant potential of MPBL. Results: The extract of MPBL, at the dose of 100 and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot plate method whereas significantly (p<0.05) reduced the writhing caused by acetic acid and the number of licks induced by formalin in a dose-dependent manner. The same ranges of doses of MPBL caused significant (p<0.05) inhibition of carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH, ONOO-, and total ROS scavenging method, MPBL showed good antioxidant potentiality with the IC50 value of 16.33±1.02, 25.16±0.61 , and 41.72±0.48 µg/ml, respectively with a significant (p<0.05) good reducing power. Conclusion: The findings of the study suggested that MPBL has strong analgesic, anti-inflammatory, and antioxidant effects, conforming the traditional use of this plant for inflammatory pain alleviation to its antioxidant potentiality. PMID:25050265

Effect of aminophylline on tryptophan and other aromatic amino acids in plasma, brain and other tissues and on brain 5-hydroxytryptamine metabolism.

PubMed

Curzon, G; Fernando, J C

1976-12-01

1 Aminophylline and other methylxanthines increase brain tryptophan and hence 5-hydroxytryptamine turnover. The mechanism of this effect of aminophylline was investigated. 2 At lower doses (greater than 100 mg/kg i.p.) the brain tryptophan increase could be explained by the lipolytic action of the drug, i.e. increased plasma unesterified fatty acid freeing plasma tryptophan from protein binding so that it became available to the brain. 3 Plasma unesterified fatty acid did not increase when aminophylline (109 mg/kg i.p.) was given to nicotinamide-treated rats but as both plasma total and free tryptophan rose, a tryptophan increase in the brain still occurred. 4 The rise in brain tryptophan concentration following the injection of a higher dose of the drug (150 mg/kg i.p.) could no longer be explained by a rise of plasma free tryptophan as the ratio of brain tryptophan to plasma free tryptophan rose considerably. Plasma total tryptophan fell and the plasma insulin concentration rose. 5 The increase of brain tryptophan concentration after injection of 150 mg/kg aminophylline appeared specific for this amino acid as brain tyrosine and phenyllanine did not increase. However as their plasma concentrations fell the brain/plasma ratio for all three amino acids rose. 6 The higher dose of aminophylline increased the muscle concentration of tryptophan but that of tyrosine fell and that of phenylalanine remained unaltered. The liver concentrations were not affected. 7 The aminophylline-induced increase of the ratio of brain tryptophan of plasma free tryptophan no longer occurred when the drug was given to animals injected with the beta-adrenoreceptor blocking agent propranolol or the diabetogenic agent streptozotocin. 8 The changes in brain tryptophan upon aminophylline injection may be explained by (a) increased availability of plasma tryptophan to the brain due to increased lipolysis and (b) increased effectiveness of uptake of tryptophan by the brain due to increased insulin secretion.

Zn-biofortification enhanced nitrogen metabolism and photorespiration process in green leafy vegetable Lactuca sativa L.

PubMed

Barrameda-Medina, Yurena; Lentini, Marco; Esposito, Sergio; Ruiz, Juan M; Blasco, Begoña

2017-04-01

Excessive rates of nitrogen (N) fertilizers may result in elevated concentrations of nitrate (NO 3 - ) in plants. Considering that many programs of biofortification with trace elements are being performed, it has become important to study how the application of these elements affects plant physiology and, particularly, N utilization in leaf crops. The main objective of the present study was to determine whether the NO 3 - accumulation and the nitrogen use efficiency was affected by the application of different doses of Zn in Lactuca sativa plants. Zn doses in the range 80-100 µmol L -1 produced an increase in Zn concentration provoking a decrease of NO 3 - concentration and increase of the nitrate reductase, glutamine synthetase and aspartate aminotransferase activities, as well as the photorespiration processes. As result, we observed an increase in reduced N, total N concentration and N utilization efficiency. Consequently, at a dose of 80 µmol L -1 of Zn, the amino acid concentration increased significantly. Adequate Zn fertilization is an important critical player in lettuce, especially at a dose of 80 µmol L -1 of Zn, because it could result in an increase in the Zn concentration, a reduction of NO 3 - levels and an increase the concentration of essential amino acids, with all of them having beneficial properties for the human diet. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Rates of Change in Naturalistic Psychotherapy: Contrasting Dose-Effect and Good-Enough Level Models of Change

ERIC Educational Resources Information Center

Baldwin, Scott A.; Berkeljon, Arjan; Atkins, David C.; Olsen, Joseph A.; Nielsen, Stevan L.

2009-01-01

Most research on the dose-effect model of change has combined data across patients who vary in their total dose of treatment and has implicitly assumed that the rate of change during therapy is constant across doses. In contrast, the good-enough level model predicts that rate of change will be related to total dose of therapy. In this study, the…

Compendium of Current Total Ionizing Dose and Displacement Damage Results from NASA Goddard Space Flight Center and NASA Electronic Parts and Packaging Program

NASA Technical Reports Server (NTRS)

Topper, Alyson D.; Campola, Michael J.; Chen, Dakai; Casey, Megan C.; Yau, Ka-Yen; Cochran, Donna J.; Label, Kenneth A.; Ladbury, Raymond L.; Mondy, Timothy K.; O'Bryan, Martha V.;

Postmastectomy radiotherapy with integrated scar boost using helical tomotherapy.

PubMed

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

2012-01-01

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

Postmastectomy radiotherapy with integrated scar boost using helical tomotherapy

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

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

2012-10-01

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

[Features of influence adenosine, AMP and hyperadrenalinemiya on the immune status, metabolic enzymes of purine nucleotides and the antioxidant defense system].

PubMed

Tapbergenov, S O; Sovetov, B S; Tapbergenov, A T

2016-11-01

Administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) increased blood levels of total leukocytes, lymphocytes, decreased T-cell suppressors, leukocyte migration inhibition reaction (LMIR) and NBT test, but increased the level of conjugated dienes (CD). Administration of AMPand adenosine increased levels of total leukocytes, lymphocytes, T- lymphocytes, T-helpers, decreased the level of malondialdehyde (MDA), LMIR, and T-cell suppressors. Sympathetic hyperactivation induced by administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) was accompanied by an increase in heart and liver activities of glutathione peroxidase (GPx), catalase, AMP deaminase (AMPD), and adenosine deaminase (AD). Administration of AMP or adenosine caused a decrease in activities of glutathione reductase (GR), GPx, catalase, a decrease in the MDA level and an increase in activities of AMPD and AD in the heart. In the liver AMP and adenosine also caused a decrease in activities of glutathione reductase (GR), GPx, a decrease in the MDA level and an increase in activities of AMPD and AD. The data obtained suggest that administration of adrenaline, AMP, and adenosine influences activity of enzymes involved in purine nucleotide metabolism. However, in contrast to adrenaline, administration of AMP or adenosine does not provoke stress reaction.

Immunocyte responses of mouse exposure by low dose 12C6+ ion beam

NASA Astrophysics Data System (ADS)

Dang, B. R.

High LET radiations such as heavy ion or neutron have an increased biological effectiveness compared to low LET radiations for cell killing cell cycle perturbations and genetic instability In this paper we investigate the peripheral blood lymphocytes thymus cell and spleen lymphocytes cycle effects of exposure with different dose of 73 74MeV u 12 C 6 ion on mouse These BalB C were irradiated with 39cGy 55cGy and 1Gy of 12 C 6 ion at 20cGy min The cell cycle and apoptosis were determined by flow cytometry and the thymus and spleen index were measured by weight When these mice were irradiated by 12 C 6 the cycle of immunocyte had some changes and the percentage of apoptosis increased with doses increasing irradiation especially blood lymphocyte It might be suggested that irradiated by 12 C 6 total-body can result in more damage for immune system than normal irradiation

Cardiohemodynamic and electrophysiological effects of a selective EP4 receptor agonist ONO--AE1--329 in the halothane-anesthetized dogs.

PubMed

Nomura, Hiroaki; Nakamura, Yuji; Cao, Xin; Honda, Atsushi; Katagi, Jun; Ohara, Hiroshi; Izumi-Nakaseko, Hiroko; Satoh, Yoshioki; Ando, Kentaro; Sugiyama, Atsushi

2015-08-15

Cardiovascular effects of a highly selective prostaglandin E2 type 4 (EP4) receptor agonist ONO-AE1-329 were assessed with the halothane-anesthetized dogs (n=6). ONO-AE1-329 was intravenously infused in three escalating doses of 0.3, 1 and 3ng/kg/min for 10min with a pause of 20min between the doses. The low dose of 0.3ng/kg/min significantly increased maximum upstroke velocity of left ventricular pressure by 18% at 20min, indicating increase of ventricular contractility. The middle dose of 1ng/kg/min significantly decreased total peripheral resistance by 24% and left ventricular end-diastolic pressure by 32% at 10min, indicating dilation of arteriolar resistance vessels and venous capacitance ones, respectively; and increased cardiac output by 25% at 10min in addition to the change induced by the low dose. The high dose of 3ng/kg/min increased heart rate by 34% at 10min; decreased mean blood pressure by 14% at 10min and atrioventricular nodal conduction time by 13% at 5min; and shortened left ventricular systolic period by 8% at 10min and electromechanical coupling defined as an interval from completion of repolarization to the start of ventricular diastole by 39% at 10min in addition to the changes induced by the middle dose. No significant change was detected in a ventricular repolarization period. These results indicate that ONO-AE1-329 may possess a similar cardiovascular profile to typical phosphodiesterase 3 inhibitors as an inodilator, and suggest that EP4 receptor stimulation can become an alternative strategy for the treatment of congestive heart failure. Copyright © 2015 Elsevier B.V. All rights reserved.

Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

PubMed

Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

2015-11-01

The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

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

NASA Technical Reports Server (NTRS)

Hall, Eric J.; Wuu, Cheng-Shie

2003-01-01

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

Effect of Intrathecal Bupivacaine Dose on the Success of External Cephalic Version for Breech Presentation: A Prospective, Randomized, Blinded Clinical Trial.

PubMed

Chalifoux, Laurie A; Bauchat, Jeanette R; Higgins, Nicole; Toledo, Paloma; Peralta, Feyce M; Farrer, Jason; Gerber, Susan E; McCarthy, Robert J; Sullivan, John T

2017-10-01

Breech presentation is a leading cause of cesarean delivery. The use of neuraxial anesthesia increases the success rate of external cephalic version procedures for breech presentation and reduces cesarean delivery rates for fetal malpresentation. Meta-analysis suggests that higher-dose neuraxial techniques increase external cephalic version success to a greater extent than lower-dose techniques, but no randomized study has evaluated the dose-response effect. We hypothesized that increasing the intrathecal bupivacaine dose would be associated with increased external cephalic version success. We conducted a randomized, double-blind trial to assess the effect of four intrathecal bupivacaine doses (2.5, 5.0, 7.5, 10.0 mg) combined with fentanyl 15 μg on the success rate of external cephalic version for breech presentation. Secondary outcomes included mode of delivery, indication for cesarean delivery, and length of stay. A total of 240 subjects were enrolled, and 239 received the intervention. External cephalic version was successful in 123 (51.5%) of 239 patients. Compared with bupivacaine 2.5 mg, the odds (99% CI) for a successful version were 1.0 (0.4 to 2.6), 1.0 (0.4 to 2.7), and 0.9 (0.4 to 2.4) for bupivacaine 5.0, 7.5, and 10.0 mg, respectively (P = 0.99). There were no differences in the cesarean delivery rate (P = 0.76) or indication for cesarean delivery (P = 0.82). Time to discharge was increased 60 min (16 to 116 min) with bupivacaine 7.5 mg or higher as compared with 2.5 mg (P = 0.004). A dose of intrathecal bupivacaine greater than 2.5 mg does not lead to an additional increase in external cephalic procedural success or a reduction in cesarean delivery.

Measles control in developing and developed countries: the case for a two-dose policy.

PubMed

Tulchinsky, T H; Ginsberg, G M; Abed, Y; Angeles, M T; Akukwe, C; Bonn, J

1993-01-01

Despite major reductions in the incidence of measles and its complications, measles control with a single dose of the currently used. Schwarz strain vaccine has failed to eradicate the disease in the developed countries. In developing countries an enormous toll of measles deaths and disability continues, despite considerable efforts and increasing immunization coverage. Empirical evidence from a number of countries suggests that a two-dose measles vaccination programme, by improving individual protection and heard immunity can make a major contribution to measles control and elimination of local circulation of the disease. Cost-benefit analysis also supports the two-dose schedule in terms of savings in health costs, and total costs to society. A two-dose measles vaccination programme is therefore an essential component of preventive health care in developing, as well as developed countries for the 1990s.

Frequency, predictors, and economic impact of upward dose adjustment of infliximab in managed care patients with rheumatoid arthritis.

PubMed

Ollendorf, Daniel A; Massarotti, Elena; Birbara, Charles; Burgess, Somali Misra

2005-06-01

To examine dosing patterns and costs among rheumatoid arthritis (RA) patients newly treated with infliximab in a large national health care claims database. Using data from a proprietary database of pharmacy and medical claims for 75 U.S. health plans, RA patients newly treated with infliximab between June 2000 and June 2002 were selected and assigned an .index date. based on the first infusion. A pretreatment period of 6 months was created; patients were also followed for a minimum of 6 months after the initial infusion. Follow-up was allowed to vary beyond this minimum 6 months in order to preserve all available patient data. A maintenance number of infliximab vials was determined as of the second infusion; patients with 1 subsequent increase in vials used or 2 intervals between infusions of <49 days were considered to have had an upward dose adjustment. Differences (i.e., between those with upward dose adjustment and those with no upward dose) in patient characteristics were examined using descriptive statistics. In addition, time to upward dose adjustment and factors influencing its likelihood were analyzed using Kaplan-Meier and Cox proportional hazards techniques. Finally, differences in RA-related and unrelated costs (medication, outpatient, inpatient, and total, expressed in 2003 dollars) were examined using Wilcoxon rank-sum tests and were also stratified by a number of patient characteristics found to differ between the 2 groups. A total of 1,236 patients met all study entry criteria and were included in these analyses. One or more upward dose adjustments were experienced by 61.7% (N=762) of patients during an average of 15 months of follow-up (median =13 months, range=6 to 31 months). The majority (63.3%) of upward dose adjustments were due to increases in the number of billed vials. Median time to upward dose adjustment was 254 days and declined steadily based on year of initiation (from 330 days in 2000 to 224 days in 2002). Factors significantly influencing upward dose adjustment included pretreatment use of leflunomide, comorbid Crohn.s disease, and pretreatment liver function testing. During followup, patients in the upward dose adjustment group used a mean (SD) of 30.28 (20.90) vials of infliximab, compared with 15.90 (14.28) among those not adjusting dose (P<0.001). Annualized (i.e., standardized to a 365-day rate) RA-related costs were higher by more than 50% among patients with upward dose adjustment (SD $22,283 [$20,517] versus $14,425 [$10,828] for those without upward dose adjustment; P<0.001); differences were driven almost entirely by the costs of infliximab itself ($16,336 [$9,490] versus $9,573 [$6,790], P<0.001). In a cohort of managed care members with RA, upward dose adjustment with infliximab was frequent and appeared to occur earlier in the drug therapy in 2002 compared with 2000. Upward dose adjustment was associated with significant increases in drug treatment costs; therefore, payers and providers should consider the impact of current dosing trends when monitoring the use of biologics for autoimmune diseases.

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

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

Chiu, J; Braunstein, S; McDermott, M

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

Dual-energy cone-beam CT with a flat-panel detector: Effect of reconstruction algorithm on material classification

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

Zbijewski, W., E-mail: wzbijewski@jhu.edu; Gang, G. J.; Xu, J.

2014-02-15

Purpose: Cone-beam CT (CBCT) with a flat-panel detector (FPD) is finding application in areas such as breast and musculoskeletal imaging, where dual-energy (DE) capabilities offer potential benefit. The authors investigate the accuracy of material classification in DE CBCT using filtered backprojection (FBP) and penalized likelihood (PL) reconstruction and optimize contrast-enhanced DE CBCT of the joints as a function of dose, material concentration, and detail size. Methods: Phantoms consisting of a 15 cm diameter water cylinder with solid calcium inserts (50–200 mg/ml, 3–28.4 mm diameter) and solid iodine inserts (2–10 mg/ml, 3–28.4 mm diameter), as well as a cadaveric knee withmore » intra-articular injection of iodine were imaged on a CBCT bench with a Varian 4343 FPD. The low energy (LE) beam was 70 kVp (+0.2 mm Cu), and the high energy (HE) beam was 120 kVp (+0.2 mm Cu, +0.5 mm Ag). Total dose (LE+HE) was varied from 3.1 to 15.6 mGy with equal dose allocation. Image-based DE classification involved a nearest distance classifier in the space of LE versus HE attenuation values. Recognizing the differences in noise between LE and HE beams, the LE and HE data were differentially filtered (in FBP) or regularized (in PL). Both a quadratic (PLQ) and a total-variation penalty (PLTV) were investigated for PL. The performance of DE CBCT material discrimination was quantified in terms of voxelwise specificity, sensitivity, and accuracy. Results: Noise in the HE image was primarily responsible for classification errors within the contrast inserts, whereas noise in the LE image mainly influenced classification in the surrounding water. For inserts of diameter 28.4 mm, DE CBCT reconstructions were optimized to maximize the total combined accuracy across the range of calcium and iodine concentrations, yielding values of ∼88% for FBP and PLQ, and ∼95% for PLTV at 3.1 mGy total dose, increasing to ∼95% for FBP and PLQ, and ∼98% for PLTV at 15.6 mGy total dose. For a fixed iodine concentration of 5 mg/ml and reconstructions maximizing overall accuracy across the range of insert diameters, the minimum diameter classified with accuracy >80% was ∼15 mm for FBP and PLQ and ∼10 mm for PLTV, improving to ∼7 mm for FBP and PLQ and ∼3 mm for PLTV at 15.6 mGy. The results indicate similar performance for FBP and PLQ and showed improved classification accuracy with edge-preserving PLTV. A slight preference for increased smoothing of the HE data was found. DE CBCT discrimination of iodine and bone in the knee was demonstrated with FBP and PLTV at 6.2 mGy total dose. Conclusions: For iodine concentrations >5 mg/ml and detail size ∼20 mm, material classification accuracy of >90% was achieved in DE CBCT with both FBP and PL at total doses <10 mGy. Optimal performance was attained by selection of reconstruction parameters based on the differences in noise between HE and LE data, typically favoring stronger smoothing of the HE data, and by using penalties matched to the imaging task (e.g., edge-preserving PLTV in areas of uniform enhancement)« less

A food effect study and dose proportionality study to assess the pharmacokinetics and safety of bardoxolone methyl in healthy volunteers.

PubMed

Teuscher, Nathan S; Kelley, Richard J; Dumas, Emily O; Klein, Cheri Enders; Awni, Walid M; Meyer, Colin J

2014-07-01

This study investigated the effect of food on the plasma pharmacokinetics of bardoxolone methyl, an antioxidant inflammation modulator, at a 20 mg dose, and the dose proportionality of bardoxolone methyl pharmacokinetics from 20 to 80 mg. It was a single-dose study conducted at a single center in 32 healthy volunteers aged 18-45 years using an amorphous spray-dried dispersion formulation of bardoxolone methyl. In Part A, 16 subjects received single 20 mg doses of bardoxolone methyl under fasting and non-fasting conditions. In Part B, 16 subjects received a single 60 or 80 mg dose of bardoxolone methyl and a matching placebo dose under fasting conditions. Blood samples for pharmacokinetic analysis were taken over 120 hours following dose administration. Single dose administration of 20, 60, and 80 mg bardoxolone methyl was safe and well-tolerated in healthy volunteers. Total bardoxolone methyl exposure was unchanged in the presence of food. However, doses of bardoxolone methyl above 20 mg appear to have a saturated dissolution or absorption process and are associated with less than proportional increases in drug exposure. © 2013, The American College of Clinical Pharmacology.

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs

PubMed Central

Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-01-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day. PMID:25874036

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs.

PubMed

Nam, Chunja; Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-03-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

Implementation of an Analytical Model for Leakage Neutron Equivalent Dose in a Proton Radiotherapy Planning System

PubMed Central

Eley, John; Newhauser, Wayne; Homann, Kenneth; Howell, Rebecca; Schneider, Christopher; Durante, Marco; Bert, Christoph

2015-01-01

Equivalent dose from neutrons produced during proton radiotherapy increases the predicted risk of radiogenic late effects. However, out-of-field neutron dose is not taken into account by commercial proton radiotherapy treatment planning systems. The purpose of this study was to demonstrate the feasibility of implementing an analytical model to calculate leakage neutron equivalent dose in a treatment planning system. Passive scattering proton treatment plans were created for a water phantom and for a patient. For both the phantom and patient, the neutron equivalent doses were small but non-negligible and extended far beyond the therapeutic field. The time required for neutron equivalent dose calculation was 1.6 times longer than that required for proton dose calculation, with a total calculation time of less than 1 h on one processor for both treatment plans. Our results demonstrate that it is feasible to predict neutron equivalent dose distributions using an analytical dose algorithm for individual patients with irregular surfaces and internal tissue heterogeneities. Eventually, personalized estimates of neutron equivalent dose to organs far from the treatment field may guide clinicians to create treatment plans that reduce the risk of late effects. PMID:25768061

Implementation of an analytical model for leakage neutron equivalent dose in a proton radiotherapy planning system.

PubMed

Eley, John; Newhauser, Wayne; Homann, Kenneth; Howell, Rebecca; Schneider, Christopher; Durante, Marco; Bert, Christoph

2015-03-11

Equivalent dose from neutrons produced during proton radiotherapy increases the predicted risk of radiogenic late effects. However, out-of-field neutron dose is not taken into account by commercial proton radiotherapy treatment planning systems. The purpose of this study was to demonstrate the feasibility of implementing an analytical model to calculate leakage neutron equivalent dose in a treatment planning system. Passive scattering proton treatment plans were created for a water phantom and for a patient. For both the phantom and patient, the neutron equivalent doses were small but non-negligible and extended far beyond the therapeutic field. The time required for neutron equivalent dose calculation was 1.6 times longer than that required for proton dose calculation, with a total calculation time of less than 1 h on one processor for both treatment plans. Our results demonstrate that it is feasible to predict neutron equivalent dose distributions using an analytical dose algorithm for individual patients with irregular surfaces and internal tissue heterogeneities. Eventually, personalized estimates of neutron equivalent dose to organs far from the treatment field may guide clinicians to create treatment plans that reduce the risk of late effects.

Substitution of starch by soluble fiber and Saccharomyces cerevisiae dose response on nutrient digestion and blood metabolites for precision-fed dairy heifers.

PubMed

Lascano, G J; Heinrichs, A J; Tricarico, J M

2012-06-01

The objective of this experiment was to determine the effects of 2 levels of dietary starch and the dose at which the effects of yeast culture (YC) derived from Saccharomyces cerevisiae (Yea-Sacc¹⁰²⁶, Alltech Inc., Nicholasville, KY) were maximized based on nutrient total-tract digestibility (AD), N utilization, and blood metabolites of precision-fed dairy heifers. A split-plot design with starch level as the whole plot and YC dose as subplot was administered in a 4-period (21 d), 4 × 4 Latin square. Eight Holstein heifers (432.49 ± 6.81 kg of body weight) were allocated to 2 starch treatments (28% starch, high starch, HS, or 17% starch, low starch, LS) and to a sequence of YC doses (0, 10, 30, and 50 g/d). Dry matter (DM) and neutral detergent fiber (NDF) AD were not different between HS and LS; however, HS decreased acid detergent fiber (ADF) and increased hemicellulose AD. Digestibility of DM and organic matter (OM) increased quadratically in response to increasing YC dose. Hemicellulose, NDF, and ADF AD increased or tended to increase quadratically with increasing YC dose. No significant effects were noted on fecal or urine output between dietary starch concentrations; YC decreased wet and dry fecal output corresponding to the effect in DM and OM. Apparent N digestibility was greater in the LS group. As YC dose increased, fecal N output decreased quadratically and was lowest at 30 g/d YC. A corresponding quadratic increase was observed for N retention expressed as a percentage of N digested: N output in urine tended to increase with increasing YC dose, resulting in no differences in retained N (g/d). Dietary starch concentration did not affect blood glucose, triglyceride, creatinine, or lactate concentration. However, HS increased plasma urea N concentration. Glucose concentration tended to increase quadratically with daily YC dose in both starch treatments, with the greatest response at 30 g/d. For triglycerides, dietary starch concentration and YC dose interacted, decreasing quadratically in the LS group and increasing in the HS group (lowest and highest value for 10 g/d respectively). We observed a significant time effect for all blood metabolites measured. We conclude that starch level did not affect DM AD, but influenced ADF and hemicellulose AD. Yeast culture had the greatest effect on DM, NDF, ADF, and hemicellulose AD when added at 30 g/d. Addition of YC influenced glucose and triglyceride concentrations differently according to the dietary starch concentration of the diet. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Continuing evaluation of bipolar linear devices for total dose bias dependency and ELDRS effects

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Gorelick, Jerry L.; Yui, Candice; Rax, Bernard G.; Wiedeman, Michael D.

2003-01-01

We present results of continuing efforts to evaluate total dose bias dependency and ELDRS effects in bipolar linear microcircuits. Several devices were evaluated, each exhibiting moderate to significant bias and/or dose rate dependency.

Galleria mellonella larvae are capable of sensing the extent of priming agent and mounting proportionatal cellular and humoral immune responses.

PubMed

Wu, Gongqing; Xu, Li; Yi, Yunhong

2016-06-01

Larvae of Galleria mellonella are useful models for studying the innate immunity of invertebrates or for evaluating the virulence of microbial pathogens. In this work, we demonstrated that prior exposure of G. mellonella larvae to high doses (1×10(4), 1×10(5) or 1×10(6) cells/larva) of heat-killed Photorhabdus luminescens TT01 increases the resistance of larvae to a lethal dose (50 cells/larva) of viable P. luminescens TT01 infection administered 48h later. We also found that the changes in immune protection level were highly correlated to the changes in levels of cellular and humoral immune parameters when priming the larvae with different doses of heat-killed P. luminescens TT01. Priming the larvae with high doses of heat-killed P. luminescens TT01 resulted in significant increases in the hemocytes activities of phagocytosis and encapsulation. High doses of heat-killed P. luminescens TT01 also induced an increase in total hemocyte count and a reduction in bacterial density within the larval hemocoel. Quantitative real-time PCR analysis showed that genes coding for cecropin and gallerimycin and galiomycin increased in expression after priming G. mellonella with heat-killed P. luminescens TT01. All the immune parameters changed in a dose-dependent manner. These results indicate that the insect immune system is capable of sensing the extent of priming agent and mounting a proportionate immune response. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Diuretic effects of medetomidine compared with xylazine in healthy dogs.

PubMed

Talukder, Md Hasanuzzaman; Hikasa, Yoshiaki

2009-07-01

This study aimed to investigate and compare the effects of medetomidine and xylazine on diuretic and hormonal variables in healthy dogs. Five dogs, used in each of 11 groups, were injected intramuscularly with physiological saline solution (control), 5, 10, 20, 40, and 80 microg/kg of medetomidine, and 0.25, 0.5, 1, 2, and 4 mg/kg of xylazine. Urine and blood samples were taken 11 times over 24 h. Both medetomidine and xylazine increased urine production in a dose-dependent manner up to 4 h after injection, but the increase was much less with medetomidine than with xylazine at the tested doses. Urine specific gravity, pH, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and arginine vasopressin (AVP) were decreased in a dose-dependent manner with both medetomidine and xylazine. Plasma osmolality and concentrations of sodium, potassium, and chloride were increased significantly with both drugs. Total amounts of urine AVP excreted and plasma AVP concentrations were significantly decreased by higher doses of medetomidine but were not significantly decreased by xylazine. Higher doses of both drugs significantly increased the plasma concentration of atrial natriuretic peptide (ANP), but the effect was greater with medetomidine than with xylazine. The results revealed that both drugs induce a profound diuresis, but medetomidine's effect is less dose-dependent than xylazine's effect. Although changes in plasma concentrations of AVP and ANP may partially influence the diuresis induced by medetomidine, other factors may be involved in the mechanism of the diuretic response to both drugs. Thus, both agents can be used clinically for transient but effective diuresis accompanied by sedation.

Pharmacokinetics of a Single Oral Dose of the MEK1/2 Inhibitor Selumetinib in Subjects With End‐Stage Renal Disease or Varying Degrees of Hepatic Impairment Compared With Healthy Subjects

PubMed Central

Dymond, Angela W.; Martin, Paul; Huang, Yifan; Severin, Paul; Holmes, Victoria; Mariani, Gabriella; Marbury, Thomas

2016-01-01

Abstract Two phase I open‐label studies were conducted to investigate the pharmacokinetics (PK), safety, and tolerability of single oral doses of selumetinib in subjects with end‐stage renal disease (ESRD) undergoing hemodialysis and subjects with varying degrees of hepatic impairment; both studies included a matched control group comprised of healthy individuals. In the renal impairment study, subjects received single doses of selumetinib 50 mg; those with ESRD received selumetinib before and after dialysis (with a between‐treatment washout period of ≥7 days). In the hepatic impairment study, subjects received varying single doses of selumetinib (20‐50 mg) depending on liver dysfunction (mild, moderate, or severe as per Child‐Pugh classification). PK, safety, and tolerability data were collected from both studies. Overall, 24 subjects were included in the renal impairment study (ESRD, N = 12; healthy subjects, N = 12). Selumetinib exposure (AUC and Cmax) was not increased in the ESRD group vs healthy subjects. Selumetinib exposure was lower when selumetinib was dosed before vs after dialysis, although individual exposure was variable. Overall, 32 subjects were included in the hepatic impairment study (mild, moderate, and severe impairment, N = 8 per group; healthy subjects, N = 8). Generally, dose‐normalized total selumetinib exposure was increased by 25% to 59% in subjects with moderate and severe hepatic impairment compared with healthy subjects. Increasing Child‐Pugh score, decreasing serum albumin, and increasing prothrombin time correlated with increasing unbound selumetinib exposure. In both studies, selumetinib was well tolerated with no new safety concerns. These studies will inform dose adjustment considerations in patients. PMID:28019010

Radiation Tests of Single Photon Avalanche Diode for Space Applications

NASA Technical Reports Server (NTRS)

Moscatelli, Francesco; Marisaldi, Martino; MacCagnani, Piera; Labanti, Claudio; Fuschino, Fabio; Prest, Michela; Berra, Alessandro; Bolognini, Davide; Ghioni, Massimo; Rech, Ivan;

The Impact of Cocoa Flavanols on Cardiovascular Health.

PubMed

Vlachojannis, Julia; Erne, Paul; Zimmermann, Benno; Chrubasik-Hausmann, Sigrun

2016-10-01

The aim of the study was to review the effect of cocoa flavanols on cardiovascular health, with emphasis on the doses ingested, and to analyze a range of cocoa products for content of these compounds. PubMed was searched from 2010 to locate systematic reviews (SR) on clinical effects of chocolate consumption. Thirteen SRs were identified and reviewed, and provided strong evidence that dark chocolate did not reduce blood pressure. The evidence was however strong for an association with increased flow-mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Our analysis showed that cocoa products with around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure in specific individuals and/or if consumed over longer periods. Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, around 100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin) would need to be consumed. Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

PubMed

Fakhrian, K; Oechsner, M; Kampfer, S; Schuster, T; Molls, M; Geinitz, H

2013-04-01

The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.

Shelf life extension of minimally processed ready-to-cook (RTC) cabbage by gamma irradiation.

PubMed

Banerjee, Aparajita; Chatterjee, Suchandra; Variyar, Prasad S; Sharma, Arun

2016-01-01

Gamma irradiation (0.5-2.5 kGy) in combination with low temperature (4-15 °C) storage was attempted to increase shelf life of ready-to-cook shredded cabbage wrapped in cling films. A maximum extension in shelf life of 8 days, while retaining the microbial and sensory quality, was obtained with an irradiation dose of 2 kGy and storage at 10 °C. Gamma irradiation also inhibited browning of shredded cabbage at their cut edges resulting in enhanced visual appeal. An increase in total antioxidant activity was observed with respect to DPPH and hydroxyl radical scavenging ability while the nitric oxide radical scavenging activity and ferric reducing property remained unaffected with irradiation. Total phenolic, flavonoid and vitamin C content remained unchanged due to irradiation. No significant migration of additives from cling films into stimulant water was observed up to a radiation dose of 2 kGy thus demonstrating the feasibility of such films for above applications.

Effects of Increasing Doses of UV-B on Main Phenolic Acids Content, Antioxidant Activity and Estimated Biomass in Lavandin (Lavandula x intermedia).

PubMed

Usano-Alemany, Jaime; Panjai, Lachinee

2015-07-01

Lavandin is a well-known aromatic plant cultivated mainly for its valuable essential oil. Nonetheless, little attention has been paid so far to the quantification of other natural products such as polyphenols. Accordingly, we examined the effect of increasing doses of UV-B radiation on the main phenolic content, antioxidant activity and estimated biomass of one year old lavandin pots compared with pots grown outdoors. Significantly higher total phenolic content and concentration of main polyphenols have been found in outdoor plants. Rosmarinic acid has been described as the major phenolic compound in methanolic extracts (max. 25.9 ± 9.7 mg/g(-1) DW). Furthermore, we found that increasing doses of UV-B promote the plant growth of this species as well as the accumulation of phenolic compounds although with less antioxidant capacity in scavenging DPPH radicals. On the other hand, our results showed a remarkable variability among individual plants regarding the content of major phenolic acids. The application of UV-B doses during plant growth could be a method to promote biomass in this species along with the promotion of higher content of valuable secondary metabolites.

Pharmacokinetics of doxylamine, a component of Bendectin, in the rhesus monkey.

PubMed

Slikker, W; Holder, C L; Lipe, G W; Bailey, J R; Young, J F

1989-01-01

The elimination of doxylamine and metabolites was determined after iv administration of [14C]doxylamine succinate at 0.7 and 13.3 mg/kg to the adult female rhesus monkey. Although the total recovery of radioactivity was the same for the low- and high-dose studies (90.2%), the rate of plasma elimination of doxylamine and its demethylated metabolite (desmethyldoxylamine) was slower for the high dose group. The 24 hr urinary excretion of doxylamine metabolites, desmethyl- and didesmethyldoxylamine, was significantly increased and the polar doxylamine metabolites were significantly decreased as the iv doxylamine succinate dose was increased. The plasma elimination of gas chromatograph (GC)-detected doxylamine was determined after oral administration of Bendectin (doxylamine succinate and pyridoxine hydrochloride) at 7, 13.3, and 27 mg/kg to adult female rhesus monkeys. As the dose increased, the clearance of doxylamine decreased. A statistically evaluated fit of the oral data to a single-compartment, parallel first-order elimination model and a single-compartment, parallel first- and second-order (Michaelis-Menten) elimination model indicated that the more complex model containing the second-order process was most consistent with the observed elimination data.

Effects of low-dose gamma-irradiation on production of shikonin derivatives in callus cultures of Lithospermum erythrorhizon S.

NASA Astrophysics Data System (ADS)

Chung, B. Y.; Lee, Y.-B.; Baek, M.-H.; Kim, J.-H.; Wi, S. G.; Kim, J.-S.

2006-09-01

The yield increase of secondary metabolite production was examined in plant cell cultures with the use of relatively low to high doses gamma irradiation. Suspension culture of Lithospermum erythrorhizon cells was irradiated to 2, 16, and 32 Gy. The gamma irradiation significantly stimulated the shikonin biosynthesis of the cells and increased the total shikonin yields (intracellular+extracellular shikonin yields) by 400% at 16 Gy and by only 240% and 180% at 2 and 32 Gy, respectively. One of the key enzymes for the shikonin biosynthesis of cells, p-hydroxylbenzoic acid (PHB) geranyltransferase, was found to be stimulated by the gamma-radiation treatments. The activity of PHB geranyltransferase was increased at 2 and 16 Gy with a negligible change at 32 Gy. In contrast, the activity of PHB glucosyltransferase was slightly changed at all doses of gamma radiation compared with the control cells. Therefore, the increase in PHB geranyltransferase activity leads to the accumulation of secondary metabolites such as a shikonin, which may contribute to plant defense against the stresses induced by gamma irradiation.

Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5'-pyrophosphate) in Sprague-Dawley rats.

PubMed

Schauss, A G; Somfai-Relle, S; Financsek, I; Glavits, R; Parent, S C; Endres, J R; Varga, T; Szücs, Z; Clewell, A

2009-01-01

The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.

Molecular weight distribution of organic matter by ozonation and biofiltration.

PubMed

Lin, Yen-Hui

2012-01-01

Molecular weight (MW) distribution of organic matter by ozonation and biofiltration was evaluated using gel chromatography. The MW distribution of organic matter by Sephadex G-25 was observed from groups 2 (MW = 1,029-7,031 g/mol) and 3 (MW = 303-1,029 g/mol) shifted to groups 2, 3 and 4 (MW < 303 g/mol) under ozone doses of 0.1 and 0.4 mg O₃/mg total organic carbon (TOC). The shift in MW increases as ozone dosage increases. Biofiltration effectively degraded the organic molecule of group 2; however, the biofiltration only slightly degraded the organic molecule of group 4. Increased ozone dose destroyed functional groups C═C in phenolic and C-O in alcoholic compounds and increased UV-insensitive biodegradable organic carbon for subsequent biofiltration. Biofiltration effectively degraded organic compounds of alcohols and alkenes at an ozone dose of 0.1 mg O₃/mg TOC. Experimental approaches in this study can be applied to evaluate and diagnose the function of a full-scale process combining ozonation and biofiltration in drinking water treatment plants.

Retrospective evaluation of xylitol ingestion in dogs: 192 cases (2007-2012).

PubMed

DuHadway, Meghan R; Sharp, Claire R; Meyers, Katherine E; Koenigshof, Amy M

2015-01-01

To summarize the signalment, clinical signs, prevalence of decreased blood glucose concentration (BG), prevalence of increased liver values, treatment, and outcome in dogs known to have ingested xylitol. Retrospective study from December 2007 to February 2012 SETTING: Three university teaching hospitals. One hundred ninety-two client-owned dogs with known or suspected xylitol ingestion. None. The median ingested xylitol dose was 0.32 g/kg (range 0.03-3.64 g/kg). Clinical signs were present in 39 (20%) dogs on presentation to the veterinary teaching hospitals. The most common clinical sign was vomiting (n = 25), followed by lethargy (12). The median duration of clinical signs prior to presentation was 93 minutes (range 0-5,040 minutes). Dogs that developed clinical signs ingested a significantly higher dose of xylitol than those that were asymptomatic. Thirty dogs became hypoglycemic (BG ≤ 3.3 mmol/L [60 mg/dL]) at some time point during their hospitalization. When evaluating all dogs, there was a significant difference between the initial and lowest BGs. Thirty dogs had increased alanine aminotransferase activity or total serum bilirubin concentration. Dogs with increases in alanine aminotransferase activity or total serum bilirubin concentration had a significantly lower nadir BG. All dogs survived to discharge and 158 were known to be alive at 28 days. The rest were lost to follow up. The prognosis for dogs evaluated by a veterinarian that ingest lower doses of xylitol and do not develop liver failure is excellent. Dogs ingesting xylitol should be hospitalized and monitored for variations in BG, because BG drops in most dogs following presentation. Additional studies are needed in dogs ingesting higher doses of xylitol before correlations between dose and the development of clinical signs or liver failure can be established. Treatment and prognosis for these dogs warrants further investigation. © Veterinary Emergency and Critical Care Society 2015.

Twelve Months of Nightly Zolpidem Does Not Lead to Dose Escalation: A Prospective Placebo-Controlled Study

PubMed Central

Roehrs, Timothy A.; Randall, Surilla; Harris, Erica; Maan, Renee; Roth, Thomas

2011-01-01

Study Objectives: To assess hypnotic self-administration and likelihood of dose escalation over 12 months of nightly use of zolpidem versus placebo in primary insomniacs. Design: Randomized, double-blind, placebo-controlled, clinical trial. Setting: Outpatient with tri-monthly one-week, sleep laboratory assessments. Participants: Thirty-three primary insomniacs, without psychiatric disorders or drug and alcohol abuse, 32–64 yrs old, 14 men and 19 women. Interventions: Participants were randomized to take zolpidem 10 mg (n = 17) or placebo (n = 16) nightly for 12 months. In probes during month 1, 4, and 12, after sampling color-coded placebo or zolpidem capsules on 2 nights, color-coded zolpidem or placebo was chosen on 5 consecutive nights and 1, 2, or 3 of the chosen capsules (5 mg each) could be self-administered on a given choice night. Results: Zolpidem was chosen more nights than placebo (80% of nights) and number of nights zolpidem was chosen did not differ over the 12 months. More zolpidem than placebo capsules were self-administered, and the total number of placebo or zolpidem capsules self-administered did not differ as a function of duration of use. In contrast, the total number of placebo capsules self-administered by the placebo group increased across time. The nightly capsule self-administration on zolpidem nights did not differ from that on placebo nights and neither nightly self-administration rates increased over the 12 months. An average 9.3 mg nightly dose was self-administered. Conclusions: Zolpidem was preferred to placebo, but its self-administration did not increase with 12 months of use. Chronic hypnotic use by primary insomniacs does not lead to dose escalation. Clinical Trial Registration: Safety and Efficacy of Chronic Hypnotic Use; # NCT01006525; http://www.clinicaltrials.gov/ Citation: Roehrs TA; Randall S; Harris E; Maan R; Roth T. Twelve months of nightly zolpidem does not lead to dose escalation: a prospective placebo-controlled study. SLEEP 2011;34(2):207–212. PMID:21286241

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

PubMed Central

Adebesin, Olumide Adedapo; Okpuzor, Joy

2014-01-01

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