SU-F-T-372: Surface and Peripheral Dose in Compensator-Based FFF Beam IMRT

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

Zhang, D; Feygelman, V; Moros, E

2016-06-15

Purpose: Flattening filter free (FFF) beams produce higher dose rates. Combined with compensator IMRT techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or compensator-based IMRT. This ‘snap shot’ IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, surface doses in FFF beam treatment are usually higher than those from flattened beams. Because of less scattering due to no flattening filter, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introducemore » beam hardening effects and scattering such that the surface dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? Methods: This study applied Monte Carlo techniques to investigate the surface and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides various thicknesses of copper slabs to simulate various thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC defined FFF and flattened beams with various openings. After normalized to Dmax, the surface and peripheral dose was compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. Results: The surface dose at the central 0.5mm depth was close between the compensator and 6FFF MLC dose distributions, and about 8% (of Dmax) higher than the flattened 6MV MLC dose. At 8cm off axis at dmax, the peripheral dose between the 6FFF and flattened 6MV MLC demonstrated similar doses, while the compensator dose was about 1% higher. Conclusion: Compensator does not reduce the surface doses but slightly increases the peripheral doses due to scatter inside compensator.« less

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

Health risk profile for terrestrial radionuclides in soil around artisanal gold mining area at Alsopag, Sudan

NASA Astrophysics Data System (ADS)

Idriss, Hajo; Salih, Isam; Alaamer, Abdulaziz S.; AL-Rajhi, M. A.; Osman, Alshfia; Adreani, Tahir Elamin; Abdelgalil, M. Y.; Ali, Nagi I.

2018-06-01

This study shows the assessment of radiation hazard parameters due to terrestrial radionuclides in the soil around artisanal gold mining for addressing the issue of natural radioactivity in mining areas. Hence, the levels 238U, 232Th, 40K and 226Ra in soil (using gamma spectrometry), 222Rn in soil and 222Rn in air were determined. Radiation hazard parameters were then computed. These include absorbed dose D, annual effective dose E, radium equivalent activity Raeq, external hazard H ex, annual gonadal dose equivalent hazard index AGDE and excess lifetime cancer risk ELCR due to the inhalation of radon (222Rn) and consumption of radium (226Ra) in vegetation. Uranium (238U), thorium (232Th) and potassium (40K) averages were, respectively, 26, 36 and 685 Becquerel per kilogram (Bq kg-1). Soil radon (4671 Bq m-3) and radon in air (14.77 Bq m-3) were found to be less than worldwide data. Nevertheless, the average 40K concentration was 685 Bq kg-1. This is slightly higher than the United Nations Scientific Committee on the Effects of Atomic Radiation average value of 412 Bq kg-1. The obtained result indicates that some of the radiation hazard parameters seem unsavory. The mean value of absorbed dose rate (62.49 nGy h-1) was slightly higher than average value of 57 nGy h-1 ( 45% from 40K), and that of AGDE (444 μSv year-1) was higher than worldwide average reported value (300 μSv year-1). This study highlights the necessity to launch extensive nationwide radiation protection program in the mining areas for regulatory control.

Dosimetry of {sup 210}Po in humans, caribou, and wolves in northern Canada

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

Thomas, P.A.

1994-06-01

Effective doses from {sup 210}Po intake with caribou meat were determined for human residents in Baker Lake and Snowdrift in the Northwest Territories of Canada and compared to doses calculated from reported {sup 210}Po tissue activities in Alaskan and British residents. Effective doses were calculated to separate body tissues, using ICRP 60 human weighting factors and the ICRP 30 metabolic model for {sup 210}Po. Baker Lake and Alaskan effective doses were similar at 0.4 mSv y{sup {minus}1} and slightly higher than Snowdrift doses (0.3 mSv y{sup {minus}1}). Alaskan tissue activities indicated higher effective doses to liver, bone surfaces and redmore » marrow and lower doses to spleen than the {sup 210}Po metabolic model (ICRP 1979a) predicts. Effective doses to Baker Lake and Snowdrift caribou and wolves, calculated from tissue activities, ranged from 7-20 mSv y{sup {minus}1} using human weighting factors for comparison to human doses only. Effective doses to northern Canadians and wildlife were, respectively, 7-11% and 1.8-5 times an estimated human background of 4 mSv y{sup {minus}} from all sources. 51 refs., 2 figs., 9 tabs.« less

Alkaline treatment of high-solids sludge and its application to anaerobic digestion.

PubMed

Li, Chenchen; Li, Huan; Zhang, Yuyao

2015-01-01

High-solids anaerobic digestion is a promising new process for sludge reduction and bioenergy recovery, requiring smaller digestion tanks and less energy for heating, but a longer digestion time, than traditional low-solids anaerobic digestion. To accelerate this process, alkaline sludge disintegration was tested as a pretreatment method for anaerobic digestion of high-solids sludge. The results showed that alkaline treatment effectively disintegrated both low-solids sludge and high-solids sludge, and treatment duration of 30 min was the most efficient. The relation between sludge disintegration degree and NaOH dose can be described by a transmutative power function model. At NaOH dose lower than 0.2 mol/L, sludge disintegration degree remained virtually unchanged when sludge total solids (TS) content increased from 2.0 to 11.0%, and decreased only slightly when sludge TS increased to 14.2%. Although high-solids sludge required a slightly higher molarity of NaOH to reach the same disintegration level of low-solids sludge, the required mass of NaOH actually decreased due to sludge thickening. From the view of NaOH consumption, sludge TS of 8-12% and a NaOH dose of 0.05 mol/L were optimum conditions for alkaline pretreatment, which resulted in a slight increase in accumulative biogas yield, but a decrease by 24-29% in digestion time during the subsequent anaerobic digestion.

Multiscale image processing and antiscatter grids in digital radiography.

PubMed

Lo, Winnie Y; Hornof, William J; Zwingenberger, Allison L; Robertson, Ian D

2009-01-01

Scatter radiation is a source of noise and results in decreased signal-to-noise ratio and thus decreased image quality in digital radiography. We determined subjectively whether a digitally processed image made without a grid would be of similar quality to an image made with a grid but without image processing. Additionally the effects of exposure dose and of a using a grid with digital radiography on overall image quality were studied. Thoracic and abdominal radiographs of five dogs of various sizes were made. Four acquisition techniques were included (1) with a grid, standard exposure dose, digital image processing; (2) without a grid, standard exposure dose, digital image processing; (3) without a grid, half the exposure dose, digital image processing; and (4) with a grid, standard exposure dose, no digital image processing (to mimic a film-screen radiograph). Full-size radiographs as well as magnified images of specific anatomic regions were generated. Nine reviewers rated the overall image quality subjectively using a five-point scale. All digitally processed radiographs had higher overall scores than nondigitally processed radiographs regardless of patient size, exposure dose, or use of a grid. The images made at half the exposure dose had a slightly lower quality than those made at full dose, but this was only statistically significant in magnified images. Using a grid with digital image processing led to a slight but statistically significant increase in overall quality when compared with digitally processed images made without a grid but whether this increase in quality is clinically significant is unknown.

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

NASA Astrophysics Data System (ADS)

Herrera, Higmar; Yañez, Elvia; Deras, Diana C.; Reyes, Francianella

2010-12-01

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55±13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

Analysis of buprenorphine/naloxone dosing impact on treatment duration, resource use and costs in the treatment of opioid-dependent adults: a retrospective study of US public and private health care claims.

PubMed

Khemiri, Amine; Kharitonova, Elizaveta; Zah, Vladimir; Ruby, Jane; Toumi, Mondher

2014-09-01

The buprenorphine/naloxone combination is used to treat the chronic relapsing disorder of opioid dependence. Adequate dosing levels are important to control cravings, prevent withdrawal syndrome, and maintain patients in treatment. The objective of this study was to estimate the impact of dosing on treatment persistence, resource utilization, and total direct health care costs. A retrospective cohort analysis was performed using administrative claims extracted from the MarketScan and Clinformatics databases from January 2007 to June and November 2012. Patients initiating treatment with buprenorphine/naloxone were classified into 2 groups based on the prescribed average dose over the entire treatment period and matched by multiple criteria. The threshold for differentiating the dosing groups was set at 15 and 15.7 mg/day for publicly and privately insured patients, respectively. Resource utilization and related costs were calculated over the 12-month period after the treatment initiation. Patient characteristics at baseline were considerably different between the privately and publicly insured patients. Publicly insured patients were slightly younger (33.1 vs 34.3 years old for privately insured) and had a higher prevalence of mental disorders (70.9% vs 64.9%). In both groups, patients treated with higher doses (> 15 mg and > 15.7 mg per day for publicly and privately insured patients, respectively) had lower risk of discontinuation (public: 11% lower; private: 9% lower) and lower probability of a psychiatric hospitalization than patients treated with lower doses (public: 17% lower; private: 41% lower). Total costs were comparable between the 2 groups (public: $14 600; private: $21 000) despite the expected higher cost of pharmacy in the higher-dose group. Treatment with higher doses of buprenorphine/naloxone was associated with a longer time to treatment discontinuation, less resource use, and lower total medical costs despite higher pharmacy acquisition cost.

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats.

PubMed

Abdel-Kader, Maged S; Abulhamd, Ashraf T; Hamad, Abubaker M; Alanazi, Abdullah H; Ali, Rizwan; Alqasoumi, Saleh I

2018-05-01

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in  Glycyrrhiza glabra  (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

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

Herrera, Higmar; Yanez, Elvia; Deras, Diana C.

2010-12-07

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher agemore » (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).« less

X-ray induced dominant lethal mutations in mature and immature oocytes of guinea-pigs and golden hamsters.

PubMed

Cox, B D; Lyon, M F

1975-06-01

The induction of dominant lethal mutations by doses of 100-400 rad X-rays in oocytes of the guinea-pig and golden hamster was studied using criteria of embryonic mortality. For both species higher yields were obtained from mature than from immature oocytes, in contrast to results for the mouse. Data on fertility indicated that in the golden hamster, as in the mouse, immature oocytes were more sensitive to killing by X-rays than mature oocytes but that the converse was true in the guinea-pig. The dose-response relationship for mutation to dominant lethals in pre-ovulatory oocytes of guinea-pig and golden hamsters was linear, both when based on pre- and post-implantation loss and when on post-implantation loss only. The rate per unit dose was higher for the golden hamster, and the old golden hamsters were possibly slightly more sensitive than young ones. The mutation rate data for mature oocytes of the mouse, using post-implantation loss alone, also fitted a linear dose-response relationship, except that the rate per unit dose was lower than for the other two species.

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

An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

PubMed

Nalamachu, Srinivas

2013-12-01

Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting <1 h. Thus, optimal relief from breakthrough pain is best attained by administering analgesics with dissolution times and bioavailabilities that closely match the onset and duration of breakthrough pain. The objective of this study was to assess complete disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

Monitoring exposure to atomic bomb radiation by somatic mutation

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

Akiyama, Mitoshi; Kyoizumi, Seishi; Kusunoki, Yoichiro

Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in femalesmore » and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). And the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure. 27 refs., 2 figs.« less

Ferromagnetism appears in nitrogen implanted nanocrystalline diamond films

NASA Astrophysics Data System (ADS)

Remes, Zdenek; Sun, Shih-Jye; Varga, Marian; Chou, Hsiung; Hsu, Hua-Shu; Kromka, Alexander; Horak, Pavel

2015-11-01

The nanocrystalline diamond films turn to be ferromagnetic after implanting various nitrogen doses on them. Through this research, we confirm that the room-temperature ferromagnetism of the implanted samples is derived from the measurements of magnetic circular dichroism (MCD) and superconducting quantum interference device (SQUID). Samples with larger crystalline grains as well as higher implanted doses present more robust ferromagnetic signals at room temperature. Raman spectra indicate that the small grain-sized samples are much more disordered than the large grain-sized ones. We propose that a slightly large saturated ferromagnetism could be observed at low temperature, because the increased localization effects have a significant impact on more disordered structure.

Radiation dose and cancer risk estimates in helical CT for pulmonary tuberculosis infections

NASA Astrophysics Data System (ADS)

Adeleye, Bamise; Chetty, Naven

2017-12-01

The preference for computed tomography (CT) for the clinical assessment of pulmonary tuberculosis (PTB) infections has increased the concern about the potential risk of cancer in exposed patients. In this study, we investigated the correlation between cancer risk and radiation doses from different CT scanners, assuming an equivalent scan protocol. Radiation doses from three 16-slice units were estimated using the CT-Expo dosimetry software version 2.4 and standard CT scan protocol for patients with suspected PTB infections. The lifetime risk of cancer for each scanner was determined using the methodology outlined in the BEIR VII report. Organ doses were significantly different (P < 0.05) between the scanners. The calculated effective dose for scanner H2 is 34% and 37% higher than scanners H3 and H1 respectively. A high and statistically significant correlation was observed between estimated lifetime cancer risk for both male (r2 = 0.943, P < 0.05) and female patients (r2 = 0.989, P < 0.05). The risk variation between the scanners was slightly higher than 2% for all ages but was much smaller for specific ages for male and female patients (0.2% and 0.7%, respectively). These variations provide an indication that the use of a scanner optimizing protocol is imperative.

Effects of various doses of selenite on stinging nettle (Urtica dioica L.).

PubMed

Krystofova, Olga; Adam, Vojtech; Babula, Petr; Zehnalek, Josef; Beklova, Miroslava; Havel, Ladislav; Kizek, Rene

2010-10-01

The aim of this study was to investigate the effects of selenium (Se) on the growth, accumulation and possible mechanisms of Se transport in certain parts (roots, leaves, stamp and apex) of nettle (Urtica dioica L.) plants. Se was supplemented by one-shot and two repeated doses to the soil (2.0 and 4.0 mg Se per kg of substrate). Selenium content in roots increased linearly with dose and was significantly higher compared to other plant parts of interest. However, growth of the above-ground parts of plant as well as roots was slightly inhibited with increasing selenium concentration in comparison to the untreated plants. The content of phytochelatin2, a low molecular mass peptide containing a sulfhydryl group, correlated well with the Se content. This suggests a possible stimulation of synthesis of this plant peptide by Se.

Mobilizing peripheral blood stem cells with high-dose G-CSF alone is as effective as with Dexa-BEAM plus G-CSF in lymphoma patients.

PubMed

Kröger, N; Zeller, W; Fehse, N; Hassan, H T; Krüger, W; Gutensohn, K; Lölliger, C; Zander, A R

1998-09-01

We compared retrospectively the efficacy of granulocyte colony stimulating factor (G-CSF) alone with chemotherapy plus G-CSF in mobilizing CD34-positive cells in patients with malignant lymphoma. 35 patients underwent peripheral blood stem cell (PBSC) collection following mobilization either with 24 microg/kg G-CSF for 4 consecutive days (n = 18) or Dexa-BEAM chemotherapy plus 5 microg/kg G-CSF (n = 17). High-dose G-CSF was well tolerated with only slight bone pain and/or myalgia. The Dexa-BEAM therapy required hospitalization with a median duration of 21 d. The median number of apheresis procedures in both groups was two (range two to four), resulting in a median of 5.3 and 5.1 x 10(6) CD34+ cells/kg. No patients in the G-CSF group, but one in the Dexa-BEAM group, failed to reach the target of collecting >2.0 x 10(6) CD34+ cells/kg. The number of CFU-GM (10.4 v 6.0 x 10(5)/kg) and of BFU-E (10.6 v 4.5 x 10(5)/kg; P = 0.04) was higher in the G-CSF group than in the Dexa-BEAM group. A subset analysis of CD34+ cells was performed in 16 patients showing a higher mean of Thy-1 (CD90w) coexpression in the G-CSF than in the Dexa-BEAM group (4.8 v 1.8%, P = 0.12). Additionally the percentage of CD34+/CD38- cells was higher in the G-CSF group (10.66% v 8.8%). However, these differences were not statistically significant. The median time to leucocyte and platelet engraftment after high-dose chemotherapy was slightly shorter in the G-CSF than in the Dexa-BEAM group (9 v 10 and 12 v 13.5 d, respectively). These results demonstrate that high-dose G-CSF is as effective as Dexa-BEAM plus G-CSF in mobilizing peripheral blood stem cells and produces prompt engraftment. The major advantages of G-CSF mobilization were the safe outpatient self-application and the fixed-day apheresis.

Author Correction: Targeted gadofullerene for sensitive magnetic resonance imaging and risk-stratification of breast cancer.

PubMed

Han, Zheng; Wu, Xiaohui; Roelle, Sarah; Chen, Chuheng; Schiemann, William P; Lu, Zheng-Rong

2018-01-08

In the original version of this Article, the penultimate sentence of the Abstract incorrectly read 'The dose of the contrast agent for effective molecular MRI is only slightly lower than that of ZD2-Cy5.5 (0.5 µmol kg -1 ) in fluorescence imaging.' The correct version states 'higher' in place of 'lower'. This error has been corrected in both the PDF and HTML versions of the Article.

SU-F-T-539: Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Whole Brain Hippocampal Sparing Radiation Therapy Treatments

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

Kendall, E; Higby, C; Algan, O

2016-06-15

Purpose: To compare the treatment plan quality and dose gradient near the hippocampus between VMAT (RapidArc) and IMRT delivery techniques for whole brain radiation therapy. Methods: Fifteen patients were evaluated in this retrospective study. All treatments were planned on Varian Eclipse TPS, using 3-Arc VMAT and 9-Field IMRT, following NRG Oncology protocol NRG-CC001 guidelines evaluated by a single radiation oncologist. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 100% of the dose covering 95% of the target volume. Identical contour sets and dose-volume constraints following protocol guidelines were also applied inmore » all plans. A paired t-test analysis was used to compare VMAT and IMRT plans. Results: NRG-CC001 protocol dose-volume constraints were met for all VMAT and IMRT plans. For the planning target volume (PTV), the average values for D2% and D98% were 6% lower and 4% higher in VMAT than in IMRT, respectively. The average mean and maximum hippocampus doses in Gy for VMAT vs IMRT plans were (11.85±0.81 vs. 12.24±0.56, p=0.10) and (16.27±0.78 vs. 16.59±0.71, p=0.24), respectively. In VMAT, the average mean and maximum chiasm doses were 3% and 1% higher than in IMRT plans, respectively. For the left optic nerve, the average mean and maximum doses were 10% and 5% higher in VMAT than in IMRT plans, respectively. These values were 12% and 3% for the right optic nerve. The average percentage of dose gradient around the hippocampus in the 0–5mm and 5–10mm abutted regions for VMAT vs. IMRT were (4.42%±2.22% /mm vs. 3.95%±2.61% /mm, p=0.43) and (4.54%±1.50% /mm vs. 4.39%±1.28% /mm, p=0.73), respectively. Conclusion: VMAT plans can achieve higher hippocampus sparing with a faster dose fall-off than IMRT plans. Though statistically insignificant, VMAT offers better PTV coverage with slightly higher doses to OARs.« less

Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients.

PubMed

Desch, Steffen; Kobler, Daniela; Schmidt, Johanna; Sonnabend, Melanie; Adams, Volker; Sareban, Mahdi; Eitel, Ingo; Blüher, Matthias; Schuler, Gerhard; Thiele, Holger

2010-06-01

Dark chocolate may have blood pressure-lowering properties. We conducted a prospective randomized open-label blinded end-point design trial to study a potential dose dependency of the presumed antihypertensive effect of dark chocolate by directly comparing low vs. higher doses of dark chocolate over the course of 3 months. We enrolled a total of 102 patients with prehypertension/stage 1 hypertension and established cardiovascular end-organ damage or diabetes mellitus. Patients were randomly assigned to receive either 6 or 25 g/day of flavanol-rich dark chocolate for 3 months. The difference in 24-h mean blood pressure between groups was defined as the primary outcome measure. Significant reductions in mean ambulatory 24-h blood pressure were observed between baseline and follow-up in both groups (6 g/day: -2.3 mm Hg, 95% confidence interval -4.1 to -0.4; 25 g/day: -1.9 mm Hg, 95% confidence interval -3.6 to -0.2). There were no significant differences in blood pressure changes between groups. In the higher-dose group, a slight increase in body weight was noted (0.8 kg, 95% confidence interval 0.06 to 1.6). The findings are consistent with the hypothesis that dark chocolate may be associated with a reduction in blood pressure (BP). However, due to the lack of a control group, confounding may be possible and the results should be interpreted with caution.

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.

Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

PubMed

Yap, Felix Boon-Bin

2017-09-01

Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

DBP formation in hot and cold water across a simulated distribution system: effect of incubation time, heating time, pH, chlorine dose, and incubation temperature.

PubMed

Liu, Boning; Reckhow, David A

2013-10-15

This paper demonstrates that disinfection byproducts (DBP) concentration profiles in heated water were quite different from the DBP concentrations in the cold tap water. Chloroform concentrations in the heated water remained constant or even decreased slightly with increasing distribution system water age. The amount of dichloroacetic acid (DCAA) was much higher in the heated water than in the cold water; however, the maximum levels in heated water with different distribution system water ages did not differ substantially. The levels of trichloroacetic acid (TCAA) in the heated water were similar to the TCAA levels in the tap water, and a slight reduction was observed after the tap water was heated for 24 h. Regardless of water age, significant reductions of nonregulated DBPs were observed after the tap water was heated for 24 h. For tap water with lower water ages, there were significant increases in dichloroacetonitrile (DCAN), chloropicrin (CP), and 1,1-dichloropropane (1,1-DCP) after a short period of heating. Heating of the tap water with low pH led to a more significant increase of chloroform and a more significant short-term increase of DCAN. High pH accelerated the loss of the nonregulated DBPs in the heated water. The results indicated that as the chlorine doses increased, levels of chloroform and DCAA in the heated water increased significantly. However, for TCAA, the thermally induced increase in concentration was only notable for the chlorinated water with very high chlorine dose. Finally, heating may lead to higher DBP concentrations in chlorinated water with lower distribution system temperatures.

SU-E-T-302: Dosimetric Comparison Between Volumetric Modulated Arc Radiotherapy and Intensity-Modulated Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma

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

Lu, J-Y; Huang, B-T; Zhang, J-Y

2015-06-15

Purpose: To compare volumetric modulated arc radiotherapy (VMAT) technique with fixed-gantry intensity-modulated radiotherapy (IMRT) technique for locally recurrent nasopharyngeal carcinoma. Methods: CT datasets of eleven nasopharyngeal-carcinoma patients were included. Dual-arc VMAT and seven-field IMRT plans were created for each case, and were then compared in terms of conformity index (CI), homogeneity index (HI) of the planning target volume (PTV), organ-at-risk (OAR) sparing, monitor unit (MU) and delivery time. Results: The D98% (near-minimal dose) of PTV in the VMAT plans was slightly lower than that of the IMRT plans (P < 0.05), while the CI was higher than that of themore » IMRT plans (P < 0.05). No significant difference was found in the HI between the two plans (P > 0.05). Compared with the IMRT plans, the VMAT plans demonstrated lower Dmean (mean dose) of the bilateral temporal lobes and the whole surrounding normal tissue (P < 0.05), but slightly higher Dmean of brainstem (P < 0.05). In terms of the other OARs, no significant differences were found (P > 0.05). The MUs of the VMAT plans (672 ± 112) was significantly lower than that of the IMRT plans (917 ± 206), by 25 ± 13% (P < 0.05). The average delivery time of the VMAT plans (2.3 ± 0.1 min) was less than that of the IMRT plans (5.1 ± 0.4 min), by 54 ± 3%. Conclusion: For locally recurrent nasopharyngeal carcinoma, the VMAT technique could achieve equivalent or superior dose distribution of the target and better protect the bilateral temporal lobes, compared with the IMRT technique. Moreover, it could reduce the MU and delivery time effectively.« less

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

PubMed

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

2017-10-01

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

SU-E-P-11: Comparison of Image Quality and Radiation Dose Between Different Scanner System in Routine Abdomen CT

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

Liao, S; Wang, Y; Weng, H

Purpose To evaluate image quality and radiation dose of routine abdomen computed tomography exam with the automatic current modulation technique (ATCM) performed in two different brand 64-slice CT scanners in our site. Materials and Methods A retrospective review of routine abdomen CT exam performed with two scanners; scanner A and scanner B in our site. To calculate standard deviation of the portal hepatic level with a region of interest of 12.5 mm x 12.5mm represented to the image noise. The radiation dose was obtained from CT DICOM image information. Using Computed tomography dose index volume (CTDIv) to represented CT radiationmore » dose. The patient data in this study were with normal weight (about 65–75 Kg). Results The standard deviation of Scanner A was smaller than scanner B, the scanner A might with better image quality than scanner B. On the other hand, the radiation dose of scanner A was higher than scanner B(about higher 50–60%) with ATCM. Both of them, the radiation dose was under diagnostic reference level. Conclusion The ATCM systems in modern CT scanners can contribute a significant reduction in radiation dose to the patient. But the reduction by ATCM systems from different CT scanner manufacturers has slightly variation. Whatever CT scanner we use, it is necessary to find the acceptable threshold of image quality with the minimum possible radiation exposure to the patient in agreement with the ALARA principle.« less

Influence of acute and chronic administration of methadone hydrochloride on NADPH-cytochrome c reductase and cytochrome P-450 of mouse liver microsomes.

PubMed

Datta, R K; Johnson, E A; Bhattacharjee, G; Stenger, R J

1976-03-01

Administration of a single acute dose (20 mg/kg body weight) of methadone hydrochloride to both male and female mice increased the specific activity of NADPH-cytochrome c reductase and did not change much the content of cytochrome P-450 of their liver microsomes. Administration of multiple acute doses of methadone in male mice increased the specific activity of cytochrome c reductase and the content of cytochrome P-450 of their liver microsomes. Chronic administration of progressively increasing doses of methadone (up to 40 mg/kg body weight) to male mice increased the specific activity of c reductase. Similar chronic administration of methadone up to 28 mg/kg body weight also increased the microsomal content of P-450, but with higher doses of methadone, the content of P-450 declined and finally dropped slightly below control levels. The levels of c reductase activity and P-450 content returned to normal about two weeks after discontinuation of methadone administration.

Uptake and toxicity of glyphosate in the lichen Xanthoria parietina (L.) Th. Fr.

PubMed

Vannini, Andrea; Guarnieri, Massimo; Bačkor, Martin; Bilová, Ivana; Loppi, Stefano

2015-12-01

This study investigated if treatment of the lichen Xanthoria parietina (L.) Th. Fr. with glyphosate caused uptake of this herbicide as well as physiological alterations. Samples were treated with Glifene SL®, a common commercial glyphosate-based herbicide, at the lowest recommended doses (3.6g/L) as well as with doses slightly higher than the highest suggested (36 g/L). The results clearly showed glyphosate uptake in X. parietina proportionally to the dose provided. Adverse physiological effects were evident on the photosynthetic apparatus (photosynthetic efficiency, chlorophyll a content, chlorophyll degradation) as well as on the fungal respiration rates and cell membrane integrity (ergosterol content, dehydrogenase activity) already after 24h from treatment, also at the low application dose. It is concluded that lichens are suitable organisms for monitoring unwanted biological effects from the application of glyphosate-based herbicides, as well as for detecting the accumulation of this compound in the biota, thus screening for its environmental fate. Copyright © 2015 Elsevier Inc. All rights reserved.

The influence of electron beam radiation in the nutritional value, chemical composition and bioactivities of edible flowers of Bauhinia variegata L. var. candida alba Buch.-Ham from Brazil.

PubMed

Villavicencio, Anna L C H; Heleno, Sandrina A; Calhelha, Ricardo C; Santos-Buelga, Celestino; Barros, Lillian; Ferreira, Isabel C F R

2018-02-15

As edible flowers are highly perishable, irradiation technology can be applied to increase their shelf life, as also for phytosanitary purposes. Herein, flowers of Bauhinia variegata L. var. candida alba Buch.-Ham were submitted to electron beam irradiation at the doses of 0.5, 0.8 and 1kGy, to study the effects in the nutritional and chemical profiles, and also in antioxidant, cytotoxic and anti-inflammatory activities. The petals of white flowers revealed interesting bioactive properties being kaempferol derivatives the most abundant compounds, especially kaempferol-3-O-rutinoside. The applied irradiation doses did not highly affect the nutritional profile. No changes were produced in cytotoxicity, but the anti-inflammatory activity slightly decreased. However, the antioxidant activity was increased, especially in the dose of 0.5kGy, in agreement with the higher content in phenolic compounds found at this dose. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antiviral activity of sandalwood oil against herpes simplex viruses-1 and -2.

PubMed

Benencia, F; Courrèges, M C

1999-05-01

Sandalwood oil, the essential oil of Santalum album L., was tested for in vitro antiviral activity against Herpes simplex viruses-1 and -2. It was found that the replication of these viruses was inhibited in the presence of the oil. This effect was dose-dependent and more pronounced against HSV-1. A slight diminution of the effect was observed at higher multiplicity of infections. The oil was not virucidal and showed no cytotoxicity at the concentrations tested.

A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

PubMed

Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

2014-08-01

Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Various Doses of Selenite on Stinging Nettle (Urtica dioica L.)

PubMed Central

Krystofova, Olga; Adam, Vojtech; Babula, Petr; Zehnalek, Josef; Beklova, Miroslava; Havel, Ladislav; Kizek, Rene

2010-01-01

The aim of this study was to investigate the effects of selenium (Se) on the growth, accumulation and possible mechanisms of Se transport in certain parts (roots, leaves, stamp and apex) of nettle (Urtica dioica L.) plants. Se was supplemented by one-shot and two repeated doses to the soil (2.0 and 4.0 mg Se per kg of substrate). Selenium content in roots increased linearly with dose and was significantly higher compared to other plant parts of interest. However, growth of the above-ground parts of plant as well as roots was slightly inhibited with increasing selenium concentration in comparison to the untreated plants. The content of phytochelatin2, a low molecular mass peptide containing a sulfhydryl group, correlated well with the Se content. This suggests a possible stimulation of synthesis of this plant peptide by Se. PMID:21139861

Dose-dependent effects of 6-hydroxy dopamine on deprivation myopia, electroretinograms, and dopaminergic amacrine cells in chickens.

PubMed

Li, X X; Schaeffel, F; Kohler, K; Zrenner, E

1992-11-01

We found that a single intravitreal injection of 6-hydroxy dopamine (6-OHDA) is highly efficient in blocking the development of deprivation-induced myopia in young chickens. To investigate the effects of 6-OHDA on retinal function, we studied electroretinograms (ERGs) in chickens aged 15-25 days, 4 days subsequent to the injection. Both spectral sensitivity and oscillatory potentials were tested. In addition, a histological examination was performed of dopaminergic amacrine cells labeled by a monoclonal antibody against tyrosine hydroxylase. We found that, at doses of 6-OHDA sufficient to suppress deprivation myopia entirely, no effect could be detected on either the ERGs or on the density and appearance of dopaminergic amacrine cells. For higher doses, spectral sensitivity and the number of dopaminergic amacrine cells declined gradually. In contrast, as doses increased, oscillatory potentials 1 and 2 grew in amplitude only to decline at the highest doses. The results indicate that (1) development of deprivation myopia requires normal retinal function and that (2) slight changes in the gains of dopaminergic pathways are sufficient to block the development of deprivation myopia.

A Characterization of the Radiation from a Rod-Pinch Diode

NASA Astrophysics Data System (ADS)

Swanekamp, Stephen B.; Allen, Raymond J.; Hinshelwood, David D.; Mosher, David; Schumer, Joseph W.

2002-12-01

Coupled PIC-Monte-Carlo simulations of the electron-flow and radiation production in a rod-pinch diode show that multiple scatterings in the rod produce incident electron energies that ranging from zero to slightly higher than the applied voltage. It is speculated that those electrons that gain energy do so by remaining in phase with a rapidly varying electric field near the tip of the rod. The simulations also show that multiple passes in the rod produce a wide spread in incident electron angles. For diode voltages of V=2 MV, the angular distribution of electrons incident on the rod is broad and peaked near 90° to the axis of the rod with a larger fraction of electrons striking the rod at angles less than 90°. The electron angular distribution for V=4 MV is narrower and peaked at 105° with a larger fraction of electrons incident on the rod with angles greater than 90°. The photon distributions are peaked along the direction of the high-energy electrons. For V=2 MV the dose filtered through 21/4-cm thick Plexiglas is peaked at 90° and is 1.8 times higher than the forward-directed [0°] dose. For V=4 MV the dose filtered through 21/4-cm thick Plexiglas is peaked at 120° and is 2.3 times higher than the forward-directed dose. Similar angular variation of the dose has been observed on the 4-MV Asterix accelerator [2] and on 1-2 MV accelerators at the Atomic Weapons Establishment [8].

Genetic effects on heavy ions in drosophila

NASA Technical Reports Server (NTRS)

Kale, P. G.

1986-01-01

Drosophila sex-linked recessive lethal mutation test was used to study the dose response relation and relative biological effectiveness of heavy ions. The experiments were performed using the heavy ion beams at BEVALAC of Lawrence Berkeley Laboratory. These experiments were undertaken according to the proposed milestones and included Ne-20, A-40 and Fe-65 ions with respective energies of 600 MeV, 840 MeV and 850 MeV. At these energies several doses of these radiations ranging from 20 to 1280 R were used. Space radiation exposure to astronauts is supposed to be quite low and therefore very low dose experiments i.e., 20 R, were also performed for the three ions. The mutation response was measured in all germ cell types i.e., spermatozoa, spermatids, spermatocytes and spermatogonia of treated Drosophila males. A linear dose frequency relation was observed for most of the range except at high doses where the saturation effect was observed. Also, a very significant difference was observed among the sensitivity of the four germ cell stages where spermatozoa and spermatids were more sensitive. At the higher doses of this range, most of the spermatogonia and spermatocytes were killed. Although comparative and identical experiments with X-rays or neutrons have not been performed, the compassion of our data with the ones available in literature suggest that the heavy ions have a high rbe and that they are several times more effective than low LET X-rays. The rbe compared to neutrons however appears to be only slightly higher.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

PubMed

Winkler-Heil, R; Hussain, M; Hofmann, W

2015-05-01

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II

NASA Technical Reports Server (NTRS)

Pecaut, Michael J.; Gridley, Daila S.; Smith, Anna L.; Nelson, Gregory A.

2002-01-01

The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.

Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy.

PubMed

Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

2002-02-21

We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.

Effect of nicotinic acid on the sleep time and tolerance induced by ethanol in the rat

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

Basilio, C.; Toro, A.; Yojay, L.

The intraperitoneal (i.p.) administration (50 mg/kg) of nicotinic acid (NA), markedly decreased the sleep time of rats pretreated (10 min before), post-treated (10 min after) or simultaneously treated with ethanol (4 g/Kg i.p.). A similar effect was observed on the sleep time induced by pentobarbital (37 mg/Kg i.p.). Blood alcohol levels (BAL) were the same or slightly higher in the animals pretreated with NA than in the control animals pre-injected with saline. Nicotinamide and NAD had no effect. A total of three doses of ethanol, each one administered weekly or biweekly, induced tolerance, which persisted for approximately six weeks. Aftermore » this period, a hypersensitivity to ethanol appeared to develop. This phenomenon was not observed when NA was pre-injected 10 min before each dose of ethanol. The sleep time of the latter animals did not change neither during the treatment period nor after six weeks without any treatment. BAL were slightly higher in NA treated than in control animals. The authors concluded that the effect of NA on the sleep time and tolerance induced by ethanol is not due to an increased rate of its metabolism and/or elimination but to a long-lasting effect that decreases the sensitivity of the nervous cells to ethanol. The mechanisms involved in the shortening of the sleep time as well as those responsible for the loss of the capacity to develop tolerance are under current investigation.« less

Characteristic of EBT-XD and EBT3 radiochromic film dosimetry for photon and proton beams

NASA Astrophysics Data System (ADS)

Khachonkham, Suphalak; Dreindl, Ralf; Heilemann, Gerd; Lechner, Wolfgang; Fuchs, Hermann; Palmans, Hugo; Georg, Dietmar; Kuess, Peter

2018-03-01

Recently, a new type of radiochromic film, the EBT-XD film, has been introduced for high dose radiotherapy. The EBT-XD film contains the same structure as the EBT3 film but has a slightly different composition and a thinner active layer. This study benchmarks the EBT-XD against EBT3 film for 6 MV and 10 MV photon beams, as well as for 97.4 MeV and 148.2 MeV proton beams and 15-100 kV x-rays. Dosimetric and film reading characteristics, such as post irradiation darkening, film orientation effect, lateral response artifact (LRA), film sensitivity, energy and beam quality dependency were investigated. Furthermore, quenching effects in the Bragg peak were investigated for a single proton beam energy for both film types, in addition measurements were performed in a spread-out Bragg peak. EBT-XD films showed the same characteristic on film darkening as EBT3. The effects between portrait and landscape orientation were reduced by 3.1% (in pixel value) for EBT-XD compared to EBT3 at a dose of 2000 cGy. The LRA is reduced for EBT-XD films for all investigated dose ranges. The sensitivity of EBT-XD films is superior to EBT3 for doses higher than 500 cGy. In addition, EBT-XD showed a similar dosimetric response for photon and proton irradiation with low energy and beam quality dependency. A quenching effect of 10% was found for both film types. The slight decrease in the thickness of the active layer and different composition configuration of EBT-XD resulted in a reduced film orientation effect and LRA, as well as a sensitivity increase in high-dose regions for both photon and proton beams. Overall, the EBT-XD film improved regarding film reading characteristics and showed advantages in the high-dose region for photon and proton beams.

Characteristic of EBT-XD and EBT3 radiochromic film dosimetry for photon and proton beams.

PubMed

Khachonkham, Suphalak; Dreindl, Ralf; Heilemann, Gerd; Lechner, Wolfgang; Fuchs, Hermann; Palmans, Hugo; Georg, Dietmar; Kuess, Peter

2018-03-15

Recently, a new type of radiochromic film, the EBT-XD film, has been introduced for high dose radiotherapy. The EBT-XD film contains the same structure as the EBT3 film but has a slightly different composition and a thinner active layer. This study benchmarks the EBT-XD against EBT3 film for 6 MV and 10 MV photon beams, as well as for 97.4 MeV and 148.2 MeV proton beams and 15-100 kV x-rays. Dosimetric and film reading characteristics, such as post irradiation darkening, film orientation effect, lateral response artifact (LRA), film sensitivity, energy and beam quality dependency were investigated. Furthermore, quenching effects in the Bragg peak were investigated for a single proton beam energy for both film types, in addition measurements were performed in a spread-out Bragg peak. EBT-XD films showed the same characteristic on film darkening as EBT3. The effects between portrait and landscape orientation were reduced by 3.1% (in pixel value) for EBT-XD compared to EBT3 at a dose of 2000 cGy. The LRA is reduced for EBT-XD films for all investigated dose ranges. The sensitivity of EBT-XD films is superior to EBT3 for doses higher than 500 cGy. In addition, EBT-XD showed a similar dosimetric response for photon and proton irradiation with low energy and beam quality dependency. A quenching effect of 10% was found for both film types. The slight decrease in the thickness of the active layer and different composition configuration of EBT-XD resulted in a reduced film orientation effect and LRA, as well as a sensitivity increase in high-dose regions for both photon and proton beams. Overall, the EBT-XD film improved regarding film reading characteristics and showed advantages in the high-dose region for photon and proton beams.

Duration of treatment for asymptomatic bacteriuria during pregnancy.

PubMed

Widmer, Mariana; Gülmezoglu, A Metin; Mignini, Luciano; Roganti, Ariel

2011-12-07

A Cochrane systematic review has shown that drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. To assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011) and reference lists of identified articles. Randomized and quasi-randomized trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. We assessed trial quality and extracted data independently. We included 13 studies, involving 1622 women. All were comparisons of single-dose treatment with four- to seven-day treatments. The trials were generally of limited quality. The 'no cure rate' for asymptomatic bacteriuria in pregnant women was slightly higher for the single-dose than for the short-course treatment; however, these results were not statistically significant and showed heterogeneity. When comparing the trials that used the same antibiotic in both treatment and control groups with the trials that used different antibiotics in both groups, the 'no cure rate' risk ratio was similar. There was no statistically significant difference in the recurrence of asymptomatic bacteriuria rate between treatment and control groups. Slight differences were detected for preterm births and pyelonephritis although, apart from one trial, the sample size of the trials was inadequate. Single-dose treatment was associated with a decrease in reports of 'any side-effects' . Single-dose regimen of antibiotics may be less effective than the seven-day regimen. Women with asymptomatic bacteriuria in pregnancy should be treated by the standard regimen of antibiotics until more data become available testing seven-day compared with three- or five-day regimens.

Trends in Childhood Influenza Vaccination Coverage—U.S., 2004–2012

PubMed Central

Lu, Peng-Jun; O'Halloran, Alissa; Meghani, Ankita; Grabowsky, Mark; Singleton, James A.

2014-01-01

Objective We compared estimates of childhood influenza vaccination coverage by health status, age, and racial/ethnic group across eight consecutive influenza seasons (2004 through 2012) based on two survey systems to assess trends in childhood influenza vaccination coverage in the U.S. Methods We used National Health Interview Survey (NHIS) and National Immunization Survey-Flu (NIS-Flu) data to estimate receipt of at least one dose of influenza vaccination among children aged 6 months to 17 years based on parental report. We computed estimates using Kaplan-Meier survival analysis methods. Results Based on the NHIS, overall influenza vaccination coverage with at least one dose of influenza vaccine among children increased from 16.2% during the 2004–2005 influenza season to 47.1% during the 2011–2012 influenza season. Children with health conditions that put them at high risk for complications from influenza had higher influenza vaccination coverage than children without these health conditions for all the seasons studied. In seven of the eight seasons studied, there were no significant differences in influenza vaccination coverage between non-Hispanic black and non-Hispanic white children. Influenza vaccination coverage estimates for children were slightly higher based on NIS-Flu data compared with NHIS data for the 2010–2011 and 2011–2012 influenza seasons (4.1 and 4.4 percentage points higher, respectively); both NIS-Flu and NHIS estimates had similar patterns of decreasing vaccination coverage with increasing age. Conclusions Although influenza vaccination coverage among children continued to increase, by the 2011–2012 influenza season, only slightly less than half of U.S. children were vaccinated against influenza. Much improvement is needed to ensure all children aged ≥6 months are vaccinated annually against influenza. PMID:25177053

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (1)--Single oral and intravenous dose toxicity studies in rats].

PubMed

Yahara, I; Furukawa, H; Sato, K; Nishimura, K; Harihara, A; Yabuuchi, K; Miyauchi, H; Kii, Y; Muraoka, Y; Kitamura, T; Kato, I

2001-05-01

A single oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) and a single intravenous dose toxicity study of its sodium salt (S-1090-Na) were conducted in rats. One dose level of 2000 mg potency/kg was set in both studies. Single oral dose toxicity study of S-1090 No deaths occurred. Diarrhea occurred on the dosing day and slightly soft feces lasted until 6 days after administration. These changes were considered to result from changes of intestinal flora induced by the antibiotic activity of S-1090. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were also observed until the next day after administration. Body weights increased favorably, and no S-1090-related pathological changes were observed. The oral lethal dose of S-1090 was estimated to be more than 2000 mg potency/kg. Single intravenous dose toxicity study of S-1090-Na No deaths occurred. The rats showed characteristic clinical signs such as hypoactivity, abnormal gait and hypopnea immediately after dosing, and some rats showed prone position or paleness of eyeballs and ear auricles in due course. These signs disappeared by 4 hr after administration. Slightly soft feces and reddish-brown feces were observed much the same as in the orally-treated rats. Body weights increased favorably. In the pathological examinations, slight cecal enlargement and increased basophilia, dilatation and calcification of the renal tubules in the kidney were observed. The intravenous lethal dose of S-1090-Na was estimated to be more than 2000 mg potency/kg.

Impact of the radiotherapy technique on the correlation between dose-volume histograms of the bladder wall defined on MRI imaging and dose-volume/surface histograms in prostate cancer patients

NASA Astrophysics Data System (ADS)

Maggio, Angelo; Carillo, Viviana; Cozzarini, Cesare; Perna, Lucia; Rancati, Tiziana; Valdagni, Riccardo; Gabriele, Pietro; Fiorino, Claudio

2013-04-01

The aim of this study was to evaluate the correlation between the ‘true’ absolute and relative dose-volume histograms (DVHs) of the bladder wall, dose-wall histogram (DWH) defined on MRI imaging and other surrogates of bladder dosimetry in prostate cancer patients, planned both with 3D-conformal and intensity-modulated radiation therapy (IMRT) techniques. For 17 prostate cancer patients, previously treated with radical intent, CT and MRI scans were acquired and matched. The contours of bladder walls were drawn by using MRI images. External bladder surfaces were then used to generate artificial bladder walls by performing automatic contractions of 5, 7 and 10 mm. For each patient a 3D conformal radiotherapy (3DCRT) and an IMRT treatment plan was generated with a prescription dose of 77.4 Gy (1.8 Gy/fr) and DVH of the whole bladder of the artificial walls (DVH-5/10) and dose-surface histograms (DSHs) were calculated and compared against the DWH in absolute and relative value, for both treatment planning techniques. A specific software (VODCA v. 4.4.0, MSS Inc.) was used for calculating the dose-volume/surface histogram. Correlation was quantified for selected dose-volume/surface parameters by the Spearman correlation coefficient. The agreement between %DWH and DVH5, DVH7 and DVH10 was found to be very good (maximum average deviations below 2%, SD < 5%): DVH5 showed the best agreement. The correlation was slightly better for absolute (R = 0.80-0.94) compared to relative (R = 0.66-0.92) histograms. The DSH was also found to be highly correlated with the DWH, although slightly higher deviations were generally found. The DVH was not a good surrogate of the DWH (R < 0.7 for most of parameters). When comparing the two treatment techniques, more pronounced differences between relative histograms were seen for IMRT with respect to 3DCRT (p < 0.0001).

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

Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles

Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Bloodmore » flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.« less

Somatic cell mutations at the glycophorin A locus in erythrocytes of atomic bomb survivors: Implications for radiation carcinogenesis

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

Kyoizumi, Seishi; Akiyama, Mitoshi; Tanabe, Kazumi

To clarify the relationship between somatic cell mutations and radiation exposure, the frequency of hemizygous mutant erythrocytes at the glycophorin A (GPA) locus was measured by flow cytometry for 1,226 heterozygous atomic bomb (A-bomb) survivors in HIroshima and Nagasaki. For statistical analysis, both GPA mutant frequency and radiation dose were log-transformed to normalize skewed distributions of these variables. The GPA mutant frequency increased slightly but significantly with age at testing and with the number of cigarettes smoked. Also, mutant frequency was significantly higher in males than in females even with adjustment for smoking and was higher to Hiroshima than inmore » Nagasaki. These characteristics of background GPA mutant frequency are qualitatively similar to those of background solid cancer incidence or mortality obtained from previous epidemiological studies of survivors. An analysis of the mutant frequency dose response using a descriptive model showed that the doubling dose is about 1.20 Sv [95% confidence interval (CI): 0.95-1.56], whereas the minimum dose for detecting a significant increase in mutant frequency is about 0.24 Sv (95% CI: 0.041-0.51). No significant effects of sex, city or age at the time of exposure on the dose response were detected. Interestingly, the doubling dose of the GPA mutant frequency was similar to that of solid cancer incidence in A-bomb survivors. This observation is in line with the hypothesis that radiation-induced somatic cell mutations are the major cause of excess cancer risk after radiation. 49 refs., 6 figs., 2 tabs.« less

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN TUNGSTEN

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

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.

2015-04-16

We used our recently developed lattice-based object kinetic Monte Carlo code; KSOME [1] to carryout simulations of radiation damage in bulk tungsten at temperatures of 300, and 2050 K for various dose rates. Displacement cascades generated from molecular dynamics (MD) simulations for PKA energies at 60, 75 and 100 keV provided residual point defect distributions. It was found that the number density of vacancies in the simulation box does not change with dose rate while the number density of vacancy clusters slightly decreases with dose rate indicating that bigger clusters are formed at larger dose rates. At 300 K, althoughmore » the average vacancy cluster size increases slightly, the vast majority of vacancies exist as mono-vacancies. At 2050 K no accumulation of defects was observed during irradiation over a wide range of dose rates for all PKA energies studied in this work.« less

Effect of iron salt type and dosing mode on Fenton-based pretreatment of rice straw for enzymatic hydrolysis.

PubMed

Gan, Yu-Yan; Zhou, Si-Li; Dai, Xiao; Wu, Han; Xiong, Zi-Yao; Qin, Yuan-Hang; Ma, Jiayu; Yang, Li; Wu, Zai-Kun; Wang, Tie-Lin; Wang, Wei-Guo; Wang, Cun-Wen

2018-06-15

Fenton-based processes with four different iron salts in two different dosing modes were used to pretreat rice straw (RS) samples to increase their enzymatic digestibility. The composition analysis shows that the RS sample pretreated by the dosing mode of iron salt adding into H 2 O 2 has a much lower hemicellulose content than that pretreated by the dosing mode of H 2 O 2 adding into iron salt, and the RS sample pretreated by the chloride salt-based Fenton process has a much lower lignin content and a slightly lower hemicellulose content than that pretreated by the sulphate salt-based Fenton process. The higher concentration of reducing sugar observed on the RS sample with lower lignin and hemicellulose contents justifies that the Fenton-based process could enhance the enzymic hydrolysis of RS by removing hemicellulose and lignin and increasing its accessibility to cellulase. FeCl 3 ·6H 2 O adding into H 2 O 2 is the most efficient Fenton-based process for RS pretreatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Embryotoxicity of benzalkonium chloride in vaginally treated rats.

PubMed

Buttar, H S

1985-12-01

The effects of the spermicide benzalkonium chloride (BKC) were studied on the conceptus of rat. Single doses (0, 25, 50, 100 or 200 mg kg-1) of aqueous solutions of BKC were administered intravaginally (1 ml kg-1) on gestational day 1. The vulval metallic clips, used to prevent leakage of the solution, were removed 24 h post-treatment. Fetuses were obtained and examined for malformations on day 21 of gestation. slight to copious amounts of vaginal discharge and vaginitis were noticed in rats treated with the two largest doses of BKC. A dose-related increase in resorptions and fetal death, reduction in litter size and weight were observed in BKC-treated dams. The conceptus loss seemed to occur both before and after implantation. BKC did not cause any discernible visceral malformations, although minor sternal defects occurred in fetuses exposed to 100 and 200 mg kg-1 of the spermicide. These results suggest that single vaginal application of BKC is embryo- and fetocidal in the rat at a dose about 143 times higher than that recommended for controlling conception in women.

[Final size attained in type 1 diabetes children].

PubMed

Galera Martínez, R; García García, E; Gámez Gómez, M D; Gómez Llorente, J L; Garrido Fernández, P; Bonillo Perales, A

2009-03-01

To describe the final height and height-gain in relation to target height, in children with type 1 diabetes mellitus, and analyse their relationship to different variables. Retrospective analysis of the growth data of 52 children (27 girls) diagnosed with type 1 diabetes mellitus before 14 years old, and followed up until their final height was attained. final height, target height, illness duration, glycated haemoglobin (HbA1c), insulin dose, BMI, and other autoimmune diseases. The height SDS (standard deviation scale) at diagnosis was slightly higher (0.734 in boys and 0.563 in girls). During the development of the disease, a growth reduction was seen, which was significantly higher in boys of prepubertal age (p = 0.016). The mean final height attained was 173.14 +/- 5.28 cm in boys and 161.9 +/- 6.97 cm in girls. Height gain was 1.56 +/- 3.66 in boys (SDS = -0.034) and 2.26 +/- 6.13 in girls (SDS = 0.385). The only variable significantly related to height gain was mean glycated-haemoglobin (growth reduction of 2 cm for every increment of 1% in mean glycated-haemoglobin). At onset, diabetic children were slightly taller than the general population. A growth reduction was shown as the disease developed, significantly higher in boys of prepubertal age. The final height in boys was slightly lower than the mean, but in girls was similar to the general population. Both sexes attained their target height, although the height gain was less in boys. Poorer metabolic control was associated with reduced height gain.

Epidemiologic study of Kawasaki disease at a single hospital in Daejeon, Korea (1987 through 2000).

PubMed

Lee, Kyung-Yil; Han, Ji-Whan; Lee, Hyung-Shin; Hong, Ja-Hyun; Hahn, Seung-Hoon; Lee, Joon-Sung; Whang, Kyung-Tai

2004-01-01

We evaluated the epidemiology and a range of clinical characteristics in children with Kawasaki disease (KD) in one area of South Korea. We retrospectively analyzed 506 medical records of children with KD, who were admitted at Daejeon St. Mary's Hospital from January 1987 through December 2000. The mean annual frequency was 36.1 +/- 11.1 cases per year. There were 55 cases (10.9%) in 1993, 50 cases (9.9%) in 1994 and 47 cases (9.3%) in 2000. There was a slightly higher occurrence in summer with no significant difference in seasonal frequency. Age distribution ranged from 2 months to 13 years of age (mean, 2.4 +/- 1.7 years) and 485 children (95.8%) were <5 years of age. The male-to-female ratio was 1.7:1. Of the total cases 0.6% was recurrent, whereas 0.4% occurred between siblings. There were no fatalities. For treatment aspirin alone (65 cases, 12.8%), divided dose intravenous immunoglobulin (IVIG) (400 to 500 mg/day for 4 to 5 days, 231 cases, 45.7%) and one dose IVIG (2.0 g/kg, 210 cases, 41.5%) were used. Between 1996 and 2000, 143 cases were treated with only one dose IVIG, and 21 cases (14.7%) showed coronary artery lesions (CAL). Among the 143 cases 22 cases (15.4%) were retreated with IVIG and/or steroid pulse therapy. The incidence of CAL in this group was 50.0%. In Daejeon, Korea, KD showed slight annual variations without seasonal differences. The rate of CAL in acute stage with one dose IVIG therapy (2 g/kg) was 8.3% in the IVIG responders.

Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

PubMed

Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

2015-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Uncertainty propagation for SPECT/CT-based renal dosimetry in 177Lu peptide receptor radionuclide therapy

NASA Astrophysics Data System (ADS)

Gustafsson, Johan; Brolin, Gustav; Cox, Maurice; Ljungberg, Michael; Johansson, Lena; Sjögreen Gleisner, Katarina

2015-11-01

A computer model of a patient-specific clinical 177Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of 177Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity.

High Atomic Number Contrast Media Offer Potential for Radiation Dose Reduction in Contrast-Enhanced Computed Tomography.

PubMed

Roessler, Ann-Christin; Hupfer, Martin; Kolditz, Daniel; Jost, Gregor; Pietsch, Hubertus; Kalender, Willi A

2016-04-01

Spectral optimization of x-ray computed tomography (CT) has led to substantial radiation dose reduction in contrast-enhanced CT studies using standard iodinated contrast media. The purpose of this study was to analyze the potential for further dose reduction using high-atomic-number elements such as hafnium and tungsten. As in previous studies, spectra were determined for which the patient dose necessary to provide a given contrast-to-noise ratio (CNR) is minimized. We used 2 different quasi-anthropomorphic phantoms representing the liver cross-section of a normal adult and an obese adult patient with the lateral widths of 360 and 460 mm and anterior-posterior heights of 200 and 300 mm, respectively. We simulated and measured on 2 different scanners with x-ray spectra from 80 to 140 kV and from 70 to 150 kV, respectively. We determined the contrast for iodine-, hafnium-, and tungsten-based contrast media, the noise, and 3-dimensional dose distributions at all available tube voltages by measurements and by simulations. The dose-weighted CNR was determined as optimization parameter. Simulations and measurements were in good agreement regarding their dependence on energy for all parameters investigated. Hafnium provided the best performance for normal and for obese patient phantoms, indicating a dose reduction potential of 30% for normal and 50% for obese patients at 120 kV compared with iodine; this advantage increased further with higher kV values. Dose-weighted CNR values for tungsten were always slightly below the hafnium results. Iodine proved to be the superior choice at voltage values of 80 kV and below. Hafnium and tungsten both seem to be candidates for contrast-medium-enhanced CT of normal and obese adult patients with strongly reduced radiation dose at unimpaired image quality. Computed tomography examinations of obese patients will decrease in dose for higher kV values.

Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate.

PubMed

da Silva, Gisela Bevilacqua Rolfsen Ferreira; Scarpa, Maria Virginia; Carlos, Iracilda Zepone; Quilles, Marcela Bassi; Lia, Raphael Carlos Comeli; do Egito, Eryvaldo Socrates Tabosa; de Oliveira, Anselmo Gomes

2015-01-01

Methyl dihydrojasmonate (MJ) has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME) has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S) ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to be nontoxic at doses higher than 350 mg/kg, which was higher than the dose that provides tumor-inhibition effect in this study. Because the MJ-loaded ME was shown to have anticancer activity comparable to doxorubicin, the ME described here may be considered a suitable vehicle for parenteral administration of MJ.

A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use.

PubMed

Schoedel, Kerri Alexandra; Chen, Nancy; Hilliard, Annie; White, Linda; Stott, Colin; Russo, Ethan; Wright, Stephen; Guy, Geoffrey; Romach, Myroslava K; Sellers, Edward M

2011-04-01

This study aimed to evaluate the abuse potential and cognitive effects of nabiximols (Sativex, GW Pharma Ltd. Salisbury, UK), an oromucosal spray primarily containing delta‐9‐tetrahydrocannabinol (THC) and cannabidiol (CBD). This was a single‐dose, randomized, double‐blind, crossover study comparing nabiximols (4, 8, and 16 consecutive sprays: 10.8, 21.6, and 43.2 mg THC, respectively) with dronabinol 20 and 40 mg (synthetic THC: Marinol, Solvay Pharmaceuticals, Brussels, Belgium) and matching placebos in 23 recreational cannabis users. Subjective and cognitive/psychomotor measures were administered over 24 h post‐dose. Dronabinol was significantly different from placebo on abuse potential measures, thereby confirming study validity. Nabiximols 10.8 mg was not significantly different from placebo on primary measures but was different on some secondary measures. Nabiximols 21.6 mg was significantly greater than placebo on some primary/secondary measures, whereas nabiximols 43.2 mg showed significant effects on most measures. Nabiximols 10.8 mg was significantly lower than dronabinol doses on most measures ( p < 0.05). Dronabinol 20 mg effects were numerically higher than nabiximols 21.6 mg but were statistically significant only for some measures. Dronabinol 40 mg and nabiximols 43.2 mg were generally not statistically different. Both dronabinol and nabiximols had significant abuse potential compared with placebo at higher doses. Nabiximols showed similar or slightly less abuse potential compared with dronabinol. Therefore, the abuse potential of nabiximols should be no higher than that of dronabinol.

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.

Naturally occurring radioactive materials (NORM) in ashes from a fuel-oil power plant in Cienfuegos, Cuba, and the associated radiation hazards.

PubMed

Alonso-Hernández, C M; Bernal-Castillo, J; Morera-Gómez, Y; Guillen-Arruebarrena, A; Cartas-Aguila, H A; Acosta-Milián, R

2014-03-01

The radioactivity of NORM was measured in ashes collected from a fuel-oil power plant in Cienfuegos, Cuba, using an HPGe gamma-ray spectrometer. The (226)Ra, (210)Pb, (40)K, (232)Th and (238)U activity concentrations reached 240, 77, 59, 70 and 15 Bq kg(-1), respectively. The potential radiological hazard of these residuals was assessed. The radium equivalent activities of the samples varied from 54 to 345 Bq kg(-1). The gamma index was calculated to be lower than that of the reference values, and the gamma absorbed dose rate was higher than the average reported for the earth's crust; however, the assessed annual effective dose was slightly lower than the annual effective dose limit for public, i.e. 1 mSv. Therefore, these bottom ashes were not dramatically enriched with radionuclides and may be used as an additive for building materials without restrictions from a radiological protection point of view.

Synthesis and thermoluminescence characterizations of Sr2B5O9Cl:Dy3+ phosphor for TL dosimetry.

PubMed

Oza, Abha H; Dhoble, N S; Park, K; Dhoble, S J

2015-09-01

The photoluminescence (PL) and thermoluminescence (TL) displayed by Dy-activated strontium haloborate (Sr2 B5 O9 Cl) were studied. A modified solid-state reaction was employed for the preparation of the phosphor. Photoluminescence spectra showed blue (484 nm) and yellow (575 nm) emissions due to incorporation of Dy(3+) into host matrix. The Dy-doped (0.5 mol%) Sr2 B5 O9 Cl was studied after exposure to γ-irradiation and revealed a prominent glow curve at 261°C with a small hump around 143°C indicating that two types of traps were generated. The glow peak at the higher temperature side (261°C) was more stable than the lower temperature glow peak. The TL intensity was 1.17 times less than that of the standard CaSO4 :Dy thermoluminescence dosimetry (TLD) phosphor, the phosphor showed a linear dose-response curve for different γ-ray irradiation doses (0.002-1.25 Gy) and fading of 5-7% was observed for higher temperature peaks upon storage. Trapping parameters and their estimated error values have been calculated by Chen's peak shape method and by the initial rise method. Values of activation energies estimated by both these techniques were comparable. The slight difference in activation energy values calculated by Chen's peak shape method indicated the formation of two kinds of traps Furthermore, slight differences in frequency values are due to various escaping and retrapping probabilities. Copyright © 2014 John Wiley & Sons, Ltd.

Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

PubMed

Chen, Xin; Feng, Shu-xian; Guo, Ping-ping; He, Yu-xia; Liu, Yu-dong; Ye, De-sheng; Chen, Shi-ling

2016-04-01

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Basic imaging properties of an indirect flat-panel detector system employing irradiation side sampling (ISS) technology for chest radiography: comparison with a computed radiographic system.

PubMed

Tanaka, Nobukazu; Yano, Yuki; Yabuuchi, Hidetake; Akasaka, Tsutomu; Sasaki, Masayuki; Ohki, Masafumi; Morishita, Junji

2013-01-01

The image quality and potential usefulness for patient skin-dose reduction of a newly developed flat-panel detector (FPD) system employing irradiation side sampling (ISS) were investigated and compared to a conventional computed radiography (CR) system. We used the X-ray beam quality of RQA 9 as noted in the standard evaluation method by the International Electrotechnical Commission 62220-1 to evaluate the image quality of the detector for chest radiography. The presampled modulation transfer function (MTF) of the ISS-FPD system was slightly higher than that of the CR system in the horizontal direction at more than 2.2 cycles/mm. However, the presampled MTF of the ISS-FPD system was slightly lower than that of the CR system in the vertical direction. The Wiener spectrum of the ISS-FPD system showed a 50-65 % lesser noise level than that of the CR system under the same exposure condition. The detective quantum efficiency of the ISS-FPD system was at least twice as great as that of the CR system. We conclude that the ISS-FPD system has the potential to reduce the patient skin dose compared to a conventional CR system for chest radiography.

[Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats].

PubMed

Mazurek-Mochol, Małgorzata

2002-01-01

Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine levels which could be responsible for toxicological symptoms.

Impact of Vitamin D Supplementation on Gross Motor Development of Healthy Term Infants: A Randomized Dose-Response Trial.

PubMed

Wicklow, Brandy; Gallo, Sina; Majnemer, Annette; Vanstone, Catherine; Comeau, Kathryn; Jones, Glenville; L'Abbe, Mary; Khamessan, Ali; Sharma, Atul; Weiler, Hope; Rodd, Celia

2016-08-01

In addition to benefits for bone health, vitamin D is implicated in muscle function in children and adults. To determine if vitamin D dosage positively correlated with gross motor development at 3 and 6 months of age. We hypothesized that higher doses would be associated with higher scores for gross motor skills. A consecutive sample of 55 healthy, term, and breastfed infants from Montreal, Canada were recruited from a randomized trial of vitamin D supplementation between 2009 and 2012. Infants were randomized to 400 International Units (IU) (n = 19), 800 IU (n = 18) or 1,200 IU (n = 18) vitamin D3/day. Motor performance at 3 and 6 months was quantified by the Alberta Infant Motor Scale (AIMS). Plasma vitamin D3 metabolites were measured by tandem mass spectrometry. AIMS scores did not differ at 3 months. However, total AIMS scores and sitting subscores were significantly higher at 6 months in infants receiving 400 IU/day compared to 800 IU/day and 1,200 IU/day groups (p < .05). There were weak negative correlations with length and C-3 epimer of 25(OH)D. In contrast to our hypothesis, gross motor achievements were significantly higher in infants receiving 400 IU/day vitamin D. Our findings also support longer infants being slightly delayed.

Development of a database of organ doses for paediatric and young adult CT scans in the United Kingdom

PubMed Central

Kim, K. P.; Berrington de González, A.; Pearce, M. S.; Salotti, J. A.; Parker, L.; McHugh, K.; Craft, A. W.; Lee, C.

2012-01-01

Despite great potential benefits, there are concerns about the possible harm from medical imaging including the risk of radiation-related cancer. There are particular concerns about computed tomography (CT) scans in children because both radiation dose and sensitivity to radiation for children are typically higher than for adults undergoing equivalent procedures. As direct empirical data on the cancer risks from CT scans are lacking, the authors are conducting a retrospective cohort study of over 240 000 children in the UK who underwent CT scans. The main objective of the study is to quantify the magnitude of the cancer risk in relation to the radiation dose from CT scans. In this paper, the methods used to estimate typical organ-specific doses delivered by CT scans to children are described. An organ dose database from Monte Carlo radiation transport-based computer simulations using a series of computational human phantoms from newborn to adults for both male and female was established. Organ doses vary with patient size and sex, examination types and CT technical settings. Therefore, information on patient age, sex and examination type from electronic radiology information systems and technical settings obtained from two national surveys in the UK were used to estimate radiation dose. Absorbed doses to the brain, thyroid, breast and red bone marrow were calculated for reference male and female individuals with the ages of newborns, 1, 5, 10, 15 and 20 y for a total of 17 different scan types in the pre- and post-2001 time periods. In general, estimated organ doses were slightly higher for females than males which might be attributed to the smaller body size of the females. The younger children received higher doses in pre-2001 period when adult CT settings were typically used for children. Paediatric-specific adjustments were assumed to be used more frequently after 2001, since then radiation doses to children have often been smaller than those to adults. The database here is the first detailed organ-specific paediatric CT scan database for the UK. As well as forming the basis for the UK study, the results and description of the methods will also serve as a key resource for paediatric CT scan studies currently underway in other countries. PMID:22228685

Development of a database of organ doses for paediatric and young adult CT scans in the United Kingdom.

PubMed

Kim, K P; Berrington de González, A; Pearce, M S; Salotti, J A; Parker, L; McHugh, K; Craft, A W; Lee, C

2012-07-01

Despite great potential benefits, there are concerns about the possible harm from medical imaging including the risk of radiation-related cancer. There are particular concerns about computed tomography (CT) scans in children because both radiation dose and sensitivity to radiation for children are typically higher than for adults undergoing equivalent procedures. As direct empirical data on the cancer risks from CT scans are lacking, the authors are conducting a retrospective cohort study of over 240,000 children in the UK who underwent CT scans. The main objective of the study is to quantify the magnitude of the cancer risk in relation to the radiation dose from CT scans. In this paper, the methods used to estimate typical organ-specific doses delivered by CT scans to children are described. An organ dose database from Monte Carlo radiation transport-based computer simulations using a series of computational human phantoms from newborn to adults for both male and female was established. Organ doses vary with patient size and sex, examination types and CT technical settings. Therefore, information on patient age, sex and examination type from electronic radiology information systems and technical settings obtained from two national surveys in the UK were used to estimate radiation dose. Absorbed doses to the brain, thyroid, breast and red bone marrow were calculated for reference male and female individuals with the ages of newborns, 1, 5, 10, 15 and 20 y for a total of 17 different scan types in the pre- and post-2001 time periods. In general, estimated organ doses were slightly higher for females than males which might be attributed to the smaller body size of the females. The younger children received higher doses in pre-2001 period when adult CT settings were typically used for children. Paediatric-specific adjustments were assumed to be used more frequently after 2001, since then radiation doses to children have often been smaller than those to adults. The database here is the first detailed organ-specific paediatric CT scan database for the UK. As well as forming the basis for the UK study, the results and description of the methods will also serve as a key resource for paediatric CT scan studies currently underway in other countries.

[Experimental study on the impact of photodynamic therapy on the normal vocal cord injury].

PubMed

Liu, Haiyan; Huang, Yongwang; Wang, Shanshan; Li, Yingxin; Yin, Huijuan; Gao, Xiaowei

2015-12-01

To investigate the reactive characteristics of normal vocal cord tissues to photodynamic therapy (PDT) and the damage effects of different concentration of photosensitizer and different light on normal rabbit vocal cord. Making the preliminary research of PDT in clinical treatment of chronic inflammation of the vocal cords and precancerous lesions. Twenty-five healthy Japanese big ear experimental rabbits were randomly divided into 5 groups: low work rate low dose group A (100 mW, 10%5-ALA), high work rate low dose group B (200 mW, 10%5-ALA), high work rate high dose group C (200 mW, 20%5-ALA), low work rate high dose group D (100 mW, 20%5-ALA) and normal control group E. The issue damage and wound recovery were observed in 1 d, 3 d, 7 d, 14 d, 28 d after intervention. A severe inflammation reaction was observed in group A, B, C, D after intervened with PDT compared to normal group. The reaction of group A was lighter, and the reaction of group C was the most serious. The content of collagenous fiber, hyaluronic acid and fibronectin in vocal fold lamina layer was significantly higher than that in normal group (P<0.05). Different degrees of fiber proliferation were observed in all groups. The content of each component of vocal fold lamina layer tended to be normal slightly higher level in 28 d. Observation by electron microscope showed that there were no significant differences in A, B, C, D, E in 28 d after intervention. Recoverable damage repair process can be detected in rabbit vocal after intervened with PDT, which began in 7 d and basically completed in 28 d. In a certain concentration (10%-20%) and dose range (100-200 mW). The higher of photodynamic dose, the more serious of the damage. And the damage was basically reversible.

Treatment of tinea capitis - griseofulvin versus fluconazole - a comparative study.

PubMed

Shemer, Avner; Plotnik, Ira Bernstein; Davidovici, Batya; Grunwald, Marcelo H; Magun, Ronen; Amichai, Boaz

2013-08-01

To compare the efficacy and safety of fluconazole and griseofulvin in the treatment of tinea capitis. Patients with tinea capitis (n = 113) with positive fungal cultures entered the study. The patients were divided into four groups with different treatment regimes. Two groups received griseofulvin 15 or 25 mg/kg/day and two groups received fluconazole 4 or 6 mg/kg/day, all for up to 12 weeks. Griseofulvin was found to be slightly better than fluconazole. The lower doses for both griseofulvin and fluconazole required significantly longer treatment duration until mycological cure than the higher doses, independent of the fungus type. Since no significant difference was found between the drugs, it is suggested that the choice should be based on tolerability, availability and cost of the drugs. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

Initial clinical results with a new needle screen storage phosphor system in chest radiograms.

PubMed

Körner, M; Wirth, S; Treitl, M; Reiser, M; Pfeifer, K-J

2005-11-01

To evaluate image quality and anatomical detail depiction in dose-reduced digital plain chest radiograms using a new needle screen storage phosphor (NIP) in comparison to full dose conventional powder screen storage phosphor (PIP) images. 24 supine chest radiograms were obtained with PIP at standard dose and compared to follow-up studies of the same patients obtained with NIP with dose reduced to 50 % of the PIP dose (all imaging systems: AGFA-Gevaert, Mortsel, Belgium). In both systems identical versions of post-processing software supplied by the manufacturer were used with matched parameters. Six independent readers blinded to both modality and dose evaluated the images for depiction and differentiation of defined anatomical regions (peripheral lung parenchyma, central lung parenchyma, hilum, heart, diaphragm, upper mediastinum, and bone). All NIP images were compared to the corresponding PIP images using a five-point scale (- 2, clearly inferior to + 2, clearly superior). Overall image quality was rated for each PIP and NIP image separately (1, not usable to 5, excellent). PIP and dose reduced NIP images were rated equivalent. Mean image noise impression was only slightly higher on NIP images. Mean image quality for NIP showed no significant differences (p > 0.05, Mann-Whitney U test). With the use of the new needle structured storage phosphors in chest radiography, dose reduction of up to 50 % is possible without detracting from image quality or detail depiction. Especially in patients with multiple follow-up studies the overall dose can be decreased significantly.

EFFECTS OF LOW-DOSE IRRADIATION AND STORAGE ON ACCEPTABILITY OF BROCCOLI, SWEET CORN, AND STRAWBERRIES

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

Martin, D.C.; Tichenor, D.A.

1962-11-01

Fresh vegetables, in some cases stored in nitrogen, were gamma irradiated with doses of 0.25 to 1.0 Mrad, then stored at 35 deg F, and evaluated for taste at various periods up to 305 days. All nitrogen-packed irradiated sweet corn was acceptable after 305 days, in contrast with unirradiated 35 deg F control samples, which were spoiled. One set of nitrogenpacked irradiated broccoli samples was acceptable after 270 days at 35 deg F; all others were unacceptable after this period. All of the irradiated strawberries were less acceptable than 35 deg F controls at all time periods. Correlation of objectivemore » color measurements with visual color scores varied with the product, but dominant wavelength, purity, or brightness was significantly related to color score for all products tested. Irradiation of strawberries resulted in bleaching of the characteristic red color, the amount of bleaching being greater at the higher dose levels. Samples irradiated at the higher levels had the lowest average dominant wavelength, closer to the orange area of the spectrum, and the lowest average purity. The pH of all strawberry syrup samples was between 3.1 and 3.5, and varied only slightly with blanching, radiation treatment, or time period. (H.H.D.)« less

Evaluation of a poliomyelitis immunization campaign in Madras city.

PubMed

Balraj, V; John, T J

1986-01-01

An annual pulse immunization campaign with oral polio vaccine (OPV) was evaluated to determine vaccine coverage, relative success of publicity methods and reasons for lack of response. The campaign was directed at 3-36 month olds in Madras city, India, in January-March 1985. The evaluation method was the "30-cluster" sample survey technique, designed by WHO, where surveys were done in 30 districts of the city on 10 children in each age group. The survey was conducted in April 1985 by 5 trained and supervised interviewers. This campaign increased the vaccine coverage to 94%, 88% and 72% for first, second and third doses of OPV. Coverage was higher in older children. Percent coverage decreased slightly over 1-3 doses, and from there rapidly up to 6-7 doses. The campaign accounted for 27% of all the OPV the study children had received. 47% of parents heard about the vaccination through word of mouth, either from health workers, volunteers or "balwadi ayahs," women day-care workers. 17% learned through television or radio. 3% cited mobile loudspeakers, handbills, posters or slides in cinemas. Many parents did not avail themselves of the vaccine because they believed that 3 doses are sufficient. Actually the WHO recommends 4 doses; the Indian Academy of Pediatrics recommends 5 doses; while criteria from research on Indian children would suggest that 5-7 doses are required to raise strong immunity.

Dose-Response Modelling of Paralytic Shellfish Poisoning (PSP) in Humans

PubMed Central

Arnich, Nathalie; Thébault, Anne

2018-01-01

Paralytic shellfish poisoning (PSP) is caused by a group of marine toxins with saxitoxin (STX) as the reference compound. Symptoms in humans after consumption of contaminated shellfish vary from slight neurological and gastrointestinal effects to fatal respiratory paralysis. A systematic review was conducted to identify reported cases of human poisoning associated with the ingestion of shellfish contaminated with paralytic shellfish toxins (PSTs). Raw data were collected from 143 exposed individuals (113 with symptoms, 30 without symptoms) from 13 studies. Exposure estimates were based on mouse bioassays except in one study. A significant relationship between exposure to PSTs and severity of symptoms was established by ordinal modelling. The critical minimal dose with a probability higher than 10% of showing symptoms is 0.37 µg STX eq./kg b.w. This means that 10% of the individuals exposed to this dose would have symptoms (without considering the severity of the symptoms). This dose is four-fold lower than the lowest-observed-adverse-effect-level (LOAEL) established by the European Food Safety Authority (EFSA, 2009) in the region of 1.5 μg STX eq./kg b.w. This work provides critical doses that could be used as point of departure to update the acute reference dose for STX. This is the first time a dose-symptoms model could be built for marine toxins using epidemiological data. PMID:29597338

210-Polonium studies in some environmental and biological matrices of Domiasiat uranium deposit area, West Khasi Hills, Meghalaya, India.

PubMed

Marbaniang, Deswyn G; Poddar, Raj K; Nongkynrih, Phlis; Khathing, Darlando T

2010-03-01

The study was performed using a silicon surface barrier alpha spectrometer at Bhabha Atomic Research Centre, Mumbai, India. Through the study, the observed (210)Po activity in water sample from different locations in the Domiasiat area ranges from 0.04 to 0.69 Bq/l. The daily and annual intake of (210)Po through water was also estimated and the mean value of 0.72 and 263.61 Bq, respectively, were observed. It is observed that the effective doses through water were higher than the World Health Organization recommended dose of 0.05 mSv/year. The total annual effective doses through terrestrial ingestion for all the locations was studied and the mean annual effective dose was observed to be 0.315 mSv, which, when compared to the worldwide and the Indian values, was observed to be slightly higher. The mean activity in soil is found to be 124.8 +/-5.7 Bq/kg and in meat the activity is 0.43 +/-0.05 Bq/kg. In fishes, an activity of 0.48 +/-0.07 Bq/kg in Garra lamta, 0.29 +/-0.02 Bq/kg in Neolissocheilus hexaganolepis, and 3.3 +/-0.1 Bq/kg in Macrobrachium sp. is observed. Activity concentration in plant samples was analyzed and the activity ranges from 0.020 +/-0.002 to 9.69 +/-0.35 Bq/kg. Committed effective dose by the adult population of the Domiasiat area through intake of (210)Po through these food items was also determined and compared with the Indian average value and the worldwide average value.

Initial Characterization of a Gel Patch Dosimeter for In Vivo Dosimetry

PubMed Central

Matrosic, C; Culberson, W; Rosen, B; Madsen, E; Frank, G; Bednarz, B

2016-01-01

In vivo dosimetry is a greatly underutilized tool for patient safety in clinical external beam radiotherapy treatments, despite being recommended by several national and international organizations (AAPM, ICRU, IAEA, NACP). The reasons for this underutilization mostly relate to the feasibility and cost of in vivo dosimetry methods. Due to the increase in the number of beam angles and dose per fraction in modern treatments, there is a compelling need for a novel dosimeter that is robust and affordable while able to operate properly in these complex conditions. This work presents a gel patch dosimeter as a novel method of in vivo dosimetry. DEFGEL, a 6%T normoxic polyacrylamide gel, was injected into 1-cm thick acrylic molds to create 1-cm thick small cylindrical patch dosimeters. To evaluate the change in optical density due to radiation induced polymerization, dosimeters were scanned before and after irradiation using an in-house developed laser densitometer. The dose-responses of three separate batches of gel were evaluated and compared to check for linearity and repeatability. The response development time was evaluated to ensure that the patch dosimeter could be high throughput. Additionally, the potential of this system to be used as an in vivo dosimeter was tested with a clinically relevant end-to-end in vivo phantom test. All irradiations were performed with a Varian Clinac 21EX at the University of Wisconsin Medical Radiation Research Center (UWMRRC). The dose response of all three batches of gel was found to be linear within the range of 2–20 Gy. At doses below 0.5 Gy the statistical uncertainties were prohibitively large to make quantitative assessments of the results. The three batches demonstrated good repeatability in the range of 2 Gy to up to 10 Gy, with only slight variations in response at higher doses. For low doses the dosimeter fully developed within an hour while at higher doses they fully developed within four hours. During the in vivo phantom test the predicted patch absorbed dose was 4.23 Gy while the readout dose was evaluated to be 4.37 Gy, which corresponds to a 3.2% discrepancy. The dosimeter and densitometer pairing shows promise as an in vivo dosimetry system, especially for hypofractionated or MRI-guided radiotherapy treatments where higher doses are prescribed. PMID:27088207

Initial characterization of a gel patch dosimeter for in vivo dosimetry

NASA Astrophysics Data System (ADS)

Matrosic, C.; Culberson, W.; Rosen, B.; Madsen, E.; Frank, G.; Bednarz, B.

2016-05-01

In vivo dosimetry is a greatly underutilized tool for patient safety in clinical external beam radiotherapy treatments, despite being recommended by several national and international organizations (AAPM, ICRU, IAEA, NACP). The reasons for this underutilization mostly relate to the feasibility and cost of in vivo dosimetry methods. Due to the increase in the number of beam angles and dose per fraction in modern treatments, there is a compelling need for a novel dosimeter that is robust and affordable while able to operate properly in these complex conditions. This work presents a gel patch dosimeter as a novel method of in vivo dosimetry. DEFGEL, a 6% T normoxic polyacrylamide gel, was injected into 1 cm thick acrylic molds to create 1 cm thick small cylindrical patch dosimeters. To evaluate the change in optical density due to radiation induced polymerization, dosimeters were scanned before and after irradiation using an in-house developed laser densitometer. The dose-responses of three separate batches of gel were evaluated and compared to check for linearity and repeatability. The response development time was evaluated to ensure that the patch dosimeter could be high throughput. Additionally, the potential of this system to be used as an in vivo dosimeter was tested with a clinically relevant end-to-end in vivo phantom test. All irradiations were performed with a Varian Clinac 21EX at the University of Wisconsin Medical Radiation Research Center (UWMRRC). The dose-response of all three batches of gel was found to be linear within the range of 2-20 Gy. At doses below 0.5 Gy the statistical uncertainties were prohibitively large to make quantitative assessments of the results. The three batches demonstrated good repeatability in the range of 2 Gy to up to 10 Gy, with only slight variations in response at higher doses. For low doses the dosimeter fully developed within an hour while at higher doses they fully developed within four hours. During the in vivo phantom test the predicted patch absorbed dose was 4.23 Gy while the readout dose was evaluated to be 4.37 Gy, which corresponds to a 3.2% discrepancy. The dosimeter and densitometer pairing shows promise as an in vivo dosimetry system, especially for hypofractionated or MRI-guided radiotherapy treatments where higher doses are prescribed.

Subacute intramuscular toxicity of the acetylcholinesterase reactivating agent Hi-6 in rats and dogs. (Reannouncement with new availability information)

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

Levine, B.S.; Tomlinson, M.J.

1993-12-31

Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture,and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters weremore » unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.« less

Ozonation of Common Textile Auxiliaries

NASA Astrophysics Data System (ADS)

Iskender, Gulen; Arslan-Alaton, Idil; Koyunluoglu, Sebnem; Yilmaz, Zeynep; Germirli Babuna, Fatos

2016-10-01

The treatability of four different commonly applied textile auxiliary chemicals, namely two tannin formulations (Tannin 1: a condensation product of aryl sulphonate; Tannin 2: natural tannic acid) and two biocidal finishing agents (Biocide 1: 2,4,4’-trichloro-2’- hydroxydiphenyl ether; Biocide 2: a nonionic diphenyl alkane derivative) with ozone was investigated. Increasing the ozone dose yielded higher COD removals for the natural tannin. Optimum ozone doses of 485 and 662 mg/h were obtained at a pH of 3.5 for natural and synthetic tannin carrying textile bath discharges, respectively. When the reaction pH was increased from 3.5 to 7.0, a slight decrease in COD removal was observed for the natural tannin due to ozone selectivity towards its polyaromatic structure. The same increase in ozonation pH enhanced COD removals for the synthetic tannin as a result of enhanced ozone decomposition rendering free radical chain reactions dominant. Optimum ozone doses of 499 and 563 mg/h were established for Biocide 1 and 2, respectively. With the increase of ozonation, pH exhibited a positive influence on COD removals for both textile tannins. A substantial improvement in terms of TOC removals was observed as the reaction pH was increased from 3.5 to 7.0 for the synthetic tannin, and from 7 to 12 for both textile biocides. Higher AOX removals were evident at pH 7 than at pH 12 for Biocide 1 as a result of the higher selectivity of the dehalogenation reaction at neutral pH.

Thyroid Adenomas After Solid Cancer in Childhood

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

Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine

Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose receivedmore » at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.« less

Comparative analysis of cell killing and autosomal mutation in mouse kidney epithelium exposed to 1 GeV protons in vitro or in vivo.

PubMed

Kronenberg, Amy; Gauny, Stacey; Kwoh, Ely; Grossi, Gianfranco; Dan, Cristian; Grygoryev, Dmytro; Lasarev, Michael; Turker, Mitchell S

2013-05-01

Human exposure to high-energy protons occurs in space flight scenarios or, where necessary, during radiotherapy for cancer or benign conditions. However, few studies have assessed the mutagenic effectiveness of high-energy protons, which may contribute to cancer risk. Mutations cause cancer and most cancer-associated mutations occur at autosomal loci. This study addresses the cytotoxic and mutagenic effects of 1 GeV protons in mouse kidney epithelium. Mutant fractions were measured for an endogenous autosomal locus (Aprt) that detects all types of mutagenic events. Results for kidneys irradiated in vivo are compared with the results for kidney cells from the same strain exposed in vitro. The results demonstrate dose-dependent cell killing in vitro and for cells explanted 3-4 months postirradiation in vivo. Incubation in vivo for longer periods (8-9 months) further attenuates proton-induced cell killing. Protons are mutagenic to cells in vitro and for in vivo irradiated kidneys. The dose-response for Aprt mutation is curvilinear after in vitro or in vivo exposure, bending upward at the higher doses. While the absolute mutant fractions are higher in vivo, the fold-increase over background is similar for both in vitro and in situ exposures. Results are also presented for a limited study on the effect of dose fractionation on the induction of Aprt mutations in kidney epithelial cells. Dose-fractionation reduces the fraction of proton-induced Aprt mutants in vitro and in vivo and also results in less cell killing. Taken together, the mutation burden in the epithelium is slightly reduced by dose-fractionation. Autosomal mutations accumulated during clinical exposure to high-energy protons may contribute to the risk of treatment-associated neoplasms, thereby highlighting the need for rigorous treatment planning to reduce the dose to normal tissues. For low dose exposures that occur during most space flight scenarios, the mutagenic effects of protons appear to be modest.

Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate

PubMed Central

da Silva, Gisela Bevilacqua Rolfsen Ferreira; Scarpa, Maria Virginia; Carlos, Iracilda Zepone; Quilles, Marcela Bassi; Lia, Raphael Carlos Comeli; do Egito, Eryvaldo Socrates Tabosa; de Oliveira, Anselmo Gomes

2015-01-01

Methyl dihydrojasmonate (MJ) has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME) has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S) ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to be nontoxic at doses higher than 350 mg/kg, which was higher than the dose that provides tumor-inhibition effect in this study. Because the MJ-loaded ME was shown to have anticancer activity comparable to doxorubicin, the ME described here may be considered a suitable vehicle for parenteral administration of MJ. PMID:25609963

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

PubMed

Molony, Julia T; Monda, Keri L; Li, Suying; Beaubrun, Anne C; Gilbertson, David T; Bradbury, Brian D; Collins, Allan J

2016-08-01

Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. Retrospective cohort study. Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

International Comparison of Adult Height in Children with Growth Hormone Deficiency and Limitations of Growth Hormone Treatment in Japan.

PubMed

Tanaka, Toshiaki

2017-03-01

The approved therapeutic dose of growth hormone (GH) for growth hormone deficiency (GHD) varies depending on the country. Japan has the lowest therapeutic dose globally, with a single dose of 0.175 mg/kg/week. GH treatment for GHD is considered as a replacement therapy and in fact, a dose of 0.175 mg/kg/week is slightly higher than GH secretion in prepubertal healthy children but nearly the same as that of pubertal children. Although the same growth rate as that of healthy children is expected in response to replacement therapy, the catch-up growth observed for the first 1 to 2 years of GH treatment was misinterpreted as an effect of the GH replacement therapy. The real effect of the GH replacement therapy was the growth rate appeared after more than 3 years of GH therapy, when patients showed nearly the same growth rate as healthy children. Therefore, children with GHD can have a higher growth rate than healthy children only for the first 1 to 2 years of GH therapy, after which their growth rate begins to wane. In the United States and Europe, the various therapeutic doses and high-dose treatment are accepted and the SD score of adult height after treatment is higher than that in Japan. The improvement degree of the height SD score and the adult height SD score with GH therapy are lower in Japan compared with other countries that administer a similar therapeutic dose. This suggests that the response to GH can be affected by race. Actual comparison of the response to GH between Japanese and Caucasian patients using KIGS (Pharmacia International Growth Database) data showed that both the short-term response and the effect on adult height were reduced in Japanese patients. As there is a strong positive correlation between adult height and height at the onset of puberty, treatment methods that can increase pubertal growth will be considered in the future for patients with GDH who enter puberty with short stature. Copyright© of YS Medical Media ltd.

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

NASA Astrophysics Data System (ADS)

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

2014-09-01

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

Biological properties and response to x-rays of first-generation transplants of spontaneous mammary carcinomas in C3H mice.

PubMed

Fowler, J F; Sheldon, P W; Begg, A C; Hill, S A; Smith, A M

1975-05-01

First-generation transplants of spontaneous mouse mammary carcinomas have been used extensively for radiobiological investigations of fractionated irradiation schedules, r.b.e. of fast neutrons and effectiveness of radiosensitizers, as reported elsewhere. The present work investigates the growth characteristics of the tumours; the criteria for the choice of end-points used in the definition of 'local control' of irradiated tumours; the reason for a decrease of 30 per cent in X-ray dose required to control tumours in females as compared with male mice; the proportion of hypoxic cells and its variation with time (reoxygenation) after a single dose of 1500 rad of X-rays; and the repair capacity of tumour cells within 24 hours after a substantial first dose of X-rays. Evidence is presented that the male-female difference was due to a higher proportion of hypoxic cells in tumours in male than in female mice. The repair of sub-lethal injury in tumour cells made hypoxic was slightly less than in skin made hypoxic but not significantly so. In the two-dose experiments on clamped tumours, no evidence of induced synchrony was found.

Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

PubMed

Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

2015-01-01

Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily dosing. Doravirine at steady state slightly reduced the exposure of coadministered midazolam, to a clinically unimportant extent.

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.

Influence of beta-radiation sterilisation in properties of new chitosan/soybean protein isolate membranes for guided bone regeneration.

PubMed

Silva, R M; Elvira, C; Mano, J F; San Román, J; Reis, R L

2004-04-01

Novel chitosan (cts) and soybean protein isolate (SI) blended membranes were prepared. These membranes were produced by solvent casting. Besides combining the advantages of both materials, cts/SI membranes exhibit a biphasic structure that will eventually originate in situ porous formation, through a two-step degradation mechanism. In this particular work the effect of beta-radiation over the properties of these membranes was evaluated. beta-radiation sterilisation was performed at three different doses (25, 50 and 100 kGy) and eventual surface chemical changes were evaluated by Fourier transformed infrared--with attenuated total reflection and contact angle measurements. Moreover, eventual bulk properties changes due to beta-radiation were assessed by means of mechanical tensile tests and water uptake measurements. In general, no substantial changes were detected on the studied properties, with the exception of the surface energy that was found to be slightly increased for higher applied doses.

Degradation of Nylon 6,6 Fire-Suppression Casing from Plutonium Glove Boxes Under Alpha and Neutron Irradiation

DOE PAGES

Millsap, Donald W.; Cournoyer, Michael E.; Landsberger, Sheldon; ...

2015-04-23

Nylon 6,6 tensile specimens, conforming to the casing for self-contained fire extinguisher systems, have been irradiated using both an accelerator He ++ ion beam and a 5-Ci PuBe neutron source to model the radiation damage these systems would likely incur over a lifetime of operation within glove boxes. Following irradiation, these samples were mechanically tested using standard practices as described in ASTM D638. The results of the He ++ study indicate that the tensile strength of the nylon specimens undergoes some slight (<10%) degradation while other properties of the samples, such as elongation and tangent modulus, appear to fluctuate withmore » increasing dose levels. The He ++-irradiated specimens also have a noticeable level of discoloration corresponding to increasing levels of dose. The neutron-irradiated samples show a higher degree of mechanical degradation than the He ++-irradiated samples.« less

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

PubMed

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

Anticonvulsant, anxiolytic and discriminative effects of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX).

PubMed

Swedberg, M D; Jacobsen, P; Honoré, T

1995-09-01

The anticonvulsant effects of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), phencyclidine (PCP) and diazepam against audiogenic seizures in DBA/2 mice and against seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in NMRI mice were compared. Motor impairment was assessed in a rotarod apparatus in DBA/2 as well as NMRI mice. At 30 min after i.p. administration, NBQX was as effective as PCP and diazepam in protecting against audiogenic seizures and had a therapeutic ratio slightly higher than diazepam's and 7-fold higher than PCP's. Whereas diazepam was fully effective, NBQX and PCP were both ineffective against seizures induced by DMCM 30 min after i.p. administration. The anticonvulsant potential and motor-impairing effects of NBQX were evaluated further by the i.p. and the i.v. routes at different time points after administration. At all pretreatment intervals, NBQX protected against audiogenic seizures more potently than it produced motor impairment. NBQX administered i.p. protected against DMCM-induced seizures when given 15 min but not 5 min before testing, whereas after i.v. administration NBQX produced anticonvulsant and motor-impairing effects in the same dose range. NBQX only slightly and non-dose-dependently attenuated the discriminative effects of pentylenetetrazole in rats, showing a limited anxiolytic potential. NBQX produced no PCP-like or morphine-like discriminative effects in rats, suggesting lack of PCP or opiate-like subjective effects. These data demonstrate that NBQX has anticonvulsant effects, has limited anxiolytic effects, and does not produce subjective effects of PCP or opiate type.

The role of Toujeo®, insulin glargine U-300, in the treatment of diabetes mellitus.

PubMed

Brown, Meagan A; Davis, Courtney S; Fleming, Laurie W; Fleming, Joshua W

2016-09-01

The purpose of this article is to educate nurse practitioners about the role of Toujeo®, insulin glargine U-300 (Gla-300), which is a new option for the treatment of diabetes mellitus. A comprehensive literature search was conducted using MEDLINE with the key terms: insulin glargine 300, Toujeo, Gla-300, and EDITION for clinical trial data. Other resources included package inserts, drug information websites, and the World Health Organization (WHO). Gla-300 appears to be a safe and effective option for basal insulin therapy. In clinical trials, it was shown to be equally efficacious as Gla-100 with fewer episodes of hypoglycemia and slightly less weight gain, and subjects receiving Gla-300 required approximately 10 units more basal insulin to obtain the same hemoglobin A1c (HbA1c) as subjects receiving Gla-100. This new basal therapy option represents a potential advantage for patients who require higher doses of insulin because of the higher concentration of Gla-300. The lower incidence of hypoglycemia and more predictable pharmacokinetics could offer a significant therapeutic benefit in difficult-to-control patients with diabetes mellitus. The biggest disadvantage of this product is the slightly higher insulin dosage that is required to improve and/or maintain patients' HbA1c. ©2016 American Association of Nurse Practitioners.

Pancreatic enzymes prepared in bicarbonate solution for administration through enteral feeding tubes.

PubMed

Boullata, Angela M; Boullata, Joseph I

2015-07-15

The dissolution and physicochemical effects of preparing delayed-release pancrelipase in a sodium bicarbonate solution before administration via an enteral feeding tube were studied. Several doses of four delayed-release pancrelipase products (Creon, Pancreaze, Ultresa, Zenpep) were studied. The intact contents of pancrelipase capsules was added to 20 mL of 8.4% sodium bicarbonate solution to dissolve the enteric coating and liberate the enzymes into solution. In addition to visual observation, the pH, relative particle count, and osmolality of each admixture were assessed immediately and 5, 10, 20, and 30 minutes after admixture preparation. The only dose of Creon that was completely dissolved at 30 minutes was the 24,000 lipase unit dose. None of the doses of Pancreaze and only the lowest dose (23,000 lipase units) of Ultresa were completely dissolved at 30 minutes. However, Zenpep doses of 20,000 and 40,000 lipase units were completely dissolved 30 minutes after preparation. Higher doses of each pancrelipase product did not completely dissolve. The baseline pH of the solvent decreased slightly at the first few time points after pancrelipase was added. The relative particle count increased over time and with increasing doses. The osmolality of the mixtures varied by pancrelipase product. The dissolution of enteric coated granules in sodium bicarbonate varied with the pancrelipase product and dose. Zenpep 40,000 lipase units was found to most efficiently dissolve in sodium bicarbonate, possibly due to the consistent size of the product's granules and visibly thinner and uniform enteric coating. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Comparison of dose response functions for EBT3 model GafChromic™ film dosimetry system.

PubMed

Aldelaijan, Saad; Devic, Slobodan

2018-05-01

Different dose response functions of EBT3 model GafChromic™ film dosimetry system have been compared in terms of sensitivity as well as uncertainty vs. error analysis. We also made an assessment of the necessity of scanning film pieces before and after irradiation. Pieces of EBT3 film model were irradiated to different dose values in Solid Water (SW) phantom. Based on images scanned in both reflection and transmission mode before and after irradiation, twelve different response functions were calculated. For every response function, a reference radiochromic film dosimetry system was established by generating calibration curve and by performing the error vs. uncertainty analysis. Response functions using pixel values from the green channel demonstrated the highest sensitivity in both transmission and reflection mode. All functions were successfully fitted with rational functional form, and provided an overall one-sigma uncertainty of better than 2% for doses above 2 Gy. Use of pre-scanned images to calculate response functions resulted in negligible improvement in dose measurement accuracy. Although reflection scanning mode provides higher sensitivity and could lead to a more widespread use of radiochromic film dosimetry, it has fairly limited dose range and slightly increased uncertainty when compared to transmission scan based response functions. Double-scanning technique, either in transmission or reflection mode, shows negligible improvement in dose accuracy as well as a negligible increase in dose uncertainty. Normalized pixel value of the images scanned in transmission mode shows linear response in a dose range of up to 11 Gy. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors.

PubMed

Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M

1992-05-01

The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha-Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha-Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes.

Novel Application of Helical Tomotherapy in Whole Skull Palliative Radiotherapy

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

Rodrigues, George; Yartsev, Slav; Coad, Terry

2008-01-01

Helical tomotherapy (HT) is a radiation planning/delivery platform that combines inversely planned IMRT with on-board megavoltage imaging. A unique HT radiotherapy whole skull brain sparing technique is described in a patient with metastatic prostate cancer. An inverse HT plan and an accompanying back-up conventional lateral 6-MV parallel opposed pair (POP) plan with corresponding isodose distributions and dose-volume histograms (DVH) were created and assessed prior to initiation of therapy. Plans conforming to the planning treatment volume (PTV) with significant sparing of brain, optic nerve, and eye were created. Dose heterogeneity to the PTV target was slightly higher in the HT planmore » compared to the back-up POP plan. Conformal sparing of brain, optic nerve, and eye was achieved by the HT plan. Similar lens and brain stem/spinal cord doses were seen with both plans. Prospective clinical evaluation with relevant end points (quality of life, symptom relief) are required to confirm the potential benefits of highly conformal therapies applied to palliative situations such as this case.« less

Do we need 3D tube current modulation information for accurate organ dosimetry in chest CT? Protocols dose comparisons.

PubMed

Lopez-Rendon, Xochitl; Zhang, Guozhi; Coudyzer, Walter; Develter, Wim; Bosmans, Hilde; Zanca, Federica

2017-11-01

To compare the lung and breast dose associated with three chest protocols: standard, organ-based tube current modulation (OBTCM) and fast-speed scanning; and to estimate the error associated with organ dose when modelling the longitudinal (z-) TCM versus the 3D-TCM in Monte Carlo simulations (MC) for these three protocols. Five adult and three paediatric cadavers with different BMI were scanned. The CTDI vol of the OBTCM and the fast-speed protocols were matched to the patient-specific CTDI vol of the standard protocol. Lung and breast doses were estimated using MC with both z- and 3D-TCM simulated and compared between protocols. The fast-speed scanning protocol delivered the highest doses. A slight reduction for breast dose (up to 5.1%) was observed for two of the three female cadavers with the OBTCM in comparison to the standard. For both adult and paediatric, the implementation of the z-TCM data only for organ dose estimation resulted in 10.0% accuracy for the standard and fast-speed protocols, while relative dose differences were up to 15.3% for the OBTCM protocol. At identical CTDI vol values, the standard protocol delivered the lowest overall doses. Only for the OBTCM protocol is the 3D-TCM needed if an accurate (<10.0%) organ dosimetry is desired. • The z-TCM information is sufficient for accurate dosimetry for standard protocols. • The z-TCM information is sufficient for accurate dosimetry for fast-speed scanning protocols. • For organ-based TCM schemes, the 3D-TCM information is necessary for accurate dosimetry. • At identical CTDI vol , the fast-speed scanning protocol delivered the highest doses. • Lung dose was higher in XCare than standard protocol at identical CTDI vol .

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

PubMed

Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

2013-12-01

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies.

PubMed

Kusawake, Tomohiro; Keirns, James J; Kowalski, Donna; den Adel, Martin; Groenendaal-van de Meent, Dorien; Takada, Akitsugu; Ohtsu, Yoshiaki; Katashima, Masataka

2017-12-01

Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants. Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations. Amenamevir was administered orally at various doses as a single dose (5-2400 mg) or daily (300 or 600 mg/day) for 7 days. Following single and multiple oral doses, amenamevir demonstrated a less than dose proportional increase in the pharmacokinetic parameters area under the plasma drug concentration versus time curve from time zero to infinity (AUC inf ) and C max . After single and multiple oral 300-mg doses of amenamevir, no apparent differences in pharmacokinetics were observed between nonelderly and elderly participants. In contrast, with the amenamevir 600-mg dose both the area under the plasma drug concentration versus time curve from time zero to 24 h and C max were slightly increased and renal clearance was decreased in elderly participants. The pharmacokinetics of amenamevir was affected by food, with AUC inf increased by about 90%. In the bioavailability study, AUC inf and C max were slightly lower following tablet versus capsule administration (decreased by 14 and 12%, respectively), with relative bioavailability of 86%. The different amenamevir doses and formulations were safe and well tolerated; no deaths or serious adverse events were reported. Amenamevir had less than dose proportional pharmacokinetic characteristics. Age may have an influence on amenamevir pharmacokinetics; however, the effect was considered minimal. The pharmacokinetics of amenamevir were affected by food, with AUC inf almost doubling when amenamevir was administered with food. The concentration versus time profile of the tablet was slightly lower than that of the capsule; the relative bioavailability of the tablet versus the capsule was 86%. Amenamevir was safe and well tolerated in the dose range investigated. Astellas Pharma. ClinicalTrials.gov identifiers NCT02852876 (15L-CL-002) and NCT02796118 (15L-CL-003).

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

Dosimetric and radiobiological characterizations of prostate intensity-modulated radiotherapy and volumetric-modulated arc therapy: A single-institution review of ninety cases

PubMed Central

Khan, Muhammad Isa; Jiang, Runqing; Kiciak, Alexander; ur Rehman, Jalil; Afzal, Muhammad; Chow, James C. L.

2016-01-01

This study reviewed prostate volumetric-modulated arc therapy (VMAT) plans with intensity-modulated radiotherapy (IMRT) plans after prostate IMRT technique was replaced by VMAT in an institution. Characterizations of dosimetry and radiobiological variation in prostate were determined based on treatment plans of 40 prostate IMRT patients (planning target volume = 77.8–335 cm3) and 50 VMAT patients (planning target volume = 120–351 cm3) treated before and after 2013, respectively. Both IMRT and VMAT plans used the same dose-volume criteria in the inverse planning optimization. Dose-volume histogram, mean doses of target and normal tissues (rectum, bladder and femoral heads), dose-volume points (D99% of planning target volume; D30%, D50%, V30 Gy and V35 Gy of rectum and bladder; D5%, V14 Gy, V22 Gy of femoral heads), conformity index (CI), homogeneity index (HI), gradient index (GI), prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman-Burman-Kutcher algorithm were calculated for each IMRT and VMAT plan. From our results, VMAT plan was found better due to its higher (1.05%) CI, lower (0.83%) HI and (0.75%) GI than IMRT. Comparing doses in normal tissues between IMRT and VMAT, it was found that IMRT mostly delivered higher doses of about 1.05% to the normal tissues than VMAT. Prostate TCP and rectal NTCP were found increased (1%) for VMAT than IMRT. It is seen that VMAT technique can decrease the dose-volume evaluation criteria for the normal tissues. Based on our dosimetric and radiobiological results in treatment plans, it is concluded that our VMAT implementation could produce comparable or slightly better target coverage and normal tissue sparing with a faster treatment time in prostate radiotherapy. PMID:27651562

Distribution of radioactive Cesium in trees and effect of decontamination of forest contaminated by the Fukushima nuclear accident

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

Iijima, K.; Funaki, H.; Tokizawa, T.

In decontamination pilot projects conducted by Japan Atomic Energy Agency (JAEA), many different techniques were tested to determine their applicability to remediate areas evacuated after the Fukushima Daiichi nuclear accident following the Great Tohoku earthquake and tsunami of March 11, 2011. In addition to buildings, roads and farmland, the forest adjacent to living areas was one of the main decontamination targets. The projects evaluated the radioactive contamination of trees and the effectiveness of decontaminating a highly contaminated evergreen forest. This forest was located 1.3 km southwest of the Fukushima Daiichi Nuclear Power Plant and is dominated by Japanese cedar treesmore » and fir trees. As the first step, three Japanese cedar trees and three fir trees were cut down and the distributions of radioactive cesium (Cs) were measured in each. The total concentrations of {sup 134}Cs and {sup 137}Cs in the leaves and branches were about 1 MBq/kg for both cedar and fir trees, and were appreciably higher than in the bark for cedar. The concentrations in the outer part of the trunks (under the bark) were lower, on the order of 10 kBq/kg, and those in the core of the trunks were lower than 1 kBq/kg for both kinds of trees. The observation that the Cs concentrations are higher in the outer part of trees, is compatible with the assumption that radio-Cs was mostly adsorbed on the surface of trees and partly penetrated into the trunks through the bark. Evolution of air dose rates in a 100 x 60 m pasture adjacent to the forest was monitored during decontamination of the forest and of the pasture itself. The dose rates in the pasture decreased drastically after stripping contaminated topsoil from the pasture and decreased slightly more after stripping contaminated topsoil of the forest floor and pruning the trees. Cutting down and removing 84 trees in the outermost area (10- m width) of the forest also slightly decreased these dose rates. After decontamination, the residual dose rates around the highly contaminated forest were mostly attributed to radioactive Cs existing in or on trees and topsoil in the untouched forest beyond the decontaminated area. (authors)« less

A comparison of volumetric modulated arc therapy and sliding-window intensity-modulated radiotherapy in the treatment of Stage I-II nasal natural killer/T-cell lymphoma

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

Liu, Xianfeng; Yang, Yong; Jin, Fu

This article is aimed to compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL). Ten patients with Stage I-II NNKTL treated with IMRT were replanned with VMAT (2 arcs). The prescribed dose of the planning target volume (PTV) was 50 Gy in 25 fractions. The VMAT plans with the Anisotropic Analytical Algorithm (Version 8.6.15) were based on an Eclipse treatment planning system; the monitor units (MUs) and treatment time (T) were scored to measure the expected treatment efficiency. All the 10 patients under the study were subjectmore » to comparisons regarding the quality of target coverage, the efficiency of delivery, and the exposure of normal adjacent organs at risk (OARs). The study shows that VMAT was associated with a better conformal index (CI) and homogeneity index (HI) (both p < 0.05) but slightly higher dose to OARs than IMRT. The MUs with VMAT (650.80 ± 24.59) were fewer than with IMRT (1300.10 ± 57.12) (relative reduction of 49.94%, p = 0.00) when using 2-Gy dose fractions. The treatment time with VMAT (3.20 ± 0.02 minutes) was shorter than with IMRT (7.38 ± 0.18 minutes) (relative reduction of 56.64%, p = 0.00). We found that VMAT and IMRT both provide satisfactory target dosimetric coverage and OARs sparing clinically. Likely to deliver a bit higher dose to OARs, VMAT in comparison with IMRT, is still a better choice for treatment of patients with Stage I-II NNKTL, thanks to better dose distribution, fewer MUs, and shorter delivery time.« less

Efficiency of early, single-dose probiotic administration methods on performance, small intestinal morphology, blood biochemistry, and immune response of Japanese quail.

PubMed

Seifi, Kazem; Karimi Torshizi, Mohammad Amir; Rahimi, Shaban; Kazemifard, Mohammad

2017-07-01

The aim of the present study was to investigate the efficacy of early probiotics (single dose) administered in different ways, on quails' performance, small intestine morphology, blood biochemistry, and immune response. In total, 192 day-old chicks were used in one of the following experimental groups before being transferred to a raising room: 1) Control (no probiotic administered), 2) oral gavage, 3) spray, and 4) vent lip. Four replicates of 12 chicks per cage were considered for each treatment and birds were raised up to 35 d in the same conditions. Probiotic treated birds had higher d 1 to 35 feed intake than the control group (P < 0.05). In addition, oral-gavaged birds had a higher body weight gain as compared to the control (P < 0.05). The values of duodenum length and villus height of the oral group and ileum length and villus height of the vent lip group were greater than that of the control (P < 0.01). Regardless of the method of administration, probiotics resulted in deeper crypts and in a higher number of goblet cells in the duodenum and ileum as compared to the control (P < 0.01). The administration of probiotics resulted in increased plasma uric acid (P < 0.05), glucose, and total protein (P < 0.01). The concentration of hemoglobin was slightly higher in probiotic-supplemented groups. While a decreased concentration of triglyceride was observed in vent-lip probiotic-administered birds compared to control (P < 0.05), the concentration of cholesterol was not significantly affected by treatments (P > 0.01). None of the immune-related parameters were affected by the probiotic (P > 0.05). Single dose usage of probiotics exerts its beneficial effects on quails' body weight gain, feed intake and mortality in 1 to 35 d period, regardless of the route of administration. This work generally supports the efficacy of single-dose usage of probiotics and suggests the spray of probiotics as an early, single-dose administration method. © 2017 Poultry Science Association Inc.

Image quality of conventional images of dual-layer SPECTRAL CT: A phantom study.

PubMed

van Ommen, Fasco; Bennink, Edwin; Vlassenbroek, Alain; Dankbaar, Jan Willem; Schilham, Arnold M R; Viergever, Max A; de Jong, Hugo W A M

2018-05-10

Spectral CT using a dual layer detector offers the possibility of retrospectively introducing spectral information to conventional CT images. In theory, the dual-layer technology should not come with a dose or image quality penalty for conventional images. In this study, we evaluate the influence of a dual-layer detector (IQon Spectral CT, Philips Healthcare) on the image quality of conventional CT images, by comparing these images with those of a conventional but otherwise technically comparable single-layer CT scanner (Brilliance iCT, Philips Healthcare), by means of phantom experiments. For both CT scanners, conventional CT images were acquired using four adult scanning protocols: (a) body helical, (b) body axial, (c) head helical, and (d) head axial. A CATPHAN 600 phantom was scanned to conduct an assessment of image quality metrics at equivalent (CTDI) dose levels. Noise was characterized by means of noise power spectra (NPS) and standard deviation (SD) of a uniform region, and spatial resolution was evaluated with modulation transfer functions (MTF) of a tungsten wire. In addition, contrast-to-noise ratio (CNR), image uniformity, CT number linearity, slice thickness, slice spacing, and spatial linearity were measured and evaluated. Additional measurements of CNR, resolution and noise were performed in two larger phantoms. The resolution levels at 50%, 10%, and 5% MTF of the iCT and IQon showed small, but significant differences up to 0.25 lp/cm for body scans, and up to 0.2 lp/cm for head scans in favor of the IQon. The iCT and IQon showed perfect CT linearity for body scans, but for head scans both scanners showed an underestimation of the CT numbers of materials with a high opacity. Slice thickness was slightly overestimated for both scanners. Slice spacing was comparable and reconstructed correctly. In addition, spatial linearity was excellent for both scanners, with a maximum error of 0.11 mm. CNR was higher on the IQon compared to the iCT for both normal and larger phantoms with differences up to 0.51. Spatial resolution did not change with phantom size, but noise levels increased significantly. For head scans, IQon had a noise level that was significantly lower than the iCT, on the other hand IQon showed noise levels significantly higher than the iCT for body scans. Still, these differences were well within the specified range of performance of iCT scanners. At equivalent dose levels, this study showed similar quality of conventional images acquired on iCT and IQon for medium-sized phantoms and slightly degraded image quality for (very) large phantoms at lower tube voltages on the IQon. Accordingly, it may be concluded that the introduction of a dual-layer detector neither compromises image quality of conventional images nor increases radiation dose for normal-sized patients, and slightly degrades dose efficiency for large patients at 120 kVp and lower tube voltages. © 2018 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Marginal effects of a large caffeine dose on heat balance during exercise-heat stress.

PubMed

Ely, Brett R; Ely, Matthew R; Cheuvront, Samuel N

2011-02-01

The use of caffeine supplements in athletic and military populations has increased in recent years. Excessive caffeine consumption in conjunction with exercise in a hot environment may predispose individuals to heat illness. To examine heat balance induced by a large dose of caffeine during exercise in a hot environment. Ten men, not heat acclimated and not habitual caffeine users, consumed either caffeine (CAF; 9 mg/kg) or placebo (PLA) before performing cycle-ergometer exercise for 30 min at 50% VO2peak in a 40 °C, 25% relative humidity environment while body temperature (core and skin) and ratings of thermal comfort (TC) were monitored. Heat-exchange variables were calculated using partitional calorimetry and thermometry. Mean body temperature (Tb) was higher (p < .05) with CAF (37.18 ± 0.15 °C) than with PLA (36.93 ± 0.15 °C) at the start of exercise. Heat production was slightly higher (~8 W, p < .05) with CAF. There were no differences in heat storage, dry heat gains, TC, or Tb during exercise. A caffeine dose of 9 mg/kg does not appreciably alter heat balance during work in a hot environment. The small increase in Tb observed with CAF was undetected by the participants and is unlikely to increase physiological strain sufficiently to affect endurance performance or risk of heat illness.

Structure of the cell wall of mango after application of ionizing radiation

NASA Astrophysics Data System (ADS)

Silva, Josenilda M.; Villar, Heldio P.; Pimentel, Rejane M. M.

2012-11-01

Cells of the mesocarp of mango cultivar Tommy Atkins were analyzed by Transmission Electron Microscope—TEM to evaluate the effects of doses of 0.5 and 1.0 kGy applied immediately after the fruit and after storage for twenty days at a temperature of 12 °C followed by 5 days of simulated marketing at a temperature of 21 °C. No alteration was found in the structure of the cell wall, middle lamella, and plasma membrane of fruits when analyzed immediately after application of doses. The mesocarp cell structure of the cell wall, middle lamella, and the plasma membrane did however undergo changes after storage. Fruits that received a dose of 0.5 kGy displayed slight changes in cell wall structure and slight disintegration of the middle lamella. Fruits that received a dose of 1.0 kGy displayed more severe changes in the structure of the cell wall, greater middle lamella degradation, and displacement of the plasma membrane.

The Impact of Monte Carlo Dose Calculations on Intensity-Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Siebers, J. V.; Keall, P. J.; Mohan, R.

The effect of dose calculation accuracy for IMRT was studied by comparing different dose calculation algorithms. A head and neck IMRT plan was optimized using a superposition dose calculation algorithm. Dose was re-computed for the optimized plan using both Monte Carlo and pencil beam dose calculation algorithms to generate patient and phantom dose distributions. Tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) were computed to estimate the plan outcome. For the treatment plan studied, Monte Carlo best reproduces phantom dose measurements, the TCP was slightly lower than the superposition and pencil beam results, and the NTCP values differed little.

SU-F-T-435: Helical Tomotherapy for Craniospinal Irradiation: What We Have Learned from a Multi-Institutional Study

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

Du, D; Kaprealian, T; Low, D

Purpose: To report cranio-spinal irradiation (CSI) planning experience, compare dosimetric quality and delivery efficiency with Tomotherapy from different institutions, and to investigate effect of planning parameters on plan quality and treatment time. Methods: Clinical helical tomotherapy IMRT plans for thirty-nine CSI cases from three academic institutions were retrospectively evaluated. The planning parameters: field width (FW), pitch, modulation factor (MF), and achieved dosimetric endpoints were cross-compared. A fraction-dose-delivery-timing index (FDTI), defined as treatment time per fraction dose per PTV length, was utilized to evaluate plan delivery efficiency. A lower FDTI indicates higher delivery efficiency. We studied the correlation between planning quality,more » treatment time and planning parameters by grouping the plans under specific planning parameters. Additionally, we created new plans using 5cm jaw for a subset of plans that used 2.5cm jaw to exam if treatment efficiency can be improved without sacrificing plan quality. Results: There were significant dosimetric differences for organ at risks (OARs) among different institutions (A,B,C). Using the lowest average MF (1.9±0.4) and 5cm field width, C had the highest lung, heart, kidney, liver mean doses and maximum doses for lens. Using the same field width of 5cm, but higher MF (2.6±0.6), B had lower doses to the OARs in the thorax and abdomen area. Most of A’s plans were planned with 2.5cm jaw, the plans yielded better PTV coverage, higher OAR doses and slightly shorter FDTI compared to institution B. The replanned 5cm jaw plans achieved comparable PTV coverage and OARs sparing, while saving up to 44.7% treatment time. Conclusion: Plan quality and delivery efficiency could vary significantly in CSI planning on Tomotheapy due to choice of different planning parameters. CSI plans using a 5cm jaw, with proper selection of pitch and MF, can achieve comparable/ better plan quality with shorter delivery time compared to 2.5cm jaw plans.« less

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

Lin, M; Pompos, A; Gu, X

Purpose: To characterize the dose distributions of Cyberknife and intensity-modulated-proton-therapy (IMPT). Methods: A total of 20 patients previously treated with Cyberknife were selected. The original planning-target-volume (PTV) was used in the ‘IMPT-ideal’ plan assuming a comparable image-guidance with Cyberknife. A 3mm expansion was made to create the proton-PTV for the ‘IMPT-3mm’ plan representing the current proton-therapy where a margin of 3mm is used to account for the inferior image-guidance. The proton range uncertainty was taken-care in beam-design by adding the proximal- and distal-margins (3%water-equivalent-depth+1mm) for both proton plans. The IMPT plans were generated to meet the same target coverage asmore » the Cyberknife-plans. The plan quality of IMPT-ideal and IMPT-3mm were compared to the Cyberknife-plan. To characterize plan quality, we defined the ratio(R) of volumes encompassed by the selected isodose surfaces for Cyberknife and IMPT plans (VCK/VIMPT). Comparisons were made for both Cyberknife versus IMPT-ideal and Cyberknife versusIMPT-3mm to further discuss the impact of setup error margins used in proton therapy and the correlation with target size and location. Results: IMPT-ideal plans yield comparable plan quality as CK plans and slightly better OAR sparing while the IMPT-3mm plan results in a higher dose to the OARs, especially for centralized tumors. Comparing to the IMPT-ideal plans, a slightly larger 80% (Ravg=1.05) dose cloud and significantly larger 50% (Ravg=1.3) and 20% (Ravg=1.60) dose clouds are seen in CK plans. However, the 3mm expansion results in a larger high and medium dose clouds in IMPT-3mm plans (Ravg=0.65 for 80%-isodose; Ravg=0.93 for 50%-isodose). The trend increases with the size of the target and the distance from the brainstem to the center of target. Conclusion: Cyberknife is more preferable for treating centralized targets and proton therapy is advantageous for the large and peripheral targets. Advanced image guidance would improve the efficacy of proton therapy for intracranial treatments.« less

Outdoor 220Rn, 222Rn and terrestrial gamma radiation levels: investigation study in the thorium rich Fen Complex, Norway.

PubMed

Mrdakovic Popic, Jelena; Bhatt, Chhavi Raj; Salbu, Brit; Skipperud, Lindis

2012-01-01

The present study was done in the Fen Complex, a Norwegian area rich in naturally occurring radionuclides, especially in thorium ((232)Th). Measurement of radioactivity levels was conducted at the decommissioned iron (Fe) and niobium (Nb) mining sites (TENORM) as well as at the undisturbed wooded sites (NORM), all open for free public access. The soil activity concentrations of (232)Th (3280-8395 Bq kg(-1)) were significantly higher than the world and the Norwegian average values and exceeded the Norwegian screening level (1000 Bq kg(-1)) for radioactive waste, while radium ((226)Ra) was present at slightly elevated levels (89-171 Bq kg(-1)). Terrestrial gamma dose rates were also elevated, ranging 2.6-4.4 μGy h(-1). Based on long-term surveys, the air concentrations of thoron ((220)Rn) and radon ((222)Rn) reached 1786 and 82 Bq m(-3), respectively. Seasonal variation in the outdoor gamma dose rates and Rn concentrations was confirmed. Correlation analyses showed a linear relationship between air radiation levels and the abundance of (232)Th in soil. The annual outdoor effective radiation doses for humans (occupancy 5 h day(-1)) were estimated to be in the range of 3.0-7.7 mSv, comparable or higher than the total average (summarized indoor and outdoor) exposure dose for the Norwegian population (2.9 mSv year(-1)). On the basis of all obtained results, this Norwegian area should be considered as enhanced natural radiation area (ENRA).

Evaluation of the effect of patient dose from cone beam computed tomography on prostate IMRT using Monte Carlo simulation.

PubMed

Chow, James C L; Leung, Michael K K; Islam, Mohammad K; Norrlinger, Bernhard D; Jaffray, David A

2008-01-01

The aim of this study is to evaluate the impact of the patient dose due to the kilovoltage cone beam computed tomography (kV-CBCT) in a prostate intensity-modulated radiation therapy (IMRT). The dose distributions for the five prostate IMRTs were calculated using the Pinnacle treatment planning system. To calculate the patient dose from CBCT, phase-space beams of a CBCT head based on the ELEKTA x-ray volume imaging system were generated using the Monte Carlo BEAMnr code for 100, 120, 130, and 140 kVp energies. An in-house graphical user interface called DOSCTP (DOSXYZnrc-based) developed using MATLAB was used to calculate the dose distributions due to a 360 degrees photon arc from the CBCT beam with the same patient CT image sets as used in Pinnacle. The two calculated dose distributions were added together by setting the CBCT doses equal to 1%, 1.5%, 2%, and 2.5% of the prescription dose of the prostate IMRT. The prostate plan and the summed dose distributions were then processed in the CERR platform to determine the dose-volume histograms (DVHs) of the regions of interest. Moreover, dose profiles along the x- and y-axes crossing the isocenter with and without addition of the CBCT dose were determined. It was found that the added doses due to CBCT are most significant at the femur heads. Higher doses were found at the bones for a relatively low energy CBCT beam such as 100 kVp. Apart from the bones, the CBCT dose was observed to be most concentrated on the anterior and posterior side of the patient anatomy. Analysis of the DVHs for the prostate and other critical tissues showed that they vary only slightly with the added CBCT dose at different beam energies. On the other hand, the changes of the DVHs for the femur heads due to the CBCT dose and beam energy were more significant than those of rectal and bladder wall. By analyzing the vertical and horizontal dose profiles crossing the femur heads and isocenter, with and without the CBCT dose equal to 2% of the prescribed dose, it was found that there is about a 5% increase of dose at the femur head. Still, such an increase in the femur head dose is well below the dose limit of the bone in our IMRT plans. Therefore, under these dose fractionation conditions, it is concluded that, though CBCT causes a higher dose deposited at the bones, there may be no significant effect in the DVHs of critical tissues in the prostate IMRT.

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

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

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

2006-10-01

Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethalmore » dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of {sup 14}C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of {sup 14}C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC{sub 15-360min}) in the systemic circulation. Exhalation of {sup 14}C-chloroform was unchanged in primed as compared to unprimed mice (AUC{sub 1-6h}). Urinary excretion of {sup 14}C-chloroform was higher in primed mice after administration of the lethal dose. However, neither slightly higher urinary elimination nor unchanged expiration can account for the difference in systemic levels of chloroform. Liver and kidney regeneration was inhibited by the lethal dose in unprimed mice leading to progressive injury, organ failure, and 90% mortality. In contrast, sustained and highly stimulated compensatory hepato- and nephrogenic repair prevented the progression of injury resulting in 100% survival of primed mice challenged with the lethal dose. These findings affirm the critical role of tissue regeneration and favorable detoxification (only in kidney) of the lethal dose of chloroform in subchronic chloroform priming-induced autoprotection.« less

A40926, a new glycopeptide antibiotic with anti-Neisseria activity.

PubMed Central

Goldstein, B P; Selva, E; Gastaldo, L; Berti, M; Pallanza, R; Ripamonti, F; Ferrari, P; Denaro, M; Arioli, V; Cassani, G

1987-01-01

In the course of a search for glycopeptide antibiotics having novel biological properties, we isolated A40926. Produced by an actinomycete of the genus Actinomadura, A40926 is a complex of four main factors which contain a fatty acid as part of a glycolipid attached to the peptide backbone. Its activity was, in most respects, similar to that of other glycopeptides, such as vancomycin and teicoplanin. However, in addition to inhibiting gram-positive bacteria, A40926 was very active against Neisseria gonorrhoeae. A40926 was rapidly bactericidal for N. gonorrhoeae clinical isolates at concentrations equal to or slightly higher than the MIC. In mice, levels in serum were higher and more prolonged than those of an equivalent subcutaneous dose of teicoplanin. These properties suggest that A40926 may have potential in the therapy of gonorrhea. PMID:2964225

Visible absorption properties of radiation exposed XR type-T radiochromic film.

PubMed

Butson, Martin J; Cheung, Tsang; Yu, Peter K N

2004-10-07

The visible absorption spectra of Gafchromic XR type-T radiochromic film have been investigated to analyse the dosimetry characteristics of the film with visible light densitometers. Common densitometers can use photospectrometry, fluorescent light (broad-band visible), helium neon (632 nm), light emitting diode (LED) or other specific bandwidth spectra. The visible absorption spectra of this film when exposed to photon radiation show peaks at 676 nm and 618 nm at 2 Gy absorbed doses which shift to slightly lower wavelengths (662 nm and 612 nm at 8 Gy absorbed dose) at higher doses. This is similar to previous models of Gafchromic film such as MD-55-2 and HS but XR type-T also includes a large absorption at lower visible wavelengths due to 'yellow' dyes placed within the film to aid with visible recognition of the film exposure level. The yellow dye band pass is produced at approximately 520 nm to 550 nm and absorbs wavelengths lower than this value within the visible spectrum. This accounts for the colour change from yellow to brown through the added absorption in the red wavelengths with radiation exposure. The film produces a relatively high dose sensitivity with up to 0.25 OD units per Gy change at 672 nm at 100 kVp x-ray energy. Variations in dose sensitivity can be achieved by varying wavelength analysis.

Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma.

PubMed

Maráz, Anikó; Cserháti, Adrienn; Uhercsák, Gabriella; Szilágyi, Éva; Varga, Zoltán; Révész, János; Kószó, Renáta; Varga, Linda; Kahán, Zsuzsanna

2018-03-15

In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study. From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62.5 mg/day in 4/2 or 2 × 2/1 scheme, second level: 75 mg/day in 4/2 or 2 × 2/1 scheme) were collected prospectively. Regarding characteristics, outcome, and toxicity data, an explorative retrospective analysis of the register was carried out, comparing treatments after and before July 1, 2013 in the study (selected patients for escalated dose) and control (standard dose) groups, respectively. The study involved 103 patients receiving sunitinib therapy with a median overall and progression free survival of 25.36 ± 2.62 and 14.2 ± 3.22 months, respectively. Slight progression was detected in 48.5% of them. First and second-level dose escalation were indicated in 18.2% and 4.1% of patients, respectively. The dosing scheme was modified in 22.2%. The median progression free survival (39.7 ± 5.1 vs 14.2 ± 1.3 months (p = 0.037)) and the overall survival (57.5 ± 10.7 vs 27.9 ± 2.5 months (p = 0.044)) were significantly better in the study group (with dose escalation) than in the control group. Patients with nephrectomy and lower Memorial Sloan Kettering Cancer Center (MSKCC) scores showed more favorable outcomes. After dose escalation, the most common adverse events were worsening or development of fatigue, hypertension, stomatitis, and weight loss of over 10%. Escalation of sunitinib dosing in selected patients with metastatic renal cell cancer, especially in case of slight progression, based on tolerable toxicity is safe and improves outcome. Dose escalation in 12.5 mg steps may be recommended for properly educated patients.

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

PubMed

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

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in the creatinine clearance in the elderly men and women. Delafloxacin was well tolerated at the tested doses, with gastrointestinal adverse effects observed more commonly at doses ≥1200 mg. Delafloxacin exhibits linear pharmacokinetic parameters that reached steady state after 3 days of daily oral dosing with minimal accumulation. Delafloxacin was well tolerated throughout both studies, with gastrointestinal effects observed at the higher doses (≥1200 mg). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A one-year neonatal mouse carcinogenesis study of quinacrine dihydrochloride.

PubMed

Cancel, Aida M; Smith, Thomas; Rehkemper, Ursula; Dillberger, John E; Sokal, David; McClain, R Michael

2006-01-01

Quinacrine is an acridine derivative under investigation for its use in nonsurgical female sterilization. Safety issues regarding the carcinogenic potential of quinacrine have been raised because it is mutagenic and clastogenic in vitro. The objective of the study was to evaluate the carcinogenic potential of quinacrine dihydrochloride (quinacrine) in neonatal mice treated with single intraperitoneal doses on postpartum days 8 and 15 and observed for 52 weeks. Neonatal Crl: CD-1 mice of each sex were randomly allocated into four treatment groups (0, 10, 50, and 150 mg/kg), dosed twice with quinacrine suspended in carboxymethylcellulose, observed for 52 weeks post dose, and then euthanized, necropsied, and subjected to a full histopathological examination. In male mice, tumor incidence was not significantly increased at any site at any dose level. In female mice, the incidence of benign uterine endometrial stromal polyps was slightly greater at the mid and high dose (> or = 50 mg/kg), as was the incidence of endometrial hyperplasia. The incidence of polyps in these groups was not significantly greater than in controls by pair-wise comparison but was significantly greater (p = .042) by the linear trend test. The authors conclude that quinacrine administered twice to neonatal mice may have enhanced or accelerated the development of endometrial hyperplasia and uterine stromal polyps at higher doses. Because uterine stromal polyps are a commonly observed benign tumor in older mice, the significance of this finding is unclear and will require a weight of evidence evaluation for a conclusion on the carcinogenic potential of quinacrine.

A study on a dental device for the prevention of mucosal dose enhancement caused by backscatter radiation from dental alloy during external beam radiotherapy.

PubMed

Katsura, Kouji; Utsunomiya, Satoru; Abe, Eisuke; Sakai, Hironori; Kushima, Naotaka; Tanabe, Satoshi; Yamada, Takumi; Hayakawa, Takahide; Yamanoi, Yoshihiko; Kimura, Syuhei; Wada, Shinichi; Aoyama, Hidefumi; Hayashi, Takafumi

2016-11-01

The changes in dose distribution caused by backscatter radiation from a common commercial dental alloy (Au-Ag-Pd dental alloy; DA) were investigated to identify the optimal material and thicknesses of a dental device (DD) for effective prevention of mucositis. To this end, 1 cm 3 of DA was irradiated with a 6-MV X-ray beam (100 MU) in a field size of 10 × 10 cm 2 using a Novalis TX linear accelerator. Ethylene vinyl acetate copolymer, polyolefin elastomer, and polyethylene terephthalate (PET) were selected as DD materials. The depth dose along the central axis was determined with respect to the presence/absence of DA and DDs at thicknesses of 1-10 mm using a parallel-plate ionization chamber. The dose in the absence of DDs showed the lowest value at a distance of 5 mm from the DA surface and gradually increased with distance between the measurement point and the DA surface for distances of ≥5 mm. Except for PET, no significant difference between the DA dose curves for the presence and absence of DDs was observed. In the dose curve, PET showed a slightly higher dose for DA with DD than for DA without DD for thicknesses of ≥4 mm. The findings herein suggest that the optimal DD material for preventing local dose enhancement of the mucosa caused by DA backscatter radiation should have a relatively low atomic number and physical density and that optimal DD thickness should be chosen considering backscatter radiation and percentage depth dose. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

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

Little, Mark P., E-mail: mark.little@nih.gov; Kleinerman, Ruth A.; Stovall, Marilyn

Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. Theremore » were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.« less

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

PubMed

Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

2015-04-01

Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

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

Rashid, Rosnani Abdul; Awang, Mat Rasol; Mohamad, Azhar

2014-09-03

Radiosensitive dosage and morphology characterization of irradiated grey oyster mushroom Pleurotus sajor-caju by gamma rays was investigated due to effects of irradiation. In order to establish the effect, mycelium of P. sajor-caju was irradiated by gamma rays at dose 0.1 to 8.0 kGy with dose rate 0.227 Gy sec{sup −1}. The irradiation of mycelia was carried out at the radiation facility in Malaysian Nuclear Agency. The radiosensitivity study was performed by evaluating the percentage of survival irradiated mycelia. The lethal dose of the mycelium P. sajor-caju was determined at 4.0 kGy and LD{sub 50} to be equal at 2.2 kGy.more » The radiation effects on morphology were evaluated based on growth rate of irradiated mycelia, mycelia types, colonization period on substrate, morphology of fruit bodies and yields. The results shown growth rate of irradiated mycelium was slightly lower than the control and decreased as the dose increased. Irradiation was found can induced the primordia formation on PDA and the BE of irradiated seed is higher than to control. The irradiation is proven to be useful for generating new varieties of mushroom with commercial value to the industry.« less

Influence of irradiation on release of endothelial microparticles (EMP) in vitro.

PubMed

Neuber, Christin; Pufe, Johanna; Pietzsch, Jens

2015-01-01

Survivors of Hodgkin's disease as well as of breast and lung cancer are at risk of radiation-associated cardiovascular disease. Recent studies demonstrated a correlation between cardiovascular risk factors and circulating endothelial microparticles (EMP) and thereby suggest increased EMP levels in circulation to be an early biomarker of endothelial dysfunction and cardiovascular risk. This prompted us to analyze the amount of EMP released by human aortic endothelial cells (HAEC) after exposure to different doses of X-ray (0.4, 2, 4, 6, and 20 Gy) using antibodies against the endothelial cell markers CD31, CD144, and CD146 by flow cytometry. In this pilot experiment only CD146 proved appropriate for quantification of HAEC-derived EMP. Exposure of HAEC to different doses of X-ray did not significantly influence formation of CD146-positive EMP. However, low doses (0.4 Gy) tended to decrease EMP formation, whereas higher doses (2 or 4 Gy) slightly increased release of CD146-positive EMP. By contrast, inflammatory activation of HAEC by TPA significantly increased EMP release about 15-fold (P <  0.01). In conclusion, under the present experimental conditions EMP did not prove a suitable biomarker for radiation-induced endothelial dysfunction in vitro.

Effects of gamma irradiation on physicochemical properties of native and acetylated wheat starches.

PubMed

Kong, Xiangli; Zhou, Xin; Sui, Zhongquan; Bao, Jinsong

2016-10-01

Effects of gamma irradiation on the physicochemical and crystalline properties of the native and acetylated wheat starches were investigated. Peak, hot paste, cool paste and setback viscosities of both native and acetylated wheat starches decreased continuously and significantly with the increase of the irradiation dose, whereas breakdown viscosity increased after irradiation. However, gamma irradiation only exerted slight effects on thermal and retrogradation properties of both native and acetylated wheat starches. X-ray diffraction and fourier transform infrared spectroscopy revealed that acetylation modification had considerable effects on the molecular structure of wheat starch, and the crystallinity of both untreated and acetylated starches increased slightly with the increase of irradiation dose. However, the V-type crystallinity of amylose-lipid complex was not affected by gamma irradiation treatments with doses up to 9kGy. Copyright © 2016 Elsevier B.V. All rights reserved.

A phase 1/2 dose-finding, safety, and activity study of cabazitaxel in pediatric patients with refractory solid tumors including tumors of the central nervous system.

PubMed

Manley, Peter E; Trippett, Tanya; Smith, Amy A; Macy, Margaret E; Leary, Sarah E S; Boklan, Jessica; Cohen, Kenneth J; Goldman, Stewart; Kilburn, Lindsay B; Dhall, Girish; Devin, Jeanne; Herzog, Cynthia E; Partap, Sonia; Fauchet, Floris; Badreddine, Emmy; Bernard, John P; Chi, Susan N

2018-05-11

This phase 1/2 study (NCT01751308) evaluated cabazitaxel in pediatric patients. Phase 1 determined the maximum tolerated dose (MTD) in patients with recurrent/refractory solid tumors, including central nervous system (CNS) tumors. Phase 2 evaluated activity in pediatric recurrent high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). In phase 1, a 3 + 3 dose-escalation study design was followed. Cabazitaxel was administered at a starting dose of 20 mg/m 2 . Dose-limiting toxicities (DLTs) during cycle 1 were assessed to determine the MTD. Tumor response and cabazitaxel pharmacokinetics were also assessed. In phase 2, patients received cabazitaxel at the MTD determined in phase 1. Tumor responses were assessed every 9 weeks (modified Response Assessment in Neuro-oncology criteria). Progression-free survival and cabazitaxel pharmacokinetics were evaluated, and overall survival was estimated. In phase 1, 23 patients were treated, including 19 with CNS tumors. One patient had a partial response; five had stable disease for >3 cycles. Common adverse events included fatigue, diarrhea, nausea and vomiting, febrile neutropenia, and hypersensitivity reactions. Two of three DLTs (febrile neutropenia) occurred with a dose of 35 mg/m 2 ; the MTD was 30 mg/m 2 . Slightly higher cabazitaxel clearance was observed compared with adult trials. In phase 2, 16 patients (eight HGG and eight DIPG) were enrolled; 11 were evaluable for response and five withdrew (three due to anaphylaxis). All 11 patients progressed within four cycles. No responses were observed; the study was stopped due to futility. The safety profile of cabazitaxel was consistent with previous studies. The MTD (30 mg/m 2 ) was higher than the adult MTD. Cabazitaxel did not demonstrate activity in recurrent/refractory HGG or DIPG. © 2018 Wiley Periodicals, Inc.

Preliminary Analysis of the Multisphere Neutron Spectrometer

NASA Technical Reports Server (NTRS)

Goldhagen, P.; Kniss, T.; Wilson, J. W.; Singleterry, R. C.; Jones, I. W.; VanSteveninck, W.

2003-01-01

Crews working on present-day jet aircraft are a large occupationally exposed group with a relatively high average effective dose from galactic cosmic radiation. Crews of future high-speed commercial aircraft flying at higher altitudes would be even more exposed. To help reduce the significant uncertainties in calculations of such exposures, the Atmospheric Ionizing Radiation (AIR) Project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on five flights of a NASA ER-2 high-altitude aircraft. The primary AIR instrument was a highly sensitive extended-energy multisphere neutron spectrometer with lead and steel shells placed within the moderators of two of its 14 detectors to enhance response at high energies. Detector responses were calculated for neutrons and charged hadrons at energies up to 100 GeV using MCNPX. Neutron spectra were unfolded from the measured count rates using the new MAXED code. We have measured the cosmic-ray neutron spectrum (thermal to greater than 10 GeV), total neutron fluence rate, and neutron effective dose and dose equivalent rates and their dependence on altitude and geomagnetic cutoff. The measured cosmic-ray neutron spectra have almost no thermal neutrons, a large "evaporation" peak near 1 MeV and a second broad peak near 100 MeV which contributes about 69% of the neutron effective dose. At high altitude, geomagnetic latitude has very little effect on the shape of the spectrum, but it is the dominant variable affecting neutron fluence rate, which was 8 times higher at the northernmost measurement location than it was at the southernmost. The shape of the spectrum varied only slightly with altitude from 21 km down to 12 km (56 - 201 grams per square centimeter atmospheric depth), but was significantly different on the ground. In all cases, ambient dose equivalent was greater than effective dose for cosmic-ray neutrons.

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings.

PubMed

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg(-1), 50 Bq kg(-1) and 500 Bq kg(-1), respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg(-1), with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h(-1), and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y(-1). For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y(-1) but complies with the upper dose principle of 1 mSv y(-1).

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings

PubMed Central

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg−1, 50 Bq kg−1 and 500 Bq kg−1, respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg-1, with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h–1, and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y–1. For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y-1 but complies with the upper dose principle of 1 mSv y−1. PMID:26473957

Image quality and absorbed dose comparison of single- and dual-source cone-beam computed tomography.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Okazue, Toshiya; Kawakubo, Atsushi; Yamada, Kiyoshi; Nagata, Yasushi

2018-05-01

Dual-source cone-beam computed tomography (DCBCT) is currently available in the Vero4DRT image-guided radiotherapy system. We evaluated the image quality and absorbed dose for DCBCT and compared the values with those for single-source CBCT (SCBCT). Image uniformity, Hounsfield unit (HU) linearity, image contrast, and spatial resolution were evaluated using a Catphan phantom. The rotation angle for acquiring SCBCT and DCBCT images is 215° and 115°, respectively. The image uniformity was calculated using measurements obtained at the center and four peripheral positions. The HUs of seven materials inserted into the phantom were measured to evaluate HU linearity and image contrast. The Catphan phantom was scanned with a conventional CT scanner to measure the reference HU for each material. The spatial resolution was calculated using high-resolution pattern modules. Image quality was analyzed using ImageJ software ver. 1.49. The absorbed dose was measured using a 0.6-cm 3 ionization chamber with a 16-cm-diameter cylindrical phantom, at the center and four peripheral positions of the phantom, and calculated using weighted cone-beam CT dose index (CBCTDI w ). Compared with that of SCBCT, the image uniformity of DCBCT was slightly reduced. A strong linear correlation existed between the measured HU for DCBCT and the reference HU, although the linear regression slope was different from that of the reference HU. DCBCT had poorer image contrast than did SCBCT, particularly with a high-contrast material. There was no significant difference between the spatial resolutions of SCBCT and DCBCT. The absorbed dose for DCBCT was higher than that for SCBCT, because in DCBCT, the two x-ray projections overlap between 45° and 70°. We found that the image quality was poorer and the absorbed dose was higher for DCBCT than for SCBCT in the Vero4DRT. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Toxicokinetics of perfluorooctane sulfonate in rabbits under environmentally realistic exposure conditions and comparative assessment between mammals and birds.

PubMed

Tarazona, J V; Rodríguez, C; Alonso, E; Sáez, M; González, F; San Andrés, M D; Jiménez, B; San Andrés, M I

2016-01-22

This article describes the toxicokinetics of perfluorooctane sulfonate (PFOS) in rabbits under low repeated dosing, equivalent to 0.085μg/kg per day, and the observed differences between rabbits and chickens. The best fitting for both species was provided by a simple pseudo monocompartmental first-order kinetics model, regulated by two rates, and accounting for real elimination as well as binding of PFOS to non-exchangeable structures. Elimination was more rapid in rabbits, with a pseudo first-order dissipation half-life of 88 days compared to the 230 days observed for chickens. By contrast, the calculated assimilation efficiency for rabbits was almost 1, very close to full absorption, significantly higher than the 0.66 with confidence intervals of 0.64 and 0.68 observed for chickens. The results confirm a very different kinetics than that observed in single-dose experiments confirming clear dose-related differences in apparent elimination rates in rabbits, as previously described for humans and other mammals; suggesting the role of a capacity-limited saturable process resulting in different kinetic behaviours for PFOS in high dose versus environmentally relevant low dose exposure conditions. The model calculations confirmed that the measured maximum concentrations were still far from the steady state situation, and that the different kinetics between birds and mammals should may play a significant role in the biomagnifications assessment and potential exposure for humans and predators. For the same dose regime, the steady state concentration was estimated at about 36μg PFOS/L serum for rabbits, slightly above one-half of the 65μg PFOS/L serum estimated for chickens. The toxicokinetic parameters presented here can be used for higher-tier bioaccumulation estimations of PFOS in rabbits and chickens as starting point for human health exposure assessments and as surrogate values for modeling PFOS kinetics in wild mammals and bird in exposure assessment of predatory species. Published by Elsevier Ireland Ltd.

Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children.

PubMed

Esposito, Susanna; Giavoli, Claudia; Trombetta, Claudia; Bianchini, Sonia; Montinaro, Valentina; Spada, Anna; Montomoli, Emanuele; Principi, Nicola

2016-01-02

Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p<0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p<0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p<0.01 for GMT values and p<0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of magnesium sulfate on airway smooth muscle contraction in rats.

PubMed

Betul Altinisik, Hatice; Kirdemir, Pakize; Altinisik, Ugur; Gokalp, Osman

2016-08-01

Aim To investigate the effect of magnesium sulfate (MgSO4) at different doses on isolated tracheal smooth muscle contraction in rats induced by different mechanisms. Methods Twelve rats' tracheas were placed into organ bath. Consecutively, acetylcholine (10-6,10-5,10-4 M), histamine(10-8,10-5,10-3 M) and KCl (30,60 mM) solutions was administered for contractions. MgSO4 from 10-4 to 10-1 M concentrations were subsequently administered after each constrictive agent and relaxation degrees were recorded. Results In the acetylcholine and KCl groups, dose dependent strong contractions were observed, but not in the histamine group and that group was excluded. Significant relaxation occurred with gradually increasing doses of MgSO4. In the high dose KCl group, a slight increase in contractions after the administration of 10-4 and 10-3 M MgSO4 was recorded. Conclusion We suggest that MgSO4 is effective in relaxing airway smooth muscle contractions caused by different factors; however, it must be considered that low doses of MgSO4 may only lead to a slight increase in contractions. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Effect of respiratory motion on internal radiation dosimetry

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

Xie, Tianwu; Zaidi, Habib, E-mail: habib.zaidi@hcuge.ch; Geneva Neuroscience Center, Geneva University, Geneva CH-1205

Purpose: Estimation of the radiation dose to internal organs is essential for the assessment of radiation risks and benefits to patients undergoing diagnostic and therapeutic nuclear medicine procedures including PET. Respiratory motion induces notable internal organ displacement, which influences the absorbed dose for external exposure to radiation. However, to their knowledge, the effect of respiratory motion on internal radiation dosimetry has never been reported before. Methods: Thirteen computational models representing the adult male at different respiratory phases corresponding to the normal respiratory cycle were generated from the 4D dynamic XCAT phantom. Monte Carlo calculations were performed using the MCNP transportmore » code to estimate the specific absorbed fractions (SAFs) of monoenergetic photons/electrons, the S-values of common positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y-86, and I-124), and the absorbed dose of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) in 28 target regions for both the static (average of dynamic frames) and dynamic phantoms. Results: The self-absorbed dose for most organs/tissues is only slightly influenced by respiratory motion. However, for the lung, the self-absorbed SAF is about 11.5% higher at the peak exhale phase than the peak inhale phase for photon energies above 50 keV. The cross-absorbed dose is obviously affected by respiratory motion for many combinations of source-target pairs. The cross-absorbed S-values for the heart contents irradiating the lung are about 7.5% higher in the peak exhale phase than the peak inhale phase for different positron-emitting radionuclides. For {sup 18}F-FDG, organ absorbed doses are less influenced by respiratory motion. Conclusions: Respiration-induced volume variations of the lungs and the repositioning of internal organs affect the self-absorbed dose of the lungs and cross-absorbed dose between organs in internal radiation dosimetry. The dynamic anatomical model provides more accurate internal radiation dosimetry estimates for the lungs and abdominal organs based on realistic modeling of respiratory motion. This work also contributes to a better understanding of model-induced uncertainties in internal radiation dosimetry.« less

Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations

NASA Astrophysics Data System (ADS)

Nogueira, P.; Zankl, M.; Schlattl, H.; Vaz, P.

2011-11-01

The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation—the germinative cells—absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV.

Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations.

PubMed

Nogueira, P; Zankl, M; Schlattl, H; Vaz, P

2011-11-07

The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation-the germinative cells-absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV.

High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

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

Yin Jiangmei; Dai Anlan; Laddy, Dominick J.

2009-10-10

Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhancedmore » the production of IFN-gamma (0.5 mg) and the proliferation of CD4{sup +} and CD8{sup +} T cells, as well as T{sub CM} levels in proliferating CD8{sup +} T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-gamma and the proliferation of CD4{sup +} and CD8{sup +} T cells and T{sub CM} levels in the proliferating CD4{sup +} and CD8{sup +} T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.« less

The effects of 19-nor-aldosterone on blood pressure of adrenalectomized spontaneously hypertensive rats.

PubMed

Morris, D J; Gorsline, J; Tresco, P A; Harnik, M

1985-12-01

The relative hypertensinogenic potencies of recently synthesized 19-nor-aldosterone and its precursor 19-OH-aldosterone were assessed in comparison to that of aldosterone (Aldo) in young (6-week-old) adrenalectomized (ADX) spontaneously hypertensive rats (SHR). Infusion of 19-nor-aldosterone for 2 weeks by Alza mini-osmotic pumps caused significant, dose-dependent increases in the systolic blood pressure (BP) of young ADX SHR; dosages of 0.1 and 0.5 microgram/day raised the BP from 127 +/- 2 mmHg to 164 +/- 9 and 180 +/- 11 mmHg, respectively. During this period, control ADX SHR receiving vehicle only remained normotensive. Similar increases in BP were seen only with infusion of slightly higher dosages of Aldo (0.5 and 1.0 micrograms/day). In contrast, 19-OH-aldosterone infused at higher dosages (10 or 25 micrograms/day) caused little change in BP of ADX SHR. Full suppression of plasma renin activity (PRA) was observed with 0.1 and 0.5 microgram/day 19-nor-aldosterone, whereas Aldo caused similar decreases in PRA only at dosages of 0.5 microgram/day and higher. Interestingly, although infusions of 19-OH-aldosterone did not cause a significant change in BP, these dosages (10 and 25 micrograms/day) significantly suppressed PRA. These studies which show that 19-nor-aldosterone is equipotent to Aldo, and perhaps slightly more active in ADX SHR, indicate that 19-nor-aldosterone is a potentially important hypertensinogenic steroid.

SU-F-T-562: Validation of EPID-Based Dosimetry for FSRS Commissioning

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

Song, Y; Saleh, Z; Obcemea, C

Purpose: The prevailing approach to frameless SRS (fSRS) small field dosimetry is Gafchromic film. Though providing continuous information, its intrinsic uncertainties in fabrication, response, scan, and calibration often make film dosimetry subject to different interpretations. In this study, we explored the feasibility of using EPID portal dosimetry as a viable alternative to film for small field dosimetry. Methods: Plans prescribed a dose of 21 Gy were created on a flat solid water phantom with Eclipse V11 and iPlan for small static square fields (1.0 to 3.0 cm). In addition, two clinical test plans were computed by employing iPlan on amore » CIRS Kesler head phantom for target dimensions of 1.2cm and 2.0cm. Corresponding portal dosimetry plans were computed using the Eclipse TPS and delivered on a Varian TrueBeam machine. EBT-XD film dosimetry was performed as a reference. The isocenter doses were measured using EPID, OSLD, stereotactic diode, and CC01 ion chamber. Results: EPID doses at the center of the square field were higher than Eclipse TPS predicted portal doses, with the mean difference being 2.42±0.65%. Doses measured by EBT-XD film, OSLD, stereotactic diode, and CC01 ion chamber revealed smaller differences (except OSLDs), with mean differences being 0.36±3.11%, 4.12±4.13%, 1.7±2.76%, 1.45±2.37% for Eclipse and −1.36±0.85%, 2.38±4.2%, −0.03±0.50%, −0.27±0.78% for iPlan. The profiles measured by EPID and EBT-XD film resembled TPS (Eclipse and iPlan) predicted ones within 3.0%. For the two clinical test plans, the EPID mean doses at the center of field were 2.66±0.68% and 2.33±0.32% higher than TPS predicted doses. Conclusion: We found that results obtained with EPID portal dosimetry were slightly higher (∼2%) than those obtained with EBT-XD film, diode, and CC01 ion chamber with the exception of OSLDs, but well within IROC tolerance (5.0%). Therefore, EPID has the potential to become a viable real-time alternative method to film dosimetry.« less

Ultrasound pretreatment of filamentous algal biomass for enhanced biogas production.

PubMed

Lee, Kwanyong; Chantrasakdakul, Phrompol; Kim, Daegi; Kong, Mingeun; Park, Ki Young

2014-06-01

The filamentous alga Hydrodictyon reticulatum harvested from a bench-scale wastewater treatment pond was used to evaluate biogas production after ultrasound pretreatment. The effects of ultrasound pretreatment at a range of 10-5000 J/mL were tested with harvested H. reticulatum. Cell disruption by ultrasound was successful and showed a higher degree of disintegration at a higher applied energy. The range of 10-5000 J/mL ultrasound was able to disintegrated H. reticulatum and the soluble COD was increased from 250 mg/L to 1000 mg/L at 2500 J/mL. The disintegrated algal biomass was digested for biogas production in batch experiments. Both cumulative gas generation and volatile solids reduction data were obtained during the digestion. Cell disintegration due to ultrasound pretreatment increased the specific biogas production and degradation rates. Using the ultrasound approach, the specific methane production at a dose of 40 J/mL increased up to 384 mL/g-VS fed that was 2.3 times higher than the untreated sample. For disintegrated samples, the volatile solids reduction was greater with increased energy input, and the degradation increased slightly to 67% at a dose of 50 J/mL. The results also indicate that disintegration of the algal cells is the essential step for efficient anaerobic digestion of algal biomass. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gamma irradiation induced effects of butyl rubber based damping material

NASA Astrophysics Data System (ADS)

Chen, Hong-Bing; Wang, Pu-Cheng; Liu, Bo; Zhang, Feng-Shun; Ao, Yin-Yong

2018-04-01

The effects of gamma irradiation on the butyl rubber based damping material (BRP) at various doses in nitrogen were investigated in this study. The results show that irradiation leads to radiolysis of BRP, with extractives increasing from 14.9 ± 0.8% of control to 37.2 ± 1.2% of sample irradiated at 350 kGy, while the swelling ratio increasing from 294 ± 3% to 766 ± 4%. The further investigation of the extractives with FTIR shows that the newly generated extractives are organic compounds containing C-H and C˭C bonds, with molecular weight ranging from 26,500 to 46,300. SEM characterization shows smoother surface with holes disappearing with increasing absorbed doses, consistent with "softer" material because of radiolysis. Dynamic mechanical study of BRP show that tan δ first slightly then obviously increases with increasing absorbed dose, while storage modulus slightly decreases. The tensile testing shows that the tensile strength decreases while the elongation at break increases with increasing dose. The positron annihilation lifetime spectroscopy show no obvious relations between free volume parameters and the damping properties, indicating the complicated influencing factors of damping properties.

Pharmacology of RG W-2938: a cardiotonic agent with vasodilator activity.

PubMed

Barrett, J A; Woltmann, R F; Swillo, R S; Kasiewski, C; Faith, W C; Campbell, H F; Perrone, M H

1990-10-01

The cardiovascular effects of RG W-2938, 6-[6-(3,4-dihydro-3-methyl-2(1H)-2-oxoquinazolinyl)]-4,5-dihydro-3 (2H-pyridazinone, a new nonglycoside, noncatecholamine cardiotonic/vasodilator agent were examined in vivo in anesthetized and conscious dogs and in vitro in isolated guinea pig hearts; in the latter, RG W-2938 5 nmol-5 mumol increased contractility in a dose-related fashion. RG W-2938 30-300 micrograms/kg administered intravenously (i.v.) to anesthetized dogs increased contractile force while decreasing arterial pressure and total peripheral resistance (TPR) in a dose-related manner. Heart rate (HR) was only slightly increased, and aortic flow was not appreciably altered. A single oral dose of RG W-2938 0.3 mg/kg administered to conscious chronically instrumented dogs produced a marked and sustained increase in contractility 15-240 min after treatment while only slightly increasing HR. The effects of RG W-2938 30-300 micrograms/kg, i.v. were studied in a mecamylamine-propranolol-induced model of heart failure. RG W-2938 effectively reversed the drug-induced heart failure by increasing myocardial contractility and decreasing arterial pressure while only slightly affecting HR. These studies show that RG W-2938 is an orally effective positive inotropic/vasodilator agent.

Costs Associated With Intravenous Darbepoetin Versus Epoetin Therapy in Hemodialysis Patients: A Randomized Controlled Trial

PubMed Central

Woodland, Andrea L.; Murphy, Sean W.; Curtis, Bryan M.; Barrett, Brendan J.

2017-01-01

Background: Anemia of chronic kidney disease is associated with adverse outcomes and a reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have improved anemia management, and 2 agents are available in Canada, epoetin alfa (EPO) and darbepoetin alfa (DA). EPO and DA are considered equally effective in achieving target hemoglobin (Hb), but it is not clear whether there is a cost difference. There have been few head-to-head comparisons; most published studies are observational switch studies. Objective: To compare the cost of DA and EPO and to determine the dose conversion ratio over a 12-month period. Design: Randomized controlled trial. Setting: Canadian outpatient hemodialysis center. Patients: Eligible patients were adult hemodialysis patients requiring ESA therapy. Measurements: The primary outcome was ESA cost (Can$) per patient over 12 months. Secondary outcomes included the dose conversion ratio, deviation from target ranges in anemia indices, iron dose and cost, and time and number of dose changes. Methods: An open-label randomized controlled trial of intravenous (IV) DA versus EPO was conducted in 50 hemodialysis patients. Participants underwent a minimum 6-week run-in phase followed by a 12-month active study phase. ESA and iron were dosed using a study algorithm. Results: The median cost was $4179 (interquartile range [IQR]: $2416-$5955) for EPO and $2303 (IQR: $1178-$4219) for DA with a difference of $1876 (P = .02). The dose conversion ratio was 280:1 (95% confidence interval [CI]: 197-362:1) at the end of the run-in phase, 360:1 (95% CI: 262-457:1) at the 3-month point of the active phase, and 382:1 (95% CI: 235-529:1) at the 6-month point of the active phase. There were no significant differences between the 2 groups in weekly iron dose, Hb, serum ferritin, or transferrin saturation. The number of dose changes and the time to Hb stability were similar. Limitations: Results may not be generalizable to hemodialysis units without algorithm-based anemia management, with subcutaneous ESA administration, or to the nondialysis chronic kidney disease population. The effective conversion ratio between EPO and DA is known to increase at higher doses; the Hb targets used in the study were slightly higher than those recommended today so it is possible that the doses used were also higher. Because of this, the cost savings estimated for DA could differ somewhat from the savings realizable in current practice. Conclusions: In this study of hemodialysis patients with comparable anemia management, IV DA cost $1876 less per year per patient than IV EPO. The dose conversion ratio was greater than 350:1 by the 3-month point. Trial registration: ClinicalTrials.gov (NCT02817555). PMID:28717516

A new warfarin dosing algorithm including VKORC1 3730 G > A polymorphism: comparison with results obtained by other published algorithms.

PubMed

Cini, Michela; Legnani, Cristina; Cosmi, Benilde; Guazzaloca, Giuliana; Valdrè, Lelia; Frascaro, Mirella; Palareti, Gualtiero

2012-08-01

Warfarin dosing is affected by clinical and genetic variants, but the contribution of the genotype associated with warfarin resistance in pharmacogenetic algorithms has not been well assessed yet. We developed a new dosing algorithm including polymorphisms associated both with warfarin sensitivity and resistance in the Italian population, and its performance was compared with those of eight previously published algorithms. Clinical and genetic data (CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, and VKORC1 3730 G > A) were used to elaborate the new algorithm. Derivation and validation groups comprised 55 (58.2% men, mean age 69 years) and 40 (57.5% men, mean age 70 years) patients, respectively, who were on stable anticoagulation therapy for at least 3 months with different oral anticoagulation therapy (OAT) indications. Performance of the new algorithm, evaluated with mean absolute error (MAE) defined as the absolute value of the difference between observed daily maintenance dose and predicted daily dose, correlation with the observed dose and R(2) value, was comparable with or slightly lower than that obtained using the other algorithms. The new algorithm could correctly assign 53.3%, 50.0%, and 57.1% of patients to the low (≤25 mg/week), intermediate (26-44 mg/week) and high (≥ 45 mg/week) dosing range, respectively. Our data showed a significant increase in predictive accuracy among patients requiring high warfarin dose compared with the other algorithms (ranging from 0% to 28.6%). The algorithm including VKORC1 3730 G > A, associated with warfarin resistance, allowed a more accurate identification of resistant patients who require higher warfarin dosage.

Effects of sterilisation by high-energy radiation on biomedical poly-(epsilon-caprolactone)/hydroxyapatite composites.

PubMed

Di Foggia, Michele; Corda, Ugo; Plescia, Elena; Taddei, Paola; Torreggiani, Armida

2010-06-01

The effects of a high energy sterilization treatment on poly-epsilon-caprolactone/carbonated hydroxyapatite composites have been investigated. Poly-epsilon-caprolactone is a biodegradable polymer used as long-term bioresorbable scaffold for bone tissue engineering and carbonated hydroxyapatite is a bioactive material able to promote bone growth. The composites were gamma-irradiated in air or under nitrogen atmosphere with doses ranging from 10 to 50 kGy (i.e. to a value higher than that recommended for sterilization). The effects of the irradiation treatment were evaluated by vibrational spectroscopy (IR and Raman spectroscopies) coupled to thermal analysis (Differential Scanning Calorimetry and Thermogravimetry) and Electron Paramagnetic Resonance spectroscopy. Irradiation with the doses required for sterilization induced acceptable structural changes and damaging effects: only a very slight fragmentation of the polymeric chains and some defects in the inorganic component were observed. Moreover, the radiation sensitivity of the composites proved almost the same under the two different atmospheres.

Phenanthrene binding by humic acid-protein complexes as studied by passive dosing technique.

PubMed

Zhao, Jian; Wang, Zhenyu; Ghosh, Saikat; Xing, Baoshan

2014-01-01

This work investigated the binding behavior of phenanthrene by humic acids (HA-2 and HA-5), proteins (bovine serum albumin (BSA)), lysozyme and pepsin), and their complexes using a passive dosing technique. All sorption isotherms were fitted well with Freundlich model and the binding capability followed an order of HA-5 > HA-2 > BSA > pepsin > lysozyme. In NaCl solution, phenanthrene binding to HA-BSA complexes was much higher than the sum of binding to individual HA and BSA, while there was no enhancement for HA-pepsin. Positively charged lysozyme slightly lowered phenanthrene binding on both HAs due to strong aggregation of HA-lysozyme complexes, leading to reduction in the number of binding sites. The binding enhancement by HA-BSA was observed under all tested ion species and ionic strengths. This enhancement can be explained by unfolding of protein, reduction of aggregate size and formation of HA-BSA complexes with favorable conformations for binding phenanthrene. Copyright © 2013 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new "B2" configuration of the RA-6 nuclear reactor.

PubMed

Monti Hughes, Andrea; Longhino, Juan; Boggio, Esteban; Medina, Vanina A; Martinel Lamas, Diego J; Garabalino, Marcela A; Heber, Elisa M; Pozzi, Emiliano C C; Itoiz, María E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2017-11-01

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in "B1" experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the "B1" results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.

Genotoxic effects of high-energy iron particles in human lymphoblasts differing in radiation sensitivity

NASA Technical Reports Server (NTRS)

Evans, H. H.; Horng, M. F.; Evans, T. E.; Jordan, R.; Schwartz, J. L.

2001-01-01

The effects of (56)Fe particles and (137)Cs gamma radiation were compared in TK6 and WTK1 human lymphoblasts, two related cell lines which differ in TP53 status and in the ability to rejoin DNA double-strand breaks. Both cell lines were more sensitive to the cytotoxic and clastogenic effects of (56)Fe particles than to those of gamma rays. However, the mutagenicity of (56)Fe particles and gamma rays at the TK locus was the same per unit dose and was higher for gamma rays than for (56)Fe particles at isotoxic doses. The respective RBEs for TK6 and WTK1 cells were 1.5 and 1.9 for cytotoxicity and 2.5 and 1.9 for clastogenicity, but only 1 for mutagenicity. The results indicate that complex lesions induced by (56)Fe particles are repaired less efficiently than gamma-ray-induced lesions, leading to fewer colony-forming cells, a slightly higher proportion of aberrant cells at the first division, and a lower frequency of viable mutants at isotoxic doses. WTK1 cells (mutant TP53) were more resistant to the cytotoxic effects of both gamma rays and (56)Fe particles, but showed greater cytogenetic and mutagenic damage than TK6 cells (TP53(+)). A deficiency in the number of damaged TK6 cells (a) reaching the first mitosis after exposure and (b) forming viable mutants can explain these results.

An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat.

PubMed

Mitchell, J M; Mengs, U; McPherson, S; Zijlstra, J; Dettmar, P; Gregson, R; Tigner, J C

2006-01-01

Senna (Tinnevelly senna fruits), a known laxative derived from plants, was administered by gavage to Sprague-Dawley (Crl:CD (SD) BR) rats once daily at dose levels of 0, 25, 100 and 300 mg/kg/day for up to 104 consecutive weeks. Based upon clinical signs related to the laxation effect of senna, the highest dose (300 mg/kg/day) was considered to be a maximum tolerated dose. Sixty animals per sex were assigned to the control and dose groups. Assessments included clinical chemistry, hematology, full histology (control and high-dose groups; in addition, low and mid dose: intestinal tract, adrenals, liver, kidneys, brain and gross lesions) and toxicokinetics. The primary treatment-related clinical observation was mucoid feces seen at 300 mg/kg/day. When compared to controls, animals administered 300 mg/kg/day had slightly reduced body weights, increased water consumption and notable changes in electrolytes in serum (increases in potassium and chloride) and urine (decreases in sodium, potassium and chloride). The changes in electrolytes are most likely physiologic adaptations to the laxative effect of senna. At necropsy, dark discoloration of the kidneys was observed in animals in all treated groups. Histological changes were seen in the kidneys of animals from all treated groups and included slight to moderate tubular basophilia and tubular pigment deposits. In addition, for all treated groups, minimal to slight hyperplasia was evident in the colon and cecum. These histological changes, together with the changes seen in the evaluation of clinical chemistry and urine parameters, have been shown to be reversible in a previous 13-week rat study of senna. No treatment-related neoplastic changes were observed in any of the examined organs. Based upon these data, it is concluded that senna is not carcinogenic even after daily administration for 2 years at dosages of up to 300 mg/kg/day in Sprague-Dawley rats.

Measurements of neutron dose equivalent for a proton therapy center using uniform scanning proton beams

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

Zheng Yuanshui; Liu Yaxi; Zeidan, Omar

Purpose: Neutron exposure is of concern in proton therapy, and varies with beam delivery technique, nozzle design, and treatment conditions. Uniform scanning is an emerging treatment technique in proton therapy, but neutron exposure for this technique has not been fully studied. The purpose of this study is to investigate the neutron dose equivalent per therapeutic dose, H/D, under various treatment conditions for uniform scanning beams employed at our proton therapy center. Methods: Using a wide energy neutron dose equivalent detector (SWENDI-II, ThermoScientific, MA), the authors measured H/D at 50 cm lateral to the isocenter as a function of proton range,more » modulation width, beam scanning area, collimated field size, and snout position. They also studied the influence of other factors on neutron dose equivalent, such as aperture material, the presence of a compensator, and measurement locations. They measured H/D for various treatment sites using patient-specific treatment parameters. Finally, they compared H/D values for various beam delivery techniques at various facilities under similar conditions. Results: H/D increased rapidly with proton range and modulation width, varying from about 0.2 mSv/Gy for a 5 cm range and 2 cm modulation width beam to 2.7 mSv/Gy for a 30 cm range and 30 cm modulation width beam when 18 Multiplication-Sign 18 cm{sup 2} uniform scanning beams were used. H/D increased linearly with the beam scanning area, and decreased slowly with aperture size and snout retraction. The presence of a compensator reduced the H/D slightly compared with that without a compensator present. Aperture material and compensator material also have an influence on neutron dose equivalent, but the influence is relatively small. H/D varied from about 0.5 mSv/Gy for a brain tumor treatment to about 3.5 mSv/Gy for a pelvic case. Conclusions: This study presents H/D as a function of various treatment parameters for uniform scanning proton beams. For similar treatment conditions, the H/D value per uncollimated beam size for uniform scanning beams was slightly lower than that from a passive scattering beam and higher than that from a pencil beam scanning beam, within a factor of 2. Minimizing beam scanning area could effectively reduce neutron dose equivalent for uniform scanning beams, down to the level close to pencil beam scanning.« less

Adaptive Iterative Dose Reduction Using Three Dimensional Processing (AIDR3D) improves chest CT image quality and reduces radiation exposure.

PubMed

Yamashiro, Tsuneo; Miyara, Tetsuhiro; Honda, Osamu; Kamiya, Hisashi; Murata, Kiyoshi; Ohno, Yoshiharu; Tomiyama, Noriyuki; Moriya, Hiroshi; Koyama, Mitsuhiro; Noma, Satoshi; Kamiya, Ayano; Tanaka, Yuko; Murayama, Sadayuki

2014-01-01

To assess the advantages of Adaptive Iterative Dose Reduction using Three Dimensional Processing (AIDR3D) for image quality improvement and dose reduction for chest computed tomography (CT). Institutional Review Boards approved this study and informed consent was obtained. Eighty-eight subjects underwent chest CT at five institutions using identical scanners and protocols. During a single visit, each subject was scanned using different tube currents: 240, 120, and 60 mA. Scan data were converted to images using AIDR3D and a conventional reconstruction mode (without AIDR3D). Using a 5-point scale from 1 (non-diagnostic) to 5 (excellent), three blinded observers independently evaluated image quality for three lung zones, four patterns of lung disease (nodule/mass, emphysema, bronchiolitis, and diffuse lung disease), and three mediastinal measurements (small structure visibility, streak artifacts, and shoulder artifacts). Differences in these scores were assessed by Scheffe's test. At each tube current, scans using AIDR3D had higher scores than those without AIDR3D, which were significant for lung zones (p<0.0001) and all mediastinal measurements (p<0.01). For lung diseases, significant improvements with AIDR3D were frequently observed at 120 and 60 mA. Scans with AIDR3D at 120 mA had significantly higher scores than those without AIDR3D at 240 mA for lung zones and mediastinal streak artifacts (p<0.0001), and slightly higher or equal scores for all other measurements. Scans with AIDR3D at 60 mA were also judged superior or equivalent to those without AIDR3D at 120 mA. For chest CT, AIDR3D provides better image quality and can reduce radiation exposure by 50%.

Values of (99m)Tc-methoxyisobutylisonitrile imaging after first-time large-dose (131)I therapy in treating differentiated thyroid cancer.

PubMed

Pan, Xiaomei; Duan, Dong; Zhu, Yuquan; Pang, Hua; Guan, Lili; Lv, Zhixiang

2016-01-01

The aim of this study is to investigate the use of (99m)Tc-methoxyisobutylisonitrile (MIBI) imaging for evaluating the treatment response of differentiated thyroid cancer (DTC) after the first administration of a high dose of (131)I. Patients with DTC who received (131)I therapy underwent (99m)Tc-MIBI imaging after successive increases in the therapeutic dose of (131)I, and the serum levels of thyroglobulin (Tg) were measured. A total of 191 patients were enrolled in the final analysis, including 65 metastases and/or thyroid remnant-positive patients (22 patients with metastases and 43 patients with thyroid remnants). The sensitivity of (99m)Tc-MIBI imaging for detecting positive cases and thyroid remnants was 56.9% and 39.5%, respectively, which was significantly lower than that of (131)I imaging (92.3% and 100%, respectively, P<0.01 for both). The sensitivity of (99m)Tc-MIBI imaging for detecting metastases was 90.9%, which was slightly higher than that of (131)I imaging (77.3%, P>0.05). The Tg levels in the positive group were significantly higher than that in the negative group (P<0.01). In addition, the Tg levels in the (99m)Tc-MIBI(+)/(131)I(-) group were significantly higher than that in the (131)I(+)/(99m)Tc-MIBI group (P<0.05). After the first (131)I therapy, although (99m)Tc-MIBI imaging was able to detect the existence of metastatic lesions in patients with DTC better, its assessment for the removal efficiency of thyroid remnants was unsatisfactory. The results of (99m)Tc-MIBI imaging showed good correlations with the Tg level.

Limited ability of DNA polymerase kappa to suppress benzo[a]pyrene-induced genotoxicity in vivo.

PubMed

Masumura, Kenichi; Toyoda-Hokaiwado, Naomi; Niimi, Naoko; Grúz, Petr; Wada, Naoko A; Takeiri, Akira; Jishage, Kou-Ichi; Mishima, Masayuki; Nohmi, Takehiko

2017-12-01

DNA polymerase kappa (Polk) is a specialized DNA polymerase involved in translesion DNA synthesis. To understand the protective roles against genotoxins in vivo, we established inactivated Polk knock-in gpt delta (inactivated Polk KI) mice that possessed reporter genes for mutations and expressed inactive Polk. In this study, we examined genotoxicity of benzo[a]pyrene (BP) to determine whether Polk actually suppressed BP-induced genotoxicity as predicted by biochemistry and in vitro cell culture studies. Seven-week-old inactivated Polk KI and wild-type (WT) mice were treated with BP at doses of 5, 15, or 50 mg/(kg·day) for three consecutive days by intragastric gavage, and mutations in the colon and micronucleus formation in the peripheral blood were examined. Surprisingly, no differences were observed in the frequencies of mutations and micronucleus formation at 5 or 50 mg/kg doses. Inactivated Polk KI mice exhibited approximately two times higher gpt mutant frequency than did WT mice only at the 15 mg/kg dose. The frequency of micronucleus formation was slightly higher in inactivated Polk KI than in WT mice at the same dose, but it was statistically insignificant. The results suggest that Polk has a limited ability to suppress BP-induced genotoxicity in the colon and bone marrow and also that the roles of specialized DNA polymerases in mutagenesis and carcinogenesis should be examined not only by in vitro assays but also by in vivo mouse studies. We also report the spontaneous mutagenesis in inactivated Polk KI mice at young and old ages. Environ. Mol. Mutagen. 58:644-653, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2013-12-01

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

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

PubMed

Valk, B I; Absalom, A R; Meyer, P; Meier, S; den Daas, I; van Amsterdam, K; Campagna, J A; Sweeney, S P; Struys, M M R F

2018-06-01

Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg -1  min -1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. NTR4735. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

SU-E-T-645: Dose Enhancement to Cell Nucleus Due to Hard Collisions of Protons with Electrons in Gold Nanospheres

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

Eley, J; Krishnan, S

2014-06-15

Purpose: The purpose of this study was to investigate the theoretical dose enhancement to a cell nucleus due to increased fluence of secondary electrons when gold nanospheres are present in the cytoplasm during proton therapy. Methods: We modeled the irradiation of prostate cancer cells using protons of variable energies when 10,000 gold nanoparticles, each with radius of 10 nm, were randomly distributed in the cytoplasm. Using simple analytical equations, we calculated the increased mean dose to the cell nucleus due to secondary electrons produced by hard collisions of 0.1, 1, 10, and 100 MeV protons with orbital electrons in gold.more » We only counted electrons with kinetic energy higher than 1 keV. In addition to calculating the increase in the mean dose to the cell nucleus, we also calculated the increase in local dose in the “shadow,” i.e., the umbra, of individual gold nanospheres due to forward scattered electrons. Results: For proton energies of 0.1, 1, 10, and 100 MeV, we calculated increases to the mean nuclear dose of 0.15, 0.09, 0.05, and 0.04%, respectively. When we considered local dose increases in the shadows of individual gold spheres, we calculated local dose increases of 5.5, 3.2, 1.9, and 1.3%, respectively. Conclusion: We found negligible, less than 0.2%, increases in the mean dose to the cell nucleus due to electrons produced by hard collisions of protons with electrons in gold nanospheres. However, we observed increases up to 5.5% in the local dose in the shadow of gold nanospheres. Considering the shadow radius of 10 nm, these local dose enhancements may have implications for slightly increased probability of clustered DNA damage when gold nanoparticles are close to the nuclear membrane.« less

Racial and ethnic disparities in end-stage kidney failure-survival paradoxes in African-Americans.

PubMed

Agodoa, Lawrence; Eggers, Paul

2007-01-01

The risk of death is nearly 45% lower in African-Americans than Caucasians undergoing chronic hemodialysis. In light of the higher mortality rate in African-Americans in the general US population, this paradox requires explanation and further investigation. Factors that may contribute to this survival advantage include a younger age at which African-Americans arrive at end-stage renal disease (ESRD) and the slightly higher body mass index. On the other hand, factors, such as lower residual renal function, lower mean hemoglobin and hematocrit, increased prevalence of hypertension, a higher prevalence of catheter use for initial dialysis, and generally lower dose of dialysis should put African-Americans on dialysis at a higher risk of death. This survival advantage seems to be completely annulled with a successful renal transplant. Finally, it should be noted that ESRD carries with it a very high mortality rate in all racial and ethnic groups. A successful renal transplant improves but does not restore the expected remaining life times. Therefore, aggressive approach is required in investigating the factors that confer such high mortality risk on ESRD patients.

SU-G-TeP4-02: A Method for Evaluating the Direct Impact of Failed IMRT QAs On Patient Dose

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

Geneser, S; Butkus, M

Purpose: We developed a method to calculate patient doses corresponding to IMRT QA measurements in order to determine and assess the actual dose delivered for plans with failed (or borderline) IMRT QA. This work demonstrates the feasibility of automatically computing delivered patient dose from portal dosimetry measurements in the Varian TPS system, which would provide a valuable and clinically viable IMRT QA tool for physicists and physicians. Methods: IMRT QA fluences were measured using portal dosimetry, processed using in-house matlab software, and imported back into Eclipse to calculate dose on the planning CT. To validate the proposed workflow, the Eclipsemore » calculated portal dose for a 5-field sliding window prostate boost plan was processed as described above. The resulting dose was compared to the planned dose and found to be within 0.5 Gy. Two IMRT QA results for the prostate boost plan (one that failed and one that passed) were processed and the resulting patient doses were evaluated. Results: The max dose difference between IMRT QA #1 and the original planned and approved dose is 4.5 Gy, while the difference between the planned and IMRT QA #2 dose is 4.0 Gy. The inferior portion of the PTV is slightly underdosed in both plans, and the superior portion is slightly overdosed. The patient dose resulting from IMRT QA #1 and #2 differs by only 0.5 Gy. With this new information, it may be argued that the evaluated plan alteration to obtain passing gamma analysis produced clinically irrelevant differences. Conclusion: Evaluation of the delivered QA dose on the planning CT provides valuable information about the clinical relevance of failed or borderline IMRT QAs. This particular workflow demonstrates the feasibility of pushing the measured IMRT QA portal dosimetry results directly back onto the patient planning CT within the Varian system.« less

SU-E-P-14: Dosimetric Effects of Magnetic Field in MRI-Guided Radiation Therapy Delivery for Breast Cancer

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

Chen, G; Currey, A; Li, X

2015-06-15

Purpose: MRI-guided radiation therapy (RT) delivery would be beneficial for breast irradiation. The electron return effect due to the presence of a transverse magnetic field (TMF) may cause dosimetric issues on dose on skin and at the lung-tissue interface. The purpose of this study is to investigate these issues. Methods: IMRT plans with tangential beams and VMAT plans with 200 degree arcs to cover ipsilateral breast were generated for 10 randomly selected breast cancer cases using a research planning system (Monaco, Elekta) utilizing Monte Carlo dose calculation with or without a TMF of 1.5 T. Plans were optimized to delivermore » uniform dose to the whole breast with an exclusion of 5 mm tissue under the skin (PTV-EVAL). All four plans for each patient were re-scaled to have the same PTV-EVAL volume to receive the same prescription dose. The skin is defined as the first 5 mm of ipsilateral-breast tissue, plus extensions in the surrounding region. Results: The presence of 1.5 T TMF resulted in (1)increased skin dose, with the mean and maximum skin dose increase of 5% and 9%, respectively; (2) similar dose homogeneity within the PTV-EVAL; (3) the slightly improved (3%) dose homogeneity in the whole breast; (4) Averages of 9 and 16% increases in V5 and V20, respectively, for ipsilateral lung; and (5) increased the mean heart dose by 34%. VMAT plans don’t improve whole breast dose uniformity as compared that to the tangential plans. Conclusion: The presence of transverse magnetic field in MRI-guided RT delivery for whole breast irradiation can Result in slightly improved dose homogeneity in the whole breast, increased dose to the ipsilateral lung, heart, and skin. Plan optimization with additional specific dose volume constraints may eliminate/reduce these dose increases. This work is partially supported by Elekta Inc.« less

Role of shielding in modulating the effects of solar particle events: Monte Carlo calculation of absorbed dose and DNA complex lesions in different organs

NASA Technical Reports Server (NTRS)

Ballarini, F.; Biaggi, M.; De Biaggi, L.; Ferrari, A.; Ottolenghi, A.; Panzarasa, A.; Paretzke, H. G.; Pelliccioni, M.; Sala, P.; Scannicchio, D.;

Role of shielding in modulating the effects of solar particle events: Monte Carlo calculation of absorbed dose and DNA complex lesions in different organs

NASA Astrophysics Data System (ADS)

Ballarini, F.; Biaggi, M.; De Biaggi, L.; Ferrari, A.; Ottolenghi, A.; Panzarasa, A.; Paretzke, H. G.; Pelliccioni, M.; Sala, P.; Scannicchio, D.; Zankl, M.

2004-01-01

Distributions of absorbed dose and DNA clustered damage yields in various organs and tissues following the October 1989 solar particle event (SPE) were calculated by coupling the FLUKA Monte Carlo transport code with two anthropomorphic phantoms (a mathematical model and a voxel model), with the main aim of quantifying the role of the shielding features in modulating organ doses. The phantoms, which were assumed to be in deep space, were inserted into a shielding box of variable thickness and material and were irradiated with the proton spectra of the October 1989 event. Average numbers of DNA lesions per cell in different organs were calculated by adopting a technique already tested in previous works, consisting of integrating into "condensed-history" Monte Carlo transport codes - such as FLUKA - yields of radiobiological damage, either calculated with "event-by-event" track structure simulations, or taken from experimental works available in the literature. More specifically, the yields of "Complex Lesions" (or "CL", defined and calculated as a clustered DNA damage in a previous work) per unit dose and DNA mass (CL Gy -1 Da -1) due to the various beam components, including those derived from nuclear interactions with the shielding and the human body, were integrated in FLUKA. This provided spatial distributions of CL/cell yields in different organs, as well as distributions of absorbed doses. The contributions of primary protons and secondary hadrons were calculated separately, and the simulations were repeated for values of Al shielding thickness ranging between 1 and 20 g/cm 2. Slight differences were found between the two phantom types. Skin and eye lenses were found to receive larger doses with respect to internal organs; however, shielding was more effective for skin and lenses. Secondary particles arising from nuclear interactions were found to have a minor role, although their relative contribution was found to be larger for the Complex Lesions than for the absorbed dose, due to their higher LET and thus higher biological effectiveness.

Haloperidol Treatment with Chronically Medicated Residents: Dose Effects on Clinical Behavior and Reinforcement Contingencies.

ERIC Educational Resources Information Center

Aman, Michael G.; And Others

1989-01-01

The study of effects of haloperidol drug therapy with 20 institutionalized mentally retarded persons found clinical changes confined to a slight reduction in stereotypic behavior and an increase in gross motor activity under the high dose condition. Subjects with high initial levels of stereotypy showed the best response to the drug. (Author/DB)

Heat Tolerance and the Peripheral Effects of Anticholinergics

DTIC Science & Technology

1988-01-30

0c. GENDER: Responses of 27 males and 12 females showed that both SR and AGD increased as a function of log MCh dose. SR was affected by gender only...at the 2 highest doses ( male SR slightly greater). At all but the lowest dose AGD was significantly greater for females. ACCLIMATION: Responses of 6... males to MCh were measured before and after 20. DISTRIBUTION /AVAILABILITY OF ABSTRACT 21. ABSTRACT SECURITY CLASSIFICATION 0 UNCLASSIFIED/UNLIMITED 0

Adaptive statistical iterative reconstruction and bismuth shielding for evaluation of dose reduction to the eye and image quality during head CT

NASA Astrophysics Data System (ADS)

Kim, Myeong Seong; Choi, Jiwon; Kim, Sun Young; Kweon, Dae Cheol

2014-03-01

There is a concern regarding the adverse effects of increasing radiation doses due to repeated computed tomography (CT) scans, especially in radiosensitive organs and portions thereof, such as the lenses of the eyes. Bismuth shielding with an adaptive statistical iterative reconstruction (ASIR) algorithm was recently introduced in our clinic as a method to reduce the absorbed radiation dose. This technique was applied to the lens of the eye during CT scans. The purpose of this study was to evaluate the reduction in the absorbed radiation dose and to determine the noise level when using bismuth shielding and the ASIR algorithm with the GE DC 750 HD 64-channel CT scanner for CT of the head of a humanoid phantom. With the use of bismuth shielding, the noise level was higher in the beam-hardening artifact areas than in the revealed artifact areas. However, with the use of ASIR, the noise level was lower than that with the use of bismuth alone; it was also lower in the artifact areas. The reduction in the radiation dose with the use of bismuth was greatest at the surface of the phantom to a limited depth. In conclusion, it is possible to reduce the radiation level and slightly decrease the bismuth-induced noise level by using a combination of ASIR as an algorithm process and bismuth as an in-plane hardware-type shielding method.

Risk of hematological malignancies among Chernobyl liquidators

PubMed Central

Kesminiene, Ausrele; Evrard, Anne-Sophie; Ivanov, Viktor K.; Malakhova, Irina V.; Kurtinaitis, Juozas; Stengrevics, Aivars; Tekkel, Mare; Anspaugh, Lynn R.; Bouville, André; Chekin, Sergei; Chumak, Vadim V.; Drozdovitch, Vladimir; Gapanovich, Vladimir; Golovanov, Ivan; Hubert, Phillip; Illichev, Sergei V.; Khait, Svetlana E.; Krjuchkov, Viktor P.; Maceika, Evaldas; Maksyoutov, Marat; Mirkhaidarov, Anatoly K.; Polyakov, Semion; Shchukina, Natalia; Tenet, Vanessa; Tserakhovich, Tatyana I.; Tsykalo, Aleksandr; Tukov, Aleksandr R.; Cardis, Elisabeth

2010-01-01

A case-control study of hematological malignancies was conducted among Chernobyl liquidators (accident recovery workers) from Belarus, Russia and Baltic countries in order to assess the effect of low-to-medium dose protracted radiation exposures on the relative risk of these diseases. The study was nested within cohorts of liquidators who had worked in 1986–87 around the Chernobyl plant. 117 cases (69 leukemia, 34 non-Hodgkin Lymphoma (NHL) and 14 other malignancies of lymphoid and hematopoietic tissue) and 481 matched controls were included in the study. Individual dose to the bone marrow and uncertainties were estimated for each subject. The main analyses were restricted to 70 cases (40 leukemia, 20 NHL and 10 other) and their 287 matched controls with reliable information on work in the Chernobyl area. Most subjects received very low doses (median 13 mGy). For all diagnoses combined, a significantly elevated OR was seen at doses of 200 mGy and above. The Excess Relative Risk (ERR) per 100 mGy was 0.60 (90% confidence interval (CI): −0.02, 2.35). The corresponding estimate for leukemia excluding chronic lymphoid leukemia (CLL) was 0.50 (90%CI −0.38, 5.7). It is slightly higher than, but statistically compatible with, those estimated from a-bomb survivors and recent low dose-rate studies. Although sensitivity analyses showed generally similar results, we cannot rule out the possibility that biases and uncertainties could have led to over or underestimation of the risk in this study. PMID:19138033

Pharmacokinetics (PK), Pharmacodynamics (PD), and PK-PD Integration of Danofloxacin in Sheep Biological Fluids

PubMed Central

Aliabadi, F. Shojaee; Landoni, M. F.; Lees, P.

2003-01-01

The fluoroquinolone antimicrobial drug danofloxacin was administered to sheep intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1.25 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of danofloxacin in serum, inflamed tissue cage fluid (exudate), and noninflamed tissue cage fluid (transudate) were established by using a tissue cage model. The in vitro and ex vivo activities of danofloxacin in serum, exudate, and transudate against a pathogenic strain of Mannheimia haemolytica were established. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 60.5, 85.6, and 45.7 h, respectively, after i.v. dosing and 55.9, 77.9, and 49.1 h, respectively, after i.m. dosing. After i.m. dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 10.8, 3.0, and 1.6, respectively. The ex vivo growth inhibition data after i.m. dosing were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.8, 20.2, and 28.7 h, and slightly higher values were obtained for transudate and exudate. It is proposed that use of these data might provide a novel approach to the rational design of dosage schedules. PMID:12543670

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

Islam, M; Ahmad, S; Jin, H

Purpose: The out-of-beam dose is important for understanding the peripheral dose in radiation therapy. In proton radiotherapy, the study of out-of-beam dose is scarce and the treatment planning system (TPS) based on pencil beam algorithm cannot accurately predict the out-of-beam dose. This study investigates the out-of-beam dose for the single-room Mevion S250 double scattering proton therapy system using experimentally measured and treatment planning software generated data. The results are compared with those reported for conventional photon beam therapy. However, this study does not incorporate the neutron contribution in the scattered dose. Methods: A total of seven proton treatment plans weremore » generated using Varian Eclipse TPS for three different sites (brain, lung, and pelvis) in an anthropomorphic phantom. Three field sizes of 5×5, 10×10, and 20×20 cm{sup 2} (lung only) with typical clinical range (13.3–22.8 g/cm{sup 2}) and modulation widths (5.3–14.0 g/cm{sup 2}) were used. A single beam was employed in each treatment plan to deliver a dose of 181.8 cGy (200.0 cGy (RBE)) to the selected target. The out-of-beam dose was measured at 2.0, 5.0, 10.0, and 15.0 cm from the beam edge in the phantom using a thimble chamber (PTW TN31010). Results: The out-of-beam dose generally increased with field size, range, and volume irradiated. For all the plans, the scattered dose sharply fell off with distance. At 2.0 cm, the out-of-beam dose ranged from 0.35% to 2.16% of the delivered dose; however, the dose was clinically negligible (<0.3%) at a distance of 5.0 cm and greater. In photon therapy, the slightly greater out-of-beam dose was reported (TG36; 4%, 2%, and 1% for 2.0, 5.0, and 10.0 cm, respectively, using 6 MV beam). Conclusion: The measured out-of-beam dose in proton therapy excluding neutron contribution was observed higher than the TPS calculated dose and comparable to that of photon beam therapy.« less

Impact on dose and image quality of a software-based scatter correction in mammography.

PubMed

Monserrat, Teresa; Prieto, Elena; Barbés, Benigno; Pina, Luis; Elizalde, Arlette; Fernández, Belén

2018-06-01

Background In 2014, Siemens developed a new software-based scatter correction (Progressive Reconstruction Intelligently Minimizing Exposure [PRIME]), enabling grid-less digital mammography. Purpose To compare doses and image quality between PRIME (grid-less) and standard (with anti-scatter grid) modes. Material and Methods Contrast-to-noise ratio (CNR) was measured for various polymethylmethacrylate (PMMA) thicknesses and dose values provided by the mammograph were recorded. CDMAM phantom images were acquired for various PMMA thicknesses and inverse Image Quality Figure (IQF inv ) was calculated. Values of incident entrance surface air kerma (ESAK) and average glandular dose (AGD) were obtained from the DICOM header for a total of 1088 pairs of clinical cases. Two experienced radiologists compared subjectively the image quality of a total of 149 pairs of clinical cases. Results CNR values were higher and doses were lower in PRIME mode for all thicknesses. IQF inv values in PRIME mode were lower for all thicknesses except for 40 mm of PMMA equivalent, in which IQF inv was slightly greater in PRIME mode. A mean reduction of 10% in ESAK and 12% in AGD in PRIME mode with respect to standard mode was obtained. The clinical image quality in PRIME and standard acquisitions resulted to be similar in most of the cases (84% for the first radiologist and 67% for the second one). Conclusion The use of PRIME software reduces, in average, the dose of radiation to the breast without affecting image quality. This reduction is greater for thinner and denser breasts.

Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

PubMed

Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

2014-01-01

Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

“Stockpile” of Slight Transcriptomic Changes Determines the Indirect Genotoxicity of Low-Dose BPA in Thyroid Cells

PubMed Central

Porreca, Immacolata; Ulloa Severino, Luisa; D’Angelo, Fulvio; Cuomo, Danila; Ceccarelli, Michele; Altucci, Lucia; Amendola, Elena; Nebbioso, Angela; Mallardo, Massimo

2016-01-01

Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity. PMID:26982218

SU-E-T-492: The Dosimetric and Clinical Impact of the Metallic Dental Implants on Radiation Dose Distributions in IMRT Head and Neck Cancer Patients.

PubMed

Wang, L; Xing, L; Le, Q

2012-06-01

In H&N cancer patients, the development of oral mucositis is related closely to the radiation dose to the oral cavity. It is generally presumed that the existence of metallic dental implants makes it worse due to the scattering effect of the metal. This study investigates the effects of the dental implants on radiation doses to PTV, tongue mucosa, and other structures for IMRT H&N cancer patients by Monte Carlo (MC) dose calculations. Two H&N cancer patients who have dental implant and are treated by IMRT technique are selected for the purpose. The BEAMnrc/DOSXYZnrc MC codes are employed for the CT-image based dose calculations. The radiation sources are the validated Varian phase-space files for 6MV linac beams. The CT image artifacts caused by the dental fillings are replaced by tissue material. Two sets of MC calculations for each patient are performed at a calculation statistics of 1%: one treats all dental implants as bones, the other substitutes the implants by metal of either titanium or gold with correct density. Doses in PTV and various tissue structures are compared for the two scenarios. With titanium implant, there is no significant difference in doses to PTV and tongue mucosa from that when treating implant as bone. With gold implant, the mean dose to PTV is slightly lowered by 1%; the mean dose to tongue mucosa is reduced by less than 0.5%, although the maximum dose is increased by 5%. The scattering dose from titanium implants is not of concern for H&N patients irradiated by 6MV IMRT beams. For gold implants, the scattering dose to tongue mucosa is not as severe as presumed; and the dose to PTV could be slightly compromised due to the attenuation effect of the metal. This work was supported in part by Varian Medical Systems. © 2012 American Association of Physicists in Medicine.

Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations.

PubMed

Doherty, Kathleen; Essajee, Shaffiq; Penazzato, Martina; Holmes, Charles; Resch, Stephen; Ciaranello, Andrea

2014-05-02

Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0-13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments.

Response of rodents to inhaled diluted diesel exhaust: biochemical and cytological changes in bronchoalveolar lavage fluid and in lung tissue

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

Henderson, R.F.; Pickrell, J.A.; Jones, R.K.

1988-10-01

The effect of long-term (24 months) inhalation of diesel exhaust on the bronchoalveolar region of the respiratory tract of rodents was assessed by serial (every 6 months) analysis of bronchoalveolar lavage fluid (BALF) and of lung tissue from F344/Crl rats and CD-1 mice (both sexes) exposed to diesel exhaust diluted to contain 0, 0.35, 3.5, or 7.0 mg soot/m3. The purpose of the study was twofold. One was to assess the potential health effects of inhaling diluted exhaust from light-duty diesel engines. The second was to determine the usefulness of BALF analysis in detecting the early stages in the developmentmore » of nononcogenic lung disease and differentiating them from the normal repair processes. No biochemical or cytological changes in BALF or in lung tissue were noted in either species exposed to the lowest, and most environmentally relevant, concentration of diesel exhaust. In the two higher levels of exposure, a chronic inflammatory response was measured in both species by dose-dependent increases in inflammatory cells, cytoplasmic and lysosomal enzymes, and protein in BALF. Histologically, after 1 year of exposure, the rats had developed focal areas of fibrosis associated with the deposits of soot, while the mice, despite a higher lung burden of soot than the rats, had only a fine fibrillar thickening of an occasional alveolar septa in the high-level exposure group. Higher increases in BALF beta-glucuronidase activity and in hydroxyproline content accompanied the greater degree of fibrosis in the rat. BALF levels of glutathione (GSH) and glutathione reductase activity increased in a dose-dependent fashion and were higher in mice than in rats. Lung tissue GSH was depleted in a dose-dependent fashion in rats but was slightly increased in mice.« less

EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

PubMed Central

Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

2016-01-01

Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

INFLUENCE OF X-IRRADIATION UPON ACTIVITY OF CHOLINESTERASE IN LIVER AND SERUM. PARTS I-III

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

Ioroi, M.

1960-01-01

The activity of cholinesterase in the liver, studied in rabbits and rats, was more inhibited when the liver was irradiated by a single x-ray dose than by fractionated doses. With l00, 300, and 600 r of whole-body irradiation, the activity of cholinesterase in the liver was stimulated; meanwhile in serum it was inhibited. With l000 and 2000 r, the activities in both serum and liver were severely inhibited. WWhen the diencephalon and spinal cord were irradiated with fractionated doses (l50 r twice a week), the activity of cholinesterase in both liver and serum showed no appreciable change. When whole-body irradiationmore » (l00 r per day) was given, the activity of cholinesterase in both liver and serum was somewhat stimulated. After liver irradiation (200 r per day; total dose 4000 r) the activity of cholinesterase in both liver and serum was inhibited. In patients who showed high activity of cholinesterase in serum before x-ray therapy, the activity was slightly inhibited after x-ray treatment, and patients who showed low activity before therapy were slightly stimulated after x irradiation. (Abstr. Japan Med., l: No. 13, l96l)« less

Performance of irradiated CVD diamond micro-strip sensors

NASA Astrophysics Data System (ADS)

Adam, W.; Berdermann, E.; Bergonzo, P.; Bertuccio, G.; Bogani, F.; Borchi, E.; Brambilla, A.; Bruzzi, M.; Colledani, C.; Conway, J.; D'Angelo, P.; Dabrowski, W.; Delpierre, P.; Deneuville, A.; Dulinski, W.; van Eijk, B.; Fallou, A.; Fizzotti, F.; Foulon, F.; Friedl, M.; Gan, K. K.; Gheeraert, E.; Hallewell, G.; Han, S.; Hartjes, F.; Hrubec, J.; Husson, D.; Kagan, H.; Kania, D.; Kaplon, J.; Kass, R.; Koeth, T.; Krammer, M.; Logiudice, A.; Lu, R.; mac Lynne, L.; Manfredotti, C.; Meier, D.; Mishina, M.; Moroni, L.; Noomen, J.; Oh, A.; Pan, L. S.; Pernicka, M.; Peitz, A.; Perera, L.; Pirollo, S.; Procario, M.; Riester, J. L.; Roe, S.; Rousseau, L.; Rudge, A.; Russ, J.; Sala, S.; Sampietro, M.; Schnetzer, S.; Sciortino, S.; Stelzer, H.; Stone, R.; Suter, B.; Tapper, R. J.; Tesarek, R.; Trischuk, W.; Tromson, D.; Vittone, E.; Walsh, A. M.; Wedenig, R.; Weilhammer, P.; Wetstein, M.; White, C.; Zeuner, W.; Zoeller, M.; Plano, R.; Somalwar, S. V.; Thomson, G. B.

2002-01-01

CVD diamond detectors are of interest for charged particle detection and tracking due to their high radiation tolerance. In this article, we present, for the first time, beam test results from recently manufactured CVD diamond strip detectors and their behavior under low doses of electrons from a β-source and the performance before and after intense (>10 15/cm 2) proton- and pion-irradiations. We find that low dose irradiation increase the signal-to-noise ratio (pumping of the signal) and slightly deteriorate the spatial resolution. Intense irradiation with protons 2.2×10 15 p/ cm2 lowers the signal-to-noise ratio slightly. Intense irradiation with pions 2.9×10 15 π/ cm2 lowers the signal-to-noise ratio more. The spatial resolution of the diamond sensors improves after irradiations.

Exposure-Response Modeling to Characterize the Relationship Between Ixekizumab Serum Drug Concentrations and Efficacy Responses at Week 12 in Patients With Moderate to Severe Plaque Psoriasis.

PubMed

Chigutsa, Emmanuel; de Mendizabal, Nieves Velez; Chua, Laiyi; Heathman, Michael; Friedrich, Stuart; Jackson, Kimberley; Reich, Kristian

2018-06-07

Ixekizumab, a high-affinity monoclonal antibody, selectively targets interleukin-17A and has been shown to be efficacious in the treatment of moderate to severe psoriasis. The objective was to describe the relationship between ixekizumab concentrations and efficacy response (static Physician Global Assessment [sPGA] and the Psoriasis Activity and Severity Index [PASI) scores] after 12 weeks of ixekizumab treatment in psoriasis patients from 3 phase 3 studies. Data from 2888 psoriasis patients randomized to receive placebo or 80 mg ixekizumab every 2 weeks or every 4 weeks were analyzed. Separate logistic regression models describing the relationship between ixekizumab concentrations and sPGA or PASI scores at week 12 were used to determine the probability of patients achieving a response and to investigate the impact of various patient factors other than drug concentrations on response rates. Both dosing regimens were efficacious, with higher rates of response achieved with the higher range of observed ixekizumab concentrations after every-2-week dosing. Although higher bodyweight, palmoplantar involvement, lower baseline disease state, or high baseline C-reactive protein were associated with slightly lower response rates, the magnitude of effect of these factors on sPGA(0,1) response was small, with all subgroups able to achieve high levels of response. Other factors tested had no effect including age, sex, and antidrug antibody status. Logistic regression modeling of ixekizumab concentration and efficacy data accurately identified the proportion of responders using sPGA or PASI end points. The higher concentration ranges achieved with 80 mg every 2 weeks versus every 4 weeks were associated with higher response levels. © 2018, The American College of Clinical Pharmacology.

Effects of pulsed atrazine exposures on autotrophic community structure, biomass, and production in field-based stream mesocosms.

PubMed

King, Ryan S; Brain, Richard A; Back, Jeffrey A; Becker, Christopher; Wright, Moncie V; Djomte, Valerie Toteu; Scott, W Casan; Virgil, Steven R; Brooks, Bryan W; Hosmer, Alan J; Chambliss, C Kevin

2016-03-01

The authors performed a multiple-pulsed atrazine experiment to measure responses of autotrophic endpoints in outdoor stream mesocosms. The experiment was designed to synthetically simulate worst-case atrazine chemographs from streams in agricultural catchments to achieve 60-d mean concentrations of 0 μg/L (control), 10 μg/L, 20 μg/L, and 30 μg/L. The authors dosed triplicate streams with pulses of 0 μg/L, 50 μg/L, 100 μg/L, and 150 μg/L atrazine for 4 d, followed by 7 d without dosing. This 11-d cycle occurred 3 times, followed by a recovery (untreated) period from day 34 to day 60. Mean ± standard error 60-d atrazine concentrations were 0.07 ± 0.03 μg/L, 10.7 ± 0.05 μg/L, 20.9 ± 0.24 μg/L, and 31.0 ± 0.17 μg/L for the control, 10-μg/L, 20-μg/L, and 30-μg/L treatments, respectively. Multivariate analyses revealed that periphyton and phytoplankton community structure did not differ among treatments on any day of the experiment, including during the atrazine pulses. Control periphyton biomass in riffles was higher immediately following the peak of the first atrazine pulse and remained slightly higher than some of the atrazine treatments on most days through the peak of the last pulse. However, periphyton biomass was not different among treatments at the end of the present study. Phytoplankton biomass was not affected by atrazine. Metaphyton biomass in pools was higher in the controls near the midpoint of the present study and remained higher on most days for the remainder of the study. Ceratophyllum demersum, a submersed macrophyte, biomass was higher in controls than in 20-μg/L and 30-μg/L treatments before pulse 3 but was not different subsequent to pulse 3 through the end of the present study. Maximum daily dissolved oxygen (DO, percentage of saturation) declined during each pulse in approximate proportion to magnitude of dose but rapidly converged among treatments after the third pulse. However, DO increased in controls relative to all atrazine treatments during the last 17 d of the experiment, likely a result of metaphyton cover in the pools. Finally, atrazine significantly limited uptake of PO4(3-) and uptake and/or denitrification of NO3(-) but only during pulses; percentage of dose removed from the water column was >85% for P and >95% for N after pulse 3 through the end of the present study. Collectively, only DO and metaphyton biomass differed at the end of the present study and only slightly. Some other endpoints were affected but only during pulses, if at all. The high levels of primary production and accumulation of algal biomass in all streams suggest that effects of pulses of atrazine at the concentrations used in the present study appear transient and likely do not represent ecologically significant adverse outcomes to periphyton, phytoplankton, and aquatic macrophytes, particularly in agricultural streams subjected to high nutrient loads. © 2015 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Incidence of intracranial bleeds in new users of low-dose aspirin: a cohort study using The Health Improvement Network.

PubMed

Cea Soriano, L; Gaist, D; Soriano-Gabarró, M; García Rodríguez, L A

2017-06-01

Essentials Intracranial bleeds (ICB) are serious clinical events that have been associated with aspirin use. Incidence rates of ICB were calculated among new-users of low-dose aspirin in the UK (2000-2012). Over a median follow-up of 5.58 years, the incidence of ICB was 0.08 per 100 person-years. Our estimates are valuable for inclusion in risk-benefit assessments of low-dose aspirin use. Background Low-dose aspirin protects against both ischemic cardiovascular (CV) events and colorectal cancer (CRC). However, low-dose aspirin may be associated with a slightly increased risk of intracranial bleeds (ICBs). Objectives To obtain the incidence rates of ICBs overall and by patient subgroups among new users of low-dose aspirin. Patients/Methods Using The Health Improvement Network (THIN) UK primary-care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N = 199 079; mean age at start of follow-up, 63.9 years) and followed them for up to 14 years (median 5.58 years). Incident ICB cases were identified and validated through linkage to hospitalization data and/or review of THIN records with free-text comments. Incidence rates with 95% confidence intervals (CIs) were calculated. Results Eight hundred and eighty-one incident ICBs cases were identified: 407 cases of intracerebral hemorrhage (ICH), 283 cases of subdural hematoma (SDH), and 191 cases of subarachnoid hemorrhage (SAH). Incidence rates per 100 person-years were 0.08 (95% CI 0.07-0.08) for all ICBs, 0.04 (95% CI 0.03-0.04) for ICH, 0.03 (95% CI 0.02-0.03) for SDH, and 0.02 (95% CI 0.01-0.02) for SAH. The ICB incidence rates per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (95% CI 0.06-0.07) and 0.09 (95% CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. Conclusions Our results provide valuable estimates of the absolute ICB risk for incorporation into risk-benefit assessments of low-dose aspirin use. © 2017 International Society on Thrombosis and Haemostasis.

Improvement of dose calculation in radiation therapy due to metal artifact correction using the augmented likelihood image reconstruction.

PubMed

Ziemann, Christian; Stille, Maik; Cremers, Florian; Buzug, Thorsten M; Rades, Dirk

2018-04-17

Metal artifacts caused by high-density implants lead to incorrectly reconstructed Hounsfield units in computed tomography images. This can result in a loss of accuracy in dose calculation in radiation therapy. This study investigates the potential of the metal artifact reduction algorithms, Augmented Likelihood Image Reconstruction and linear interpolation, in improving dose calculation in the presence of metal artifacts. In order to simulate a pelvis with a double-sided total endoprosthesis, a polymethylmethacrylate phantom was equipped with two steel bars. Artifacts were reduced by applying the Augmented Likelihood Image Reconstruction, a linear interpolation, and a manual correction approach. Using the treatment planning system Eclipse™, identical planning target volumes for an idealized prostate as well as structures for bladder and rectum were defined in corrected and noncorrected images. Volumetric modulated arc therapy plans have been created with double arc rotations with and without avoidance sectors that mask out the prosthesis. The irradiation plans were analyzed for variations in the dose distribution and their homogeneity. Dosimetric measurements were performed using isocentric positioned ionization chambers. Irradiation plans based on images containing artifacts lead to a dose error in the isocenter of up to 8.4%. Corrections with the Augmented Likelihood Image Reconstruction reduce this dose error to 2.7%, corrections with linear interpolation to 3.2%, and manual artifact correction to 4.1%. When applying artifact correction, the dose homogeneity was slightly improved for all investigated methods. Furthermore, the calculated mean doses are higher for rectum and bladder if avoidance sectors are applied. Streaking artifacts cause an imprecise dose calculation within irradiation plans. Using a metal artifact correction algorithm, the planning accuracy can be significantly improved. Best results were accomplished using the Augmented Likelihood Image Reconstruction algorithm. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

PubMed

Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

2018-02-01

Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas.

PubMed

Infante, Jeffrey R; Cassier, Philippe A; Gerecitano, John F; Witteveen, Petronella O; Chugh, Rashmi; Ribrag, Vincent; Chakraborty, Abhijit; Matano, Alessandro; Dobson, Jason R; Crystal, Adam S; Parasuraman, Sudha; Shapiro, Geoffrey I

2016-12-01

Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth in preclinical models with intact retinoblastoma protein (Rb + ). This first-in-human study investigated the MTD, recommended dose for expansion (RDE), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of ribociclib in patients with Rb + advanced solid tumors or lymphomas. Patients received escalating doses of ribociclib (3-weeks-on/1-week-off or continuous). Dose escalation was guided by a Bayesian Logistic Regression Model with overdose control principle. Among 132 patients, 125 received ribociclib 3-weeks-on/1-week-off and 7 were dosed continuously. Nine dose-limiting toxicities were observed among 70 MTD/RDE evaluable patients during cycle 1, most commonly neutropenia (n = 3) and thrombocytopenia (n = 2). The MTD and RDE were established as 900 and 600 mg/day 3-weeks-on/1-week-off, respectively. Common treatment-related adverse events were (all-grade; grade 3/4) neutropenia (46%; 27%), leukopenia (43%; 17%), fatigue (45%; 2%), and nausea (42%; 2%). Asymptomatic Fridericia's corrected QT prolongation was specific to doses ≥600 mg/day (9% of patients at 600 mg/day; 33% at doses >600 mg/day). Plasma exposure increases were slightly higher than dose proportional; mean half-life at the RDE was 32.6 hours. Reduced Ki67 was observed in paired skin and tumor biopsies, consistent with ribociclib-mediated antiproliferative activity. There were 3 partial responses and 43 patients achieved a best response of stable disease; 8 patients were progression-free for >6 months. Ribociclib demonstrated an acceptable safety profile, dose-dependent plasma exposure, and preliminary signs of clinical activity. Phase I-III studies of ribociclib are under way in various indications. Clin Cancer Res; 22(23); 5696-705. ©2016 AACR. ©2016 American Association for Cancer Research.

Metabolic fate and disposition of [14C]hydroquinone given orally to Sprague-Dawley rats.

PubMed

Divincenzo, G D; Hamilton, M L; Reynolds, R C; Ziegler, D A

1984-10-01

Hydroquinone (HQ) is used widely in industry and in commerce and is considered to have a low degree of toxicity. Although the metabolism of HQ has been studied elsewhere, a complete materials balance has not been reported. We investigated the metabolism of HQ in naive and HQ pretreated male Sprague-Dawley rats. [14C]HQ was administered by gavage in single doses of 5, 30, or 200 mg/kg to naive rats. HQ was given repeatedly by gavage to male rats at 200 mg/kg for 4 consecutive days followed by a single dose with 200 mg/kg of [14C]HQ. In separate studies rats were fed 5.6% unlabeled HQ in the diet for 2 days or were dosed by gavage with 311 mg/kg [14C]HQ. The excretion patterns of [14C]HQ and its metabolites were similar for rats dosed singly or repeatedly. Rats given a single dose of 200 mg/kg of [14C]HQ excreted 91.9% of the dose in the urine within 2-4 days; 3.8% was excreted in the feces, about 0.4% was excreted in expired air, and 1.2% remained in the carcass. Radioactivity was widely distributed throughout the tissues with higher concentrations in the liver and kidneys. A decrease in 14C tissue concentrations occurred from 48 to 96 h. The only radiolabeled compounds in the urine were HQ (1.1-8.6% of the dose), hydroquinone monosulfate (25-42%), and hydroquinone monoglucuronide (56-66%). Similar findings were observed for rats given HQ in the feed. There were no significant increases from controls for absolute or relative liver weights, liver microsomal protein concentrations, cytochrome b-5, cytochrome P-450 or cytochrome c reductase activity in rats dosed repeatedly with 200 mg/kg HQ. Cytochrome P-450 values were slightly but significantly decreased in rats dosed repeatedly with HQ compared with controls.

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

PubMed

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

2017-11-15

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

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

Small, Katherine; Kelly, Chris; Beldham-Collins, Rachael

A comparative study was conducted comparing the difference between (1) conformal radiotherapy (CRT) to the whole breast with sequential boost excision cavity plans and (2) intensity-modulated radiation therapy (IMRT) to the whole breast with simultaneously integrated boost to the excision cavity. The computed tomography (CT) data sets of 25 breast cancer patients were used and the results analysed to determine if either planning method produced superior plans. CT data sets from 25 past breast cancer patients were planned using (1) CRT prescribed to 50 Gy in 25 fractions (Fx) to the whole-breast planning target volume (PTV) and 10 Gy inmore » 5Fx to the excision cavity and (2) IMRT prescribed to 60 Gy in 25Fx, with 60 Gy delivered to the excision cavity PTV and 50 Gy delivered to the whole-breast PTV, treated simultaneously. In total, 50 plans were created, with each plan evaluated by PTV coverage using conformity indices, plan maximum dose, lung dose, and heart maximum dose for patients with left-side lesions. CRT plans delivered the lowest plan maximum doses in 56% of cases (average CRT = 6314.34 cGy, IMRT = 6371.52 cGy). They also delivered the lowest mean lung dose in 68% of cases (average CRT = 1206.64 cGy, IMRT = 1288.37 cGy) and V20 in 88% of cases (average CRT = 20.03%, IMRT = 21.73%) and V30 doses in 92% of cases (average CRT = 16.82%, IMRT = 17.97%). IMRT created more conformal plans, using both conformity index and conformation number, in every instance, and lower heart maximum doses in 78.6% of cases (average CRT = 5295.26 cGy, IMRT = 5209.87 cGy). IMRT plans produced superior dose conformity and shorter treatment duration, but a slightly higher planning maximum and increased lung doses. IMRT plans are also faster to treat on a daily basis, with shorter fractionation.« less

TH-AB-202-09: Direct-Aperture Optimization for Combined MV+kV Dose Planning in Fluoroscopic Real-Time Tumor-Tracking Radiation Therapy

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

Liu, X; Belcher, AH; Grelewicz, Z

Purpose: Real-time kV fluoroscopic tumor tracking has the benefit of direct tumor position monitoring. However, there is clinical concern over the excess kV imaging dose cost to the patient when imaging in continuous fluoroscopic mode. This work addresses this specific issue by proposing a combined MV+kV direct-aperture optimization (DAO) approach to integrate the kV imaging beam into a treatment planning such that the kV radiation is considered as a contributor to the overall dose delivery. Methods: The combined MV+kV DAO approach includes three algorithms. First, a projected Quasi-Newton algorithm (L-BFGS) is used to find optimized fluence with MV+kV dose formore » the best possible dose distribution. Then, Engel’s algorithm is applied to optimize the total number of monitor units and heuristically optimize the number of apertures. Finally, an aperture shape optimization (ASO) algorithm is applied to locally optimize the leaf positions of MLC. Results: Compared to conventional DAO MV plans with continuous kV fluoroscopic tracking, combined MV+kV DAO plan leads to a reduction in the total number of MV monitor units due to inclusion of kV dose as part of the PTV, and was also found to reduce the mean and maximum doses on the organs at risk (OAR). Compared to conventional DAO MV plan without kV tracking, the OAR dose in the combined MV+kV DAO plan was only slightly higher. DVH curves show that combined MV+kV DAO plan provided about the same PTV coverage as that in the conventional DAO plans without kV imaging. Conclusion: We report a combined MV+kV DAO approach that allows real time kV imager tumor tracking with only a trivial increasing on the OAR doses while providing the same coverage to PTV. The approach is suitable for clinic implementation.« less

Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

PubMed

Goldberg, J; Freund, E; Beckers, B; Hinzmann, R

2001-02-01

Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler.

Comparison of the efficacy of gamma and UV irradiation in sanitization of fresh carrot juice

NASA Astrophysics Data System (ADS)

Jo, Cheorun; Lee, Kyung Haeng

2012-08-01

As there is no pasteurization procedure for the manufacture of fresh vegetable juice, both industry and consumers have sought a method for improving the storage stability and shelf-life of this category of products. In this study, the effects of commercially available, non-thermal pasteurization processes, such as gamma and UV irradiation, were compared for their efficacy in sanitizing fresh carrot juice (FCJ). FCJ was manufactured, packaged, and gamma irradiated with doses of 0, 1, 3, and 5 kGy. The manufactured FCJ was also passed through 4 UV light lamps at doses of 3.67, 4.69, and 6.50 kGy. The total aerobic bacterial count of the FCJ approached the legal limit (105 CFU/mL) after manufacturing. Both treatments were effective in reducing the number of total aerobic bacteria, and the reduced number was maintained during storage for 7 days. Gamma irradiation was more effective in suppressing microbial growth during storage. When the doses for UV treatment and gamma irradiation were higher, the inactivation effects were higher. The reduction of ascorbic acid content was greater upon gamma irradiation than UV treatment. No difference was found in the contents of flavonoids and polyphenols in FCJ after either treatment. After 3 days of refrigerated storage, the sensory scores of gamma- or UV-irradiated FCJ were superior to those of the control. The results indicate that both non-thermal treatments were effective in improving storage stability and extending shelf-life, but gamma irradiation was slightly better in suppressing microbial growth after treatment.

Ferrous iron/peroxymonosulfate oxidation as a pretreatment for ceramic ultrafiltration membrane: Control of natural organic matter fouling and degradation of atrazine.

PubMed

Cheng, Xiaoxiang; Liang, Heng; Ding, An; Tang, Xiaobin; Liu, Bin; Zhu, Xuewu; Gan, Zhendong; Wu, Daoji; Li, Guibai

2017-04-15

Ferrous iron/peroxymonosulfate (Fe(II)/PMS) oxidation was employed as a pretreatment method for ultrafiltration process to control membrane fouling caused by natural organic matter, including humic acid (HA), sodium alginate (SA), bovine serum albumin (BSA), and their mixture (HA-SA-BSA). To evaluate the mechanism of fouling mitigation, the effects of Fe(II)/PMS pretreatment on the characteristics of feed water were examined. The degradation of atrazine (ATZ) was also investigated and the species of generated radicals were preliminarily determined. Under the test exposure (15 and 50 μM), Fe(II)/PMS pretreatment effectively mitigated membrane fouling caused by HA, SA and HA-SA-BSA mixture, and the performance improved with the increase of Fe(II) or PMS dose; whereas aggravated BSA fouling at lower doses and fouling alleviation was observed only at a higher dose (50/50 μΜ). The fouling mitigation was mainly attributed to the effective reduction of organic loadings by coagulation with in-situ formed Fe(III). Its performance was comparable or even slightly higher than single coagulation with Fe(III), most likely due to the oxidation by Fe(II)/PMS process. Fe(II)/PMS oxidation showed better performance in reducing DOC and UV 254 , fluorescence intensities of fluorescent components and UV-absorbing compounds than single coagulation. In addition, Fe(II)/PMS pretreatment was efficient in ATZ degradation due to the generation of sulfate and hydroxyl radicals, whereas coagulation was ineffective to remove it. Copyright © 2017 Elsevier Ltd. All rights reserved.

Volumetric-modulated arc therapy vs c-IMRT in esophageal cancer: A treatment planning comparison

PubMed Central

Yin, Li; Wu, Hao; Gong, Jian; Geng, Jian-Hao; Jiang, Fan; Shi, An-Hui; Yu, Rong; Li, Yong-Heng; Han, Shu-Kui; Xu, Bo; Zhu, Guang-Ying

2012-01-01

AIM: To compare the volumetric-modulated arc therapy (VMAT) plans with conventional sliding window intensity-modulated radiotherapy (c-IMRT) plans in esophageal cancer (EC). METHODS: Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning system: three using c-IMRT with 5 fields (5F), 7 fields (7F) and 9 fields (9F), and two using VMAT with a single arc (1A) and double arcs (2A). The treatment plans were designed to deliver a dose of 60 Gy to the planning target volume (PTV) with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normalized to 95% of the PTV that received 100% of the prescribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk (OAR) such as lungs, spinal cord and heart. Monitor units (MU) and normal tissue complication probability (NTCP) of OAR were also reported. RESULTS: Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different locations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions: in cervical and upper thoracic EC, the conformity index (CI) was higher in VMAT (1A 0.78 and 2A 0.8) than in c-IMRT (5F 0.62, 7F 0.66 and 9F 0.73) and homogeneity was slightly better in c-IMRT (7F 1.09 and 9F 1.07) than in VMAT (1A 1.1 and 2A 1.09). Lung V30 was lower in VMAT (1A 12.52 and 2A 12.29) than in c-IMRT (7F 14.35 and 9F 14.81). The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT (1A 0.76 and 2A 0.74) was higher than in c-IMRT (5F 0.63 Gy and 7F 0.67 Gy), and homogeneity was almost similar between VMAT and c-IMRT. V20 (2A 21.49 Gy vs 7F 24.59 Gy and 9F 24.16 Gy) and V30 (2A 9.73 Gy vs 5F 12.61 Gy, 7F 11.5 Gy and 9F 11.37 Gy) of lungs in VMAT were lower than in c-IMRT, but low doses to lungs (V5 and V10) were increased. V30 (1A 48.12 Gy vs 5F 59.2 Gy, 7F 58.59 Gy and 9F 57.2 Gy), V40 and V50 of heart in VMAT was lower than in c-IMRT. MUs in VMAT plans were significantly reduced in comparison with c-IMRT, maximum doses to the spinal cord and mean doses of lungs were similar between the two techniques. NTCP of spinal cord was 0 for all cases. NTCP of lungs and heart in VMAT were lower than in c-IMRT. The advantage of VMAT plan was enhanced by doubling the arc. CONCLUSION: Compared with c-IMRT, VMAT, especially the 2A, slightly improves the OAR dose sparing, such as lungs and heart, and reduces NTCP and MU with a better PTV coverage. PMID:23066322

Volumetric-modulated arc therapy vs. c-IMRT in esophageal cancer: a treatment planning comparison.

PubMed

Yin, Li; Wu, Hao; Gong, Jian; Geng, Jian-Hao; Jiang, Fan; Shi, An-Hui; Yu, Rong; Li, Yong-Heng; Han, Shu-Kui; Xu, Bo; Zhu, Guang-Ying

2012-10-07

To compare the volumetric-modulated arc therapy (VMAT) plans with conventional sliding window intensity-modulated radiotherapy (c-IMRT) plans in esophageal cancer (EC). Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning system: three using c-IMRT with 5 fields (5F), 7 fields (7F) and 9 fields (9F), and two using VMAT with a single arc (1A) and double arcs (2A). The treatment plans were designed to deliver a dose of 60 Gy to the planning target volume (PTV) with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normalized to 95% of the PTV that received 100% of the prescribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk (OAR) such as lungs, spinal cord and heart. Monitor units (MU) and normal tissue complication probability (NTCP) of OAR were also reported. Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different locations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions: in cervical and upper thoracic EC, the conformity index (CI) was higher in VMAT (1A 0.78 and 2A 0.8) than in c-IMRT (5F 0.62, 7F 0.66 and 9F 0.73) and homogeneity was slightly better in c-IMRT (7F 1.09 and 9F 1.07) than in VMAT (1A 1.1 and 2A 1.09). Lung V30 was lower in VMAT (1A 12.52 and 2A 12.29) than in c-IMRT (7F 14.35 and 9F 14.81). The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT (1A 0.76 and 2A 0.74) was higher than in c-IMRT (5F 0.63 Gy and 7F 0.67 Gy), and homogeneity was almost similar between VMAT and c-IMRT. V20 (2A 21.49 Gy vs. 7F 24.59 Gy and 9F 24.16 Gy) and V30 (2A 9.73 Gy vs. 5F 12.61 Gy, 7F 11.5 Gy and 9F 11.37 Gy) of lungs in VMAT were lower than in c-IMRT, but low doses to lungs (V5 and V10) were increased. V30 (1A 48.12 Gy vs. 5F 59.2 Gy, 7F 58.59 Gy and 9F 57.2 Gy), V40 and V50 of heart in VMAT was lower than in c-IMRT. MUs in VMAT plans were significantly reduced in comparison with c-IMRT, maximum doses to the spinal cord and mean doses of lungs were similar between the two techniques. NTCP of spinal cord was 0 for all cases. NTCP of lungs and heart in VMAT were lower than in c-IMRT. The advantage of VMAT plan was enhanced by doubling the arc. Compared with c-IMRT, VMAT, especially the 2A, slightly improves the OAR dose sparing, such as lungs and heart, and reduces NTCP and MU with a better PTV coverage.

Improving target coverage and organ-at-risk sparing in intensity-modulated radiotherapy for cervical oesophageal cancer using a simple optimisation method.

PubMed

Lu, Jia-Yang; Cheung, Michael Lok-Man; Huang, Bao-Tian; Wu, Li-Li; Xie, Wen-Jia; Chen, Zhi-Jian; Li, De-Rui; Xie, Liang-Xi

2015-01-01

To assess the performance of a simple optimisation method for improving target coverage and organ-at-risk (OAR) sparing in intensity-modulated radiotherapy (IMRT) for cervical oesophageal cancer. For 20 selected patients, clinically acceptable original IMRT plans (Original plans) were created, and two optimisation methods were adopted to improve the plans: 1) a base dose function (BDF)-based method, in which the treatment plans were re-optimised based on the original plans, and 2) a dose-controlling structure (DCS)-based method, in which the original plans were re-optimised by assigning additional constraints for hot and cold spots. The Original, BDF-based and DCS-based plans were compared with regard to target dose homogeneity, conformity, OAR sparing, planning time and monitor units (MUs). Dosimetric verifications were performed and delivery times were recorded for the BDF-based and DCS-based plans. The BDF-based plans provided significantly superior dose homogeneity and conformity compared with both the DCS-based and Original plans. The BDF-based method further reduced the doses delivered to the OARs by approximately 1-3%. The re-optimisation time was reduced by approximately 28%, but the MUs and delivery time were slightly increased. All verification tests were passed and no significant differences were found. The BDF-based method for the optimisation of IMRT for cervical oesophageal cancer can achieve significantly better dose distributions with better planning efficiency at the expense of slightly more MUs.

[Pharmacological study of nicergoline. (III). Effects on cerebral and peripheral circulation in animals].

PubMed

Shintomi, K; Ogawa, Y; Yoshimoto, K; Narita, H

1986-05-01

Effects of nicergoline on the cerebral and peripheral circulation were compared with those of dihydroergotoxine (DHE) and papaverine (PAP) in anesthetized and/or immobilized cats. The i.a. injection of nicergoline (0.032 approximately 32 micrograms/kg), similarly to PAP, caused dose-dependent increases in intramaxillary artery (as the human intracarotid artery) blood flow (IMBF) and femoral artery blood flow, but the injection of DHE had no effect on these blood flows. The i.v. injection of nicergoline (32 approximately 128 micrograms/kg) caused a dose-dependent fall in blood pressure (BP) and a transient slight decrease in cerebral vascular resistance, but did not affect IMBF, regional cerebral blood flow (r-CBF), intracranial pressure (ICP) and heart rate (HR). The i.v. injection of DHE produced a slight fall in BP and a marked long-lasting decrease in HR, without affecting other parameters. The i.v. injection of PAP (4 mg/kg) induced marked increases in IMBF, r-CBF, ICP and HR and caused a transient fall followed by a marked elevation in BP. The p.o. administration of nicergoline (0.06 approximately 4 mg/kg) caused a dose-dependent fall in BP and selective inhibition of pressure response to adrenaline (ID50: 0.25 mg/kg). The administration of DHE produced marked inhibition of pressure responses to both adrenaline and noradrenaline, accompanied with a slight fall in BP. Furthermore, the administration of nicergoline (3 approximately 100 mg/kg) induced a dose-dependent fall in BP in SHR. These results suggest that the cerebral and peripheral circulatory effects of nicergoline may be due to direct vasodilating action and alpha-blocking action in the animals.

Corticotropin-releasing hormone-mediated metamorphosis in the neotenic axolotl Ambystoma mexicanum: synergistic involvement of thyroxine and corticoids on brain type II deiodinase.

PubMed

Kühn, Eduard R; De Groef, Bert; Van der Geyten, Serge; Darras, Veerle M

2005-08-01

In the present study, morphological changes leading to complete metamorphosis have been induced in the neotenic axolotl Ambystoma mexicanum using a submetamorphic dose of T(4) together with an injection of corticotropin-releasing hormone (CRH). An injection of CRH alone is ineffective in this regard presumably due to a lack of thyrotropic stimulation. Using this low hormone profile for induction of metamorphosis, the deiodinating enzymes D2 and D3 known to be present in amphibians were measured in liver and brain 24h following an intraperitoneal injection. An injection of T(4) alone did not influence liver nor brain D2 and D3, but dexamethasone (DEX) or CRH alone or in combination with T(4) decreased liver D2 and D3. Brain D2 activity was slightly increased with a higher dose of DEX, though CRH did not have this effect. A profound synergistic effect occurred when T(4) and DEX or CRH were injected together, in the dose range leading to metamorphosis, increasing brain D2 activity more than fivefold. This synergistic effect was not found in the liver. It is concluded that brain T(3) availability may play an important role for the onset of metamorphosis in the neotenic axolotl.

Analyses of risks associated with radiation exposure from past major solar particle events

NASA Technical Reports Server (NTRS)

Weyland, Mark D.; Atwell, William; Cucinotta, Francis A.; Wilson, John W.; Hardy, Alva C.

1991-01-01

Radiation exposures and cancer induction/mortality risks were investigated for several major solar particle events (SPE's). The SPE's included are: February 1956, November 1960, August 1972, October 1989, and the September, August, and October 1989 events combined. The three 1989 events were treated as one since all three could affect a single lunar or Mars mission. A baryon transport code was used to propagate particles through aluminum and tissue shield materials. A free space environment was utilized for all calculations. Results show the 30-day blood forming organs (BFO) limit of 25 rem was surpassed by all five events using 10 g/sq cm of shielding. The BFO limit is based on a depth dose of 5 cm of tissue, while a more detailed shield distribution of the BFO's was utilized. A comparison between the 5 cm depth dose and the dose found using the BFO shield distribution shows that the 5 cm depth value slightly higher than the BFO dose. The annual limit of 50 rem was exceeded by the August 1972, October 1989, and the three combined 1989 events with 5 g/sq cm of shielding. Cancer mortality risks ranged from 1.5 to 17 percent at 1 g/sq cm and 0.5 to 1.1 percent behind 10 g/sq cm of shielding for five events. These ranges correspond to those for a 45 year old male. It is shown that secondary particles comprise about 1/3 of the total risk at 10 g/sq cm of shielding. Utilizing a computerized Space Shuttle shielding model to represent a typical spacecraft configuration in free space at the August 1972 SPE, average crew doses exceeded the BFO dose limit.

Delivery time comparison for intensity-modulated radiation therapy with/without flattening filter: a planning study

NASA Astrophysics Data System (ADS)

Fu, Weihua; Dai, Jianrong; Hu, Yimin; Han, Dongsheng; Song, Yixin

2004-04-01

The treatment delivery time of intensity-modulated radiation therapy (IMRT) with a multileaf collimator (MLC) is generally longer than that of conventional radiotherapy. In theory, removing the flattening filter from the treatment head may reduce the beam-on time by enhancing the output dose rate, and then reduce the treatment delivery time. And in practice, there is a possibility of delivering the required fluence distribution by modulating the unflattened non-uniform fluence distribution. However, the reduction of beam-on time may be discounted by the increase of leaf-travel time and (or) verification-and-recording (V&R) time. Here we investigate the overall effect of flattening filter on the treatment delivery time of IMRT with MLCs implemented in the step and shoot method, as well as with compensators on six hybrid machines. We compared the treatment delivery time with/without flattening filter for ten nasopharynx cases and ten prostate cases by observing the variations of the ratio of the beam-on time, segment number, leaf-travel time and the treatment delivery time with dose rate, leaf speed and V&R time. The results show that, without the flattening filter, the beam-on time reduces for both static MLC and compensator-based techniques; the number of segments and the leaf-travel time increase slightly for the static MLC technique; the relative IMRT treatment delivery time decreases more with lower dose rate, higher leaf speed and shorter V&R overhead time. The absolute treatment delivery time reduction depends on the fraction dose. It is not clinically significant at a fraction dose of 2 Gy for the technique of removing the flattening filter, but becomes significant when the fraction dose is as high as that for radiosurgery.

Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination.

PubMed

Vigne, Claire; Dupuy, Martin; Richetin, Aline; Guy, Bruno; Jackson, Nicholas; Bonaparte, Matthew; Hu, Branda; Saville, Melanie; Chansinghakul, Danaya; Noriega, Fernando; Plennevaux, Eric

2017-09-02

Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT 50 ) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2-3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries.

Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination

PubMed Central

Vigne, Claire; Dupuy, Martin; Richetin, Aline; Guy, Bruno; Jackson, Nicholas; Bonaparte, Matthew; Hu, Branda; Saville, Melanie; Chansinghakul, Danaya; Noriega, Fernando; Plennevaux, Eric

2017-01-01

ABSTRACT Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT50) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2–3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries. PMID:28598256

Consideration of the ICRP 2006 revised tissue weighting factors on age-dependent values of the effective dose for external photons

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lee, Choonik; Han, Eun Young; Bolch, Wesley E.

2007-01-01

The effective dose recommended by the International Commission on Radiological Protection (ICRP) is the sum of organ equivalent doses weighted by corresponding tissue weighting factors, wT. ICRP is in the process of revising its 1990 recommendations on the effective dose where new values of organs and tissue weighting factors have been proposed and published in draft form for consultation by the radiological protection community. In its 5 June 2006 draft recommendations, new organs and tissues have been introduced in the effective dose which do not exist within the 1987 Oak Ridge National Laboratory (ORNL) phantom series (e.g., salivary glands). Recently, the investigators at University of Florida have updated the series of ORNL phantoms by implementing new organ models and adopting organ-specific elemental composition and densities. In this study, the effective dose changes caused by the transition from the current recommendation of ICRP Publication 60 to the 2006 draft recommendations were investigated for external photon irradiation across the range of ICRP reference ages (newborn, 1-year, 5-year, 10-year, 15-year and adult) and for six idealized irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO). Organ-absorbed doses were calculated by implementing the revised ORNL phantoms in the Monte Carlo radiation transport code, MCNPX2.5, after which effective doses were calculated under the 1990 and draft 2006 evaluation schemes of the ICRP. Effective doses calculated under the 2006 draft scheme were slightly higher than estimated under ICRP Publication 60 methods for all irradiation geometries exclusive of the AP geometry where an opposite trend was observed. The effective doses of the adult phantom were more greatly affected by the change in tissue weighting factors than that seen within the paediatric members of the phantom series. Additionally, dose conversion coefficients for newly identified radiosensitive organs—salivary glands, gall bladder, heart and prostate—were reported, as well as the brain, which was originally considered in ICRP Publication 60 as a member of the remainder category of the effective dose.

Combined Exposure to Anti-Androgens Exacerbates Disruption of Sexual Differentiation in the Rat

PubMed Central

Hass, Ulla; Scholze, Martin; Christiansen, Sofie; Dalgaard, Majken; Vinggaard, Anne Marie; Axelstad, Marta; Metzdorff, Stine Broeng; Kortenkamp, Andreas

2007-01-01

Objective The aim of this study was to assess whether the joint effects of three androgen receptor antagonists (vinclozolin, flutamide, procymidone) on male sexual differentiation after in utero and postnatal exposures can be predicted based on dose–response data of the individual chemicals. Methods Test chemicals and mixtures were administered by gavage to time-mated nulliparous, young adult Wistar rats from gestational day 7 to the day before expected birth, and from postnatal days 1–16. Changes in anogenital distance (AGD) and nipple retention (NR) in male offspring rats were chosen as end points for extensive dose–response studies. Vinclozolin, flutamide, and procymidone were combined at a mixture ratio proportional to their individual potencies for causing retention of six nipples in male offspring. Results With AGD as the end point, the joint effects of the three anti-androgens were essentially dose additive. The observed responses for NR were slightly higher than those expected on the basis of dose addition. A combination of doses of each chemical, which on its own did not produce statistically significant AGD alterations, induced half-maximal mixture effects. At individual doses associated with only modest effects on NR, the mixture induced NR approaching female values in the males. Conclusions Effects of a mixture of similarly acting anti-androgens can be predicted fairly accurately on the basis of the potency of the individual mixture components by using the dose addition concept. Exposure to anti-androgens, which individually appears to exert only small effects, may induce marked responses in concert with, possibly unrecognized, similarly acting chemicals. PMID:18174960

A novel radiation detector for removing scattered radiation in chest radiography: Monte Carlo simulation-based performance evaluation

NASA Astrophysics Data System (ADS)

Roh, Y. H.; Yoon, Y.; Kim, K.; Kim, J.; Kim, J.; Morishita, J.

2016-10-01

Scattered radiation is the main reason for the degradation of image quality and the increased patient exposure dose in diagnostic radiology. In an effort to reduce scattered radiation, a novel structure of an indirect flat panel detector has been proposed. In this study, a performance evaluation of the novel system in terms of image contrast as well as an estimation of the number of photons incident on the detector and the grid exposure factor were conducted using Monte Carlo simulations. The image contrast of the proposed system was superior to that of the no-grid system but slightly inferior to that of the parallel-grid system. The number of photons incident on the detector and the grid exposure factor of the novel system were higher than those of the parallel-grid system but lower than those of the no-grid system. The proposed system exhibited the potential for reduced exposure dose without image quality degradation; additionally, can be further improved by a structural optimization considering the manufacturer's specifications of its lead contents.

Sodium citrate inhibits the proliferation of human gastric adenocarcinoma epithelia cells

PubMed Central

Xia, Yuan; Zhang, Xulong; Bo, Agula; Sun, Juan; Li, Minhui

2018-01-01

The objective of the present study was to investigate the cytotoxic effects of sodium citrate on human gastric adenocarcinoma epithelia AGS cells. Numerous cytotoxicity-associated sodium citrate-induced effects were assessed, including cell viability and proliferation, cytokine expression and caspase activity. In vitro studies demonstrated that incubation with sodium citrate (>3.125 mM) inhibited AGS cell viability and proliferation in a dose-dependent manner. Incubation with sodium citrate for 24 h revealed that the levels of interleukin-1β (IL-1β), IL-8 and tumor necrosis factor increased with an increasing of dose of sodium citrate, whereas the IL-6 levels exhibited only a slight alteration. In addition, increases in caspase-3 and −9 activities were associated with increased duration of treatment and dosage of sodium citrate. Collectively, the results of the present study demonstrated that treatment with sodium citrate at higher concentrations or for longer durations exerts a cytotoxic effect on AGS cells via the induction of the intrinsic apoptosis pathway and the alteration in the levels of certain cytokines. PMID:29616124

Effects of three related amides on microecosystem stability

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

Flum, T.F.; Shannon, L.J.

1987-04-01

Three related amides (diuron, 2-(octyloxy) acetanilide, and salicylanilide) were evaluated for toxicity to aquatic microcosm communities. Effects were measured at the ecosystem level using changes in pH, Eh (redox potential), and dissolved oxygen as indicators of toxicity. These values were used to calculate the resistance, resilience, and relative instability of the microecosystems to each compound at comparable dose levels of approximately 2500 micrograms/liter. Such measures have often been used in a theoretical context, but have not received wide practical application. The systems showed low resistance and no resilience to diuron, high resistance and low resilience to 2-(octyloxy) acetanilide, and nomore » response to salicylanilide. At a higher exposure level (9800 micrograms/liter salicylanilide), the systems showed low resistance and high resilience. Both this approach and more traditional dose-response measures of toxicity indicated that diuron was clearly the most toxic compound, followed by 2-(octyloxy) acetanilide and salicylanilide. While microcosm toxicity tests were slightly less sensitive than some single species tests, they provided important additional information on the extent of perturbations and the rate of ecosystem recovery.« less

Effect of Propranolol on Thyroxine-Induced Changes in Body Temperature and Metabolism During Exercise in Dogs

NASA Technical Reports Server (NTRS)

Kaciuba-Uscilko, Hanna; Brzezinska, Zofia; Greenleaf, John E.

1976-01-01

Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s. c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (T(sub re)) during exercise as early as 5 h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest T(sub re), blood FFA (free fatty acid) and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in T(sub re) and blood LA concentrations during the next 30 min of exercise.

Effect of di(n-butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid rats.

PubMed

Lee, Ena; Ahn, Mee Young; Kim, Hee Jin; Kim, In Young; Han, Soon Young; Kang, Tae Seok; Hong, Jin Hwan; Park, Kui Lea; Lee, Byung Mu; Kim, Hyung Sik

2007-06-01

This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 microg/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor alpha-1 (TRalpha-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP.

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.

Comparisons between MCNP, EGS4 and experiment for clinical electron beams.

PubMed

Jeraj, R; Keall, P J; Ostwald, P M

1999-03-01

Understanding the limitations of Monte Carlo codes is essential in order to avoid systematic errors in simulations, and to suggest further improvement of the codes. MCNP and EGS4, Monte Carlo codes commonly used in medical physics, were compared and evaluated against electron depth dose data and experimental backscatter results obtained using clinical radiotherapy beams. Different physical models and algorithms used in the codes give significantly different depth dose curves and electron backscattering factors. The default version of MCNP calculates electron depth dose curves which are too penetrating. The MCNP results agree better with experiment if the ITS-style energy-indexing algorithm is used. EGS4 underpredicts electron backscattering for high-Z materials. The results slightly improve if optimal PRESTA-I parameters are used. MCNP simulates backscattering well even for high-Z materials. To conclude the comparison, a timing study was performed. EGS4 is generally faster than MCNP and use of a large number of scoring voxels dramatically slows down the MCNP calculation. However, use of a large number of geometry voxels in MCNP only slightly affects the speed of the calculation.

SU-E-T-400: Evaluation of Shielding and Activation at Two Pencil Beam Scanning Proton Facilities

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

Remmes, N; Mundy, D; Classic, K

2015-06-15

Purpose: To verify acceptably low dose levels around two newly constructed identical pencil beam scanning proton therapy facilities and to evaluate accuracy of pre-construction shielding calculations. Methods: Dose measurements were taken at select points of interest using a WENDI-2 style wide-energy neutron detector. Measurements were compared to pre-construction shielding calculations. Radiation badges with neutron dose measurement capabilities were worn by personnel and also placed at points throughout the facilities. Seven neutron and gamma detectors were permanently installed throughout the facility, continuously logging data. Potential activation hazards have also been investigated. Dose rates near water tanks immediately after prolonged irradiation havemore » been measured. Equipment inside the treatment room and accelerator vault has been surveyed and/or wipe tested. Air filters from air handling units, sticky mats placed outside of the accelerator vault, and water samples from the magnet cooling water loops have also been tested. Results: All radiation badges have been returned with readings below the reporting minimum. Measurements of mats, air filters, cooling water, wipe tests and surveys of equipment that has not been placed in the beam have all come back at background levels. All survey measurements show the analytical shielding calculations to be conservative by at least a factor of 2. No anomalous events have been identified by the building radiation monitoring system. Measurements of dose rates close to scanning water tanks have shown dose rates of approximately 10 mrem/hr with a half-life less than 5 minutes. Measurements around the accelerator show some areas with dose rates slightly higher than 10 mrem/hr. Conclusion: The shielding design is shown to be adequate. Measured dose rates are below those predicted by shielding calculations. Activation hazards are minimal except in certain very well defined areas within the accelerator vault and for objects placed directly in the path of the beam.« less

SU-F-T-513: Dosimetric Validation of Spatially Fractionated Radiotherapy Using Gel Dosimetry

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

Papanikolaou, P; Watts, L; Kirby, N

2016-06-15

Purpose: Spatially fractionated radiation therapy, also known as GRID therapy, is used to treat large solid tumors by irradiating the target to a single dose of 10–20Gy through spatially distributed beamlets. We have investigated the use of a 3D gel for dosimetric characterization of GRID therapy. Methods: GRID therapy is an external beam analog of volumetric brachytherapy, whereby we produce a distribution of hot and cold dose columns inside the tumor volume. Such distribution can be produced with a block or by using a checker-like pattern with MLC. We have studied both types of GRID delivery. A cube shaped acrylicmore » phantom was filled with polymer gel and served as a 3D dosimeter. The phantom was scanned and the CT images were used to produce two plans in Pinnacle, one with the grid block and one with the MLC defined grid. A 6MV beam was used for the plan with a prescription of 1500cGy at dmax. The irradiated phantom was scanned in a 3T MRI scanner. Results: 3D dose maps were derived from the MR scans of the gel dosimeter and were found to be in good agreement with the predicted dose distribution from the RTP system. Gamma analysis showed a passing rate of 93% for 5% dose and 2mm DTA scoring criteria. Both relative and absolute dose profiles are in good agreement, except in the peripheral beamlets where the gel measured slightly higher dose, possibly because of the changing head scatter conditions that the RTP is not fully accounting for. Our results have also been benchmarked against ionization chamber measurements. Conclusion: We have investigated the use of a polymer gel for the 3D dosimetric characterization and evaluation of GRID therapy. Our results demonstrated that the planning system can predict fairly accurately the dose distribution for GRID type therapy.« less

Immunogenicity and Protective Efficacy in Mice and Hamsters of a β-Propiolactone Inactivated Whole Virus SARS-CoV Vaccine

PubMed Central

Roberts, Anjeanette; Lamirande, Elaine W.; Vogel, Leatrice; Baras, Benoît; Goossens, Geneviève; Knott, Isabelle; Chen, Jun; Ward, Jerrold M.; Vassilev, Ventzislav

2010-01-01

Abstract The immunogenicity and efficacy of β-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01B and AS03A were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01B adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01B-adjuvanted vaccine being slightly more immunogenic than the AS03A-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01B were immunogenic, and two doses of 2 μg of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies. PMID:20883165

Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice.

PubMed

Yamazaki-Nishioka, Miho; Shimizu, Makiko; Suemizu, Hiroshi; Nishiwaki, Megumi; Mitsui, Marina; Yamazaki, Hiroshi

2018-02-01

1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide. 3. Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high. 4. The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.

Patient-specific CT dosimetry calculation: a feasibility study.

PubMed

Fearon, Thomas; Xie, Huchen; Cheng, Jason Y; Ning, Holly; Zhuge, Ying; Miller, Robert W

2011-11-15

Current estimation of radiation dose from computed tomography (CT) scans on patients has relied on the measurement of Computed Tomography Dose Index (CTDI) in standard cylindrical phantoms, and calculations based on mathematical representations of "standard man". Radiation dose to both adult and pediatric patients from a CT scan has been a concern, as noted in recent reports. The purpose of this study was to investigate the feasibility of adapting a radiation treatment planning system (RTPS) to provide patient-specific CT dosimetry. A radiation treatment planning system was modified to calculate patient-specific CT dose distributions, which can be represented by dose at specific points within an organ of interest, as well as organ dose-volumes (after image segmentation) for a GE Light Speed Ultra Plus CT scanner. The RTPS calculation algorithm is based on a semi-empirical, measured correction-based algorithm, which has been well established in the radiotherapy community. Digital representations of the physical phantoms (virtual phantom) were acquired with the GE CT scanner in axial mode. Thermoluminescent dosimeter (TLDs) measurements in pediatric anthropomorphic phantoms were utilized to validate the dose at specific points within organs of interest relative to RTPS calculations and Monte Carlo simulations of the same virtual phantoms (digital representation). Congruence of the calculated and measured point doses for the same physical anthropomorphic phantom geometry was used to verify the feasibility of the method. The RTPS algorithm can be extended to calculate the organ dose by calculating a dose distribution point-by-point for a designated volume. Electron Gamma Shower (EGSnrc) codes for radiation transport calculations developed by National Research Council of Canada (NRCC) were utilized to perform the Monte Carlo (MC) simulation. In general, the RTPS and MC dose calculations are within 10% of the TLD measurements for the infant and child chest scans. With respect to the dose comparisons for the head, the RTPS dose calculations are slightly higher (10%-20%) than the TLD measurements, while the MC results were within 10% of the TLD measurements. The advantage of the algebraic dose calculation engine of the RTPS is a substantially reduced computation time (minutes vs. days) relative to Monte Carlo calculations, as well as providing patient-specific dose estimation. It also provides the basis for a more elaborate reporting of dosimetric results, such as patient specific organ dose volumes after image segmentation.

Effects of low-dose ionizing radiation and menadione, an inducer of oxidative stress, alone and in combination in a vertebrate embryo model.

PubMed

Bladen, Catherine L; Kozlowski, David J; Dynan, William S

2012-11-01

Prior work has established the zebrafish embryo as an in vivo model for studying the biological effects of exposure to low doses of ionizing radiation. One of the known effects of radiation is to elevate the levels of reactive oxygen species (ROS) in tissue. However, ROS are also produced as by-products of normal metabolism and, regardless of origin, ROS produce similar chemical damage to DNA. Here we use the zebrafish embryo model to investigate whether the effects of low-dose (0-1.5 Gy) radiation and endogenous ROS are mechanistically distinct. We increased levels of endogenous ROS by exposure to low concentrations of the quinone drug, menadione. Imaging studies in live embryos showed that exposure to 3 μM or higher concentrations of menadione dramatically increased ROS levels. This treatment was associated with a growth delay and morphologic abnormalities, which were partially or fully reversible. By contrast, exposure to low doses of ionizing radiation had no discernable effects on overall growth or morphology, although, there was an increase in TUNEL-positive apoptotic cells, consistent with the results of prior studies. Further studies showed that the combined effect of radiation and menadione exposure are greater than with either agent alone, and that attenuation of the expression of Ku80, a gene important for repair of radiation-induced DNA damage, had only a slight effect on menadione sensitivity. Together, results suggest that ionizing radiation and menadione affect the embryo by distinct mechanisms.

Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations

PubMed Central

2014-01-01

Background Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. Methods We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0–13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. Results The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. Conclusions The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments. PMID:24885453

Ovipositional responses of the pulse beetle, Bruchus chinensis (Coleoptera: Bruchidae) to extracts and compounds of Capparis decidua.

PubMed

Upadhyay, Ravi K; Rohatgi, Leena; Chaubey, Mukesh K; Jain, Subhash C

2006-12-27

Extracts of Capparis decidua stems and flowers showed insecticidal and oviposition inhibitory activities against Bruchus chinensis. The LC50 values of these extracts were found to increase with the increase in the polarity of the extract at different exposure periods. For instance, after 96 h, the LC50 values were found to be 3.619, 7.319, and 10.151 microg for CD1, CD2, and CD3, respectively. Extract CD7 was effective only at higher doses. The toxicity was found to be dose- and time-dependent. The females laid lesser number of eggs, when exposed to sublethal doses of different extracts and pure compounds, as compared to control. The maximum oviposition deterrence index was found for extract CD1 followed in decreasing order by CD2, CD3, and CD7. From extract CD1, two compounds were isolated and characterized as triacontanol (C1) and 2-carboxy-1,1-dimethylpyrrolidine (C2). When the females were exposed to sublethal doses of these compounds, they laid lesser number of eggs as compared to the control. C2 was found to have a slightly greater oviposition inhibition effect than C1. From fraction CD7, one novel compound labeled as CDF1 has been isolated and identified as 6-(1-hydroxy-non-3-enyl)tetrahydropyran-2-one. CDF1 has also shown insecticidal and oviposition inhibitory activities against B. chinensis at low concentrations.

[Exposure to fluorides from drinking water in the city of Aguascalientes, Mexico].

PubMed

Trejo-Vázquez, R; Bonilla-Petriciolet, A

2001-08-01

Determine the fluoride content in all the wells that supply drinking water to the city of Aguascalientes, Mexico, in order to establish the population's degree of exposure. The fluoride content of the 126 wells that supply drinking water to the city of Aguascalientes was determined, using the SPADNS method, in accordance with two Mexican regulations, NMX-AA-77-1982 and NMX-014-SSAI-1993. Using that data, we created fluoride isopleth maps showing the distribution of fluoride concentrations in the water supplies for the city of Aguascalientes. We also estimated exposure doses for the city's inhabitants. The mean analysis uncertainty was 3.9%. Seventy-three wells had a fluoride concentration of" 1.5 mg/L, which was the maximum permissible value set by the Mexican standards then in effect. All the maximum exposure doses surpassed the minimum risk level set by Agency for Toxic Substances and Disease Registry (ATSDR) of the Department of Health and Human Services of the United States of America. In the children under 1 year of age, even the minimum does was slightly higher than the ATSDR risk level. From estimating the fluoride exposure doses caused by water consumption in the city of Aguascalientes and comparing those doses with ones from other states in Mexico, we concluded that the fluoride intake in Aguascalientes represents a potential risk for inhabitants' health. The fluoride content of the city's drinking water should be reduced to 0.69 mg/L.

Preparation of modified waterworks sludge particles as adsorbent to enhance coagulation of slightly polluted source water.

PubMed

Chen, Wei; Gao, Xiaohong; Xu, Hang; Wang, Kang; Chen, Taoyuan

2017-08-01

Without treatment, waterworks sludge is ineffective as an adsorbent. In this study, raw waterworks sludge was used as the raw material to prepare modified sludge particles through high-temperature calcination and alkali modification. The feasibility of using a combination of modified particles and polyaluminum chloride (PAC) as a coagulant for treatment of slightly polluted source water was also investigated. The composition, structure, and surface properties of the modified particles were characterized, and their capabilities for removing ammonia nitrogen and turbidity were determined. The results indicate that the optimal preparation conditions for the modified sludge particles were achieved by preparing the particles with a roasting temperature of 483.12 °C, a roasting time of 3.32 h, and a lye concentration of 3.75%. Furthermore, enhanced coagulation is strengthened with the addition of modified sludge particles, which is reflected by reduction of the required PAC dose and enhancement of the removal efficiency of ammonia nitrogen and turbidity by over 80 and 93%, respectively. Additional factors such as pH, temperature, dose, and dosing sequence were also evaluated. The optimum doses of modified particles and PAC were 40 and 15 mg/L, respectively, and adding modified particles at the same time as or prior to adding PAC improves removal efficiency.

The thermoregulatory mechanism of melatonin-induced hypothermia in chicken.

PubMed

Rozenboim, I; Miara, L; Wolfenson, D

1998-01-01

The involvement of melatonin (Mel) in body temperature (Tb) regulation was studied in White Leghorn layers. In experiment 1, 35 hens were injected intraperitoneally with seven doses of Mel (0, 5, 10, 20, 40, 80, or 160 mg Mel/kg body wt) dissolved in ethanol. Within 1 h, Mel had caused a dose-dependent reduction in Tb. To eliminate a possible vehicle effect, 0, 80, and 160 mg/kg body wt Mel dissolved in N-methyl-2-pyrrolidone (NMP) was injected. NMP had no effect on Tb, with Mel again causing a dose-dependent hypothermia. In experiment 2 (n = 30), Mel injected before exposure of layers to heat reduced Tb and prevented heat-induced hyperthermia. Injection after heat stress had begun did not prevent hyperthermia. Under cold stress, Mel induced hypothermia, which was not observed in controls. In experiment 3 (n = 12), Mel injection reduced Tb and increased metatarsal and comb temperatures (but not feathered-skin temperature), respiratory rate, and evaporative water loss. Heart rate rose and then declined, and blood pressure increased 1 h after Mel injection. Heat production rose slightly during the first hour, then decreased in parallel to the Tb decline. We conclude that pharmacological doses of Mel induce hypothermia in hens by increasing nonevaporative skin heat losses and slightly increasing respiratory evaporation.

The use of gamma radiation from cobalt-60 in the control of diseases of the honey-bee and the sterilization of honey

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

Katznelson, H.; Robb, J. A.

1962-04-01

Honeycomb and honey heavily contaminated with spores of Bacillus larvae (agent of American foulbrood disease of honeybee larvae) were exposed to gamma radiation from Co 60. Sterility was achieved by a dose of 1.5 x 10 4 to 2.0 x 10 6 rad. Sugar-tolerant yeasts in honey were effectively destroyed by a dose of 1 x 10 6 rad whereas cysts of Nosema apis (agent of nosema disease of adult bees) were inactivated by a dose of 0.2 x 10 6 rad. The honey samples before testing were golden-brown and irradiation caused a progressive decrease in the intensity of thismore » color resulting in a straw-colored liquid on treatment with a dose of 2 Mrad. There was a slight change in honey flavor and gas evolution occurred in all treated samples. The results show that pasteurization or sterilization of honey can be achieved with relatively little difficulty and with a comparatively small irradiation unit. However, a slight intensification of flavor as a result of gamma irradiation and a distinct change from a dark to a light color requires further study in relation to the food and market value of the honey.« less

No adaptive response is induced by chronic low-dose radiation from Ra-226 in the CHSE/F fish embryonic cell line and the HaCaT human epithelial cell line

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

Shi, Xiaopei, E-mail: shix22@mcmaster.ca; Mothersi

Purpose: To determine whether chronic low-dose α-particle radiation from Ra-226 over multiple cell generations can lead to an adaptive response in CHSE/F fish embryonic cells or HaCaT human epithelial cells receiving subsequent acute high-dose γ-ray radiation. Methods: CHSE/F and HaCaT cells were exposed to very low doses of Ra-226 in medium for multiple generations prior to being challenged by a higher dose γ-ray radiation. The clonogenic assay was used to test the clonogenic survival of cells with or without being pretreated by radiation from Ra-226. Results: In general, pretreatment with chronic radiation has no significant influence on the reaction ofmore » cells to the subsequent challenge radiation. Compared to unprimed cells, the change in clonogenic survival of primed cells after receiving challenge radiation is mainly due to the influence of the chronic exposure, and there's little adaptive response induced. However at several dose points, pretreatment of CHSE/F fish cells with chronic radiation resulted in a radiosensitive response to a challenge dose of γ-ray radiation, and pretreatment of HaCaT cells resulted in no effect except for a slightly radioresistant response to the challenge radiation which was not significant. Conclusion: The results suggest that chronic low-dose radiation is not effective enough to induce adaptive response. There was a difference between human and fish cells and it may be important to consider results from multiple species before making conclusions about effects of chronic or low doses of radiation in the environment. The term “radiosensitive” or “adaptive” make no judgment about whether such responses are ultimately beneficial or harmful. - Highlights: • No obvious adaptive response is induced by chronic low-dose radiation from Ra-226. • Priming radiation from Ra-226 sensitized CHSE/F cells to the challenge radiation. • Linear model is inconsistent with current work using chronic low-dose radiation.« less

The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams.

PubMed

Masunaga, Shin-Ichiro; Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Sakurai, Yoshinori; Tanaka, Hiroki; Tano, Keizo; Sanada, Yu; Suzuki, Minoru; Maruhashi, Akira; Ono, Koji

2015-08-01

The aim of the study was to clarify the effect of p53 status of tumor cells on radiosensitivity of solid tumors following accelerated carbon-ion beam irradiation compared with γ-rays or reactor neutron beams, referring to the response of intratumor quiescent (Q) cells. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays or accelerated carbon-ion beams at a high or reduced dose-rate. Other tumor-bearing mice received reactor thermal or epithermal neutrons at a reduced dose-rate. Immediately or 9 hours after the high dose-rate irradiation (HDRI), or immediately after the reduced dose-rate irradiation (RDRI), the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The difference in radiosensitivity between the total (P + Q) and Q cells after γ-ray irradiation was markedly reduced with reactor neutron beams or carbon-ion beams, especially with a higher linear energy transfer (LET) value. Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. In both total and Q cells within both SAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especially with a higher LET, showed little recovery capacity through leaving an interval between HDRI and the assay or decreasing the dose-rate. The recovery from radiation-induced damage after γ-ray irradiation was a p53-dependent event, but little recovery was found after carbon-ion beam irradiation. With RDRI, the radiosensitivity to reactor thermal and epithermal neutron beams was slightly higher than that to carbon-ion beams. For tumor control, including intratumor Q-cell control, accelerated carbon-ion beams, especially with a higher LET, and reactor thermal and epithermal neutron beams were very useful for suppressing the recovery from radiation-induced damage irrespective of p53 status of tumor cells.

The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams

PubMed Central

Masunaga, Shin-ichiro; Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Sakurai, Yoshinori; Tanaka, Hiroki; Tano, Keizo; Sanada, Yu; Suzuki, Minoru; Maruhashi, Akira; Ono, Koji

2015-01-01

Background The aim of the study was to clarify the effect of p53 status of tumor cells on radiosensitivity of solid tumors following accelerated carbon-ion beam irradiation compared with γ-rays or reactor neutron beams, referring to the response of intratumor quiescent (Q) cells. Methods Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor-bearing mice received 5-bromo-2’-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays or accelerated carbon-ion beams at a high or reduced dose-rate. Other tumor-bearing mice received reactor thermal or epithermal neutrons at a reduced dose-rate. Immediately or 9 hours after the high dose-rate irradiation (HDRI), or immediately after the reduced dose-rate irradiation (RDRI), the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Results The difference in radiosensitivity between the total (P + Q) and Q cells after γ-ray irradiation was markedly reduced with reactor neutron beams or carbon-ion beams, especially with a higher linear energy transfer (LET) value. Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. In both total and Q cells within both SAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especially with a higher LET, showed little recovery capacity through leaving an interval between HDRI and the assay or decreasing the dose-rate. The recovery from radiation-induced damage after γ-ray irradiation was a p53-dependent event, but little recovery was found after carbon-ion beam irradiation. With RDRI, the radiosensitivity to reactor thermal and epithermal neutron beams was slightly higher than that to carbon-ion beams. Conclusion For tumor control, including intratumor Q-cell control, accelerated carbon-ion beams, especially with a higher LET, and reactor thermal and epithermal neutron beams were very useful for suppressing the recovery from radiation-induced damage irrespective of p53 status of tumor cells. PMID:28983338

Adaptive Liver Stereotactic Body Radiation Therapy: Automated Daily Plan Reoptimization Prevents Dose Delivery Degradation Caused by Anatomy Deformations

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

Leinders, Suzanne M.; Delft University of Technology, Delft; Breedveld, Sebastiaan

Purpose: To investigate how dose distributions for liver stereotactic body radiation therapy (SBRT) can be improved by using automated, daily plan reoptimization to account for anatomy deformations, compared with setup corrections only. Methods and Materials: For 12 tumors, 3 strategies for dose delivery were simulated. In the first strategy, computed tomography scans made before each treatment fraction were used only for patient repositioning before dose delivery for correction of detected tumor setup errors. In adaptive second and third strategies, in addition to the isocenter shift, intensity modulated radiation therapy beam profiles were reoptimized or both intensity profiles and beam orientationsmore » were reoptimized, respectively. All optimizations were performed with a recently published algorithm for automated, multicriteria optimization of both beam profiles and beam angles. Results: In 6 of 12 cases, violations of organs at risk (ie, heart, stomach, kidney) constraints of 1 to 6 Gy in single fractions occurred in cases of tumor repositioning only. By using the adaptive strategies, these could be avoided (<1 Gy). For 1 case, this needed adaptation by slightly underdosing the planning target volume. For 2 cases with restricted tumor dose in the planning phase to avoid organ-at-risk constraint violations, fraction doses could be increased by 1 and 2 Gy because of more favorable anatomy. Daily reoptimization of both beam profiles and beam angles (third strategy) performed slightly better than reoptimization of profiles only, but the latter required only a few minutes of computation time, whereas full reoptimization took several hours. Conclusions: This simulation study demonstrated that replanning based on daily acquired computed tomography scans can improve liver stereotactic body radiation therapy dose delivery.« less

Chromosome aberrations in the blood lymphocytes of astronauts after space flight

NASA Technical Reports Server (NTRS)

George, K.; Durante, M.; Wu, H.; Willingham, V.; Badhwar, G.; Cucinotta, F. A.

2001-01-01

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.

Chromosome aberrations in the blood lymphocytes of astronauts after space flight.

PubMed

George, K; Durante, M; Wu, H; Willingham, V; Badhwar, G; Cucinotta, F A

2001-12-01

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.

Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism

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

Fang Cheng; Behr, Melissa; Xie Fang

2008-02-15

Chloroform causes hepatic and renal toxicity in a number of species. In vitro studies have indicated that chloroform can be metabolized by P450 enzymes in the kidney to nephrotoxic intermediate, although direct in vivo evidence for the role of renal P450 in the nephrotoxicity has not been reported. This study was to determine whether chloroform renal toxicity persists in a mouse model with a liver-specific deletion of the P450 reductase (Cpr) gene (liver-Cpr-null). Chloroform-induced renal toxicity and chloroform tissue levels were compared between the liver-Cpr-null and wild-type mice at 24 h following differing doses of chloroform. At a chloroform dosemore » of 150 mg/kg, the levels of blood urea nitrogen (BUN) were five times higher in the exposed group than in the vehicle-treated one for the liver-Cpr-null mice, but they were only slightly higher in the exposed group than in the vehicle-treated group for the wild-type mice. Severe lesions were found in the kidney of the liver-Cpr-null mice, while only mild lesions were found in the wild-type mice. At a chloroform dose of 300 mg/kg, severe kidney lesions were observed in both strains, yet the BUN levels were still higher in the liver-Cpr-null than in the wild-type mice. Higher chloroform levels were found in the tissues of the liver-Cpr-null mice. These findings indicated that loss of hepatic P450-dependent chloroform metabolism does not protect against chloroform-induced renal toxicity, suggesting that renal P450 enzymes play an essential role in chloroform renal toxicity.« less

Clindamycin enhances a nondepolarizing neuromuscular blockade.

PubMed

Becker, L D; Miller, R D

1976-07-01

Neuromuscular blockades induced by clindamycin alone and with d-tubocurarine or pancuronium were examined in the in-vitro guinea pig lumbrical muscle-nerve preparation. Clindamycin, 80-240 mug/ml, initially increased twitch tension. With higher concentrations (180-240 mug/ml) twitch tension subsequently decreased. With 15 to 20 per cent depression of twitch tension by clindamycin, neostigmine (5-20 ng/ml) or calcium (81 mug/ml) slightly but not completely antagonized the blockade. Clindamycin, 40 mug/ml, a dose that did not depress twitch tension, potentiated d-tubocurarine- or pancuronium-induced neuromuscular bloackade. Plasma concentrations of clindamycin of 10-40 mug/ml were recommended for treating serious infections. The authors conclude that the administration of clindamycin may augment nondepolarizing blockade in man, and antagonism by neostigmine and calcium may be incomplete.

Apparent respiration rate of the human corneal epithelium with tetracaine HCl and benoxinate HCl.

PubMed

Bentley, C R; Larke, J R

1983-12-01

Local anesthetics may have a cytotoxic effect which causes a depression in the apparent epithelial oxygen uptake rate (AEOR) of the cornea. We measured the AEOR of human corneas in vivo before and after applying 1% tetracaine (amethocaine) HCl and 0.4% benoxinate HCl. These drugs had no effect on AEOR. In human corneas that had been subjected to a period of hypoxia, AEOR was slightly higher after administration of benoxinate, a result in the opposite direction to that expected on the grounds of toxicity. The increase was not statistically significant. We conclude that clinical doses of tetracaine HCl and benoxinate HCl normally have a minimal cytotoxic effect, and that this is similarly true when benoxinate is applied to the cornea after contact lens wear.

SP-B and SP-C Containing New Synthetic Surfactant for Treatment of Extremely Immature Lamb Lung

PubMed Central

Sato, Atsuyasu; Ikegami, Machiko

2012-01-01

Although superiority of synthetic surfactant over animal-driven surfactant has been known, there is no synthetic surfactant commercially available at present. Many trials have been made to develop synthetic surfactant comparable in function to animal-driven surfactant. The efficacy of treatment with a new synthetic surfactant (CHF5633) containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, SP-B analog, and SP-C analog was evaluated using immature newborn lamb model and compared with animal lung tissue-based surfactant Survanta. Lambs were treated with a clinical dose of 200 mg/kg CHF5633, 100 mg/kg Survanta, or air after 15 min initial ventilation. All the lambs treated with air died of respiratory distress within 90 min of age. During a 5 h study period, Pco2 was maintained at 55 mmHg with 24 cmH2O peak inspiratory pressure for both groups. The preterm newborn lamb lung functions were dramatically improved by CHF5633 treatment. Slight, but significant superiority of CHF5633 over Survanta was demonstrated in tidal volume at 20 min and dynamic lung compliance at 20 and 300 min. The ultrastructure of CHF5633 was large with uniquely aggregated lipid particles. Increased uptake of CHF5633 by alveolar monocytes for catabolism was demonstrated by microphotograph, which might be associated with the higher treatment dose of CHF5633. The higher catabolism of CHF5633 was also suggested by the similar amount of surfactant lipid in bronchoalveolar lavage fluid (BALF) between CHF5633 and Survanta groups, despite the 2-fold higher treatment dose of CHF5633. Under the present ventilation protocol, lung inflammation was minimal for both groups, evaluated by inflammatory cell numbers in BALF and expression of IL-1β, IL-6, IL-8, and TNFα mRNA in the lung tissue. In conclusion, the new synthetic surfactant CHF5633 was effective in treating extremely immature newborn lambs with surfactant deficiency during the 5 h study period. PMID:22808033

Mitigation of radon and thoron decay products by filtration.

PubMed

Wang, Jin; Meisenberg, Oliver; Chen, Yongheng; Karg, Erwin; Tschiersch, Jochen

2011-09-01

Inhalation of indoor radon ((222)Rn) and thoron ((220)Rn) decay products is the most important source of exposure to ionizing radiation for the human respiratory tract. Decreasing ventilation rates due to energy saving reasons in new buildings suggest additional active mitigation techniques to reduce the exposure in homes with high radon and thoron concentrations but poor ventilation. Filtration techniques with HEPA filters and simple surgical mask material have been tested for their potential to reduce the indoor exposure in terms of the total effective dose for mixed radon and thoron indoor atmospheres. The tests were performed inside an experimental room providing stable conditions. Filtration (at filtration rates of 0.2 h(-1) and larger) removes attached radon and thoron decay products effectively but indoor aerosol as well. Therefore the concentration of unattached decay products (which have a higher dose coefficient) may increase. The decrease of the attached decay product concentrations could be theoretically described by a slowly decreasing exponential process. For attached radon decay products, it exhibited a faster but weaker removal process compared to attached thoron decay products (-70% for attached radon decay products and -80% for attached thoron decay products at a filtration rate of 0.5 h(-1) with an HEPA filter). The concentration of unattached thoron decay products increased distinctly during the filtration process (+300%) while that of unattached radon decay products rose only slightly though at a much higher level (+17%). In the theoretical description these observed differences could be attributed to the different half-lives of the nuclides. Considering both effects, reduced attached and increased unattached decay product concentrations, filtration could significantly decrease the total effective dose from thoron whereas the overall effect on radon dose is small. A permanent filtration is recommended because of the slow decrease of the thoron decay product concentrations. Copyright © 2011 Elsevier B.V. All rights reserved.

Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation.

PubMed

Beltrán-Pardo, Eliana; Jönsson, K Ingemar; Harms-Ringdahl, Mats; Haghdoost, Siamak; Wojcik, Andrzej

2015-01-01

Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at ~ 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation.

Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation

PubMed Central

Beltrán-Pardo, Eliana; Jönsson, K. Ingemar; Harms-Ringdahl, Mats; Haghdoost, Siamak; Wojcik, Andrzej

2015-01-01

Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at ~ 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation. PMID:26208275

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.

Evaluation of organ doses in CT examinations with an infant anthropomorphic phantom.

PubMed

Fujii, K; Akahane, K; Miyazaki, O; Horiuchi, T; Shimada, A; Nagmatsu, H; Yamauchi, M; Yamauchi-Kawaura, C; Kawasaki, T

2011-09-01

The aim of this study is to evaluate organ doses in infant CT examinations with multi-detector row CT scanners. Radiation doses were measured with radiophotoluminescence glass dosemeters set in various organ positions within a 1-y-old child anthropomorphic phantom and organ doses were evaluated from the measurement values. Doses for tissues or organs within the scan range were 28-36 mGy in an infant head CT, 3-11 mGy in a chest CT, 5-11 mGy in an abdominal-pelvic CT and 2-14 mGy in a cardiac CT. The doses varied by the differences in the types of CT scanners and scan parameters used at each medical facility. Compared with those for children of various ages, the doses in an infant CT protocol were found to be similar to or slightly smaller than those in a paediatric CT for 5- or 6-y-old children.

The bioavailability and adverse impacts of lead and decabromodiphenyl ether on soil microbial activities.

PubMed

Chen, Lei; Zhang, Wei; Zhang, Rong; Lin, Kuangfei; He, Lei; Wu, Liqun

2015-08-01

Lead (Pb) and decabromodiphenyl ether (BDE209) are the main pollutants at electronic waste (e-waste) recycling sites (EWRSs), and their potential toxic effects on soil organisms have received extensive attention. However, the impact on soil microorganisms of joint exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed to explore the adverse impacts of Pb and BDE209 on soil microbial activities and chemical transformation for the first time. The results have demonstrated that BDE209 was barely degraded in all treated groups, indicating that the presence of Pb hardly affected BDE209 dissipation. The fractions analysis according to Tessier suggested that Pb gradually transformed towards more stable fractions in the slightly alkaline soil, thus reducing the bioavailability of Pb. Additionally, increased Pb doses caused significantly higher bioavailability (p < 0.05), and the same trend was clearly observed after simultaneous exposure to BDE209. Generally, single Pb or BDE209 exposure markedly inhibited (p < 0.05 or 0.01) soil microbial biomass C (C mic), while soil basal respiration (SBR) indicated the opposite response trend (inhibition or stimulation for BDE209 or Pb alone, respectively). Compared to the controls, Pb dramatically (p < 0.01) facilitated soil metabolic quotient (qCO2) during the incubation period. After joint exposure to Pb and BDE209, C mic generally declined with increasing exposure concentration, following certain dose-response relationships. However, SBR and qCO2 were highly significantly stimulated (p < 0.01), and more doses of Pb and BDE209 resulted in higher values. The results of these observations have provided a basic understanding of the potential ecological risk of Pb and BDE209 in soil at EWRSs.

Association of Acute Radiation Syndrome and Rain after the Bombings in Atomic Bomb Survivors.

PubMed

Ozasa, K; Sakata, R; Cullings, H M; Grant, E J

2016-06-01

Acute radiation-induced symptoms reported in survivors after the atomic bombings in Hiroshima and Nagasaki have been suspected to be associated with rain that fell after the explosions, but this association has not been evaluated in an epidemiological study that considers the effects of the direct dose from the atomic bombs and other factors. The aim of this study was to evaluate this association using information from a fixed cohort, comprised of 93,741 members of the Life Span Study who were in the city at the time of the bombing. Information on acute symptoms and exposure to rain was collected in surveys conducted by interviewers, primarily in the 1950s. The proportion of survivors developing severe epilation was around 60% at levels of direct radiation doses of 3 Gy or higher and less than 0.2% at levels <0.005 Gy regardless of reported rain exposure status. The low prevalence of acute symptoms at low direct doses indicates that the reported fallout rain was not homogeneously radioactive at a level sufficient to cause a substantial probability of acute symptoms. We observed that the proportion of reported acute symptoms was slightly higher among those who reported rain exposure in some subgroups, however, suggestions that rain was the cause of these reported symptoms are not supported by analyses specific to the known areas of radioactive fallout. Misclassification of exposure and outcome, including symptoms due to other causes and recall bias, appears to be a more plausible explanation. However, the insufficient and retrospective nature of the available data limited our ability to quantify the attribution to those possible causes.

First insights into the protective effects of a recombinant swinepox virus expressing truncated MRP of Streptococcus suis type 2 in mice.

PubMed

Huang, Dongyan; Zhu, Haodan; Lin, Huixing; Xu, Jiarong; Lu, Chengping

2012-01-01

To explore the potential of the swinepox virus (SPV) as vector for Streptococcus suis vaccines, a vector system was developed for the construction of a recombinant SPV carrying bacterial genes. Using this system, a recombinant virus expressing truncated muramidase-released protein (MRP) of S. suis type 2 (SS2), designated rSPV-MRP, was produced and identified by PCR, western blotting and immunofluorescence assays. The rSPV-MRP was found to be only slightly attenuated in PK-15 cells, when compared with the wild-type virus. After immunization intramuscularly with rSPV-MRP, SS2 inactive vaccine (positive control), wild-type SPV (negative control) and PBS (blank control) respectively, all CD1 mice were challenged with a lethal dose or a sublethal dose of SS2 highly virulent strain ZY05719. While SS2 inactive vaccine protected all mice, immunization with rSPV-MRP resulted in 60% survival and protected mice against a lethal dose of the highly virulent SS2 strain, compared with the negative control (P < 0.05). Our data indicate that animals immunized with rSPV-MRP had a significantly reduced bacterial burden in all organs examined, compared to negative controls and blank controls (P <0.05). Antibody titers of the rSPV-MRP-vaccinated group were significantly higher (P <0.001), when compared to negative controls and blank controls. Antibody titers were also significantly higher in the vaccinated group at all time points post-vaccination (P <0.001), compared with the positive controls. These initial results demonstrated that the rSPV-MRP provided mice with protection from systemic SS2 infection. If SPV recombinants have the potential as S. suis vaccines for the use in pigs has to be evaluated in further studies.

Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease.

PubMed

Barreto, Fellype C; de Oliveira, Rodrigo B; Benchitrit, Joyce; Louvet, Loïc; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Riser, Bruce L; Massy, Ziad A

2014-11-01

Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.

Recolonization by heterotrophic bacteria after UV irradiation or ozonation of seawater; a simulation of ballast water treatment.

PubMed

Hess-Erga, Ole-Kristian; Blomvågnes-Bakke, Bente; Vadstein, Olav

2010-10-01

Transport of ballast water with ships represents a risk for introduction of foreign species. If ballast water is treated during uptake, there will be a recolonization of the ballast water by heterotrophic bacteria during transport. We investigated survival and succession of heterotrophic bacteria after disinfection of seawater in the laboratory, representing a model system of ballast water treatment and transport. The seawater was exposed to ultraviolet (UV) irradiation, ozone (2 doses) or no treatment, incubated for 16 days and examined with culture-dependent and -independent methods. The number of colony-forming units (CFU) was reduced below the detection level after disinfection with UV and high ozone dose (700 mV), and 1% of the initial level for the low ozone dose (400 mV). After less than 3 days, the CFU was back or above the starting point for the control, UV and low ozone treatment, whereas it took slightly more than 6 days for the high ozone treatment. Disinfection increased substrate availability and reduced cell densities. Lack of competition and predation induced the recolonization by opportunistic bacteria (r-strategists), with significant increase in bacterial numbers and a low diversity (based on DGGE band pattern). All cultures stabilized after the initial recolonization phase (except Oz700) where competition due to crowding and nutrient limitation favoured bacteria with high substrate affinity (K-strategists), resulting in higher species richness and diversity (based on DGGE band pattern). The bacterial community was significantly altered qualitatively and quantitatively and may have a higher potential as invaders in the recipient depending on disinfection method and the time of release. These results have implications for the treatment strategy used for ballast water. Copyright © 2010 Elsevier Ltd. All rights reserved.

Backscattering from dental restorations and splint materials during therapeutic radiation

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

Farman, A.G.; Sharma, S.; George, D.I.

1985-08-01

Models were constructed to simulate as closely as possible the human oral cavity. Radiation absorbed doses were determined for controls and various test situations involving the presence of dental restorative and splint materials during cobalt-60 irradiation of the models. Adjacent gold full crowns and adjacent solid dental silver amalgam cores both increased the dose to the interproximal gingivae by 20%. Use of orthodontic full bands for splinting the jaws increased the dose to the buccal tissues by an average of 10%. Augmentation of dose through backscatter radiation was determined to be only slight for intracoronal amalgam fillings and stainless steelmore » or plastic bracket splints.« less

SU-F-303-12: Implementation of MR-Only Simulation for Brain Cancer: A Virtual Clinical Trial

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

Glide-Hurst, C; Zheng, W; Kim, J

2015-06-15

Purpose: To perform a retrospective virtual clinical trial using an MR-only workflow for a variety of brain cancer cases by incorporating novel imaging sequences, tissue segmentation using phase images, and an innovative synthetic CT (synCT) solution. Methods: Ten patients (16 lesions) were evaluated using a 1.0T MR-SIM including UTE-DIXON imaging (TE = 0.144/3.4/6.9ms). Bone-enhanced images were generated from DIXON-water/fat and inverted UTE. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating intersection and Dice similarity coefficients (DSC) using CT-SIM as ground truth. SynCTs were generated using voxel-based weighted summation incorporating T2, FLAIR, UTE1,more » and bone-enhanced images. Mean absolute error (MAE) characterized HU differences between synCT and CT-SIM. Dose was recalculated on synCTs; differences were quantified using planar gamma analysis (2%/2 mm dose difference/distance to agreement) at isocenter. Digitally reconstructed radiographs (DRRs) were compared. Results: On average, air maps intersected 80.8 ±5.5% (range: 71.8–88.8%) between MR-SIM and CT-SIM yielding DSCs of 0.78 ± 0.04 (range: 0.70–0.83). Whole-brain MAE between synCT and CT-SIM was 160.7±8.8 HU, with the largest uncertainty arising from bone (MAE = 423.3±33.2 HU). Gamma analysis revealed pass rates of 99.4 ± 0.04% between synCT and CT-SIM for the cohort. Dose volume histogram analysis revealed that synCT tended to yield slightly higher doses. Organs at risk such as the chiasm and optic nerves were most sensitive due to their proximities to air/bone interfaces. DRRs generated via synCT and CT-SIM were within clinical tolerances. Conclusion: Our approach for MR-only simulation for brain cancer treatment planning yielded clinically acceptable results relative to the CT-based benchmark. While slight dose differences were observed, reoptimization of treatment plans and improved image registration can address this limitation. Future work will incorporate automated registration between setup images (cone-beam CT and kilovoltage images) for synCT and CT-SIM. Submitting institution holds research agreements with Philips HealthCare, Best, Netherlands and Varian Medical Systems, Palo Alto, CA. Research partially sponsored via an Internal Mentored Research Grant.« less

Efficacy of virtual block objects in reducing the lung dose in helical tomotherapy planning for cervical oesophageal cancer: a planning study.

PubMed

Ito, Makoto; Shimizu, Hidetoshi; Aoyama, Takahiro; Tachibana, Hiroyuki; Tomita, Natsuo; Makita, Chiyoko; Koide, Yutaro; Kato, Daiki; Ishiguchi, Tsuneo; Kodaira, Takeshi

2018-04-04

Intensity-modulated radiotherapy is useful for cervical oesophageal carcinoma (CEC); however, increasing low-dose exposure to the lung may lead to radiation pneumonitis. Nevertheless, an irradiation technique that avoids the lungs has never been examined due to the high difficulty of dose optimization. In this study, we examined the efficacy of helical tomotherapy that can restrict beamlets passing virtual blocks during dose optimization computing (block plan) in reducing the lung dose. Fifteen patients with CEC were analysed. The primary/nodal lesion and prophylactic nodal region with adequate margins were defined as the planning target volume (PTV)-60 Gy and PTV-48 Gy, respectively. Nineteen plans per patient were made and compared (total: 285 plans), including non-block and block plans with several shapes and sizes. The most appropriate block model was semi-circular, 8 cm outside of the tracheal bifurcation, with a significantly lower lung dose compared to that of non-block plans; the mean lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and the mean lung dose were 31.3% vs. 48.0% (p <  0.001), 22.4% vs. 39.4% (p <  0.001), 13.2% vs. 16.0% (p = 0.028), and 7.1 Gy vs. 9.6 Gy (p <  0.001), respectively. Both the block and non-block plans were comparable in terms of the homogeneity and conformity indexes of PTV-60 Gy: 0.05 vs. 0.04 (p = 0.100) and 0.82 vs. 0.85 (p = 0.616), respectively. The maximum dose of the spinal cord planning risk volume increased slightly (49.4 Gy vs. 47.9 Gy, p = 0.002). There was no significant difference in the mean doses to the heart and the thyroid gland. Prolongation of the delivery time was less than 1 min (5.6 min vs. 4.9 min, p = 0.010). The block plan for CEC could significantly reduce the lung dose, with acceptable increment in the spinal dose and a slightly prolonged delivery time.

SU-E-T-616: Comparison of Plan Dose Accuracy for Anterior Vs. Lateral Fields in Proton Therapy of Prostate Cancer

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

Moteabbed, M; Trofimov, A; Testa, M

2014-06-01

Purpose: With the anticipated introduction of in vivo range verification methods, the use of anterior fields for proton therapy of prostate cancer may become an attractive treatment option, and improve upon the dose distributions achievable with conventional lateral-opposed fields. This study aimed to evaluate and compare the planned dose accuracy for lateral versus anterior oblique field arrangements. Methods: Four patients with low/intermediate risk prostate cancer, participating in a clinical trial at our institution, were selected for this study. All patients were treated using lateral-opposed fields (LAT). The clinical target volume (CTV) received a total dose of 79.2 Gy in 44more » fractions. Anterior oblique research plans (ANT) were created using the clinical planning system, and featured beams with ±35-degree gantry angle, 1.2 cm aperture margins, 3-mm range compensator smearing and no range uncertainty margins. Monte Carlo (MC) simulations were performed for both beam arrangements using TOPAS. Dose volume histograms were analyzed and compared for planned and MC dose distributions. Differences between MC and planned DVH parameters were computed as a percentage of the total prescribed dose. Results: For all patients, CTV dose was systematically lower (∼2–2.5%) for MC than the plan. This discrepancy was slightly larger (∼0.5%) for LAT compared to ANT plans for all cases. Although the dose differences for bladder and anterior rectal wall remained within 0.7% for all LAT cases, they were slightly larger for ANT plans, especially for case 3 due to larger patient size and MC-plan range difference. The EUD difference for femoral heads was within 0.6% for both LAT and ANT cases. Conclusion: The dose calculated by the treatment planning system using pencil beam algorithm agrees with MC to within 2.5% and is comparable for lateral and anterior scenarios. The dose agreement in the anterior rectal wall is range- and hence, patient-dependent for ANT treatments.« less

Space Motion Sickness - Analysis of Medical Debriefs Data for Incidence and Treatment

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi; Younker, D.; Daniels, V.

2011-01-01

Astronauts use medications for the treatment of a variety of illnesses during space travel. Data mining efforts to assess minor clinical conditions occurring during Shuttle flights STS-1 through STS-94 revealed that space motion sickness (SMS) was the most common ailment during early flight days, occurring in approx.40% of crewmembers, followed by digestive system disturbances (9%) and infectious diseases, which most commonly involved the respiratory or urinary tracts. A more recent analysis of postflight medical debriefs data to examine trends with respect to medication use by astronauts during spaceflights indicated that 37% of all prescriptions recorded was for pain followed by sleep (22%), SMS (18%), decongestion (14%), and all others (14%). Further analysis revealed that about 150 of 317 crewmembers experienced symptoms of SMS. Nearly all (132 of 150) crewmembers took medication for the treatment of symptoms with a total of 387 doses. Promethazine was taken most often (201 doses); in most cases this resulted in alleviation of symptoms with 130 crewmembers (65%) reporting feeling much or somewhat better. Although fewer total doses of the combination of promethazine and dextroamphetamine (Phen/Dex) were taken (45 doses), slightly more than half of these doses resulted in improvement. The combination of scopolamine and dextroamphetamine (Scop/Dex) was reported to be effective in only 37% of cases, with 36 of 97 total doses resulting in improvement. A higher percentage (24%) of Scop/Dex doses was reported to be ineffective compared with promethazine alone or as Phen/Dex (10% and 7%, respectively). Comparisons of the effectiveness of the different dosage forms of promethazine revealed that intramuscular injection was most effective in alleviating symptoms with 55% feeling much better, 16% feeling somewhat better, and only 7% feeling no effect or worse. Overall, it appears that promethazine alone was used more frequently during flight and was reported effective for the treatment of SMS.

Safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects.

PubMed

Jiao, Hui-Wen; Sun, Lu-Ning; Li, Yue-Qi; Yu, Lei; Zhang, Hong-Wen; Wang, Mei-Feng; Yu, Li-Yuan; Yuan, Zi-Qing-Yun; Xie, Li-Jun; Chen, Juan; Meng, Ling; Zhang, Xue-Hui; Wang, Yong-Qing

2018-03-01

The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects. The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(-)-PPZ, 40 mg of single and multiple intravenous administration of S-(-)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(-)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(-)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination. All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(-)-PPZ were dose proportional over the range of 20-80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(-)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(-)-PPZ than 40 mg PPZ; however, the differences were not statistically significant. Twice daily of 40 mg S-(-)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(-)-PPZ, while a few subjects showed faster metabolic rate of S-(-)-PPZ in vivo.

Study on the measurement of photo-neutron for15 MV photon beam from medical linear accelerator under different irradiation geometries using passive detectors.

PubMed

Thekkedath, Siji Cyriac; Raman, R Ganapathi; Musthafa, M M; Bakshi, A K; Pal, Rupali; Dawn, Sandipan; Kummali, Abdul Haneefa; Huilgol, Nagraj G; Selvam, T Palani; Datta, D

2016-01-01

The photo-neutron dose equivalents of 15 MV Elekta precise accelerators were measured for different depths in phantom, for various field sizes, at different distances from the isocenter in the patient plane and for various wedged fields. Fast and thermal neutrons are measured using passive detectors such as Columbia Resin-39 and pair of thermoluminescent dosimetry (TLD) 600 and TLD 700 detector from Elekta medical linear accelerator. It is found that fast photo-neutron dose rate decreases as the depth increases, with a maximum of 0.57 ± 0.08 mSv/Gy photon dose at surface and minimum of 0.09 ± 0.02 mSv/Gy photon dose at 15 cm depth of water equivalent phantom with 10 cm backscatter. Photo neutrons decreases from 1.28 ± 0.03 mSv/Gy to 0.063 ± 0.032 when measured at isocenter and at 100 cm far from the field edge along the longitudinal direction in the patient plane. Fast and thermal neutron doses increases from 0.65 ± 0.05 mSv/Gy to 1.08 ± 0.07 mSv/Gy as the field size increases; from 5 cm × 5 cm to 30 cm × 30 cm for fast neutrons. With increase in wedge field angle from 0° to 60°, it is observed that the fast neutron dose increases from 0.42 ± 0.03 mSv/Gy to 0.95 ± 0.05 mSv/Gy.s Measurements indicate the photo-neutrons at few field sizes are slightly higher than the International Electrotechnical Commission standard specifications. Photo-neutrons from Omni wedged fields are studied in details. These studies of the photo-neutron energy response will enlighten the neutron dose to radiation therapy patients and are expected to further improve radiation protection guidelines.

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

Xu, H; Cape Breton Cancer Centre, Sydney, NS

Purpose: To perform the comparison of dose distributions and dosevolume- histograms generated by VMAT and conventional field-in-field technique for left-sided breast and chestwall cancers; to determine whether VMAT offers more dosimetric benefits than does the field-in-field technique. Methods: All VMAT and field-in-filed plans were produced in Eclipse(version 10). Five plans were generated for left-sided breast and leftsided chestwall with supraclavicular nodes, respectively. A clockwise arc (CW) and a counter-clockwise arc (CCW) were used with start and stop angles being 310o±10o and 140o±10o. Collimator angles were 30o for CW and 330o for CCW. The conformity index (CI) is the ratio ofmore » V95% over PTV. The homogeneity index (HI) is the ratio of the difference between D2% and D98% over the prescribed dose. The V5, as an indicator of low dose bath to organs-at-risk, was used for ipsilateral lung, heart, contralateral lung, and contralateral breast. The V20, as an indicator of radiation pneumonitis, was used for ipsilateral lung. Results: Breast/chestwall VMAT delivers much higher low dose bath to ipsilateral lung, contralateral lung and contralateral breast/chestwall for both intact breast and chestwall with nodes. V5 for heart is increased in VMAT plans. V20 for ipsilateral lung is lower in VMAT plans. PTV coverage is similar for both techniques. For one particular chestwall patient with supraclavicular and internal mammary nodes, VMAT offers superior dose coverage of PTVs with slightly more low-dose-wash to heart, contralateral lung and contralateral breast. Conclusion: This study indicates that there is generally no benefit using VMAT for left-sided intact breast, due to large low-dose-bath (5Gy) to normal tissues with insignificant improvement in PTV coverage. Dosimetric benefits will be seen in VMAT plans for some chestwall patients with large size, and/or internal mammary nodes, etc. Whether a chestwall patient is treated with VMAT should be carefully analyzed on an individual basis.« less

SU-E-T-146: Reference Dosimetry for Protons and Light-Ion Beams Based on Graphite Calorimetry.

PubMed

Rossomme, S; Palmans, H; Thomas, R; Lee, N; Bailey, M; Shipley, D; Al-Sulaiti, L; Cirrone, P; Romano, F; Kacperek, A; Bertrand, D; Vynckier, S

2012-06-01

The IAEA TRS-398 code of practice can be applied for the measurement of absorbed dose to water under reference conditions with an ionization chamber. For protons, the combined relative standard uncertainty on those measurements is less than 2% while for light-ion beams, it is considerably larger, i.e. 3.2%, mainly due to the higher uncertainty contributions for the water to air stopping power ration and the W air-value on the beam quality correction factors kQ,Q 0 . To decrease this uncertainty, a quantification of kQ,Q 0 is proposed using a primary standard level graphite calorimeter. This work includes numerical and experimental determinations of dose conversion factors to derive dose to water from graphite calorimetry. It also reports on the first experimental data obtained with the graphite calorimeter in proton, alpha and carbon ion beams. Firstly, the dose conversion has been calculated with by Geant4 Monte-Carlo simulations through the determination of the water to graphite stopping power ratio and the fluence correction factor. The latter factor was also derived by comparison of measured ionization curves in graphite and water. Secondly, kQ,Q 0 was obtained by comparison of the dose response of ionization chambers with that of the calorimeter. Stopping power ratios are found to vary by no more than 0.35% up to the Bragg peak, while fluence correction factors are shown to increase slightly above unity close to the Bragg peak. The comparison of the calorimeter with ionization chambers is currently under analysis. For the modulated proton beam, preliminary results on W air confirm the value recommended in TRS-398. Data in both the non-modulated proton and light-ion beams indicate higher values but further investigation of heat loss corrections is needed. The application of graphite calorimetry to proton, alpha and carbon ion beams has been demonstrated successfully. Other experimental campaigns will be held in 2012. This work is supported by the BioWin program of the Wallon Government. © 2012 American Association of Physicists in Medicine.

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

NASA Astrophysics Data System (ADS)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient radiopharmaceutical for the treatment of bone metastases than 153Sm and 89Sr, if the diffusion of 219Rn to the bone marrow is insignificant.

Kinetic assessment and modeling of an ozonation step for full-scale municipal wastewater treatment: micropollutant oxidation, by-product formation and disinfection.

PubMed

Zimmermann, Saskia G; Wittenwiler, Mathias; Hollender, Juliane; Krauss, Martin; Ort, Christoph; Siegrist, Hansruedi; von Gunten, Urs

2011-01-01

The kinetics of oxidation and disinfection processes during ozonation in a full-scale reactor treating secondary wastewater effluent were investigated for seven ozone doses ranging from 0.21 to 1.24 g O(3) g(-1) dissolved organic carbon (DOC). Substances reacting fast with ozone, such as diclofenac or carbamazepine (k(P, O3) > 10(4) M(-1) s(-1)), were eliminated within the gas bubble column, except for the lowest ozone dose of 0.21 g O(3) g(-1) DOC. For this low dose, this could be attributed to short-circuiting within the reactor. Substances with lower ozone reactivity (k(P, O3) < 10(4) M(-1) s(-1)) were only fully eliminated for higher ozone doses. The predictions of micropollutant oxidation based on coupling reactor hydraulics with ozone chemistry and reaction kinetics were up to a factor of 2.5 higher than full-scale measurements. Monte Carlo simulations showed that the observed differences were higher than model uncertainties. The overestimation of micropollutant oxidation was attributed to a protection of micropollutants from ozone attack by the interaction with aquatic colloids. Laboratory-scale batch experiments using wastewater from the same full-scale treatment plant could predict the oxidation of slowly-reacting micropollutants on the full-scale level within a factor of 1.5. The Rct value, the experimentally determined ratio of the concentrations of hydroxyl radicals and ozone, was identified as a major contribution to this difference. An increase in the formation of bromate, a potential human carcinogen, was observed with increasing ozone doses. The final concentration for the highest ozone dose of 1.24 g O(3) g(-1) DOC was 7.5 μg L(-1), which is below the drinking water standard of 10 μg L(-1). N-Nitrosodimethylamine (NDMA) formation of up to 15 ng L(-1) was observed in the first compartment of the reactor, followed by a slight elimination during sand filtration. Assimilable organic carbon (AOC) increased up to 740 μg AOC L(-1), with no clear trend when correlated to the ozone dose, and decreased by up to 50% during post-sand filtration. The disinfection capacity of the ozone reactor was assessed to be 1-4.5 log units in terms of total cell counts (TCC) and 0.5 to 2.5 log units for Escherichia coli (E. coli). Regrowth of up to 2.5 log units during sand filtration was observed for TCC while no regrowth occurred for E. coli. E. coli inactivation could not be accurately predicted by the model approach, most likely due to shielding of E. coli by flocs. Copyright © 2010 Elsevier Ltd. All rights reserved.

The absolute bioavailability and metabolic disposition of the novel antimigraine compound zolmitriptan (311C90)

PubMed Central

Seaber, E.; On, N.; Dixon*, R. M.; Gibbens, M.; Leavens, W. J.; Liptrot, J.; Chittick, G.; Posner, J.; Rolan†, P. E.; Peck, R. W.

1997-01-01

Aims Two open studies in healthy volunteers were conducted to determine the absolute bioavailability and metabolic disposition of zolmitriptan (311C90), a novel 5HT1D agonist for the acute treatment of migraine. Methods After an initial test i.v. infusion, bioavailabilty was assessed by comparison of AUC after an i.v. infusion (3.5 mg) and an oral tablet (10 mg), in six men and six women using a randomised, crossover design. Disposition was studied by administration of a 25 mg capsule, labelled with 100 μCi []> 14C]-zolmitriptan, to five men and one woman on a single occasion. Results Zolmitriptan was well tolerated by both i.v. and oral routes. Adverse events were mostly mild, consistent with earlier studies and characteristic of this class of drug. Reports were similar in nature and number after both oral and iv dosing. Mean±s.d. oral bioavailability was 0.49±0.24 (0.38±0.16 in men and 0.60±0.28 in women). After oral dosing, Cmax and AUC values in women were approximately double those in men. Relative to zolmitriptan concentrations, metabolite concentrations were higher after oral dosing than after i.v., and higher in men compared with women. Half-life was significantly longer after oral dosing (mean 22%, 95% CI 6–35%). Mean±s.d. values for CL, Vz and t1/2,z after i.v. dosing (all subjects) were 8.7±1.7 ml min−1 kg−1, 122±32 l and 2.30±0.59 h respectively. Following administration of 25 mg [14C]-zolmitriptan, 91.5% of the dose was recovered in 7 days, 64.4±6.5% in urine and 27.1±6.0% in faeces. Less than 10% was recovered unchanged in urine, with 31.1±6.4% recovered as the inactive indole acetic acid metabolite. Most of the faecal material was unchanged zolmitriptan, representing unabsorbed drug. Plasma concentrations of [14C] were slightly higher than those of the summed concentrations of known analytes zolmitriptan, the active N-desmethyl metabolite (183C91), the inactive N-oxide (1652W92) and indole acetic acid (2161W92) metabolites, which accounted for 86% of total plasma radioactivity. No other significant metabilites were detected in plasma. Some minor additional metabolites were detected in urine, none of which contributed more than 5% of the dose. Conclusions The data suggest that zolmitriptan undergoes first-pass metabolism and this is more extensive in men than in women. Zolmitriptan has suitable bioavailabilty for an acute oral migraine treatment and there are no significant unidentified metabolites in man. PMID:9205817

Initial Investigation of Factors Influencing Radiation Dose to Patients Undergoing Barium-Based Fluoroscopy Procedures in Tanzania.

PubMed

Ngaile, J E; Msaki, P K; Kazema, R R; Schreiner, L J

2017-04-25

The aim of this study was to investigate the nature and causes of radiation dose imparted to patients undergoing barium-based X-ray fluoroscopy procedures in Tanzania and to compare these doses to those reported in the literature from other regions worldwide. The air kerma area product (KAP) to patient undergoing barium investigations of gastrointestinal tract system was obtained from four consultant hospitals. The KAP was determined using a flat transparent transmission ionization chamber. Mean values of KAP for barium swallow (BS), barium meal (BM) and barium enema (BE) were 2.79, 2.62 and 15.04 Gy cm2, respectively. The mean values of KAP per hospital for the BS, BM and BE procedures varied by factors of up to 7.3, 1.6 and 2.0, respectively. The overall difference between individual patient doses across the four consultant hospitals investigated differed by factors of up to 53, 29.5 and 12 for the BS, BM and BE procedures, respectively. The majority of the mean values of KAP was lower than the reported values for Ghana, Greece, Spain and the UK, while slightly higher than those reported for India. The observed wide variation of KAP values for the same fluoroscopy procedure within and among the hospitals was largely attributed to the dynamic nature of the procedures, the patient characteristics, the skills and experience of personnel, and the different examination protocols employed among hospitals. The observed great variations of procedural protocols and patient doses within and across the hospitals call for the need to standardize examination protocols and optimize barium-based fluoroscopy procedures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

PubMed

Kleiter, Miriam M; Yu, Daohai; Mohammadian, Lenore A; Niehaus, Nelsen; Spasojevic, Ivan; Sanders, Linda; Viglianti, Benjamin L; Yarmolenko, Pavel S; Hauck, Marlene; Petry, Neil A; Wong, Terence Z; Dewhirst, Mark W; Thrall, Donald E

2006-11-15

A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)-labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

Time-to-Seizure Modeling of Lacosamide Used in Monotherapy in Patients with Newly Diagnosed Epilepsy.

PubMed

Lindauer, Andreas; Laveille, Christian; Stockis, Armel

2017-11-01

To quantify the relationship between exposure to lacosamide monotherapy and seizure probability, and to simulate the effect of changing the dose regimen. Structural time-to-event models for dropouts (not because of a lack of efficacy) and seizures were developed using data from 883 adult patients newly diagnosed with epilepsy and experiencing focal or generalized tonic-clonic seizures, participating in a trial (SP0993; ClinicalTrials.gov identifier: NCT01243177) comparing the efficacy of lacosamide and carbamazepine controlled-release monotherapy. Lacosamide dropout and seizure models were used for simulating the effect of changing the initial target dose on seizure freedom. Repeated time-to-seizure data were described by a Weibull distribution with parameters estimated separately for the first and subsequent seizures. Daily area under the plasma concentration-time curve was related linearly to the log-hazard. Disease severity, expressed as the number of seizures during the 3 months before the trial (baseline), was a strong predictor of seizure probability: patients with 7-50 seizures at baseline had a 2.6-fold (90% confidence interval 2.01-3.31) higher risk of seizures compared with the reference two to six seizures. Simulations suggested that a 400-mg/day, rather than a 200-mg/day initial target dose for patients with seven or more seizures at baseline could potentially result in an additional 8% of seizure-free patients for 6 months at the last evaluated dose level. Patients receiving lacosamide had a slightly lower dropout risk compared with those receiving carbamazepine. Baseline disease severity was the most important predictor of seizure probability. Simulations suggest that an initial target dose >200 mg/day could potentially benefit patients with greater disease severity.

Influence of the estrus cycle on the evaluation of a vaginal irritation study in intact and ovariectomized rats

PubMed Central

Ishii, Aiko; Ogawa, Bunichiro; Koyama, Tomoko; Nakanishi, Yutaka; Sasaki, Minoru

2017-01-01

When conducting vaginal irritation studies, ovariectomized rats or rabbits are typically used according to practical reports. In the present study, we evaluated the influence of the estrus cycle in a vaginal irritation study using intact rats and ovariectomized rats, which exhibit a late diestrus-like condition, to determine whether intact rats can be useful for evaluating vaginal irritancy. Rats were divided into 4 groups: proestrus, estrus, and metestrus or diestrus in intact rats and ovariectomized rats. All the rats in each group were treated with a vehicle or sodium dodecyl sulfate, as the irritant, in single-dose and 4-day repeat-dose vaginal irritation studies. Each rat’s vagina was examined histopathologically, and the irritation score was calculated using a semiquantitative scoring system. In the single-dose study, the irritation scores for the proestrus or ovariectomized groups treated with sodium dodecyl sulfate were higher than those of the estrus group or metestrus or diestrus group. In the 4-day repeat-dose study, a significant histopathological difference was not found among the intact rats (proestrus, estrus, and metestrus or diestrus groups), and the irritation score range of the intact rats was similar to that of the ovariectomized rats, though the mean score of the intact rats was slightly lower than that of the ovariectomized rats. These results suggest that intact rats might be well suited for 4-day vaginal irritation studies and useful for evaluating vaginal irritancy using not only the mean score, but also individual irritation score ranges, whereas the estrus cycle would need to be identified in single-dose vaginal irritation studies. PMID:28458454

Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.

PubMed

Semvua, Hadija H; Mtabho, Charles M; Fillekes, Quirine; van den Boogaard, Jossy; Kisonga, Riziki M; Mleoh, Liberate; Ndaro, Arnold; Kisanga, Elton R; van der Ven, Andre; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Burger, David M

2013-01-01

To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART). A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using 125I seeds

PubMed Central

Wang, Zhong-Min; Lu, Jian; Zhang, Li-Yun; Lin, Xiao-Zhu; Chen, Ke-Min; Chen, Zhi-Jin; Liu, Fen-Ju; Yan, Fu-Hua; Teng, Gao-Jun; Mao, Ai-Wu

2015-01-01

AIM: To determine the mechanism of the radiation-induced biological effects of 125I seeds on pancreatic carcinoma cells in vitro. METHODS: SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment. Gray’s model of iodine-125 (125I) seed irradiation was used. In vitro, exponential phase SW1990, and PANC-1 cells were exposed to 0, 2, 4, 6, and 8 Gy using 125I radioactive seeds, with an initial dose rate of 12.13 cGy/h. A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies. Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells. DNA synthesis was measured via a tritiated thymidine (3H-TdR) incorporation experiment. After continuous low-dose-rate irradiation with 125I radioactive seeds, the survival fractions at 2 Gy (SF2), percentage apoptosis, and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared. RESULTS: The survival fractions of the PANC-1 and SW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased. No significant difference in SF2 was observed between SW1990 and PANC-1 cells (0.766 ± 0.063 vs 0.729 ± 0.045, P < 0.05). The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990 and PANC-1 cells. The rate of apoptosis increased with increasing radiation dosage. The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells. Dose-dependent G2/M cell-cycle arrest was observed after 125I seed irradiation, with a peak value at 6 Gy. As the dose increased, the percentage of G2/M cell cycle arrest increased in both cell lines, whereas the rate of DNA incorporation decreased. In the 3H-TdR incorporation experiment, the dosimetry results of both the SW1990 and PANC-1 cells decreased as the radiation dose increased, with a minimum at 6 Gy. There were no significant differences in the dosimetry results of the two cell lines when they were exposed to the same dose of radiation. CONCLUSION: The pancreatic cancer cell-killing effects induced by 125I radioactive seeds mainly occurred via apoptosis and G2/M cell cycle arrest. PMID:25741139

Evaluation of XD/A Plus and ST8G films for cephalometric radiography with Grenex G8 and BH-III screens.

PubMed

Wakoh, M; Farman, A G; Scarfe, W C; Shibuya, H; Nishikawa, K; Kuroyanagi, K

1997-02-01

Sensitometric properties, clinical image quality, and patient dose requirements are important considerations when selecting film for cephalometrics. Two recently released films, XD/A Plus and ST 8G green sensitive films, were studied. The films were each combined with Grenex G8 (Fuji Medical) green-fluorescing matched and BH-III (Kasei Optonix) blue-fluorescing mismatched intensifying screens. The density response and resolution for each screen-film combination were evaluated by use of the characteristic curve and modulation transfer function. The kilovoltage settings providing clinically acceptable images were assessed individually by 12 observers. Clinically acceptable images for each combination were also compared, and the skin entrance doses in the temporomandibular joint region were determined. The average contrast at the most effective density range was found to be slightly higher for the BH-III group than for the G8 group. The modulation transfer function for the BH-III group was inferior to that for the G8 screens. There were no significant differences in diagnostically acceptable image quality among the four combinations; nevertheless the BH-III screen group required two to three times more exposure than the G8 screen group. XD/A Plus and ST8G films provide acceptable image detail for cephalometrics. To minimize the patient dose they should be used with green-emitting screens.

Effects of Vigabatrin, an Irreversible GABA Transaminase Inhibitor, on Ethanol Reinforcement and Ethanol Discriminative Stimuli in Mice

PubMed Central

Griffin, William C.; Nguyen, Shaun A.; Deleon, Christopher P.; Middaugh, Lawrence D.

2012-01-01

We tested the hypothesis that the irreversible gamma-amino butyric acid (GABA) transaminase inhibitor, γ-vinyl GABA (Vigabatrin; VGB) would reduce ethanol reinforcement and enhance the discriminative stimulus effect of ethanol, effectively reducing ethanol intake. The present studies used adult C57BL/6J (B6) mice in well-established operant, two-bottle choice consumption, locomotor activity and ethanol discrimination procedures, to examine comprehensively the effects of VGB on ethanol-supported behaviors. VGB dose-dependently reduced operant responding for ethanol as well as ethanol consumption for long periods of time. Importantly, a low dose (200 mg/kg) of VGB was selective for reducing ethanol responding without altering intake of food or water reinforcement. Higher VGB doses (>200 mg/kg) still reduced ethanol intake, but also significantly increased water consumption and, more modestly, increased food consumption. While not affecting locomotor activity on its own, VGB interacted with ethanol to reduce the stimulatory effects of ethanol on locomotion. Finally, VGB (200 mg/kg) significantly enhanced the discriminative stimulus effects of ethanol as evidenced by significant left-ward and up-ward shifts in ethanol generalization curves. Interestingly, VGB treatment was associated with slight increases in blood ethanol concentrations. The reduction in ethanol intake by VGB appears to be related to the ability of VGB to potentiate the pharmacological effects of ethanol. PMID:22336593

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

PubMed

Gorur, F Korkmaz; Camgoz, H

2014-10-01

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

Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases : Plan comparison and early clinical evaluation.

PubMed

Rieber, J; Tonndorf-Martini, E; Schramm, O; Rhein, B; Stefanowicz, S; Kappes, J; Hoffmann, H; Lindel, K; Debus, J; Rieken, S

2016-11-01

Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 × 20 Gy or 1 × 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 × 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (-1.1 %, -29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (-1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6‑month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity.

A diamond detector in the dosimetry of high-energy electron and photon beams.

PubMed

Laub, W U; Kaulich, T W; Nüsslin, F

1999-09-01

A diamond detector type 60003 (PTW Freiburg) was examined for the purpose of dosimetry with 4-20 MeV electron beams and 4-25 MV photon beams. Results were compared with those obtained by using a Markus chamber for electron beams and an ionization chamber for photon beams. Dose distributions were measured in a water phantom with the detector connected to a Unidos electrometer (PTW Freiburg). After a pre-irradiation of about 5 Gy the diamond detector shows a stability in response which is better than that of an ionization chamber. The current of the diamond detector was measured under variation of photon beam dose rate between 0.1 and 7 Gy min(-1). Different FSDs were chosen. Furthermore the pulse repetition frequency and the depth of the detector were changed. The electron beam dose rate was varied between 0.23 and 4.6 Gy min(-1) by changing the pulse-repetition frequency. The response shows no energy dependence within the covered photon-beam energy range. Between 4 MeV and 18 MeV electron beam energy it shows only a small energy dependence of about 2%, as expected from theory. For smaller electron energies the response increases significantly and an influence of the contact material used for the diamond detector can be surmised. A slight sublinearity of the current and dose rate was found. Detector current and dose rate are related by the expression i alpha Ddelta, where i is the detector current, D is the dose rate and delta is a correction factor of approximately 0.963. Depth-dose curves of photon beams, measured with the diamond detector, show a slight overestimation compared with measurements with the ionization chamber. This overestimation is compensated for by the above correction term. The superior spatial resolution of the diamond detector leads to minor deviations between depth-dose curves of electron beams measured with a Markus chamber and a diamond detector.

A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel.

PubMed

Skouby, Sven O; Endrikat, Jan; Düsterberg, Bernd; Schmidt, Werner; Gerlinger, Christoph; Wessel, Jens; Goldstein, Henri; Jespersen, Joergen

2005-02-01

To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives. In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained. We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers. Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.

Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation.

PubMed

Dorr, R T; Briggs, A; Kintzel, P; Meyers, R; Chow, H-H S; List, A

2003-04-01

The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P=0.056). Conversely, the volume of distribution was slightly, 33%, larger (P=0.052) and clearance was increased with the E infusion (P=0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.

Gamma irradiation induces acetylcholine-evoked, endothelium-independent relaxation and activatesk-channels of isolated pulmonary artery of rats

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

Eder, Veronique; Gautier, Mathieu; Boissiere, Julien

2004-12-01

Purpose: To test the effects of irradiation (R*) on the pulmonary artery (PA). Methods and materials: Isolated PA rings were submitted to gamma irradiation (cesium, 8 Gy/min{sup -1}) at doses of 20 Gy-140 Gy. Rings were placed in an organ chamber, contracted with serotonin (10{sup -4} M 5-hydroxytryptamine [5-HT]), then exposed to acetylcholine (ACh) in incremental concentrations. Smooth muscle cell (SMC) membrane potential was measured with microelectrodes. Results: A high dose of irradiation (60 Gy) increased 5HT contraction by 20%, whereas lower (20 Gy) doses slightly decreased it compared with control. In the absence of the endothelium, 5-HT precontracted ringsmore » exposed to 20 Gy irradiation developed a dose-dependent relaxation induced by acetylcholine (EI-ACh) with maximal relaxation of 60 {+-} 17% (n = 13). This was totally blocked by L-NAME (10{sup -4} M), partly by 7-nitro indazole; it was abolished by hypoxia and iberiotoxin, decreased by tetra-ethyl-ammonium, and not affected by free radical scavengers. In irradiated rings, hypoxia induced a slight contraction which was never observed in control rings. No differences in SMC membrane potential were observed between irradiated and nonirradiated PA rings. Conclusion: Irradiation mediates endothelium independent relaxation by a mechanism involving the nitric oxide pathway and K-channels.« less

Global transport and deposition of 137Cs following the Fukushima nuclear power plant accident in Japan: emphasis on Europe and Asia using high-resolution model versions and radiological impact assessment of the human population and the environment using interactive tools.

PubMed

Evangeliou, Nikolaos; Balkanski, Yves; Cozic, Anne; Møller, Anders Pape

2013-06-04

The earthquake and the subsequent tsunami that occurred offshore of Japan resulted in an important loss of life and a serious accident at the nuclear facility of Fukushima. The "hot spots" of the release are evaluated here applying the model LMDZORINCA for (137)Cs. Moreover, an assessment is attempted for the population and the environment using the dosimetric scheme of the WHO and the interactive tool ERICA, respectively. Cesium-137 was deposited mostly in Pacific and Atlantic Oceans and North Pole (80%), whereas the rest in the continental areas of North America and Eurasia contributed slightly to the natural background (0.5-5.0 kBq m(-2)). The effective dose from (137)Cs and (134)Cs (radiocesium) irradiation during the first 3 months was estimated between 1-5 mSv in Fukushima and the neighboring prefectures. In the rest of Japan, the respective doses were found to be less than 0.5 mSv, whereas in the rest of the world it was less than 0.1 mSv. Such doses are equivalent with the obtained dose from a simple X-ray; for the highly contaminated regions, they are close to the dose limit for exposure due to radon inhalation (10 mSv). The calculated dose rates from radiocesium exposure on reference organisms ranged from 0.03 to 0.18 μGy h(-1), which are 2 orders of magnitude below the screening dose limit (10 μGy h(-1)) that could result in obvious effects on the population. However, these results may underestimate the real situation, since stable soil density was used in the calculations, a zero radiocesium background was assumed, and dose only from two radionuclides was estimated, while more that 40 radionuclides have been deposited in the vicinity of the facility. When monitoring data applied, much higher dose rates were estimated certifying ecological risk for small mammals and reptiles in terms of cytogenetic damage and reproduction.

Effects of caffeic and chlorogenic acids on the rat skeletal system.

PubMed

Folwarczna, J; Pytlik, M; Zych, M; Cegieła, U; Nowinska, B; Kaczmarczyk-Sedlak, I; Sliwinski, L; Trzeciak, H; Trzeciak, H I

2015-02-01

Caffeic acid, predominantly as esters linked to quinic acid (chlorogenic acids), is a phenolic acid present at high levels in coffee. The aim of the study was to investigate effects of caffeic and chlorogenic acids on the skeletal system of female rats with normal estrogen levels and estrogen-deficient. Caffeic acid (5 and 50 mg/kg p.o. daily) and chlorogenic acid (100 mg/kg p.o. daily) were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized mature Wistar rats, and their effects were compared with appropriate controls. Moreover, estradiol (0.2 mg/kg p.o. daily) was administered to ovariectomized rats. Bone turnover markers, mass, mineralization and mechanical properties were examined. Although caffeic acid at a low dose exerted some unfavorable effects on the skeletal system, at high doses, caffeic and chlorogenic acids slightly increased mineralization in the tibia and improved mechanical properties of the femoral diaphysis (compact bone). Unlike estradiol, they did not counteract the worsening of the tibial metaphysis bone strength (cancellous bone) and increases in osteocalcin concentration induced by estrogen deficiency. High doses of the phenolic acids slightly favorably affected the rat skeletal system independently of the estrogen status.

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

Acar, H; Cebe, M; Mabhouti, H

Purpose: Stereotactic body radiosurgery (SBRT) for spine metastases involves irradiation using a single high dose fraction. The purpose of this study was to investigate a Hybrid VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for spine SBRT in terms of its dosimetric quality and treatment efficiency using Radiation Therapy Oncology Group (RTOG) 0631 guidelines. Methods: 7 fields IMRT, 2 full arcs VMAT and Hybrid VMAT/IMRT were created for ten previously treated patients. The Hybrid VMAT/IMRT technique consisted of 1 full VMAT arc and 5 IMRT fields. Hybrid VMAT/IMRT plans were compared with IMRTmore » and VMAT plans in terms of the dose distribution, spinal cord sparing, homogeneity, conformity and gradient indexies, monitor unit (MU) and beam on time (BOT). RTOG 0631 recommendations were applied for treatment planning. All plans were normalized and prescribed to deliver 18.0 Gy in a single fraction to 90% of the target volume. Results: The Hybrid VMAT/IMRT technique significantly improved target dose homogeneity and conformity compared with IMRT and VMAT techniques. Providing sharp dose gradient Hybrid VMAT/IMRT plans spare the spinal cord and healthy tissue more effectively. Although, both MU and BOT slightly increased in Hybrid VMAT/IMRT plans there is no statistically meaningful difference between VMAT and Hybrid VMAT/IMRT plans. Conclusion: In IMRT, a smaller volume of healthy tissue can be irradiated in the low dose region, VMAT plans provide better target volume coverage, favorable dose gradient, conformity and better OAR sparing and also they require a much smaller number of MUs and thus a shorter treatment time than IMRT plans. Hybrid plan offers a sinergy through combination of these two techniques with slightly increased number of MU and thus more treatment time.« less

[Repeated dose toxicity studies of taltirelin tetrahydrate(TA-0910) by oral administration to rats].

PubMed

Inui, T; Fujiwara, T; Susami, M; Hishida, N; Kuwamura, Y; Kuse, H; Kawai, Y; Kudow, S

1997-11-01

Four-, 13- and 52-week repeated dose toxicity studies of taltirelin tetrahydrate(TA-0910), a thyrotropin-releasing hormone(TRH) analogue, were carried out in rats. Through the three studies, TA-0910 solution was administered orally at doses of 3, 30 and 300 mg/kg/day. The animals receiving TA-0910 showed hyperlocomotion, grooming and wet dog shaking which were attributable to the central effects similar to those of TRH, but there was no death nor obvious deterioration of health caused by the treatment. Body weights decreased in males of 300 mg/kg group, and food consumption was on the upward trend in females in 300 mg/kg group. In 13- and 52-week studies, females receiving 300 mg/kg showed elongated estrous cycle, although it was not an evident change. Blood examinations revealed increases in erythrocyte count, hemoglobin and hematocrit in 300 mg/kg group. Reductions in serum(plasma) proteins and lipids, and drug-metabolizing enzyme activity of the liver were regarded as non-specific changes, as they were sporadic and slight in 300 mg/kg group. Salivary gland and adrenal weights increased in 300 mg/kg group. For the thyroid, weights increased in 300 mg/kg group in the 4- and 13-week studies, and increases of microfollicles and cell debris were observed microscopically in each treated group in the 52-week study. These changes seemed to be related with hormonal action of TA-0910, but the effects on animals were judged slight from plasma TSH and thyroid hormone levels after 4 weeks of dosing. The non-toxic dose was estimated to be 30 mg/kg/day, through the rat repeated dose toxicity studies. All the above changes were alleviated or abolished by 4-week recovery period.

SU-E-I-82: Improving CT Image Quality for Radiation Therapy Using Iterative Reconstruction Algorithms and Slightly Increasing Imaging Doses

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

Noid, G; Chen, G; Tai, A

2014-06-01

Purpose: Iterative reconstruction (IR) algorithms are developed to improve CT image quality (IQ) by reducing noise without diminishing spatial resolution or contrast. For CT in radiation therapy (RT), slightly increasing imaging dose to improve IQ may be justified if it can substantially enhance structure delineation. The purpose of this study is to investigate and to quantify the IQ enhancement as a result of increasing imaging doses and using IR algorithms. Methods: CT images were acquired for phantoms, built to evaluate IQ metrics including spatial resolution, contrast and noise, with a variety of imaging protocols using a CT scanner (Definition ASmore » Open, Siemens) installed inside a Linac room. Representative patients were scanned once the protocols were optimized. Both phantom and patient scans were reconstructed using the Sinogram Affirmed Iterative Reconstruction (SAFIRE) and the Filtered Back Projection (FBP) methods. IQ metrics of the obtained CTs were compared. Results: IR techniques are demonstrated to preserve spatial resolution as measured by the point spread function and reduce noise in comparison to traditional FBP. Driven by the reduction in noise, the contrast to noise ratio is doubled by adopting the highest SAFIRE strength. As expected, increasing imaging dose reduces noise for both SAFIRE and FBP reconstructions. The contrast to noise increases from 3 to 5 by increasing the dose by a factor of 4. Similar IQ improvement was observed on the CTs for selected patients with pancreas and prostrate cancers. Conclusion: The IR techniques produce a measurable enhancement to CT IQ by reducing the noise. Increasing imaging dose further reduces noise independent of the IR techniques. The improved CT enables more accurate delineation of tumors and/or organs at risk during RT planning and delivery guidance.« less

Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice.

PubMed

Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Silva, Paula Regina Pereira; Borelli, Primavera; Fock, Ricardo Ambrósio; Trevisan, Maria Teresa Salles; Mauad, Thais

2011-06-01

Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24h after oral administration of 250 mg/kg AAs. Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Sci—Fri PM: Dosimetry—01: Radiation-induced refraction artefacts in the optical CT readout of polymer gel dosimeters

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

Campbell, Warren G; Jirasek, Andrew; Wells, Derek M

2014-08-15

Polymer gel dosimeters (PGDs) are a desirable tool for the verification of advanced radiotherapy treatments. Fully 3D, deformable, and tissue-equivalent, the PGD polymerizes wherever it absorbs dose. To measure the dose absorbed by a PGD, optical computed tomography (CT) can be used to evaluate, in full 3D, the opacity distribution that coincides with polymerization. In addition to an increase in opacity with dose, an increase in refractive index (RI) is also known to occur in irradiated polymer gels. The increase in RI is slight and was previously assumed insignificant. This work reveals the effects that radiation-induced RI changes can havemore » on the optical CT readout of PGDs. A fan-beam optical CT scanner was used to image a cylindrical PGD irradiated by a pair of 3×3 cm{sup 2}, 6 MV photon beams in an orthogonal arrangement. Investigative scans were performed to evaluate refraction errors occurring: i) within the plane, and ii) out of the plane of the fan-beam. In-plane refraction was shown to cause distinct streaking artefacts along dose gradients (i.e. RI gradients) due to higher intensity rays being refracted into more opaque regions. Out-of-plane refraction was shown to produce severe, widespread artefacts due to rays missing the detector array. An iterative Savitzky-Golay filtering technique was developed to reduce both types of artefacts by specifically targeting structured errors in sinogram space. Results introduce a new category of imaging artefacts to be aware of when using optical CT for PGD readout.« less

Effects of Low-Dose Ionizing Radiation and Menadione, an Inducer of Oxidative Stress, Alone and in Combination in a Vertebrate Embryo Model

PubMed Central

Bladen, Catherine L.; Kozlowski, David J.; Dynan, William S.

2014-01-01

Prior work has established the zebrafish embryo as an in vivo model for studying the biological effects of exposure to low doses of ionizing radiation. One of the known effects of radiation is to elevate the levels of reactive oxygen species (ROS) in tissue. However, ROS are also produced as byproducts of normal metabolism and, regardless of origin, ROS produce similar chemical damage to DNA. Here we use the zebrafish embryo model to investigate whether the effects of low-dose (0–1.5 Gy) radiation and endogenous ROS are mechanistically distinct. We increased levels of endogenous ROS by exposure to low concentrations of the quinone drug, menadione. Imaging studies in live embryos showed that exposure to 3 μM or higher concentrations of menadione dramatically increased ROS levels. This treatment was associated with a growth delay and morphologic abnormalities, which were partially or fully reversible. By contrast, exposure to low doses of ionizing radiation had no discernable effects on overall growth or morphology, although, there was an increase in TUNEL-positive apoptotic cells, consistent with the results of prior studies. Further studies showed that the combined effect of radiation and menadione exposure are greater than with either agent alone, and that attenuation of the expression of Ku80, a gene important for repair of radiation-induced DNA damage, had only a slight effect on menadione sensitivity. Together, results suggest that ionizing radiation and menadione affect the embryo by distinct mechanisms. PMID:23092554

Sensitivity to psychostimulants in mice bred for high and low stimulation to methamphetamine.

PubMed

Kamens, H M; Burkhart-Kasch, S; McKinnon, C S; Li, N; Reed, C; Phillips, T J

2005-03-01

Methamphetamine (MA) and cocaine induce behavioral effects primarily through modulation of dopamine neurotransmission. However, the genetic regulation of sensitivity to these two drugs may be similar or disparate. Using selective breeding, lines of mice were produced with extreme sensitivity (high MA activation; HMACT) and insensitivity (low MA activation; LMACT) to the locomotor stimulant effects of acute MA treatment. Studies were performed to determine whether there is pleiotropic genetic influence on sensitivity to the locomotor stimulant effect of MA and to other MA- and cocaine-related behaviors. The HMACT line exhibited more locomotor stimulation in response to several doses of MA and cocaine, compared to the LMACT line. Both lines exhibited locomotor sensitization to 2 mg/kg of MA and 10 mg/kg of cocaine; the magnitude of sensitization was similar in the two lines. However, the lines differed in the magnitude of sensitization to a 1 mg/kg dose of MA, a dose that did not produce a ceiling effect that may confound interpretation of studies using higher doses. The LMACT line consumed more MA and cocaine in a two-bottle choice drinking paradigm; the lines consumed similar amounts of saccharin and quinine, although the HMACT line exhibited slightly elevated preference for a low concentration of saccharin. These results suggest that some genes that influence sensitivity to the acute locomotor stimulant effect of MA have a pleiotropic influence on the magnitude of behavioral sensitization to MA and sensitivity to the stimulant effects of cocaine. Further, extreme sensitivity to MA may protect against MA and cocaine self-administration.

Effect of irradiation on the patulin content and chemical composition of apple juice concentrate.

PubMed

Zegota, H; Zegota, A; Bachman, S

1988-09-01

The influence of ionizing radiation on the patulin content of apple juice concentrate was investigated. The results indicated that patulin, at an initial concentration of about 2 mg/kg, disappeared after irradiation of the concentrate with doses as low as 2.5 kGy. For lower doses, the extent of patulin degradation was proportional to the absorbed dose. Irradiation of the concentrate with doses sufficient for patulin disappearance did not change the titratable acidity, the content of reducing sugars and carbonyl compounds or the amino acid composition. The content of ascorbic acid slightly decreased and the colour of the concentrate brightened. The intensity of the patulin absorption spectra after irradiation of mycotoxin in aqueous solutions decreased.

Single oral dose safety of D-allulose in dogs.

PubMed

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

2016-07-01

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

Does infrared or ultraviolet light damage the lens?

PubMed Central

Söderberg, P G; Talebizadeh, N; Yu, Z; Galichanin, K

2016-01-01

In daylight, the human eye is exposed to long wavelength ultraviolet radiation (UVR), visible radiation and short wavelength infrared radiation (IRR). Almost all the UVR and a fraction of the IRR waveband, respectively, left over after attenuation in the cornea, is absorbed in the lens. The time delay between exposure and onset of biological response in the lens varies from immediate-to-short-to-late. After exposure to sunlight or artificial sources, generating irradiances of the same order of magnitude or slightly higher, biological damage may occur photochemically or thermally. Epidemiological studies suggest a dose-dependent association between short wavelength UVR and cortical cataract. Experimental data infer that repeated daily in vivo exposures to short wavelength UVR generate photochemically induced damage in the lens, and that short delay onset cataract after UVR exposure is photochemically induced. Epidemiology suggests that daily high-intensity short wavelength IRR exposure of workers, is associated with a higher prevalence of age-related cataract. It cannot be excluded that this effect is owing to a thermally induced higher denaturation rate. Recent experimental data rule out a photochemical effect of 1090 nm in the lens but other wavelengths in the near IRR should be investigated. PMID:26768915

Celecoxib Versus Placebo in Tonsillectomy: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial.

PubMed

Van Daele, Douglas J; Bodeker, Kellie L; Trask, Douglas K

2016-10-01

Celecoxib is a cyclooxygenase-2-specific inhibitor indicated to treat acute pain and pain secondary to osteoarthritis and rheumatoid arthritis. Surgical models of acute pain have demonstrated superior pain relief to placebo. The objective of this study was to test the safety and efficacy of celecoxib for pain relief after tonsillectomy compared to placebo. Adult subjects were randomized to 200 mg celecoxib versus placebo with a loading dose the night before surgery then twice daily for 10 days. Subjects were instructed to supplement the study drug with hydrocodone/acetaminophen liquid or acetaminophen for pain as needed. Subjects completed a daily diary regarding their pain, nausea, vomiting, diet, and activity. Seventeen subjects enrolled. Intraoperative blood loss was similar between groups, and no subject had postoperative bleeding. Three patients returned to the emergency department for treatment, and 2 patients could not complete the diaries, all in the placebo group. Subjects in the placebo group required statistically significant (P < .05) higher doses of narcotic and acetaminophen to control pain. Pain and diet rating scores were slightly better in the celecoxib group compared to placebo. In this small cohort, celecoxib reduced postoperative narcotic and acetaminophen requirements compared to placebo without complications. © The Author(s) 2016.

Biophysical characterization of a relativistic proton beam for image-guided radiosurgery

PubMed Central

Yu, Zhan; Vanstalle, Marie; La Tessa, Chiara; Jiang, Guo-Liang; Durante, Marco

2012-01-01

We measured the physical and radiobiological characteristics of 1 GeV protons for possible applications in stereotactic radiosurgery (image-guided plateau-proton radiosurgery). A proton beam was accelerated at 1 GeV at the Brookhaven National Laboratory (Upton, NY) and a target in polymethyl methacrylate (PMMA) was used. Clonogenic survival was measured after exposures to 1–10 Gy in three mammalian cell lines. Measurements and simulations demonstrate that the lateral scattering of the beam is very small. The lateral dose profile was measured with or without the 20-cm plastic target, showing no significant differences up to 2 cm from the axis A large number of secondary swift protons are produced in the target and this leads to an increase of approximately 40% in the measured dose on the beam axis at 20 cm depth. The relative biological effectiveness at 10% survival level ranged between 1.0 and 1.2 on the beam axis, and was slightly higher off-axis. The very low lateral scattering of relativistic protons and the possibility of using online proton radiography during the treatment make them attractive for image-guided plateau (non-Bragg peak) stereotactic radiosurgery. PMID:22843629

A Study of Gamma-Ray Exposure of Cu-SiO2 Programmable Metallization Cells

NASA Astrophysics Data System (ADS)

Chen, W.; Barnaby, H. J.; Kozicki, M. N.; Edwards, A. H.; Gonzalez-Velo, Y.; Fang, R.; Holbert, K. E.; Yu, S.; Yu, W.

2015-12-01

The Cu-SiO2 based programmable metallization cell (PMC) is a promising alternative to the Ag-chalcogenide glass PMC because of its low power consumption and CMOS-compatibility. Understanding its total ionizing dose (TID) response helps in assessing the reliability of this technology in ionizing radiation environments and benefits its expansion in the space electronics market. In this paper, the impacts of TID on the switching characteristics of Cu-SiO2 PMC are investigated for the first time. The devices were step irradiated with 60Co gamma-rays to a maximum dose of 7.1 Mrad ( SiO2). The results show that gamma-ray irradiation has a negligible impact on the virgin-state and on-state resistance of Cu-SiO2 PMCs. The off-state resistance slightly decreases after the first 1.5 Mrad( SiO2) of exposure, but this reduction saturates after higher levels of TID. Other switching characteristics such as the set voltage, multilevel switching capability and endurance were also studied, all of which did not show observable changes after gamma-ray radiation. The immunity to ionizing radiation is attributed to the suppression of the photo-doping process.

Laser biostimulation therapy planning supported by imaging

NASA Astrophysics Data System (ADS)

Mester, Adam R.

2018-04-01

Ultrasonography and MR imaging can help to identify the area and depth of different lesions, like injury, overuse, inflammation, degenerative diseases. The appropriate power density, sufficient dose and direction of the laser treatment can be optimally estimated. If required minimum 5 mW photon density and required optimal energy dose: 2-4 Joule/cm2 wouldn't arrive into the depth of the target volume - additional techniques can help: slight compression of soft tissues can decrease the tissue thickness or multiple laser diodes can be used. In case of multiple diode clusters light scattering results deeper penetration. Another method to increase the penetration depth is a second pulsation (in kHz range) of laser light. (So called continuous wave laser itself has inherent THz pulsation by temporal coherence). Third solution of higher light intensity in the target volume is the multi-gate technique: from different angles the same joint can be reached based on imaging findings. Recent developments is ultrasonography: elastosonography and tissue harmonic imaging with contrast material offer optimal therapy planning. While MRI is too expensive modality for laser planning images can be optimally used if a diagnostic MRI already was done. Usual DICOM images offer "postprocessing" measurements in mm range.

Comparison of calculated beta- and gamma-ray doses after the Fukushima accident with data from single-grain luminescence retrospective dosimetry of quartz inclusions in a brick sample

PubMed Central

Endo, Satoru; Fujii, Keisuke; Kajimoto, Tsuyoshi; Tanaka, Kenichi; Stepanenko, Valeriy; Kolyzhenkov, Timofey; Petukhov, Aleksey; Akhmedova, Umukusum; Bogacheva, Viktoriia

2018-01-01

Abstract To estimate the beta- and gamma-ray doses in a brick sample taken from Odaka, Minami-Soma City, Fukushima Prefecture, Japan, a Monte Carlo calculation was performed with Particle and Heavy Ion Transport code System (PHITS) code. The calculated results were compared with data obtained by single-grain retrospective luminescence dosimetry of quartz inclusions in the brick sample. The calculated result agreed well with the measured data. The dose increase measured at the brick surface was explained by the beta-ray contribution, and the slight slope in the dose profile deeper in the brick was due to the gamma-ray contribution. The skin dose was estimated from the calculated result as 164 mGy over 3 years at the sampling site. PMID:29385528

Comparison of calculated beta- and gamma-ray doses after the Fukushima accident with data from single-grain luminescence retrospective dosimetry of quartz inclusions in a brick sample.

PubMed

Endo, Satoru; Fujii, Keisuke; Kajimoto, Tsuyoshi; Tanaka, Kenichi; Stepanenko, Valeriy; Kolyzhenkov, Timofey; Petukhov, Aleksey; Akhmedova, Umukusum; Bogacheva, Viktoriia

2018-05-01

To estimate the beta- and gamma-ray doses in a brick sample taken from Odaka, Minami-Soma City, Fukushima Prefecture, Japan, a Monte Carlo calculation was performed with Particle and Heavy Ion Transport code System (PHITS) code. The calculated results were compared with data obtained by single-grain retrospective luminescence dosimetry of quartz inclusions in the brick sample. The calculated result agreed well with the measured data. The dose increase measured at the brick surface was explained by the beta-ray contribution, and the slight slope in the dose profile deeper in the brick was due to the gamma-ray contribution. The skin dose was estimated from the calculated result as 164 mGy over 3 years at the sampling site.

Effect of electron beam irradiation on thermal and mechanical properties of epoxy polymer

NASA Astrophysics Data System (ADS)

Nguyen, A. T.; Visakh, P. M.; Nazarenko, O. B.; Chandran, C. S.; Melnikova, T. V.

2017-01-01

This study investigates the thermal and mechanical properties of epoxy polymer after exposure to different doses of electron beam irradiation. The epoxy polymer was prepared using epoxy-diane resin ED-20 cured by polyethylenepolyamine. The irradiation of the samples was carried out with doses of 30, 100 and 300 kGy. The effects of doses on thermal and mechanical properties of the epoxy polymer were investigated by the methods of thermal gravimetric analysis, tensile test, and dynamic mechanical analysis. The thermal properties of the epoxy polymer slightly increased after irradiation at the heating in air. The tensile strength and Young’s modulus of the epoxy polymer increased by the action of electron beam up to dose of 100 kGy and then decreased. The elongation at break decreased with increasing the irradiation dose.

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

PubMed

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

2015-09-01

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

Patient‐specific CT dosimetry calculation: a feasibility study

PubMed Central

Xie, Huchen; Cheng, Jason Y.; Ning, Holly; Zhuge, Ying; Miller, Robert W.

2011-01-01

Current estimation of radiation dose from computed tomography (CT) scans on patients has relied on the measurement of Computed Tomography Dose Index (CTDI) in standard cylindrical phantoms, and calculations based on mathematical representations of “standard man”. Radiation dose to both adult and pediatric patients from a CT scan has been a concern, as noted in recent reports. The purpose of this study was to investigate the feasibility of adapting a radiation treatment planning system (RTPS) to provide patient‐specific CT dosimetry. A radiation treatment planning system was modified to calculate patient‐specific CT dose distributions, which can be represented by dose at specific points within an organ of interest, as well as organ dose‐volumes (after image segmentation) for a GE Light Speed Ultra Plus CT scanner. The RTPS calculation algorithm is based on a semi‐empirical, measured correction‐based algorithm, which has been well established in the radiotherapy community. Digital representations of the physical phantoms (virtual phantom) were acquired with the GE CT scanner in axial mode. Thermoluminescent dosimeter (TLDs) measurements in pediatric anthropomorphic phantoms were utilized to validate the dose at specific points within organs of interest relative to RTPS calculations and Monte Carlo simulations of the same virtual phantoms (digital representation). Congruence of the calculated and measured point doses for the same physical anthropomorphic phantom geometry was used to verify the feasibility of the method. The RTPS algorithm can be extended to calculate the organ dose by calculating a dose distribution point‐by‐point for a designated volume. Electron Gamma Shower (EGSnrc) codes for radiation transport calculations developed by National Research Council of Canada (NRCC) were utilized to perform the Monte Carlo (MC) simulation. In general, the RTPS and MC dose calculations are within 10% of the TLD measurements for the infant and child chest scans. With respect to the dose comparisons for the head, the RTPS dose calculations are slightly higher (10%–20%) than the TLD measurements, while the MC results were within 10% of the TLD measurements. The advantage of the algebraic dose calculation engine of the RTPS is a substantially reduced computation time (minutes vs. days) relative to Monte Carlo calculations, as well as providing patient‐specific dose estimation. It also provides the basis for a more elaborate reporting of dosimetric results, such as patient specific organ dose volumes after image segmentation. PACS numbers: 87.55.D‐, 87.57.Q‐, 87.53.Bn, 87.55.K‐ PMID:22089016

Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

PubMed

Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg

2018-02-13

There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly better (n = 20, P = 0.039) motion-artifact suppression was noted in the synthesized images. The noninferiority test rejects the inferiority of the synthesized to true full-dose images for image quality (95% CI: -14-9%), artifacts suppression (95% CI: -5-20%), and contrast enhancement (95% CI: -13-6%). With the proposed deep learning method, gadolinium dose can be reduced 10-fold while preserving contrast information and avoiding significant image quality degradation. 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Helical Tomotherapy vs. Intensity-Modulated Proton Therapy for Whole Pelvis Irradiation in High-Risk Prostate Cancer Patients: Dosimetric, Normal Tissue Complication Probability, and Generalized Equivalent Uniform Dose Analysis

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

Widesott, Lamberto, E-mail: widesott@yahoo.it; Pierelli, Alessio; Fiorino, Claudio

2011-08-01

Purpose: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. Methods and Materials: The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100{sup o}; 100{sup o}) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normalmore » tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. Results: A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving {>=}95% of the prescribed dose (V{sub 95%}) was on average >97% in HT and >99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. Conclusions: Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.« less

TH-E-BRE-05: Analysis of Dosimetric Characteristics in Two Leaf Motion Calculator Algorithms for Sliding Window IMRT

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

Wu, L; Huang, B; Rowedder, B

Purpose: The Smart leaf motion calculator (SLMC) in Eclipse treatment planning system is an advanced fluence delivery modeling algorithm as it takes into account fine MLC features including inter-leaf leakage, rounded leaf tips, non-uniform leaf thickness, and the spindle cavity etc. In this study, SLMC and traditional Varian LMC (VLMC) algorithms were investigated, for the first time, in dosimetric characteristics and delivery accuracy of sliding window (SW) IMRT. Methods: The SW IMRT plans of 51 cancer cases were included to evaluate dosimetric characteristics and dose delivery accuracy from leaf motion calculated by SLMC and VLMC, respectively. All plans were deliveredmore » using a Varian TrueBeam Linac. The DVH and MUs of the plans were analyzed. Three patient specific QA tools - independent dose calculation software IMSure, Delta4 phantom, and EPID portal dosimetry were also used to measure the delivered dose distribution. Results: Significant differences in the MUs were observed between the two LMCs (p≤0.001).Gamma analysis shows an excellent agreement between the planned dose distribution calculated by both LMC algorithms and delivered dose distribution measured by three QA tools in all plans at 3%/3 mm, leading to a mean pass rate exceeding 97%. The mean fraction of pixels with gamma < 1 of SLMC is slightly lower than that of VLMC in the IMSure and Delta4 results, but higher in portal dosimetry (the highest spatial resolution), especially in complex cases such as nasopharynx. Conclusion: The study suggests that the two LMCs generates the similar target coverage and sparing patterns of critical structures. However, SLMC is modestly more accurate than VLMC in modeling advanced MLC features, which may lead to a more accurate dose delivery in SW IMRT. Current clinical QA tools might not be specific enough to differentiate the dosimetric discrepancies at the millimeter level calculated by these two LMC algorithms. NIH/NIGMS grant U54 GM104944, Lincy Endowed Assistant Professorship.« less

Pharmacokinetics of Intravenous Finafloxacin in Healthy Volunteers

PubMed Central

Chiesa, Joseph; Lückermann, Mark; Fischer, Carsten; Dalhoff, Axel; Fuhr, Uwe

2017-01-01

ABSTRACT Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to determine the pharmacokinetics of finafloxacin using a noncompartmental approach. Standard safety and tolerability data were documented. Finafloxacin had a volume of distribution of 90 to 127 liters (range) at steady state and 446 to 550 liters at pseudoequilibrium, indicating the elimination of a large fraction before pseudoequilibrium was reached. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg · h/ml and 2.56 to 20.2 μg/ml, respectively), the terminal elimination half-life increased (10.6 to 17.1 h), and the urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1,000 mg). The pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. The values of the parameters were similar for single and multiple administrations. The coefficient of variation for the between-subject variability of exposure ranged from 10% (≤600 mg) to 38% (>600 mg). Adverse events were mild and nonspecific, with no dependence of adverse events on dose or treatment (including placebo) being detected. Despite a relatively high interindividual variability at higher doses, the level of exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety and tolerability profile. (This study has been registered at ClinicalTrials.gov under registration no. NCT01910883.) PMID:28784673

Chronic aerial exposure to glucorticoids or beta-agonists affects avoidance learning and exploratory motivation in rats.

PubMed

Elías, Pedro C; Sagua, Delia; Alvarez, Edgardo O

2004-02-04

The purpose of the present work was to examine if the conventional asthma treatments in humans (inhalation of glucocorticoids or beta-agonists, administered in a chronic regimen) might affect behavioral processes (learning and exploratory motivation) in rats. Adult male rats were exposed to an atmosphere saturated with either saline, budesonide (a glucocorticoid), or salbutamol (a beta-adrenergic receptor agonist) in a forced ventilation cage, connected to a nebulizer for 5 min twice a day for 15 days at the same hours of the day. Doses of budesonide in the nebulizing solution were 0.116, 1.16, and 11.6mM. Doses of salbutamol in the nebulizing solution were 1.3, 13, and 130 mM. Forty-eight hours after treatment, the different groups were subjected to exploration of an elevated asymmetric plus-maze (APM, model of exploratory motivation), and 24h later to learning of an avoidance response to an ultrasonic tone in a two-compartment cage (model of memory and learning). Results showed that budesonide induces moderate effects on exploratory motivation. In one of the fear-inducing arms (single wall arm), exploration decreased and this effect was not dose dependent. In the cognitive model, glucocorticoids affected slightly the latency to escape but with no interference in memory efficiency. On the other hand, at the lower dose in the APM, salbutamol increased significantly the exploration of both fear-inducing arms (no walls and single wall arms). In the learning model, the beta-agonist induced two opposing effects. The lower dose (1.3mM) facilitated learning and the higher dose (13 mM) inhibited learning instead. In conclusion, results are compatible with the notion that inhaled glucocorticoids or beta-agonists might cross the lung aerial barrier into the blood compartment, exerting effects on learning and motivation functions.

Comparison of the Current Center of Site Annual Neshap Dose Modeling at the Savannah River Site with Other Assessment Methods.

PubMed

Minter, Kelsey M; Jannik, G Timothy; Stagich, Brooke H; Dixon, Kenneth L; Newton, Joseph R

2018-04-01

The U.S. Environmental Protection Agency (EPA) requires the use of the model CAP88 to estimate the total effective dose (TED) to an offsite maximally exposed individual (MEI) for demonstrating compliance with 40 CFR 61, Subpart H: The National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. For NESHAP compliance at the Savannah River Site (SRS), the EPA, the U.S. Department of Energy (DOE), South Carolina's Department of Health and Environmental Control, and SRS approved a dose assessment method in 1991 that models all radiological emissions as if originating from a generalized center of site (COS) location at two allowable stack heights (0 m and 61 m). However, due to changes in SRS missions, radiological emissions are no longer evenly distributed about the COS. An area-specific simulation of the 2015 SRS radiological airborne emissions was conducted to compare to the current COS method. The results produced a slightly higher dose estimate (2.97 × 10 mSv vs. 2.22 × 10 mSv), marginally changed the overall MEI location, and noted that H-Area tritium emissions dominated the dose. Thus, an H-Area dose model was executed as a potential simplification of the area-specific simulation by adopting the COS methodology and modeling all site emissions from a single location in H-Area using six stack heights that reference stacks specific to the tritium production facilities within H-Area. This "H-Area Tritium Stacks" method produced a small increase in TED estimates (3.03 × 10 mSv vs. 2.97 × 10 mSv) when compared to the area-specific simulation. This suggests that the current COS method is still appropriate for demonstrating compliance with NESHAP regulations but that changing to the H-Area Tritium Stacks assessment method may now be a more appropriate representation of operations at SRS.

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

[Behavioral pharmacological properties of nicergoline. Effects on gross-behavior in rats and monkeys and on DRL response, CER, and CAR in rats].

PubMed

Yamamura, M; Maeda, K; Nakagawa, H; Ishida, R

1986-02-01

Whether nicergoline has psychotropic-like pharmacological properties was examined through the gross-behavioral and operant behavioral observations in rats and monkeys. In gross-behavioral observations, slight decrement of spontaneous motor activity, lying on the abdomen and relaxation of abdominal tone were observed in rats when nicergoline was administered intravenously (1 mg/kg or more) and intraperitoneally (4 mg/kg or more). However, when it was administered orally, slight decrement of spontaneous motor activity was observed only at large doses of 32 and 128 mg/kg. In monkeys, nicergoline produced decrement of spontaneous motor activity, palpebral ptosis, and lacrimation when administered intraperitoneally at doses of 1 mg/kg or more. Under a differential reinforcement of low rate (DRL) schedule for food reinforcement in rats, nicergoline depressed the response at 4 mg/kg, i.p., or 128 mg/kg, orally. In conditioned emotional response (CER), nicergoline had no effect on the responses during both the alarm and safe periods at doses of 0.25, 1, and 4 mg/kg, i.p., or 8, 32, and 128 mg/kg, p.o. In Sidman continuous avoidance response (CAR), nicergoline (0.25, 1, and 4 mg/kg, i.p., or 8, 32, and 128 mg/kg, p.o.) slightly depressed the response and increased the total shock. These results were compared with those of chlorpromazine, chlordiazepoxide, pentobarbital, and methamphetamine and the following conclusion was drawn: Inhibitory effects of nicergoline on gross and operant behaviors seem to be non-specific, and its behavioral pharmacological properties are qualitatively different from those of anti-psychotics, anti-anxietics, hypnotics, and stimulants.

Non-Clinical Safety Studies of IMT504, a Unique Non-CpG Oligonucleotide

PubMed Central

Franco, Raúl; Rodriguez, Juan M.; Elías, Fernanda; Hernando-Insúa, Andrés; Fló, Juan; López, Ricardo; Nagle, Carlos; Lago, Néstor; Zorzopulos, Jorge; Horn, David L.

2014-01-01

IMT504 is a non-CpG 24-mer oligodeoxynucleotide (ODN) with immunomodulatory as well as tissue repair activity. IMT504 has been previously proven to be effective in animal models of vaccine potency, chronic lymphocytic leukemia, tissue regeneration, and sepsis. Here, we assessed the safety, including pharmacokinetics and toxicity studies in rats and monkeys, of IMT504 in a single- or repeated-dose administration by the subcutaneous (SC) or intravenous (IV) routes. In rats, the maximum tolerated dose was determined to be 50 mg/kg when administered SC. Adverse effects at 50 mg/kg were mild and reversible liver injury, revealed as lobular inflammation, focal necrosis, and small changes in the transaminase profile. Dose-dependent splenomegaly and lymphoid hyperplasia, most probably associated with immune stimulation, were commonly observed. Rats and monkeys were also IV injected with a single dose of 10 or 3.5 mg/kg, and no adverse effects were observed. Rats injected IV with 10 mg/kg showed a transient increase in spleen weight, together with a slight increase in the marginal zone of the white pulp and in leukocyte count 2 days post-administration. In monkeys, this dosage caused slight changes in total serum complement and leukocyte count on day 14. No adverse effects were observed at 3.5 mg/kg IV in rats or monkeys. Therefore, this dose was defined as the “no observed adverse effect level” for this route. Furthermore, repeated-dose toxicity studies were performed in these species using 3.5 or 0.35 mg/kg/day IV for 6 weeks. A transient increase in the spleen and liver weight was observed at 3.5 mg/kg/day only in female rats. No changes in clotting time and activation of the alternative complement pathway were observed. The toxicity profile of IMT504 herein reported suggests a dose range in which IMT504 can be used safely in clinical trials. PMID:24720569

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

Liu, R; Liu, T; Qi, S

Purposes: There has been growing interest in treating breast cancer using VMAT technique. Our goal is to compare the dosimetry and treatment delivery parameters for the left-sided breast cancer treatment using various VMAT platforms from commercially available planning systems. Methods: Five consecutive left-sided breast cancer patients initially treated with conventional 3D-conformal radiotherapy (3DCRT) were selected. Four VMAT plans using most popular treatment planning systems, including Eclipse (Version 11, Varian), Pinnacle (Version 9.8, Philips), Monaco (Version 2.03, Elekta) and helical Tomotherapy (V4.0, Accuray). The same structure set and same planning goals were used for all VMAT plans. The dosimetric parameters includingmore » target coverage and minimum/maximum/mean, dose-volume endpoints for the selected normal structures: the heart, ipsilateral-/contralateral lung and breast, were evaluated. Other dosimetric indices including heterogeneity index (HI) were evaluated. The treatment delivery parameters, such as monitor unit (MUs) and delivery time were also compared. Results: VMAT increases dose homogeneity to the treated volume and reduces the irradiated heart and left-lung volumes. Compared to the 3DCRT technique, all VMAT plans offer better heart and left-lung dose sparing; the mean heart doses were 4.5±1.6(Monaco), 1.2±0.4(Pinnacle), 1.3± (Eclipse) and 5.6±4.4(Tomo), the mean left-lung doses were 5.9±1.5(Monaco), 3.7±0.7(Pinnacle), 1.4± (Eclipse) and 5.2±1.6 (Tomo), while for the 3DCRT plan, the mean heart and left-Lung doses were 2.9±2.0, and 6.8±4.4 (Gy) respectively. The averaged contralateral-breast and lung mean doses were higher in VMAT plans than the 3DCRT plans but were not statistically significant. Among all the VMAT plans, the Pinnacle plans often yield the lowest right-lung/breast mean doses, and slightly better heterogeneity indices that are similar to Tomotherapy plans. Treatment delivery time of the VMAT plans (except helical Tomotherapy IMRT) is estimated to be comparable with the conventional 3DCRT. Conclusion: VMAT achieves equal or better PTV coverage and comparable OARs sparing compared to the conventional 3DCRT techniques.« less

Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown.

PubMed

do Vale, T Gurgel; Furtado, E Couto; Santos, J G; Viana, G S B

2002-12-01

Citral, myrcene and limonene (100 and 200 mg/kg body wt., i.p.), constituents of essential oils from Lippia alba chemotypes, decreased not only the number of crossings but also numbers for rearing and grooming, as measured by the open-field test in mice. Although muscle relaxation detected by the rota rod test was seen only at the highest doses of citral (200 mg/kg body wt.) and myrcene (100 and 200 mg/kg body wt.), this effect was observed even at the lowest dose of limonene (50 mg/kg body wt.). Also, citral and myrcene (100 and 200 mg/kg body wt.) increased barbiturate sleeping time as compared to control. Limonene was also effective at the highest dose, and although citral did not increase the onset of sleep, it increased the duration of sleep, which is indicative of a potentiation of sleeping time. Citral (100 and 200 mg/kg body wt.) increased 2.3 and 3.5 times, respectively, the barbiturate sleeping time in mice. Similar effects were observed for myrcene and limonene at the highest dose (200 mg/kg body wt.) which increased the sleeping time around 2.6 times. In the elevated-plus maze, no effect was detected with citral up to 25 mg/kg body wt., while at a high dose it decreased by 46% the number of entries in the open arms. A smaller but significant effect was detected with limonene (5 mg/kg body wt.). While myrcene (10 mg/kg body wt.) decreased only by 22% the number of entries in the open arms, this parameter was decreased by 48% at the highest dose. Our study showed that citral, limonene and myrcene presented sedative as well as motor relaxant effects. Although only at the highest dose, they also produced a potentiation of the pentobarbital-induced sleeping time in mice, which was more intense in the presence of citral. In addition, neither of them showed an anxiolytic effect, but rather a slight anxiogenic type of effect at the higher doses.

Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

PubMed

Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

2013-12-02

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

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

Rash, Dominique L.; Lee, Yongsook C.; Kashefi, Amir

Purpose: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. Methods and Materials: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response,more » assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. Results: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. Conclusions: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.« less

SU-G-TeP3-15: Radiation Dose Enhancement by Anatase TiO2NPs

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

Youkhana, E; Geso, M; Feltis, B

2016-06-15

Purpose: This work investigates radiation dose enhancement caused by TiO2 nanoparticles covering entire X-ray energy ranges used in radiation therapy. Methods: Anatase TiO2NPs crystal were synthesised and modified as hydrophilic and hydrophobic to disperse in culture-medium and halocarbons (PRESAGE chemical composition) respectively. TiO2NPs were characterised using TEM, XPS, XRD, TGA and FTIR. Various Concentrations have been utilised for determination of radiation-dose enhancement. This investigation is carried out in two ways; one using PRESAGE dosimeter/phantom and the other is radiobiological and based on in vitro study using two types of cell lines, Human Keratinocyte (HaCaT) and prostate cancer cell lines. Themore » x-ray used are both kilovoltage and megavoltage separately. The prepared PRESAGE dosimeters were scanned using optical CT scanner. Clonogenic and MTS assays were employed for cell cytotoxicity and viability measurements for determination of the levels of dose enhancement. Results: Significant about (50%, 45%) dose enhancement by TiO2-NPs for kV x-rays is measured in both ways (Presage and Cells study). Slightly more is detected with the cells. However, the dose enhancement with megavoltage beams was insignificant using Presage and under same conditions the cells survival curves indicates around 20% which is relatively high. This difference can only be attributed to some biochemical effects. Such as generation of reactive oxygen species (ROS), this can affect the cells while it can’t be detected by Presage. Elevation of hydroxyl radicals (•OH) of many orders is observed with the inclusion of TiO2-NPs in cells-medium. Conclusion: Dose enhancement inflicted by TiO2-NPs is proven to be significant with megavoltage beams and minimal with kV. The high dose enhancements obtained can be attributed to higher levels of ROS generated. Since MV beams are most commonly used, this research proves potential value for more efficient beam delivery. This has potential to be applied in future clinical radiotherapy applications The research is supported and funded by RMIT university-Melbourne/Australia.« less

SU-E-T-408: Determination of KQ,Q0-Factors From Water and Graphite Calorimetry in a 60 MeV Proton Beam

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

Rossomme, S; Renaud, J; Sarfehnia, A

2014-06-01

Purpose: To reduce the uncertainty of the beam quality correction factor k Q,Q0, for scattered proton beams (SPB). This factor is used in dosimetry protocols, to determine absorbed dose-to-water with ionization chambers. For the Roos plane parallel chambers (RPPICs), the IAEA TRS-398 protocol estimates k Q,Q0-factor to be 1.004(for a beam quality Rres=2 g.cm{sup 2}), with an uncertainty of 2.1%. Methods: A graphite calorimeter (GCal), a water calorimeter (WCal) and RPPICs were exposed, in a single experiment, to a 60 MeV non-modulated SPB. RPPICs were calibrated in terms of absorbed dose-to-water in a 20 MeV electron beam. The calibration coefficientmore » is traceable to NPL's absorbed dose standards. Chamber measurements were corrected for environmental conditions, recombination and polarity. The WCal corrections include heat loss, heat defect and vessel perturbation. The GCal corrections include heat loss and absorbed dose conversion. Except for heat loss correction and its uncertainty in the WCal system, all major corrections were included in the analysis. Other minor corrections, such as beam profile non-uniformity, are still to be evaluated. Experimental k Q,Q0-factors were derived by comparing the results obtained with both calorimeters and ionometry. Results: The absorbed dose-to-water from both calorimeters was found to be within 1.3% with an uncertainty of 1.2%. k Q,Q0-factor for a RPPIC was found to be 0.998 and 1.011, with a standard uncertainty of 1.4% and 0.9% when the dose is based on the GCal and the WCal, respectively. Conclusion: Results suggest the possibility to determine k Q,Q0-values for PPICs in SPB with a lower uncertainty than specified in the TRS-398 thereby helping to reduce uncertainty on absorbed dose-to-water. The agreement between calorimeters confirms the possibility to use GCal or WCal as primary standard in SPB. Because of the dose conversion, the use of GCal may lead to slightly higher uncertainty, but is, at present, considerably easier to operate.« less

Comparative disposition of the nephrotoxicant N-(3, 5-dichlorophenyl)succinimide and the non-nephrotoxicant N-(3, 5-difluorophenyl)succinimide in Fischer 344 rats.

PubMed

Henesey, C M; Kellner-Weibel, G L; Tarloff, J B; Harvison, P J

1999-06-01

Disposition of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) was compared with that of a nontoxic analog, N-(3, 5-difluorophenyl)succinimide (DFPS). Male Fischer 344 rats were administered 0.2 or 0.6 mmol/kg [14C]NDPS or [14C]DFPS (i.p. in corn oil). Plasma concentrations were determined from blood samples obtained through the carotid artery. Urine samples were analyzed for metabolite content by HPLC. Rats were sacrificed at 3 h (DFPS) or 6 h (NDPS) and tissue radiolabel content and covalent binding were determined. [14C]NDPS-derived plasma radioactivity levels were 6- to 21-fold higher and peaked later than those from [14C]DFPS. Six hours after dosing, NDPS was 40% eliminated in the urine compared with approximately 90% for DFPS. By 48 h, only 67% of the NDPS dose was eliminated in urine. In contrast, DFPS excretion was virtually complete within 24 h. NDPS underwent oxidative metabolism to a slightly greater extent than DFPS. Distribution of [14C]NDPS-derived radioactivity into the kidneys was 3- to 6-fold higher than that into the liver or heart, and was more extensive than with [14C]DFPS. NDPS also covalently bound to plasma, renal, and hepatic proteins to a greater extent than DFPS. In summary, NDPS achieves higher tissue and plasma concentrations, covalently binds to a greater extent, and is eliminated more slowly than DFPS. Differences in the lipid solubility of NDPS metabolites and DFPS metabolites may help explain these results. The overall greater tissue exposure of NDPS and its metabolites may contribute to differential toxicity of these analogs.

A review of studies on the effects of ultraviolet irradiation on the resistance to infections: evidence from rodent infection models and verification by experimental and observational human studies.

PubMed

Termorshuizen, F; Garssen, J; Norval, M; Koulu, L; Laihia, J; Leino, L; Jansen, C T; De Gruijl, F; Gibbs, N K; De Simone, C; Van Loveren, H

2002-02-01

Recent studies on the immunosuppressive effects of ultraviolet radiation (UVR) and the related resistance to infections in rodents and humans are presented. The waveband dependency of trans-to-cis isomerisation of urocanic acid in the stratum corneum and the role of DNA damage in UVR-induced erythema and immunosuppression were investigated to further elucidate the underlying mechanisms. Furthermore, human experimental studies on UVR-induced immunomodulation were performed. It appeared that the doses needed to suppress various immune parameters in humans (e.g. NK activity, contact hypersensitivity) were higher than those needed in experiments in rodents. Still, extrapolation of experimental animal data to the human situation showed that UVR may impair the resistance to different systemic infections at relevant outdoor doses. In observational human studies we aimed to substantiate the relevance of UVR for infections in humans. It was shown that sunny season was associated with a slightly retarded but clinically non-relevant antibody response to hepatitis B vaccination. Furthermore, sunny season appeared to be associated with a small decline in the number of CD4+ T-helper cells in a cohort of HIV-infected persons and a higher recurrence of herpes simplex and herpes zoster in a cohort of renal transplant recipients. However, in a study among young children a higher exposure to solar UVR was associated with a lower occurrence of upper respiratory tract symptoms. As disentangling the effects of UVR from other relevant factors is often impossible in observational studies, concise quantitative risk estimations for the human situation cannot be given at present.

Radiobiological Impact of Planning Techniques for Prostate Cancer in Terms of Tumor Control Probability and Normal Tissue Complication Probability

PubMed Central

Rana, S; Cheng, CY

2014-01-01

Background: The radiobiological models describe the effects of the radiation treatment on cancer and healthy cells, and the radiobiological effects are generally characterized by the tumor control probability (TCP) and normal tissue complication probability (NTCP). Aim: The purpose of this study was to assess the radiobiological impact of RapidArc planning techniques for prostate cancer in terms of TCP and normal NTCP. Subjects and Methods: A computed tomography data set of ten cases involving low-risk prostate cancer was selected for this retrospective study. For each case, two RapidArc plans were created in Eclipse treatment planning system. The double arc (DA) plan was created using two full arcs and the single arc (SA) plan was created using one full arc. All treatment plans were calculated with anisotropic analytical algorithm. Radiobiological modeling response evaluation was performed by calculating Niemierko's equivalent uniform dose (EUD)-based Tumor TCP and NTCP values. Results: For prostate tumor, the average EUD in the SA plans was slightly higher than in the DA plans (78.10 Gy vs. 77.77 Gy; P = 0.01), but the average TCP was comparable (98.3% vs. 98.3%; P = 0.01). In comparison to the DA plans, the SA plans produced higher average EUD to bladder (40.71 Gy vs. 40.46 Gy; P = 0.03) and femoral heads (10.39 Gy vs. 9.40 Gy; P = 0.03), whereas both techniques produced NTCP well below 0.1% for bladder (P = 0.14) and femoral heads (P = 0.26). In contrast, the SA plans produced higher average NTCP compared to the DA plans (2.2% vs. 1.9%; P = 0.01). Furthermore, the EUD to rectum was slightly higher in the SA plans (62.88 Gy vs. 62.22 Gy; P = 0.01). Conclusion: The SA and DA techniques produced similar TCP for low-risk prostate cancer. The NTCP for femoral heads and bladder was comparable in the SA and DA plans; however, the SA technique resulted in higher NTCP for rectum in comparison with the DA technique. PMID:24761232

[Hypothyroidism in patients with heart disease].

PubMed

Jiskra, Jan

Hypothyroidism is frequently found in patients with heart disease. It is a risk factor for atherosclerosis and ischemic heart disease and has a direct negative effect on both the left and right ventricular functions (hypothyroidism-induced cardiomyopathy). The confirmed manifest hypothyroidism is always a reason for replacement therapy with levothyroxine; regarding patients with heart disease, we always begin treatment with a small dose and increase it gradually. The treatment of subclinical hypothyroidism in patients with heart disease is disputable and its benefits probably depend on age. At a higher age, the therapy-related risks often outweigh its benefits, so we make do with the target levels of the thyroid stimulating hormone being within the upper band of the normal range, or even slightly above it, rather than overdosing the patient. To summarize in a simplified way, the treatment of subclinical hypothyroidism in patients with heart disease is the most effective in younger individuals, mainly those aged below 65, while at a higher age > 80 years the risk usually outweighs the benefit.Key words: cardiovascular risk - hypothyroidism - ischemic heart disease - left ventricular dysfunction - right ventricular dysfunction - subclinical hypothyroidism - thyroid peroxidase antibodies.

Characterization of a commercial hybrid iterative and model-based reconstruction algorithm in radiation oncology

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

Price, Ryan G.; Vance, Sean; Cattaneo, Richard

2014-08-15

Purpose: Iterative reconstruction (IR) reduces noise, thereby allowing dose reduction in computed tomography (CT) while maintaining comparable image quality to filtered back-projection (FBP). This study sought to characterize image quality metrics, delineation, dosimetric assessment, and other aspects necessary to integrate IR into treatment planning. Methods: CT images (Brilliance Big Bore v3.6, Philips Healthcare) were acquired of several phantoms using 120 kVp and 25–800 mAs. IR was applied at levels corresponding to noise reduction of 0.89–0.55 with respect to FBP. Noise power spectrum (NPS) analysis was used to characterize noise magnitude and texture. CT to electron density (CT-ED) curves were generatedmore » over all IR levels. Uniformity as well as spatial and low contrast resolution were quantified using a CATPHAN phantom. Task specific modulation transfer functions (MTF{sub task}) were developed to characterize spatial frequency across objects of varied contrast. A prospective dose reduction study was conducted for 14 patients undergoing interfraction CT scans for high-dose rate brachytherapy. Three physicians performed image quality assessment using a six-point grading scale between the normal-dose FBP (reference), low-dose FBP, and low-dose IR scans for the following metrics: image noise, detectability of the vaginal cuff/bladder interface, spatial resolution, texture, segmentation confidence, and overall image quality. Contouring differences between FBP and IR were quantified for the bladder and rectum via overlap indices (OI) and Dice similarity coefficients (DSC). Line profile and region of interest analyses quantified noise and boundary changes. For two subjects, the impact of IR on external beam dose calculation was assessed via gamma analysis and changes in digitally reconstructed radiographs (DRRs) were quantified. Results: NPS showed large reduction in noise magnitude (50%), and a slight spatial frequency shift (∼0.1 mm{sup −1}) with application of IR at L6. No appreciable changes were observed for CT-ED curves between FBP and IR levels [maximum difference ∼13 HU for bone (∼1% difference)]. For uniformity, differences were ∼1 HU between FBP and IR. Spatial resolution was well conserved; the largest MTF{sub task} decrease between FBP and IR levels was 0.08 A.U. No notable changes in low-contrast detectability were observed and CNR increased substantially with IR. For the patient study, qualitative image grading showed low-dose IR was equivalent to or slightly worse than normal dose FBP, and is superior to low-dose FBP (p < 0.001 for noise), although these did not translate to differences in CT number, contouring ability, or dose calculation. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using the most aggressive IR level [−1.2 ± 4.9 HU (range: −17.6–12.5 HU)]. No clinically significant contour differences were found between IR and FBP, with OIs and DSCs ranging from 0.85 to 0.95. Negligible changes in dose calculation were observed. DRRs preserved anatomical detail with <2% difference in intensity from FBP combined with aggressive IRL6. Conclusions: These results support integrating IR into treatment planning. While slight degradation in edges and shift in texture were observed in phantom, patient results show qualitative image grading, contouring ability, and dosimetric parameters were not adversely affected.« less

Impact of grid size on uniform scanning and IMPT plans in XiO treatment planning system for brain cancer

PubMed Central

Zheng, Yuanshui

2015-01-01

The main purposes of this study are to: 1) evaluate the accuracy of XiO treatment planning system (TPS) for different dose calculation grid size based on head phantom measurements in uniform scanning proton therapy (USPT); and 2) compare the dosimetric results for various dose calculation grid sizes based on real computed tomography (CT) dataset of pediatric brain cancer treatment plans generated by USPT and intensity‐modulated proton therapy (IMPT) techniques. For phantom study, we have utilized the anthropomorphic head proton phantom provided by Imaging and Radiation Oncology Core (IROC). The imaging, treatment planning, and beam delivery were carried out following the guidelines provided by the IROC. The USPT proton plan was generated in the XiO TPS, and dose calculations were performed for grid size ranged from 1 to 3 mm. The phantom containing thermoluminescent dosimeter (TLDs) and films was irradiated using uniform scanning proton beam. The irradiated TLDs were read by the IROC. The calculated doses from the XiO for different grid sizes were compared to the measured TLD doses provided by the IROC. Gamma evaluation was done by comparing calculated planar dose distribution of 3 mm grid size with measured planar dose distribution. Additionally, IMPT plan was generated based on the same CT dataset of the IROC phantom, and IMPT dose calculations were performed for grid size ranged from 1 to 3 mm. For comparative purpose, additional gamma analysis was done by comparing the planar dose distributions of standard grid size (3 mm) with that of other grid sizes (1, 1.5, 2, and 2.5 mm) for both the USPT and IMPT plans. For patient study, USPT plans of three pediatric brain cancer cases were selected. IMPT plans were generated for each of three pediatric cases. All patient treatment plans (USPT and IMPT) were generated in the XiO TPS for a total dose of 54 Gy (relative biological effectiveness [RBE]). Treatment plans (USPT and IMPT) of each case was recalculated for grid sizes of 1, 1.5, 2, and 2.5 mm; these dosimetric results were then compared with that of 3 mm grid size. Phantom study results: There was no distinct trend exhibiting the dependence of grid size on dose calculation accuracy when calculated point dose of different grid sizes were compared to the measured point (TLD) doses. On average, the calculated point dose was higher than the measured dose by 1.49% and 2.63% for the right and left TLDs, respectively. The gamma analysis showed very minimal differences among planar dose distributions of various grid sizes, with percentage of points meeting gamma index criteria 1% and 1 mm to be from 97.92% to 99.97%. The gamma evaluation using 2% and 2 mm criteria showed both the IMPT and USPT plans have 100% points meeting the criteria. Patient study results: In USPT, there was no very distinct relationship between the absolute difference in mean planning target volume (PTV) dose and grid size, whereas in IMPT, it was found that the decrease in grid size slightly increased the PTV maximum dose and decreased the PTV mean dose and PTV D50%. For the PTV doses, the average differences were up to 0.35 Gy (RBE) and 1.47 Gy (RBE) in the USPT and IMPT plans, respectively. Dependency on grid size was not very clear for the organs at risk (OARs), with average difference ranged from −0.61 Gy (RBE) to 0.53 Gy (RBE) in the USPT plans and from −0.83 Gy (RBE) to 1.39 Gy (RBE) in the IMPT plans. In conclusion, the difference in the calculated point dose between the smallest grid size (1 mm) and the largest grid size (3 mm) in phantom for USPT was typically less than 0.1%. Patient study results showed that the decrease in grid size slightly increased the PTV maximum dose in both the USPT and IMPT plans. However, no distinct trend was obtained between the absolute difference in dosimetric parameter and dose calculation grid size for the OARs. Grid size has a large effect on dose calculation efficiency, and use of 2 mm or less grid size can increase the dose calculation time significantly. It is recommended to use grid size either 2.5 or 3 mm for dose calculations of pediatric brain cancer plans generated by USPT and IMPT techniques in XiO TPS. PACS numbers: 87.55.D‐, 87.55.ne, 87.55.dk PMID:26699310

Caffeine at a Moderate Dose Did Not Affect the Skeletal System of Rats with Streptozotocin-Induced Diabetes.

PubMed

Folwarczna, Joanna; Janas, Aleksandra; Cegieła, Urszula; Pytlik, Maria; Śliwiński, Leszek; Matejczyk, Magdalena; Nowacka, Anna; Rudy, Karolina; Krivošíková, Zora; Štefíková, Kornélia; Gajdoš, Martin

2017-10-30

Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally) alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally). Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.

Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial

PubMed Central

McAfee, Tim; Davis, Kevin C; Shafer, Paul; Patel, Deesha; Alexander, Robert; Bunnell, Rebecca

2017-01-01

Background While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose–response from the campaign was only assessed by self-report. Objective Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. Methods A 3-month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. Results In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard-dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. Conclusions The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non-smokers and further increasing quit attempts among smokers, especially African-Americans. PMID:26678518

Dosimetric study of uniform scanning proton therapy planning for prostate cancer patients with a metal hip prosthesis, and comparison with volumetric‐modulated arc therapy

PubMed Central

Cheng, ChihYao; Zheng, Yuanshui; Hsi, Wen; Zeidan, Omar; Schreuder, Niek; Vargas, Carlos; Larson, Gary

2014-01-01

The main purposes of this study were to 1) investigate the dosimetric quality of uniform scanning proton therapy planning (USPT) for prostate cancer patients with a metal hip prosthesis, and 2) compare the dosimetric results of USPT with that of volumetric‐modulated arc therapy (VMAT). Proton plans for prostate cancer (four cases) were generated in XiO treatment planning system (TPS). The beam arrangement in each proton plan consisted of three fields (two oblique fields and one lateral or slightly angled field), and the proton beams passing through a metal hip prosthesis was avoided. Dose calculations in proton plans were performed using the pencil beam algorithm. From each proton plan, planning target volume (PTV) coverage value (i.e., relative volume of the PTV receiving the prescription dose of 79.2 CGE) was recorded. The VMAT prostate planning was done using two arcs in the Eclipse TPS utilizing 6 MV X‐rays, and beam entrance through metallic hip prosthesis was avoided. Dose computation in the VMAT plans was done using anisotropic analytical algorithm, and calculated VMAT plans were then normalized such that the PTV coverage in the VMAT plan was the same as in the proton plan of the corresponding case. The dose‐volume histograms of calculated treatment plans were used to evaluate the dosimetric quality of USPT and VMAT. In comparison to the proton plans, on average, the maximum and mean doses to the PTV were higher in the VMAT plans by 1.4% and 0.5%, respectively, whereas the minimum PTV dose was lower in the VMAT plans by 3.4%. The proton plans had lower (or better) average homogeneity index (HI) of 0.03 compared to the one for VMAT (HI = 0.04). The relative rectal volume exposed to radiation was lower in the proton plan, with an average absolute difference ranging from 0.1% to 32.6%. In contrast, using proton planning, the relative bladder volume exposed to radiation was higher at high‐dose region with an average absolute difference ranging from 0.4% to 0.8%, and lower at low‐ and medium‐dose regions with an average absolute difference ranging from 2.7% to 10.1%. The average mean dose to the rectum and bladder was lower in the proton plans by 45.1% and 22.0%, respectively, whereas the mean dose to femoral head was lower in VMAT plans by an average difference of 79.6%. In comparison to the VMAT, the proton planning produced lower equivalent uniform dose (EUD) for the rectum (43.7 CGE vs. 51.4 Gy) and higher EUD for the femoral head (16.7 CGE vs. 9.5 Gy), whereas both the VMAT and proton planning produced comparable EUDs for the prostate tumor (76.2 CGE vs. 76.8 Gy) and bladder (50.3 CGE vs. 51.1 Gy). The results presented in this study show that the combination of lateral and oblique fields in USPT planning could potentially provide dosimetric advantage over the VMAT for prostate cancer involving a metallic hip prosthesis. PACS number: 87.55.D‐, 87.55.ne, 87.55.dk PMID:24892333

High dose-per-pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use.

PubMed

Jaccard, Maud; Durán, Maria Teresa; Petersson, Kristoffer; Germond, Jean-François; Liger, Philippe; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François; Bailat, Claude

2018-02-01

The Oriatron eRT6 is an experimental high dose-per-pulse linear accelerator (linac) which was designed to deliver an electron beam with variable dose-rates, ranging from a few Gy/min up to hundreds of Gy/s. It was built to study the radiobiological effects of high dose-per-pulse/dose-rate electron beam irradiation, in the context of preclinical and cognitive studies. In this work, we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype linac. The beam was characterized in different steps. The output stability was studied by performing repeated measurements over a period of 20 months. The relative output variations caused by changing beam parameters, such as the temporal electron pulse width, the pulse repetition frequency and the pulse amplitude were also analyzed. Finally, depth dose curves and field sizes were measured for two different beam settings, resulting in one beam with a conventional radiotherapy dose-rate and one with a much higher dose-rate. Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced Markus ionization chamber. In addition, we developed a beam current monitoring system based on the signals from an induction torus positioned at the beam exit of the waveguide and from a graphite beam collimator. The stability of the output over repeated measurements was found to be good, with a standard deviation smaller than 1%. However, non-negligible day-to-day variations of the beam output were observed. Those output variations showed different trends depending on the dose-rate. The analysis of the relative output variation as a function of various beam parameters showed that in a given configuration, the dose-rate could be reliably varied over three orders of magnitude. Interdependence effects on the output variation between the parameters were also observed. The beam energy and field size were found to be slightly dose-rate-dependent and suitable mainly for small animal irradiation. The beam monitoring system was able to measure in a reproducible way the total charge of electrons that exit the machine, as long as the electron pulse amplitude remains above a given threshold. Furthermore, we were able to relate the charge measured with the monitoring system to the absorbed dose in a solid water phantom. The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose-per-pulse irradiation. © 2017 American Association of Physicists in Medicine.

Clinical Pharmacokinetics of IPX066: Evaluation of Dose Proportionality and Effect of Food in Healthy Volunteers

PubMed Central

Yao, Hsuan-Ming; Hsu, Ann; Gupta, Suneel; Modi, Nishit B.

2016-01-01

Objectives IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on the pharmacokinetics of IPX066 in healthy volunteers. Methods Three open-label studies were conducted. In the first study, subjects received 1 capsule of each IPX066 strength (23.75–95, 36.25–145, 48.75–195, and 61.25–245 mg of CD-LD). In the second study, subjects received 1 and 2 capsules of IPX066 245-mg LD under fasting conditions. In the third study, subjects received 2 capsules of IPX066 245-mg LD under 3 conditions: fasting; following a high-fat, high-calorie breakfast; and with the capsule contents sprinkled on applesauce under fasting conditions. Results Peak plasma concentrations (Cmax) and systemic exposure (AUCt, AUCinf) for LD and CD increased dose-proportionally over the range of the IPX066 capsule strengths. Comparison of 1 and 2 IPX066 245-mg LD capsules showed dose-proportional pharmacokinetics for Cmax and AUCt. Sprinkling the capsule contents on applesauce did not affect the pharmacokinetics. A high-fat, high-calorie meal delayed the initial increase in LD concentration by approximately 1 to 2 hours, reduced Cmax by 21%, and increased AUCinf by 13% compared with the fasted state. Conclusions IPX066 shows dose-proportional pharmacokinetics. Sprinkling the capsule contents on applesauce does not affect the pharmacokinetics; a high-fat, high-calorie meal delayed absorption by 1 to 2 hours, slightly reduced Cmax, and slightly increased extent of absorption. PMID:26626430

Clinical Pharmacokinetics of IPX066: Evaluation of Dose Proportionality and Effect of Food in Healthy Volunteers.

PubMed

Yao, Hsuan-Ming; Hsu, Ann; Gupta, Suneel; Modi, Nishit B

2016-01-01

IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on the pharmacokinetics of IPX066 in healthy volunteers. Three open-label studies were conducted. In the first study, subjects received 1 capsule of each IPX066 strength (23.75-95, 36.25-145, 48.75-195, and 61.25-245 mg of CD-LD). In the second study, subjects received 1 and 2 capsules of IPX066 245-mg LD under fasting conditions. In the third study, subjects received 2 capsules of IPX066 245-mg LD under 3 conditions: fasting; following a high-fat, high-calorie breakfast; and with the capsule contents sprinkled on applesauce under fasting conditions. Peak plasma concentrations (Cmax) and systemic exposure (AUCt, AUCinf) for LD and CD increased dose-proportionally over the range of the IPX066 capsule strengths. Comparison of 1 and 2 IPX066 245-mg LD capsules showed dose-proportional pharmacokinetics for Cmax and AUCt. Sprinkling the capsule contents on applesauce did not affect the pharmacokinetics. A high-fat, high-calorie meal delayed the initial increase in LD concentration by approximately 1 to 2 hours, reduced Cmax by 21%, and increased AUCinf by 13% compared with the fasted state. IPX066 shows dose-proportional pharmacokinetics. Sprinkling the capsule contents on applesauce does not affect the pharmacokinetics; a high-fat, high-calorie meal delayed absorption by 1 to 2 hours, slightly reduced Cmax, and slightly increased extent of absorption.

Biodistribution of radiomercury in rabbits and efficacy of dimercaptopropanesulfonic acid (DMPS) and dimercaprol (BAL) to reduce tracer-level kidney (kid) burden of radiomercury in rats

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

Coveney, J.R.; Robbins, M.S.

There is clinical interest in /sup 195m/Hg//sup 195m/Au generators for radionuclide angiocardiography. Generators are /sup 195m/Hg-impregnated columns through which S/sub 2/O/sub 3//sup 2 -//NO/sub 3//sup -/ eluant is passed to recover /sup 195m/Au daughter (t/sub 1/2p/ approx. 30s) permitting repeated patient study at short intervals, but co-elution of some /sup 195m/Hg (t/sub 1/2p approx. 40h) limits per-study dose: eluate was injected i.v. to male and female New Zealand White rabbits (1.4-2.4 kg, 12 ml eluate ea.); approx. 40% of injected dose (ID) of /sup 195m/Hg was in kids by 3d and approx. 20% ID remained after 14d; only 37% IDmore » was excreted (2/3 in feces) at 7d. To evaluate DMPS action upon kid /sup 195m/Hg burden, male Sprague-Dawley rats (187-240 g) were injected i.v. with 2ml eluate containing 0.02 mg DMPS/ml or eluate alone. DMPS slightly reduced % ID /sup 195m/Hg in kids 22h later: 12.2 +/- 0.3 to 8.5 +/- 0.3 (mean +/- s.e.m., n = 4). Additional rats were given 5 mg BAL/kg, i.p., or 2ml propylene glycol vehicle/kg 3-4' before 2ml eluate, i.v.; % ID of Hg was again only slightly reduced (14.4 +/- 0.2 to 10.7 +/- 0.1). Neither BAL nor DMPS, useful in repeat-dose regimens in heavy metal poisoning, are suitable in single doses for reducing absorbed radiation dose in /sup 195m/Au angiocardiography.« less

Radiation risk assessment in neonatal radiographic examinations of the chest and abdomen: a clinical and Monte Carlo dosimetry study

NASA Astrophysics Data System (ADS)

Makri, T.; Yakoumakis, E.; Papadopoulou, D.; Gialousis, G.; Theodoropoulos, V.; Sandilos, P.; Georgiou, E.

2006-10-01

Seeking to assess the radiation risk associated with radiological examinations in neonatal intensive care units, thermo-luminescence dosimetry was used for the measurement of entrance surface dose (ESD) in 44 AP chest and 28 AP combined chest-abdominal exposures of a sample of 60 neonates. The mean values of ESD were found to be equal to 44 ± 16 µGy and 43 ± 19 µGy, respectively. The MCNP-4C2 code with a mathematical phantom simulating a neonate and appropriate x-ray energy spectra were employed for the simulation of the AP chest and AP combined chest-abdominal exposures. Equivalent organ dose per unit ESD and energy imparted per unit ESD calculations are presented in tabular form. Combined with ESD measurements, these calculations yield an effective dose of 10.2 ± 3.7 µSv, regardless of sex, and an imparted energy of 18.5 ± 6.7 µJ for the chest radiograph. The corresponding results for the combined chest-abdominal examination are 14.7 ± 7.6 µSv (males)/17.2 ± 7.6 µSv (females) and 29.7 ± 13.2 µJ. The calculated total risk per radiograph was low, ranging between 1.7 and 2.9 per million neonates, per film, and being slightly higher for females. Results of this study are in good agreement with previous studies, especially in view of the diversity met in the calculation methods.

Efficacy trial of Vi polysaccharide vaccine against typhoid fever in south-western China.

PubMed Central

Yang, H. H.; Wu, C. G.; Xie, G. Z.; Gu, Q. W.; Wang, B. R.; Wang, L. Y.; Wang, H. F.; Ding, Z. S.; Yang, Y.; Tan, W. S.; Wang, W. Y.; Wang, X. C.; Qin, M.; Wang, J. H.; Tang, H. A.; Jiang, X. M.; Li, Y. H.; Wang, M. L.; Zhang, S. L.; Li, G. L.

2001-01-01

OBJECTIVE: To test the efficacy of locally produced Vi vaccine over a time period of longer than one year. METHODS: A double-blinded, randomized field trial was performed in Guangxi Zhuang Autonomous Region in south-western China, using 30 micrograms doses of locally produced Vi. Enrolled subjects were 3-50 years of age, although the majority (92%) were school-aged children, who have the highest rate of typhoid fever in this setting. A total of 131,271 people were systematically allocated a single dose of 30 micrograms of Vi polysaccharide or saline placebo. The study population was followed for 19 months, with passive surveillance conducted in the Ministry of Health and the Regional Health and Anti-epidemic Centre (HAEC). Clinically suspected cases of typhoid fever were confirmed by blood culture, or by serological reaction with O-antigen (Widal tests). FINDINGS: After 19 months, there were 23 culture-confirmed cases of typhoid fever in the placebo group versus 7 cases in the Vi group (Protective efficacy (PE) = 69%; 95% CI = 28%, 87%). Most of the isolates were from school-aged children: 22 cases in the placebo group versus 6 in the Vi group (PE = 72%; 95% CI = 32%, 82%). No serious post-injection reactions were observed. The locally produced Vi polysaccharide vaccine showed levels of protective efficacy similar to those for Vi vaccine produced in industrial countries. CONCLUSION: The slightly higher dose of vaccine did not seem to alter efficacy significantly in China. PMID:11477965

D-1 and D-2 receptor blockade have additive cataleptic effects in mice, but receptor effects may interact in opposite ways.

PubMed

Klemm, W R; Block, H

1988-02-01

The dopaminergic role of D-1 and D-2 receptors in catalepsy was evaluated using drugs with preferential receptor affinities. The D-1 antagonist, SCH 23390, caused distinct catalepsy in mice at 1, 2, and 10 mg/kg, IP, but not at two lower doses. The selective D-1 blocker, molindone, also caused catalepsy at 5 and 10 mg/kg; and blockade of both receptor types produced additive cataleptogenic effects. Apomorphine (4 mg/kg), which is an agonist for both receptors, potentiated SCH 23390-induced catalepsy much more than it did the catalepsy induced by molindone; the potentiation was produced by higher, not lower, doses of apomorphine. To determine if the apomorphine potentiation was mediated by D-1 or D-2 receptors, we tested selective agonists in mice that were concurrently injected with selective blockers. SCH 23390-induced catalepsy was potentiated by a large dose of the D-2 agonist, bromocriptine. The catalepsy of D-2 blockade with molindone was not potentiated by the D-1 agonist, SKF 38393, which slightly disrupted the catalepsy of D-2 blockade. We conclude that catalepsy is not a simple D-2 blockade phenomenon and that preferential antagonism of either receptor type can cause catalepsy. Catalepsy is most profound when both receptor types are blocked. Dopamine agonists, in large concentrations, are known to promote movements, and thus it is not surprising that they tend to disrupt catalepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological observations on the hypotensive action of extracts of teleost fish urophyses (urotensin I) in the rat

PubMed Central

Lederis, K.; Medaković, M.

1974-01-01

1 Intravenous injections of urotensin I regularly caused a long-lasting, dose-related, lowering of blood pressure and an increase in heart rate in conscious rats, or a reduction in perfusion pressure in the isolated hind limb of the rat. 2 After subcutaneous administration, the hypotensive effect of urotensin I was greater in extent and in duration (> 24 hours). 3 Anaesthesia with ether, chloralose, pentobarbitone and thiobarbitone caused a decrease in blood pressure and only slightly diminished the hypotensive effect of urotensin. 4 Mecamylamine, hexamethonium, atropine, phenoxybenzamine, propranolol and diphenhydramine did not alter the effect of urotensin in conscious rats or in the isolated hind limb, although the effects of the respective agonists, i.e. nicotine, acetylcholine, noradrenaline, isoprenaline and histamine were inhibited. 5 In conscious rats, pressor effects of adrenaline, noradrenaline, nicotine and angiotensin II, and depressor effects of acetylcholine and bradykinin, were decreased or inhibited, whereas the hypotensive effect of phenoxybenzamine was potentiated by previous administration of urotensin I. Carotid occlusion reflex was partially inhibited by lower doses of urotensin and abolished by higher doses in rats lightly anaesthetized with chloralose. Urotensin elicited postural hypotension in rats anaesthetized with pentobarbitone. 6 The increase in heart rate produced by urotensin was not affected by phenoxybenzamine, but was abolished by propranolol or ganglion blocking agents (mecamylamine or hexamethonium). 7 It is concluded that urotensin elicits hypotension in the rat by a direct dilatory action on the resistance vessels causing a simultaneous reflex tachycardia. PMID:4375526

Evaluation of a LED-based flatbed document scanner for radiochromic film dosimetry in transmission mode.

PubMed

Lárraga-Gutiérrez, José Manuel; García-Garduño, Olivia Amanda; Treviño-Palacios, Carlos; Herrera-González, José Alfredo

2018-03-01

Flatbed scanners are the most frequently used reading instrument for radiochromic film dosimetry because its low cost, high spatial resolution, among other advantages. These scanners use a fluorescent lamp and a CCD array as light source and detector, respectively. Recently, manufacturers of flatbed scanners replaced the fluorescent lamp by light emission diodes (LED) as a light source. The goal of this work is to evaluate the performance of a commercial flatbed scanner with LED based source light for radiochromic film dosimetry. Film read out consistency, response uniformity, film-scanner sensitivity, long term stability and total dose uncertainty was evaluated. In overall, the performance of the LED flatbed scanner is comparable to that of a cold cathode fluorescent lamp (CCFL). There are important spectral differences between LED and CCFL lamps that results in a higher sensitivity of the LED scanner in the green channel. Total dose uncertainty, film response reproducibility and long-term stability of LED scanner are slightly better than those of the CCFL. However, the LED based scanner has a strong non-uniform response, up to 9%, that must be adequately corrected for radiotherapy dosimetry QA. The differences in light emission spectra between LED and CCFL lamps and its potential impact on film-scanner sensitivity suggest that the design of a dedicated flat-bed scanner with LEDs may improve sensitivity and dose uncertainty in radiochromic film dosimetry. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Transfer of interferon alfa into human breast milk.

PubMed

Kumar, A R; Hale, T W; Mock, R E

2000-08-01

Originally assumed to be antiviral substances, the efficacy of interferons in a number of pathologies, including malignancies, multiple sclerosis, and other immune syndromes, is increasingly recognized. This study provides data on the transfer of interferon alfa (2B) into human milk of a patient receiving massive intravenous doses for the treatment of malignant melanoma. Following an intravenous dose of 30 million IU, the amount of interferon transferred into human milk was only slightly elevated (1551 IU/mL) when compared to control milk (1249 IU/mL). These data suggest that even following enormous doses, interferon is probably too large in molecular weight to transfer into human milk in clinically relevant amounts.

[An in vitro study on toxic effect of vanadium-titanium-magnetite dust on alveolar macrophage in rabbits].

PubMed

Song, Y; Chen, Q; Guan, Y

1998-11-01

To study the toxic effect of vanadium-titanium-magnetite (VTM) dust on alveolar macrophage (AM) and its hazardous extent. Survival rates, morphology and function of AM were compared in rabbits exposed to dust of VTM, vanadium oxide, titanium dioxide and silica in various doses and length of time with in vitro cell culture and putamen membrane cover glass transmission electron microscopy, and changes in activities of lactic dehydrogenase (LDH) and acid phosphatase (ACP) in cell culture were measured. Exposure to all the four kinds of dust could lead to decrease in survival rate of AM, increase in activities of LDH and ACP in the cell culture, and changes in their morphology and function to the extent dependent on the nature of dust. Toxic effect of exposure to VTM dust was lower than that to vanadium oxide and silica, but higher than that to titanium dioxide, which had slight toxic effect.

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

NASA Technical Reports Server (NTRS)

Bourrieau, J.

1993-01-01

One of the objectives of the AO 138-7 experiment on board the Long Duration Exposure Facility (LDEF) was a total dose measurement with Thermo Luminescent Detectors (TLD 100). Two identical packages, both of them including five TLD's inside various aluminum shields, are exposed to the space environment in order to obtain the absorbed dose profile. Radiation fluence received during the total mission length was computed, taking into account the trapped particles (AE8 and AP8 models during solar maximum and 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 aluminum are computed with the radiation transport codes available at DERTS. The dose profile obtained is in good agreement with the evaluation by E.V. Benton. TLD readings are performed after flight; due to the mission duration increase a post flight calibration was necessary in order to cover the range of the in flight induced dose. The results obtained, similar (plus or minus 30 percent) for both packages, are compared with the dose profile computation. For thick shields it seems that the measurements exceed the forecast (about 40 percent). That can be due to a cosmic ray and trapped proton contributions coming from the backside (assumed as perfectly shielded by the LDEF structure in the computation), or to an underestimate of the proton or cosmic ray fluences. A fine structural shielding analysis should be necessary in order to determine the origin of this slight discrepancy between forecast and in flight measurements. For the less shielded dosimeters, mainly exposed to the trapped electron flux, a slight overestimation of the dose (less than 40 percent) appears. Due to the dispersion of the TLD's response, this cannot be confirmed. In practice these results obtained on board LDEF, with less than a factor 1.4 between measurements and forecast, reinforce the validity of the computation methods and models used for the long term evaluation of the radiation levels (flux and dose) encountered in space on low inclination and altitude Earth orbits.

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

NASA Astrophysics Data System (ADS)

Bourrieau, J.

1993-04-01

One of the objectives of the AO 138-7 experiment on board the Long Duration Exposure Facility (LDEF) was a total dose measurement with Thermo Luminescent Detectors (TLD 100). Two identical packages, both of them including five TLD's inside various aluminum shields, are exposed to the space environment in order to obtain the absorbed dose profile. Radiation fluence received during the total mission length was computed, taking into account the trapped particles (AE8 and AP8 models during solar maximum and 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 aluminum are computed with the radiation transport codes available at DERTS. The dose profile obtained is in good agreement with the evaluation by E.V. Benton. TLD readings are performed after flight; due to the mission duration increase a post flight calibration was necessary in order to cover the range of the in flight induced dose. The results obtained, similar (plus or minus 30 percent) for both packages, are compared with the dose profile computation. For thick shields it seems that the measurements exceed the forecast (about 40 percent). That can be due to a cosmic ray and trapped proton contributions coming from the backside (assumed as perfectly shielded by the LDEF structure in the computation), or to an underestimate of the proton or cosmic ray fluences. A fine structural shielding analysis should be necessary in order to determine the origin of this slight discrepancy between forecast and in flight measurements. For the less shielded dosimeters, mainly exposed to the trapped electron flux, a slight overestimation of the dose (less than 40 percent) appears. Due to the dispersion of the TLD's response, this cannot be confirmed. In practice these results obtained on board LDEF, with less than a factor 1.4 between measurements and forecast, reinforce the validity of the computation methods and models used for the long term evaluation of the radiation levels (flux and dose) encountered in space on low inclination and altitude Earth orbits.

Effects of a new glucocorticoid, oxazacort, on some variables connected with bone metabolism in man: a comparison with prednisone.

PubMed

Caniggia, A; Marchetti, M; Gennari, C; Vattimo, A; Nicolis, F B

1977-03-01

The urinary elimination of calcium, other electrolytes, and hydroxyproline and the oral absorption of 47Ca have been evaluated in three groups of 8 patients before and during a 15-day treatment with prednisone at daily doses of 25 and 50 mg and with oxazacort, a new glucocorticoid, at a daily dose of 50 mg. The results obtained demonstrate that oxazacort in short-term teatment with a high dose has no significant effect on the urinary elimination of calcium and hydroxypyroline in experimental conditions in which prednisone produces statistically significant and clinically relevant increase, both when given at the same dose and when given at half that dose. On the other hand, the oral absorption of 47Ca is decreased by oxazacort, but less than by prednisone at the same dose. As the antirheumatic activity of oxazacort appears to be only slightly lower than that of prednisone (activity ratio of about 0.84: 1), these findings may have interesting therapeutic implications.

A double-blind, randomized, multiple-dose, parallel-group study to characterize the occurrence of diarrhea following two different dosing regimens of neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor.

PubMed

Abbas, Richat; Hug, Bruce A; Leister, Cathie; Sonnichsen, Daryl

2012-07-01

Neratinib, a potent, low-molecular-weight, orally administered, irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity in ErbB2 + breast cancer. The objective of this study was to characterize the onset, severity, and duration of diarrhea after administration of neratinib 240 mg once daily (QD) and 120 mg twice daily (BID) for ≤14 days in healthy subjects. A randomized, double-blind, parallel-group, inpatient study was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID with food for ≤14 days. The primary endpoint was the proportion of subjects with diarrhea of at least moderate severity (grade 2; 5-7 loose stools/day). In subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic profiles were characterized for neratinib on Days 1 and 7. No severe (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea. Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence interval (CI): 28-72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 % CI: 52-90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma concentration and Day 7 steady-state exposure were higher with the QD regimen than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no correlation with severity or onset of diarrhea. Incidences and onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID dosing compared with QD dosing.

Diet-Induced Obesity Alters Vincristine Pharmacokinetics in Blood and Tissues of Mice

PubMed Central

Behan, James W.; Avramis, Vassilios I.; Yun, Jason P.; Louie, Stan G.; Mittelman, Steven D.

2010-01-01

Obesity is associated with poorer outcome from many cancers, including leukemia. One possible contributor to this could be suboptimal chemotherapy dosing in obese patients. We have previously found that vincristine (VCR) is less effective in obese compared to non-obese mice with leukemia, despite weight-based dosing. In the present study, we administered 3H-VCR to obese and control mice to determine whether obesity would cause suboptimal VCR exposure. Blood VCR concentrations were fitted with a 3-compartment model using pharmacokinetic analysis (two-stage PK) in 3 subsets of VCR concentrations vs. time method. Tissue and blood VCR concentrations were also analyzed using non-compartmental modeling. Blood VCR concentrations showed a triexponential decay and tended to be slightly higher in the obese mice at all time-points. However, the t½β and t½γ were shorter in the obese mice (9.7 vs. 44.5 minutes and 60.3 vs. 85.6 hours, respectively), resulting in a lower AUC0→∞ (13,099 vs. 15,384 ng/ml*hr). Had the dose of VCR been “capped”, as is done in clinical practice, the AUC0→∞ would have been 36% lower in the obese mice than the controls. Tissue disposition of VCR revealed a biexponential decay from spleen, liver, and adipose. Interestingly, VCR slowly accumulated in the bone marrow of control mice, but had a slow decay from the marrow in the obese mice. Thus, obesity alters VCR PK, causing a lower overall exposure in circulation and bone marrow. Given the high prevalence of obesity, additional PK studies should be performed in obese subjects to optimize chemotherapy dosing regimens. PMID:20083201

Thoracoabdominal Computed Tomography in Trauma Patients: A Cost-Consequences Analysis

PubMed Central

van Vugt, Raoul; Kool, Digna R.; Brink, Monique; Dekker, Helena M.; Deunk, Jaap; Edwards, Michael J.

2014-01-01

Background: CT is increasingly used during the initial evaluation of blunt trauma patients. In this era of increasing cost-awareness, the pros and cons of CT have to be assessed. Objectives: This study was performed to evaluate cost-consequences of different diagnostic algorithms that use thoracoabdominal CT in primary evaluation of adult patients with high-energy blunt trauma. Materials and Methods: We compared three different algorithms in which CT was applied as an immediate diagnostic tool (rush CT), a diagnostic tool after limited conventional work-up (routine CT), and a selective tool (selective CT). Probabilities of detecting and missing clinically relevant injuries were retrospectively derived. We collected data on radiation exposure and performed a micro-cost analysis on a reference case-based approach. Results: Both rush and routine CT detected all thoracoabdominal injuries in 99.1% of the patients during primary evaluation (n = 1040). Selective CT missed one or more diagnoses in 11% of the patients in which a change of treatment was necessary in 4.8%. Rush CT algorithm costed € 2676 (US$ 3660) per patient with a mean radiation dose of 26.40 mSv per patient. Routine CT costed € 2815 (US$ 3850) and resulted in the same radiation exposure. Selective CT resulted in less radiation dose (23.23 mSv) and costed € 2771 (US$ 3790). Conclusions: Rush CT seems to result in the least costs and is comparable in terms of radiation dose exposure and diagnostic certainty with routine CT after a limited conventional work-up. However, selective CT results in less radiation dose exposure but a slightly higher cost and less certainty. PMID:25337521

A Phase I Trial of a Human Papillomavirus (HPV) DNA Vaccine for HPV16+ Cervical Intraepithelial Neoplasia 2/3

PubMed Central

Trimble, Cornelia L.; Peng, Shiwen; Kos, Ferdynand; Gravitt, Patti; Viscidi, Raphael; Sugar, Elizabeth; Pardoll, Drew; Wu, TC

2010-01-01

Purpose: To evaluate the safety and immunogenicity of a therapeutic HPV16 DNA vaccine administered to women with HPV16+CIN2/3. Experimental Design: This phase I trial incorporated the standard ‘3+3” dose escalation design with an additional 6 patients allocated to the maximally tolerated dose (MTD). Healthy adult women with colposcopically-directed biopsy-proven HPV16+ CIN2/3 received three intramuscular (IM) vaccinations (0.5 mg, 1 mg, or 3mg) of a plasmid expressing a Sig-E7(detox)-HSP70 fusion protein on days 0, 28 and 56, and underwent standard therapeutic resection of the cervical squamocolumnar junction at day 105 (week 15). Safety and immunogenicity of the vaccine and histologic outcome based on resection at week 15 were assessed. Results: Fifteen patients were evaluable (3 each at 0.5 mg and 1mg, 9 at 3mg). The vaccine was well tolerated: most adverse events were mild transient injection-site discomfort; no dose-limiting toxicities were observed. Although HPVE7-specific T-cell responses to E7 detected by enzyme-linked immunospot assays (IFNγ) were of low frequency and magnitude, detectable increases in response subsequent to vaccination were identified in subjects in the second and third cohorts. Complete histologic regression occurred in 3/9 (33%, CI: 7%-70%)) individuals in the highest dose cohort, Although the difference is not significant, it is slightly higher than would be expected in an unvaccinated cohort (25%). Conclusions: This HPV16 DNA vaccine was safe and well tolerated. While it appears possible to elicit HPV-specific T cell responses in patients with established dysplastic lesions, other factors are likely to play a role in lesion regression. PMID:19118066

The effect of pregnancy on renal clearance of boron in rats given boric acid orally.

PubMed

Vaziri, N D; Oveisi, F; Culver, B D; Pahl, M V; Andersen, M E; Strong, P L; Murray, F J

2001-04-01

Boric acid (H(3)BO(3)) has been shown to cause developmental abnormalities in the offspring of pregnant rats. Comparative data on the renal clearance of boron (B) in rats and humans, both pregnant and nonpregnant, exposed to boric acid (BA) would reduce uncertainty in interspecies extrapolation from rats to humans. The purpose of this study was to evaluate the effect of pregnancy on the plasma half-life and renal clearance of boron in Sprague-Dawley rats given a single oral dose of boric acid. For the half-life study, nonpregnant and pregnant (gestation day 16) rats were given a single dose of 30 mg/kg of boric acid by gavage, and plasma samples were collected at 2-3 h intervals. The plasma half-life of boron was determined to be 2.9 +/- 0.2 and 3.2 +/- 0.3 h in nonpregnant and pregnant rats, respectively. In the clearance study, nonpregnant and pregnant (GD 16) rats were given a single gavage dose of 0.3, 3, or 30 mg/kg of boric acid. Boron clearance was slightly higher in pregnant rats (3.3 +/- 0.6, 3.2 +/- 0.5, and 3.4 +/- 0.5 ml/min/kg, respectively) compared to nonpregnant rats (3.1 +/- 0.8, 3.0 +/- 0.6, and 3.2 +/- 0.5 ml/min/kg, respectively), but the difference was not statistically significant and not dose-related. Boron clearance was less than creatinine clearance, suggesting tubular reabsorption in both groups. In conclusion, pregnancy did not appear to significantly alter the renal clearance or the plasma half-life of boron in Sprague-Dawley rats under the conditions of this study.

Prophylactic and metaphylactic antimicrobial use in Belgian fattening pig herds.

PubMed

Callens, Bénédicte; Persoons, Davy; Maes, Dominiek; Laanen, Maria; Postma, Merel; Boyen, Filip; Haesebrouck, Freddy; Butaye, Patrick; Catry, Boudewijn; Dewulf, Jeroen

2012-09-01

The monitoring of antimicrobial use is an essential step to control the selection and spread of antimicrobial resistance. Between January and October 2010 data on prophylactic and metaphylactic antimicrobial use were collected retrospectively on 50 closed or semi-closed pig herds. Ninety-three percent of the group treatments were prophylactic whereas only 7% were methaphylactic. The most frequently used antimicrobials orally applied at group level were colistin (30.7%), amoxicillin (30.0%), trimethoprim-sulfonamides (13.1%), doxycycline (9.9%) and tylosin (8.1%). The most frequently applied injectable antimicrobials were tulathromycin (45.0%), long acting ceftiofur (40.1%) and long acting amoxicillin (8.4%). The treatment incidences (TI) based on the used daily dose pig (UDD(pig) or the actually administered dose per day per kg pig of a drug) for all oral and injectable antimicrobial drugs was on average 200.7 per 1000 pigs at risk per day (min=0, max=699.0), while the TI based on the animal daily dose pig (ADD(pig) or the national defined average maintenance dose per day per kg pig of a drug used for its main indication) was slightly higher (average=235.8, min=0, max=1322.1). This indicates that in reality fewer pigs were treated with the same amount of antimicrobials than theoretically possible. Injectable products were generally overdosed (79.5%), whereas oral treatments were often underdosed (47.3%). In conclusion, this study shows that prophylactic group treatment was applied in 98% of the visited herds and often includes the use of critically important and broad-spectrum antimicrobials. In Belgium, the guidelines for prudent use of antimicrobials are not yet implemented. Copyright © 2012 Elsevier B.V. All rights reserved.

HDPE/HA composites obtained in solution: Effect of the gamma radiation

NASA Astrophysics Data System (ADS)

Carmen, Albano; Arquímedes, Karam; Rosestela, Perera; Gema, González; Nohemy, Domínguez; Jeanette, González; Yanixia, Sánchez

2006-06-01

Radiation is employed to sterilize composite materials used in the biomedical field. Due to the changes induced by radiation onto polymeric materials, it is important to study variations in their melt flow index (MFI), as well as in their mechanical and thermal properties. In this work, those previous parameters were determined in composites obtained via solution of a high-density polyethylene (HDPE) in decalin, with different amounts of hydroxyapatite (HA), varying from 10 to 30 parts per hundred, after being exposed to gamma radiation at absorbed doses between 25 and 100 kGy. After the irradiation, the MFI of HDPE dissolved in decalin and precipitated afterwards and without filler increased from 6 to 24 g/10 min at the highest absorbed doses. This behavior was also observed in composites with 10 pph of HA, being the increase less pronounced, specifically in the range between 50 and 100 kGy. Composites with 20 and 30 pph of HA showed a maximum MFI value at 50 kGy, which decreased at higher doses. This implies that the filler begin to exert an influence because it does not melt at the test temperature and consequently, it does not flow. It was observed that Young's modulus increased with HA addition due to rigidity of the ceramic filler. Radiation did not significantly affect this tensile property. On the other hand, the tensile strength did not show significant variations at the different doses but the filler content did affect this property improving it. Finally, elongation at break showed a drastic decrease with filler addition. When the thermal behavior was studied it was noticed that crystallization and melting temperatures remained unchanged. Instead, crystallinity degree slightly increased in the composites, and a little decrease was obtained when they were irradiated.

Diet-induced obesity alters vincristine pharmacokinetics in blood and tissues of mice.

PubMed

Behan, James W; Avramis, Vassilios I; Yun, Jason P; Louie, Stan G; Mittelman, Steven D

2010-05-01

Obesity is associated with poorer outcome from many cancers, including leukemia. One possible contributor to this could be suboptimal chemotherapy dosing in obese patients. We have previously found that vincristine (VCR) is less effective in obese compared to non-obese mice with leukemia, despite weight-based dosing. In the present study, we administered (3)H-VCR to obese and control mice to determine whether obesity would cause suboptimal VCR exposure. Blood VCR concentrations were fitted with a three-compartment model using pharmacokinetic analysis (two-stage PK) in three subsets of VCR concentrations vs. time method. Tissue and blood VCR concentrations were also analyzed using non-compartmental modeling. Blood VCR concentrations showed a triexponential decay and tended to be slightly higher in the obese mice at all time-points. However, the t(1/2,beta) and t(1/2,gamma) were shorter in the obese mice (9.7 min vs. 44.5 min and 60.3h vs. 85.6h, respectively), resulting in a lower AUC(0-infinity) (13,099 ng/m Lh vs. 15,384 ng/mL h). Had the dose of VCR been "capped", as is done in clinical practice, the AUC(0-infinity) would have been 36% lower in the obese mice than the controls. Tissue disposition of VCR revealed a biexponential decay from spleen, liver, and adipose. Interestingly, VCR slowly accumulated in the bone marrow of control mice, but had a slow decay from the marrow in the obese mice. Thus, obesity alters VCR PK, causing a lower overall exposure in circulation and bone marrow. Given the high prevalence of obesity, additional PK studies should be performed in obese subjects to optimize chemotherapy dosing regimens. (c) 2010 Elsevier Ltd. All rights reserved.

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

PubMed

Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

2016-09-08

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. © 2016 The Authors.

Potential benefit of the CT adaptive statistical iterative reconstruction method for pediatric cardiac diagnosis

NASA Astrophysics Data System (ADS)

Miéville, Frédéric A.; Ayestaran, Paul; Argaud, Christophe; Rizzo, Elena; Ou, Phalla; Brunelle, Francis; Gudinchet, François; Bochud, François; Verdun, Francis R.

2010-04-01

Adaptive Statistical Iterative Reconstruction (ASIR) is a new imaging reconstruction technique recently introduced by General Electric (GE). This technique, when combined with a conventional filtered back-projection (FBP) approach, is able to improve the image noise reduction. To quantify the benefits provided on the image quality and the dose reduction by the ASIR method with respect to the pure FBP one, the standard deviation (SD), the modulation transfer function (MTF), the noise power spectrum (NPS), the image uniformity and the noise homogeneity were examined. Measurements were performed on a control quality phantom when varying the CT dose index (CTDIvol) and the reconstruction kernels. A 64-MDCT was employed and raw data were reconstructed with different percentages of ASIR on a CT console dedicated for ASIR reconstruction. Three radiologists also assessed a cardiac pediatric exam reconstructed with different ASIR percentages using the visual grading analysis (VGA) method. For the standard, soft and bone reconstruction kernels, the SD is reduced when the ASIR percentage increases up to 100% with a higher benefit for low CTDIvol. MTF medium frequencies were slightly enhanced and modifications of the NPS shape curve were observed. However for the pediatric cardiac CT exam, VGA scores indicate an upper limit of the ASIR benefit. 40% of ASIR was observed as the best trade-off between noise reduction and clinical realism of organ images. Using phantom results, 40% of ASIR corresponded to an estimated dose reduction of 30% under pediatric cardiac protocol conditions. In spite of this discrepancy between phantom and clinical results, the ASIR method is as an important option when considering the reduction of radiation dose, especially for pediatric patients.

[A comparative study of the effectiveness and tolerability of a procedure involving slow dose-escalation of rivastigmine in patients with mild or moderate Alzheimer-type dementia: the SCALEX study].

PubMed

Agüera-Ortiz, L F; Ramos-García, M; Gobartt, A L

To determine and to compare the tolerability and effectiveness of a slow escalation of the dose of rivastigmine in patients with Alzheimer's disease with respect to using it with a faster escalation. We conducted a multi-centre, naturalistic, open-label, randomised trial with 429 hospital outpatients diagnosed with Alzheimer-type dementia (according to DSM-IV and NINCDS-ADRA criteria) and in whom treatment with rivastigmine was clinically indicated. Two study groups were established: slow escalation and fast escalation (in accordance with usual clinical practice); effectiveness and tolerability variables were analysed in the two groups, as was the proportion of patients who reached therapeutic doses (> 6 mg/day). The scores obtained on the CGI, MMSE, NPI and Barthel index scales were analysed, together with adverse events and reactions concerning spontaneous communication, and scores on the UKU scale. The slow escalation group displayed slightly higher percentages of sub-therapeutic anticipated interruptions than the fast escalation group (chi-square test; p < 0.05). On comparing the two treatment groups, no statistically significant differences were observed for the evolution of the scores on the different scales of effectiveness; no statistically significant differences were found between the two groups in the safety and tolerability analyses (chi-square test, exact test; p > 0.05) for most of the parameters that were studied (adverse reactions in spontaneous communication and the modified UKU scale). Slow escalation of the dose of rivastigmine did not display greater effectiveness or tolerability in comparison to an escalation applied in accordance with usual clinical practice.

Particle-related exposure, dose and lung cancer risk of primary school children in two European countries.

PubMed

Pacitto, A; Stabile, L; Viana, M; Scungio, M; Reche, C; Querol, X; Alastuey, A; Rivas, I; Álvarez-Pedrerol, M; Sunyer, J; van Drooge, B L; Grimalt, J O; Sozzi, R; Vigo, P; Buonanno, G

2018-03-01

Schools represent a critical microenvironment in terms of air quality due to the proximity to outdoor particle sources and the frequent lack of proper ventilation and filtering systems. Moreover, the population exposed in schools (i.e. children) represents a susceptible population due to their age. Air quality-based studies involving students' exposure at schools are still scarce and often limited to mass-based particle metrics and may thus underestimate the possible effect of sub-micron particles and particle toxicity. To this purpose, the present paper aims to evaluate the exposure to different airborne particle metrics (including both sub- and super-micron particles) and attached carcinogenic compounds. Measurements in terms of particle number, lung-deposited surface area, and PM fraction concentrations were measured inside and outside schools in Barcelona (Spain) and Cassino (Italy). Simultaneously, PM samples were collected and chemically analysed to obtain mass fractions of carcinogenic compounds. School time airborne particle doses received by students in classrooms were evaluated as well as their excess lung cancer risk due to a five-year primary school period. Median surface area dose received by students during school time in Barcelona and Cassino resulted equal to 110mm 2 and 303mm 2 , respectively. The risk related to the five-year primary school period was estimated as about 2.9×10 -5 and 1.4×10 -4 for students of Barcelona and Cassino, respectively. The risk in Barcelona is slightly higher with respect to the maximum tolerable value (10 -5 , according to the U.S. Environmental Protection Agency), mainly due to toxic compounds on particles generated from anthropogenic emissions (mainly industry). On the other hand, the excess lung cancer risk in Cassino is cause of concern, being one order of magnitude higher than the above-mentioned threshold value due to the presence of biomass burning heating systems and winter thermal inversion that cause larger doses and great amount of toxic compounds on particles. Copyright © 2017 Elsevier B.V. All rights reserved.

Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial.

PubMed

McAfee, Tim; Davis, Kevin C; Shafer, Paul; Patel, Deesha; Alexander, Robert; Bunnell, Rebecca

2017-01-01

While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose-response from the campaign was only assessed by self-report. Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. A 3-month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard-dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non-smokers and further increasing quit attempts among smokers, especially African-Americans. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer.

PubMed

McDermott, Ronan L; Armstrong, John G; Thirion, Pierre; Dunne, Mary; Finn, Marie; Small, Cormac; Byrne, Mary; O'Shea, Carmel; O'Sullivan, Lydia; Shannon, Aoife; Kelly, Emma; Hacking, Dayle J

2018-05-01

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487. Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high. In contrast, this non-randomised, single-arm trial was designed to assess if more technically advanced treatment techniques would result in equivalent symptom relief and reduce the side-effect of symptomatic oesophagitis. Thirty-five evaluable patients with symptomatic locally advanced or metastatic NSCLC were treated using a three-dimensional conformal technique (3-DCRT) and standardised dose regimens of 39 Gy in 13 fractions, 20 Gy in 5 fractions or 17 Gy in 2 fractions. Treatment plans sought to minimise oesophageal dose. Oesophagitis was recorded during treatment, at two weeks, one month and three months following radiation therapy and 3-6 monthly thereafter. Mean dose to the irradiated oesophagus was calculated for all treatment plans. Five patients (14%) had experienced grade 2 oesophagitis or dysphagia or both during treatment and 2 other patients had these side effects at the 2-week follow-up. At follow-up of one month after therapy, there was no grade two or higher oesophagitis or dysphagia reported. 22 patients were eligible for assessment of late toxicity. Five of these patients reported oesophagitis or dysphagia (one had grade 3 dysphagia, two had grade 2 oesophagitis, one of whom also had grade 2 dysphagia). Quality of Life (QoL) data at baseline and at 1-month follow up were available for 20 patients. At 1-month post radiation therapy, these patients had slightly less trouble taking a short walk, less shortness of breath, did not feel as weak, had better appetite and generally had a better overall quality of life than they did at baseline. They did report being slightly more tired. This trial is the first of its kind showing that 3-DCRT provides patients with lower rates of oesophageal toxicity whilst yielding acceptable rates of symptom control. (Sponsored by Cancer Trials Ireland (ICORG) Study number 06-34, the Friends of St. Luke's and the St. Luke's Institute of Cancer Research.). Copyright © 2018 Elsevier B.V. All rights reserved.

In vivo genotoxicity of furan in F344 rats at cancer bioassay doses

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

Ding, Wei, E-mail: Wei.Ding@fda.hhs.gov; Petibone, Dayton M.; Latendresse, John R.

2012-06-01

Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8 mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 andmore » 16 mg/kg. Rats were killed 3 h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity. -- Highlights: ► Furan is a potent rodent liver carcinogen and represents a human cancer risk. ► Furan induces DNA damage in rat liver at cancer bioassay doses. ► Furan induces oxidative stress, inflammation and cell proliferation in rat liver. ► Expression of DNA damage repair-related genes is reduced in furan-treated rat livers. ► Furan induces rat liver cancer mainly through a secondary genotoxic mechanism.« less

Potential for Improved Intelligence Quotient Using Volumetric Modulated Arc Therapy Compared With Conventional 3-Dimensional Conformal Radiation for Whole-Ventricular Radiation in Children

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

Qi, X. Sharon, E-mail: xqi@mednet.ucla.edu; Department of Radiation Oncology, University of Colorado Denver, Aurora, Colorado; Stinauer, Michelle

Purpose: To compare volumetric modulated arc therapy (VMAT) with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of localized intracranial germinoma. We modeled the effect of the dosimetric differences on intelligence quotient (IQ). Method and Materials: Ten children with intracranial germinomas were used for planning. The prescription doses were 23.4 Gy to the ventricles followed by 21.6 Gy to the tumor located in the pineal region. For each child, a 3D-CRT and full arc VMAT was generated. Coverage of the target was assessed by computing a conformity index and heterogeneity index. We also generated VMAT plans with explicit temporal lobemore » sparing and with smaller ventricular margin expansions. Mean dose to the temporal lobe was used to estimate IQ 5 years after completion of radiation, using a patient age of 10 years. Results: Compared with the 3D-CRT plan, VMAT improved conformality (conformity index 1.10 vs 1.85), with slightly higher heterogeneity (heterogeneity index 1.09 vs 1.06). The averaged mean doses for left and right temporal lobes were 31.3 and 31.7 Gy, respectively, for VMAT plans and 37.7 and 37.6 Gy for 3D-CRT plans. This difference in mean temporal lobe dose resulted in an estimated IQ difference of 3.1 points at 5 years after radiation therapy. When the temporal lobes were explicitly included in the VMAT optimization, the mean temporal lobe dose was reduced 5.6-5.7 Gy, resulting in an estimated IQ difference of an additional 3 points. Reducing the ventricular margin from 1.5 cm to 0.5 cm decreased mean temporal lobe dose 11.4-13.1 Gy, corresponding to an estimated increase in IQ of 7 points. Conclusion: For treatment of children with intracranial pure germinomas, VMAT compared with 3D-CRT provides increased conformality and reduces doses to normal tissue. This may result in improvements in IQ in these children.« less

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

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

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

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

SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

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

Algan, O; Giem, J; Young, J

Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-testmore » analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

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

PubMed

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

2015-01-01

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

Impact of same day vs day before pre-operative lymphoscintigraphy for sentinel lymph node biopsy for early breast cancer (local Australian experience).

PubMed

Huang, Yang Yang; Maurel, Amelie; Hamza, Saud; Jackson, Lee; Al-Ogaili, Zeyad

2018-06-01

To assess the impact of delayed vs immediate pre-operative lymphoscintigraphy (LSG) for sentinel lymph node biopsy in a single Australian tertiary breast cancer centre. Retrospective cohort study analysing patients with breast cancer or DCIS who underwent lumpectomy or mastectomy with pre-operative LSG and intra-operative sentinel lymph node biopsy from January 2015 to June 2016. A total of 182 LSG were performed. Group A patients had day before pre-operative LSG mapping (n = 79) and Group B had LSG mapping on the day of surgery (n = 103). The overall LSG localisation rate was 97.3% and no statistical difference was detected between the two groups. The overall sentinel lymph node biopsies (SLN) were identified in 99.6% of patients. The number of nodes excised was slightly higher in Group A (1.90 vs 1.72); however, this was not statistically significant. In addition, the number of nodes on histopathology and the incidence of second echelon nodal detection were also similar between the two groups without statistical significance. In conclusion, the 2-day LSG protocol had no impact on overall SLNB and LSG detection rates although slightly higher second tier nodes but this did not translate to any difference between the number of harvest nodes between the two groups. The 2-day LSG allows for greater flexibility in theatre planning and more efficient use of theatre time. We recommend a dose of 40 Mbq of Tc99 m pertechnetate-labelled colloid be given day prior to surgery within a 24-hour timeframe. © 2017 The Royal Australian and New Zealand College of Radiologists.

A Pharmacokinetic Bioequivalence Study Comparing Pirfenidone Tablet and Capsule Dosage Forms in Healthy Adult Volunteers.

PubMed

Pan, Lin; Belloni, Paula; Ding, Han Ting; Wang, Jianshuang; Rubino, Christopher M; Putnam, Wendy S

2017-09-01

Pirfenidone film-coated tablets were developed to offer an alternative to the marketed capsule formulation. This study assessed the bioequivalence of the tablet and capsule formulations under fed and fasted states. A Phase I, open-label, randomized, four-treatment-period, four-sequence, crossover pharmacokinetics study (NCT02525484) was conducted. Each subject received an 801-mg single dose of pirfenidone as three 267-mg capsules or one 801-mg tablet under fasted and fed conditions. Pirfenidone plasma C max , AUC 0-t and AUC 0-∞ were used to assess bioequivalence. Forty-four subjects were randomized to treatment. The 801-mg tablet in the fasted state met bioequivalence criteria [90% confidence intervals (CI) 80.00-125.00%] for the GLSM ratios of natural log-transformed C max , AUC 0-t and AUC 0-∞ . Under fed conditions, the 801-mg tablet met the bioequivalence criteria for AUC 0-t and AUC 0-∞ , but slightly exceeded the bioequivalence criteria for the C max (90% CI of 108.26-125.60%). The tablet C max was approximately 17% higher than that of the capsules. In the fed state, the tablet C max , and both AUC 0-t and AUC 0-∞ were reduced by 39% and 17%, respectively, relative to the fasted state. The tablet and capsules had acceptable tolerability profiles. The pirfenidone 801-mg tablet met bioequivalence criteria when compared with three 267-mg capsules in the fasted state. The tablet C max was slightly higher relative to capsules in the fed state, but this is not expected to have a clinically meaningful impact on the benefit-risk profile of pirfenidone. This work was supported by F. Hoffmann-La Roche Ltd.

Measurements of air dose rates in and around houses in the Fukushima Prefecture in Japan after the Fukushima accident.

PubMed

Matsuda, Norihiro; Mikami, Satoshi; Sato, Tetsuro; Saito, Kimiaki

2017-01-01

Measurements of air dose rates for 192 houses in a less contaminated area (<0.5 μSv h -1 ) of the Fukushima Prefecture in Japan were conducted in both living rooms and/or bedrooms using optically stimulated luminescence (OSL) dosimeters and around the houses via a man-borne survey at intervals of several meters. The relation of the two air dose rates (inside and outside) for each house, including the background from natural radionuclides, was divided into several categories, determined by construction materials (light and heavy) and floor number, with the dose reduction factors being expressed as the ratio of the dose inside to that outside the house. For wooden and lightweight steel houses (classed as light), the dose rates inside and outside the houses showed a positive correlation and linear regression with a slope-intercept form due to the natural background, although the degree of correlation was not very high. The regression coefficient, i.e., the average dose reduction factor, was 0.38 on the first floor and 0.49 on the second floor. It was found that the contribution of natural radiation cannot be neglected when we consider dose reduction factors in less contaminated areas. The reductions in indoor dose rates are observed because a patch of ground under each house is not contaminated (this is the so-called uncontaminated effect) since the shielding capability of light construction materials is typically low. For reinforced steel-framed concrete houses (classed as heavy), the dose rates inside the houses did not show a correlation with those outside the houses due to the substantial shielding capability of these materials. The average indoor dose rates were slightly higher than the arithmetic mean value of the outdoor dose rates from the natural background because concrete acts as a source of natural radionuclides. The characteristics of the uncontaminated effect were clarified through Monte Carlo simulations. It was found that there is a great variation in air dose rates even within one house, depending on the height of the area and its closeness to the outside boundary. Measurements of outdoor dose rates required consideration of local variations depending on the environment surrounding each house. The representative value was obtained from detailed distributions of air dose rates around the house, as measured by a man-borne survey. Therefore, it is imperative to recognize that dose reduction factors fluctuate in response to various factors such as the size and shape of a house, construction materials acting as a shield and as sources, position (including height) within a room, floor number, total number of floors, and surrounding environment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

PubMed Central

Koulu, M; Scheinin, M; Kaarttinen, A; Kallio, J; Pyykkö, K; Vuorinen, J; Zimmer, R H

1989-01-01

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged. PMID:2469451

A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

PubMed

Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

2015-01-01

The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear. We investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.

A Low-Dose β1-Blocker in Combination with Milrinone Improves Intracellular Ca2+ Handling in Failing Cardiomyocytes by Inhibition of Milrinone-Induced Diastolic Ca2+ Leakage from the Sarcoplasmic Reticulum

PubMed Central

Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

2015-01-01

Objectives The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. Background The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca2+ handling in heart failure remains unclear. Methods We investigated the effect of milrinone plus landiolol on intracellular Ca2+ transient (CaT), cell shortening (CS), the frequency of diastolic Ca2+ sparks (CaSF), and sarcoplasmic reticulum Ca2+ concentration ({Ca2+}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). Results In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca2+}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca2+}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. Conclusion A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca2+ leak. PMID:25614983

SU-E-J-109: Evaluation of Deformable Accumulated Parotid Doses Using Different Registration Algorithms in Adaptive Head and Neck Radiotherapy

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

Xu, S; Chinese PLA General Hospital, Beijing, 100853 China; Liu, B

2015-06-15

Purpose: Three deformable image registration (DIR) algorithms are utilized to perform deformable dose accumulation for head and neck tomotherapy treatment, and the differences of the accumulated doses are evaluated. Methods: Daily MVCT data for 10 patients with pathologically proven nasopharyngeal cancers were analyzed. The data were acquired using tomotherapy (TomoTherapy, Accuray) at the PLA General Hospital. The prescription dose to the primary target was 70Gy in 33 fractions.Three DIR methods (B-spline, Diffeomorphic Demons and MIMvista) were used to propagate parotid structures from planning CTs to the daily CTs and accumulate fractionated dose on the planning CTs. The mean accumulated dosesmore » of parotids were quantitatively compared and the uncertainties of the propagated parotid contours were evaluated using Dice similarity index (DSI). Results: The planned mean dose of the ipsilateral parotids (32.42±3.13Gy) was slightly higher than those of the contralateral parotids (31.38±3.19Gy)in 10 patients. The difference between the accumulated mean doses of the ipsilateral parotids in the B-spline, Demons and MIMvista deformation algorithms (36.40±5.78Gy, 34.08±6.72Gy and 33.72±2.63Gy ) were statistically significant (B-spline vs Demons, P<0.0001, B-spline vs MIMvista, p =0.002). And The difference between those of the contralateral parotids in the B-spline, Demons and MIMvista deformation algorithms (34.08±4.82Gy, 32.42±4.80Gy and 33.92±4.65Gy ) were also significant (B-spline vs Demons, p =0.009, B-spline vs MIMvista, p =0.074). For the DSI analysis, the scores of B-spline, Demons and MIMvista DIRs were 0.90, 0.89 and 0.76. Conclusion: Shrinkage of parotid volumes results in the dose increase to the parotid glands in adaptive head and neck radiotherapy. The accumulated doses of parotids show significant difference using the different DIR algorithms between kVCT and MVCT. Therefore, the volume-based criterion (i.e. DSI) as a quantitative evaluation of registration accuracy is essential besides the visual assessment by the treating physician. This work was supported in part by the grant from Chinese Natural Science Foundation (Grant No. 11105225)« less

Subclinical hyperthyroidism: possible danger of overzealous thyroxine replacement therapy.

PubMed

Ross, D S

1988-12-01

Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.

Effects of long term treatment with high doses of odanacatib on bone mass, bone strength, and remodeling/modeling in newly ovariectomized monkeys.

PubMed

Duong, L T; Pickarski, M; Cusick, T; Chen, C M; Zhuo, Y; Scott, K; Samadfam, R; Smith, S Y; Pennypacker, B L

2016-07-01

The objectives here were to evaluate the effects of odanacatib (ODN) at doses exceeding the clinical exposure on biomechanical properties of lumbar vertebrae (LV), hip and central femur (CF), and compare ODN to alendronate (ALN) on bone remodeling/modeling in ovariectomized (OVX) monkeys. Ten days post-surgery, animals were treated with vehicle (VEH), ODN-L (2mg/kg/day, p.o.), ODN-H (8/4mg/kg/day), or ALN (30μg/kg/week, s.c.) for 20months. An intact group was also included. ODN-L provided systemic exposures of 1.8-fold of clinical exposure. ODN-H started at 20-fold for 5.5months, and then reduced to 7.8-fold of clinical exposure, compared to ALN at approximated clinical exposure. From cross sectional analyses, LV density and peak load in ODN at both doses or ALN were not different from VEH or Intact. However, cortical thickness of femoral neck (FN) and CF in ODN were higher (21-34%, p<0.05) than VEH, due to smaller endocortical (Ec) perimeter of FN (10-11%; p<0.05) and CF (9-12%; ODN-L, p<0.05), and larger CF periosteal (Ps) perimeter (2-12%; ODN-H, p<0.001) versus VEH. ODN groups also showed slightly higher cortical porosity and Ps non-lamellar bone in CF. ODN-H treatment resulted in higher CF peak load (p<0.05) versus VEH. For all bone sites analyzed, a positive, linear relationship (r(2)=0.46-0.69, p<0.0001) of peak load to density or structural parameters was demonstrated. No treatment-related differences in the derived intrinsic strength properties were evidenced as compared between groups. ALN reduced all remodeling surfaces without affecting Ps modeling. Trabecular and intracortical remodeling were reduced in ODN groups, similar to ALN. Ec mineralizing surface in ODN-H trended to be lower than VEH by month 20, but Ec bone formation indices in ODN groups generally were not different from VEH. Ps modeling in ODN groups was significantly higher than other treatment groups. This study overall demonstrated the bone safety profile of ODN and its unique mechanism on cortical bone supporting the clinical application for osteoporosis treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Bioequivalence Study of Warfarin in Healthy Chinese Volunteers With a Validated High-Performance Liquid Chromatography-Mass Spectrometry Method.

PubMed

Li, Wenlong; Bu, Fanlong; Li, Rong; Wang, Benjie; Shaikh, Abdul Sami; Zhang, Yunyun; Guo, Ruichen; Zhang, Rui

2018-03-01

This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma. A sensitive liquid chromatography mass spectrometry method was established to determine warfarin in plasma. Drug and Statistics 2.1.1 was applied to calculate the pharmacokinetics parameters. The main pharmacokinetic parameters for film-coated and sugar-coated warfarin were the following: t ½ , 103.5 ± 18.8 and 105.8 ± 21.3 hours; T max , 0.7 ± 0.5 and 1.3 ± 0.8 hours; C max , 347.8 ± 74.8 and 322.9 ± 75.7 ng/mL; AUC 0∼360 , 16,024.2 ± 3713.9 and 15,586.6 ± 3477.0 ng·mL -1 ·h; AUC 0∼∞ , 17,335.7 ± 4089.1 and 16,912.0 ± 3911.2 ng·mL -1 ·h, respectively. The human pharmacokinetics of film-coated and sugar-coated warfarin were slightly different. The oral absorption and bioavailability of innovative film-coated warfarin were slightly higher than those of the sugar-coated warfarin. This study is vital to clinical usage of warfarin not only because of the pharmacokinetic parameters of the 2 pharmaceutical dosage forms of warfarin but also to obtain data on the prevalence of CYP2C9 and VKORC1 genes and their influence on the concentration of warfarin. © 2017, The American College of Clinical Pharmacology.

Induction of non-apoptotic cell death by morphinone in human promyelocytic leukemia HL-60 cells.

PubMed

Takeuchi, Risa; Hoshijima, Hiroshi; Nagasaka, Hiroshi; Chowdhury, Shahead Ali; Kikuchi, Hirotaka; Kanda, Yumiko; Kunii, Shiro; Kawase, Masami; Sakagami, Hiroshi

2006-01-01

As previously suggested, codeinone (oxidation product of codeine) induces non-apoptotic cell death, characterized by marginal caspase activation and the lack of DNA fragmentation in HL-60 human promyelocytic leukemia cells, which was inhibited by N-acetyl-L-cysteine. Whether, morphinone, an oxidative metabolite of morphine, also induced a similar type of cell death in HL-60 cells was investigated. Morphinone showed slightly higher cytotoxic activity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, HSC-4, NA, Ca9-22, promyelocytic leukemia HL-60, cervical carcinoma HeLa) than against normal oral human cells (gingival fibroblast HGF, pulp cells HPC, periodontal ligament fibroblast HPLF). Morphinone also induced an almost undetectable level of internucleosomal DNA fragmentation in the HL-60 cells. Morphinone did not activate caspase-8 or -9 in these cells. Morphinone dose-dependently activated caspase-3 in both HL-60 and HSC-2 cell lines, but to a much lesser extent than actinomycin D. Electron microscopy demonstrated that morphinone induced mitochondrial shrinkage, vacuolization and production of autophagosome and the loss of cell surface microvilli, without destruction of cell surface and nuclear membranes in the HL-60 cells. The autophagy inhibitor 3-methyladenine (0.3-10 mM) slightly inhibited the morphinone-induced cytotoxicity, when corrected for its own cytotoxicity. These data suggest that morphinone induces non-apoptotic cell death in HL-60 cells.

Duloxetine in the treatment of elderly people with major depressive disorder.

PubMed

Del Casale, Antonio; Girardi, Paolo; Brugnoli, Roberto; Sani, Gabriele; Di Pietro, Simone; Brugnoli, Chiara; Caccia, Federica; Angeletti, Gloria; Serata, Daniele; Rapinesi, Chiara; Tatarelli, Roberto; Kotzalidis, Giorgio D

2012-01-01

The elderly population is more frequently subjected to depressive mood compared to the general population and show peculiarities affecting responsiveness; furthermore, aged people need also special care. Duloxetine is a relatively new antidepressant that proved to be effective in adult depression, but has received little attention in elderly population heretofore. To review the evidence of duloxetine in late-life major depressive disorder (MDD). A systematic review of studies focusing on the use of duloxetine in MDD in the elderly has been carried out through the principal specialized databases, including PubMed, PsycLIT, and Embase. Only a handful of papers were specifically dedicated to this issue. Duloxetine was found to be effective and safe in old-age MDD, to be better than placebo on many clinical measures in all studies, and to better differentiate from placebo with respect to selective serotonin reuptake inhibitors. Compared to placebo, its side-effect profile is slightly unfavorable and its drop-out rate is slightly higher. Furthermore, when pain is present in old-age MDD, duloxetine is able to reduce it. The efficacy and safety of duloxetine in old-age depression are similar to those encountered in adult MDD. There is a relative lack of comparative studies other than with placebo. The special needs of elderly patients with MDD must be addressed with close patient contact to avoid the perils of inappropriate dosing.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

Isoproterenol exacerbates hyperglycemia and modulates chromium distribution in mice fed with a high fat diet.

PubMed

Chang, Geng-Ruei; Chen, Wen-Kai; Hou, Po-Hsun; Mao, Frank Chiahung

2017-12-01

Isoproterenol (ISO), a nonselective β-adrenoceptor agonist for treating bradycardia and asthma, has been proposed to raise blood glucose level. Little is known regarding the relationship between ISO treatment, the induced chromium (Cr) redistribution, and changes in glucose metabolism. We aimed to characterize the effects of a single dose of ISO on glucose homeostasis and Cr level changes in an obesity mouse model. Mice (C57BL6/j strain) were first fed for a continuous period of 12 weeks with either a high fat diet (HFD), to develop an obesity animal model, or a standard diet (SD), to develop a lean animal model as controls. These groups were each separated into two subgroups to receive either a single dose of ISO or saline (control). We measured in vivo their metabolic parameters, fasting glucose level, area under the curve (AUC) for glucose level time profile, insulin level time profile, insulin sensitivity index, and chromium distribution. After a single dose of ISO, the SD-fed mice had slightly higher blood glucose levels compared with the SD controls, when the level was measured 30 and 60min after injection. By contrast, the ISO-treated HFD-fed mice had significantly higher blood glucose levels and AUC during the entire 120min following one administration compared with the HFD control group. Additionally, they had a substantially lower HOMA-IR index, whereas insulin levels remained unchanged. The Cr level in their bones and liver was decreased, and loss of Cr through urinary excretion was elevated. The results demonstrated that ISO exacerbated hyperglycemic syndrome in the obesity animal model. ISO induced a net negative Cr balance as a result of increased urinary excretion, leading to Cr mobilization that was not desirable to overcome the hyperglycemia. Copyright © 2017 Elsevier GmbH. All rights reserved.

Betaine in sub-acute and sub-chronic rat studies.

PubMed

Hayes, K C; Pronczuk, Andrzej; Cook, Melvyn W; Robbins, Mark C

2003-12-01

To evaluate the sub-acute and sub-chronic effect of large doses of betaine, this trimethyl glycine compound was fed to rats. Initial studies at BIBRA in the UK evaluated intakes of 0, 1, 2, and 5% betaine added to a maintenance chow designed for use in toxicology studies. Male and female Sprague-Dawley rats were followed for up to 90 days. No toxicity occurred, but at higher betaine intakes several serum chemistries were altered slightly, the MCV, MCH, and MCHC of red cells were reduced, and hepatocytes developed fatty droplets in direct proportion to betaine intake. Females were more affected than males. In a second study to assess reversibility in females, betaine effects were induced for 28 days, followed by a 28 day betaine-free period. All perturbations, except the reduced MCV and MCH, were reversed. As a follow up to BIBRA investigations, both 28 and 90 day feeding trials were conducted at Brandeis University using a rat chow with higher levels of energy, protein, and fat, with betaine added at 0, 0.5, 0.75, 1.0 and 5.0% of the diet. A similar broad range of clinical chemistries and physiological parameters were monitored, and hepatic lipid droplets were investigated in more detail. Liver lipid was actually reduced by betaine, and no significant adverse effects of clinical importance resulted from any dose. However, the MCV was again reduced at 5% betaine in the 28 day study. By 90 days all parameters were normal and comparable to controls. Based on these collective data, it was concluded that even at these high doses, betaine is nontoxic. Differences observed between the BIBRA and Brandeis studies were attributed to differences in the dietary formulations. Significant betainexdietxgrowth interactions were thought to reflect primary disparities in protein and energy concentrations, more than the addition of betaine per se.

Factors predicting recurrence of chronic subdural haematoma: the influence of intraoperative irrigation and low-molecular-weight heparin thromboprophylaxis.

PubMed

Tahsim-Oglou, Yasemin; Beseoglu, Kerim; Hänggi, Daniel; Stummer, Walter; Steiger, Hans-Jakob

2012-06-01

Burr-hole drainage has become the accepted treatment of choice for chronic subdural haematoma (cSDH), although still burdened with a major recurrence rate. The current analysis was initiated to determine management-related risk factors for recurrence, i.e. postoperative low-molecular-weight heparin thromboprophylaxis, and the importance of rinsing the subdural space. Two-hundred and forty-seven patients with computerised tomography (CT) defined symptomatic cSDH were managed by two burr-hole trepanations and drainage between January 2005 and November 2008. Postoperative thromboprophylaxis with 40 mg enoxaparine daily was given only during the first half of the study period. For the current analysis the amount of rinsing fluid, postoperative low-dose thromboprophylaxis, as well as age and gender, bilaterality, preoperative and postoperative blood coagulation studies, platelet counts and decrease of subdural fluid on early postoperative CT, were recorded and correlated with recurrence. Statistical calculation was done by univariate and multivariate analysis. A total of 62 of 247 patients needed revision surgery for recurrence (25.1 %). Recurrence rates were significantly lower in the patients treated without postoperative enoxaparine (18.84 %) than in the group with postoperative low-dose enoxaparine thromboprophylaxis (32.11 %) and enoxaparine was administered in a higher proportion of the patients suffering recurrence (P = 0.013). A median intraoperative irrigation volume of 863 ml saline was used in the patients suffering recurrence and 1,500 ml in patients without recurrence (P < 0.001). The median age was slightly higher in the patients suffering from recurrence. Male gender predominated in both groups but was slightly more pronounced in the recurrence group. Preoperative and postoperative platelet counts and plasmatic coagulation indices did not differ significantly between the groups. Relative residual subdural fluid collection on early postoperative CT remained larger in patients finally suffering recurrence (P = 0.03). Multivariate analysis confirmed a small amount of rinsing fluid, male gender and the use of enoxaparine as the most important risk factors for recurrence, although that latter factor did not reach statistical significance in the multivariate analysis. The investigation provides evidence that copious intraoperative irrigation and avoidance of postoperative low-molecular-weight heparin thromboprophylaxis may reduce the recurrence rate of cSDH.

Influenza vaccination coverage among US children from 2004/2005 to 2015/2016.

PubMed

Tian, Changwei; Wang, Hua; Wang, Wenming; Luo, Xiaoming

2018-05-15

Quantify the influenza vaccine coverage is essential to identify emerging concerns and to immunization programs for targeting interventions. Data from National Health Interview Survey were used to estimate receipt of at least one dose of influenza vaccination among children 6 months to 17 years of age. Influenza vaccination coverage increased from 16.70% during 2004/2005 to 49.43% during 2015/2016 (3.18% per year, P < 0.001); however, the coverage increased slightly after 2010/2011. Children at high risk of influenza complications had higher influenza vaccination coverage than non at-risk children. Boys and girls had similar coverage each year. While the coverage increased from 2004/2005 to 2015/2016 for all age groups, the coverage decreased with age each year (-0.64 to -1.58% per age group). There was a higher and rapid increase of coverage in Northeast than Midwest, South and West. American Indian or Alaskan Native and Asian showed higher coverage than other race groups (White, Black/African American, Multiple race). Multivariable analysis showed that high-risk status and region had the greatest associations with levels of vaccine coverage. Although the influenza vaccination coverage among children had increased remarkably since 2004/2005, establishing more effective immunization programs are warranted to achieve the Healthy People 2020 target.

Absence of cross-resistance between two alkylating agents: BCNU vs bifunctional galactitol.

PubMed

Institóris, E; Szikla, K; Otvös, L; Gál, F

1989-01-01

Dianhydrogalactitol (DAG) increased the life span of both BCNU-sensitive and -resistant L1210 tumor-bearing mice. However, the BCNU-resistant strain showed slightly lower sensitivity against DAG, which could be overcome by an increase in drug dose of ca. 20%. The somewhat lower sensitivity was proportional to a slightly reduced DNA cross-linking formation induced by DAG in BCNU-resistant cells. The amount of DNA cross-links was determined by measurement of the 1,6-di(guaninyl)-galactitol content of DNA. The slight reduction in cross-links is not attributable to DNA repair but rather to other factors that seem to prevent the formation of DNA-drug adducts. The absence of cross-resistance is explained by different kinds of DNA damage caused by the two alkylating agents and the presumably different defense mechanisms developed by cells against these lesions.

A randomized trial of hospital vs home self administration of vaginal misoprostol for medical abortion.

PubMed

Shrestha, A; Sedhai, L B

2014-01-01

A combination of mifepristone followed after 24 hrs by misoprostol has proved a safe and effective abortifacient for termination of early pregnancy. Home use of misoprostol for medical abortion is still controversial in many countries including ours where women's literacy rate is low. Particularly in developing countries, this method markedly decreased the hospital visit which would be beneficial to patients and hospital staff. To see whether the home self administration of vaginal misoprostol was equally effective as administered by trained staff in terms of successful termination of early pregnancy. Secondary outcomes were bleeding and pain duration during medical abortion, side effects, reason for termination of pregnancy and women's acceptability of the procedure. One hundred and eighty eight women requesting medical abortion with pregnancy less than 63 days gestation were randomized into two groups either self administration of vaginal misoprostol (800 mcg) at home or hospital administration 24 hours after oral 200 mg mifepristone. Ultrasound was performed after 14 days to confirm complete abortion. The overall success rate was similar in two groups: 89.13% on home group Vs 86.9% in hospital group. Eleven out of 18 women (61.1%) having incomplete abortion had successful termination after 2nd dose misoprostol( 400 mcg). None of the women had continued pregnancy. Multigravida had slightly higher risk of failure (R.R: 1.04). Home self administration of vaginal misoprostol was safe and effective for early termination of medical abortion and was acceptable. Use of extra dose of misoprostol has advantage of higher completion rate of abortion.

H1N1 antibody persistence 1 year after immunization with an adjuvanted or whole-virion pandemic vaccine and immunogenicity and reactogenicity of subsequent seasonal influenza vaccine: a multicenter follow-on study.

PubMed

Walker, Woolf T; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T; Miller, Elizabeth; Faust, Saul N; Snape, Matthew D; Finn, Adam; Pollard, Andrew J

2012-03-01

We investigated antibody persistence in children 1 year after 2 doses of either an AS03(B)-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03(B)-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%-100%) vs 32.4% (95% CI, 21.5%-44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%-99.4%) vs 65.9% (95% CI, 55.3%-75.5%) in those 3-12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03(B)-adjuvanted vaccine. This study provides serological evidence that 2 doses of AS03(B)-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

PubMed Central

Walker, Woolf T.; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M.; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T.; Miller, Elizabeth; Snape, Matthew D.; Finn, Adam; Pollard, Andrew J.

2012-01-01

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain. PMID:22267719

Radiological Modeling for Determination of Derived Concentration Levels of an Area with Uranium Residual Material - 13533

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

Perez-Sanchez, Danyl

As a result of a pilot project developed at the old Spanish 'Junta de Energia Nuclear' to extract uranium from ores, tailings materials were generated. Most of these residual materials were sent back to different uranium mines, but a small amount of it was mixed with conventional building materials and deposited near the old plant until the surrounding ground was flattened. The affected land is included in an area under institutional control and used as recreational area. At the time of processing, uranium isotopes were separated but other radionuclides of the uranium decay series as Th-230, Ra-226 and daughters remainmore » in the residue. Recently, the analyses of samples taken at different ground's depths confirmed their presence. This paper presents the methodology used to calculate the derived concentration level to ensure that the reference dose level of 0.1 mSv y-1 used as radiological criteria. In this study, a radiological impact assessment was performed modeling the area as recreational scenario. The modelization study was carried out with the code RESRAD considering as exposure pathways, external irradiation, inadvertent ingestion of soil, inhalation of resuspended particles, and inhalation of radon (Rn-222). As result was concluded that, if the concentration of Ra-226 in the first 15 cm of soil is lower than, 0.34 Bq g{sup -1}, the dose would not exceed the reference dose. Applying this value as a derived concentration level and comparing with the results of measurements on the ground, some areas with a concentration of activity slightly higher than latter were found. In these zones the remediation proposal has been to cover with a layer of 15 cm of clean material. This action represents a reduction of 85% of the dose and ensures compliance with the reference dose. (authors)« less

Response of rat skin to boron neutron capture therapy with p-boronophenylalanine or borocaptate sodium.

PubMed

Morris, G M; Coderre, J A; Hopewell, J W; Micca, P L; Rezvani, M

1994-08-01

The effects of boron neutron capture irradiation employing either BPA or BSH as neutron capture agents has been assessed using the dorsal skin of Fischer 344 rats. Pharmacokinetic studies, using prompt gamma spectrometry, revealed comparable levels of boron-10 (10B) in blood and skin after the intravenous infusion of BSH (100 mg/kg body wt.). The 10B content of blood (12.0 +/- 0.5 micrograms/g) was slightly higher than that of skin (10.0 +/- 0.5 micrograms/g) after oral dosing with BPA. Biphasic skin reactions were observed after irradiation with the thermal neutron beam alone or in combination with BPA or BSH. The time of onset of the first phase of the skin reaction, moist desquamation, was approximately 2 weeks. The time at which the second-wave skin reaction, dermal necrosis, became evident was dose-related and occurred after a latent interval of > or = 24 weeks, well after the acute epithelial reaction had healed. The incidence of both phases of skin damage was also dose-related. The radiation doses required to produce skin damage in 50% of skin sites (ED50 values) were calculated from dose-effect curves and these values were used to determine relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for both moist desquamation and dermal necrosis. It was concluded on the basis of these calculations that the microdistribution of the two neutron capture agents had a critical bearing on the overall biological effect after thermal neutron activation. BSH, which was possibly excluded from the cytoplasm of epidermal cells, had a low CBE factor value (0.56 +/- 0.06) while BPA, which may be selectively accumulated in epidermal cells had a very high CBE factor (3.74 +/- 0.7). For the dermal reaction, where vascular endothelial cells represent the likely target cell population, the CBE factor values were comparable, at 0.73 +/- 0.42 and 0.86 +/- 0.08 for BPA ad BSH, respectively.

Eficiency of different doses of rituximab in rheumatoid arthritis.

PubMed

Mena-Vázquez, Natalia; Manrique-Arija, Sara; Ureña-Garnica, Inmaculada; Romero-Barco, Carmen M; Jiménez-Núñez, Francisco G; Coret, Virginia; Irigoyen-Oyarzábal, María Victoria; Fernández-Nebro, Antonio

2016-01-01

Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Arsenic exposure and bladder cancer: quantitative assessment of studies in human populations to detect risks at low doses.

PubMed

Tsuji, Joyce S; Alexander, Dominik D; Perez, Vanessa; Mink, Pamela J

2014-03-20

While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[Dosimetry verification of radioactive seed implantation with 3D printing template and CT guidance for paravertebral/retroperitoneal malignant tumor].

PubMed

Ji, Z; Jiang, Y L; Guo, F X; Peng, R; Sun, H T; Fan, J H; Wang, J J

2017-04-04

Objective: To compare the dose distributions of postoperative plans with preoperative plans for seeds implantations of paravertebral/retroperitoneal tumors assisted by 3D printing guide template and CT guidance, explore the effects of the technology for seeds implantations in dosimetry level and provide data support for the optimization and standardization in seeds implantation. Methods: Between December 2015 and July 2016, a total of 10 patients with paravertebral/retroperitoneal tumors (12 lesions) received 3D printing template assist radioactive seeds implantations in department of radiation oncology of Peking University Third Hospital, and included in the study. The diseases included cervical cancer, kidney cancer, abdominal stromal tumor, leiomyosarcoma of kidney, esophageal cancer and carcinoma of ureter. The prescribed doses was 110-150 Gy. All patients received preoperative planning design, individual template design and production, and the dose distribution of postoperative plan was compared with preoperative plan. Dose parameters including D(90), MPD, V(100), V(150,)conformal index(CI), EI of target volume and D(2cc) of organs at risk (spinal cord, aorta, kidney). Statistical software was SPSS 19.0 and statistical method was non-parameters Wilcoxon symbols test. Results: A total of 10 3D printing templates were designed and produced which were including 12 treatment areas.The mean D(90) of postoperative target area (GTV) was 131.1 (97.8-167.4 Gy) Gy. The actual seeds number of post operation increased by 3 to 12 in 5 cases (42.0%). The needle was well distributed. For postoperative plans, the mean D(90,)MPD, V(100,)V(150) was 131.1 Gy, 69.3 Gy, 90.2% and 65.2%, respectively, and which was 140.2 Gy, 65.6 Gy, 91.7% and 26.8%, respectively, in preoperative plans. This meant that the actual dose of target volume was slightly lower than preplanned dose, and the high dose area of target volume was larger than preplanned range, but there was no statistical difference in P value between the two groups except V(150)( P =0.004). The actual dose conformity of target volume was worse than preplanned (CI was 0.58 and 0.62, respectively) and the difference was statistically significant( P =0.019). The actual dose of external target volume was higher than preplanned (EI was 55% and 45.9%, respectively) and the difference had no significance. For organs at risk, the actual mean D(2cc) of spinal cord, aorta and kidney was 24.7, 54.4 and 29.7 Gy, respectively, which was higher than preplanned(20.6, 51.6 and 28.6 Gy, respectively), and there was no significant difference in two groups. Conclusions: Most parameters of postoperative validations for 3D printing template assisted seeds implantation in paravertebral/retroperitoneal are closed to the expectations of preoperative plans which means the improvement of accuracy in treatment.

Adrenal steroid inhibition of the vasopressin-neurophysin neurosecretory system to the median eminence of the rat. Differential effects of corticosterone and deoxycorticosterone administration after adrenalectomy.

PubMed

Silverman, A J; Hoffman, D; Gadde, C A; Krey, L C; Zimmermann, E A

1981-03-01

Neurophysin and vasopressin-containing terminals in the zona externa of the median eminence (ZE) show a large increase in immunoreactive peptide following adrenalectomy which can be prevented by dexamethazone replacement therapy. The present study was undertaken to determine the effectiveness of a glucocorticoid (corticosterone; CS) and a mineralocorticoid (deoxycorticosterone: DOC) in exerting negative feedback on this system. Animals were adrenalectomized and implanted with various sized pellets of either steroid or cholesterol. The amount of neurophysin-immunoreactivity in the ZE 2 weeks after adrenalectomy was estimated on a zero to four rank scale independently by three observers. The data were analyzed by the X2 statistic. Low doses of CS (50 mg) reduced the amount of staining in comparison to cholesterol-replaced animals by approximately 50%. The ZE of animals receiving higher doses (100--200 mg) were identical to those of intact animals. DOC, however, at the 50 or 100 mg level produced only a slight inhibition of the response to adrenalectomy. Larger pellets (150--200 mg) did not result in a level of ZE staining as low as for intact animals. These findings suggest that the vasopressin neurosecretory system to the ZE is regulated by glucocorticoids.

CD uniformity control for thick resist process

NASA Astrophysics Data System (ADS)

Huang, Chi-hao; Liu, Yu-Lin; Wang, Weihung; Yang, Mars; Yang, Elvis; Yang, T. H.; Chen, K. C.

2017-03-01

In order to meet the increasing storage capacity demand and reduce bit cost of NAND flash memories, 3D stacked flash cell array has been proposed. In constructing 3D NAND flash memories, the higher bit number per area is achieved by increasing the number of stacked layers. Thus the so-called "staircase" patterning to form electrical connection between memory cells and word lines has become one of the primarily critical processes in 3D memory manufacture. To provide controllable critical dimension (CD) with good uniformity involving thick photo-resist has also been of particular concern for staircase patterning. The CD uniformity control has been widely investigated with relatively thinner resist associated with resolution limit dimension but thick resist coupling with wider dimension. This study explores CD uniformity control associated with thick photo-resist processing. Several critical parameters including exposure focus, exposure dose, baking condition, pattern size and development recipe, were found to strongly correlate with the thick photo-resist profile accordingly affecting the CD uniformity control. To minimize the within-wafer CD variation, the slightly tapered resist profile is proposed through well tailoring the exposure focus and dose together with optimal development recipe. Great improvements on DCD (ADI CD) and ECD (AEI CD) uniformity as well as line edge roughness were achieved through the optimization of photo resist profile.

National Collegiate Athletic Association Division I Athletes’ Use of Nonprescription Medication

PubMed Central

Wolf, Douglas A.; Miller, Thomas W.; Pescatello, Linda S.; Barnes, Christopher

2011-01-01

Background: Athletes are known to use over-the-counter pain medication. However, the frequency of such use among National Collegiate Athletic Association (NCAA) Division I-A football athletes is unknown. Hypothesis: NCAA Division I-A football athletes who use nonprescription analgesics for pain misuse these medications. Study Design: Cross-sectional study. Methods: The football players (N, 144) who met the criteria and agreed to participate were from 8 NCAA Division I-A schools. The participants were administered the Over the Counter Drug Screen for Athletes, which measures attitudes toward the use of a spectrum of substances. Results: Among football athletes surveyed who took nonprescription analgesics for football-related pain, 37% reported taking more than the recommended dose. This was slightly higher than the 28% of players who stated they have not taken nonprescription analgesics for football-related pain. Thirty-four percent of all athletes reported using more than the recommended dose of nonprescription analgesics. Athletes who purchased their own nonprescription analgesics communicated poorly regarding nonprescription analgesics use. Those lacking knowledge about nonprescription analgesics and those using nonprescription analgesics in anticipation of pain or to avoid missing a practice or game were most likely to misuse nonprescription analgesics. Conclusion: NCAA Division I-A football athletes who use nonprescription analgesics for athletic competition do not misuse nonprescription analgesics. PMID:23015987

Efficacy and safety of additional 200-mg dose of celecoxib in adult patients with postoperative pain following extraction of impacted third mandibular molar: a multicenter, randomized, double-blind, placebo-controlled, phase II study in Japan.

PubMed

Saito, Ken'ichi; Kaneko, Akihiro; Machii, Katsuyuki; Ohta, Hiroyoshi; Ohkura, Masayuki; Suzuki, Makoto

2012-02-01

Although third mandibular molar extraction is a widely used and validated model of acute pain for evaluating analgesic efficacy, a large proportion of patients experience moderate or severe pain following this procedure and require analgesia. Current treatment options have been associated with safety concerns and alternative therapies are sought. Our aim was to assess the efficacy and safety of an additional 200-mg dose of celecoxib, administered 5 to 12 hours after an initial 400-mg dose of the drug for the treatment of moderate or severe acute pain following extraction of an impacted third mandibular molar. This was a multicenter, randomized, double-blind, placebo-controlled, Phase II study. Patients experiencing moderate or severe pain within 1 to 2 hours following extraction of an impacted third mandibular molar received an initial 400-mg dose of celecoxib. Patients requiring additional analgesia were subsequently randomized to receive either an additional 200-mg dose of celecoxib or placebo 5 to 12 hours after the initial dose. The study was designed and conducted by Pfizer Inc. for approval of celecoxib in Japan for the indication of acute pain. The primary end point was the patient's impression of efficacy (4-category global evaluation scale). Secondary efficacy end points included pain intensity on a 4-category pain intensity scale, pain intensity on a 100-mm visual analog scale (VAS), and the pain intensity difference (100-mm VAS). In an exploratory analysis, use of rescue medication was evaluated. Primary and secondary end points were analyzed using the full analysis set. Assessment of the safety profile included a physical examination, measurement of pulse rate and blood pressure, standard 12-lead ECG, and laboratory tests. A total of 69 patients (celecoxib, 42/64 [65.6%]; placebo, 27/58 [46.6%]) received the additional dose of study medication; all completed the study without the need for rescue medication. A significantly higher proportion of patients in the celecoxib 200 mg group (41/64 [64.1%]) compared with the placebo group (15/58 [25.9%]) rated the study medication as "good" or "excellent" ≥ 2 hours after the additional dose (P < 0.0001). Pain intensity (VAS) 2 hours after the additional dose was significantly higher in the placebo group than in the celecoxib 200 mg group (P = 0.0003). The reduction in pain intensity from baseline to 2 hours after the additional dose of study medication was also significantly greater in the celecoxib 200 mg group than in the placebo group (P < 0.0001). The incidence of treatment-related, all-cause adverse events was slightly lower in patients receiving celecoxib 200 mg (20.3%) compared with placebo (31.0%). Overall, an additional 200-mg dose of celecoxib was well tolerated and efficacious in reducing the pain associated with extraction of an impacted third mandibular molar in the study population. ClinicalTrials.gov identifier: NCT01062113. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

SU-F-T-448: Use of Mixed Photon Energy Beam in Volumetric Modulated Arc Therapy (VMAT) Treatment Plan for Prostate Cancer

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

Manigandan, D; Kumar, M; Mohandas, P

Purpose: To study the impact of different photon beam combination during VMAT planning and treatment delivery. Methods: Five prostate patients with no nodal involvement were chosen for the study and only prostate was considered as target (7920cGy/44fractions). In each case, three different VMAT plans were generated with two arcs (200°–160°&160°–200°). First plan used only 6MV in both arcs (6X-6X) and second utilized 6MV&15MV (6X-15X), whereas third one used 15MV&15MV (15X-15X). For consistency, all the plans were generated by the same planner using Monaco− treatment planning system (V5.1) for Elekta Synergy− linear accelerator with 1cm leaf-width. For plan comparison, target meanmore » dose, conformity index (CI)=Planning target volume (PTV) covered by 95% of prescription dose/PTV were analyzed. Mean doses of bladder, rectum, left femur and right femur were analyzed. Integral dose (liter-Gray) to normal tissue (patient volume minus PTV), total monitor unit (MU) required to deliver a plan and gamma pass rate for each plan was analyzed. Results: The CI for PTV was 0.9937±0.0037, 0.9917±0.0033, and 0.9897±0.0048 for 6X-6X, 6X-15X and 15X-15X, respectively. Mean dose to target slightly increases with the decrease of energy. Mean doses to bladder were 3546.23±692.13cGy, 3487.43±715.53cGy and 3504.40±683.1cGy for 6X-6X, 6X-15X and 15X-15X, respectively. Mean doses to rectum were 4294.60±309.5cGy, 4277.07±279.93cGy and 4290.77±379.07cGy. Mean doses to left femur were 2737.13±545.93cGy, 2668.67±407.12cGy and 2416.77±300.73cGy and mean doses to the right femur were 2682.70±460.81cGy, 2722.58±541.92cGy and 2598.57±481.83cGy. Higher Integral doses to normal tissue observed for 6X-6X (163.06±24.6 Litre-Gray) followed by 6X-15X (154.35±24.74 Litre-Gray) and 15X-15X (145.84±26.03 Litre-Gray). Average MU required to deliver one fraction was 680.75±72.09, 634.81±95.07 and 605.06±114.65. Gamma pass rates were 99.83±0.21, 99.53±0.27 and 99.2±0.20. Conclusion: 6X-15X VMAT plan offer dosimetric advantage compared to 6X-6X in terms of lesser MU and integral dose without significant compromise in plan quality, where as in 15X-15X, neutron contamination risk is relatively higher.« less

SU-F-18C-06: Prospective Patient Evaluation of Iterative Reconstruction in Radiation Oncology

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

Price, R; Vance, S; Cattaneo, R

2014-06-15

Purpose: This work incorporates iterative reconstruction (IR) into a dose reduction study to characterize image quality metrics, delineation, and dosimetric assessment, with the goal of reducing imaging dose in Radiation Oncology. Methods: Three-dimensional noise power spectrum (NPS) analysis characterized noise magnitude/texture (120 kVp, 50–200 mAs, IR levels 1–6 yielding noise reduction of 0.89–0.55 compared to filtered backprojection (FBP)). Task-specific Modulation Transfer Functions (MTFtask) were characterized across varied subject contrasts. A prospective dose reduction study (500 to 150 mAs) was conducted for 12 patients (43 inter-fraction CTs) for high-dose rate brachytherapy. Three physicians performed qualitative image assessment between full-dose FBP (FD-FBP,more » 500 mAs), low-dose FBP (LD-FBP, 150–250 mAs), and low-dose IRL5-6 (LD-IR) scans for image noise, cuff/bladder interface detectability, spatial resolution, texture, and segmentation confidence. Comparisons between LD-FBP and LD-IR were conducted for the following metrics: delineation (bladder and rectum evaluated via overlap indices (OI) and Dice similarity coefficients (DSC)), noise, boundary changes, dose calculation, and digitally reconstructed radiographs (DRRs). Results: NPS showed ∼50% reduction in noise magnitude and ∼0.1 1/mm spatial frequency shift with IRL6. The largest MTFtask decrease between FBP and IR was 0.08 A.U. Qualitative patient image evaluation revealed LD-IR was equivalent or slightly worse than FD-FBP, and superior to LD-FBP for all metrics except low contrast interface and texture. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using IRL6 (−1.2 ± 4.9 HU (range: −17.6 – 12.5 HU)). No significant contour differences (OIs and DSCs = 0.85 – 0.95) and dose calculation discrepancy (<0.02%) were observed. DRRs preserved anatomical detail and demonstrated <2% difference in intensity between LD-FBP and LD-IRL6. Conclusion: While phantom analysis showed slight noise texture differences with IR, patient results revealed that image quality, contouring ability, and dosimetric parameters were not adversely affected, thus support integrating IR into treatment planning. Research supported in part by a grant from Philips HealthCare.« less

Evaluation of the peripheral dose to uterus in breast carcinoma radiotherapy.

PubMed

Martín Rincón, C; Jerez Sainz, I; Modolell Farré, I; España López, M L; López Franco, P; Muñiz, J L; Romero, A M; Rodríguez, R

2002-01-01

The absorbed dose outside of the direct fields of radiotherapy treatment (or peripheral dose, PD) is responsible for radiation exposure of the fetus in pregnant women. Because the radiological protection of the unborn child is of particular concern in the early period of the pregnancy, the aim of this study is to estimate the PD in order to assess the absorbed dose in the uterus in a pregnant patient irradiated for breast carcinoma therapy. The treatment was simulated on an Alderson-Rando anthropomorphic phantom, and the radiation dose to the fetus was measured using an ionisation chamber and thermoluminescence dosemeters. Two similar treatments plans with and without wedges were delivered, using a 6 MV photon beam with two isocentric opposite tangential fields with a total dose of 50 Gy, in accordance with common established procedures. Average field parameters for more than 300 patients were studied. Measurements showed the fetal dose to be slightly lower than 50 mGy, a level at which the risk to the fetus is uncertain, although several authors consider this value as the dose threshold for deterministic effects. The planning system (PS) underestimated PD values and no significant influence was found with the use of wedge filters.

Effect of gamma irradiation on physicochemical properties of stored pigeon pea (Cajanus cajan) flour

PubMed Central

Bamidele, Oluwaseun P; Akanbi, Charles T

2013-01-01

The effect of gamma irradiation at various doses (5, 10, 15, 20 kGy) was observed on pigeon pea flour stored for 3 months on proximate composition, functional properties, and peroxide value. Sensory evaluation was also carried out on bean cake (moinmoin) made from nonirradiated and irradiated pigeon pea flour. The results showed that stored gamma-irradiated samples had significantly lower (P < 0.05) value of protein and little or no effect on moisture content. There were slight decreases in crude fiber and ash content of the irradiated samples compared with the control sample. The result of functional properties of the irradiated flours showed slight increase in water absorption capacity, swelling capacity and bulk density. The peroxide value of crude oil increased significantly with dose increases for the period of storage. The sensory evaluation of moinmoin samples prepared from irradiated pigeon pea flour showed no significant difference from the moinmoin sample prepared from nonirradiated flour. It can be concluded that gamma irradiation can extend the shelf life of pigeon pea flour. PMID:24804044

Effect of gamma irradiation on physicochemical properties of stored pigeon pea (Cajanus cajan) flour.

PubMed

Bamidele, Oluwaseun P; Akanbi, Charles T

2013-09-01

The effect of gamma irradiation at various doses (5, 10, 15, 20 kGy) was observed on pigeon pea flour stored for 3 months on proximate composition, functional properties, and peroxide value. Sensory evaluation was also carried out on bean cake (moinmoin) made from nonirradiated and irradiated pigeon pea flour. The results showed that stored gamma-irradiated samples had significantly lower (P < 0.05) value of protein and little or no effect on moisture content. There were slight decreases in crude fiber and ash content of the irradiated samples compared with the control sample. The result of functional properties of the irradiated flours showed slight increase in water absorption capacity, swelling capacity and bulk density. The peroxide value of crude oil increased significantly with dose increases for the period of storage. The sensory evaluation of moinmoin samples prepared from irradiated pigeon pea flour showed no significant difference from the moinmoin sample prepared from nonirradiated flour. It can be concluded that gamma irradiation can extend the shelf life of pigeon pea flour.

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

PubMed

Lundy, P M

1978-04-01

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Differences in survival on peritoneal dialysis between oriental Asians and Caucasians: one center's experience.

PubMed

Wang, Tao; Tziviskou, Effie; Chu, Maggie; Bargman, Joanne; Jassal, Vanita; Vas, Stephen; Oreopoulos, Dimitrios G

2003-01-01

Recently it has been suggested that the survival of dialysis patients may differ among different races. Both registry data and data from Asian countries indicates that Asians on peritoneal dialysis may survive longer than their Caucasian counterparts. In the present study, we performed a detailed analysis of survival differences between oriental Asians and Caucasians on peritoneal dialysis in our multiethnic, multicultural program. Retrospectively we analyzed the survival data for patients who started peritoneal dialysis after January 1, 1996 and before December 31, 1999, in our hospital. They were followed for at least for two years. Excluded from the present analysis were those who survived for less than three months on peritoneal dialysis. The patient demographic characteristics, comorbidities, and residual renal function at the start of dialysis were collected. Indices for adequacy of dialysis were collected 1-3 months after the initiation of dialysis. Actuarial survival rates were determined by the Kaplan-Meier method. The Cox proportional hazards model was used to classify risk factors for a high mortality. There were 87 Caucasians and 29 Oriental Asian peritoneal dialysis patients. No differences were found in age, gender, primary renal disease, and residual renal function between the two groups. The Caucasians had significantly higher body surface area and urea volume and higher incidence of cardiovascular diseases. Even with slightly higher dialysis dose, the peritoneal creatinine clearance was significantly lower among the Caucasians than among Asians. There was no difference in the peritoneal D/P value between the two groups. However, compared to the Caucasians, the 24hr peritoneal fluid removal and total fluid removal volumes were significantly lower in the Asian patients. The one, two, three and four year survival rates were 95.8%, 91%, 86% and 80% for Asians and 91.3%, 78.1%, 64.7% and 54.1% for Caucasians. Significant predictors for a higher mortality were the presence of cardiovascular disease (42% increase in risk), Caucasians (39% increase in risk) and older age (37% increase in risk for age older than 65). Our study confirms that oriental Asians on peritoneal dialysis patients survive much longer than their Caucasian counterparts; this was partly due to the fact that Asian patients have less cardiovascular disease when they began peritoneal dialysis. Due to their smaller body size, the Asians tended to have a higher peritoneal small solute clearances despite their smaller dialysis doses, indicating that, to achieve the same solute clearance targets, Asians need a smaller dialysis dose compared to Caucasians.

[Efficacy of vaccination against hepatitis B in adult with HIV infection].

PubMed

Kalinowska-Nowak, Anna; Bociaga-Jasik, Monika; Garlicki, Aleksander; Mach, Tomasz

2007-01-01

The aim of the study was to evaluate the efficacy of vaccination against hepatitis B in HIV infected individuals and the influence of the stage of HIV infection and antiretroviral therapy (HAART). Response for additional doses of hepatitis B vaccine among the patients who do not develop protective anti-HBs level after routine vaccination schedule was analysed. Fifty-four HIV infected individuals, 20 women (37%) and 34 men (63%), 20 to 64 years old (mean age 32 years) were analysed. 32 patients (59.6%), 22 men and 10 women were treated with antiretroviral drugs. Stage of HIV infection was assessed on the basis of data derived from medical records (lowest CD4 cells count, highest viral load), and immunological status at the moment of introduction of vaccination (CD4 cells count, viral load). Efficacy of vaccination was compared with control group, which consisted of 56 healthy volunteers. In both groups hepatitis B virus infection was excluded by serologic tests. HBvaxPro vaccine produced by Merck Sharp & Dohme Company, dose registered for adults (10 ug) was injected at month 0-1-6. Patients with anti-HBs <10 IU/l have received booster doses of vaccine month intervals, no more then three. Protective level of antibodies was found in 52 (92.9%) persons from control group and 32 (63%) HIV infected individuals. Anti-HBs > 100 IU/l was twice more common in control group (80%) than in investigated group (46.3%) (p < 0.001). Protective level of anti-HBs had 14.3% patients with CD4 below 200 cells/pl, none of them had anti-HBs > 100 IU/l. Patients with higher CD4 cell count had better response for vaccination (p = 0.015). Differences between patients with high and low viral load were not statistically significant (p = 0.015). Patients with viral load below 10,000 copies/ml had slightly better response then those with higher viral load. Efficacy of vaccination was also associated with the level of distraction of immunological system before introduction of HAART. Patients with CD4 < 200 cells/microl or HIV-RNA > 50,000 copies/ml had worst immunological response for vaccination. After the fist additional dose of vaccine anti-HBs >10 IU/l had 79.7% patients, 87.1% after the second dose and 90.7% after the third dose. Anti-HBs >100 IU/l had subsequently 57.4%, 66.7%, 79.6% patients. We concluded that efficacy of the routine vaccination schedule was lower among HIV individuals in comparison with healthy volunteers. Influence of the progression of HIV infection on the response for vaccination was detected. Additional vaccine's doses have improved efficacy of immunisation which was comparable with general population.

Comparative studies on the conformational change and aggregation behavior of irradiated carrageenans and agar by dynamic light scattering.

PubMed

Abad, Lucille; Okabe, Satoshi; Shibayama, Mitsuhiro; Kudo, Hisaaki; Saiki, Seiichi; Aranilla, Charito; Relleve, Lorna; de la Rosa, Alumanda

2008-01-01

The conformational associative properties of kappa-, iota-, and lambda-carrageenan and agar with irradiation dose were studied by dynamic light scattering. The random scission of the carrageenans and agar by gamma irradiation resulted in the formation of polydispersed lower molecular weight fragments. At high doses, the system moves towards uniformity. Conformational change from coil to helix was observed in all carrageenans and agar at doses up to 100 kGy. The conformational change in lambda-carrageenan may be due to the irregular and hybrid structure of this polysaccharide. Only agar and lambda-carrageenan still undergo conformational transition at a high dose of 200 kGy. Gelation is observed for kappa-, iota-carrageenan up to a dose of 50 kGy while gelation is still observed at 100 kGy for agar. Increase in the hydrodynamic radius with decreasing temperatures for the non-irradiated carrageenans follows this order: lambda-carrageenan>kappa-carrageenan>iota-carrageenan. Slight increases in hydrodynamic radius were observed with irradiation.

Dose-Rate Effects in Breaking DNA Strands by Short Pulses of Extreme Ultraviolet Radiation.

PubMed

Vyšín, Luděk; Burian, Tomáš; Ukraintsev, Egor; Davídková, Marie; Grisham, Michael E; Heinbuch, Scott; Rocca, Jorge J; Juha, Libor

2018-05-01

In this study, we examined dose-rate effects on strand break formation in plasmid DNA induced by pulsed extreme ultraviolet (XUV) radiation. Dose delivered to the target molecule was controlled by attenuating the incident photon flux using aluminum filters as well as by changing the DNA/buffer-salt ratio in the irradiated sample. Irradiated samples were examined using agarose gel electrophoresis. Yields of single- and double-strand breaks (SSBs and DSBs) were determined as a function of the incident photon fluence. In addition, electrophoresis also revealed DNA cross-linking. Damaged DNA was inspected by means of atomic force microscopy (AFM). Both SSB and DSB yields decreased with dose rate increase. Quantum yields of SSBs at the highest photon fluence were comparable to yields of DSBs found after synchrotron irradiation. The average SSB/DSB ratio decreased only slightly at elevated dose rates. In conclusion, complex and/or clustered damages other than cross-links do not appear to be induced under the radiation conditions applied in this study.

[Correction of the combined vitamin deficiency in growing rats fed fiber enriched diets with different doses of vitamins].

PubMed

Beketova, N A; Kodentsova, V M; Vrzhesinskaia, O A; Kosheleva, O V; Pereverzeva, O G; Sokol'nikov, A A; Aksenov, I V

2014-01-01

The effect of 5% dietary wheat bran (WB) on the correction of combined vitamin deficiency by two doses of vitamins (physiological and enhanced) has been analyzed using a rat model (8 groups, n = 8/group). Vitamin deficiency in male weanling Wistar rats (58.1 ± 0.5 g) was induced by 5-fold reduction of vitamin mixture amount in the feed and complete vitamin E, B1 and B2 exclusion from the mixture for 30 days, then deficit was corrected within 5 days. Rats from control group were fed a complete semisynthetic diet containing microcrystalline cellulose 2%. Vitamin deficient diet for 35 days resulted in reduced (p < 0.05) levels of vitamin A in the liver by 25 fold, vitamin E and B1--2.0-2.3 fold, vitamin B2--by 40%, 25(OH)D blood plasma concentration--by 21% compared with the control. Feed consumption of the animals treated with vitamin deficient diet and WB was higher by 43% than in rats with vitamin deficit. Their rate of weight occupied the intermediate position between the rates of weight in deficit and in control animals, and they could not serve a full control to evaluate the WB impact on vitamin sufficiency. After filling the vitamin diet content to an adequate level vitamin E liver content was fully restored. To restore vitamins B1 and B2 liver level higher doses of vitamins (120-160% of adequate content) were required, and to restore the reduced levels of vitamin A in rat liver even 2-fold increased dose of vitamin A was insufficient. The diet enrichment with WB had no effect on vitamin B1 and B2 liver content, regardless of the amount of vitamins in the diet. Adding fiber to the diet of animals adequately provided with vitamins resulted in significantly 1,3-fold increase of 25(OH)D blood plasma concentration and a slight but significant decrease of α-tocopherol liver level by 16% as compared to rats not receiving WB. The enrichment of rat diet with dietary fibers worsened restoration of the reduced vitamin E status not only by filling vitamin content in the diet to an adequate level, but also by using 2-fold enhanced dose of vitamin. Within 5 days deficiency of vitamins A, B1, B2 was not eliminated with increasing vitamin diet content to an adequate level. Higher doses of vitamins are needed for the complete correction of vitamin status. The addition of vitamins to an adequate level was sufficient to normalize the elevated liver levels of MDA in rats with combined vitamin deficiency that may be associated with vitamin E status improvement. The diet enrichment with fiber did not affect on the intensity of lipid peroxidation in rat liver regardless of their provision with vitamins.

Estimation of background radiation doses for the Peninsular Malaysia's population by ESR dosimetry of tooth enamel.

PubMed

Rodzi, Mohd; Zhumadilov, Kassym; Ohtaki, Megu; Ivannikov, Alexander; Bhattacharjee, Deborshi; Fukumura, Akifumi; Hoshi, Masaharu

2011-08-01

Background radiation dose is used in dosimetry for estimating occupational doses of radiation workers or determining radiation dose of an individual following accidental exposure. In the present study, the absorbed dose and the background radiation level are determined using the electron spin resonance (ESR) method on tooth samples. The effect of using different tooth surfaces and teeth exposed with single medical X-rays on the absorbed dose are also evaluated. A total of 48 molars of position 6-8 were collected from 13 district hospitals in Peninsular Malaysia. Thirty-six teeth had not been exposed to any excessive radiation, and 12 teeth had been directly exposed to a single X-ray dose during medical treatment prior to extraction. There was no significant effect of tooth surfaces and exposure with single X-rays on the measured absorbed dose of an individual. The mean measured absorbed dose of the population is 34 ± 6.2 mGy, with an average tooth enamel age of 39 years. From the slope of a regression line, the estimated annual background dose for Peninsular Malaysia is 0.6 ± 0.3 mGy y(-1). This value is slightly lower than the yearly background dose for Malaysia, and the radiation background dose is established by ESR tooth measurements on samples from India and Russia.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

PubMed Central

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

[Study on ultra-structural pathological changes of rats poisoned by tetramine].

PubMed

Zhi, Chuan-hong; Liu, Liang; Liu, Yan

2005-05-01

To observe ultra-structural pathological changes of materiality viscera of rats poisoned by different dose of tetramine and to study the toxic mechanism. Acute and subacute tetramine toxicity models were made by oral administration with different dose of tetramine. Brain, heart, liver, spleen and kidney were extracted and observed by electromicroscopic examination. The injuries of brain cells, cardiocytes and liver cells were induced by different dose of tetramine. These were not obviously different of the injuries of the kindy cells and spleen cells of rats poisoned by different dose of tetramine. Ultra-structural pathological changes were abserved including mitochondria slight swelling and neurolemma's array turbulence in the brain cells, mitochondria swelling or abolish and rupture of muscle fiber in the heart cells, mitochondria swelling and the glycogen decreased in the liver cells. The toxic target organs of tetramine are the heart, brain and liver.

Atipamezole in the management of detomidine overdose in a pony.

PubMed

Di Concetto, Stefano; Michael Archer, R; Sigurdsson, Sigurdur F; Clarke, Kw

2007-01-01

A pony undergoing elective castration accidentally received an overdose of IV detomidine (200 microg kg(-1)) before anaesthesia was induced with ketamine and midazolam. A further 100 microg kg(-1) IV dose of detomidine was administered during anaesthesia. The mistake was recognized only when the animal failed to recover from anaesthesia in the expected time. The overdose (300 microg kg(-1) in total) was treated successfully with atipamezole, initially given IV and subsequently IM and titrated to effect to a total dose of 1100 microg kg(-1). The pony regained the standing position. A further injection of atipamezole (76 microg kg(-1) IM) was given 5 hours later to counteract slight signs of re-sedation. Atipamezole proved an effective antagonist for detomidine in a pony at an initial dose 3.65 x and a final total dose 3.9 x greater than the alpha2 agonist.

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

Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

PubMed

Poon, R; Park, G; Viau, C; Chu, I; Potvin, M; Vincent, R; Valli, V

1998-01-01

The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate glands in the high dose males. No other significant microscopic changes were observed in the tissues of treated animals. Based on the marked increase in urinary ascorbic acid and albumin in the high dose males and the decreased forelimb grip strength in the high dose females, we concluded that the no-observed adverse effect level (NOAEL) of methanol/gasoline vapour is 500/30 ppm.

SU-E-T-153: Burst-Mode Modulated Arc Therapy with Flattening-Filter-Free Beams Versus Flattening-Filtered Beams

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

Kainz, K; Lawton, C; Li, X

2015-06-15

Purpose: To compare the dosimetry and delivery of burst-mode modulated arc radiotherapy using flattening-filter-free (FFF) and flattening-filtered (FF) beams. Methods: Burst-mode modulated arc therapy (mARC, Siemens) plans were generated for six prostate cases with FFF and FF beam models, using the Elekta Monaco v. 5.00 planning system. One 360-degree arc was used for five cases, and for one case two 360-degree coplanar arcs were used. The maximum number of optimization points (OPs) per arc was set to 91, and OPs with less than 4 MU were disregarded. All plans were delivered on the Siemens Artiste linear accelerator with 6MV FFmore » (300 MU/min) and comparable-energy FFF (2000 MU/min, labeled as 7UF) beams. Results: For all cases studied, the plans with FFF beams exhibited DVHs for the PTV, rectum, and bladder that were nearly identical to those for the plans with FF beams. The FFF plan yielded reduced dose to the right femoral head for 5 cases, and lower mean dose to the left femoral head for 4 cases. For all but the two-arc case, the FFF and FF plans resulted in an identical number of segments. The total number of MUs was slightly lower for the FF plans for five cases. The total delivery time per fraction was substantially lower for the FFF plans, ranging from 25 to 50 percent among all cases, as compared to the FF plans. Conclusion: For mARC plans, FFF and FF beams provided comparable PTV coverage and rectum and bladder sparing. For the femoral heads, the mean dose was slightly lower in most cases when using the FFF beam. Although the flat beam plans typically required slightly fewer MUs, FFF beams required substantially less time to deliver a plan of similar quality. This work was supported by Siemens Medical Solutions and the MCW Cancer Center Fotsch Foundation.« less

Attenuation-based size metric for estimating organ dose to patients undergoing tube current modulated CT exams

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

Bostani, Maryam, E-mail: mbostani@mednet.ucla.edu; McMillan, Kyle; Lu, Peiyun

2015-02-15

Purpose: Task Group 204 introduced effective diameter (ED) as the patient size metric used to correlate size-specific-dose-estimates. However, this size metric fails to account for patient attenuation properties and has been suggested to be replaced by an attenuation-based size metric, water equivalent diameter (D{sub W}). The purpose of this study is to investigate different size metrics, effective diameter, and water equivalent diameter, in combination with regional descriptions of scanner output to establish the most appropriate size metric to be used as a predictor for organ dose in tube current modulated CT exams. Methods: 101 thoracic and 82 abdomen/pelvis scans frommore » clinically indicated CT exams were collected retrospectively from a multidetector row CT (Sensation 64, Siemens Healthcare) with Institutional Review Board approval to generate voxelized patient models. Fully irradiated organs (lung and breasts in thoracic scans and liver, kidneys, and spleen in abdominal scans) were segmented and used as tally regions in Monte Carlo simulations for reporting organ dose. Along with image data, raw projection data were collected to obtain tube current information for simulating tube current modulation scans using Monte Carlo methods. Additionally, previously described patient size metrics [ED, D{sub W}, and approximated water equivalent diameter (D{sub Wa})] were calculated for each patient and reported in three different ways: a single value averaged over the entire scan, a single value averaged over the region of interest, and a single value from a location in the middle of the scan volume. Organ doses were normalized by an appropriate mAs weighted CTDI{sub vol} to reflect regional variation of tube current. Linear regression analysis was used to evaluate the correlations between normalized organ doses and each size metric. Results: For the abdominal organs, the correlations between normalized organ dose and size metric were overall slightly higher for all three differently (global, regional, and middle slice) reported D{sub W} and D{sub Wa} than they were for ED, but the differences were not statistically significant. However, for lung dose, computed correlations using water equivalent diameter calculated in the middle of the image data (D{sub W,middle}) and averaged over the low attenuating region of lung (D{sub W,regional}) were statistically significantly higher than correlations of normalized lung dose with ED. Conclusions: To conclude, effective diameter and water equivalent diameter are very similar in abdominal regions; however, their difference becomes noticeable in lungs. Water equivalent diameter, specifically reported as a regional average and middle of scan volume, was shown to be better predictors of lung dose. Therefore, an attenuation-based size metric (water equivalent diameter) is recommended because it is more robust across different anatomic regions. Additionally, it was observed that the regional size metric reported as a single value averaged over a region of interest and the size metric calculated from a single slice/image chosen from the middle of the scan volume are highly correlated for these specific patient models and scan types.« less

TH-C-18A-01: Is Automatic Tube Current Modulation Still Necessary with Statistical Iterative Reconstruction?

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

Li, K; Zhao, W; Gomez-Cardona, D

Purpose: Automatic tube current modulation (TCM) has been widely used in modern multi-detector CT to reduce noise spatial nonuniformity and streaks to improve dose efficiency. With the advent of statistical iterative reconstruction (SIR), it is expected that the importance of TCM may diminish, since SIR incorporates statistical weighting factors to reduce the negative influence of photon-starved rays. The purpose of this work is to address the following questions: Does SIR offer the same benefits as TCM? If yes, are there still any clinical benefits to using TCM? Methods: An anthropomorphic CIRS chest phantom was scanned using a state-of-the-art clinical CTmore » system equipped with an SIR engine (Veo™, GE Healthcare). The phantom was first scanned with TCM using a routine protocol and a low-dose (LD) protocol. It was then scanned without TCM using the same protocols. For each acquisition, both FBP and Veo reconstructions were performed. All scans were repeated 50 times to generate an image ensemble from which noise spatial nonuniformity (NSN) and streak artifact levels were quantified. Monte-Carlo experiments were performed to estimate skin dose. Results: For FBP, noise streaks were reduced by 4% using TCM for both routine and LD scans. NSN values were actually slightly higher with TCM (0.25) than without TCM (0.24) for both routine and LD scans. In contrast, for Veo, noise streaks became negligible (<1%) with or without TCM for both routine and LD scans, and the NSN was reduced to 0.10 (low dose) or 0.08 (routine). The overall skin dose was 2% lower at the shoulders and more uniformly distributed across the skin without TCM. Conclusion: SIR without TCM offers superior reduction in noise nonuniformity and streaks relative to FBP with TCM. For some clinical applications in which skin dose may be a concern, SIR without TCM may be a better option. K. Li, W. Zhao, D. Gomez-Cardona: Nothing to disclose; G.-H. Chen: Research funded, General Electric Company Research funded, Siemens AG Research funded, Varian Medical Systems, Research funded, Hologic, Inc.« less

Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure

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

Abou-Elwafa Abdallah, Mohamed, E-mail: mae_abdallah@yahoo.co.uk; Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut; Pawar, Gopal

Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm{sup 2}, finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24 h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPPmore » and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P > 0.05). Estimated permeability constants (K{sub p}, cm/h) showed a significant negative correlation with log K{sub ow} for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs = 36 ng/kg bw day) than adults (median ΣPFRs = 4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure. - Highlights: • Human dermal absorption of PFRs was studied using human ex vivo skin and EPISKIN™. • Absorbed fractions of TCEP, TCIPP and TDCIPP were 28%, 25% and 13% of applied dose. • Permeability constants showed significant negative correlation to log K{sub ow} of PFRs. • Skin washing reduced the overall dermal absorption of target PFRs to varying degrees. • Toddlers are more exposed to PFRs via dermal contact with indoor dust than adults.« less

TH-C-12A-02: Comparison of Two RapidArc Delivery Strategies in Stereotactic Body Radiotherapy of Stage I and II Peripheral Lung Tumors with Unflattened Beams

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

Huang, B; Lu, J; Chen, J

2014-06-15

Purpose: The full arcs strategy used in SBRT with RapidArc and unflattened (FFF) beams in large and heterogeneous peripheral non-smallcell lung cancer (NSCLC) appears to be suboptimal as it increases the disadvantageous dose to the contralateral lung, which potentially increases the toxicity to surrounding tissues. In this study, we investigated, for the first time, the dose delivery strategies using partial arcs (PA) and the fully rotational arcs with avoidance sectors (FAAS) for SBRT with FFF beams in peripheral NSCLC patients. Methods: Eighteen patients with NSCLC (stage I and II) were selected for this study. Nine patients with a GTV <=more » 10cc were designated as the small tumor group. The remaining nine patients with a GTV between 10 cc and 44 cc were assigned to the large tumor group. The treatment plans were generated in eighteen patients using PA and FAAS, respectively, and delivered with a Varian TrueBeam Linac. Dosimetry of the target and organs at risk (OAR), total MU, out-of-field dose, and delivery time were analyzed. Delta4 and Portal dosimetry were employed to evaluate the delivery accuracy. Results: or the small tumor group, the FAAS plans significantly achieved a better conformity index, the lower total MU and out-of-field dose, a shorter treatment time, and the reduced doses to cord, heart, and lung (p < 0.05). But the target doses were slightly higher than that delivered by PA plans. For the large tumor group, the PA plans significantly attained a better conformity index and a shorter treatment time (p < 0.05). Furthermore, all plans achieved a high pass rate, with all the gamma indices greater than 97% at the Γ{sub 3mm,} {sub 3%} threshold. Conclusion: This study suggests that FAAS strategy is more beneficial for small tumor patients undergoing lung SBRT with FFF beams. However, for large tumor patients, PA strategy is recommended. NIH/NIGMS grant U54 GM104944, Lincy Endowed Assistant Professorship.« less

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

NASA Technical Reports Server (NTRS)

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

Radiation protection during hybrid procedures: innovation creates new challenges.

PubMed

Sawdy, Jaclynn M; Gocha, Mark D; Olshove, Vincent; Chisolm, Joanne L; Hill, Sharon L; Phillips, Alistair; Galantowicz, Mark; Cheatham, John P; Holzer, Ralf J

2009-09-01

The cooperation between interventional cardiologists and cardiothoracic surgeons has expanded the spectrum of treatment modalities for patients with congenital heart disease. These hybrid techniques have created new challenges, one of which being the provision of adequate but practical radiation protection. This study evaluates the use of a lightweight radiation protection drape (RADPAD) that may be suitable for shielding during hybrid procedures. To simulate a pediatric patient, an 8.7 liter water-filled tub was placed on an X-ray table and exposed to 10-second cine acquisition runs. Radiation exposure was measured at twelve specified locations around the table using a model with three different levels of radiation protection: no shielding, shielding using a traditional 0.35 mm lead-equivalent apron, and shielding using the 0.25 mm lead-equivalent RADPAD. The traditional lead apron and the RADPAD significantly reduced the amount of radiation dose when compared with no shielding. The standard lead apron provided slightly greater radiation protection than the RADPAD (0.000064 radiation absorbed dose [rad] vs. 0.000091 rad; p = 0.012). The measured rad was significantly higher on the right side of the table, and the measured radiation dose decreased significantly with increasing distance from the table. The RADPAD has been shown to function as an efficient shielding device, even though it does not quite match the protection that can be expected from a standard lead apron. It complies with regulatory radiation protection requirements and its lightweight and sterile use make it particularly useful during hybrid procedures in the operating room.

Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

PubMed

Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-02-01

Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

Enkephalinase inhibitor potentiates mammalian tachykinin-induced contraction in ferret trachea.

PubMed

Sekizawa, K; Tamaoki, J; Graf, P D; Basbaum, C B; Borson, D B; Nadel, J A

1987-12-01

To determine the roles of endogenous enkephalinase (EC.3.4.24.11) in regulating tachykinin-induced contraction of airway smooth muscle, the authors studied the effects of the enkephalinase inhibitor leucine-thiorphan on the contractile responses to substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in isolated ferret tracheal smooth muscle segments. Leucine-thiorphan shifted, in concentration-dependent fashions, the dose-response curves to all tachykinins to lower concentrations. Leucine-thiorphan changed the rank order of tachykinin potency from NKA greater than SP greater than NKB to NKA = NKB greater than SP. Removal of the epithelium slightly enhanced the contractile responses to SP and NKA but not to NKB. Atropine shifted the dose-response curves of all tachykinins to higher concentrations. Each tachykinin increased the contractile response to electrical field stimulation (5 Hz, 20 sec of duration, 20 V) in a dose-dependent fashion. This effect was not altered by hexamethonium, indomethacin, BW755C or naloxone but was potentiated by leucine-thiorphan and inhibited by the tachykinin receptor antagonist (D-Pro2, D-Trp7,9)-SP and by atropine. Because tachykinins did not affect contractile responses to acetylcholine significantly, their effects were probably on presynaptic postganglionic nerves. Captopril, bestatin and leupeptin did not alter contractile responses, suggesting that angiotensin converting enzyme, aminopeptidases and serine proteinases did not modulate tachykinin-induced effects. Enkephalinase immunofluorescence was found in the smooth muscle and epithelium and confirmed the authors' finding of enkephalinase-like activity in the muscle. The results suggest that tracheal enkephalinase is an important modulator of tachykinin-induced effects.

Effects of hospital generic drug substitution on diabetes therapy

PubMed Central

Chen, Hui-Yin; Chang, Hui-Ru; Lang, Hui-Chu

2014-01-01

Objectives To evaluate the effects on physicians’ prescribing behavior and on the therapeutic outcome of non-insulin-dependent diabetes patients of substituting different generic brands of metformin. Methods We adopt a retrospective cohort study involving 280 type-2 diabetes patients who regularly used the outpatient services of one medical center and who had changed metformin brands five times between 2003 and 2008. The aim was to examine the effects of switching brands. The generalized estimating equation was used to determine whether drug brand switching affected patient glycated hemoglobin A1c (HbA1c) levels, their prescribed daily dose, or their adherence to medication with metformin. Results HbA1c levels increased from 7.91 to 8.34 throughout the study period, although it was found that brand switching did not adversely affect HbA1c levels after controlling for patient characteristics and the time course of the study. Furthermore, the prescribed daily dose of metformin was stable throughout the study period, and was approximately 0.8 of the defined daily dose. Finally, although adherence was significantly higher with the original metformin than with the four generic brands, patients still maintained high levels of adherence of >0.8. Conclusion Although switching between different brands of metformin slightly affected the prescribing behavior of the physicians, there was no unfavorable effect on patient HbA1c levels. Thus, the policy of substituting between different generic brands of metformin is a good cost-effective approach that does not adversely affect the quality of diabetes patient care. PMID:24511228

Daily doses of 20 mg of elemental iron compensate for iron loss in regular blood donors: a randomized, double-blind, placebo-controlled study.

PubMed

Radtke, Hartmut; Tegtmeier, Joanna; Röcker, Lothar; Salama, Abdulgabar; Kiesewetter, Holger

2004-10-01

A considerable number of regular blood donors develops an iron deficiency, and the exact amount of iron required to compensate for the iron loss from whole-blood donation in males and females is still unknown. A total of 526 regular blood donors (289 male and 237 female) were randomly assigned to treatment with either 40 mg, 20 mg, or 0 mg per day of elemental iron as ferrous gluconate for a period of 6 months, during which one unit of whole blood was collected on four occasions (males) or three occasions (females). Hemoglobin level, serum ferritin, and soluble transferrin receptor levels were measured before each donation. Daily doses of either 40 mg or 20 mg of elemental iron adequately compensated for iron loss in males, who gave blood at 2-month intervals, but did not result in a positive iron balance or an increase in storage iron as reflected by the logarithm of the ratio of transferrin receptor to ferritin concentration. In females, who donated at 3-month intervals, the same daily doses not only restored the iron balance but also led to an increase in storage iron. The number of gastrointestinal side effects due to iron supplementation (12%) was only slightly higher in both iron groups than in the placebo group. The results of this study indicate that 20 mg of elemental iron per day can adequately compensate for iron loss in males and females who donate whole blood up to four (females) or six times per year (males).

Association among Working Hours, Occupational Stress, and Presenteeism among Wage Workers: Results from the Second Korean Working Conditions Survey.

PubMed

Jeon, Sung-Hwan; Leem, Jong-Han; Park, Shin-Goo; Heo, Yong-Seok; Lee, Bum-Joon; Moon, So-Hyun; Jung, Dal-Young; Kim, Hwan-Cheol

2014-03-24

The purpose of the present study was to identify the association between presenteeism and long working hours, shiftwork, and occupational stress using representative national survey data on Korean workers. We analyzed data from the second Korean Working Conditions Survey (KWCS), which was conducted in 2010, in which a total of 6,220 wage workers were analyzed. The study population included the economically active population aged above 15 years, and living in the Republic of Korea. We used the chi-squared test and multivariate logistic regression to test the statistical association between presenteeism and working hours, shiftwork, and occupational stress. Approximately 19% of the workers experienced presenteeism during the previous 12 months. Women had higher rates of presenteeism than men. We found a statistically significant dose-response relationship between working hours and presenteeism. Shift workers had a slightly higher rate of presenteeism than non-shift workers, but the difference was not statistically significant. Occupational stress, such as high job demand, lack of rewards, and inadequate social support, had a significant association with presenteeism. The present study suggests that long working hours and occupational stress are significantly related to presenteeism.

Efficient removal of chromate and arsenate from individual and mixed system by malachite nanoparticles.

PubMed

Saikia, Jiban; Saha, Bedabrata; Das, Gopal

2011-02-15

Malachite nanoparticles of 100-150 nm have been efficiently and for the first time used as an adsorbent for the removal of toxic arsenate and chromate. We report a high adsorption capacity for chromate and arsenate on malachite nanoparticle from both individual and mixed solution in pH ∼4-5. However, the adsorption efficiency decreases with the increase of solution pH. Batch studies revealed that initial pH, temperature, malachite nanoparticles dose and initial concentration of chromate and arsenate were important parameters for the adsorption process. Thermodynamic analysis showed that adsorption of chromate and arsenate on malachite nanoparticles is endothermic and spontaneous. The adsorption of these anions has also been investigated quantitatively with the help of adsorption kinetics, isotherm, and selectivity coefficient (K) analysis. The adsorption data for both chromate and arsenate were fitted well in Langmuir isotherm and preferentially followed the second order kinetics. The binding affinity of chromate is found to be slightly higher than arsenate in a competitive adsorption process which leads to the comparatively higher adsorption of chromate on malachite nanoparticles surface. Copyright © 2010 Elsevier B.V. All rights reserved.

Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid.

PubMed

Cleuvers, Michael

2004-11-01

The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.

Chemical composition and antiprolifrative activity of Artemisia persica Boiss. and Artemisia turcomanica Gand. essential oils

PubMed Central

Nikbakht, M.R.; Sharifi, S.; Emami, S.A.; Khodaie, L.

2014-01-01

Essential oils obtained from aerial parts of Artemisia persica and Artemisia turcomanica were analyzed by GC/MS. While 28 components representing 91.01 % of A. persica were identified, the identity of 50 components, constituting 81.93 % of the total oil, was confirmed in A. turcomanica. β-thujone was the main compound (75.23%) in A. persica while the major identified phytochemicals in A. turcomanica were 1,8-cineol (19.23%), camphor (15.55%) and filifolone (15.53%). Both of the essential oils were predominantly made up of monoterpenes. Time- and dose-dependent cytotoxic effects of A. persica and A. turcomanica on MCF-7 cell line evaluated by MTT assay at 24, 48 and 72 h, showed that the highest cytotoxic effect of A. persica and A. turcomanica were appeared at 72 h incubation. At that incubation period, CI50 of A. persica was found to be 0.15 μg/ml, while that of A. turcomanica was 0.1 μg/ml. Thus, cytotoxicity of A. turcomanica was slightly higher than A. persica which could be attributed to the higher content of sesquiterpene present in A. turcomanica. As a conclusion, these volatile oils could have chemotherapeutic potentials. PMID:25657784

Chemical composition and antiprolifrative activity of Artemisia persica Boiss. and Artemisia turcomanica Gand. essential oils.

PubMed

Nikbakht, M R; Sharifi, S; Emami, S A; Khodaie, L

2014-01-01

Essential oils obtained from aerial parts of Artemisia persica and Artemisia turcomanica were analyzed by GC/MS. While 28 components representing 91.01 % of A. persica were identified, the identity of 50 components, constituting 81.93 % of the total oil, was confirmed in A. turcomanica. β-thujone was the main compound (75.23%) in A. persica while the major identified phytochemicals in A. turcomanica were 1,8-cineol (19.23%), camphor (15.55%) and filifolone (15.53%). Both of the essential oils were predominantly made up of monoterpenes. Time- and dose-dependent cytotoxic effects of A. persica and A. turcomanica on MCF-7 cell line evaluated by MTT assay at 24, 48 and 72 h, showed that the highest cytotoxic effect of A. persica and A. turcomanica were appeared at 72 h incubation. At that incubation period, CI50 of A. persica was found to be 0.15 μg/ml, while that of A. turcomanica was 0.1 μg/ml. Thus, cytotoxicity of A. turcomanica was slightly higher than A. persica which could be attributed to the higher content of sesquiterpene present in A. turcomanica. As a conclusion, these volatile oils could have chemotherapeutic potentials.

Phytotoxicity assessment on corn stover biochar, derived from fast pyrolysis, based on seed germination, early growth, and potential plant cell damage.

PubMed

Li, Yang; Shen, Fei; Guo, Haiyan; Wang, Zhanghong; Yang, Gang; Wang, Lilin; Zhang, Yanzong; Zeng, Yongmei; Deng, Shihuai

2015-06-01

The potential phytotoxicity of water extractable toxicants in a typical corn stover biochar, the product of fast pyrolysis, was investigated using an aqueous biochar extract on a soil-less bioassay with tomato plants. The biochar dosage of 0.0-16.0 g beaker(-1) resulted in an inverted U-shaped dose-response relationship between biochar doasage and seed germination/seedling growth. This indicated that tomato growth was slightly stimulated by low dosages of biochar and inhibited with higher dosages of biochar. Additionally, antioxidant enzyme activities in the roots and leaves were enhanced at lower dosages, but rapidly decreased with higher dosages of biochar. With the increased dosages of biochar, the malondialdehyde content in the roots and leaves increased, in addition with the observed morphology of necrotic root cells, suggesting that serious damage to tomato seedlings occurred. EC50 of root length inhibition occurred with biochar dosages of 9.2 g beaker(-1) (3.5th day) and 16.7 g beaker(-1) (11th day) (equivalent to 82.8 and 150.3 t ha(-1), respectively), which implied that toxicity to the early growth of tomato can potentially be alleviated as the plant grows.

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

Burnham, A K; Weese, R K; Adrzejewski, W J

Accelerated aging tests play an important role in assessing the lifetime of manufactured products. There are two basic approaches to lifetime qualification. One tests a product to failure over range of accelerated conditions to calibrate a model, which is then used to calculate the failure time for conditions of use. A second approach is to test a component to a lifetime-equivalent dose (thermal or radiation) to see if it still functions to specification. Both methods have their advantages and limitations. A disadvantage of the 2nd method is that one does not know how close one is to incipient failure. Thismore » limitation can be mitigated by testing to some higher level of dose as a safety margin, but having a predictive model of failure via the 1st approach provides an additional measure of confidence. Even so, proper calibration of a failure model is non-trivial, and the extrapolated failure predictions are only as good as the model and the quality of the calibration. This paper outlines results for predicting the potential failure point of a system involving a mixture of two energetic materials, HMX (nitramine octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) and CP (2-(5-cyanotetrazalato) pentaammine cobalt (III) perchlorate). Global chemical kinetic models for the two materials individually and as a mixture are developed and calibrated from a variety of experiments. These include traditional thermal analysis experiments run on time scales from hours to a couple days, detonator aging experiments with exposures up to 50 months, and sealed-tube aging experiments for up to 5 years. Decomposition kinetics are determined for HMX (nitramine octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) and CP (2-(5-cyanotetrazalato) pentaammine cobalt (III) perchlorate) separately and together. For high levels of thermal stress, the two materials decompose faster as a mixture than individually. This effect is observed both in high-temperature thermal analysis experiments and in long-term thermal aging experiments. An Arrhenius plot of the 10% level of HMX decomposition by itself from a diverse set of experiments is linear from 120 to 260 C, with an apparent activation energy of 165 kJ/mol. Similar but less extensive thermal analysis data for the mixture suggests a slightly lower activation energy for the mixture, and an analogous extrapolation is consistent with the amount of gas observed in the long-term detonator aging experiments, which is about 30 times greater than expected from HMX by itself for 50 months at 100 C. Even with this acceleration, however, it would take {approx}10,000 years to achieve 10% decomposition at {approx}30 C. Correspondingly, negligible decomposition is predicted by this kinetic model for a few decades aging at temperatures slightly above ambient. This prediction is consistent with additional sealed-tube aging experiments at 100-120 C, which are estimated to have an effective thermal dose greater than that from decades of exposure to temperatures slightly above ambient.« less

Effect of simulated climate warming on the morphological and physiological traits of Elsholtzia haichowensis in copper contaminated soil.

PubMed

Guan, Ming; Jin, Zexin; Li, Junmin; Pan, Xiaocui; Wang, Suizi; Li, Yuelin

2016-01-01

The aim of this study was to investigate the effects of temperature and Cu on the morphological and physiological traits of Elsholtzia haichowensis grown in soils amended with four Cu concentrations (0, 50, 500, and 1000 mg kg(-1)) under ambient temperature and slight warming. At the same Cu concentration, the height, shoot dry weight, total plant dry weight, and root morphological parameters such as length, surface area and tip number of E. haichowensis increased due to the slight warming. The net photosynthetic rate, stomatal conductance, transpiration, light use efficiency were also higher under the slight warming than under ambient temperature. The increased Cu concentrations, total Cu uptake, bioaccumulation factors and tolerance indexes of shoots and roots were also observed at the slight warming. The shoot dry weight, root dry weight, total plant dry weight and the bioaccumulation factors of shoots and roots at 50 mg Cu kg(-1) were significantly higher than those at 500 and 1000 mg Cu kg(-1) under the slight warming. Therefore, the climate warming may improve the ability of E. haichowensis to phytoremediate Cu-contaminated soil, and the ability improvement greatly depended on the Cu concentrations in soils.

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.

Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.

PubMed

Raber, Jacob; Torres, Eileen Ruth S; Akinyeke, Tunde; Lee, Joanne; Weber Boutros, Sydney J; Turker, Mitchell S; Kronenberg, Amy

2018-04-20

The space radiation environment includes helium (⁴He) ions that may impact brain function. As little is known about the effects of exposures to ⁴He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with ⁴He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. ⁴He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear conditioning tests. Taken together, the results indicate that some aspects of cognitive performance are altered in male mice exposed to ⁴He ions, but that the response is task-dependent. Furthermore, the sensitive doses can vary within each task in a non-linear fashion. This highlights the importance of assessing the cognitive and behavioral effects of charged particle exposure with a variety of assays and at multiple doses, given the possibility that lower doses may be more damaging due to the absence of induced compensatory mechanisms at higher doses.

Absorbed dose to water based dosimetry versus air kerma based dosimetry for high-energy photon beams: an experimental study.

PubMed

Palmans, Hugo; Nafaa, Laila; De, Jans Jo; Gillis, Sofie; Hoornaert, Marie-Thérèse; Martens, Chantal; Piessens, Marleen; Thierens, Hubert; Van der Plaetsen, Ann; Vynckier, Stefaan

2002-02-07

In recent years, a change has been proposed from air kerma based reference dosimetry to absorbed dose based reference dosimetry for all radiotherapy beams of ionizing radiation. In this paper, a dosimetry study is presented in which absorbed dose based dosimetry using recently developed formalisms was compared with air kerma based dosimetry using older formalisms. Three ionization chambers of each of three different types were calibrated in terms of absorbed dose to water and air kerma and sent to five hospitals. There, reference dosimetry with all the chambers was performed in a total of eight high-energy clinical photon beams. The selected chamber types were the NE2571, the PTW-30004 and the Wellhöfer-FC65G (previously Wellhöfer-IC70). Having a graphite wall, they exhibit a stable volume and the presence of an aluminium electrode ensures the robustness of these chambers. The data were analysed with the most important recommendations for clinical dosimetry: IAEA TRS-398, AAPM TG-51, IAEA TRS-277, NCS report-2 (presently recommended in Belgium) and AAPM TG-21. The necessary conversion factors were taken from those protocols, or calculated using the data in the different protocols if data for a chamber type are lacking. Polarity corrections were within 0.1% for all chambers in all beams. Recombination corrections were consistent with theoretical predictions, did not vary within a chamber type and only slightly between different chamber types. The maximum chamber-to-chamber variations of the dose obtained with the different formalisms within the same chamber type were between 0.2% and 0.6% for the NE2571, between 0.2% and 0.6% for the PTW-30004 and 0.1% and 0.3% for the Wellhöfer-FC65G for the different beams. The absorbed dose results for the NE2571 and Wellhöfer-FC65G chambers were in good agreement for all beams and all formalisms. The PTW-30004 chambers gave a small but systematically higher result compared to the result for the NE2571 chambers (on the average 0.1% for IAEA TRS-277, 0.3% for NCS report-2 and AAPM TG-21 and 0.4% for IAEA TRS-398 and AAPM TG-51). Within the air kerma based protocols, the results obtained with the TG-21 protocol were 0.4-0.8% higher mainly due to the differences in the data used. Both absorbed dose to water based formalisms resulted in consistent values within 0.3%. The change from old to new formalisms is discussed together with the traceability of calibration factors obtained at the primary absorbed dose and air kerma standards in the reference beams (60Co). For the particular situation in Belgium (calibrations at the Laboratory for Standard Dosimetry of Ghent) the change amounts to 0.1-0.6%. This is similar to the magnitude of the change determined in other countries.

A Swiss cheese error detection method for real-time EPID-based quality assurance and error prevention.

PubMed

Passarge, Michelle; Fix, Michael K; Manser, Peter; Stampanoni, Marco F M; Siebers, Jeffrey V

2017-04-01

To develop a robust and efficient process that detects relevant dose errors (dose errors of ≥5%) in external beam radiation therapy and directly indicates the origin of the error. The process is illustrated in the context of electronic portal imaging device (EPID)-based angle-resolved volumetric-modulated arc therapy (VMAT) quality assurance (QA), particularly as would be implemented in a real-time monitoring program. A Swiss cheese error detection (SCED) method was created as a paradigm for a cine EPID-based during-treatment QA. For VMAT, the method compares a treatment plan-based reference set of EPID images with images acquired over each 2° gantry angle interval. The process utilizes a sequence of independent consecutively executed error detection tests: an aperture check that verifies in-field radiation delivery and ensures no out-of-field radiation; output normalization checks at two different stages; global image alignment check to examine if rotation, scaling, and translation are within tolerances; pixel intensity check containing the standard gamma evaluation (3%, 3 mm) and pixel intensity deviation checks including and excluding high dose gradient regions. Tolerances for each check were determined. To test the SCED method, 12 different types of errors were selected to modify the original plan. A series of angle-resolved predicted EPID images were artificially generated for each test case, resulting in a sequence of precalculated frames for each modified treatment plan. The SCED method was applied multiple times for each test case to assess the ability to detect introduced plan variations. To compare the performance of the SCED process with that of a standard gamma analysis, both error detection methods were applied to the generated test cases with realistic noise variations. Averaged over ten test runs, 95.1% of all plan variations that resulted in relevant patient dose errors were detected within 2° and 100% within 14° (<4% of patient dose delivery). Including cases that led to slightly modified but clinically equivalent plans, 89.1% were detected by the SCED method within 2°. Based on the type of check that detected the error, determination of error sources was achieved. With noise ranging from no random noise to four times the established noise value, the averaged relevant dose error detection rate of the SCED method was between 94.0% and 95.8% and that of gamma between 82.8% and 89.8%. An EPID-frame-based error detection process for VMAT deliveries was successfully designed and tested via simulations. The SCED method was inspected for robustness with realistic noise variations, demonstrating that it has the potential to detect a large majority of relevant dose errors. Compared to a typical (3%, 3 mm) gamma analysis, the SCED method produced a higher detection rate for all introduced dose errors, identified errors in an earlier stage, displayed a higher robustness to noise variations, and indicated the error source. © 2017 American Association of Physicists in Medicine.

Characterization of a new transmission detector for patient individualized online plan verification and its influence on 6MV X-ray beam characteristics.

PubMed

Thoelking, Johannes; Sekar, Yuvaraj; Fleckenstein, Jens; Lohr, Frank; Wenz, Frederik; Wertz, Hansjoerg

2016-09-01

Online verification and 3D dose reconstruction on daily patient anatomy have the potential to improve treatment delivery, accuracy and safety. One possible implementation is to recalculate dose based on online fluence measurements with a transmission detector (TD) attached to the linac. This study provides a detailed analysis of the influence of a new TD on treatment beam characteristics. The influence of the new TD on surface dose was evaluated by measurements with an Advanced Markus Chamber (Adv-MC) in the build-up region. Based on Monte Carlo simulations, correction factors were determined to scale down the over-response of the Adv-MC close to the surface. To analyze the effects beyond dmax percentage depth dose (PDD), lateral profiles and transmission measurements were performed. All measurements were carried out for various field sizes and different SSDs. Additionally, 5 IMRT-plans (head & neck, prostate, thorax) and 2 manually created test cases (3×3cm(2) fields with different dose levels, sweeping gap) were measured to investigate the influence of the TD on clinical treatment plans. To investigate the performance of the TD, dose linearity as well as dose rate dependency measurements were performed. With the TD inside the beam an increase in surface dose was observed depending on SSD and field size (maximum of +11%, SSD = 80cm, field size = 30×30cm(2)). Beyond dmax the influence of the TD on PDDs was below 1%. The measurements showed that the transmission factor depends slightly on the field size (0.893-0.921 for 5×5cm(2) to 30×30cm(2)). However, the evaluation of clinical IMRT-plans measured with and without the TD showed good agreement after using a single transmission factor (γ(2%/2mm) > 97%, δ±3% >95%). Furthermore, the response of TD was found to be linear and dose rate independent (maximum difference <0.5% compared to reference measurements). When placed in the path of the beam, the TD introduced a slight, clinically acceptable increase of the skin dose even for larger field sizes and smaller SSDs and the influence of the detector on the dose beyond dmax as well as on clinical IMRT-plans was negligible. Since there was no dose rate dependency and the response was linear, the device is therefore suitable for clinical use. Only its absorption has to be compensated during treatment planning, either by the use of a single transmission factor or by including the TD in the incident beam model. Copyright © 2015. Published by Elsevier GmbH.

Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

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

Stavri, Simona; Trusca, Violeta G.; Simionescu, Maya

The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated thatmore » LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition.« less

Dose to organs at risk in the upper abdomen in patients treated with extended fields by helical tomotherapy: a dosimetric and clinical preliminary study

PubMed Central

2013-01-01

Background The aim of this work was to determine the technical feasibility and safety of extended-field radiotherapy (EF), performed by Helical TomoTherapy, in patients with positive pelvic and/or para-aortic nodes. Dosimetric data were collected and acute and sub-acute toxicities of the upper abdominal organs at risk (OAR) were evaluated. Methods Twenty-nine patients suitable for EF irradiation for local disease and/or nodal disease in the pelvic or para-aortic area were treated. The prescription dose was 50.4/54 Gy (1.7-1.8 Gy/fraction) for prophylactic lymph nodes (N-) and 60–70.5 Gy (2–2.35 Gy/fraction) for clinically evident gross disease (N+). Modulation factor (MF), pitch and field width (FW) were chosen to optimize dose distribution and treatment duration. Dose values of PTVs and OAR were analysed. The length of the treatment field, the N + and N- volumes, and treatment duration were reported. To evaluate the safety of treatment, haematological, hepatic, renal and pancreatic functions were assessed before, during and after treatment. The median follow-up time was 17.6 months (range: 6–22 months). Results The treatment was well tolerated and all patients but one completed treatment without interruption. Four of the 29 patients experienced G3 haematological acute toxicity (13.8%), but no patient experienced sub-acute grade G3 toxicity. Ten patients experienced G1 and three G2 acute gastrointestinal toxicity (nausea). No sub-acute gastrointestinal or renal toxicity was observed. Only one (3.7%) patient had a persistent slight increase of pancreatic enzymes and two (7.4%) patients a slight increase of hepatic enzymes six months after radiotherapy (G1 toxicity). Conclusions With our treatment design and dose regimen, we found that EF treatment by TomoTherapy could be safely and effectively delivered with minimal acute and sub-acute toxicities in the upper abdomen area. PMID:24160769

Dose to organs at risk in the upper abdomen in patients treated with extended fields by helical tomotherapy: a dosimetric and clinical preliminary study.

PubMed

Bresciani, Sara; Garibaldi, Elisabetta; Cattari, Gabriella; Maggio, Angelo; Di Dia, Amalia; Delmastro, Elena; Gabriele, Domenico; Stasi, Michele; Gabriele, Pietro

2013-10-25

The aim of this work was to determine the technical feasibility and safety of extended-field radiotherapy (EF), performed by Helical TomoTherapy, in patients with positive pelvic and/or para-aortic nodes. Dosimetric data were collected and acute and sub-acute toxicities of the upper abdominal organs at risk (OAR) were evaluated. Twenty-nine patients suitable for EF irradiation for local disease and/or nodal disease in the pelvic or para-aortic area were treated. The prescription dose was 50.4/54 Gy (1.7-1.8 Gy/fraction) for prophylactic lymph nodes (N-) and 60-70.5 Gy (2-2.35 Gy/fraction) for clinically evident gross disease (N+). Modulation factor (MF), pitch and field width (FW) were chosen to optimize dose distribution and treatment duration. Dose values of PTVs and OAR were analysed. The length of the treatment field, the N + and N- volumes, and treatment duration were reported. To evaluate the safety of treatment, haematological, hepatic, renal and pancreatic functions were assessed before, during and after treatment. The median follow-up time was 17.6 months (range: 6-22 months). The treatment was well tolerated and all patients but one completed treatment without interruption. Four of the 29 patients experienced G3 haematological acute toxicity (13.8%), but no patient experienced sub-acute grade G3 toxicity. Ten patients experienced G1 and three G2 acute gastrointestinal toxicity (nausea). No sub-acute gastrointestinal or renal toxicity was observed. Only one (3.7%) patient had a persistent slight increase of pancreatic enzymes and two (7.4%) patients a slight increase of hepatic enzymes six months after radiotherapy (G1 toxicity). With our treatment design and dose regimen, we found that EF treatment by TomoTherapy could be safely and effectively delivered with minimal acute and sub-acute toxicities in the upper abdomen area.

The effect of low larkspur (Delphinium spp.) co-administration on the acute toxicity of death camas (Zigadenus spp.) in sheep.

PubMed

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

2013-12-15

In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in the same area. Two poisonous plants that are often found growing simultaneously in the same location are death camas (Zigadenus spp.) and low larkspur (Delphinium spp.). Sheep are known to be susceptible to death camas poisoning while they are thought to be resistant to larkspur. The objective of this study was to determine if co-administration of low larkspur would exacerbate the toxicity of death camas in sheep. A dose finding study was performed to find a dose of death camas that caused minimal clinical signs of poisoning. Sheep were observed for clinical signs of poisoning as well as changes in heart rate and muscle fatigue. Sheep dosed with 1.14 g of death camas per kg BW showed slight frothing and lethargy, whereas sheep dosed with death camas and low larkspur showed slightly more noticeable clinical signs of poisoning. Sheep dosed with only low larkspur, at 7.8 g/kg BW, showed no signs of poisoning. Although we observed a qualitative difference in clinical signs of intoxication in sheep co-treated with death camas and low larkspur we did not detect any quantitative differences in heart rate, exercise-induced muscle fatigue, or differences in serum zygacine kinetics. Consequently, the results from this study suggest that low larkspur does not affect the toxicity of death camas in sheep. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas and low larkspur in sheep. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for ranchers and in designing additional experiments to study the toxicity of death camas to other livestock species. Published by Elsevier Ltd.

Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PubMed

Park, Jeong Bae; Shin, Joon-Han; Kim, Dong-Soo; Youn, Ho-Joong; Park, Seung Woo; Shim, Wan Joo; Park, Chang Gyu; Kim, Dong-Woon; Lee, Hae-Young; Choi, Dong-Ju; Rim, Se-Joong; Lee, Sung-Yun; Kim, Ju-Han

2016-04-01

Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Dose evaluation of Grid Therapy using a 6 MV flattening filter-free (FFF) photon beam: A Monte Carlo study.

PubMed

Martínez-Rovira, Immaculada; Puxeu-Vaqué, Josep; Prezado, Yolanda

2017-10-01

Spatially fractionated radiotherapy is a strategy to overcome the main limitation of radiotherapy, i.e., the restrained normal tissue tolerances. A well-known example is Grid Therapy, which is currently performed at some hospitals using megavoltage photon beams delivered by Linacs. Grid Therapy has been successfully used in the management of bulky abdominal tumors with low toxicity. The aim of this work was to evaluate whether an improvement in therapeutic index in Grid Therapy can be obtained by implementing it in a flattening filter-free (FFF) Linac. The rationale behind is that the removal of the flattening filter shifts the beam energy spectrum towards lower energies and increase the photon fluence. Lower energies result in a reduction of lateral scattering and thus, to higher peak-to-valley dose ratios (PVDR) in normal tissues. In addition, the gain in fluence might allow using smaller beams leading a more efficient exploitation of dose-volume effects, and consequently, a better normal tissue sparing. Monte Carlo simulations were used to evaluate realistic dose distributions considering a 6 MV FFF photon beam from a standard medical Linac and a cerrobend mechanical collimator in different configurations: grid sizes of 0.3 × 0.3 cm 2 , 0.5 × 0.5 cm 2 , and 1 × 1 cm 2 and a corresponding center-to-center (ctc) distance of 0.6, 1, and 2 cm, respectively (total field size of 10 × 10 cm 2 ). As figure of merit, peak doses in depth, PVDR, output factors (OF), and penumbra values were assessed. Dose at the entrance is slightly higher than in conventional Grid Therapy. However, it is compensated by the large PVDR obtained at the entrance, reaching a maximum of 35 for a grid size of 1 × 1 cm 2 . Indeed, this grid size leads to very high PVDR values at all depths (≥ 10), which are much higher than in standard Grid Therapy. This may be beneficial for normal tissues but detrimental for tumor control, where a lower PVDR might be requested. In that case, higher valley doses in the tumor could be achieved by using an interlaced approach and/or adapting the ctc distance. The smallest grid size (0.3 × 0.3 cm 2 ) leads to low PVDR at all depths, comparable to standard Grid Therapy. However, the use of very thin beams might increase the normal tissue tolerances with respect to the grid size commonly used (1 × 1 cm 2 ). The gain in fluence provided by FFF implies that the important OF reduction (0.6) will not increase treatment time. Finally, the intermediate configuration (0.5 × 0.5 cm 2 ) provides high PVDR in the first 5 cm, and comparable PVDR to previous Grid Therapy works at depth. Therefore, this configuration might allow increasing the normal tissue tolerances with respect to Grid Therapy thanks to the higher PVDR and thinner beams, while a similar tumor control could be expected. The implementation of Grid Therapy in an FFF photon beam from medical Linac might lead to an improvement of the therapeutic index. Among the cases evaluated, a grid size of 0.5 × 0.5 cm 2 (1-cm-ctc) is the most advantageous configuration from the physics point of view. Radiobiological experiments are needed to fully explore this new avenue and to confirm our results. © 2017 American Association of Physicists in Medicine.

Effects of Pyridostigmine bromide on SH-SY5Y cells: An in vitro neuroblastoma neurotoxicity model.

PubMed

Azzolin, VerÔnica Farina; Barbisan, Fernanda; Lenz, Luana Suéling; Teixeira, Cibele Ferreira; Fortuna, Milena; Duarte, Thiago; Duarte, Marta Maria Frescura Medeiros; da Cruz, Ivana Beatrice Mânica

2017-11-01

Pyridostigmine bromide (PB) is a reversible acetylcholinesterase (AChE) inhibitor and the first-choice for the treatment of symptoms associated with myasthenia gravis and other neuromuscular junction disorders. However, evidence suggested that PB could be associated with the Gulf War Illness characterised by the presence of fatigue, headaches, cognitive dysfunction, and musculoskeletal respiratory and gastrointestinal disturbances. Given that a potential neurotoxic effect of PB has not yet been completely elucidated, the present investigation used neural SH-SY5Y cells to evaluate the effect of PB on the cellular viability, cell apoptosis, modulation of the cell cycle, oxidative stress, and genotoxicity variables, which indicate neurodegeneration. As expected, a PB concentration curve based on the therapeutic dose of the drug showed an inhibition of the AChE activity. However, this effect was transient and did not involve differential AChE gene regulation by PB. These results confirmed that undifferentiated SH-SY5Y cells can be used as a cholinergic in vitro model. In general, PB did not trigger oxidative stress, and at a slightly higher PB concentration (80ng/mL), higher levels of protein carbonylation and DNA damage were detected, as determined by the marker 8-deoxyguanosine. The PB genotoxic effects at 80ng/mL were confirmed by the upregulation of the p53 and DNA methyltransferase 1 (DNMT1) genes, which are associated with cellular DNA repair. PB at 40ng/mL, which is the minimal therapeutic dose, led to higher cell proliferation and mitochondrial activity compared with the control group. The effects of PB were corroborated by the upregulation of the telomerase gene. In summary, despite the methodological constrains related to the in vitro protocols, our results suggested that exposure of neural cells to PB, without other chemical and physical stressors did not cause extensive toxicity or indicate any neurodegeneration patterns. Copyright © 2017 Elsevier B.V. All rights reserved.

Current use of metformin in addition to insulin in pediatric patients with type 1 diabetes mellitus: an analysis based on a large diabetes registry in Germany and Austria.

PubMed

Konrad, Katja; Datz, Nicolin; Engelsberger, Ilse; Grulich-Henn, Jürgen; Hoertenhuber, Thomas; Knauth, Burkhild; Meissner, Thomas; Wiegand, Susanna; Woelfle, Joachim; Holl, Reinhard W

2015-11-01

With increasing obesity in childhood and adolescence, weight gain, and insulin resistance become also more frequent in patients with type 1 diabetes mellitus (T1DM). Especially during puberty, insulin therapy often has to be intensified and higher insulin doses are necessary. Some studies point to a beneficial effect of metformin in addition to insulin in these patients. In order to describe current practice and possible benefits, we compared pediatric T1DM patients with insulin plus metformin (n = 525) to patients with insulin therapy only (n = 57 487) in a prospective multicenter analysis. Auxological and treatment data from 58 012 patients aged <21 yr with T1DM in the German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registry were analyzed by multivariable mixed regression modeling. Patients with additional metformin were older [median (interquartile range)]: [16.1 (14.1-17.6) vs. 15.2 (11.5-17.5) yr] with female preponderance (61.0 vs. 47.2%, p < 0.01). They had higher body mass index-standard deviation score (BMI-SDS) [+2.03 (+1.29 to +2.56) vs. +0.51 (-0.12 to +1.15); p < 0.01] and glycated hemoglobin (HbA1c) (9.0 vs. 8.6%, p < 0.01). Hypertension (43.7 vs. 24.8%) and dyslipidemia (58.4 vs. 40.6%) were significantly more prevalent. Adjusted insulin dose was significantly higher (0.98 vs. 0.93 IU/kg bodyweight). In a subgroup of 285 patients followed-up longitudinally (average treatment period 1.42 yr), addition of metformin resulted in a slight reduction of BMI-SDS [-0.01 (-2.01 to +1.40)], but did not improve HbA1c or insulin requirement. Additional metformin therapy in T1DM is primarily used in obese females. Additional therapy with metformin was associated with minor benefits. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Triiodothyronine-predominant Graves' disease in childhood: detection and therapeutic implications.

PubMed

Harvengt, Julie; Boizeau, Priscilla; Chevenne, Didier; Zenaty, Delphine; Paulsen, Anne; Simon, Dominique; Guilmin Crepon, Sophie; Alberti, Corinne; Carel, Jean-Claude; Léger, Juliane

2015-06-01

To assess in a pediatric population, the clinical characteristics and management of triiodothyronine-predominant Graves' disease (T3-P-GD), a rare condition well known in adults, but not previously described in children. We conducted a university hospital-based observational study. All patients with GD followed for more than 1 year between 2003 and 2013 (n=60) were included. T3-P-GD (group I) was defined as high free T3 (fT3) concentration (>8.0 pmol/l) associated with a normal free thyroxine (fT4) concentration and undetectable TSH more than 1 month after the initiation of antithyroid drug (ATD) treatment. Group II contained patients with classical GD without T3-P-GD. Eight (13%) of the patients were found to have T3-P-GD, a median of 6.3 (3.0-10.5) months after initial diagnosis (n=4) or 2.8 (2.0-11.9) months after the first relapse after treatment discontinuation (n=4). At GD diagnosis, group I patients were more likely to be younger (6.8 (4.3-11.0) vs 10.7 (7.2-13.7) years) and had more severe disease than group II patients, with higher serum TSH receptor autoantibodies (TRAb) levels: 40 (31-69) vs 17 (8-25) IU/l, P<0.04, and with slightly higher serum fT4 (92 (64-99) vs 63 (44-83) pmol/l) and fT3 (31 (30-46) vs 25 (17-31) pmol/l) concentrations. During the 3 years following T3-P-GD diagnosis, a double dose of ATD was required and median serum fT4:fT3 ratio remained lower in group I than in group II. Severe hyperthyroidism, with particularly high TRAb concentrations at diagnosis, may facilitate the identification of patients requiring regular serum fT3 determinations and potentially needing higher doses of ATD dosage during follow-up. © 2015 European Society of Endocrinology.

Comparative pathogenesis in specific-pathogen-free chickens of two strains of avian hepatitis E virus recovered from a chicken with Hepatitis-Splenomegaly syndrome and from a clinically healthy chicken.

PubMed

Billam, P; LeRoith, T; Pudupakam, R S; Pierson, F W; Duncan, R B; Meng, X J

2009-11-18

Avian hepatitis E virus (avian HEV) is the primary causative agent of Hepatitis-Splenomegaly (HS) syndrome in chickens. Recently, a genetically unique strain of avian HEV, designated avian HEV-VA, was recovered from healthy chickens in Virginia. The objective of this study was to experimentally compare the pathogenicity of the prototype strain recovered from a chicken with HS syndrome and the avian HEV-VA strain in specific-pathogen-free chickens. An infectious stock of the avian HEV-VA strain was first generated and its infectivity titer determined in chickens. For the comparative pathogenesis study, 54 chickens of 6-week-old were assigned to 3 groups of 18 chickens each. The group 1 chickens were each intravenously inoculated with 5x10(2.5) 50% chicken infectious dose of the prototype strain. The group 2 received the same dose of the avian HEV-VA strain, and the group 3 served as negative controls. Six chickens from each group were necropsied at 2, 3 and 4 weeks post-inoculation (wpi). Most chickens in both inoculated groups seroconverted by 3wpi, and the mean anti-avian HEV antibody titers were higher for the prototype strain group than the avian HEV-VA strain group. There was no significant difference in the patterns of viremia and fecal virus shedding. Blood analyte profiles did not differ between treatment groups except for serum creatine phosphokinase levels which were higher for prototype avian HEV group than avian HEV-VA group. The hepatic lesion score was higher for the prototype strain group than the other two groups. The results indicated that the avian HEV-VA strain is only slightly attenuated compared to the prototype strain, suggesting that the full spectrum of HS syndrome is likely associated with other co-factors.

[Impact of exposure dose reduction of radiation treatment planning CT using low tube voltage technique].

PubMed

Kouno, Takuya; Kuga, Noriyuki; Enzaki, Masahiro; Yamashita, Yuuki; Kitazato, Yumiko; Shimotabira, Haruhiko; Jinnouchi, Takashi; Kusuhara, Kazuo; Kawamura, Shinji

2015-04-01

The aim of this study was to reduce the exposed dose of radiotherapy treatment planning computed tomography (CT) by using low tube voltage technique. We used tube voltages of 80 kV, 100 kV, and 120 kV, respectively. First, we evaluated exposure dose with CT dose index (CTDI) for each voltage. Second, we compared image quality indexes such as modulation transfer function (MTF), noise power spectrum (NPS), and contrast to noise ratio (CNR) of phantom images with each voltage. Third, CT to electron density tables were measured in three voltages and monitor unit value was calculated along with clinical cases. Finally, CT surface exposed dose of chest skin was measured by thermoluminescent dosimeter (TLD). In image evaluation MTF and NPS were approximately equal; CNR slightly decreased, 2.0% for 100 kV. We performed check radiation dose accuracy for each tube voltage with each model phantom. As a result, the difference of MU value was not accepted. Finally, compared with 120 kV, CTDIvol and TLD value showed markedly decreased radiation dose, 60% for 80 kV and 30% for 100 kV. Using a technique with low tube voltages, especially 100 kV, is useful in radiotherapy treatment planning to obtain 20% dose reduction without compromising 120 kV image quality.

SU-F-T-415: Differences in Lung Sparing in Deep Inspiration Breath-Hold and Free Breathing Breast Plans Calculated in Pinnacle and Monaco

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

Saenz, D; Stathakis, S

Purpose: Deep inspiration breath-hold (DIBH) is used for left-sided breast radiotherapy to spare the heart and lung. The magnitude of sparing has been shown to be significant. Monte Carlo, furthermore, has the potential to calculate most accurately the dose in the heterogeneous lung medium at the interface with the lung wall. The lung dose was investigated in Monaco to determine the level of sparing relative to that calculated in Pinnacle{sup 3}. Methods: Five patients undergoing DIBH radiotherapy on an Elekta Versa HD linear accelerator in conjunction with the Catalyst C-RAD surface imaging system were planned using Phillips Pinnacle{sup 3}. Freemore » breathing plans were also created to clinically assure a benefit. Both plans were re-calculated in Monaco to determine if there were any significant differences. The mean heart dose, mean left lung, and mean total lung dose were compared in addition to the V20 for left and both lungs. Dose was calculated as dose to medium as well as dose to water with a statistical precision of 0.7%. Results: Mean lung dose was significantly different (p < 0.003) between the two calculations for both DIBH (11.6% higher in Monaco) and free breathing (14.2% higher in Monaco). V20 was also higher in Monaco (p < 0.05) for DIBH (5.7% higher) and free breathing (4.9% higher). The mean heart dose was not significantly different between the dose calculations for either DIBH or free breathing. Results were no more than 0.1% different when calculated as dose to water. Conclusion: The use of Monte Carlo can provide insight on the lung dose for both free breathing and DIBH techniques for whole breast irradiation. While the sparing (dose reductions with DIBH as compared to free breathing) is equivalent for either planning system, the lung doses themselves are higher when calculated with Monaco.« less

Maximizing dermal targeting and minimizing transdermal penetration by magnolol/honokiol methoxylation.

PubMed

Lin, Chwan-Fwu; Hwang, Tsong-Long; Al-Suwayeh, Saleh A; Huang, Yu-Ling; Hung, Yi-Yun; Fang, Jia-You

2013-03-10

Magnolol and honokiol, predominant active compounds in the family Magnoliaceae, are known to exhibit strong anti-inflammatory activities against dermal disorders. We attempted to modify the structures of magnolol and honokiol by methoxylation to optimize the skin delivery ability. Absorption of these permeants into and through the skin was performed at both an infinite dose and saturated solubility. Superoxide anion and elastase released from human neutrophils were the biomarkers used to examine anti-inflammatory potencies of these permeants. The safety of the permeants was evaluated by keratinocyte viability and in vivo bioengineering techniques. Topical magnolol and honokiol at an infinite dose (7.5 mM) showed skin accumulations of 0.22 and 0.16 nmol/mg, respectively. Methoxylation significantly enhanced their skin absorption. Deposition amounts of dimethylmagnolol and dimethylhonokiol were respectively 15- and 7-fold greater than those of magnolol and honokiol. Contrary to the skin accumulation results, the transdermal penetration across skin decreased following methoxylation. No transdermal delivery occurred for dimethylhonokiol. Skin uptake of 4'-O-methylhonokiol was 2-fold higher than that of 2-O-methylhonokiol, although they are isomers. Methoxylated permeants demonstrated selective absorption into follicles, which showed 3-5-fold higher follicular amounts compared to magnolol and honokiol. The relative order of anti-inflammatory activities was honokiol>2-O-methylmagnolol>dimethylhonokiol>magnolol. The other compounds exhibited negligible or negative responses in activated neutrophils. Magnolol and honokiol induced slight but significant keratinocyte cytotoxicity and stratum corneum disruption. Daily administration of methoxylated permeants, especially dimethylhonokiol, produced no skin irritation for up to 7 days. Methoxylated magnolol and honokiol can be efficient and safe candidates for treating inflammatory skin disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of lindane, paraquat, toxaphene, and 2,4,5-trichlorophenoxyacetic acid on mallard embryo development.

PubMed

Hoffman, D J; Eastin, W C

1982-01-01

The effects were determined of externally treating mallard (Anas platyrhynchos) eggs with two insecticides (lindane and toxaphene) and two herbicides (paraquat and 2,4,5-T) with formulations and concentrations similar to field applications. Paraquat was the most embryotoxic of the four compounds regardless of the type of vehicle. The LC50 for paraquat was 1.5 lb of active ingredient/acre in aqueous emulsion and 0.1 lb/acre in the oil vehicle. The other compounds had LC50's that were several orders of magnitude higher. Both paraquat and toxaphene caused some mortality at 1/2 of the field level of application. Paraquat impaired growth and was slightly teratogenic at 1/2 of the field level of application, but required higher concentrations (1.5 to 3 times the field level) to produce brain and visceral defects. Lindane was teratogenic, resulting in multiple defects but only at doses that were greater than five times the field level of application. Toxaphene resulted in defects of the joints at doses close to or exceeding the LC50. The herbicide 2,4,5-T resulted in few toxic effects and relatively few abnormal survivors with gross defects. The overall embryotoxicity with either vehicle was paraquat greater than lindane greater than toxaphene greater than 2,4,5-T on a lb per acre basis. However the potential hazard at exposures of up to five times the field level of application was paraquat greater than toxaphene; neither lindane nor 2,4,5-T constituted much of a hazard. Both paraquat and lindane were more toxic on lb-per-acre basis when administered in oil vehicle but only paraquat represented a potential hazard at five times the field level of application.

Effects of lindane, paraquat, toxaphene, and 2,4,5-trichlorophenoxyacetic acid on mallard embryo development

USGS Publications Warehouse

Hoffman, D.J.; Eastin, W.C.

1982-01-01

The effects were determined of externally treating mallard (Anas platyrhynchos) eggs with two insecticides (lindane and toxaphene) and two herbicides (paraquat and 2,4,5-T) with formulations and concentrations similar to field applications. Paraquat was the most embryotoxic of the four compounds regardless of the type of vehicle. The LC50 for paraquat was 1.5 lb of active ingredient/ acre in aqueous emulsion and 0.1 lb/acre in the oil vehicle. The other compounds had LC50's that were several orders of magnitude higher. Both paraquat and toxaphene caused some mortality at 1/2 of the field level of application. Paraquat impaired growth and was slightly teratogenic at 1/2 of the field level of application, but required higher concentrations (1.5 to 3 times the field level) to produce brain and visceral defects. Lindane was teratogenic, resulting in multiple defects but only at doses that were greater than five times the field level of application. Toxaphene resulted in defects of the joints at doses close to or exceeding the LC50. The herbicide 2,4,5-T resulted in few toxic effects and relatively few abnormal survivors with gross defects. The overall embryotoxicity with either vehicle was paraquat > lindane > toxaphene > 2,4,5-T on a lb per acre basis. However the potential hazard at exposures of up to five times the field level of application was paraquat > toxaphene; neither lindane nor 2,4,5-T constituted much of a hazard. Both paraquat and lindane were more toxic on a lb-peracre basis when administered in oil vehicle but only paraquat represented a potential hazard at five times the field level of application.

Therapeutically equivalent pharmacokinetic profile across three application sites for AG200-15, a novel low-estrogen dose contraceptive patch.

PubMed

Stanczyk, Frank Z; Archer, David F; Rubin, Arkady; Foegh, Marie

2013-06-01

AG200-15 Agile Patch (AP) is a novel 7-day contraceptive patch providing ethinyl estradiol (EE) exposure comparable to low-dose combination oral contraceptives. This study determined whether application of the AP to three different anatomical sites (lower abdomen, buttock and upper torso) influences the pharmacokinetic profile of EE and levonorgestrel (LNG). In this open-label, three-period, crossover study, 24 subjects were randomized to one of six treatment sequences; each included application of patch to abdomen, buttock and upper torso, with the AP worn on one site for 7 days. After a 7-day washout, a new patch was applied to the next anatomical site. Multiple blood samples were collected up to 240 h after patch application. For plasma EE levels, median time to maximum drug concentration (Tmax, 24-48 h) and mean maximum concentration (Cmax, 47.9-61.5 pg/mL) were similar among application sites. Compared with lower abdomen, EE exposure was higher (16%-30%) at buttock and upper torso (15%-22%). For plasma LNG levels, median Tmax (72-120 h) and mean Cmax (1436-1589 pg/mL) were similar across application sites. Compared with lower abdomen, LNG exposure was higher at buttock (1%-7%) and upper torso (16%-17%). No serious adverse events (AEs) or AE-related discontinuations occurred. The most common treatment-emergent AEs were nausea, application site pruritus and headache, with frequencies comparable across anatomical sites. Absorption from the abdomen was slightly lower versus other sites; however, exposure to EE and LNG for all sites was therapeutically equivalent. The AP was well tolerated at all three anatomical sites. Copyright © 2013 Elsevier Inc. All rights reserved.

Elimination of Cancer Stem-Like Cells and Potentiation of Temozolomide Sensitivity by Honokiol in Glioblastoma Multiforme Cells

PubMed Central

Lai, I-Chun; Shih, Ping-Hsiao; Yao, Chih-Jung; Yeh, Chi-Tai; Wang-Peng, Jacqueline; Lui, Tai-Ngar; Chuang, Suang-En; Hu, Tsai-Shu; Lai, Tung-Yuan; Lai, Gi-Ming

2015-01-01

Glioblastoma multiforme (GBM) is the most common adult malignant glioma with poor prognosis due to the resistance to radiotherapy and chemotherapy, which might be critically involved in the repopulation of cancer stem cells (CSCs) after treatment. We had investigated the characteristics of cancer stem-like side population (SP) cells sorted from GBM cells, and studied the effect of Honokiol targeting on CSCs. GBM8401 SP cells possessed the stem cell markers, such as nestin, CD133 and Oct4, and the expressions of self-renewal related stemness genes, such as SMO, Notch3 and IHH (Indian Hedgehog). Honokiol inhibited the proliferation of both GBM8401 parental cells and SP cells in a dose-dependent manner, the IC50 were 5.3±0.72 and 11±1.1 μM, respectively. The proportions of SP in GBM8401 cells were diminished by Honokiol from 1.5±0.22% down to 0.3±0.02% and 0.2±0.01% at doses of 2.5 μM and 5 μM, respectively. The SP cells appeared to have higher expression of O 6-methylguanine-DNA methyltransferase (MGMT) and be more resistant to Temozolomide (TMZ). The resistance to TMZ could be only slightly reversed by MGMT inhibitor O 6-benzylguanine (O 6-BG), but markedly further enhanced by Honokiol addition. Such significant enhancement was accompanied with the higher induction of apoptosis, greater down-regulation of Notch3 as well as its downstream Hes1 expressions in SP cells. Our data indicate that Honokiol might have clinical benefits for the GBM patients who are refractory to TMZ treatment. PMID:25763821

SU-E-T-766: Treatment Planning Comparison Study On Two Different Multileaf Collimators Delivered with Volumetric Modulated Arc Therapy

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

Zhang, R; Xiaomei, F; Bai, W

2015-06-15

Purpose: To compare and evaluate the performance of two different multileaf collimators(MLCi2 and Agility) delivery with volumetric modulated arc therapy techniques. Methods: Treatment plans were graded four (Low, Moderate, Moderate-High and High complexity) accorrding to the complexity. This includes 1 Low complexity(brain metastasis), 2 Moderate complexity(Lung and Liver), 1 Moderate-High complexity(prostate) and 1 High complexity ( head and neck) cases. Total dose of 60 Gy was given for all the plans. All cases were desigined two VMAT plans, one with MLCi2(group A) and the other with Agility(group B). All plans were done on Elekta VMAT with Monaco treatment planning system.more » All plans were generated with 6 MV X-rays for both Plan A and Plan B. Plans were evaluated based on the ability to meet the dose volume histogram, radiation conformity index, estimated radiation delivery time, dose homogeneity index(HI) and monitor units(MU) needed to deliver the prescribed dose. Results: Plans of group B achieved the best HI (HI = 1.05 Vs. 1.06) at the Low complexity cases while plans of group A were slightly better at the high complexity cases (HI = 1.12 Vs. 1.14). Faster VMAT plan delivery with Agility than with MLCi2 as plan complexity increased (Low complexity:52s Vs.52s, Moderate complexity:58s Vs. 55s, Moderate-High complexity: 171s Vs.152s, High complexity : 326s Vs. 202s ), especially for the most complex paradigms delivered time can be decresed 38%. No Significant changes were observed between the group B and group A plans in terms of the healthy tissue mean dose and MU. Both plans respected the planning objective for all organs at risk. Conclusion: The study concludes that VMAT plans with the novel Agility MLC can significant decrease the delivering time at the high complexity cases, while a slight compromise in the dose homogeneity index should be noted. This work was supported by The Medical Science Foundation of The health department of Hebei Province (No. 20130253)« less

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats

PubMed Central

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

Objective: To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Materials and Methods: Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. Results: At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Conclusions: Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women. PMID:25097281

Effect of 99 GHz continuous millimeter wave electro-magnetic radiation on E. coli viability and metabolic activity.

PubMed

Cohen, Irena; Cahan, Rivka; Shani, Gad; Cohen, Eyal; Abramovich, Amir

2010-05-01

To investigate time exposure dependence of continuous millimeter wave (CW) 99 GHz radiation on Escherichia coli bacterial cell viability and metabolic activity. Suspensions of E. coli bacterial cells with an optical density of OD(660 nm) = 0.1 were used for viability tests and OD(660 nm) = 1.0 for metabolic activity tests. These suspensions were exposed to 99 GHz CW electromagnetic radiation, generated by a Backward Wave Oscillator (BWO) tube base instrument with a horn antenna at the BWO exit, to obtain an almost ideal Gaussian beam. Calculations of the Gaussian beam show that a power of 0.2 mW/cm(2) was obtained at the bacterial plane. The experimental results show that 1 hour of exposure to 99 GHz CW electromagnetic radiation had no effect on E. coli viability and colony characterisation. In 19 h of radiation, the number of colonies forming units was half order of magnitude higher than the sham-exposed and the control. However, 19 h of exposure did not affect the E. coli metabolic activity. Exposure of E. coli to millimeter wave (MW) CW 99 GHz radiation for a short period did not affect the viability of E. coli bacterial cells. However, exposure for 19 h caused a slight proliferation but did not influence the metabolic activities of about 90 biochemical reactions that were examined. Hence, we assume that the slight proliferation (half order of magnitude) after 19 h of exposure dose not have a biological meaning.

Pharmacokinetics of heparin and related polysaccharides

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

Boneu, B.; Dol, F.; Caranobe, C.

1989-01-01

The pharmacodynamic profile of standard heparin (SH), a low molecular weight derivative (CY 216) and of dermatan sulfate (DS), a new potential antithrombotic drug, was investigated in the rabbit over a large range of doses. After bolus i.v. injection of low doses, the biological activity of SH disappeared exponentially; however, its half-life was prolonged when the dose injected increased, and over 158 micrograms/kg (100 anti-factor Xa U/kg) the biological activity disappeared as a concave-convex curve. CY 216 disappeared more slowly than SH at low doses but faster than SH at higher doses. More than 90% of the DS biological activitymore » present 1 minute after the i.v. injection disappeared exponentially without dose-dependent effects. Increasing doses of the three drugs were then delivered for 5 h under continuous infusions. Below 500 micrograms/kg/h the DS and CY 216 plateau concentrations were higher than that of SH while above this dose the SH concentration was higher than that of DS and CY 216. These observations may be explained by the results of pharmacokinetics experiments where /sup 125/I-labeled compounds were delivered by bolus i.v. injection in association with increasing doses of their unlabeled counterparts. For SH there was a 10-fold difference between the half-life of the lower dose (32 micrograms/kg or 5 anti-factor Xa U/kg) and that of the higher dose (3200 micrograms/kg); it was demonstrated that the half-life of SH continuously shortened as its plasma concentration decreased. In contrast the CY 216 and DS half-lives were very close, independent of the dose delivered, and therefore longer than that of SH at low doses and shorter than that of SH at higher doses.« less

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

Iwai, P; Lins, L Nadler

Purpose: There is a lack of studies with significant cohort data about patients using pacemaker (PM), implanted cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device undergoing radiotherapy. There is no literature comparing the cumulative doses delivered to those cardiac implanted electronic devices (CIED) calculated by different algorithms neither studies comparing doses with heterogeneity correction or not. The aim of this study was to evaluate the influence of the algorithms Pencil Beam Convolution (PBC), Analytical Anisotropic Algorithm (AAA) and Acuros XB (AXB) as well as heterogeneity correction on risk categorization of patients. Methods: A retrospective analysis of 19 3DCRT ormore » IMRT plans of 17 patients was conducted, calculating the dose delivered to CIED using three different calculation algorithms. Doses were evaluated with and without heterogeneity correction for comparison. Risk categorization of the patients was based on their CIED dependency and cumulative dose in the devices. Results: Total estimated doses at CIED calculated by AAA or AXB were higher than those calculated by PBC in 56% of the cases. In average, the doses at CIED calculated by AAA and AXB were higher than those calculated by PBC (29% and 4% higher, respectively). The maximum difference of doses calculated by each algorithm was about 1 Gy, either using heterogeneity correction or not. Values of maximum dose calculated with heterogeneity correction showed that dose at CIED was at least equal or higher in 84% of the cases with PBC, 77% with AAA and 67% with AXB than dose obtained with no heterogeneity correction. Conclusion: The dose calculation algorithm and heterogeneity correction did not change the risk categorization. Since higher estimated doses delivered to CIED do not compromise treatment precautions to be taken, it’s recommend that the most sophisticated algorithm available should be used to predict dose at the CIED using heterogeneity correction.« less

Lethal mobilization of DDT by cowbirds

USGS Publications Warehouse

Van Velzen, A.C.; Stiles, W.B.; Stickel, L.F.

1972-01-01

This study is an experimental demonstration of lethal mobilization of DDT by brown-headed cowbirds (Molothrus ater) and the effects of food deprivation on the distribution and loss of DDT, DDD, and DDE. The principal experimental group consisted of 20 birds fed a dietary dosage of 100 ppm of DDT for 13 days. After 2 days of full rations of untreated food, they were subjected to food restriction. Food was reduced to 43 percent of normal. Seven of the 20 birds died within 4 days. No birds died in the three control groups, treated as follows: ( 1 ) 20 birds fed 100 ppm DDT for 13 days and full rations of untreated food thereafter, (2) 20 birds fed only untreated food but subjected to food restriction, and (3) 20 birds fed full rations of untreated food throughout. In a pilot study, birds were fed 100, 200, or 300 ppm of DDT and subjected to two periods of food restriction, the first of these immediately after dosage ceased and the second 4 months later. DDT-dosed birds from all dosage levels died in each period of food restriction. Before the weight loss that accompanied food restriction, the brains of DDT-dosed birds had concentrations of DDT and DDD that were far below the lethal range. Concentrations increased rapidly to lethal levels. In these birds, DDT in carcasses decreased while DDD increased. DDT-dosed birds that died during food restriction lost 16 percent of their total body burden of DDT + DDD + DDE, 21 percent of their weight, and 81 percent of their fat. The DDT-dosed birds that were subjected to food restriction but survived lost a significantly greater proportion of their body burden of residues than similarly dosed birds not subjected to weight loss. Brain levels of DDT and DDD in birds that died during food restriction soon after dosage did not differ significantly from brain levels of birds that died in a period of food restriction 4 months after dosage. Concentrations of DDE were significantly higher in the latter group, although they were lower than concentrations considered to be lethal. In contrast, carcass levels of DDT and DDD were significantly lower, and DDE was only slightly higher, in the birds that died in the second period of food restriction. It is concluded that stored DDT residues present a hazard to birds, which utilize stored fat during periods of stress due to reproduction, cold weather, disease, injury, limited food supply, or migration.

SU-E-T-417: The Impact of Normal Tissue Constraints On PTV Dose Homogeneity for Intensity Modulated Radiotherapy (IMRT), Volume Modulated Arc Therapy (VMAT) and Tomotherapy

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

Peng, J; McDonald, D; Ashenafi, M

2014-06-01

Purpose: Complex intensity modulated arc therapy tends to spread low dose to normal tissue(NT)regions to obtain improved target conformity and homogeneity and OAR sparing.This work evaluates the trade-offs between PTV homogeneity and reduction of the maximum dose(Dmax)spread to NT while planning of IMRT,VMAT and Tomotherapy. Methods: Ten prostate patients,previously planned with step-and-shoot IMRT,were selected.To fairly evaluate how PTV homogeneity was affected by NT Dmax constraints,original IMRT DVH objectives for PTV and OARs(femoral heads,and rectal and bladder wall)applied to 2 VMAT plans in Pinnacle(V9.0), and Tomotherapy(V4.2).The only constraint difference was the NT which was defined as body contours excluding targets,OARs andmore » dose rings.NT Dmax constraint for 1st VMAT was set to the prescription dose(Dp).For 2nd VMAT(VMAT-NT)and Tomotherapy,it was set to the Dmax achieved in IMRT(~70-80% of Dp).All NT constraints were set to the lowest priority.Three common homogeneity indices(HI),RTOG-HI=Dmax/Dp,moderated-HI=D95%/D5% and complex-HI=(D2%-D98%)/Dp*100 were calculated. Results: All modalities with similar dosimetric endpoints for PTV and OARs.The complex-HI shows the most variability of indices,with average values of 5.9,4.9,9.3 and 6.1 for IMRT,VMAT,VMAT-NT and Tomotherapy,respectively.VMAT provided the best PTV homogeneity without compromising any OAR/NT sparing.Both VMAT-NT and Tomotherapy,planned with more restrictive NT constraints,showed reduced homogeneity,with VMAT-NT showing the worst homogeneity(P<0.0001)for all HI.Tomotherapy gave the lowest NT Dmax,with slightly decreased homogeneity compared to VMAT. Finally, there was no significant difference in NT Dmax or Dmean between VMAT and VMAT-NT. Conclusion: PTV HI is highly dependent on permitted NT constraints. Results demonstrated that VMAT-NT with more restrictive NT constraints does not reduce Dmax NT,but significantly receives higher Dmax and worse target homogeneity.Therefore, it is critical that planners do not use too restrictive NT constraints during VMAT optimization.Tomotherapy plan was not as sensitive to NT constraints,however,care shall be taken to ensure NT is not pushed too hard.These results are relevant for clinical practice.The biological effect of higher Dmax and increased target heterogeneity needs further study.« less

Dose-Response Relationship between Antimicrobial Drugs and Livestock-Associated MRSA in Pig Farming1

PubMed Central

Dohmen, Wietske; Bos, Marian E.H.; Verstappen, Koen M.; Houben, Manon; Wagenaar, Jaap A.; Heederik, Dick J.J.

2015-01-01

The farming community can be a vehicle for introduction of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in hospitals. During 2011–2013, an 18-month longitudinal study aimed at reducing the prevalence of LA-MRSA was conducted on 36 pig farms in the Netherlands. Evaluations every 6 months showed a slight decrease in MRSA prevalence in animals and a stable prevalence in farmers and family members. Antimicrobial use, expressed as defined daily dosages per animal per year, decreased 44% during the study period and was associated with declining MRSA prevalence in pigs. MRSA carriage in animals was substantially higher at farms using cephalosporins. Antimicrobial use remained strongly associated with LA-MRSA in humans regardless of the level of animal contact. A risk factor analysis outlined potential future interventions for LA-MRSA control. These results should encourage animal and public health authorities to maintain their efforts in reducing antimicrobial use in livestock and ask for future controlled intervention studies. PMID:25989456

Rapid detection of microorganisms based on active and passive modes of QCM.

PubMed

Farka, Zdeněk; Kovář, David; Skládal, Petr

2014-12-23

Label-free immunosensors are well suited for detection of microorganisms because of their fast response and reasonable sensitivity comparable to infection doses of common pathogens. Active (lever oscillator and frequency counter) and passive (impedance analyzer) modes of quartz crystal microbalance (QCM) were used and compared for rapid detection of three strains of E. coli. Different approaches for antibody immobilization were compared, the immobilization of reduced antibody using Sulfo-SMCC was most effective achieving the limit of detection (LOD) 8 × 104 CFU·mL-1 in 10 min. For the passive mode, software evaluating impedance characteristics in real-time was developed and used. Almost the same results were achieved using both active and passive modes confirming that the sensor properties are not limited by the frequency evaluation method but mainly by affinity of the antibody. Furthermore, reference measurements were done using surface plasmon resonance. Effect of condition of cells on signal was observed showing that cells ruptured by ultrasonication provided slightly higher signal changes than intact microbes.

Interactions of green coffee bean phenolics with wheat bread matrix in a model of simulated in vitro digestion.

PubMed

Świeca, Michał; Gawlik-Dziki, Urszula; Sęczyk, Łukasz; Dziki, Dariusz; Sikora, Małgorzata

2018-08-30

Interactions of phenolics from green coffee bean flour (GCS) with the matrix of wheat bread have been studied employing direct (electrophoretic and chromatographic techniques) and indirect tests (nutrient digestibility). According to the chromatograms of digests, the antiradical activity of enriched bread was exhibited by free phenolics. An increase the area of chromatograms and some additional peaks observed for enriched bread may confirm some interactions of proteins with phenolics. The electrophoretic profile of these extracts showed that the band corresponding to a protein with molecular mass of 38 kDA had much higher intensity in enriched bread. Electrophoretic analysis of pellets remaining after digestion revealed GCS dose-dependent differences in bands corresponding to proteins with molecular masses of 52 kDa and 23 kDa. The relative digestibility of both starch and proteins was slightly decreased by addition of GCS; however, these changes did not exceed 10%, which justifies the use of this functional material. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rapid Detection of Microorganisms Based on Active and Passive Modes of QCM

PubMed Central

Farka, Zdeněk; Kovář, David; Skládal, Petr

2015-01-01

Label-free immunosensors are well suited for detection of microorganisms because of their fast response and reasonable sensitivity comparable to infection doses of common pathogens. Active (lever oscillator and frequency counter) and passive (impedance analyzer) modes of quartz crystal microbalance (QCM) were used and compared for rapid detection of three strains of E. coli. Different approaches for antibody immobilization were compared, the immobilization of reduced antibody using Sulfo‐SMCC was most effective achieving the limit of detection (LOD) 8 × 104 CFU·mL−1 in 10 min. For the passive mode, software evaluating impedance characteristics in real-time was developed and used. Almost the same results were achieved using both active and passive modes confirming that the sensor properties are not limited by the frequency evaluation method but mainly by affinity of the antibody. Furthermore, reference measurements were done using surface plasmon resonance. Effect of condition of cells on signal was observed showing that cells ruptured by ultrasonication provided slightly higher signal changes than intact microbes. PMID:25545267

SOME CLINICAL OBSERVATIONS ON COWS FOLLOWING THE ADMINISTRATION OF RADIUM$sup 224$ AND CALCIUM$sup 4$$sup 5$

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

Sansom, B.F.; Garner, R.J.; West, L.C.

1964-01-01

In experiments designed to investigate the relative behavior of the alkaline earth elements in bovine metabolism, two pairs of lactating Ayrshire X Redpoll cows received doses of /sup 224/Ra and /sup 45/Ca. One pair (W258 and W259) received 24 mc /sup 224/Ra + 2 mc /sup 45/Ca administered intravenously, and the others (U45 and U402) received 2 mc /sup 224/Ra + /sup 45/Ca intravenously followed after 77 days by 5 mc /sup 224/Ra + 5 mc /sup 45/Ca orally. Four days after the oral dose, W258 and W259 were both off their feed and badly constipated, and their milk yieldmore » was down. They remained ill for 2 days but then showed steady improvement until, a week after the first symptoms, they were eating well and their milk yield was improving. Similar symptoms, but without constipation, were observed after the intravenous dose to these cows. Cows U45 and U402 showed no clinical symptoms after either the irtravenous or oral dose. In W258 and W259 the white cell counts made 4 days after oral dosing were within the normal range but on the 7th and 11th days there was a moderate leukopenia in both cows with minimum white cel1 counts of 2.82 and 1.56 x 10/sup 3//mm/sup 3/. The differential counts showed this to be due mainly to a fall in the number of neutrophils. By the 18th day the neutrophils had recovered to their normal proportion of about 30%, and only a slight leukopenia was apparent. Seven days after the intravenous dose, a moderate leukopenia was seen in both cows, with white cell counts of 2.2 x 10/sup 3/ and 1.8 x 10/sup 3//mm/sup 3/, mainly to neutropenia. In this instance recovery was slower, and the values were still very abnormal 14 days after the injection. Both doses also caused slight but progressive thrombocytopenia and anemia. No abnormalities in the blood picture of U45 and U402 were observed at any time after the irtravenous or oral doses. Although in man the most sensitive indication of radiation damage is a fall in the numbers of lymphocytes and platelets, the clearest reaction in cows to the feeding or injection of /sup 224/Ra and /sup 45/Ca was a transient neutropenia. Radiation doses were estimated, and it was shown that the threshold dose to produce changes in the blood picture of cows of sufficient magnitude to be recognized during routine hematological examination lies between 35 and 60 rem. For most mammalian species the threshold dose for significant effects on the hematopoietic system is approximates 100 r of gamma radiation. In a large animal this air dose would be roughly equivalent to an absorbed dose of 50 rem. (BBB)« less

In Vivo Toxicity Studies of Europium Hydroxide Nanorods in Mice

PubMed Central

Patra, Chitta Ranjan; Abdel Moneim, Soha S.; Wang, Enfeng; Dutta, Shamit; Patra, Sujata; Eshed, Michal; Mukherjee, Priyabrata; Gedanken, Aharon; Shah, Vijay H; Mukhopadhyay, Debabrata

2009-01-01

Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence properties and pro-angiogenic to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [EuIII(OH)3] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mgKg−1day−1) and time dependent manner (8–60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice sacrificed on day 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods. PMID:19616569

Simplified MPN method for enumeration of soil naphthalene degraders using gaseous substrate.

PubMed

Wallenius, Kaisa; Lappi, Kaisa; Mikkonen, Anu; Wickström, Annika; Vaalama, Anu; Lehtinen, Taru; Suominen, Leena

2012-02-01

We describe a simplified microplate most-probable-number (MPN) procedure to quantify the bacterial naphthalene degrader population in soil samples. In this method, the sole substrate naphthalene is dosed passively via gaseous phase to liquid medium and the detection of growth is based on the automated measurement of turbidity using an absorbance reader. The performance of the new method was evaluated by comparison with a recently introduced method in which the substrate is dissolved in inert silicone oil and added individually to each well, and the results are scored visually using a respiration indicator dye. Oil-contaminated industrial soil showed slightly but significantly higher MPN estimate with our method than with the reference method. This suggests that gaseous naphthalene was dissolved in an adequate concentration to support the growth of naphthalene degraders without being too toxic. The dosing of substrate via gaseous phase notably reduced the work load and risk of contamination. The result scoring by absorbance measurement was objective and more reliable than measurement with indicator dye, and it also enabled further analysis of cultures. Several bacterial genera were identified by cloning and sequencing of 16S rRNA genes from the MPN wells incubated in the presence of gaseous naphthalene. In addition, the applicability of the simplified MPN method was demonstrated by a significant positive correlation between the level of oil contamination and the number of naphthalene degraders detected in soil.

Effects of extracellular calcium on viability and osteogenic differentiation of bone marrow stromal cells in vitro.

PubMed

Cheng, Shaowen; Wang, Wei; Lin, Zhongqin; Zhou, Ping; Zhang, Xiaolei; Zhang, Wei; Chen, Qingyu; Kou, Dongquan; Ying, Xiaozhou; Shen, Yue; Cheng, Xiaojie; Yu, Ziming; Peng, Lei; Lu, Chuanzhu

2013-09-01

Bone marrow stromal cells (BMSCs) have been extensively used for tissue engineering. However, the effect of Ca(2+) on the viability and osteogenic differentiation of BMSCs has yet to be evaluated. To determine the dose-dependent effect of Ca(2+) on viability and osteogenesis of BMSCs in vitro, BMSCs were cultured in calcium-free DMEM medium supplemented with various concentrations of Ca(2+) (0, 1, 2, 3, 4, and 5 mM) from calcium citrate. Cell viability was analyzed by MTT assay and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) assay, Von Kossa staining, and real-time PCR. Ca(2+) stimulated BMSCs viability in a dose-dependent manner. At slightly higher concentrations (4 and 5 mM) in the culture, Ca(2+) significantly inhibited the activity of ALP on days 7 and 14 (P < 0.01 or P < 0.05), significantly suppressed collagen synthesis (P < 0.01 or P < 0.05), and significantly elevated calcium deposition (P < 0.01) and mRNA levels of osteocalcin (P < 0.01 or P < 0.05) and osteopontin (P < 0.01 or P < 0.05). Therefore, elevated concentrations of extracellular calcium may promote cell viability and late-stage osteogenic differentiation, but may suppress early-stage osteogenic differentiation in BMSCs.

Analysis and recent advances in gamma heating measurements in MINERVE facility by using TLD and OSLD techniques

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

Amharrak, H.; Di Salvo, J.; Lyoussi, A.

2011-07-01

The objective of this study is to develop nuclear heating measurement methods in Zero Power experimental reactors. This paper presents the analysis of Thermo-Luminescent Detector (TLD) and Optically Stimulated Luminescent Detectors (OSLD) experiments in the UO{sub 2} core of the MINERVE research reactor at the CEA Cadarache. The experimental sources of uncertainties on the gamma dose have been reduced by improving the conditions, as well as the repeatability, of the calibration step for each individual TLD. The interpretation of these measurements needs to take into account calculation of cavity correction factors, related to calibration and irradiation configurations, as well asmore » neutron corrections calculations. These calculations are based on Monte Carlo simulations of neutron-gamma and gamma-electron transport coupled particles. TLD and OSLD are positioned inside aluminum pillboxes. The comparison between calculated and measured integral gamma-ray absorbed doses using TLD, shows that calculation slightly overestimates the measurement with a C/E value equal to 1.05 {+-} 5.3 % (k = 2). By using OSLD, the calculation slightly underestimates the measurement with a C/E value equal to 0.96 {+-} 7.0% (k = 2. (authors)« less

Radioactivity concentrations in soils in the Qingdao area, China.

PubMed

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

2008-10-01

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

Reproducibility of CVD diamond detectors for radiotherapy dosimetry

NASA Astrophysics Data System (ADS)

Betzel, G. T.; Lansley, S. P.; McKay, D.; Meyer, J.

2012-11-01

Three in-house X-ray detectors based on diamond chemical vapor deposition (CVD) from the same manufactured batch of single crystal films were investigated for their reproducibility. Leakage current, priming dose, response dynamics, dose linearity, dependence on dose rate and angular dependence were used to evaluate differences between detectors. Slight differences were seen in leakage currents before (<1.5 pA) and after (<12 pA) irradiation. A priming dose of ˜7 Gy and rise and fall times of 2 s were found for all three detectors. Sensitivities differed by up to 10%. Dependence on dose rate were similar (∆=0.92-0.94). Angular dependence was minimal (97-102% avg.). Differences in detector performance appeared to be primarily due to film thickness, which can significantly change sensitivities (nC Gy-1) and applied fields (V μm-1) for detectors with small sensitive volumes. Results suggest that preselection of CVD diamond films according to thickness in addition to material quality would be required to avoid individual calibration, which is performed for commercially available natural diamond detectors.

A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

PubMed

Harper, David N; Langen, Anna-Lena; Schenk, Susan

2014-01-01

Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.

Assessment of Maillard reaction evolution, prebiotic carbohydrates, antioxidant activity and α-amylase inhibition in pulse flours.

PubMed

Moussou, Nadia; Corzo-Martínez, Marta; Sanz, María Luz; Zaidi, Farid; Montilla, Antonia; Villamiel, Mar

2017-03-01

In this paper, the quality of bean, chickpea, fava beans, lentil and pea flours from Algeria has been evaluated. Maillard reaction (MR) indicators, modifications in the carbohydrate and protein fractions, antioxidant activity and α-amylase inhibitor of raw, toasted and stored samples were evaluated. Fava beans, beans and peas showed higher content of raffinose family oligosaccharides while chickpeas and lentils showed higher polyol content. Toasting and storage caused slightly change in pulse quality; MR showed slight losses of lysine but increased antioxidant activity. Moreover, inhibition of α-amylase was slightly augmented during processing; this could increase the undigested carbohydrates that reach the colon, modulating the glycemic response. These results point out the suitability of these flours for preparing high-quality foodstuffs intended for a wide spectrum of the population, including hyperglycemic and gluten intolerant individuals.

Michigan's forest resources in 2004

Treesearch

Mark H. Hansen; Gary J. Brand

2006-01-01

The sixth inventory of Michigan's forests was completed in 2004. The 18.7 million acres of timberland found is slightly higher than the 18.6 million acres found in the 1993 inventory. The standing timber volume has increased slightly at a rate of 0.22 percent per year. Detailed inventory results can be obtained at

USING THE HERMITE POLYNOMIALS IN RADIOLOGICAL MONITORING NETWORKS.

PubMed

Benito, G; Sáez, J C; Blázquez, J B; Quiñones, J

2018-03-15

The most interesting events in Radiological Monitoring Network correspond to higher values of H*(10). The higher doses cause skewness in the probability density function (PDF) of the records, which there are not Gaussian anymore. Within this work the probability of having a dose >2 standard deviations is proposed as surveillance of higher doses. Such probability is estimated by using the Hermite polynomials for reconstructing the PDF. The result is that the probability is ~6 ± 1%, much >2.5% corresponding to Gaussian PDFs, which may be of interest in the design of alarm level for higher doses.

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.

The antipyretic effect of indomethacin.

PubMed Central

Clark, W G; Cumby, H R

1975-01-01

1. Several possible mechanisms of the antipyretic action of indomethacin administered cat. 2. Indomethacin did not decrease bacterial endotoxin-induced release of endogenous pyrogen in vivo. 3. Indomethacin (5-40 mug/kg) inhibited the pyrogenic effect of peripherally or centrally administered leucocytic progen. A dose of 10 mug/kg caused a parallel shift to the right of the log dose-response curve for I.V. leucocytic pyrogen and reduced the potency of the pyrogen at least 50%. 4. Incubation of leucocytic pyrogen with indomethacin did not alter its pyrogenic potency. 5. Indomethacin exerted only a slight non-dose-related hypothermic effect in afebrile animals. 6. Indomethacin (up to 1 mg/kg) did not diminish the hyperthermic response to intraventricular administration of prostaglandin E1. 7. This pattern of activity indicates that indomethacin acts centrally to inhibit an effect of leucocytic pyrogen. PMID:1151840

The relative bioavailability of diclofenac with respect to time of administration.

PubMed Central

Mustofa, M; Suryawati, S; Dwiprahasto, I; Santoso, B

1991-01-01

The pharmacokinetics of diclofenac after a single oral dose (50 mg) were studied in 10 healthy adults on two occasions separated by 2 weeks, once in the morning (dose administered at 07.00 h) and once in the evening (dose at 19.00 h). Peak serum drug concentrations as well as the area under the drug concentration-time curve were significantly less during the night compared with the day (Cmax: 1886 +/- s.d 901 vs 2791 +/- 1565 ng ml-1 and AUC: 2807 +/- 1376 vs 3681 +/- 1986 ng ml-1 h). However, the time to reach peak concentration (tmax) and the half-life of diclofenac (t1/2) were not significantly different on the two occasions. We suggest that the extent of diclofenac absorption is slightly lower following administration in the evening compared with administration in the morning. PMID:1931476

THE STATE OF IMMUNITY IN GUINEA-PIGS IMMUNIZED WITH LIVE BRUCELLOSIS VACCINE AND EXPOSED TO RADIATION

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

Shevtsova, Z.V.

1960-01-01

On immunization with 19-BA live brucellosis vaccine on the 3rd and 10th days after exposure to radiation in a dose of 200 r, guinea pigs died 4 and 2 times more frequently than unvaccinated guinea pigs. If immunization was carried out on the 30th day after irradiation the mortality among irradiated animals showed only a slight increase compared with the mortality among unvaccinated control animals. Immunization carried out before exposure to radiation had no influence upon the mortality of the animals caused by radiation sickness. Guinea pigs immunized after exposure to radiation were insusceptible when infected with the doses ofmore » virulent strains of Brucella usually employed to challenge immunity (2-4 infective doses). If, however, the animals were infected with a dose twice as high (8 infective doses) the degree of immunity proved to be lower in guinea pigs exposed to radiation, than in guinea pigs immunized and not exposed to radiation. Exposure of guinea pigs to radiation at a time when immunity had already developed had no influence upon the degree of immunity on infection with 4 infective doses of the virulent strain. (auth)« less

Limited PCB antagonism of TCDD-induced malformations in mice

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

Morrissey, R.E.; Harris, M.W.; Diliberto, J.J.

1992-01-01

Mice used to model induction of cleft palate and kidney malformations in offspring following maternal treatment with TCDD, were dosed on gestation day with hexachlorobiphenyl (HCB) and/or with tetrachlorodibenzo-p-dioxin (TCDD) to investigate the potential protective effects of HCB against TCDD-induced teratogenicity. At the doses used in the study, there was no effect of either compound on number of live or dead offspring. Fetal body weight was slightly decreased in all groups dosed with = or > 250 mg HCB/kg. HCB did not induce cleft palate at a dose of 1000 mg/kg, but did induce increases in hydronephrosis and hydroureter atmore » 500 and 1000 mg/kg. Combinations of HCB and TCDD decreased the incidence of cleft palate induced by TCDD alone, but only at doses of 15 microgram TCDD/kg combined with 125-500 mg HCB/kg. The window for antagonism of hydronephrosis (incidence and severity) appeared narrower (15 microgram TCDD/kg + 500 mg HCB/kg). HCB induced increases (3 fold) in EROD activity at doses of 500 and 1000 mg/kg, suggesting that the limited antagonism of TCDD teratogenicity by HCB would be consistent with control by Ah receptor. (Copyright (c) 1992 Elsevier Science Publishers B.V.)« less

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

NASA Astrophysics Data System (ADS)

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

2000-03-01

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

Impact of Efavirenz on Intestinal Metabolism and Transport: Insights From an Interaction Study With Ezetimibe in Healthy Volunteers

PubMed Central

Oswald, S; zu Schwabedissen, HE Meyer; Nassif, A; Modess, C; Desta, Z; Ogburn, ET; Mostertz, J; Keiser, M; Jia, J; Hubeny, A; Ulrich, A; Runge, D; Marinova, M; Lütjohann, D; Kroemer, HK; Siegmund, W

2013-01-01

Hypercholesterolemia frequently occurs in patients treated with efavirenz who cannot be treated adequately with statins because of drug interactions. These patients may benefit from cholesterol-lowering therapy with ezetimibe. This study determined the influence of single-dose and multiple-dose efavirenz (400 mg/day for 9 days) on the pharmacokinetics and sterol-lowering of ezetimibe (10 mg) in 12 healthy subjects. In addition, the influence of efavirenz on genome-wide intestinal expression and in vitro function of ABCB1, ABCC2, UGT1A1, and OATP1B1 was studied. Efavirenz (multiple dose) had no influence on the pharmacokinetics and lipid-lowering functions of ezetimibe. Intestinal expression of enzymes and transporters (e.g., ABCB1, ABCC2, and UGT1A1) was not affected by chronic efavirenz. Efavirenz (single dose) slightly increased ezetimibe absorption and markedly decreased exposure to ezetimibe-glucuronide (single dose and multiple dose), which may be explained by inhibition of UGT1A1 and ABCB1 (in vitro data). Ezetimibe had no effect on the disposition of efavirenz. Consequently, ezetimibe may be a safe and efficient therapeutic option in patients with HIV infection. PMID:22297387

Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

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

Gautier, Jean-Charles, E-mail: jean-charles.gautie

Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- andmore » multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.« less

SU-F-18C-14: Hessian-Based Norm Penalty for Weighted Least-Square CBCT Reconstruction

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

Sun, T; Sun, N; Tan, S

Purpose: To develop a Hessian-based norm penalty for cone-beam CT (CBCT) reconstruction that has a similar ability in suppressing noise as the total variation (TV) penalty while avoiding the staircase effect and better preserving low-contrast objects. Methods: We extended the TV penalty to a Hessian-based norm penalty based on the Frobenius norm of the Hessian matrix of an image for CBCT reconstruction. The objective function was constructed using the penalized weighted least-square (PWLS) principle. An effective algorithm was developed to minimize the objective function using a majorization-minimization (MM) approach. We evaluated and compared the proposed penalty with the TV penaltymore » on a CatPhan 600 phantom and an anthropomorphic head phantom, each acquired at a low-dose protocol (10mA/10ms) and a high-dose protocol (80mA/12ms). For both penalties, contrast-to-noise (CNR) in four low-contrast regions-of-interest (ROIs) and the full-width-at-half-maximum (FWHM) of two point-like objects in constructed images were calculated and compared. Results: In the experiment of CatPhan 600 phantom, the Hessian-based norm penalty has slightly higher CNRs and approximately equivalent FWHM values compared with the TV penalty. In the experiment of the anthropomorphic head phantom at the low-dose protocol, the TV penalty result has several artificial piece-wise constant areas known as the staircase effect while in the Hessian-based norm penalty the image appears smoother and more similar to that of the FDK result using the high-dose protocol. Conclusion: The proposed Hessian-based norm penalty has a similar performance in suppressing noise to the TV penalty, but has a potential advantage in suppressing the staircase effect and preserving low-contrast objects. This work was supported in part by National Natural Science Foundation of China (NNSFC), under Grant Nos. 60971112 and 61375018, and Fundamental Research Funds for the Central Universities, under Grant No. 2012QN086.« less

Volumetric modulated arc therapy planning for primary prostate cancer with selective intraprostatic boost determined by 18F-choline PET/CT.

PubMed

Kuang, Yu; Wu, Lili; Hirata, Emily; Miyazaki, Kyle; Sato, Miles; Kwee, Sandi A

2015-04-01

This study evaluated expected tumor control and normal tissue toxicity for prostate volumetric modulated arc therapy (VMAT) with and without radiation boosts to an intraprostatically dominant lesion (IDL), defined by (18)F-choline positron emission tomography/computed tomography (PET/CT). Thirty patients with localized prostate cancer underwent (18)F-choline PET/CT before treatment. Two VMAT plans, plan79 Gy and plan100-105 Gy, were compared for each patient. The whole-prostate planning target volume (PTVprostate) prescription was 79 Gy in both plans, but plan100-105 Gy added simultaneous boost doses of 100 Gy and 105 Gy to the IDL, defined by 60% and 70% of maximum prostatic uptake on (18)F-choline PET (IDLsuv60% and IDLsuv70%, respectively, with IDLsuv70% nested inside IDLsuv60% to potentially enhance tumor specificity of the maximum point dose). Plan evaluations included histopathological correspondence, isodose distributions, dose-volume histograms, tumor control probability (TCP), and normal tissue complication probability (NTCP). Planning objectives and dose constraints proved feasible in 30 of 30 cases. Prostate sextant histopathology was available for 28 cases, confirming that IDLsuv60% adequately covered all tumor-bearing prostate sextants in 27 cases and provided partial coverage in 1 case. Plan100-105 Gy had significantly higher TCP than plan79 Gy across all prostate regions for α/β ratios ranging from 1.5 Gy to 10 Gy (P<.001 for each case). There were no significant differences in bladder and femoral head NTCP between plans and slightly lower rectal NTCP (endpoint: grade ≥ 2 late toxicity or rectal bleeding) was found for plan100-105 Gy. VMAT can potentially increase the likelihood of tumor control in primary prostate cancer while observing normal tissue tolerances through simultaneous delivery of a steep radiation boost to a (18)F-choline PET-defined IDL. Copyright © 2015 Elsevier Inc. All rights reserved.

Soil nematode assemblages as bioindicators of radiation impact in the Chernobyl Exclusion Zone.

PubMed

Lecomte-Pradines, C; Bonzom, J-M; Della-Vedova, C; Beaugelin-Seiller, K; Villenave, C; Gaschak, S; Coppin, F; Dubourg, N; Maksimenko, A; Adam-Guillermin, C; Garnier-Laplace, J

2014-08-15

In radioecology, the need to understand the long-term ecological effects of radioactive contamination has been emphasised. This requires that the health of field populations is evaluated and linked to an accurate estimate of received radiological dose. The aim of the present study was to assess the effects of current radioactive contamination on nematode assemblages at sites affected by the fallout from the Chernobyl accident. First, we estimated the total dose rates (TDRs) absorbed by nematodes, from measured current soil activity concentrations, Dose Conversion Coefficients (DCCs, calculated using EDEN software) and soil-to-biota concentration ratios (from the ERICA tool database). The impact of current TDRs on nematode assemblages was then evaluated. Nematodes were collected in spring 2011 from 18 forest sites in the Chernobyl Exclusion Zone (CEZ) with external gamma dose rates, measured using radiophotoluminescent dosimeters, varying from 0.2 to 22 μGy h(-1). These values were one order of magnitude below the TDRs. A majority of bacterial-, plant-, and fungal-feeding nematodes and very few of the disturbance sensitive families were identified. No statistically significant association was observed between TDR values and nematode total abundance or the Shannon diversity index (H'). The Nematode Channel Ratio (which defines the relative abundance of bacterial- versus fungal-feeding nematodes) decreased significantly with increasing TDR, suggesting that radioactive contamination may influence nematode assemblages either directly or indirectly by modifying their food resources. A greater Maturity Index (MI), usually characterising better soil quality, was associated with higher pH and TDR values. These results suggest that in the CEZ, nematode assemblages from the forest sites were slightly impacted by chronic exposure at a predicted TDR of 200 μGy h(-1). This may be imputable to a dominant proportion of pollutant resistant nematodes in all sites. This might result from a selection at the expense of sensitive species after the accident. Copyright © 2013 Elsevier B.V. All rights reserved.

GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.

PubMed

Engberg, G; Kling-Petersen, T; Nissbrandt, H

1993-11-01

Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.

A randomized study of the immunogenicity and safety of Japanese encephalitis chimeric virus vaccine (JE-CV) in comparison with SA14-14-2 vaccine in children in the Republic of Korea.

PubMed

Kim, Dong Soo; Houillon, Guy; Jang, Gwang Cheon; Cha, Sung-Ho; Choi, Soo-Han; Lee, Jin; Kim, Hwang Min; Kim, Ji Hong; Kang, Jin Han; Kim, Jong-Hyun; Kim, Ki Hwan; Kim, Hee Soo; Bang, Joon; Naimi, Zulaikha; Bosch-Castells, Valérie; Boaz, Mark; Bouckenooghe, Alain

2014-01-01

A new live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) has been developed based on innovative technology to give protection against JE with an improved immunogenicity and safety profile. In this phase 3, observer-blind study, 274 children aged 12-24 months were randomized 1:1 to receive one dose of JE-CV (Group JE-CV) or the SA14-14-2 vaccine currently used to vaccinate against JE in the Republic of Korea (Group SA14-14-2). JE neutralizing antibody titers were assessed using PRNT50 before and 28 days after vaccination. The primary endpoint of non-inferiority of seroconversion rates on D28 was demonstrated in the Per Protocol analysis set as the difference between Group JE-CV and Group SA14-14-2 was 0.9 percentage points (95% confidence interval [CI]: -2.35; 4.68), which was above the required -10%. Seroconversion and seroprotection rates 28 days after administration of a single vaccine dose were 100% in Group JE-CV and 99.1% in Group SA14-14-2; all children except one (Group SA14-14-2) were seroprotected. Geometric mean titers (GMTs) increased in both groups from D0 to D28; GM of titer ratios were slightly higher in Group JE-CV (182 [95% CI: 131; 251]) than Group SA14-14-2 (116 [95% CI: 85.5, 157]). A single dose of JE-CV was well tolerated and no safety concerns were identified. In conclusion, a single dose of JE-CV or SA14-14-2 vaccine elicited a comparable immune response with a good safety profile. Results obtained in healthy Korean children aged 12-24 months vaccinated with JE-CV are consistent with those obtained in previous studies conducted with JE-CV in toddlers.

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

Šefl, Martin, E-mail: martin.sefl@gmail.com; Kyriakou, Ioanna; Emfietzoglou, Dimitris, E-mail: demfietz@cc.uoi.gr

Purpose: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. Methods: The instantaneous-uptake model of O’Donoghue [“The impact of tumor cell proliferation in radioimmunotherapy,” Cancer 73, 974–980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). Results: Surviving fractions aremore » calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1–24 h, extrapolated initial dose-rates 0.5–1 Gy h{sup −1}, and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy{sup −1}. It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. Conclusions: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.« less

Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA.

PubMed

Dayan, Gustavo H; Thakur, Manoj; Boaz, Mark; Johnson, Carol

2013-10-17

A candidate recombinant, live-attenuated, CYD tetravalent dengue vaccine (CYD-TDV) has recently demonstrated immunogenicity, efficacy and good tolerability. This study was performed to evaluate three CYD-TDV formulations in adults. This was a randomized, double-blind, multicenter, phase II trial. The vaccine formulations were: CYD-TDV 5555 (≈5log10 tissue culture infectious dose 50% [TCID50] of serotypes 1-4); CYD-TDV 5553 (≈5log10 TCID50 of serotypes 1-3 and ≈3log10 TCID50 of serotype 4); and CYD-TDV 4444 (≈4log10 TCID50 of serotypes 1-4). Vaccinations were administered at 0, 6 and 12 months. Immunogenicity was assessed using the plaque reduction neutralization test. In total, 260 individuals were enrolled. The 5555 formulation elicited a superior serotype 4 response versus the 5553 formulation, with seropositivity rates of 89.7% and 58.3%, respectively, after the second dose (between-group difference 31.4%; 95% confidence interval 18.2-43.2). After each of the three doses, seropositivity rates for serotypes 1-3 were numerically highest with CYD-TDV 5553 and lowest with the 4444 formulation; seropositivity rates for serotype 4 were similar with the 5555 and 4444 formulations, and much lower among recipients of CYD-TDV 5553. Geometric mean titers followed the same pattern as that seen with seropositivity rates. Safety/reactogenicity results were similar for all three vaccine formulations, although the percentage of participants reporting solicited injection site reactions was lower with CYD-TDV 4444 than with the other two formulations. All serious adverse events were unrelated to vaccination. Reducing the dose of serotype 4 antigen (5553 formulation) creates an imbalance in the immune response to CYD-TDV. Immune responses to CYD-TDV 5555 were slightly higher than to the 4444 formulation. Development of CYD-TDV 5555 has subsequently been pursued. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Dosimetric comparison of non-small cell lung cancer treatment with multi fields dynamic-MLC IMRT].

PubMed

Hao, Longying; Wang, Delin; Cao, Yujuan; Du, Fang; Cao, Feng; Liu, Chengwei

2015-05-19

We compared the dosimetric differences between the target and surrounding tissues/organs of the 5-field and 7,9-field (Hereinafter referred to as F5, F7, F9) treatment plan in non-small cell lung cancer (NSCLC) by the dynamic intensity-modulated radiotherapy (dIMRT), to provide reference for clinical application. Using Varian planning system (Eclipse 7.3), we randomly selected 30 cases of patients who received dIMRT to study, all patients were 5, 7, 9 fixed field dynamics intensity-modulated radiotherapy plans to meet the target prescription requirements (95% dose curve enveloping 100% of the PTV), by comparing dose-volume histogram DVH evaluation, and the maximum dose D(max), the minimum dose D(min), and the mean dose D(mean), and conformal index CI of PTV,organs at risk of spinal cord the maximum dose D(max), lung V(5), V(10), V(20), V(30), heart V(30) and esophageal V(50), V(60) of F5,F7 and F9 dIMRT plans,and compare the mu of the three treatment programs. The D(max), D(min) and D(mean) values of F5's PTV are (7 203 ± 128), (5 493 ± 331), (6 900 ± 138) cGy respectively; the D(max), D(min) and D(mean) values of F7's PTV are (7 304 ± 96), (5 526 ± 296), (6 976 ± 130) cGy respectively; and the D(max), D(min) and D(mean) values of F9's PTV are (7 356 ± 54), (5 578 ± 287), (7 019 ± 56) cGy respectively. The data shows that while we increased the numbers of fields, the isodose line surrounding the target area would also promote slightly. The conformity index CI of target became better with the increase of radiation fields. The whole lung V(5) and V(10) slightly became larger with increase of fields and the V(20) showed no significant difference in three models, V(30) of double lungs slightly decreased with the increase of fields. The above date was statistically meaningless (P > 0.05). With the increase of fields esophagus V(50) were reduced by 3% and 5% respectively, V(60) of the esophagus were reduced by 6% and 11%, the average dose reduced by 5% and 10% and spinal cord D(max) decreased by 9% and 13%. In the F7 and F9, heart V5 were lower than F5 plan by 11%, 19%. The mu of them were increased with the increase of radiation fields, Treatment time of F7 and F9 plan were longer by 15% and 25%. Through comparing the three fixed dIMRT plans, we could draw a conclusion that the three multi-field intensity-modulated radiotherapy in non-small cell lung cancer can meet the clinical target volume dose requirements. If the treatment is required to protect the patient's spinal cord, esophagus and heart, we can choose 7 or 9 fields. While other ordinary patients should be treated with 5 fields plan, to shorten the treatment time and improve the biological effects of lesions, and lower mu of plans to avoid unnecessary irradiation of normal tissues.

Booster and higher antigen doses of inactivated influenza vaccine in HIV-infected patients.

PubMed

Johnston, Jessica A; Tincher, Lindsey B; Lowe, Denise K

2013-12-01

To review the literature regarding booster or higher doses of influenza antigen for increasing immunogenicity of inactivated influenza vaccine (IIV) in HIV-infected patients. MEDLINE (1966 to September 2013) was searched using the terms immunize, influenza, vaccine, and HIV or AIDS in combination with two-dose, booster-dose, increased antigen, or high-dose. One trial of booster dosing with standard doses (SDs) of IIV, trivalent (IIV3); 2 trials of booster dosing with intermediate doses (ID) of H1N1 IIV or IIV3; and 1 trial of high-dose (HD) IIV3 were identified. Trials administering 2-dose, booster-dose, or increased antigen of influenza vaccine to patients with HIV were reviewed. Because adjuvanted IIV is not available and IIV, quadrivalent was recently approved in the United States, studies evaluating these vaccines were excluded. HIV-infected individuals are at high risk for influenza-related complications; however, vaccination with SD IIV may not confer optimal protection. It has been postulated that booster or higher doses of influenza antigen may lead to increased immunogenicity. When ID and SD or ID with boosters were evaluated in HIV-infected patients, significant increases in surrogate markers for influenza protection were not achieved. However, HD IIV3 did result in significant increases in seroprotective antibody levels, though 'clinical' influenza was not evaluated. Currently, evidence is insufficient to reach conclusions about the efficacy of booster dosing, ID, or HD influenza vaccine in HIV-infected patients. Trials evaluating booster or higher-antigen doses of IIV for 'clinical' influenza are necessary before routinely recommending for HIV-infected patients.

Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis.

PubMed

Liberato, Isabella Ramos de Oliveira; Lopes, Edmundo Pessoa de Almeida; Cavalcante, Maria Alina Gomes de Mattos; Pinto, Tiago Costa; Moura, Izolda Fernades; Loureiro Júnior, Luiz

2012-01-01

The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before the session. Taken together, the present data suggest that hemodilution could alter the serum levels of liver enzymes.

Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of antioxidant enzyme systems.

PubMed

Mandal, Tapas K; Das, Nildari S

2010-02-01

Intraperitoneal injection of cannabis extract at low doses (total doses ranging from 40 mg to 60 mg per mouse) induced adverse effect on testes and oxidative stress. At low doses, there was a significant increase in lipid peroxidation and decrease in testicular lipid content, but the effects were significantly less at higher doses and at the withdrawal of cannabis treatment (recovery dose). There was a marked decrease in antioxidant enzyme profiles (superoxide dismutase, catalase and glutathione peroxidase) and glutathione content at low doses, but these effects were higher at higher dose and at withdrawal of the treatment (recovery effect). Histology revealed significant shrinkage of tubular diameter and detrimental changes in seminiferous epithelium of testis with resulting lowered serum testosterone and pituitary gonadotropins (follicular stimulating [FSH] and luteinizing hormones [LH]) levels at low doses. But at higher doses and particularly at withdrawal of the treatment, regression of various germ cell layers of testes through the revival of testosterone hormone and pituitary gonadotropins (FSH and LH) were observed, indicating that recovery effects on testes became operative possibly through the corrective measure of endogenous testicular antioxidant enzymes profiles and pituitary gonadotropins hormones feedback mechanisms.

The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits.

PubMed

Wojakowski, W; Gminski, J; Siemianowicz, K; Goss, M; Machalski, M

2001-03-01

Aortic elastin turnover is significantly accelerated in atherosclerosis, partly because of activation of the renin-angiotensin-aldosterone system caused by hypercholesterolaemia. We postulated that angiotensin-converting enzyme inhibitors (ACE-I) prevent the aortic elastin loss in experimental hypercholesterolaemia. Two doses of ACE-I (captopril, enalapril and quinapril) were used: a dose equivalent to that applied to human subjects and a dose 10 times higher. We found that the increase in serum and aortic elastolytic activity in cholesterol-fed rabbits was prevented by high-dose captopril. The elastin content in aorta homogenates from cholesterol-fed rabbits was significantly decreased. The higher dose of captopril, but no other ACE-I, prevented this decrease in aortic elastin content. In cholesterol-fed rabbits the elastin-bound calcium content was significantly elevated. The higher doses of captopril and enalapril lowered the elastin-bound calcium content. In serum and aortic homogenates of cholesterol-fed rabbits, ACE activity was elevated by 15% and 77%, respectively. Both doses of captopril, enalapril and quinapril prevented this cholesterol-induced increase in serum and aortic ACE activity. We conclude that: 1) administration of captopril at doses 10 times higher than those used in humans prevents hypercholesterolaemia increased aortic elastin loss. 2) higher doses of captopril and enalapril prevent the hypercholesterolaemia-induced increase in aortic elastin-bound calcium.

Cranial CT with adaptive statistical iterative reconstruction: improved image quality with concomitant radiation dose reduction.

PubMed

Rapalino, O; Kamalian, Shervin; Kamalian, Shahmir; Payabvash, S; Souza, L C S; Zhang, D; Mukta, J; Sahani, D V; Lev, M H; Pomerantz, S R

2012-04-01

To safeguard patient health, there is great interest in CT radiation-dose reduction. The purpose of this study was to evaluate the impact of an iterative-reconstruction algorithm, ASIR, on image-quality measures in reduced-dose head CT scans for adult patients. Using a 64-section scanner, we analyzed 100 reduced-dose adult head CT scans at 6 predefined levels of ASIR blended with FBP reconstruction. These scans were compared with 50 CT scans previously obtained at a higher routine dose without ASIR reconstruction. SNR and CNR were computed from Hounsfield unit measurements of normal GM and WM of brain parenchyma. A blinded qualitative analysis was performed in 10 lower-dose CT datasets compared with higher-dose ones without ASIR. Phantom data analysis was also performed. Lower-dose scans without ASIR had significantly lower mean GM and WM SNR (P = .003) and similar GM-WM CNR values compared with higher routine-dose scans. However, at ASIR levels of 20%-40%, there was no statistically significant difference in SNR, and at ASIR levels of ≥60%, the SNR values of the reduced-dose scans were significantly higher (P < .01). CNR values were also significantly higher at ASIR levels of ≥40% (P < .01). Blinded qualitative review demonstrated significant improvements in perceived image noise, artifacts, and GM-WM differentiation at ASIR levels ≥60% (P < .01). These results demonstrate that the use of ASIR in adult head CT scans reduces image noise and increases low-contrast resolution, while allowing lower radiation doses without affecting spatial resolution.

Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study

PubMed Central

Sirich, Tammy L.; Fong, Kara D.; Plummer, Natalie S.; Shafi, Tariq; Hwang, Seungyoung; Banerjee, Tanushree; Zhu, Yunnuo; Powe, Neil R.; Hai, Xin; Hostetter, Thomas H.

2016-01-01

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (−9%; 95% confidence interval [95% CI], −2% to −15%), indoxyl sulfate (−11%; 95% CI, −6% to −15%), and methylguanidine (−22%; 95% CI, −18% to −27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea. In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy. PMID:27026365

Impact of age on the selection of nuclear cardiology stress protocols: The INCAPS (IAEA nuclear cardiology protocols) study.

PubMed

Al-Mallah, Mouaz H; Pascual, Thomas N B; Mercuri, Mathew; Vitola, João V; Karthikeyan, Ganesan; Better, Nathan; Dondi, Maurizio; Paez, Diana; Einstein, Andrew J

2018-05-15

There is growing concern about radiation exposure from nuclear myocardial perfusion imaging (MPI), particularly among younger patients who are more prone to develop untoward effects of ionizing radiation, and hence US and European professional society guidelines recommend age as a consideration in weighing radiation risk from MPI. We aimed to determine how patient radiation doses from MPI vary across age groups in a large contemporary international cohort. Data were collected as part of a global cross-sectional study of centers performing MPI coordinated by the International Atomic Energy Agency (IAEA). Sites provided information on each MPI study completed during a single week in March-April 2013. We compared across age groups laboratory adherence to pre-specified radiation-related best practices, radiation effective dose (ED; a whole-body measure reflecting the amount of radiation to each organ and its relative sensitivity to radiation's deleterious effects), and the proportion of patients with ED ≤ 9 mSv, a target level specified in guidelines. Among 7911 patients undergoing MPI in 308 laboratories in 65 countries, mean ED was 10.0 ± 4.5 mSv with slightly higher exposure among younger age groups (trend p value < 0.001). There was no difference in the proportion of patients with ED ≤ 9 mSv across age groups, or in adherence to best practices based on the median age of patients in a laboratory. In contemporary nuclear cardiology practice, the age of the patient appears not to impact protocol selection and radiation dose, contrary to professional society guidelines. Copyright © 2018. Published by Elsevier B.V.

Carcinogenic and Cocarcinogenic Effects of Radon and Radon Daughters in Rats.

PubMed Central

Monchaux, G; Morlier, JP; Morin, M; Chameaud, J; Lafuma, J; Masse, R

1994-01-01

It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures. Images p64-a Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. PMID:9719670

Cost-Effectiveness Analysis of Atorvastatin versus Rosuvastatin in Primary and Secondary Cardiovascular Prevention Populations in Brazil and Columbia.

PubMed

Mould-Quevedo, Joaquín F; Gutiérrez-Ardila, Magda Vianey; Ordóñez Molina, Jaime Eduardo; Pinsky, Brett; Vargas Zea, Nicolás

2014-12-01

Latin America has witnessed a marked increase in cardiovascular (CV) disease, the leading cause of death in many countries. The benefits of lipid-lowering therapy to reduce CV-related events are widely accepted. Clinical evidence suggests that rosuvastatin is associated with slightly greater reductions in low-density lipoprotein cholesterol levels than is atorvastatin at comparable doses. Rosuvastatin, however, is often priced at a premium. Our objective was to examine the cost-effectiveness of using atorvastatin versus rosuvastatin in reducing CV events in Brazil and Colombia using real-world prices. A global Markov cohort model of primary and secondary CV prevention was developed and adapted to Brazilian and Colombian settings. The risks and costs of major CV events and efficacy, adherence, and costs of statins were considered. Total gains in life-years, quality-adjusted life-years, major CV events avoided, and costs over the lifetime horizon were estimated. Several dose comparisons were considered. In the Colombian analyses, differences in drug costs between therapies were considerable while outcomes were similar. The incremental cost per quality-adjusted life-year gained for rosuvastatin versus atorvastatin was more than $700,000 and $200,000 in primary and secondary prevention, respectively. Brazilian analyses found lower incremental cost-effectiveness ratios for rosuvastatin at some dose comparisons due to similar pricing between statins. Sensitivity analyses revealed that changes in treatment efficacy and adherence had the largest impact on results. In primary and secondary CV prevention, the efficacy advantage of rosuvastatin was minimal, while its acquisition cost was higher, particularly in Colombia. The incremental cost-effectiveness ratios were, therefore, generally in favor of atorvastatin being the cost-effective option. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 1st communication: effects on general behavior and central nervous system.

PubMed

Arisawa, Hirohiko; Imai, Eiichi; Fujise, Nobuaki; Fukui, Kenji; Masunaga, Hiroaki

2002-01-01

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on general behavior and the central nervous system were investigated in mice, rats and cats. 1. General behavior: When SNI-2011 was administered orally to mice at 100 mg/kg, mydriasis, a decrease of spontaneous motor activity, tremor, convulsions, salivation, abnormal posture, abnormal gait, reduced grip strength and reduced response against external stimulating were observed, and 2 out of 6 animals died. At 10 mg/kg or lower, no particular sign was observed except mydriasis, which appeared to be caused via the peripheral muscarinic acetylcholine receptors. 2. Central nervous system: SNI-2011 had no effect on the motor coordination in mice. Hypothermia was observed in rats and reduced spontaneous motor activity, analgesia and enhanced maximum electroshock-induced convulsions were observed in mice after oral administration of 30 mg/kg SNI-2011. Slight increase in the rate of theta-wave band in the hippocampal EEG of rats and spinal multisynaptic reflexes in cats were observed after intravenous injection of 10 mg/kg SNI-2011. At an oral dose of 10 mg/kg, prolongation of thiopental-induced sleeping time in mice was observed. The prolongation of sleeping time was inhibited by a peripheral muscarinic antagonist. These results suggest that SNI-2011 has muscarinic effects on general behavior and the central nervous system at the doses approximately 10-fold higher than the effective doses needed for saliva secretion.

Biopharmaceutical characterisation of insulin and recombinant human growth hormone loaded lipid submicron particles produced by supercritical gas micro-atomisation.

PubMed

Salmaso, Stefano; Bersani, Sara; Elvassore, Nicola; Bertucco, Alberto; Caliceti, Paolo

2009-09-08

Homogeneous dispersions of insulin and recombinant human growth hormone (rh-GH) in tristearin/phosphatidylcholine/PEG mixtures (1.3:1.3:0.25:0.15 w/w ratio) were processed by supercritical carbon dioxide gas micro-atomisation to produce protein-loaded lipid particles. The process yielded spherical particles, with a 197+/-94 nm mean diameter, and the insulin and rh-GH recovery in the final product was 57+/-8% and 48+/-5%, respectively. In vitro, the proteins were slowly released for about 70-80 h according to a diffusive mechanism. In vivo, the insulin and glucose profiles in plasma obtained by subcutaneous administration of a dose of particles containing 2 microg insulin to diabetic mice overlapped that obtained with 2 microg of insulin in solution. Administration of a dose of particles containing 5 microg insulin resulted in faster and longer glycaemia reduction. Oral administration of 20 and 50 microg insulin equivalent particles produced a significant hypoglycaemic effect. The glucose levels decreased since 2h after administration, reaching about 50% and 70% glucose reduction in 1-2h with the lower and higher dose, respectively. As compared to subcutaneous administration, the relative pharmacological bioavailability obtained with 20 and 50 microg equivalent insulin particles was 7.7% and 6.7%, respectively. Daily subcutaneous administration of 40 microg of rh-GH-loaded particles to hypophysectomised rats induced similar body weight increase as 40 microg rh-GH in solution. The daily oral administration of 400 microg rh-GH equivalent particles elicited a slight body weight increase, which corresponded to a relative pharmacological bioavailability of 3.4% compared to subcutaneous administration.

Microdistribution of fluorescently-labeled monoclonal antibody in a peritoneal dissemination model of ovarian cancer

NASA Astrophysics Data System (ADS)

Kosaka, Nobuyuki; Ogawa, Mikako; Paik, David S.; Paik, Chang H.; Choyke, Peter L.; Kobayashi, Hisataka

2010-02-01

The microdistribution of therapeutic monoclonal antibodies within a tumor is important for determining clinical response. Nonuniform microdistribution predicts therapy failure. Herein, we developed a semiquantitative method for measuring microdistribution of an antibody within a tumor using in situ fluorescence microscopy and sought to modulate the microdistribution by altering the route and timing of antibody dosing. The microdistribution of a fluorescently-labeled antibody, trastuzumab (50-μg and 150-μg intraperitoneal injection (i.p.), and 100-μg intravenous injection (i.v.)) was evaluated in a peritoneal dissemination mouse model of ovarian cancer. In addition, we evaluated the microdistribution of concurrently-injected (30-μg i.p. and 100-μg i.v.) or serial (two doses of 30-μg i.p.) trastuzumab using in situ multicolor fluorescence microscopy. After the administration of 50-μg i.p. and 100-μg i.v. trastuzumab fluorescence imaging showed no significant difference in the central to peripheral signal ratio (C/P ratio) and demonstrated a peripheral-dominant accumulation, whereas administration of 150-μg i.p. trastuzumab showed relatively uniform, central dominant accumulation. With concurrent-i.p.-i.v. injections trastuzumab showed slightly higher C/P ratio than concurrently-injected i.p. trastuzumab. Moreover, in the serial injection study, the second injection of trastuzumab distributed more centrally than the first injection, while no difference was observed in the control group. Our results suggest that injection routes do not affect the microdistribution pattern of antibody in small peritoneal disseminations. However, increasing the dose results in a more uniform antibody distribution within peritoneal nodules. Furthermore, the serial i.p. injection of antibody can modify the microdistribution within tumor nodules. This work has implications for the optimal delivery of antibody based cancer therapies.