Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

PubMed

Wang, Li-hong; Wang, Xu; Yu, Xi-zhong; Xu, Wen-ting

2016-02-01

To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

Effect of Two Different Doses of Dexmedetomidine on Stress Response in Laparoscopic Pyeloplasty: A Randomized Prospective Controlled Study.

PubMed

Shamim, Rafat; Srivastava, Shashi; Rastogi, Amit; Kishore, Kamal; Srivastava, Aneesh

2017-01-01

Clonidine, opioids, β-blockers, and dexmedetomidine have been tried to attenuate stress responses during laparoscopic surgery. We evaluated the efficacy of dexmedetomidine in two different doses in attenuating stress responses on patients undergoing laparoscopic pyeloplasty. Ninety patients were assigned to one of the three groups: Group A, Group B, and Group C. Group B received dexmedetomidine 1 mcg/kg as loading dose, followed by 0.7 mcg/kg/h for maintenance; Group C received dexmedetomidine 0.7 mcg/kg as a loading dose, followed by 0.5 mcg/kg/h for maintenance. Group A received normal saline. Stress responses were assessed by the variations in heart rate (HR), mean arterial pressure (MAP), blood glucose levels, and serum cortisol levels. One-way analysis of variance test was applied. Multiple comparisons between groups were done with post hoc Bonferroni test. The HR and MAP were found to be higher in Group A. The difference was statistically significant ( P < 0.05) during intubation, carbon dioxide insufflation, and extubation when compared with Groups B and C. Blood glucose levels at postintubation and at extubation were higher in Group A and statistically significant ( P < 0.05) when compared with Groups B and C. Serum cortisol levels at postintubation, during midsurgery, and 2 h after extubation were higher in Group A and statistically significant ( P < 0.05) when compared with Groups B and C. However, HR, MAP, blood glucose levels, and serum cortisol levels were similar in dexmedetomidine groups. Dexmedetomidine decreases stress response and provides good condition for maintenance of anesthesia. Dexmedetomidine when used in lower dose in Group C decreases stress response comparable to higher dose in Group B.

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

PubMed

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

2016-02-01

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

Comparison of internal dose estimates obtained using organ-level, voxel S value, and Monte Carlo techniques

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

Grimes, Joshua, E-mail: grimes.joshua@mayo.edu; Celler, Anna

2014-09-15

Purpose: The authors’ objective was to compare internal dose estimates obtained using the Organ Level Dose Assessment with Exponential Modeling (OLINDA/EXM) software, the voxel S value technique, and Monte Carlo simulation. Monte Carlo dose estimates were used as the reference standard to assess the impact of patient-specific anatomy on the final dose estimate. Methods: Six patients injected with{sup 99m}Tc-hydrazinonicotinamide-Tyr{sup 3}-octreotide were included in this study. A hybrid planar/SPECT imaging protocol was used to estimate {sup 99m}Tc time-integrated activity coefficients (TIACs) for kidneys, liver, spleen, and tumors. Additionally, TIACs were predicted for {sup 131}I, {sup 177}Lu, and {sup 90}Y assuming themore » same biological half-lives as the {sup 99m}Tc labeled tracer. The TIACs were used as input for OLINDA/EXM for organ-level dose calculation and voxel level dosimetry was performed using the voxel S value method and Monte Carlo simulation. Dose estimates for {sup 99m}Tc, {sup 131}I, {sup 177}Lu, and {sup 90}Y distributions were evaluated by comparing (i) organ-level S values corresponding to each method, (ii) total tumor and organ doses, (iii) differences in right and left kidney doses, and (iv) voxelized dose distributions calculated by Monte Carlo and the voxel S value technique. Results: The S values for all investigated radionuclides used by OLINDA/EXM and the corresponding patient-specific S values calculated by Monte Carlo agreed within 2.3% on average for self-irradiation, and differed by as much as 105% for cross-organ irradiation. Total organ doses calculated by OLINDA/EXM and the voxel S value technique agreed with Monte Carlo results within approximately ±7%. Differences between right and left kidney doses determined by Monte Carlo were as high as 73%. Comparison of the Monte Carlo and voxel S value dose distributions showed that each method produced similar dose volume histograms with a minimum dose covering 90% of the volume (D90) agreeing within ±3%, on average. Conclusions: Several aspects of OLINDA/EXM dose calculation were compared with patient-specific dose estimates obtained using Monte Carlo. Differences in patient anatomy led to large differences in cross-organ doses. However, total organ doses were still in good agreement since most of the deposited dose is due to self-irradiation. Comparison of voxelized doses calculated by Monte Carlo and the voxel S value technique showed that the 3D dose distributions produced by the respective methods are nearly identical.« less

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

PubMed

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or 150 IU once daily [QD], or 150 IU every other day [QAD], 10 subjects each) and 27 subjects received 150 IU Gonal-f, 150 IU Bravelle, or placebo for 7 days (11/10/6 subjects). Blood samples for measuring PK as well as PD parameters were collected systematically before, during and after dosing. Adverse events (AEs) and other relevant safety parameters were recorded. Data were summarized using descriptive statistics. The single- and multiple-dose PK parameters maximum concentration (Cmax) and area under the concentration-time curve (AUC0-last) increased in a linear fashion with increasing dose levels of follitropin epsilon. Follitropin epsilon showed PK characteristics comparable to the comparators indicating that well established treatment schemes could be applied. There was a dose-response effect of single and multiple doses of follitropin epsilon on follicular growth, which was shown for the biomarker inhibin B as well as for the mean number and size of follicles. Multiple doses of 75 IU follitropin epsilon given daily, as well as 150 IU follitropin epsilon every second day, showed a follicle growth comparable with 150 IU Gonal-f given daily, while in case of daily administration of 150 IU Bravelle only weak follicle stimulation was observed. Multiple doses of 150 IU follitropin epsilon induced a much higher follicle growth compared to the same dose of Gonal-f. All single and multiple follitropin epsilon doses tested were safe and well tolerated, and overall there were no relevant differences between follitropin epsilon and the comparators in terms of safety. The average number of AEs increased with increasing dose levels. No clinically relevant abnormalities were reported for any of the other safety parameters assessed. No follitropin epsilon anti-drug antibodies were observed. The studies were conducted as a single-blind design. Hormone levels or other parameters assessed in serum are generally not considered as being subject to bias. Other assessments directly performed by the investigators, such as transvaginal ultrasound assessments, may have been subject to personal bias. No prospective calculations of statistical power had been made, as is common practice for first in human and early phase I studies in healthy volunteers. These early development studies showed that follitropin epsilon exhibits comparable PK characteristics, as well as inducing stronger PD effects in terms of follicle growth and serum inhibin B, than the comparators. Follitropin epsilon induced a dose-dependent increase in follicular growth. The results warrant further studies with this new fully human recombinant FSH. The studies were sponsored by GLYCOTOPE GmbH, Berlin, Germany. K.A-E. is an employee of QPS-Netherlands, B.V., which received funding for the studies from Glycotope GmbH; I.D. and C.K. are employees of Dinox B.V., which received funding for the studies from Glycotope GmbH; L.S. and S.G. are employees and shareholders of Glycotope GmbH; B.D. and K.E. are employees of Glycotope GmbH. www.clinicaltrials.gov: NCT01354886 (single-dose); NCT01477073 (multiple-dose). The single-dose trial was registered on 11 May 2011 while the multiple-dose trial was registered on 09 November 2011. First subject was enroled in the single-dose trial in 27 April 2011 and in the multiple-dose trial in 02 October 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

The Effects of Aloe Vera on TNF-a Levels, the Percentage of Nk Cells and Th 17 Cells in Rat That Received Izoniazid and Rifampycin.

PubMed

Mawarti, Herin; Rajin, Mukhamad; Asumta, Zulfikar

2017-10-01

The present study was undertaken to investigate the hepatoprotective effect of Aloe vera against side effect of antituberculosis drug. Twenty-five rats will be divided into five groups, namely the control group (without any treatment), the group of rats treated with anti-tuberculosis drugs, and a group of rats were treated antituberculosis drugs and got Aloe vera extract at a dose of 40; 80; and 120 mg/kg body weight. Antituberculosis drugs are isoniazid and rifampicin a dose of 50 mg/kg body weight. Antituberculosis treated group showed significantly increase levels of TNF-a, the percentage of NK cells and the number of Th17 cells compared with the control group ( p < 0.05). All doses of Aloe vera reduce levels of TNF-a compared with the antituberculosis group ( p < 0.05), although it has not yet reached levels comparable to the control group ( p > 0.05). Aloe vera at first and the third dose lower the number of NK cells compared to the antituberculosis group, although it has not yet reached a significant difference ( p > 0.05). The first dose of Aloe vera was significantly decreased the percentage of Th17 cells compared to the antituberculosis drug group ( p < 0.05), although it has not yet reached levels comparable to the control group ( p > 0.05). It was concluded that administration of Aloe vera can suppress the production of TNF-a and the percentage of Th17 cells as a result of antituberculosis drug administration. Thus, Aloe vera can be a useful alternative to natural materials in the successful treatment of tuberculosis through the inhibition of side effect.

Salicylic acid plasma levels following multiple doses of Norgesic Forte and aspirin.

PubMed

Harrison, L I; Kehe, C R; Goldlust, M B; Kvam, D C; Bianchine, J R

1983-01-01

Plasma salicyclic acid levels from the recommended multiple dose regimen of Norgesic Forte (orphenadrine citrate, aspirin, and caffeine) were compared to those from an equivalent multiple dose regimen of aspirin alone in 24 volunteers. The drugs were administered double-blind so that side effects could also be compared. No statistically significant differences were found between Norgesic Forte and aspirin in peak or trough levels, time to peak level, area under the curve, or mean steady-state level of salicylic acid. Mean steady-state levels averaged 154 +/- 46 (+/- SD) and 152 +/- 49 micrograms/ml on days 5 and 10 following Norgesic Forte versus 161 +/- 49 and 154 +/- 47 micrograms/ml following aspirin. Thus, the aspirin in Norgesic Forte provides an anti-inflammatory amount of salicylic acid equivalent to that of plain aspirin. There was no evidence that the combination of orphenadrine citrate, caffeine, and aspirin in Norgesic Forte caused increased or unusual side effects compared with aspirin alone.

Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer?

PubMed

Kopelman, Tammy R; O'Neill, Patrick J; Pieri, Paola G; Salomone, Jeffrey P; Hall, Scott T; Quan, Asia; Wells, Jordan R; Pressman, Melissa S

2013-12-01

Inadequate anti-factor Xa levels and increased venous thromboembolic events occur in trauma patients receiving standard prophylactic enoxaparin dosing. The aim of this study was to test the hypothesis that higher dosing (40 mg twice daily) would improve peak anti-Xa levels and decrease venous thromboembolism. A retrospective review was performed of trauma patients who received prophylactic enoxaparin and peak anti-Xa levels over 27 months. Patients were divided on the basis of dose: group A received 30 mg twice daily, and group B received 40 mg twice daily. Demographics and rates of venous thromboembolism were compared between dose groups and patients with inadequate or adequate anti-Xa levels. One hundred twenty-four patients were included, 90 in group A and 34 in group B. Demographics were similar, except that patients in group B had a higher mean body weight. Despite this, only 9% of group B patients had inadequate anti-Xa levels, compared with 33% of those in group A (P = .01). Imaging studies were available in 69 patients and revealed 8 venous thromboembolic events (P = NS, group A vs group B) with significantly more venous thromboembolic events occurring in patients with low anti-Xa levels (P = .02). Although higher dosing of enoxaparin led to improved anti-Xa levels, this did not equate to a statistical decrease in venous thromboembolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison of 2-Dose and 3-Dose 9-Valent Human Papillomavirus Vaccine Schedules in the United States: A Cost-effectiveness Analysis.

PubMed

Laprise, Jean-François; Markowitz, Lauri E; Chesson, Harrell W; Drolet, Mélanie; Brisson, Marc

2016-09-01

A recent clinical trial using the 9-valent human papillomavirus virus (HPV) vaccine has shown that antibody responses after 2 doses are noninferior to those after 3 doses, suggesting that 2 and 3 doses may have comparable vaccine efficacy. We used an individual-based transmission-dynamic model to compare the population-level effectiveness and cost-effectiveness of 2- and 3-dose schedules of 9-valent HPV vaccine in the United States. Our model predicts that if 2 doses of 9-valent vaccine protect for ≥20 years, the additional benefits of a 3-dose schedule are small as compared to those of 2-dose schedules, and 2-dose schedules are likely much more cost-efficient than 3-dose schedules. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Different Doses of Tripterygium Glycosides in the Treatment of Diabetic Nephropathy: Effects on Blood Lipids.

PubMed

Wang, Wei

2018-06-07

The aim of this study was to investigate the therapeutic effect of different doses of tripterygium glycosides (TG) in the treatment of diabetic nephropathy (DN). The effect of TG on blood lipids and safety were also evaluated. Sixty patients with type 2 DN were randomly divided into three groups (n=20 per group): low-dose (30 mg/day TG), double-dose (60 mg/day TG) and control (placebo) groups, all three times daily for 6 months. The levels of triglycerides, total cholesterol, urinary protein, plasma albumin and serum tumour necrosis factor (TNF)-α were compared between the three groups. After treatment, urinary protein and TNF-α level significantly decreased in patients in the treatment groups, compared with the control group. This decrease was significantly larger in the double-dose group than in the low-dose group. However, there was no significant decrease in triglycerides and total cholesterol in the two treatment groups. Furthermore, plasma albumin was lower in the treatment groups than in the control group. The double dose of TG has improved clinical efficacy, compared with the low dose, and the same safety profile. © 2018 The Author(s). Published by S. Karger AG, Basel.

Does Digital Video Advertising Increase Population-Level Reach of Multimedia Campaigns? Evidence From the 2013 Tips From Former Smokers Campaign

PubMed Central

Shafer, Paul R; Rodes, Robert; Kim, Annice; Hansen, Heather; Patel, Deesha; Coln, Caryn; Beistle, Diane

2016-01-01

Background Federal and state public health agencies in the United States are increasingly using digital advertising and social media to promote messages from broader multimedia campaigns. However, little evidence exists on population-level campaign awareness and relative cost efficiencies of digital advertising in the context of a comprehensive public health education campaign. Objective Our objective was to compare the impact of increased doses of digital video and television advertising from the 2013 Tips From Former Smokers (Tips) campaign on overall campaign awareness at the population level. We also compared the relative cost efficiencies across these media platforms. Methods We used data from a large national online survey of approximately 15,000 US smokers conducted in 2013 immediately after the conclusion of the 2013 Tips campaign. These data were used to compare the effects of variation in media dose of digital video and television advertising on population-level awareness of the Tips campaign. We implemented higher doses of digital video among selected media markets and randomly selected other markets to receive similar higher doses of television ads. Multivariate logistic regressions estimated the odds of overall campaign awareness via digital or television format as a function of higher-dose media in each market area. All statistical tests used the .05 threshold for statistical significance and the .10 level for marginal nonsignificance. We used adjusted advertising costs for the additional doses of digital and television advertising to compare the cost efficiencies of digital and television advertising on the basis of costs per percentage point of population awareness generated. Results Higher-dose digital video advertising was associated with 94% increased odds of awareness of any ad online relative to standard-dose markets (P<.001). Higher-dose digital advertising was associated with a marginally nonsignificant increase (46%) in overall campaign awareness regardless of media format (P=.09). Higher-dose television advertising was associated with 81% increased odds of overall ad awareness regardless of media format (P<.001). Increased doses of television advertising were also associated with significantly higher odds of awareness of any ad on television (P<.001) and online (P=.04). The adjusted cost of each additional percentage point of population-level reach generated by higher doses of advertising was approximately US $440,000 for digital advertising and US $1 million for television advertising. Conclusions Television advertising generated relatively higher levels of overall campaign awareness. However, digital video was relatively more cost efficient for generating awareness. These results suggest that digital video may be used as a cost-efficient complement to traditional advertising modes (eg, television), but digital video should not replace television given the relatively smaller audience size of digital video viewers. PMID:27627853

Does Digital Video Advertising Increase Population-Level Reach of Multimedia Campaigns? Evidence From the 2013 Tips From Former Smokers Campaign.

PubMed

Davis, Kevin C; Shafer, Paul R; Rodes, Robert; Kim, Annice; Hansen, Heather; Patel, Deesha; Coln, Caryn; Beistle, Diane

2016-09-14

Federal and state public health agencies in the United States are increasingly using digital advertising and social media to promote messages from broader multimedia campaigns. However, little evidence exists on population-level campaign awareness and relative cost efficiencies of digital advertising in the context of a comprehensive public health education campaign. Our objective was to compare the impact of increased doses of digital video and television advertising from the 2013 Tips From Former Smokers (Tips) campaign on overall campaign awareness at the population level. We also compared the relative cost efficiencies across these media platforms. We used data from a large national online survey of approximately 15,000 US smokers conducted in 2013 immediately after the conclusion of the 2013 Tips campaign. These data were used to compare the effects of variation in media dose of digital video and television advertising on population-level awareness of the Tips campaign. We implemented higher doses of digital video among selected media markets and randomly selected other markets to receive similar higher doses of television ads. Multivariate logistic regressions estimated the odds of overall campaign awareness via digital or television format as a function of higher-dose media in each market area. All statistical tests used the .05 threshold for statistical significance and the .10 level for marginal nonsignificance. We used adjusted advertising costs for the additional doses of digital and television advertising to compare the cost efficiencies of digital and television advertising on the basis of costs per percentage point of population awareness generated. Higher-dose digital video advertising was associated with 94% increased odds of awareness of any ad online relative to standard-dose markets (P<.001). Higher-dose digital advertising was associated with a marginally nonsignificant increase (46%) in overall campaign awareness regardless of media format (P=.09). Higher-dose television advertising was associated with 81% increased odds of overall ad awareness regardless of media format (P<.001). Increased doses of television advertising were also associated with significantly higher odds of awareness of any ad on television (P<.001) and online (P=.04). The adjusted cost of each additional percentage point of population-level reach generated by higher doses of advertising was approximately US $440,000 for digital advertising and US $1 million for television advertising. Television advertising generated relatively higher levels of overall campaign awareness. However, digital video was relatively more cost efficient for generating awareness. These results suggest that digital video may be used as a cost-efficient complement to traditional advertising modes (eg, television), but digital video should not replace television given the relatively smaller audience size of digital video viewers.

A national patient dose survey and setting of reference levels for interventional radiology in Bulgaria.

PubMed

Zotova, R; Vassileva, J; Hristova, J; Pirinen, M; Järvinen, H

2012-06-01

A national study on patient dose values in interventional radiology and cardiology was performed in order to assess current practice in Bulgaria, to estimate the typical patient doses and to propose reference levels for the most common procedures. Fifteen units and more than 1,000 cases were included. Average values of the measured parameters for three procedures-coronary angiography (CA), combined procedure (CA + PCI) and lower limb arteriography (LLA)--were compared with data published in the literature. Substantial variations were observed in equipment and procedure protocols used. This resulted in variations in patient dose: air-kerma area product ranges were 4-339, 6-1,003 and 0.2-288 Gy cm(2) for CA, CA + PCI and LLA respectively. Reference levels for air kerma-area product were proposed: 40 Gy cm(2) for CA, 140 Gy cm(2) for CA + PCI and 45 Gy cm(2) for LLA. Auxiliary reference intervals were proposed for other dose-related parameters: fluoroscopy time, number of images and entrance surface air kerma rate in fluoroscopy and cine mode. There is an apparent necessity for improvement in the classification of peripheral procedures and for standardisation of the protocols applied. It is important that patient doses are routinely recorded and compared with reference levels. • Patient doses in interventional radiology are high and vary greatly • Better standardisation of procedures and techniques is needed to improve practice • Dose reference levels for most common procedures are proposed.

Quantitative Image Quality and Histogram-Based Evaluations of an Iterative Reconstruction Algorithm at Low-to-Ultralow Radiation Dose Levels: A Phantom Study in Chest CT

PubMed Central

Lee, Ki Baek

2018-01-01

Objective To describe the quantitative image quality and histogram-based evaluation of an iterative reconstruction (IR) algorithm in chest computed tomography (CT) scans at low-to-ultralow CT radiation dose levels. Materials and Methods In an adult anthropomorphic phantom, chest CT scans were performed with 128-section dual-source CT at 70, 80, 100, 120, and 140 kVp, and the reference (3.4 mGy in volume CT Dose Index [CTDIvol]), 30%-, 60%-, and 90%-reduced radiation dose levels (2.4, 1.4, and 0.3 mGy). The CT images were reconstructed by using filtered back projection (FBP) algorithms and IR algorithm with strengths 1, 3, and 5. Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were statistically compared between different dose levels, tube voltages, and reconstruction algorithms. Moreover, histograms of subtraction images before and after standardization in x- and y-axes were visually compared. Results Compared with FBP images, IR images with strengths 1, 3, and 5 demonstrated image noise reduction up to 49.1%, SNR increase up to 100.7%, and CNR increase up to 67.3%. Noteworthy image quality degradations on IR images including a 184.9% increase in image noise, 63.0% decrease in SNR, and 51.3% decrease in CNR, and were shown between 60% and 90% reduced levels of radiation dose (p < 0.0001). Subtraction histograms between FBP and IR images showed progressively increased dispersion with increased IR strength and increased dose reduction. After standardization, the histograms appeared deviated and ragged between FBP images and IR images with strength 3 or 5, but almost normally-distributed between FBP images and IR images with strength 1. Conclusion The IR algorithm may be used to save radiation doses without substantial image quality degradation in chest CT scanning of the adult anthropomorphic phantom, down to approximately 1.4 mGy in CTDIvol (60% reduced dose). PMID:29354008

Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel.

PubMed

Hajsadeghi, Shokoufeh; Chitsazan, Mandana; Chitsazan, Mitra; Salehi, Negar; Amin, Ahmad; Bidokhti, Arash Amin; Babaali, Nima; Bordbar, Armin; Hejrati, Maral; Moghadami, Samar

2016-01-01

A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix(®); loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient(®); loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62-23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25-22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI.

Ampicillin levels in sputum, serum, and saliva

PubMed Central

Stewart, Sheila M.; Fisher, Mary; Young, Joy E.; Lutz, W.

1970-01-01

The ampicillin levels in sputum, serum, and saliva from 40 patients receiving a dose of 250 mg., 26 patients receiving a dose of 500 mg., and 11 patients receiving a dose of 1 g. were estimated. The ampicillin was given orally four times daily. The 1-2 hour and 2-3 hour sputum levels were similar in individual patients. There was no difference in the range or mean sputum or saliva levels between specimens from patients receiving 250 mg. and 500 mg., but the levels were significantly higher after the 1 g. dose. The mean serum level showed a small increase after 500 mg. ampicillin as compared with the 250 mg. dose and a big increase after the 1 g. dose: only the latter difference was significant. The sputum levels were approximately 30 to 40 times lower than the corresponding serum levels. There was considerable scatter in the sputum level for any level of ampicillin in the serum: in only two of the 1-2 hour sputum specimens was there no detectable ampicillin. There was no correlation between the sputum levels and either the body weight or the dose in milligrams per kilogram. There was no evidence that corticosteroids or diuretics affected the sputum level. It was not possible to demonstrate any relationship between the purulence of the sputum and the level of ampicillin after doses of 250 mg. or 500 mg., but higher levels were found in the more purulent specimens after 1 g. doses. PMID:4318047

Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

PubMed Central

Durcan, Laura; Clarke, William A; Magder, Laurence S.; Petri, Michelle

2015-01-01

OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =<0.0001). CONCLUSION There was a trend towards higher disease activity with lower hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol.

PubMed

Matsui, Sumika; Yasui, Toshiyuki; Kasai, Kana; Keyama, Kaoru; Yoshida, Kanako; Kato, Takeshi; Uemura, Hirokazu; Kuwahara, Akira; Matsuzaki, Toshiya; Irahara, Minoru

2017-07-01

Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 μg) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 μg) as a transdermal group. In addition, the women received dydrogesterone continuously (5 mg) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin-antithrombin complex and plasmin-α2 plasmin inhibitor complex were measured before and 3 months after the start of treatment. SHBG was significantly increased at 3 months in the oral ultra-low-dose group, but not in the transdermal group. However, percent changes in SHBG were not significantly different between the two groups. In both groups, ATIII was significantly decreased at 3 months. In conclusion, even ultra-low-dose oestradiol orally increases circulating SHBG level. However, the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. Impact statement Oral oestrogen replacement therapy increases production of SHBG which may be related to increase in VTE risk. However, the effect of oral ultra-low-dose oestradiol on SHBG has not been clarified. Even ultra-low-dose oestradiol orally increases circulating SHBG levels, but the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. VTE risk in women receiving oral ultra-low-dose oestradiol may be comparable to that in women receiving transdermal oestradiol.

Fewer doses of HPV vaccine result in immune response similar to three-dose regimen

Cancer.gov

NCI scientists report that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody levels against two of the most carcinogenic types of HPV (16 and 18), compared to a standard three dose regimen.

Improving spot-scanning proton therapy patient specific quality assurance with HPlusQA, a second-check dose calculation engine.

PubMed

Mackin, Dennis; Li, Yupeng; Taylor, Michael B; Kerr, Matthew; Holmes, Charles; Sahoo, Narayan; Poenisch, Falk; Li, Heng; Lii, Jim; Amos, Richard; Wu, Richard; Suzuki, Kazumichi; Gillin, Michael T; Zhu, X Ronald; Zhang, Xiaodong

2013-12-01

The purpose of this study was to validate the use of HPlusQA, spot-scanning proton therapy (SSPT) dose calculation software developed at The University of Texas MD Anderson Cancer Center, as second-check dose calculation software for patient-specific quality assurance (PSQA). The authors also showed how HPlusQA can be used within the current PSQA framework. The authors compared the dose calculations of HPlusQA and the Eclipse treatment planning system with 106 planar dose measurements made as part of PSQA. To determine the relative performance and the degree of correlation between HPlusQA and Eclipse, the authors compared calculated with measured point doses. Then, to determine how well HPlusQA can predict when the comparisons between Eclipse calculations and the measured dose will exceed tolerance levels, the authors compared gamma index scores for HPlusQA versus Eclipse with those of measured doses versus Eclipse. The authors introduce the αβγ transformation as a way to more easily compare gamma scores. The authors compared measured and calculated dose planes using the relative depth, z∕R × 100%, where z is the depth of the measurement and R is the proton beam range. For relative depths than less than 80%, both Eclipse and HPlusQA calculations were within 2 cGy of dose measurements on average. When the relative depth was greater than 80%, the agreement between the calculations and measurements fell to 4 cGy. For relative depths less than 10%, the Eclipse and HPlusQA dose discrepancies showed a negative correlation, -0.21. Otherwise, the correlation between the dose discrepancies was positive and as large as 0.6. For the dose planes in this study, HPlusQA correctly predicted when Eclipse had and had not calculated the dose to within tolerance 92% and 79% of the time, respectively. In 4 of 106 cases, HPlusQA failed to predict when the comparison between measurement and Eclipse's calculation had exceeded the tolerance levels of 3% for dose and 3 mm for distance-to-agreement. The authors found HPlusQA to be reasonably effective (79% ± 10%) in determining when the comparison between measured dose planes and the dose planes calculated by the Eclipse treatment planning system had exceeded the acceptable tolerance levels. When used as described in this study, HPlusQA can reduce the need for patient specific quality assurance measurements by 64%. The authors believe that the use of HPlusQA as a dose calculation second check can increase the efficiency and effectiveness of the QA process.

The value of fixed rasburicase dosing versus weight-based dosing in the treatment and prevention of tumor lysis syndrome.

PubMed

Boutin, Alyssa; Blackman, Alison; O'Sullivan, David M; Forcello, Nicholas

2018-01-01

Background Rasburicase is a recombinant urate oxidase enzyme used for the treatment and prevention of tumor lysis syndrome. Our objective was to assess the efficacy of indication-based, low-dose rasburicase administration compared to the Food and Drug Administration-approved weight-based dosing. Methods This was a retrospective cohort study utilizing data from a tertiary medical center including patients admitted from 2012 to 2016, who received at least one dose of rasburicase. The primary outcome was achieving a uric acid level less than 7.5 mg/dl after a single dose of rasburicase in the preprotocol (Food and Drug Administration-approved weight-based dosing) and postprotocol (indication-based, low-dose) groups. Secondary outcomes included the change in uric acid levels between the pre- and postprotocol groups, adherence to the new institutional protocol, need for repeat rasburicase doses, and a cost analysis. Results Sixty-four patients received at least one dose of rasburicase between 1 January 2012 and 1 December 2016. Twenty-seven (79.4%) doses in the preprotocol group and 28 (82.4%) doses in the postprotocol group successfully achieved a uric acid level less than 7.5 mg/dl after a single dose of rasburicase (p=1.000). The average total monthly cost of rasburicase was reduced by 59.9% after adoption of the new protocol. Conclusions Indication-based, low-dose rasburicase displayed significantly more value when compared to weight-based dosing as shown by achieving cost savings without compromising clinical efficacy.

Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

PubMed Central

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2015-01-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. PMID:25391313

Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway.

PubMed

Zhao, Jing; Liu, Ge-Li; Wei, Ying; Jiang, Li-Hong; Bao, Peng-Li; Yang, Qing-Yan

2016-09-01

The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high‑fat‑diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3‑kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate‑1 (IRS‑1), glucose transporter type 4 (GLUT‑4), nuclear factor (NF)‑κB and tumor necrosis factor (TNF)‑α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high‑fat‑diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high‑dose testosterone treatment. Low‑dose testosterone induced upregulation in the levels of IRS‑1, AKT, GLUT‑4 protein, NF‑κB, TNF‑α and PI3K, compared with those in the animals fed a high‑fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT, GLUT‑4, NF‑κB, TNF‑α and PI3K. Compared with the rats in the high‑fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS‑1, AKT and GLUT‑4, and downregulation of the mRNA levels of NF‑κB, TNF‑α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT and GLUT‑4, and marked increases in the mRNA levels of NF‑κB, TNF‑α and PI3K, compared with the low dose group. Castration induced marked disorders of glucolipid metabolism and vascular injuries in the pubescent male rats. Low‑dose testosterone treatment was found to ameliorate the vascular damage caused by castration via the PI3K/AKT signaling pathway.

Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

PubMed

Strange, P; Schwartz, S L; Graf, R J; Polvino, W; Weston, I; Marbury, T C; Huang, W C; Goldberg, R B

1999-01-01

The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Different doses of partial liver irradiation promotes hepatic regeneration in rat

PubMed Central

Liu, Ying; Shi, Changzheng; Cui, Meng; Yang, Zhenhua; Gan, Danhui; Wang, Yiming

2015-01-01

The aim of this study is to investigate whether partial liver irradiation promotes hepatic regeneration in rat. Left-half liver of rat was irradiated to 10 Gy, and the Right-half to 0, 5, 10 and 15 Gy, respectively. Then, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were evaluated on 0 day, 15-day, 30-day, 45-day and 60-day after liver irradiation. Next, the serum HGF, NF-κB and TGF-β1 levels were also analyzed on 60-day after liver irradiation. Lastly, the cyclinD1 protein expression was appraised by western blots on 60-day after liver irradiation. ALT, AST and ALP levels were reduced compared with that of controls. The serum HGF, NF-κB and TGF-β1 levels, and the cyclinD1 protein expression in liver irradiation group were increased compared with that of controls group. However, hepatic regeneration of higher dose-irradiated cirrhotic liver was triggered a more enhanced regeneration, compared with that of higher doses group. In summary, these results suggest that different doses of partial liver irradiation promotes hepatic regeneration in rat. PMID:26261535

Radiation dose-rate meter using an energy-sensitive counter

DOEpatents

Kopp, Manfred K.

1988-01-01

A radiation dose-rate meter is provided which uses an energy-sensitive detector and combines charge quantization and pulse-rate measurement to monitor radiation dose rates. The charge from each detected photon is quantized by level-sensitive comparators so that the resulting total output pulse rate is proportional to the dose-rate.

Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

PubMed

Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

2014-09-01

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence of hypoglycemia was 4.1%, 2.0%, and 6.3%, respectively (P = 0.557). The currently proposed weight-based insulin glargine dose titration regimen is effective, tolerable, and user-friendly at achieving FBG target levels in hospitalized patients with hyperglycemia. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

The impact of shock wave therapy at varied energy and dose levels on functional and structural changes in erectile tissue.

PubMed

Müller, Alexander; Akin-Olugbade, Yemi; Deveci, Serkan; Donohue, John F; Tal, Raanan; Kobylarz, Keith A; Palese, Michael; Mulhall, John P

2008-03-01

Only minimal literature exists on consequences of shock wave therapy (SWT) on erectile function in treatment of Peyronie's disease (PD). This study was undertaken to define SWT impact at varied energy/dose levels at different time points on functional and structural changes in erectile tissue. In 45 rats 2000 shock waves (sw) at 2 BAR were applied to the penis weekly sorted by one, two, and three sessions (high-dose/energy level, HD-1, HD-2, HD-3). Each group was followed for 1, 7, or 28 d before measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Fifteen control animals (C1, C7, C28) underwent anesthesia alone. Another 15 animals were exposed to three SWT sessions applying 1000 sw at 1 BAR and analyzed identically (low-dose/energy level, LD-3-1, -7, -28). Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling assay was used to define the apoptotic index (AI) and Masson's trichrome (MT) staining was prepared to evaluate smooth muscle-to-collagen ratios. ICP/MAP ratios for all C groups displayed a mean of 64%. All SWT groups demonstrated significantly reduced ICP/MAP ratios compared to their corresponding C groups (p<0.05). The LD-3 groups showed a trend toward improved ICP/MAP ratios. LD-3-28 demonstrated significant recovery compared to HD-3-28 (55+/-8% vs. 41+/-10%, p=0.004), but remained reduced compared to C28 (63+/-5%, p=0.03). No statistical differences were seen for MT staining in SWT groups compared to C (p>0.05). AIs for the LD-3 groups were significantly lower compared to the HD-3 groups (p<0.001), but all AIs were significantly increased compared to C groups (p<0.01). Overall, at both energy/dose levels, SWT resulted in a time- and treatment-dependent reduction of ICP/MAP ratios, which might be mediated partly through apoptosis and collagenization of corporal smooth muscle.

Pleiotropic effects of fenofibrate therapy on rats with hypertriglycemia.

PubMed

Sun, Bing; Xie, Yuan; Jiang, Jinfa; Wang, Yiping; Xu, Xiaolin; Zhao, Cuimei; Huang, Feifei

2015-04-14

Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia. Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks. At baseline, 4 weeks of fructose administration and 2 weeks of fenofibrate therapy, parameters of interest were evaluated and compared. At baseline, no significant differences of parameter were observed between groups. After 4 weeks of fructose prescription, triglyceride level increased in company with high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) decreased. C-reactive protein (CRP) and malondialdehyde (MDA) levels were also elevated. Endothelial function was impaired as reflected by reduced nitric oxide (NO) production and elevated serum asymmetric dimethylarginine (ADMA) level. All these changes were significant as compared to the control group (P<0.05), suggesting that short-term of triglyceride elevation could potently initiate atherosclerosis. With 2 weeks of fenofibrate therapy, in comparison to un-treated group, triglyceride level was significantly reduced in parallel with HDL-C and ApoA1 elevation. Inflammation and oxidation were also profoundly ameliorated as reflected by CRP and MDA reduction. Notably, NO production was enhanced in company with serum ADMA level decrease. Overall, these improvements manifested in a dose-dependent manner, which was supported by multivariate regression analysis showing that after adjusted to other variables, the dose of fenofibrate therapy remained significantly associated with NO production and serum ADMA level, with OR of 1.042 (high-dose versus low-dose, 95% CI 1.028-1.055, P<0.05). Fenofibrate therapy not only could reduce triglyceride level but also confer pleiotropic effects in terms of endothelium-protection and amelioration of inflammation and oxidation in a dose-dependent manner.

TH-C-18A-08: A Management Tool for CT Dose Monitoring, Analysis, and Protocol Review

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

Wang, J; Chan, F; Newman, B

2014-06-15

Purpose: To develop a customizable tool for enterprise-wide managing of CT protocols and analyzing radiation dose information of CT exams for a variety of quality control applications Methods: All clinical CT protocols implemented on the 11 CT scanners at our institution were extracted in digital format. The original protocols had been preset by our CT management team. A commercial CT dose tracking software (DoseWatch,GE healthcare,WI) was used to collect exam information (exam date, patient age etc.), scanning parameters, and radiation doses for all CT exams. We developed a Matlab-based program (MathWorks,MA) with graphic user interface which allows to analyze themore » scanning protocols with the actual dose estimates, and compare the data to national (ACR,AAPM) and internal reference values for CT quality control. Results: The CT protocol review portion of our tool allows the user to look up the scanning and image reconstruction parameters of any protocol on any of the installed CT systems among about 120 protocols per scanner. In the dose analysis tool, dose information of all CT exams (from 05/2013 to 02/2014) was stratified on a protocol level, and within a protocol down to series level, i.e. each individual exposure event. This allows numerical and graphical review of dose information of any combination of scanner models, protocols and series. The key functions of the tool include: statistics of CTDI, DLP and SSDE, dose monitoring using user-set CTDI/DLP/SSDE thresholds, look-up of any CT exam dose data, and CT protocol review. Conclusion: our inhouse CT management tool provides radiologists, technologists and administration a first-hand near real-time enterprise-wide knowledge on CT dose levels of different exam types. Medical physicists use this tool to manage CT protocols, compare and optimize dose levels across different scanner models. It provides technologists feedback on CT scanning operation, and knowledge on important dose baselines and thresholds.« less

Improving spot-scanning proton therapy patient specific quality assurance with HPlusQA, a second-check dose calculation engine

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

Mackin, Dennis; Li, Yupeng; Taylor, Michael B.

Purpose: The purpose of this study was to validate the use of HPlusQA, spot-scanning proton therapy (SSPT) dose calculation software developed at The University of Texas MD Anderson Cancer Center, as second-check dose calculation software for patient-specific quality assurance (PSQA). The authors also showed how HPlusQA can be used within the current PSQA framework.Methods: The authors compared the dose calculations of HPlusQA and the Eclipse treatment planning system with 106 planar dose measurements made as part of PSQA. To determine the relative performance and the degree of correlation between HPlusQA and Eclipse, the authors compared calculated with measured point doses.more » Then, to determine how well HPlusQA can predict when the comparisons between Eclipse calculations and the measured dose will exceed tolerance levels, the authors compared gamma index scores for HPlusQA versus Eclipse with those of measured doses versus Eclipse. The authors introduce the αβγ transformation as a way to more easily compare gamma scores.Results: The authors compared measured and calculated dose planes using the relative depth, z/R × 100%, where z is the depth of the measurement and R is the proton beam range. For relative depths than less than 80%, both Eclipse and HPlusQA calculations were within 2 cGy of dose measurements on average. When the relative depth was greater than 80%, the agreement between the calculations and measurements fell to 4 cGy. For relative depths less than 10%, the Eclipse and HPlusQA dose discrepancies showed a negative correlation, −0.21. Otherwise, the correlation between the dose discrepancies was positive and as large as 0.6. For the dose planes in this study, HPlusQA correctly predicted when Eclipse had and had not calculated the dose to within tolerance 92% and 79% of the time, respectively. In 4 of 106 cases, HPlusQA failed to predict when the comparison between measurement and Eclipse's calculation had exceeded the tolerance levels of 3% for dose and 3 mm for distance-to-agreement.Conclusions: The authors found HPlusQA to be reasonably effective (79%± 10%) in determining when the comparison between measured dose planes and the dose planes calculated by the Eclipse treatment planning system had exceeded the acceptable tolerance levels. When used as described in this study, HPlusQA can reduce the need for patient specific quality assurance measurements by 64%. The authors believe that the use of HPlusQA as a dose calculation second check can increase the efficiency and effectiveness of the QA process.« less

A randomized clinical trial comparing metabolic parameters after 48 weeks of standard- and low-dose stavudine therapy and tenofovir disoproxil fumarate therapy in HIV-infected South African patients.

PubMed

Menezes, C N; Crowther, N J; Duarte, R; Van Amsterdam, D; Evans, D; Dickens, C; Dix-Peek, T; Rassool, M; Prinsloo, A; Raal, F; Sanne, I

2014-01-01

Low-dose stavudine therapy may have a lower toxicity profile compared with standard dose. A randomized controlled trial comparing these two doses of stavudine with tenofovir disoproxil fumarate (tenofovir DF) was performed to assess the effects on anthropometry, markers of inflammation, and lipid and glucose metabolism in Black South African patients. Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or tenofovir DF (300 mg), each combined with lamivudine and efavirenz, for 48 weeks. Anthropometry, markers of inflammation, and lipid and glucose metabolism were assessed using standard techniques. In all three treatment arms, there was a significant increase in lipid levels over the study period. At 48 weeks, fasting glucose level (P < 0.005) and homeostasis model assessment (HOMA) score (P < 0.05) increased significantly in the standard-dose stavudine arm, as did insulin and C-peptide levels in both the standard- and low-dose stavudine arms. At week 48, a significant decrease (P < 0.05) in adiponectin was noted in the standard-dose stavudine arm, but there was an increase (P < 0.005) in the tenofovir DF arm. In both the stavudine arms, significant increases in anthropometric measures occurred at 24 weeks but these decreased by week 48. Mitochondrial toxicities occurred in both the stavudine arms. Immunological and virological outcomes were similar for all three arms. This study highlights the occurrence of metabolic abnormalities with both stavudine and tenofovir DF treatment. Awareness of the potential increased cardiovascular risk should be of concern with the use of both these therapies. © 2013 British HIV Association.

Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

PubMed Central

Pawluski, Jodi L.; van Donkelaar, Eva; Abrams, Zipporah; Steinbusch, Harry W. M.; Charlier, Thierry D.

2014-01-01

Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat. PMID:24757568

Vitamin D Replacement in Children, Adolescents and Pregnant Women in the Middle East and North Africa

PubMed Central

Chakhtoura, M; El Ghandour, S; Shawwa, K; Akl, EA; Arabi, A; Mahfoud, Z; Habib, RH; Hoballah, H; El Hajj Fuleihan, G

2017-01-01

Introduction Hypovitaminosis D affects one-third to two-thirds of children and pregnant women from the Middle East and North Africa (MENA) region. Objective To evaluate in infants, children, adolescents and pregnant women, from the MENA region, the effect of supplementation with different vitamin D doses on the change in 25-hydroxyvitamin D [25(OH)D] level reached, and other skeletal and non-skeletal outcomes. Methods This is a systematic review of randomized controlled trials of vitamin D supplementation conducted in the MENA region. We conducted a comprehensive literature search in 7 databases, without language or time restriction, until November 2016. Two reviewers abstracted data from the included studies, independently and in duplicate. We calculated the mean difference (MD) and 95% CI of 25(OH)D level reached when at least 2 studies were eligible in each comparison (low (< 800 IU), intermediate (800–2,000 IU) or high (> 2,000 IU) daily dose of vitamin D, or placebo). We pooled data using RevMan version 5.3. Results We identified a total of 15 eligible trials: one in infants, 4 in children and adolescents and 10 in pregnant women. In children and adolescents, an intermediate vitamin D dose (1,901 IU/d), resulted in a mean difference in 25(OH)D level of 13.5 (95% Confidence Interval (CI) 8.1;18.8) ng/ml, compared to placebo, favoring the intermediate dose (p < 0.001). The proportion of children and adolescents reaching a 25(OH)D level ≥ 20 ng/ml was 74% in the intermediate dose group. In pregnant women, four trials started supplementation at 12–16 weeks of gestation and continued until delivery, and six trials started supplementation at 20–28 weeks gestation and stopped it at delivery. The MD in 25(OH)D level reached was 8.6 (95% CI 5.3–11.9) ng/ml (p <0.001) comparing the high dose (3,662 IU/d) to the intermediate dose (1,836 IU/d), and 12.3 (95% CI 6.4–18.2) ng/ml (p <0.001), comparing the high dose (3,399 IU/d) to the low dose (375 IU/d). Comparing the intermediate (1,832 IU/d) to the low dose (301 IU/d), the MD in 25(OH)D level achieved was 7.8 (95% CI 4.5–10.8) ng/ml (p < 0.001). The proportion of pregnant women reaching a 25(OH)D level ≥ 20 ng/ml was 80–90%, 73% and 27–43% in the high, intermediate, and low dose groups, respectively. The risk of bias in the included studies, for children, adolescents and pregnant women, ranged from low to high. Conclusion In children, adolescents and pregnant women from the MENA, an intermediate vitamin D dose of 1,000–2,000 IU seems necessary to allow for the majority of the population to reach a desirable 25(OH)D level of 20 ng/ml. Further high quality RCTs are required to confirm/refute the beneficial impact of vitamin D supplementation on various clinically important outcomes. PMID:28403940

Dual-energy computed tomography of the head: a phantom study assessing axial dose distribution, eye lens dose, and image noise level

NASA Astrophysics Data System (ADS)

Matsubara, Kosuke; Kawashima, Hiroki; Hamaguchi, Takashi; Takata, Tadanori; Kobayashi, Masanao; Ichikawa, Katsuhiro; Koshida, Kichiro

2016-03-01

The aim of this study was to propose a calibration method for small dosimeters to measure absorbed doses during dual- source dual-energy computed tomography (DECT) and to compare the axial dose distribution, eye lens dose, and image noise level between DE and standard, single-energy (SE) head CT angiography. Three DE (100/Sn140 kVp 80/Sn140 kVp, and 140/80 kVp) and one SE (120 kVp) acquisitions were performed using a second-generation dual-source CT device and a female head phantom, with an equivalent volumetric CT dose index. The axial absorbed dose distribution at the orbital level and the absorbed doses for the eye lens were measured using radiophotoluminescent glass dosimeters. CT attenuation numbers were obtained in the DE composite images and the SE images of the phantom at the orbital level. The doses absorbed at the orbital level and in the eye lens were lower and standard deviations for the CT attenuation numbers were slightly higher in the DE acquisitions than those in the SE acquisition. The anterior surface dose was especially higher in the SE acquisition than that in the DE acquisitions. Thus, DE head CT angiography can be performed with a radiation dose lower than that required for a standard SE head CT angiography, with a slight increase in the image noise level. The 100/Sn140 kVp acquisition revealed the most balanced axial dose distribution. In addition, our proposed method was effective for calibrating small dosimeters to measure absorbed doses in DECT.

Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes

PubMed Central

de Oliveira, Miriane; Síbio, Maria Teresa De; Olimpio, Regiane Marques Castro; Moretto, Fernanda Cristina Fontes; Luvizotto, Renata de Azevedo Melo; Nogueira, Celia Regina

2015-01-01

Objective To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. Methods 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey’s test or Student’s t test, were used to analyze data, and significance level was set at 5%. Results Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. Conclusion These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases. PMID:25993072

Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes.

PubMed

Oliveira, Miriane de; de Síbio, Maria Teresa; Olimpio, Regiane Marques Castro; Moretto, Fernanda Cristina Fontes; Luvizotto, Renata de Azevedo Melo; Nogueira, Celia Regina

2015-01-01

To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey's test or Student's t test, were used to analyze data, and significance level was set at 5%. Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases.

Musculoskeletal imaging with a prototype photon-counting detector.

PubMed

Gruber, M; Homolka, P; Chmeissani, M; Uffmann, M; Pretterklieber, M; Kainberger, F

2012-01-01

To test a digital imaging X-ray device based on the direct capture of X-ray photons with pixel detectors, which are coupled with photon-counting readout electronics. The chip consists of a matrix of 256 × 256 pixels with a pixel pitch of 55 μm. A monolithic image of 11.2 cm × 7 cm was obtained by the consecutive displacement approach. Images of embalmed anatomical specimens of eight human hands were obtained at four different dose levels (skin dose 2.4, 6, 12, 25 μGy) with the new detector, as well as with a flat-panel detector. The overall rating scores for the evaluated anatomical regions ranged from 5.23 at the lowest dose level, 6.32 at approximately 6 μGy, 6.70 at 12 μGy, to 6.99 at the highest dose level with the photon-counting system. The corresponding rating scores for the flat-panel detector were 3.84, 5.39, 6.64, and 7.34. When images obtained at the same dose were compared, the new system outperformed the conventional DR system at the two lowest dose levels. At the higher dose levels, there were no significant differences between the two systems. The photon-counting detector has great potential to obtain musculoskeletal images of excellent quality at very low dose levels.

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.

PubMed

Huang, Zhenhua; Liang, Lining; Li, Lingyu; Xu, Miao; Li, Xiang; Sun, Hao; He, Songwei; Lin, Lilong; Zhang, Yixin; Song, Yancheng; Yang, Man; Luo, Yuling; Loh, Horace H; Law, Ping-Yee; Zheng, Dayong; Zheng, Hui

2016-03-08

Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.

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

PubMed

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

2008-04-15

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

Comparison of low-contrast detectability between two CT reconstruction algorithms using voxel-based 3D printed textured phantoms.

PubMed

Solomon, Justin; Ba, Alexandre; Bochud, François; Samei, Ehsan

2016-12-01

To use novel voxel-based 3D printed textured phantoms in order to compare low-contrast detectability between two reconstruction algorithms, FBP (filtered-backprojection) and SAFIRE (sinogram affirmed iterative reconstruction) and determine what impact background texture (i.e., anatomical noise) has on estimating the dose reduction potential of SAFIRE. Liver volumes were segmented from 23 abdominal CT cases. The volumes were characterized in terms of texture features from gray-level co-occurrence and run-length matrices. Using a 3D clustered lumpy background (CLB) model, a fitting technique based on a genetic optimization algorithm was used to find CLB textures that were reflective of the liver textures, accounting for CT system factors of spatial blurring and noise. With the modeled background texture as a guide, four cylindrical phantoms (Textures A-C and uniform, 165 mm in diameter, and 30 mm height) were designed, each containing 20 low-contrast spherical signals (6 mm diameter at nominal contrast levels of ∼3.2, 5.2, 7.2, 10, and 14 HU with four repeats per signal). The phantoms were voxelized and input into a commercial multimaterial 3D printer (Object Connex 350), with custom software for voxel-based printing (using principles of digital dithering). Images of the textured phantoms and a corresponding uniform phantom were acquired at six radiation dose levels (SOMATOM Flash, Siemens Healthcare) and observer model detection performance (detectability index of a multislice channelized Hotelling observer) was estimated for each condition (5 contrasts × 6 doses × 2 reconstructions × 4 backgrounds = 240 total conditions). A multivariate generalized regression analysis was performed (linear terms, no interactions, random error term, log link function) to assess whether dose, reconstruction algorithm, signal contrast, and background type have statistically significant effects on detectability. Also, fitted curves of detectability (averaged across contrast levels) as a function of dose were constructed for each reconstruction algorithm and background texture. FBP and SAFIRE were compared for each background type to determine the improvement in detectability at a given dose, and the reduced dose at which SAFIRE had equivalent performance compared to FBP at 100% dose. Detectability increased with increasing radiation dose (P = 2.7 × 10 -59 ) and contrast level (P = 2.2 × 10 -86 ) and was higher in the uniform phantom compared to the textured phantoms (P = 6.9 × 10 -51 ). Overall, SAFIRE had higher d' compared to FBP (P = 0.02). The estimated dose reduction potential of SAFIRE was found to be 8%, 10%, 27%, and 8% for Texture-A, Texture-B, Texture-C and uniform phantoms. In all background types, detectability was higher with SAFIRE compared to FBP. However, the relative improvement observed from SAFIRE was highly dependent on the complexity of the background texture. Iterative algorithms such as SAFIRE should be assessed in the most realistic context possible.

Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial.

PubMed

Isanaka, Sheila; Mugusi, Ferdinand; Hawkins, Claudia; Spiegelman, Donna; Okuma, James; Aboud, Said; Guerino, Chalamilla; Fawzi, Wafaie W

2012-10-17

Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART. To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART. A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance. The composite of HIV disease progression or death from any cause. The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels. Clinicaltrials.gov Identifier: NCT00383669.

Neuroprotection of dietary virgin olive oil on brain lipidomics during stroke.

PubMed

Rabiei, Zahra; Bigdeli, Mohammad Reza; Rasoulian, Bahram

2013-08-01

Recent studies suggest that dietary virgin olive oil reduces hypoxia-reoxygenation injury in rat brain. This study investigated the effect of pretreatment with different doses of dietary virgin olive oil on brain lipidomics during stroke. In this experimental trial, 60 male Wistar rats were studied in 5 groups of 12 each. The control group received distilled water while three treatment groups received oral virgin olive oil for 30 days (0.25, 0.5 and 0.75 ml/kg/day respectively). Also the sham group received distilled water. Two hours after the last dose, the animals divided two groups. The middle cerebral artery occlusion (MCAO) group subjected to 60 min of middle cerebral artery occlusion (MCAO) and intact groups for brain lipids analysis. The brain phosphatidylcholine, cholesterol ester and cholesterol levels increased significantly in doses of 0.5 and 0.75 ml/kg/day compare with control group. VOO in all three doses increased the brain triglyceride levels. VOO with dose 0.75 ml/kg increased the brain cerebroside levels when compared with control group. VOO pretreatment for 30 days decreased the brain ceramide levels in doses of 0.5 and 0.75 ml/kg/day (p<0.05). Although further studies are needed, the results indicate that the VOO pretreatment improved the injury of ischemia and reperfusion and might be beneficial in patients with these disorders and seems to partly exert their effects via change in brain lipid levels in rat.

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

PubMed

Rao, Shripada C; Srinivasjois, Ravisha; Moon, Kwi

2016-12-06

Animal studies and trials in older children and adults suggest that a 'one dose per day' regimen of gentamicin is superior to a 'multiple doses per day' regimen. To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) in the Cochrane Library (searched 8 April 2016), MEDLINE (1966 to 8 April 2016), Embase (1980 to 8 April 2016), and CINAHL (December 1982 to 8 April 2016). All randomised or quasi-randomised controlled trials comparing one dose per day ('once a day') compared to multiple doses per day ('multiple doses a day') of gentamicin to newborn infants. Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. Eleven RCTs were included (N = 574) and 28 excluded. All except one study enrolled infants of more than 32 weeks' gestation. Limited information suggested that infants in both 'once a day' as well as 'multiple doses a day' regimens showed adequate clearance of sepsis (typical RR 1.00, 95% CI 0.84 to 1.19; typical RD 0.00, 95% CI -0.19 to 0.19; 3 trials; N = 37). 'Once a day' gentamicin regimen was associated with fewer failures to attain peak level of at least 5 µg/ml (typical RR 0.22, 95% CI 0.11 to 0.47; typical RD -0.13, 95% CI -0.19 to -0.08; number needed to treat for an additional beneficial outcome (NNTB) = 8; 9 trials; N = 422); and fewer failures to achieve trough levels of 2 µg/ml or less (typical RR 0.38, 95% CI 0.27 to 0.55; typical RD -0.22, 95% CI -0.29 to -0.15; NNTB = 4; 11 trials; N = 503). 'Once a day' gentamicin achieved higher peak levels (MD 2.58, 95% CI 2.26 to 2.89; 10 trials; N = 440) and lower trough levels (MD -0.57, 95% CI -0.69 to -0.44; 10 trials; N = 440) than 'multiple doses a day' regimen. There was no significant difference in ototoxicity between two groups (typical RR 1.69, 95% CI 0.18 to 16.25; typical RD 0.01, 95% CI -0.04 to 0.05; 5 trials; N = 214). Nephrotoxicity was not noted with either of the treatment regimens. Overall, the quality of evidence was considered to be moderate on GRADE analysis, given the small sample size and unclear/high risk of bias in some of the domains in a few of the included studies. There is insufficient evidence from the currently available RCTs to conclude whether a 'once a day' or a 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggest that pharmacokinetic properties of a 'once a day' gentamicin regimen are superior to a 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There was no change in nephrotoxicity or auditory toxicity. Based on the assessment of pharmacokinetics, a 'once a day regimen' may be superior in treating sepsis in neonates of more than 32 weeks' gestation.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

PubMed

Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

2016-10-01

We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Effects of ursolic acid on glucose metabolism, the polyol pathway and dyslipidemia in non-obese type 2 diabetic mice.

PubMed

Lee, Jin; Lee, Hae-In; Seo, Kown-Il; Cho, Hyun Wook; Kim, Myung-Joo; Park, Eun-Mi; Lee, Mi-Kyung

2014-07-01

Ursolic acid (UA) is a pentacyclic triterpenoid compound that naturally occurs in fruits, leaves and flowers of medicinal herbs. This study investigated the dose-response efficacy of UA (0.01 and 0.05%) on glucose metabolism, the polyol pathway and dyslipidemia in streptozotocin/nicotinamide-induced diabetic mice. Supplement with both UA doses reduced fasting blood glucose and plasma triglyceride levels in non-obese type 2 diabetic mice. High-dose UA significantly lowered plasma free fatty acid, total cholesterol and VLDL-cholesterol levels compared with the diabetic control mice, while LDL-cholesterol levels were reduced with both doses. UA supplement effectively decreased hepatic glucose-6-phosphatase activity and increased glucokinase activity, the glucokinase/glucose-6-phosphatase ratio, GLUT2 mRNA levels and glycogen content compared with the diabetic control mice. UA supplement attenuated hyperglycemia-induced renal hypertrophy and histological changes. Renal aldose reductase activity was higher, whereas sorbitol dehydrogenase activity was lower in the diabetic control group than in the non-diabetic group. However, UA supplement reversed the biochemical changes in polyol pathway to normal values. These results demonstrated that low-dose UA had preventive potency for diabetic renal complications, which could be mediated by changes in hepatic glucose metabolism and the renal polyol pathway. High-dose UA was more effective anti-dyslipidemia therapy in non-obese type 2 diabetic mice.

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparative Benchmark Dose Modeling as a Tool to Make the First Estimate of Safe Human Exposure Levels to Lunar Dust

NASA Technical Reports Server (NTRS)

James, John T.; Lam, Chiu-wing; Scully, Robert R.

2013-01-01

Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.

Immunogenicity Following One, Two, or Three Doses of the 7-valent Pneumococcal Conjugate Vaccine

PubMed Central

Russell, FM; Balloch, A; Tang, MLK; Carapetis, JR; Licciardi, P; Nelson, J; Jenney, AWJ; Tikoduadua, L; Waqatakirewa, L; Pryor, J; Byrnes, GB; Cheung, YB; Mulholland, EK

2009-01-01

The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following 3 PCV doses, geometric mean concentration (GMC) to all 7 serotypes were ≥ 1.0μg/mL, and >85% of children achieved antibody levels ≥0.35μg/mL at 18 weeks. Following 2 doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with 3 doses. Following a single dose, significant responses were seen for all serotypes post primary series compared with the unvaccinated. By 12 months, differences between 2 and 3 doses persisted for serotype 14 only. Although GMC following 3 doses are higher than after 2 doses, the differences were small. A single dose may offer some protection for most serotypes. PMID:19616498

The Impact of Different Levels of Adaptive Iterative Dose Reduction 3D on Image Quality of 320-Row Coronary CT Angiography: A Clinical Trial

PubMed Central

Feger, Sarah; Rief, Matthias; Zimmermann, Elke; Martus, Peter; Schuijf, Joanne Désirée; Blobel, Jörg; Richter, Felicitas; Dewey, Marc

2015-01-01

Purpose The aim of this study was the systematic image quality evaluation of coronary CT angiography (CTA), reconstructed with the 3 different levels of adaptive iterative dose reduction (AIDR 3D) and compared to filtered back projection (FBP) with quantum denoising software (QDS). Methods Standard-dose CTA raw data of 30 patients with mean radiation dose of 3.2 ± 2.6 mSv were reconstructed using AIDR 3D mild, standard, strong and compared to FBP/QDS. Objective image quality comparison (signal, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contour sharpness) was performed using 21 measurement points per patient, including measurements in each coronary artery from proximal to distal. Results Objective image quality parameters improved with increasing levels of AIDR 3D. Noise was lowest in AIDR 3D strong (p≤0.001 at 20/21 measurement points; compared with FBP/QDS). Signal and contour sharpness analysis showed no significant difference between the reconstruction algorithms for most measurement points. Best coronary SNR and CNR were achieved with AIDR 3D strong. No loss of SNR or CNR in distal segments was seen with AIDR 3D as compared to FBP. Conclusions On standard-dose coronary CTA images, AIDR 3D strong showed higher objective image quality than FBP/QDS without reducing contour sharpness. Trial Registration Clinicaltrials.gov NCT00967876 PMID:25945924

Pulmonary Nodule Volumetry at Different Low Computed Tomography Radiation Dose Levels With Hybrid and Model-Based Iterative Reconstruction: A Within Patient Analysis.

PubMed

den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evertjan P A; Schilham, Arnold M R; Lammers, Jan-Willem J; Luijk, Bart; Budde, Ricardo P J; Leiner, Tim; de Jong, Pim A

2016-01-01

The aim of the study was to determine the effects of dose reduction and iterative reconstruction (IR) on pulmonary nodule volumetry. In this prospective study, 25 patients scheduled for follow-up of pulmonary nodules were included. Computed tomography acquisitions were acquired at 4 dose levels with a median of 2.1, 1.2, 0.8, and 0.6 mSv. Data were reconstructed with filtered back projection (FBP), hybrid IR, and model-based IR. Volumetry was performed using semiautomatic software. At the highest dose level, more than 91% (34/37) of the nodules could be segmented, and at the lowest dose level, this was more than 83%. Thirty-three nodules were included for further analysis. Filtered back projection and hybrid IR did not lead to significant differences, whereas model-based IR resulted in lower volume measurements with a maximum difference of -11% compared with FBP at routine dose. Pulmonary nodule volumetry can be accurately performed at a submillisievert dose with both FBP and hybrid IR.

Direct Measurement of Perchlorate Exposure Biomarkers in a Highly Exposed Population: A Pilot Study

PubMed Central

Wong, Michelle; Copan, Lori; Olmedo, Luis; Patton, Sharyle; Haas, Robert; Atencio, Ryan; Xu, Juhua; Valentin-Blasini, Liza

2011-01-01

Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 µg/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment. PMID:21394205

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

PubMed

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

2013-01-01

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

Characteristics and Dose Levels for Spent Reactor Fuels

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

Coates, Cameron W

2007-01-01

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

Anti-diabetic activity of Vaccinium bracteatum Thunb. leaves' polysaccharide in STZ-induced diabetic mice.

PubMed

Wang, Li; Zhang, Ying; Xu, Maochao; Wang, Yingyao; Cheng, Sujiao; Liebrecht, Alex; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

2013-10-01

Vaccinium bracteatum Thunb. (VBT) is a traditional Chinese herbal medicine. The anti-diabetic activity of VBT leaves' polysaccharide (VBTLP) is studied in this paper. The results indicated VBTLP had a dose-dependent decrease on the blood glucose (BG) level, and the time effect of VBTLP on BG level was also significant. The insulin level of high dose group (HDG) was significantly higher (p<0.05) than that of model control (MC) group. Compared to MC, HDG and lose dose group (LDG) had significantly lower (p<0.05) TC and LDL-C levels, however, TG and HDL-C levels are similar. Compared to non-diabetic control (NC), HDG and LDG had similar plasma lipid levels except for higher LDL-C level. Although body weights of LDG and HDG were significant lower (p<0.05) than that of NC from week 2 to week 6, they were similar to that of PC. The results indicate VBTLP possesses a potential hypoglycemic effect in streptozotocin-induced diabetic mice. Copyright © 2013 Elsevier B.V. All rights reserved.

Incidence of deep vein thrombosis is increased with 30 mg twice daily dosing of enoxaparin compared with 40 mg daily.

PubMed

Riha, Gordon M; Van, Philbert Y; Differding, Jerome A; Schreiber, Martin A

2012-05-01

The purpose of this study was to analyze whether 2 standard dosing regimens of enoxaparin (30 mg twice daily vs 40 mg once daily) would result in different deep vein thrombosis (DVT) rates and anti-factor Xa activity (anti-Xa) in surgical patients. Patients who required enoxaparin for prophylaxis were followed prospectively. Demographics were recorded. Patients underwent standardized duplex screening. Peak anti-Xa levels were drawn on 4 consecutive days. Sixty-three patients were followed up (28 patients on 30 mg twice daily, 35 patients on 40 mg once daily). There was no significant difference in demographics between groups. Twenty-five percent of patients on 30 mg twice daily developed a DVT, whereas 2.9% of patients on 40 mg once daily developed a DVT. Patients on 30 mg twice daily had significantly lower anti-Xa levels. The incidence of DVT is increased in surgical patients who receive 30 mg twice daily dosing of enoxaparin compared with 40 mg daily. Dosing of 40 mg once daily results in significantly higher peak anti-Xa levels compared with 30 mg twice daily. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Automatic exposure control systems designed to maintain constant image noise: effects on computed tomography dose and noise relative to clinically accepted technique charts.

PubMed

Favazza, Christopher P; Yu, Lifeng; Leng, Shuai; Kofler, James M; McCollough, Cynthia H

2015-01-01

To compare computed tomography dose and noise arising from use of an automatic exposure control (AEC) system designed to maintain constant image noise as patient size varies with clinically accepted technique charts and AEC systems designed to vary image noise. A model was developed to describe tube current modulation as a function of patient thickness. Relative dose and noise values were calculated as patient width varied for AEC settings designed to yield constant or variable noise levels and were compared to empirically derived values used by our clinical practice. Phantom experiments were performed in which tube current was measured as a function of thickness using a constant-noise-based AEC system and the results were compared with clinical technique charts. For 12-, 20-, 28-, 44-, and 50-cm patient widths, the requirement of constant noise across patient size yielded relative doses of 5%, 14%, 38%, 260%, and 549% and relative noises of 435%, 267%, 163%, 61%, and 42%, respectively, as compared with our clinically used technique chart settings at each respective width. Experimental measurements showed that a constant noise-based AEC system yielded 175% relative noise for a 30-cm phantom and 206% relative dose for a 40-cm phantom compared with our clinical technique chart. Automatic exposure control systems that prescribe constant noise as patient size varies can yield excessive noise in small patients and excessive dose in obese patients compared with clinically accepted technique charts. Use of noise-level technique charts and tube current limits can mitigate these effects.

Assessing The Impact Of Cancer Therapies On Ovarian Reserve

PubMed Central

Gracia, Clarisa R.; Sammel, Mary D.; Freeman, Ellen; Prewitt, Maureen; Carlson, Claire; Ray, Anushree; Vance, Ashley; Ginsberg, Jill P.

2013-01-01

Objective To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared to healthy controls of similar age and late-reproductive age. Design Cross-sectional analysis of data from a prospective cohort study Setting University Medical Center Patients 71 cancer survivors age 15-39; 67 healthy, similarly aged unexposed subjects; 69 regularly menstruating women of late-reproductive age (40-52 years). Interventions: None Main Outcome measures Early follicular phase hormones (FSH, Estradiol, Inhibin B, AMH) and ovarian ultrasound measurements (ovarian volume and Antral Follicle Counts) were compared using multivariable linear regression. Results In adjusted models, FSH, AMH and AFC differed between exposed vs. unexposed (FSH 11.12mIU/ml vs. 7.25mIU/ml, p=0.001; AMH 0.81ng/ml vs. 2.85ng/ml, p<0.001; AFC: 14.55 vs. 27.20, p<0.001. In participants with an FSH<10, survivors had lower levels of AMH and AFC compared to controls. Alkylating agent dose score was associated with increased levels of FSH (p= 0.016) and decreased levels of AMH (p=0.003). Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC and ovarian volume. AMH was similar in women previously exposed to high-dose cancer therapy and 40-42 year old controls. Conclusions Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared to unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to late-reproductive women. The predictive value of measures for pregnancy and menopause must be studied. PMID:22137491

The effects of slice thickness and radiation dose level variations on computer-aided diagnosis (CAD) nodule detection performance in pediatric chest CT scans

NASA Astrophysics Data System (ADS)

Emaminejad, Nastaran; Lo, Pechin; Ghahremani, Shahnaz; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael F.

2017-03-01

For pediatric oncology patients, CT scans are performed to assess treatment response and disease progression. CAD may be used to detect lung nodules which would reflect metastatic disease. The purpose of this study was to investigate the effects of reducing radiation dose and varying slice thickness on CAD performance in the detection of solid lung nodules in pediatric patients. The dataset consisted of CT scans of 58 pediatric chest cases, from which 7 cases had lung nodules detected by radiologist, and a total of 28 nodules were marked. For each case, the original raw data (sinogram data) was collected and a noise addition model was used to simulate reduced-dose scans of 50%, 25% and 10% of the original dose. In addition, the original and reduced-dose raw data were reconstructed at slice thicknesses of 1.5 and 3 mm using a medium sharp (B45) kernel; the result was eight datasets (4 dose levels x 2 thicknesses) for each case An in-house CAD tool was applied on all reconstructed scans, and results were compared with the radiologist's markings. Patient level mean sensitivities at 3mm thickness were 24%, 26%, 25%, 27%, and at 1.5 mm thickness were 23%, 29%, 35%, 36% for 10%, 25%, 50%, and 100% dose level, respectively. Mean FP numbers were 1.5, 0.9, 0.8, 0.7 at 3 mm and 11.4, 3.5, 2.8, 2.8 at 1.5 mm thickness for 10%, 25%, 50%, and 100% dose level respectively. CAD sensitivity did not change with dose level for 3mm thickness, but did change with dose for 1.5 mm. False Positives increased at low dose levels where noise values were high.

Significant increase in salivary substance p level after a single oral dose of cevimeline in humans.

PubMed

Suzuki, Yosuke; Itoh, Hiroki; Amada, Kohei; Yamamura, Ryota; Sato, Yuhki; Takeyama, Masaharu

2013-01-01

Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30-240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline.

Significant Increase in Salivary Substance P Level after a Single Oral Dose of Cevimeline in Humans

PubMed Central

Suzuki, Yosuke; Itoh, Hiroki; Amada, Kohei; Yamamura, Ryota; Sato, Yuhki; Takeyama, Masaharu

2013-01-01

Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30–240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline. PMID:23589717

Developmental toxicity study of D-tagatose in rats.

PubMed

Kruger, C L; Whittaker, M H; Frankos, V H; Schroeder, R E

1999-04-01

D-tagatose is a low-calorie sweetener that tastes like sucrose. The developmental toxicity of D-tagatose was investigated in Crl:CD(SD)BR rats administered D-tagatose at three dose levels (4000, 12,000, and 20,000 mg/kg body wt/day) via gastric intubation on days 6-15 of gestation. No compound-related toxicity was seen among any of the maternal groups. No treatment-related clinical effects were seen in the maternal animals at the 4000 mg/kg/day dose level. At the mid- and high-dose levels, most maternal animals had unformed or watery stools; this effect was most prominent early in the treatment period (Gestation Days 6-8). This effect was attributed to the osmotic effect of the large amount of D-tagatose given to the animals at these doses. Since D-tagatose is not digested or absorbed to a large extent, most of the sugar passes into the colon where it absorbs water and is fermented by colonic bacteria. Mean weight gain for the low- and mid-dose animals was comparable to the control; however, the high-dose group experienced a mean weight loss over the Gestation Day 6-9 interval. Over the entire treatment interval, however, mean weight gain for the high-dose animals was comparable to control. The decreased weight gain in the high-dose animals during the Gestation Day 6-9 interval was considered to be a direct result of laxation. In addition to the effect of laxation on body weight, reduced food consumption also contributed to the decreased weight gain. In the low-dose animals, no effect on food consumption was seen; however, both mid- and high-dose animals had food consumption values that were statistically significantly lower than the control. Food consumption was lowest during the Gestation Day 6-9 interval, the period when laxation was most prominent. Food consumption rebounded and was statistically significantly higher than the control for the mid- and high-dose animals during the posttreatment interval. Maternal liver weight for the low-dose animals was comparable to the control. However, a statistically significant increase in mean maternal liver weight was noted for the mid-and high-dose animals. Based on a lack of any corresponding histopathology, the increased liver weights were not considered toxicologically significant. There were no adverse effects on reproductive performance noted in any treatment group. No adverse treatment-related fetal effects on fetal weight, sex distribution, liver weight, or external, skeletal, or visceral malformations were noted at any dose level. Copyright 1999 Academic Press.

The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics

PubMed Central

Formgren, H.

1976-01-01

1 The effect of metoprolol, a new β1-adrenoceptor blocking agent, was compared to practolol in the treatment of hypertension in seventeen asthmatics during concurrent optimum bronchodilator therapy with a selective β2-adrenoceptor-stimulant. 2 The two β-adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice-daily dosage schedule, at 12 h intervals, for 17 days. The comparison was made double-blind and a crossover design was used. The drugs were given in randomized order. The study started with a run-in placebo period and there was a washout period on placebo between the treatment periods. Spirometry, blood pressures and heart rates were recorded in a standardized manner. 3 At the lower dose levels no influence on FEV1 was noted, and no difference was found between the two active drugs. At the higher dose level FEV1 was reduced by both β-adrenoceptor-blocking drugs. Four out of twelve patients given the higher dose experienced exacerbation of their asthma. The heart rate fell with both drugs and at both dose levels. During the placebo period a marked increase of heart rate was noted. The blood pressure fell at both dose levels compared to placebo, no difference being recorded between the two drugs. 4 Metoprolol and practolol are equally effective β1-adrenoceptor blocking drugs. In this study it was found that metoprolol could be used in asthmatics who had indications for β-adrenoceptor blockade, provided that the total daily dose did not exceed 100 mg. Optimal bronchodilator treatment with a bronchoselective β-adrenoceptor agonist is an absolute prerequisite in order to avoid the risk of aggravation of asthma. PMID:22216522

Comparative toxicity of 4 commonly used intravitreal corticosteroids on rat retina.

PubMed

Citirik, Mehmet; Dilsiz, Nihat; Batman, Cosar; Zilelioglu, Orhan

2009-06-01

To investigate the effects of 4 commonly used steroids (dexamethasone, triamcinolone, betamethasone, and methylprednisolone) on 50 retinas of 25 adult pigmented rats. Experimental animal study. Twenty-five pigmented Long-Evans male rats. Each steroid drug with 2 different doses (0.025 mL and 0.050 mL) was injected into the vitreous of each eye of 5 rats. The low drug dose was injected into the right eye and the high dose was injected into the left eye. Ten eyes of 5 randomly selected rats were used as a control group and intravitreal saline was injected into these eyes. Oxidative damage and intrinsic antioxidative capacity were determined by measuring retinal malondialdehyde (MDA) and glutathione (GSH) levels, respectively. No statistically meaningful difference was observed in retinal GSH and MDA measurements in the low- and high-dose triamcinolone (1 and 2 mg), low-dose betamethasone (0.075 mg), and low-dose dexamethasone (0.1 mg) groups, compared with the control group. Both doses of methylprednisolone (1.6 mg and 3.2 mg), high-dose betamethasone (0.15 mg), and high-dose dexamethasone (0.2 mg) markedly altered retinal GSH and MDA levels. The results of our study show that the toxicity of triamcinolone is not evident even in high doses. It may be used safely. We also suggest that intravitreal use of low doses of betamethasone and dexamethasone is safer than higher doses of these drugs and both doses of methylprednisolone.

Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

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

Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl; Laboratory for Health Protection Research, National Institute for Public Health and the Environment; Verhoef, Aart

The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 atmore » doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the developing immune system for DEHP.« less

Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

2012-01-01

Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

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

PubMed

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

2014-11-26

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

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV-infected patients: a randomized trial.

PubMed

Menezes, C N; Duarte, R; Dickens, C; Dix-Peek, T; Van Amsterdam, D; John, M-A; Ive, P; Maskew, M; Macphail, P; Fox, M P; Raal, F; Sanne, I; Crowther, N J

2013-04-01

Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first-line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open-label, randomized controlled trial comparing standard- and low-dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV-infected patients. Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed. A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard-dose (P < 0.05) and low-dose stavudine (P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor-1 (NRF1) and mitochondrial cytochrome B (MTCYB) gene expression levels were affected by stavudine, with a significantly (P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF. No significant differences were observed in markers of inflammation and lipid and glucose metabolism. These results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared with patients on TDF. © 2012 British HIV Association.

Z-Index Parameterization for Volumetric CT Image Reconstruction via 3-D Dictionary Learning.

PubMed

Bai, Ti; Yan, Hao; Jia, Xun; Jiang, Steve; Wang, Ge; Mou, Xuanqin

2017-12-01

Despite the rapid developments of X-ray cone-beam CT (CBCT), image noise still remains a major issue for the low dose CBCT. To suppress the noise effectively while retain the structures well for low dose CBCT image, in this paper, a sparse constraint based on the 3-D dictionary is incorporated into a regularized iterative reconstruction framework, defining the 3-D dictionary learning (3-DDL) method. In addition, by analyzing the sparsity level curve associated with different regularization parameters, a new adaptive parameter selection strategy is proposed to facilitate our 3-DDL method. To justify the proposed method, we first analyze the distributions of the representation coefficients associated with the 3-D dictionary and the conventional 2-D dictionary to compare their efficiencies in representing volumetric images. Then, multiple real data experiments are conducted for performance validation. Based on these results, we found: 1) the 3-D dictionary-based sparse coefficients have three orders narrower Laplacian distribution compared with the 2-D dictionary, suggesting the higher representation efficiencies of the 3-D dictionary; 2) the sparsity level curve demonstrates a clear Z-shape, and hence referred to as Z-curve, in this paper; 3) the parameter associated with the maximum curvature point of the Z-curve suggests a nice parameter choice, which could be adaptively located with the proposed Z-index parameterization (ZIP) method; 4) the proposed 3-DDL algorithm equipped with the ZIP method could deliver reconstructions with the lowest root mean squared errors and the highest structural similarity index compared with the competing methods; 5) similar noise performance as the regular dose FDK reconstruction regarding the standard deviation metric could be achieved with the proposed method using (1/2)/(1/4)/(1/8) dose level projections. The contrast-noise ratio is improved by ~2.5/3.5 times with respect to two different cases under the (1/8) dose level compared with the low dose FDK reconstruction. The proposed method is expected to reduce the radiation dose by a factor of 8 for CBCT, considering the voted strongly discriminated low contrast tissues.

Radiation dose reduction in abdominal computed tomography during the late hepatic arterial phase using a model-based iterative reconstruction algorithm: how low can we go?

PubMed

Husarik, Daniela B; Marin, Daniele; Samei, Ehsan; Richard, Samuel; Chen, Baiyu; Jaffe, Tracy A; Bashir, Mustafa R; Nelson, Rendon C

2012-08-01

The aim of this study was to compare the image quality of abdominal computed tomography scans in an anthropomorphic phantom acquired at different radiation dose levels where each raw data set is reconstructed with both a standard convolution filtered back projection (FBP) and a full model-based iterative reconstruction (MBIR) algorithm. An anthropomorphic phantom in 3 sizes was used with a custom-built liver insert simulating late hepatic arterial enhancement and containing hypervascular liver lesions of various sizes. Imaging was performed on a 64-section multidetector-row computed tomography scanner (Discovery CT750 HD; GE Healthcare, Waukesha, WI) at 3 different tube voltages for each patient size and 5 incrementally decreasing tube current-time products for each tube voltage. Quantitative analysis consisted of contrast-to-noise ratio calculations and image noise assessment. Qualitative image analysis was performed by 3 independent radiologists rating subjective image quality and lesion conspicuity. Contrast-to-noise ratio was significantly higher and mean image noise was significantly lower on MBIR images than on FBP images in all patient sizes, at all tube voltage settings, and all radiation dose levels (P < 0.05). Overall image quality and lesion conspicuity were rated higher for MBIR images compared with FBP images at all radiation dose levels. Image quality and lesion conspicuity on 25% to 50% dose MBIR images were rated equal to full-dose FBP images. This phantom study suggests that depending on patient size, clinically acceptable image quality of the liver in the late hepatic arterial phase can be achieved with MBIR at approximately 50% lower radiation dose compared with FBP.

Initiation of labor analgesia with injection of local anesthetic through the epidural needle compared to the catheter.

PubMed

Ristev, Goran; Sipes, Angela C; Mahoney, Bryan; Lipps, Jonathan; Chan, Gary; Coffman, John C

2017-01-01

The rationale for injection of epidural medications through the needle is to promote sooner onset of pain relief relative to dosing through the epidural catheter given that needle injection can be performed immediately after successful location of the epidural space. Some evidence indicates that dosing medications through the epidural needle results in faster onset and improved quality of epidural anesthesia compared to dosing through the catheter, though these dosing techniques have not been compared in laboring women. This investigation was performed to determine whether dosing medication through the epidural needle improves the quality of analgesia, level of sensory blockade, or onset of pain relief measured from the time of epidural medication injection. In this double-blinded prospective investigation, healthy term laboring women (n=60) received labor epidural placement upon request. Epidural analgesia was initiated according to the assigned randomization group: 10 mL loading dose (0.125% bupivacaine with fentanyl 2 µg/mL) through either the epidural needle or the catheter, given in 5 mL increments spaced 2 minutes apart. Verbal rating scale (VRS) pain scores (0-10) and pinprick sensory levels were documented to determine the rates of analgesic and sensory blockade onset. No significant differences were observed in onset of analgesia or sensory blockade from the time of injection between study groups. The estimated difference in the rate of pain relief (VRS/minute) was 0.04 (95% CI: -0.01 to 0.11; p =0.109), and the estimated difference in onset of sensory blockade (sensory level/minute) was 0.63 (95% CI: -0.02 to 0.15; p =0.166). The time to VRS ≤3 and level of sensory block 20 minutes after dosing were also similar between groups. No differences in patient satisfaction, or maternal or fetal complications were observed. This investigation observed that epidural needle and catheter injection of medications result in similar onset of analgesia and sensory blockade, quality of labor analgesia, patient satisfaction, and complication rates.

Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer

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

Cilla, Savino, E-mail: savinocilla@gmail.com; Macchia, Gabriella; Sabatino, Domenico

2013-04-01

The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in thismore » analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.« less

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

PubMed Central

Adebesin, Olumide Adedapo; Okpuzor, Joy

2014-01-01

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

Effect of High-Dose vs Standard-Dose Multivitamin Supplementation at the Initiation of HAART on HIV Disease Progression and Mortality in Tanzania

PubMed Central

Isanaka, Sheila; Mugusi, Ferdinand; Hawkins, Claudia; Spiegelman, Donna; Okuma, James; Aboud, Said; Guerino, Chalamilla; Fawzi, Wafaie W.

2013-01-01

Context Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART. Objective To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART. Design, Setting, and Participants A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. Intervention The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance. Main Outcome Measure The composite of HIV disease progression or death from any cause. Results The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96–1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11–1.87) vs standard-dose supplementation. Conclusion In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels. Trial Registration clinicaltrials.gov Identifier: NCT00383669 PMID:23073950

Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

PubMed

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2015-05-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

PubMed

Mergenthal, Michelle C; Senapati, Suneeta; Zee, Jarcy; Allen-Taylor, Lynne; Whittaker, Paul G; Takacs, Peter; Sammel, Mary D; Barnhart, Kurt T

2016-11-01

Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P = .011, P < .001, and P = .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P = .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution. In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. Copyright © 2016 Elsevier Inc. All rights reserved.

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group (mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable. © 2017 by the Society for Academic Emergency Medicine.

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.

Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.

PubMed

Withers, Mark R; McKinney, Denise; Ogutu, Bernhards R; Waitumbi, John N; Milman, Jessica B; Apollo, Odika J; Allen, Otieno G; Tucker, Kathryn; Soisson, Lorraine A; Diggs, Carter; Leach, Amanda; Wittes, Janet; Dubovsky, Filip; Stewart, V Ann; Remich, Shon A; Cohen, Joe; Ballou, W Ripley; Holland, Carolyn A; Lyon, Jeffrey A; Angov, Evelina; Stoute, José A; Martin, Samuel K; Heppner, D Gray

2006-11-24

Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine. This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator. The study was conducted in a rural population in Kombewa Division, western Kenya. Subjects were 135 children, aged 12-47 mo. Subjects received 10, 25, or 50 microg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 microL, respectively, of AS02A, or they received a comparator (Imovax (rabies vaccine). We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination. Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 microg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 microg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F(3,1047) = 10.78, or F(3, 995) = 11.22, p < 0.001); however, the comparison of 25 microg and 50 microg recipients indicated no significant difference (F(1,1047) = 0.05; p = 0.82). The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.

Safety and Reactogenicity of an MSP-1 Malaria Vaccine Candidate: A Randomized Phase Ib Dose-Escalation Trial in Kenyan Children

PubMed Central

Withers, Mark R; McKinney, Denise; Ogutu, Bernhards R; Waitumbi, John N; Milman, Jessica B; Apollo, Odika J; Allen, Otieno G; Tucker, Kathryn; Soisson, Lorraine A; Diggs, Carter; Leach, Amanda; Wittes, Janet; Dubovsky, Filip; Stewart, V. Ann; Remich, Shon A; Cohen, Joe; Ballou, W. Ripley; Holland, Carolyn A; Lyon, Jeffrey A; Angov, Evelina; Stoute, José A; Martin, Samuel K; Heppner, D. Gray

2006-01-01

Objective: Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine. Design: This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator. Setting: The study was conducted in a rural population in Kombewa Division, western Kenya. Participants: Subjects were 135 children, aged 12–47 mo. Interventions: Subjects received 10, 25, or 50 μg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 μL, respectively, of AS02A, or they received a comparator (Imovax® rabies vaccine). Outcome Measures: We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination. Results: Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 μg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 μg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F3,1047 = 10.78, or F3, 995 = 11.22, p < 0.001); however, the comparison of 25 μg and 50 μg recipients indicated no significant difference (F1,1047 = 0.05; p = 0.82). Conclusions: The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 μg doses was superior to that of the 10 μg dose. PMID:17124529

Impact of Paclitaxel Dose on Tissue Pharmacokinetics and Vascular Healing: A Comparative Drug-Coated Balloon Study in the Familial Hypercholesterolemic Swine Model of Superficial Femoral In-Stent Restenosis.

PubMed

Gongora, Carlos A; Shibuya, Masahiko; Wessler, Jeffrey D; McGregor, Jenn; Tellez, Armando; Cheng, Yanping; Conditt, Gerard B; Kaluza, Greg L; Granada, Juan F

2015-07-01

This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In.Pact Pacific = 3 μg/mm(2), Lutonix = 2 μg/mm(2) and Ranger = 2 μg/mm(2)) in the experimental setting. The optimal therapeutic dose for PCB use has not been determined yet. Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In.Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment. All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In.Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In.Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-μg/mm(2) PCB groups. Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Automatic Exposure Control Systems Designed to Maintain Constant Image Noise: Effects on Computed Tomography Dose and Noise Relative to Clinically Accepted Technique Charts

PubMed Central

Favazza, Christopher P.; Yu, Lifeng; Leng, Shuai; Kofler, James M.; McCollough, Cynthia H.

2015-01-01

Objective To compare computed tomography dose and noise arising from use of an automatic exposure control (AEC) system designed to maintain constant image noise as patient size varies with clinically accepted technique charts and AEC systems designed to vary image noise. Materials and Methods A model was developed to describe tube current modulation as a function of patient thickness. Relative dose and noise values were calculated as patient width varied for AEC settings designed to yield constant or variable noise levels and were compared to empirically derived values used by our clinical practice. Phantom experiments were performed in which tube current was measured as a function of thickness using a constant-noise-based AEC system and the results were compared with clinical technique charts. Results For 12-, 20-, 28-, 44-, and 50-cm patient widths, the requirement of constant noise across patient size yielded relative doses of 5%, 14%, 38%, 260%, and 549% and relative noises of 435%, 267%, 163%, 61%, and 42%, respectively, as compared with our clinically used technique chart settings at each respective width. Experimental measurements showed that a constant noise–based AEC system yielded 175% relative noise for a 30-cm phantom and 206% relative dose for a 40-cm phantom compared with our clinical technique chart. Conclusions Automatic exposure control systems that prescribe constant noise as patient size varies can yield excessive noise in small patients and excessive dose in obese patients compared with clinically accepted technique charts. Use of noise-level technique charts and tube current limits can mitigate these effects. PMID:25938214

Selection of the initial design for the two-stage continual reassessment method.

PubMed

Jia, Xiaoyu; Ivanova, Anastasia; Lee, Shing M

2017-01-01

In the two-stage continual reassessment method (CRM), model-based dose escalation is preceded by a pre-specified escalating sequence starting from the lowest dose level. This is appealing to clinicians because it allows a sufficient number of patients to be assigned to each of the lower dose levels before escalating to higher dose levels. While a theoretical framework to build the two-stage CRM has been proposed, the selection of the initial dose-escalating sequence, generally referred to as the initial design, remains arbitrary, either by specifying cohorts of three patients or by trial and error through extensive simulations. Motivated by a currently ongoing oncology dose-finding study for which clinicians explicitly stated their desire to assign at least one patient to each of the lower dose levels, we proposed a systematic approach for selecting the initial design for the two-stage CRM. The initial design obtained using the proposed algorithm yields better operating characteristics compared to using a cohort of three initial design with a calibrated CRM. The proposed algorithm simplifies the selection of initial design for the two-stage CRM. Moreover, initial designs to be used as reference for planning a two-stage CRM are provided.

Characterization of beta-phenylethylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study.

PubMed

Nakamura, M; Ishii, A; Nakahara, D

1998-05-22

In vivo microdialysis was used to investigate the effect of beta-phenylethylamine on extracellular levels of monoamines and their metabolites in the nucleus accumbens of conscious rats. At all doses tested (1, 10 and 100 microM), infusion of beta-phenylethylamine through the microdialysis probe significantly increased extracellular levels of dopamine in the nucleus accumbens. These increases were dose-related. The increase in dopamine levels induced by 100 microM beta-phenylethylamine was not affected by co-perfusion of 4 microM tetrodotoxin. The ability of 100 microM beta-phenylethylamine to increase the extracellular level of dopamine was comparable to that of the same dose of methamphetamine. On the other hand, beta-phenylethylamine had a much less potent enhancing effect on 5-hydroxytryptamine (5-HT) than dopamine levels. Only the highest dose (100 microM) caused a statistically significant effect on 5-HT levels. Over the dose range tested (1, 10 and 100 microM), beta-phenylethylamine had no effect on extracellular metabolite levels of dopamine and 5-HT. The results suggest that beta-phenylethylamine increases the efflux of monoamines, preferentially dopamine, without affecting monoamine metabolism, in the nucleus accumbens.

Dose reduction potential of iterative reconstruction algorithms in neck CTA-a simulation study.

PubMed

Ellmann, Stephan; Kammerer, Ferdinand; Allmendinger, Thomas; Brand, Michael; Janka, Rolf; Hammon, Matthias; Lell, Michael M; Uder, Michael; Kramer, Manuel

2016-10-01

This study aimed to determine the degree of radiation dose reduction in neck CT angiography (CTA) achievable with Sinogram-affirmed iterative reconstruction (SAFIRE) algorithms. 10 consecutive patients scheduled for neck CTA were included in this study. CTA images of the external carotid arteries either were reconstructed with filtered back projection (FBP) at full radiation dose level or underwent simulated dose reduction by proprietary reconstruction software. The dose-reduced images were reconstructed using either SAFIRE 3 or SAFIRE 5 and compared with full-dose FBP images in terms of vessel definition. 5 observers performed a total of 3000 pairwise comparisons. SAFIRE allowed substantial radiation dose reductions in neck CTA while maintaining vessel definition. The possible levels of radiation dose reduction ranged from approximately 34 to approximately 90% and depended on the SAFIRE algorithm strength and the size of the vessel of interest. In general, larger vessels permitted higher degrees of radiation dose reduction, especially with higher SAFIRE strength levels. With small vessels, the superiority of SAFIRE 5 over SAFIRE 3 was lost. Neck CTA can be performed with substantially less radiation dose when SAFIRE is applied. The exact degree of radiation dose reduction should be adapted to the clinical question, in particular to the smallest vessel needing excellent definition.

Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase.

PubMed

Torremadé, Noelia; Bozic, Milica; Goltzman, David; Fernandez, Elvira; Valdivielso, José M

2017-01-01

The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals. The dose needed to decrease PTH levels in CYP27B1-/- mice with CKD was 50 ng/g. That dose restored blood calcium levels without modifying phosphate levels, and increased the expression of genes responsible for calcium absorption (TRPV5 and calbindinD- 28K in the kidney, TRPV6 and calbindinD-9k in the intestine). The same dose of 25(OH)D3 did not modify PTH in CYP27B1+/+ animals with CKD. Blood calcium remained normal, while phosphate increased significantly. Blood levels of 25(OH)D3 in CYP27B1-/- mice were extremely high compared to those in CYP27B1+/+ animals. CYP27B1+/+ animals with CKD showed increases in TRPV5, TRPV6, calbindinD-28K and calbindinD-9K, which were not further elevated with the treatment. Furthermore, CYP27B1+/+ animals displayed an increase in vascular calcification. We conclude that the dose of 25(OH)D3 effective in decreasing PTH levels in CYP27B1-/- mice with CKD, has a potentially toxic effect in CYP27B1+/+ animals with CKD.

Estimation of skin entrance doses (SEDs) for common medical X-ray diagnostic examinations in India and proposed diagnostic reference levels (DRLs).

PubMed

Sonawane, A U; Shirva, V K; Pradhan, A S

2010-02-01

Skin entrance doses (SEDs) were estimated by carrying out measurements of air kerma from 101 X-ray machines installed in 45 major and selected hospitals in the country by using a silicon detector-based dose Test-O-Meter. 1209 number of air kerma measurements of diagnostic projections for adults have been analysed for seven types of common diagnostic examinations, viz. chest (AP, PA, LAT), lumbar spine (AP, LAT), thoracic spine (AP, LAT), abdomen (AP), pelvis (AP), hip joints (AP) and skull (PA, LAT) for different film-screen combinations. The values of estimated diagnostic reference levels (DRLs) (third quartile values of SEDs) were compared with guidance levels/DRLs of doses published by the IAEA-BSS-Safety Series No. 115, 1996; HPA (NRPB) (2000 and 2005), UK; CRCPD/CDRH (USA), European Commission and other national values. The values of DRLs obtained in this study are comparable with the values published by the IAEA-BSS-115 (1996); HPA (NRPB) (2000 and 2005) UK; EC and CRCPD/CDRH, USA including values obtained in previous studies in India.

A single dose comparison of a combination of fenoterol and ipratropium aerosols in bronchial asthma.

PubMed Central

Lawford, P.; Palmer, K. N.

1983-01-01

Nine patients with reversible obstructive airways disease were studied to compare the bronchodilator response to a combination of fenoterol and ipratropium aerosols with two dose levels of fenoterol alone. Using a double-blind, cross-over, single dose regime, 200 micrograms fenoterol hydrobromide and 80 micrograms ipratropium bromide was compared to 400 micrograms fenoterol + placebo, and to 200 micrograms fenoterol + placebo. There was no significant difference between the combination and either dose of fenoterol in terms of peak or duration of response as determined by absolute or percent change in forced expiratory volume in one second, or forced vital capacity, over baseline. PMID:6223289

National dosimetric audit network finds discrepancies in AAA lung inhomogeneity corrections.

PubMed

Dunn, Leon; Lehmann, Joerg; Lye, Jessica; Kenny, John; Kron, Tomas; Alves, Andrew; Cole, Andrew; Zifodya, Jackson; Williams, Ivan

2015-07-01

This work presents the Australian Clinical Dosimetry Service's (ACDS) findings of an investigation of systematic discrepancies between treatment planning system (TPS) calculated and measured audit doses. Specifically, a comparison between the Anisotropic Analytic Algorithm (AAA) and other common dose-calculation algorithms in regions downstream (≥2cm) from low-density material in anthropomorphic and slab phantom geometries is presented. Two measurement setups involving rectilinear slab-phantoms (ACDS Level II audit) and anthropomorphic geometries (ACDS Level III audit) were used in conjunction with ion chamber (planar 2D array and Farmer-type) measurements. Measured doses were compared to calculated doses for a variety of cases, with and without the presence of inhomogeneities and beam-modifiers in 71 audits. Results demonstrate a systematic AAA underdose with an average discrepancy of 2.9 ± 1.2% when the AAA algorithm is implemented in regions distal from lung-tissue interfaces, when lateral beams are used with anthropomorphic phantoms. This systemic discrepancy was found for all Level III audits of facilities using the AAA algorithm. This discrepancy is not seen when identical measurements are compared for other common dose-calculation algorithms (average discrepancy -0.4 ± 1.7%), including the Acuros XB algorithm also available with the Eclipse TPS. For slab phantom geometries (Level II audits), with similar measurement points downstream from inhomogeneities this discrepancy is also not seen. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Dose-response study of sajabalssuk ethanol extract from Artemisia princeps Pampanini on blood glucose in subjects with impaired fasting glucose or mild type 2 diabetes.

PubMed

Choi, Ji-Young; Shin, Su-Kyung; Jeon, Seon-Min; Baek, Nam-In; Chung, Hae-Gon; Jeong, Tae-Sook; Lee, Kyung Tae; Lee, Mi-Kyung; Choi, Myung-Sook

2011-01-01

Previously we reported that an ethanol extract from Artemisia princeps Pampanini lowered blood glucose in db/db mice. Here we report a preliminary study in which the blood glucose-lowering effects of two different doses of sajabalssuk ethanol extract (SBE), containing eupatilin and jaseocidin, were examined in hyperglycemic subjects with fasting blood glucose (FBG) levels of 100-150 mg/dL. Subjects were randomized into four groups: negative control (2,000 mg of lactose /day), positive control (1,140 mg of pinitol/day), low-dose SBE (2,000 mg of SBE/day), and high-dose SBE (4,000 mg of SBE/day). After 8 weeks of supplementation, FBG and glycosylated hemoglobin levels were significantly lowered in low-and high-dose SBE groups compared to the baseline values; high-dose SBE also resulted in significantly lower plasma free fatty acid levels and systolic blood pressure. This study demonstrated that supplementation of 2 g or 4 g of SBE daily can significantly reduce blood glucose in hyperglycemic subjects, although high-dose SBE seemed to be more effective than low-dose SBE for lowering plasma free fatty acid level and systolic blood pressure.

Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

PubMed

Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

2004-11-01

The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P < .05). However, predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup. ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage. Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

Solar Modulation of Atmospheric Cosmic Radiation:. Comparison Between In-Flight and Ground-Level Measurements

NASA Astrophysics Data System (ADS)

Iles, R. H. A.; Taylor, G. C.; Jones, J. B. L.

January 2000 saw the start of a collaborative study involving the Mullard Space Science Laboratory, Virgin Atlantic Airways, the Civil Aviation Authority and the National Physical Laboratory in a program to investigate the cosmic radiation exposure to aircrew. The study has been undertaken in view of EU Directive 96/291 (May 2000) which requires the assessment of the level of radiation exposure to aircrew. The project's aims include validation of radiation dose models and evaluation of space weather effects on atmospheric cosmic radiation levels, in particular those effects not accounted for by the models. Ground level measurements are often used as a proxy for variations in cosmic radiation dose levels at aircraft altitudes, especially during Forbush Decreases (FDs) and Solar Energetic Particle (SEP) events. Is this estimation realistic and does the ground level data accurately represent what is happening at altitude? We have investigated the effect of a FD during a flight from Hong Kong to London Heathrow on the 15th July 2000 and compared count rate and dose measurements with simultaneous variations measured at ground level. We have also compared the results with model outputs.

Fully Convolutional Architecture for Low-Dose CT Image Noise Reduction

NASA Astrophysics Data System (ADS)

Badretale, S.; Shaker, F.; Babyn, P.; Alirezaie, J.

2017-10-01

One of the critical topics in medical low-dose Computed Tomography (CT) imaging is how best to maintain image quality. As the quality of images decreases with lowering the X-ray radiation dose, improving image quality is extremely important and challenging. We have proposed a novel approach to denoise low-dose CT images. Our algorithm learns directly from an end-to-end mapping from the low-dose Computed Tomography images for denoising the normal-dose CT images. Our method is based on a deep convolutional neural network with rectified linear units. By learning various low-level to high-level features from a low-dose image the proposed algorithm is capable of creating a high-quality denoised image. We demonstrate the superiority of our technique by comparing the results with two other state-of-the-art methods in terms of the peak signal to noise ratio, root mean square error, and a structural similarity index.

[Effect of red maca (Lepidium meyenii) on INF-γ levels in ovariectomized rats].

PubMed

Leiva-Revilla, Johanna; Guerra-Castañon, Félix; Olcese-Mori, Paola; Lozada, Iván; Rubio, Julio; Gonzales, Carla; Gonzales, Gustavo F

2014-01-01

Compare the effect of different doses of red maca on gamma interferon (IFN-γ) levels in ovariectomized rats (OVX). Adult female rats were randomly divided into the following six groups: Group 1: pseudo-ovariectomized rats (PO); Group 2: OVX rats; Group 3: OVX rats treated with 4 ug/kg estradiol; and Group 4, 5 and 6: OVX rats treated with red maca extracts with 2.15, 4.3 and 8.6 mg polyphenols/body weight kilogram, respectively. OVX rats showed low levels of IFN-γ compared to PO rats. Estradiol and red maca reversed the effect of ovariectomy on the IFN-γ levels. A positive dose-response effect of red maca on IFN-γ levels was shown (r = 0.57, p <0.05). Red maca administration increases levels of IFN-γ in ovariectomized rats.

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.

PubMed

Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten-A; Söder, Olle; Roche, Edna; Hoey, Hilary; Dunger, David B; Juul, Anders

2014-10-01

Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children. © 2014 European Society of Endocrinology.

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

PubMed

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

2016-02-01

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

Demand- and supply-side determinants of diphtheria-pertussis-tetanus nonvaccination and dropout in rural India.

PubMed

Ghosh, Arpita; Laxminarayan, Ramanan

2017-02-15

Although 93% of 12- to 23-month-old children in India receive at least one vaccine, typically Bacillus Calmette-Guérin, only 75% complete the recommended three doses of diphtheria-pertussis-tetanus (DPT, also referred to as DTP) vaccine. Determinants can be different for nonvaccination and dropout but have not been examined in earlier studies. We use the three-dose DPT series as a proxy for the full sequence of recommended childhood vaccines and examine the determinants of DPT nonvaccination and dropout between doses 1 and 3. We analyzed data on 75,728 6- to 23-month-old children in villages across India to study demand- and supply-side factors determining nonvaccination with DPT and dropout between DPT doses 1 and 3, using a multilevel approach. Data come from the District Level Household and Facility Survey 3 (2007-08). Individual- and household-level factors were associated with both DPT nonvaccination and dropout between doses 1 and 3. Children whose mothers had no schooling were 2.3 times more likely not to receive any DPT vaccination and 1.5 times more likely to drop out between DPT doses 1 and 3, compared with children whose mothers had 10 or more years of schooling. Although supply-side factors related to availability of public health facilities and immunization-related health workers in villages were not correlated with dropout between DPT doses 1 and 3, children in districts where 46% or more villages had a healthcare subcentre were 1.5 times more likely to receive at least one dose of DPT vaccine compared with children in districts where 30% or fewer villages had subcentres. Nonvaccination with DPT in India is influenced by village- and district-level contextual factors over and above individuals' background characteristics. Dropout between DPT doses 1 and 3 is associated more strongly with demand-side factors than with village- and district-level supply-side factors. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Differential response of two cell lines sequentially irradiated with low X-ray doses.

PubMed

Güerci, A M; Dulout, F N; Grillo, C A; Seoane, A I

2005-05-01

An experiment was designed to compare the effect of repeated low doses of X-rays in two different cell lines: one transformed, epithelial like and aneuploid Chinese hamster ovary K-1 (CHO-K1); the other originated from a human primary culture, fibroblast, diploid and non-transformed, MRC-5. CHO and MRC-5 cells were cultured for 14 or eight passages, respectively. Irradiation was performed once per passage when cells were in the quiescent state (90 - 95% in G1/G0). Cells were exposed to 10.0 mSv X-ray doses. Ionizing radiation did not induce apoptosis or necrosis in the exposed CHO cell population. Significant increases of low-level damaged cells (degrees 1 and 2) were found for the 14 cycles of radiation when compared with controls, except for the first irradiation cycle. No significant increases in the frequency of cells with severe damage were observed. The frequency of MRC-5 cells with low-level damage increased significantly when compared with controls for radiation cycles seven and eight. Significant increases of apoptosis, necrosis and severe damage were found only for the highest dose. Transformed and non-transformed cell types responded differently to direct and indirect damage using low-dose repeat exposures to ionizing radiation. Though more investigation is needed to understand the mechanisms of radiation effects in chronic low-dose-exposed cell populations, cellular type should be taken into account in the design of in vitro experiments for understanding low-dose-irradiation effects.

Efficacy of multiple exposure with low level He-Ne laser dose on acute wound healing: a pre-clinical study

NASA Astrophysics Data System (ADS)

Prabhu, Vijendra; Rao, Bola Sadashiva S.; Mahato, Krishna Kishore

2014-02-01

Investigations on the use of Low Level Laser Therapy (LLLT) for wound healing especially with the red laser light have demonstrated its pro-healing potential on a variety of pre-clinical and surgical wounds. However, until now, in LLLT the effect of multiple exposure of low dose laser irradiation on acute wound healing on well-designed pre-clinical model is not much explored. The present study aimed to investigate the effect of multiple exposure of low dose Helium Neon laser on healing progression of full thickness excision wounds in Swiss albino mice. Further, the efficacy of the multiple exposure of low dose laser irradiation was compared with the single exposure of optimum dose. Full thickness excision wounds (circular) of 15 mm diameter were created, and subsequently illuminated with the multiple exposures (1, 2, 3, 4 and 5 exposure/ week until healing) of He-Ne (632.8 nm, 4.02 mWcm-2) laser at 0.5 Jcm-2 along with single exposure of optimum laser dose (2 J/cm-2) and un-illuminated controls. Classical biophysical parameters such as contraction kinetics, area under the curve and the mean healing time were documented as the assessment parameters to examine the efficacy of multiple exposures with low level laser dose. Experimental findings substantiated that either single or multiple exposures of 0.5 J/cm2 failed to produce any detectable alterations on wound contraction, area under the curve and mean healing time compared to single exposure of optimum dose (2 Jcm-2) and un-illuminated controls. Single exposure of optimum, laser dose was found to be ideal for acute wound healing.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

PubMed

Narula, Neeraj; Cooray, Mohan; Anglin, Rebecca; Muqtadir, Zack; Narula, Alisha; Marshall, John K

2017-02-01

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. NCT02615288.

Synthesis, Characterization, Antioxidant Status, and Toxicity Study of Vanadium-Rutin Complex in Balb/c Mice.

PubMed

Roy, Souvik; Majumdar, Sumana; Singh, Amit Kumar; Ghosh, Balaram; Ghosh, Nilanjan; Manna, Subhadip; Chakraborty, Tania; Mallick, Sougato

2015-08-01

A new trend was developed for the formation of a complex between vanadium and flavonoid derivatives in order to increase the intestinal absorption and to reduce the toxicity of vanadium compounds. The vanadium-rutin complex was characterized by several spectroscopic techniques like ultraviolet (UV)-visible, Fourier transform infrared (FTIR), NMR, mass spectrometry, and microscopic evaluation by scanning electron microscopy. The mononuclear complex was formed by the interaction between vanadium and rutin with 1:2 metal to ligand stoichiometry. Antioxidant activity of the complex was evaluated by 1,1-diphenyl-2 picrylhydrazyl, ferric-reducing power, and 2,2'-azin-obis 3-ethylbenzothiazoline-6-sulphonic acid methods. It was shown that radical scavenging activity and ferric-reducing potential of free rutin was lower as compared with vanadium-rutin complex. The study was also investigated for oral acute toxicity and 28 days repeated oral subacute toxicity study of vanadium-rutin complex in balb/c mice. The vanadium-rutin complex showed mortality at a dose of 120 mg/kg in the balb/c mice. In 28 days repeated oral toxicity study, vanadium-rutin complex was administered to both sex of balb/c mice at dose levels of 90, 45, and 20 ppm, respectively. In addition, subacute toxicity study of vanadium-rutin complex (at 90 ppm dose level) showed increase levels of white blood cell (WBC), total bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen and decrease level of total protein (TP) as compared with control group. Histopathological study of vanadium-rutin showed structural alteration in the liver, kidney, and stomach at 90 ppm dose level. No observed toxic level of vanadium-rutin complex at 20 ppm dose level could be good for further study.

High dose vitamin D may improve lower urinary tract symptoms in postmenopausal women.

PubMed

Oberg, Johanna; Verelst, Margareta; Jorde, Rolf; Cashman, Kevin; Grimnes, Guri

2017-10-01

Lower urinary tract symptoms (LUTS) are common in postmenopausal women, and have been reported inversely associated with vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels. The aim of this study was to investigate if high dose vitamin D supplementation would affect LUTS in comparison to standard dose. In a randomized controlled study including 297 postmenopausal women with low bone mineral density, the participants were allocated to receive capsules of 20 000IU of vitamin D 3 twice a week (high dose group) or similar looking placebo (standard dose group). In addition, all the participants received 1g of calcium and 800IU of vitamin D daily. A validated questionnaire regarding LUTS was filled in at baseline and after 12 months. At baseline, 76 women in the high dose group and 82 in the standard dose group reported any LUTS. Levels of serum 25(OH)D increased significantly more in the high dose group (from 64.7 to 164.1nmol/l compared to from 64.1 to 81.8nmol/l, p<0.01). No differences between the groups were seen regarding change in LUTS except for a statistically significant reduction in the reported severity of urine incontinence in the high dose group as compared to the standard dose group after one year (p<0.05). The results need confirmation in a study specifically designed for this purpose. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glycerol phenylbutyrate treatment in children with urea cycle disorders: pooled analysis of short and long-term ammonia control and outcomes.

PubMed

Berry, Susan A; Lichter-Konecki, Uta; Diaz, George A; McCandless, Shawn E; Rhead, William; Smith, Wendy; Lemons, Cynthia; Nagamani, Sandesh C S; Coakley, Dion F; Mokhtarani, Masoud; Scharschmidt, Bruce F; Lee, Brendan

2014-05-01

To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). UCD patients (n=26) ages 2months through 17years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammonia exposure (AUC0-24) and glutamine levels during equivalent steady-state dosing of GPB and sodium phenylbutyrate (NaPBA). These 26 patients plus an additional 23 patients also received GPB in one of three 12-month, open label extension studies, which assessed long-term ammonia control, hyperammonemic (HA) crises, amino acid levels, and patient growth. Mean ammonia exposure on GPB was non-inferior to NaPBA in each of the individual crossover studies. In the pooled analyses, it was significantly lower on GPB vs. NaPBA (mean [SD] AUC0-24: 627 [302] vs. 872 [516] μmol/L; p=0.008) with significantly fewer abnormal values (15% on GPB vs. 35% on NaPBA; p=0.02). Mean ammonia levels remained within the normal range during 12months of GPB dosing and, when compared with the 12months preceding enrollment, a smaller percentage of patients (24.5% vs. 42.9%) experienced fewer (17 vs. 38) HA crises. Glutamine levels tended to be lower with GPB than with NaPBA during short-term dosing (mean [SD]: 660.8 [164.4] vs. 710.0 [158.7] μmol/L; p=0.114) and mean glutamine and branched chain amino acid levels, as well as other essential amino acids, remained within the normal range during 12months of GPB dosing. Mean height and weight Z-scores were within normal range at baseline and did not change significantly during 12months of GPB treatment. Dosing with GPB was associated with 24-hour ammonia exposure that was non-inferior to that during dosing with NaPBA in individual studies and significantly lower in the pooled analysis. Long-term GPB dosing was associated with normal levels of glutamine and essential amino acids, including branched chain amino acids, age-appropriate growth and fewer HA crises as compared with the 12month period preceding enrollment. Copyright © 2014 Elsevier Inc. All rights reserved.

Glycerol Phenylbutyrate Treatment in Children with Urea Cycle Disorders: Pooled Analysis of Short and Long-term Ammonia Control and Outcomes

PubMed Central

Berry, Susan A.; Lichter-Konecki, Uta; Diaz, George A.; McCandless, Shawn E.; Rhead, William; Smith, Wendy; LeMons, Cynthia; Nagamani, Sandesh C.S.; Coakley, Dion F.; Mokhtarani, Masoud; Scharschmidt, Bruce F.; Lee, Brendan

2015-01-01

Objective To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). Study Design UCD patients (n=26) ages 2 months through 17 years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammonia exposure (AUC0–24) and glutamine levels during equivalent steady-state dosing of GPB and sodium phenylbutyrate (NaPBA). These 26 patients plus an additional 23 patients also received GPB in one of three 12-month, open label extension studies, which assessed long-term ammonia control, hyperammonemic (HA) crises, amino acids levels, and patient growth. Results Mean ammonia exposure on GPB was non-inferior to NaPBA in each of the individual crossover studies. In the pooled analyses, it was significantly lower on GPB vs. NaPBA (mean [SD] AUC0–24: 627 [302] vs. 872 [516] µmol/L; p=0.008) with significantly fewer abnormal values (15% on GPB vs. 35% on NaPBA; p = 0.02). Mean ammonia levels remained within the normal range during 12 months of GPB dosing and, when compared with the 12 months preceding enrollment, a smaller percentage of patients (24.5% vs. 42.9%) experienced fewer (17 vs. 38) HA crises. Glutamine levels tended to be lower with GPB than with NaPBA during short-term dosing (mean [SD]: 660.8 [164.4] vs. 710.0 [158.7] µmol/L; p=0.114) and mean glutamine and branched chain amino acids levels, as well as other essential amino acids, remained within the normal range during 12 months of GPB dosing. Mean height and weight Z-scores were within normal range at baseline and did not change significantly during 12 months of GPB treatment. Conclusions Dosing with GPB was associated with 24-hour ammonia exposure that was non-inferior to that during dosing with NaPBA in individual studies and significantly lower in the pooled analysis. Long-term GPB dosing was associated with normal levels of glutamine and essential amino acids, including branched chain amino acids, age-appropriate growth and fewer HA crises as compared with the 12 month period preceding enrollment. PMID:24630270

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

PubMed

Santarmaki, Valentini; Kourkoutas, Yiannis; Zoumpopoulou, Georgia; Mavrogonatou, Eleni; Kiourtzidis, Mikis; Chorianopoulos, Nikos; Tassou, Chrysoula; Tsakalidou, Effie; Simopoulos, Constantinos; Ypsilantis, Petros

2017-09-01

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats

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

Moser, Virginia C., E-mail: Moser.ginger@epa.gov

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavagemore » dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administered dose, the differences based on internal concentrations were less, with γ-cyhalothrin being 1.3- to 1.6-fold more potent than λ-cyhalothrin. These potency differences are consistent with the purity of the λ-isomer (approximately 43%) compared to the enriched isomer γ-cyhalothrin (approximately 98%). Thus, administered dose as well as differences in cyhalothrin isomers is a good predictor of behavioral effects. - Highlights: • Acute changes in locomotor activity were produced by λ- and γ-cyhalothrin. • γ-Cyhalothrin was about 2-fold more potent than λ-cyhalothrin. • Brain and plasma levels were tightly correlated across doses. • Activity changes correlated well with brain and plasma concentrations.« less

Update of a comparative analysis of cost minimization following the introduction of newly available intravenous iron therapies in hospital practice

PubMed Central

Bhandari, Sunil

2011-01-01

Background The clinical need to be able to administer high doses of intravenous iron conveniently as a rapid infusion has been addressed by the recent introduction of ferric carboxymaltose and subsequently iron isomaltoside 1000. Neither requires a test dose. The maximum dose of ferric carboxymaltose is 1000 mg. The maximum dose of iron isomaltoside 1000 is based on 20 mg/kg body weight without a specified ceiling dose, thereby increasing the scope of being able to achieve total iron repletion with a single infusion. This ability to give high doses of iron is important in the context of managing iron deficiency anemia, which is associated with a number of clinical conditions where demands for iron are high. It is also an important component of the strategy as an alternative to blood transfusion. Affordability is a key issue for health services. Recent price changes affecting iron sucrose and ferric carboxymaltose, plus modifications to the manufacturers’ prescribing information, have provoked this update. Methods This study is a comparative analysis of the costs of acquiring and administering the newly available intravenous iron formulations against standard treatments in the hospital setting. The costs include the medication, nursing costs, equipment, and patient transportation. Three dosage levels (600 mg, 1000 mg, and 1600 mg) are considered. Results and conclusion The traditional standard treatments, blood and iron sucrose, cost more than the alternative intravenous iron preparations across the dose spectrum and sensitivities. Low molecular weight iron dextran is the least expensive option at the 1600 mg dose level but has the caveat of a prolonged administration time and requirement for a test dose. At 600 mg and 1000 mg dose levels, both iron isomaltoside 1000 and ferric carboxymaltose are more economical than low molecular weight iron dextran. Iron isomaltoside 1000 is less expensive than ferric carboxymaltose at all dose levels. Newly available iron preparations appear to be clinically promising, cost effective, and practical alternatives to current standards of iron repletion. PMID:22241947

Determination of cytokine protein levels in oral secretions in patients undergoing radiotherapy for head and neck malignancies

PubMed Central

2012-01-01

Background Cytokines may be elevated in tumor and normal tissues following irradiation. Cytokine expression in these tissues may predict for toxicity or tumor control. The purpose of this pilot study was to determine the feasibility of measuring local salivary cytokine levels using buccal sponges in patients receiving chemo-radiation for head and neck malignancies. Patients and methods 11 patients with epithelial malignancies of the head and neck were recruiting to this study. All patients received radiotherapy to the head and neck region with doses ranging between 60 – 67.5 Gy. Chemotherapy was delivered concurrently with radiation in all patients. Salivary samples were obtained from high dose and low dose regions prior to treatment and at three intervals during treatment for assessment of cytokine levels (IL-4, IL-6, IL-8, IL-10, EGF, MCP-1, TNF-α, and VEGF). Results Cytokine levels were detectable in the salivary samples. Salivary cytokine levels of IL-4, IL-6, IL-8, EGF, MCP-1, TNF- α , and VEGF were higher in the high dose region compared to the low dose region at all time points (p < 0.05). A trend toward an increase in cytokine levels as radiation dose increased was observed for IL-6, IL-8, MCP-1, and TNF-α. Conclusion Assessment of salivary cytokine levels may provide a novel method to follow local cytokine levels during radiotherapy and may provide a mechanism to study cytokine levels in a regional manner. PMID:22537315

Performance of toxicity probability interval based designs in contrast to the continual reassessment method

PubMed Central

Horton, Bethany Jablonski; Wages, Nolan A.; Conaway, Mark R.

2016-01-01

Toxicity probability interval designs have received increasing attention as a dose-finding method in recent years. In this study, we compared the two-stage, likelihood-based continual reassessment method (CRM), modified toxicity probability interval (mTPI), and the Bayesian optimal interval design (BOIN) in order to evaluate each method's performance in dose selection for Phase I trials. We use several summary measures to compare the performance of these methods, including percentage of correct selection (PCS) of the true maximum tolerable dose (MTD), allocation of patients to doses at and around the true MTD, and an accuracy index. This index is an efficiency measure that describes the entire distribution of MTD selection and patient allocation by taking into account the distance between the true probability of toxicity at each dose level and the target toxicity rate. The simulation study considered a broad range of toxicity curves and various sample sizes. When considering PCS, we found that CRM outperformed the two competing methods in most scenarios, followed by BOIN, then mTPI. We observed a similar trend when considering the accuracy index for dose allocation, where CRM most often outperformed both the mTPI and BOIN. These trends were more pronounced with increasing number of dose levels. PMID:27435150

Modelling the effects of booster dose vaccination schedules and recommendations for public health immunization programs: the case of Haemophilus influenzae serotype b.

PubMed

Charania, Nadia A; Moghadas, Seyed M

2017-09-13

Haemophilus influenzae serotype b (Hib) has yet to be eliminated despite the implementation of routine infant immunization programs. There is no consensus regarding the number of primary vaccine doses and an optimal schedule for the booster dose. We sought to evaluate the effect of a booster dose after receiving the primary series on the long-term disease incidence. A stochastic model of Hib transmission dynamics was constructed to compare the long-term impact of a booster vaccination and different booster schedules after receiving the primary series on the incidence of carriage and symptomatic disease. We parameterized the model with available estimates for the efficacy of Hib conjugate vaccine and durations of both vaccine-induced and naturally acquired immunity. We found that administering a booster dose substantially reduced the population burden of Hib disease compared to the scenario of only receiving the primary series. Comparing the schedules, the incidence of carriage for a 2-year delay (on average) in booster vaccination was comparable or lower than that observed for the scenario of booster dose within 1 year after primary series. The temporal reduction of symptomatic disease was similar in the two booster schedules, suggesting no superiority of one schedule over the other in terms of reducing the incidence of symptomatic disease. The findings underscore the importance of a booster vaccination for continued decline of Hib incidence. When the primary series provides a high level of protection temporarily, delaying the booster dose (still within the average duration of protection conferred by the primary series) may be beneficial to maintain longer-term protection levels and decelerate the decline of herd immunity in the population.

Vitamin E reduces hepatic fibrosis in mice with Schistosoma japonicum infection.

PubMed

Wang, Xuefeng; Zhang, Rongbo; Du, Jiuwei; Hu, Youying; Xu, Lifa; Lu, Jun; Ye, Song

2012-02-01

To investigate whether vitamin E protects against hepatic fibrosis in mice with Schistosoma japonicum infection, 24 pathogen-free Kunming mice were selected and randomly divided into four groups: control (uninfected, untreated), model (infected, untreated), low-dose intervention (infected, vitamin E-treated, 30 mg/g bodyweight/day) and high-dose intervention (infected, vitamin E-treated, 60 mg/g bodyweight/day). Mice were infected with Schistosoma japonicum by inoculating abdominal skin with snail hosts. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were detected in hepatic tissue by colorimetry. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type Ⅲ (PC-III) and type Ⅳ collagen (IV-C) were detected in the serum by radioimmunoassay. Finally, areas and numbers of granulomas were assessed through histopathology 42 days following treatment. The results revealed that mean areas of granulomas were smaller in the low- and high-dose intervention groups compared to those in the model group. Furthermore, the higher dose of vitamin E resulted in smaller granulomas than the low dose. The levels of LN, HA, PC-III and IV-C in the serum were lower following vitamin E treatment than in the model group. By contrast, activity of SOD, GPx and CAT in hepatic tissue was higher following vitamin E treatment compared to the model group. The activity of MDA was lower in hepatic tissue following vitamin E treatment compared to the model group, but was higher compared to controls. In general, the higher dose of vitamin E affected measurements to a greater extent than the lower dose. In conclusion, vitamin E treatment may reduce the growth of granulomas, slowing the process of hepatic fibrosis, and this effect may be the result of the altered activity of the oxidation-reduction enzyme system.

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

PubMed

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

2001-01-01

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

Intra-individual diagnostic image quality and organ-specific-radiation dose comparison between spiral cCT with iterative image reconstruction and z-axis automated tube current modulation and sequential cCT.

PubMed

Wenz, Holger; Maros, Máté E; Meyer, Mathias; Gawlitza, Joshua; Förster, Alex; Haubenreisser, Holger; Kurth, Stefan; Schoenberg, Stefan O; Groden, Christoph; Henzler, Thomas

2016-01-01

To prospectively evaluate image quality and organ-specific-radiation dose of spiral cranial CT (cCT) combined with automated tube current modulation (ATCM) and iterative image reconstruction (IR) in comparison to sequential tilted cCT reconstructed with filtered back projection (FBP) without ATCM. 31 patients with a previous performed tilted non-contrast enhanced sequential cCT aquisition on a 4-slice CT system with only FBP reconstruction and no ATCM were prospectively enrolled in this study for a clinical indicated cCT scan. All spiral cCT examinations were performed on a 3rd generation dual-source CT system using ATCM in z-axis direction. Images were reconstructed using both, FBP and IR (level 1-5). A Monte-Carlo-simulation-based analysis was used to compare organ-specific-radiation dose. Subjective image quality for various anatomic structures was evaluated using a 4-point Likert-scale and objective image quality was evaluated by comparing signal-to-noise ratios (SNR). Spiral cCT led to a significantly lower (p < 0.05) organ-specific-radiation dose in all targets including eye lense. Subjective image quality of spiral cCT datasets with an IR reconstruction level 5 was rated significantly higher compared to the sequential cCT acquisitions (p < 0.0001). Consecutive mean SNR was significantly higher in all spiral datasets (FBP, IR 1-5) when compared to sequential cCT with a mean SNR improvement of 44.77% (p < 0.0001). Spiral cCT combined with ATCM and IR allows for significant-radiation dose reduction including a reduce eye lens organ-dose when compared to a tilted sequential cCT while improving subjective and objective image quality.

Definition of Local Diagnostic Reference Levels in a Radiology Department Using a Dose Tracking Software.

PubMed

Ghetti, C; Ortenzia, O; Palleri, F; Sireus, M

2017-06-01

Dose optimization in radiological examinations is a mandatory issue: in this study local Diagnostic Reference Levels (lDRLs) for Clinical Mammography (MG), Computed Tomography (CT) and Interventional Cardiac Procedures (ICP) performed in our Radiology Department were established. Using a dose tracking software, we have collected Average Glandular Dose (AGD) for two clinical mammographic units; CTDIvol, Size-Specific Dose Estimate (SSDE), Dose Length Product (DLP) and total DLP (DLPtot) for five CT scanners; Fluoro Time, Fluoro Dose Area Product (DAP) and total DAP (DAPtot) for two angiographic systems. Data have been compared with Italian Regulation and with the recent literature. The 75th percentiles of the different dosimetric indices have been calculated. Automated methods of radiation dose data collection allow a fast and detailed analysis of a great amount of data and an easy determination of lDRLs for different radiological procedures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Patient doses from chest radiography in Victoria.

PubMed

Cardillo, I; Boal, T J; Einsiedel, P F

1997-06-01

This survey examines doses from PA chest radiography at radiology practices, private hospitals and public hospitals throughout metropolitan and country Victoria. Data were collected from 111 individual X-ray units at 86 different practices. Entrance skin doses in air were measured for exposure factors used by the centre for a 23 cm thick male chest. A CDRH LucA1 chest phantom was used when making these measurements. About half of the centres used grid technique and half used non-grid technique. There was a factor of greater than 10 difference in the entrance dose delivered between the highest dose centre and the lowest dose centre for non-grid centres; and a factor of about 5 for centres using grids. Factors contributing to the high doses recorded at some centres were identified. Guidance levels for chest radiography based on the third quartile value of the entrance doses from this survey have been recommended and compared with guidance levels recommended in other countries.

Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure.

PubMed

Maier, Joscha; Sawall, Stefan; Kachelrieß, Marc

2014-05-01

Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the best performance. At 50 mGy, the deviation from the reference obtained at 500 mGy were less than 4%. Also the LDPC algorithm provides reasonable results with deviation less than 10% at 50 mGy while PCF and MKB reconstruction show larger deviations even at higher dose levels. LDPC and HDTV increase CNR and allow for quantitative evaluations even at dose levels as low as 50 mGy. The left ventricular volumes exemplarily illustrate that cardiac parameters can be accurately estimated at lowest dose levels if sophisticated algorithms are used. This allows to reduce dose by a factor of 10 compared to today's gold standard and opens new options for longitudinal studies of the heart.

Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidence in rodent bioassays.

PubMed

Paini, Alicia; Scholz, Gabriele; Marin-Kuan, Maricel; Schilter, Benoît; O'Brien, John; van Bladeren, Peter J; Rietjens, Ivonne M C M

2011-09-01

This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate whether a correlation can be obtained, using a benchmark dose (BMD) approach. Dose-response data on both carcinogenicity and in vivo DNA adduct formation were available for six compounds, i.e. 2-acetylaminofluorene, aflatoxin B1, methyleugenol, safrole, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and tamoxifen. BMD(10) values for liver carcinogenicity were calculated using the US Environmental Protection Agency BMD software. DNA adduct levels at this dose were extrapolated assuming linearity of the DNA adduct dose response. In addition, the levels of DNA adducts at the BMD(10) were compared to available data on endogenous background DNA damage in the target organ. Although for an individual carcinogen the tumour response increases when adduct levels increase, our results demonstrate that when comparing different carcinogens, no quantitative correlation exists between the level of DNA adduct formation and carcinogenicity. These data confirm that the quantity of DNA adducts formed by a DNA-reactive compound is not a carcinogenicity predictor but that other factors such as type of adduct and mutagenic potential may be equally relevant. Moreover, comparison to background DNA damage supports the notion that the mere occurrence of DNA adducts above or below the level of endogenous DNA damage is neither correlated to development of cancer. These data strongly emphasise the need to apply the mode of action framework to understand the contribution of other biological effect markers playing a role in carcinogenicity.

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

PubMed Central

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

2010-01-01

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

Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis.

PubMed

Tvete, Ingunn Fride; Natvig, Bent; Gåsemyr, Jørund; Meland, Nils; Røine, Marianne; Klemp, Marianne

2015-01-01

Rheumatoid arthritis patients have been treated with disease modifying anti-rheumatic drugs (DMARDs) and the newer biologic drugs. We sought to compare and rank the biologics with respect to efficacy. We performed a literature search identifying 54 publications encompassing 9 biologics. We conducted a multiple treatment comparison regression analysis letting the number experiencing a 50% improvement on the ACR score be dependent upon dose level and disease duration for assessing the comparable relative effect between biologics and placebo or DMARD. The analysis embraced all treatment and comparator arms over all publications. Hence, all measured effects of any biologic agent contributed to the comparison of all biologic agents relative to each other either given alone or combined with DMARD. We found the drug effect to be dependent on dose level, but not on disease duration, and the impact of a high versus low dose level was the same for all drugs (higher doses indicated a higher frequency of ACR50 scores). The ranking of the drugs when given without DMARD was certolizumab (ranked highest), etanercept, tocilizumab/ abatacept and adalimumab. The ranking of the drugs when given with DMARD was certolizumab (ranked highest), tocilizumab, anakinra/rituximab, golimumab/ infliximab/ abatacept, adalimumab/ etanercept [corrected]. Still, all drugs were effective. All biologic agents were effective compared to placebo, with certolizumab the most effective and adalimumab (without DMARD treatment) and adalimumab/ etanercept (combined with DMARD treatment) the least effective. The drugs were in general more effective, except for etanercept, when given together with DMARDs.

Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis

PubMed Central

Tvete, Ingunn Fride; Natvig, Bent; Gåsemyr, Jørund; Meland, Nils; Røine, Marianne; Klemp, Marianne

2015-01-01

Rheumatoid arthritis patients have been treated with disease modifying anti-rheumatic drugs (DMARDs) and the newer biologic drugs. We sought to compare and rank the biologics with respect to efficacy. We performed a literature search identifying 54 publications encompassing 9 biologics. We conducted a multiple treatment comparison regression analysis letting the number experiencing a 50% improvement on the ACR score be dependent upon dose level and disease duration for assessing the comparable relative effect between biologics and placebo or DMARD. The analysis embraced all treatment and comparator arms over all publications. Hence, all measured effects of any biologic agent contributed to the comparison of all biologic agents relative to each other either given alone or combined with DMARD. We found the drug effect to be dependent on dose level, but not on disease duration, and the impact of a high versus low dose level was the same for all drugs (higher doses indicated a higher frequency of ACR50 scores). The ranking of the drugs when given without DMARD was certolizumab (ranked highest), etanercept, tocilizumab/ abatacept and adalimumab. The ranking of the drugs when given with DMARD was certolizumab (ranked highest), tocilizumab, anakinra, rituximab, golimumab/ infliximab/ abatacept, adalimumab/ etanercept. Still, all drugs were effective. All biologic agents were effective compared to placebo, with certolizumab the most effective and adalimumab (without DMARD treatment) and adalimumab/ etanercept (combined with DMARD treatment) the least effective. The drugs were in general more effective, except for etanercept, when given together with DMARDs. PMID:26356639

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

PubMed Central

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

2016-01-01

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

[Comparison of anti-inflammatory activity between crude Atractylodes lancea and their processed products by stir-baking with bran in rat models of gastric ulcer].

PubMed

Yu, Yan; Jia, Tian-Zhu; Cai, Qian

2016-02-01

To compare the anti-inflammatory activity of the crude Atractylodes lancea (AL) and AL processed products by stir-baking with bran in rat models of gastric ulcer, and preliminarily explore the anti-ulcer mechanisms of AL, the model of gastric ulcer was imitated by local acetic acid injection into gastric mucosa in rats by surgery according to the modified Okabe method. All rats were randomly divided into the following 10 groups： sham-operation group, model group, omeprazole group, Sanjiu Weitai granule group, crude AL low dose group, crude AL middle dose group, crude AL high dose group, processed AL low dose group, processed AL middle dose group, and processed AL high dose group. Rats were administered via intragastric (ig) two times each day, for 10 consecutive days. Blood was collected from the abdominal aorta, serum was separated, and the ulcer tissues were taken. The levels of inflammatory factors interleukin 6, 8 (IL-6, 8), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of TNF-α and IL-8 in gastric tissues were detected by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of TNF-α and IL-8 in gastric tissues were detected by immunohistochemistry. Compared with sham-operation group, the levels of TNF-α, IL-8, IL-6, PGE2 as well as the mRNA expressions and protein expressions of TNF-α, IL-8 in gastric tissues were significantly higher in model group. The above levels were reduced in different degrees in all treatment groups. Compared with the crude AL, same dose of processed AL was more effective in decreasing the levels of TNF-α, IL-8, IL-6, PGE2 in serum and gastric tissues and down-regulating the mRNA expressions of TNF-α and IL-8 in gastric tissues, with significant difference in middle dose groups and high dose groups. The results showed that AL had potent anti-inflammatory effects in rat models of gastric ulcer induced by acetic acid, and the processed AL had more obvious effect. The anti-ulcer action of AL could be attributed partly to down-regulating the levels of TNF-α, IL-8, IL-6 and PGE2. Copyright© by the Chinese Pharmaceutical Association.

ESTIMATION OF ADULT PATIENT DOSES FOR CHEST X-RAY EXAMINATIONS AND COMPARISON WITH DIAGNOSTIC REFERENCE LEVELS (DRLs).

PubMed

Bas Mor, H; Altinsoy, N; Söyler, I

2018-05-08

The aim of this study was to evaluate the radiation doses to patient during chest (posterior anterior/and lateral) examinations. The study was performed in three public hospitals of İstanbul province with a total of 300 adult patients. Entrance surface dose (ESD) measurements were conducted on computed radiography, digital radiography and screen film system. ESD was estimated by using International Atomic Energy Agency (IAEA) model and Davies model which are the common indirect models. Results were compared with diagnostic reference levels from the European Commission, IAEA and National Radiological Protection Board. Although the results are compatible with the international diagnostic reference levels, they present variations between the hospitals. Dose variations for the same type of X-ray examination support the idea that further optimization is possible.

High-dose tranexamic acid reduces intraoperative and postoperative blood loss in posterior lumbar interbody fusion.

PubMed

Kushioka, Junichi; Yamashita, Tomoya; Okuda, Shinya; Maeno, Takafumi; Matsumoto, Tomiya; Yamasaki, Ryoji; Iwasaki, Motoki

2017-03-01

OBJECTIVE Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery. Previous studies included limitations in terms of different TXA dose regimens, different levels and numbers of fused segments, and different surgical techniques. Therefore, the authors decided to strictly limit TXA dose regimens, surgical techniques, and fused segments in this study. There have been no reports of using TXA for prevention of intraoperative and postoperative blood loss in posterior lumbar interbody fusion (PLIF). The purpose of the study was to evaluate the efficacy of high-dose TXA in reducing blood loss and its safety during single-level PLIF. METHODS The study was a nonrandomized, case-controlled trial. Sixty consecutive patients underwent single-level PLIF at a single institution. The first 30 patients did not receive TXA. The next 30 patients received 2000 mg of intravenous TXA 15 minutes before the skin incision was performed and received the same dose again 16 hours after the surgery. Intra- and postoperative blood loss was compared between the groups. RESULTS There were no statistically significant differences in preoperative parameters of age, sex, body mass index, preoperative diagnosis, or operating time. The TXA group experienced significantly less intraoperative blood loss (mean 253 ml) compared with the control group (mean 415 ml; p < 0.01). The TXA group also had significantly less postoperative blood loss over 40 hours (mean 321 ml) compared with the control group (mean 668 ml; p < 0.01). Total blood loss in the TXA group (mean 574 ml) was significantly lower than in the control group (mean 1080 ml; p < 0.01). From 2 hours to 40 hours, postoperative blood loss in the TXA group was consistently significantly lower. There were no perioperative complications, including thromboembolic events. CONCLUSIONS High-dose TXA significantly reduced both intra- and postoperative blood loss without causing any complications during or after single-level PLIF.

Effects of irradiation source and dose level on quality characteristics of processed meat products

NASA Astrophysics Data System (ADS)

Ham, Youn-Kyung; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Kim, Yong-Jae; Choi, Yun-Sang; Song, Beom-Seok; Park, Jong-Heum; Kim, Cheon-Jei

2017-01-01

The effect of irradiation source (gamma-ray, electron-beam, and X-ray) and dose levels on the physicochemical, organoleptic and microbial properties of cooked beef patties and pork sausages was studied, during 10 days of storage at 30±1 °C. The processed meat products were irradiated at 0, 2.5, 5, 7.5, and 10 kGy by three different irradiation sources. The pH of cooked beef patties and pork sausages was unaffected by irradiation sources or their doses. The redness of beef patties linearly decreased with increasing dose level (P<0.05), obviously by e-beam irradiation compared to gamma-ray and X-ray (P<0.05). The redness of pork sausages was increased by gamma-ray irradiation, whereas it decreased by e-beam irradiation depending on absorbed dose level. No significant changes in overall acceptability were observed for pork sausages regardless of irradiation source (P>0.05), while gamma-ray irradiated beef patties showed significantly decreased overall acceptability in a dose-dependent manner (P<0.05). Lipid oxidation of samples was accelerated by irradiation depending on irradiation sources and dose levels during storage at 30 °C. E-beam reduced total aerobic bacteria of beef patties more effectively, while gamma-ray considerably decreased microbes in pork sausages as irradiation dose increased. The results of this study indicate that quality attributes of meat products, in particular color, lipid oxidation, and microbial properties are significantly influenced by the irradiation sources.

Effect of ultra-low doses, ASIR and MBIR on density and noise levels of MDCT images of dental implant sites.

PubMed

Widmann, Gerlig; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Al-Ekrish, Asma'a A

2017-05-01

Differences in noise and density values in MDCT images obtained using ultra-low doses with FBP, ASIR, and MBIR may possibly affect implant site density analysis. The aim of this study was to compare density and noise measurements recorded from dental implant sites using ultra-low doses combined with FBP, ASIR, and MBIR. Cadavers were scanned using a standard protocol and four low-dose protocols. Scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Density (mean Hounsfield units [HUs]) of alveolar bone and noise levels (mean standard deviation of HUs) was recorded from all datasets and measurements were compared by paired t tests and two-way ANOVA with repeated measures. Significant differences in density and noise were found between the reference dose/FBP protocol and almost all test combinations. Maximum mean differences in HU were 178.35 (bone kernel) and 273.74 (standard kernel), and in noise, were 243.73 (bone kernel) and 153.88 (standard kernel). Decreasing radiation dose increased density and noise regardless of reconstruction technique and kernel. The effect of reconstruction technique on density and noise depends on the reconstruction kernel used. • Ultra-low-dose MDCT protocols allowed more than 90 % reductions in dose. • Decreasing the dose generally increased density and noise. • Effect of IRT on density and noise varies with reconstruction kernel. • Accuracy of low-dose protocols for interpretation of bony anatomy not known. • Effect of low doses on accuracy of computer-aided design models unknown.

Reproducibility of three-dimensional cephalometric landmarks in cone-beam and low-dose computed tomography.

PubMed

Olszewski, R; Frison, L; Wisniewski, M; Denis, J M; Vynckier, S; Cosnard, G; Zech, F; Reychler, H

2013-01-01

The purpose of this study is to compare the reproducibility of three-dimensional cephalometric landmarks on three-dimensional computed tomography (3D-CT) surface rendering using clinical protocols based on low-dose (35-mAs) spiral CT and cone-beam CT (I-CAT). The absorbed dose levels for radiosensitive organs in the maxillofacial region during exposure in both 3D-CT protocols were also assessed. The study population consisted of ten human dry skulls examined with low-dose CT and cone-beam CT. Two independent observers identified 24 cephalometric anatomic landmarks at 13 sites on the 3D-CT surface renderings using both protocols, with each observer repeating the identification 1 month later. A total of 1,920 imaging measurements were performed. Thermoluminescent dosimeters were placed at six sites around the thyroid gland, the submandibular glands, and the eyes in an Alderson phantom to measure the absorbed dose levels. When comparing low-dose CT and cone-beam CT protocols, the cone-beam CT protocol proved to be significantly more reproducible for four of the 13 anatomical sites. There was no significant difference between the protocols for the other nine anatomical sites. Both low-dose and cone-beam CT protocols were equivalent in dose absorption to the eyes and submandibular glands. However, thyroid glands were more irradiated with low-dose CT. Cone-beam CT was more reproducible and procured less irradiation to the thyroid gland than low-dose CT. Cone-beam CT should be preferred over low-dose CT for developing three-dimensional bony cephalometric analyses.

How Does Patient Radiation Exposure Compare With Low-dose O-arm Versus Fluoroscopy for Pedicle Screw Placement in Idiopathic Scoliosis?

PubMed

Su, Alvin W; McIntosh, Amy L; Schueler, Beth A; Milbrandt, Todd A; Winkler, Jennifer A; Stans, Anthony A; Larson, A Noelle

Intraoperative C-arm fluoroscopy and low-dose O-arm are both reasonable means to assist in screw placement for idiopathic scoliosis surgery. Both using pediatric low-dose O-arm settings and minimizing the number of radiographs during C-arm fluoroscopy guidance decrease patient radiation exposure and its deleterious biological effect that may be associated with cancer risk. We hypothesized that the radiation dose for C-arm-guided fluoroscopy is no less than low-dose O-arm scanning for placement of pedicle screws. A multicenter matched-control cohort study of 28 patients in total was conducted. Fourteen patients who underwent O-arm-guided pedicle screw insertion for spinal fusion surgery in 1 institution were matched to another 14 patients who underwent C-arm fluoroscopy guidance in the other institution in terms of the age of surgery, body weight, and number of imaged spine levels. The total effective dose was compared. A low-dose pediatric protocol was used for all O-arm scans with an effective dose of 0.65 mSv per scan. The effective dose of C-arm fluoroscopy was determined using anthropomorphic phantoms that represented the thoracic and lumbar spine in anteroposterior and lateral views, respectively. The clinical outcome and complications of all patients were documented. The mean total effective dose for the O-arm group was approximately 4 times higher than that of the C-arm group (P<0.0001). The effective dose for the C-arm patients had high variability based on fluoroscopy time and did not correlate with the number of imaged spine levels or body weight. The effective dose of 1 low-dose pediatric O-arm scan approximated 85 seconds of the C-arm fluoroscopy time. All patients had satisfactory clinical outcomes without major complications that required returning to the operating room. Radiation exposure required for O-arm scans can be higher than that required for C-arm fluoroscopy, but it depends on fluoroscopy time. Inclusion of more medical centers and surgeons will better account for the variability of C-arm dose due to distinct patient characteristics, surgeon's preference, and individual institution's protocol. Level III-case-control study.

Towards quantitative imaging: stability of fully automated nodule segmentation across varied dose levels and reconstruction parameters in a low-dose CT screening patient cohort

NASA Astrophysics Data System (ADS)

Wahi-Anwar, M. Wasil; Emaminejad, Nastaran; Hoffman, John; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael F.

2018-02-01

Quantitative imaging in lung cancer CT seeks to characterize nodules through quantitative features, usually from a region of interest delineating the nodule. The segmentation, however, can vary depending on segmentation approach and image quality, which can affect the extracted feature values. In this study, we utilize a fully-automated nodule segmentation method - to avoid reader-influenced inconsistencies - to explore the effects of varied dose levels and reconstruction parameters on segmentation. Raw projection CT images from a low-dose screening patient cohort (N=59) were reconstructed at multiple dose levels (100%, 50%, 25%, 10%), two slice thicknesses (1.0mm, 0.6mm), and a medium kernel. Fully-automated nodule detection and segmentation was then applied, from which 12 nodules were selected. Dice similarity coefficient (DSC) was used to assess the similarity of the segmentation ROIs of the same nodule across different reconstruction and dose conditions. Nodules at 1.0mm slice thickness and dose levels of 25% and 50% resulted in DSC values greater than 0.85 when compared to 100% dose, with lower dose leading to a lower average and wider spread of DSC values. At 0.6mm, the increased bias and wider spread of DSC values from lowering dose were more pronounced. The effects of dose reduction on DSC for CAD-segmented nodules were similar in magnitude to reducing the slice thickness from 1.0mm to 0.6mm. In conclusion, variation of dose and slice thickness can result in very different segmentations because of noise and image quality. However, there exists some stability in segmentation overlap, as even at 1mm, an image with 25% of the lowdose scan still results in segmentations similar to that seen in a full-dose scan.

A phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory colorectal cancer.

PubMed

Fakih, Marwan G; Pendyala, Lakshmi; Fetterly, Gerald; Toth, Karoli; Zwiebel, James A; Espinoza-Delgado, Igor; Litwin, Alan; Rustum, Youcef M; Ross, Mary Ellen; Holleran, Julianne L; Egorin, Merrill J

2009-05-01

We conducted a phase I study to determine the maximum tolerated dose of vorinostat in combination with fixed doses of 5-fluorouracil (FU), leucovorin, and oxaliplatin (FOLFOX). Vorinostat was given orally twice daily for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat. The vorinostat starting dose was 100 mg twice daily. Escalation occurred in cohorts of three to six patients. Pharmacokinetics of vorinostat, FU, and oxaliplatin were studied. Twenty-one patients were enrolled. Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased in frequency and severity at higher dose levels of vorinostat. Two of 4 evaluable patients at dose level 4 (vorinostat 400 mg orally twice daily) developed dose-limiting fatigue. One of 10 evaluable patients at dose level 3 (vorinostat 300 mg orally twice daily) had dose-limiting fatigue, anorexia, and dehydration. There were significant relationships between vorinostat dose and the area under the curve on days 1 and 5 (Pearson, < 0.001). The vorinostat area under the curve increased (P = 0.005) and clearance decreased (P = 0.003) on day 5 compared with day 1. The median C(max) of FU at each dose level increased significantly with increasing doses of vorinostat, suggesting a pharmacokinetic interaction between FU and vorinostat. Vorinostat-induced thymidylate synthase (TS) modulation was not consistent; only two of six patients had a decrease in intratumoral TS expression by reverse transcription-PCR. The maximum tolerated dose of vorinostat in combination with FOLFOX is 300 mg orally twice daily x 1 week every 2 weeks. Alternative vorinostat dosing schedules may be needed for optimal down-regulation of TS expression.

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

PubMed

Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

2016-10-01

Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

PubMed

Provenzano, Robert; Besarab, Anatole; Wright, Steven; Dua, Sohan; Zeig, Steven; Nguyen, Peter; Poole, Lona; Saikali, Khalil G; Saha, Gopal; Hemmerich, Stefan; Szczech, Lynda; Yu, K H Peony; Neff, Thomas B

2016-06-01

Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. Short treatment duration and small sample size. In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Intensity-Modulated and 3D-Conformal Radiotherapy for Whole-Ventricular Irradiation as Compared With Conventional Whole-Brain Irradiation in the Management of Localized Central Nervous System Germ Cell Tumors

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

Chen, Michael Jenwei, E-mail: michaelchen@einstein.b; Silva Santos, Adriana da; Sakuraba, Roberto Kenji

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a 'boost' to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluatedmore » at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.« less

Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study.

PubMed

Jensterle, Mojca; Goricar, Katja; Janez, Andrej

2016-04-01

Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Higher doses are more effective than lower doses, although higher doses are also more poorly tolerated. Metformin may enhance the weight-lowering potential of LIRA via the stimulatory modulation of incretin in addition to its direct beneficial effects in PCOS. The aim of the present study was to evaluate whether metformin as an adjunct to low-dose LIRA affects body weight with increased efficacy compared with low-dose LIRA alone in obese patients with PCOS. In a 12-week study, 44 obese women with PCOS were randomly offered either combined treatment (COMBO) with 1,000 mg metformin twice a day and 1.2 mg LIRA once a day, or treatment with 1.2 mg LIRA alone. The primary outcome of treatment was an alteration in the levels of obesity. A total of 43 patients [aged 30.3±4.4 years; body mass index (BMI) 37.2±4.5 kg/m 2 ; mean ± standard deviation] completed the study. The subjects treated with COMBO lost on average 6.2±2.4 kg compared with a 3.8±3.5 kg weight loss in the patients treated with LIRA alone (P=0.024). The BMI decreased by 2.2±0.8 kg/m 2 in patients treated with COMBO and by 1.4±1.2 kg/m 2 in patients treated with LIRA alone (P=0.024). A clinically significant ≥5% weight reduction was achieved in 59.1% of patients treated with COMBO and 42.9% of patients treated with LIRA alone. Reductions in glucose levels following oral glucose tolerance testing, as well as in androstenedione levels in the COMBO group were significantly greater compared with those in the LIRA group. The side effects were mild and transient in the two treatment groups. A combination of metformin and low-dose LIRA was more effective than low-dose LIRA alone in reducing body weight in obese patients with PCOS.

Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study.

PubMed

Staerk, L; Gerds, T A; Lip, G Y H; Ozenne, B; Bonde, A N; Lamberts, M; Fosbøl, E L; Torp-Pedersen, C; Gislason, G H; Olesen, J B

2018-01-01

Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban. © 2017 The Association for the Publication of the Journal of Internal Medicine.

NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis: II. Reduction in biomarkers of aflatoxin exposure in blood and urine.

PubMed

Wang, P; Afriyie-Gyawu, E; Tang, Y; Johnson, N M; Xu, L; Tang, L; Huebner, H J; Ankrah, N-A; Ofori-Adjei, D; Ellis, W; Jolly, P E; Williams, J H; Wang, J-S; Phillips, T D

2008-05-01

The efficacy of NovaSil clay (NS) to reduce aflatoxin (AF) biomarkers of exposure was evaluated in 656 blood samples and 624 urine samples collected from study participants during a 3-month phase IIa clinical intervention trial in Ghana. NS was delivered before meals via capsules. Serum AFB (1)-albumin adduct was measured by radioimmunoassay and urinary AFM (1) metabolites were quantified by immunoaffinity-high-performance liquid chromatography (HPLC)-fluorescence methods. Levels of AFB (1) -albumin adduct in serum samples collected at baseline and at 1 month were similar (p = 0.2354 and p = 0.3645, respectively) among the placebo (PL), low dose (LD, 1.5 g NS day (-1)), and high dose (HD, 3.0 g NS day (-1)) groups. However, the levels of AFB (1)-albumin adduct at 3 months were significantly decreased in both the LD group (p < 0.0001) and the HD group (p < 0.0001) compared with levels in the PL group. Levels of AFM(1) in urine samples collected at baseline and at 1 month were not statistically different among the three study groups. However, a significant decrease (up to 58%) in the median level of AFM (1) in samples collected at 3 months was found in the HD group when compared with the median level in the PL group (p < 0.0391). In addition, significant effects were found for dose, time, and dose-time interaction with serum AFB(1)-albumin adduct and dose-time interaction with urinary AFM (1) metabolites. The results suggest that capsules containing NS clay can be used to reduce effectively the bioavailability of dietary AF based on a reduction of AF-specific biomarkers.

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

PubMed

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

2016-09-02

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

Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation

PubMed Central

Amrolia, Persis J.; Muccioli-Casadei, Giada; Huls, Helen; Adams, Stuart; Durett, April; Gee, Adrian; Yvon, Eric; Weiss, Heidi; Cobbold, Mark; Gaspar, H. Bobby; Rooney, Cliona; Kuehnle, Ingrid; Ghetie, Victor; Schindler, John; Krance, Robert; Heslop, Helen E.; Veys, Paul; Vitetta, Ellen; Brenner, Malcolm K.

2006-01-01

Poor T lymphocyte reconstitution limits the use of haploidentical stem cell transplantation (SCT) because it results in a high mortality from viral infections. One approach to overcome this problem is to infuse donor T cells from which alloreactive lymphocytes have been selectively depleted, but the immunologic benefit of this approach is unknown. We have used an anti-CD25 immunotoxin to deplete alloreactive lymphocytes and have compared immune reconstitution after allodepleted donor T cells were infused at 2 dose levels into recipients of T-cell–depleted haploidentical SCT. Eight patients were treated at 104 cells/kg/dose, and 8 patients received 105 cells/kg/dose. Patients receiving 105 cells/kg/dose showed significantly improved T-cell recovery at 3, 4, and 5 months after SCT compared with those receiving 104 cells/kg/dose (P < .05). Accelerated T-cell recovery occurred as a result of expansion of the effector memory (CD45RA–CCR-7-) population (P < .05), suggesting that protective T-cell responses are likely to be long lived. T-cell–receptor signal joint excision circles (TRECs) were not detected in reconstituting T cells in dose-level 2 patients, indicating they are likely to be derived from the infused allodepleted cells. Spectratyping of the T cells at 4 months demonstrated a polyclonal Vβ repertoire. Using tetramer and enzyme-linked immunospot (ELISPOT) assays, we have observed cytomegalovirus (CMV)– and Epstein-Barr virus (EBV)–specific responses in 4 of 6 evaluable patients at dose level 2 as early as 2 to 4 months after transplantation, whereas such responses were not observed until 6 to 12 months in dose-level 1 patients. The incidence of significant acute (2 of 16) and chronic graft-versus-host disease (GVHD; 2 of 15) was low. These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach. PMID:16741253

The value of thyroid shielding in intraoral radiography

PubMed Central

Hazenoot, Bart; Sanderink, Gerard C H; Berkhout, W Erwin R

2016-01-01

Objectives: To evaluate the utility of the application of a thyroid shield in intraoral radiography when using rectangular collimation. Methods: Experimental data were obtained by measuring the absorbed dose at the position of the thyroid gland in a RANDO® (The Phantom Laboratory, Salem, NY) male phantom with a dosemeter. Four protocols were tested: round collimation and rectangular collimation, both with and without thyroid shield. Five exposure positions were deployed: upper incisor (Isup), upper canine (Csup), upper premolar (Psup), upper molar (Msup) and posterior bitewing (BW). Exposures were made with 70 kV and 7 mA and were repeated 10 times. The exposure times were as recommended for the exposure positions for the respective collimator type by the manufacturer for digital imaging. The data were statistically analyzed with a three-way ANOVA test. Significance was set at p < 0.01. Results: The ANOVA test revealed that the differences between mean doses of all protocols and geometries were statistically significant, p < 0.001. For the Isup, thyroid dose levels were comparable with both collimators at a level indicating primary beam exposure. Thyroid shield reduced this dose with circa 75%. For the Csup position, round collimation also revealed primary beam exposure, and thyroid shield yield was 70%. In Csup with rectangular collimation, the thyroid dose was reduced with a factor 4 compared with round collimation and thyroid shield yielded an additional 42% dose reduction. The thyroid dose levels for the Csup, Psup, Msup and BW exposures were lower with rectangular collimation without thyroid shield than with round collimation with thyroid shield. With rectangular collimation, the thyroid shield in Psup, Msup and BW reduced the dose 10% or less, where dose levels were already low, implying no clinical significance. Conclusions: For the exposures in the upper anterior region, thyroid shield results in an important dose reduction for the thyroid. For the other exposures, thyroid shield augments little to the reduction achieved by rectangular collimation. The use of thyroid shield is to be advised, when performing upper anterior radiography. PMID:27008105

Effects of 2 different medetomidine infusion rates on selected neurohormonal and metabolic parameters in dogs

PubMed Central

Lamont, Leigh; Burton, Shelley; Caines, Deanne; Masaoud, Elmabrok; Troncy, Eric

2012-01-01

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin. PMID:23024457

SU-E-I-57: Estimating the Occupational Eye Lens Dose in Interventional Radiology Using Active Personal Dosimeters Worn On the Chest

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

Omar, A; Marteinsdottir, M; Kadesjo, N

Purpose: To provide a general formalism for determination of occupational eye lens dose based on the response of an active personal dosimeter (APD) worn at chest level above the radiation protection apron. Methods: The formalism consists of three factors: (1) APD conversion factor converting the reading at chest level (APDchest) to the corresponding personal dose equivalent at eye level, (2) Dose conversion factor transferring the measured dose quantity, Hp(10), into a dose quantity relevant for the eye lens dose, (3) Correction factor accounting for differences in exposure of the eye(s) compared to the exposure at chest level (e.g., due tomore » protective lead glasses).The different factors were investigated and evaluated based on phantom and clinical measurements performed in an x-ray angiography suite for interventional cardiology. Results: The eye lens dose can be conservatively estimated by assigning an appropriate numerical value to each factor entering the formalism that in most circumstances overestimates the dose. Doing so, the eye lens dose to the primary operator and assisting staff was estimated in this work as D-eye,primary = 2.0 APDchest and D-eye,assisting = 1.0 APDchest, respectively.The annual eye lens dose to three nurses and one cardiologist was estimated to be 2, 2, 2, and 13 mSv (Hp(0.07)), respectively, using a TLD dosimeter worn at eye level. In comparison, using the formalism and APDchest measurements, the respective doses were 2, 2, 2, and 16 mSv (Hp(3)). Conclusion: The formalism outlined in this work can be used to estimate the occupational eye lens dose from the response of an APD worn on the chest. The formalism is general and could be applied also to other types of dosimeters. However, the numerical value of the different factors may differ from those obtained with the APD’s used in this work due to differences in dosimeter properties.« less

Initiation of labor analgesia with injection of local anesthetic through the epidural needle compared to the catheter

PubMed Central

Ristev, Goran; Sipes, Angela C; Mahoney, Bryan; Lipps, Jonathan; Chan, Gary; Coffman, John C

2017-01-01

Background The rationale for injection of epidural medications through the needle is to promote sooner onset of pain relief relative to dosing through the epidural catheter given that needle injection can be performed immediately after successful location of the epidural space. Some evidence indicates that dosing medications through the epidural needle results in faster onset and improved quality of epidural anesthesia compared to dosing through the catheter, though these dosing techniques have not been compared in laboring women. This investigation was performed to determine whether dosing medication through the epidural needle improves the quality of analgesia, level of sensory blockade, or onset of pain relief measured from the time of epidural medication injection. Methods In this double-blinded prospective investigation, healthy term laboring women (n=60) received labor epidural placement upon request. Epidural analgesia was initiated according to the assigned randomization group: 10 mL loading dose (0.125% bupivacaine with fentanyl 2 µg/mL) through either the epidural needle or the catheter, given in 5 mL increments spaced 2 minutes apart. Verbal rating scale (VRS) pain scores (0–10) and pinprick sensory levels were documented to determine the rates of analgesic and sensory blockade onset. Results No significant differences were observed in onset of analgesia or sensory blockade from the time of injection between study groups. The estimated difference in the rate of pain relief (VRS/minute) was 0.04 (95% CI: −0.01 to 0.11; p=0.109), and the estimated difference in onset of sensory blockade (sensory level/minute) was 0.63 (95% CI: −0.02 to 0.15; p=0.166). The time to VRS ≤3 and level of sensory block 20 minutes after dosing were also similar between groups. No differences in patient satisfaction, or maternal or fetal complications were observed. Conclusion This investigation observed that epidural needle and catheter injection of medications result in similar onset of analgesia and sensory blockade, quality of labor analgesia, patient satisfaction, and complication rates. PMID:29263693

Virtual single source CT using dual source acquisition: Clinical applicability in run-off CT-angiography for intra-individual comparison of different scan protocols.

PubMed

Werncke, T; Hinrichs, J B; Alikhani, B; Maschke, S; Wacker, F K; Meyer, B C

2018-04-01

Virtual single source computed tomography (VSS-CT) acquisition on a dual source CT (DSCT) has been demonstrated to allow for dose-neutral intra-individual comparison of three acquisition protocols at different radiation dose levels (RDL) within one acquisition in a phantom. The purpose of this study was twofold: first to evaluate the applicability of VSS-CT in patients and second to optimize the task-dependent trade-off between radiation dose and image quality of lower extremity CT angiography (run-off CTA). In this IRB-approved prospective study 52 patients underwent run-off CTA between 06/2012 and 06/2013. VSS-CT acquisition was conducted using a first generation DSCT applying equal X-ray tube settings (120 kVp), collimation (2 × 32 × 0.6 mm), and slice thickness (1.0 mm) but different effective tube current-time products (tube A: 80 mAs, tube B: 40 mAs). Three different image datasets representing three different radiation dose levels (RDL40, RDL80, RDL120) were reconstructed using a soft kernel from the raw data of tube B, tube A or both tubes combined. Dose length products (DLP) of each raw data set were documented. Quantitative image quality (IQ) was assessed for five anatomical levels using image noise and contrast-to-noise ratio (CNR). To investigate dose efficiency of each acquisition, the dose-weighted CNR (CNRD) was determined. Qualitative IQ was evaluated by two blinded readers in consensus using a 5-point Likert scale and compared with a Friedman- and posthoc Wilcoxon test. Mean DLP was 200 ± 40, 400 ± 90 and 600 ± 130 mGy·cm for the RDL40, RDL80 and RDL120, respectively. Image noise and CNR were best for RDL120 and decreased significantly for RDL80 and RDL40, independent of the anatomic level (p < 0.001). CNRD showed no significant differences at the abdominal and pelvic level between the investigated radiation dose levels. However, for thigh to foot level a significant increase of CNRD was noted between RDL120, RDL80 and RDL40. Significant differences of qualitative IQ were observed between RDL120 and RDL40 from the abdominal to the foot level, whereas no difference was seen for the other dose levels. Radiation dose splitting with VSS-CT can be applied to run-off CTA facilitating intra-individual comparison of different acquisition protocols without additional radiation exposure. Furthermore, a radiation dose reduction potential for run-off CTA of approximately 1/3 as compared to the acquisition protocol recommended by the manufacturer could be identified in this study. Copyright © 2018 Elsevier B.V. All rights reserved.

Antidiabetic effects of scoparic acid D isolated from Scoparia dulcis in rats with streptozotocin-induced diabetes.

PubMed

Latha, Muniappan; Pari, Leelavinothan; Ramkumar, Kunga Mohan; Rajaguru, Palanisamy; Suresh, Thangaraj; Dhanabal, Thangavel; Sitasawad, Sandhya; Bhonde, Ramesh

2009-01-01

We evaluated the antihyperglycaemic effect of scoparic acid D (SAD), a diterpenoid isolated from the ethanol extract of Scoparia dulcis in streptozotocin (STZ)-induced diabetic male Wistar rats. SAD was administered orally at a dose of 10, 20 and 40 mg kg(-1) bodyweight for 15 days. At the end of the experimental period, the SAD-treated STZ diabetic rats showed decreased levels of glucose as compared with diabetic control rats. The improvement in blood glucose levels of SAD-treated rats was associated with a significant increase in plasma insulin levels. SAD at a dose of 20 mg kg(-1) bodyweight exhibited a significant effect when compared with other doses. Further, the effect of SAD was tested on STZ-treated rat insulinoma cell lines (RINm5F cells) and isolated islets in vitro. SAD at a dose of 20 microg mL(-1) evoked two-fold stimulation of insulin secretion from isolated islets, indicating its insulin secretagogue activity. Further, SAD protected STZ-mediated cytotoxicity and nitric oxide (NO) production in RINm5F cells. The present study thus confirms the antihyperglycaemic effect of SAD and also demonstrated the consistently strong cytoprotective properties of SAD.

A random walk rule for phase I clinical trials.

PubMed

Durham, S D; Flournoy, N; Rosenberger, W F

1997-06-01

We describe a family of random walk rules for the sequential allocation of dose levels to patients in a dose-response study, or phase I clinical trial. Patients are sequentially assigned the next higher, same, or next lower dose level according to some probability distribution, which may be determined by ethical considerations as well as the patient's response. It is shown that one can choose these probabilities in order to center dose level assignments unimodally around any target quantile of interest. Estimation of the quantile is discussed; the maximum likelihood estimator and its variance are derived under a two-parameter logistic distribution, and the maximum likelihood estimator is compared with other nonparametric estimators. Random walk rules have clear advantages: they are simple to implement, and finite and asymptotic distribution theory is completely worked out. For a specific random walk rule, we compute finite and asymptotic properties and give examples of its use in planning studies. Having the finite distribution theory available and tractable obviates the need for elaborate simulation studies to analyze the properties of the design. The small sample properties of our rule, as determined by exact theory, compare favorably to those of the continual reassessment method, determined by simulation.

Student's music exposure: Full-day personal dose measurements.

PubMed

Washnik, Nilesh Jeevandas; Phillips, Susan L; Teglas, Sandra

2016-01-01

Previous studies have shown that collegiate level music students are exposed to potentially hazardous sound levels. Compared to professional musicians, collegiate level music students typically do not perform as frequently, but they are exposed to intense sounds during practice and rehearsal sessions. The purpose of the study was to determine the full-day exposure dose including individual practice and ensemble rehearsals for collegiate student musicians. Sixty-seven college students of classical music were recruited representing 17 primary instruments. Of these students, 57 completed 2 days of noise dose measurements using Cirrus doseBadge programed according to the National Institute for Occupational Safety and Health criterion. Sound exposure was measured for 2 days from morning to evening, ranging from 7 to 9 h. Twenty-eight out of 57 (49%) student musicians exceeded a 100% daily noise dose on at least 1 day of the two measurement days. Eleven student musicians (19%) exceeded 100% daily noise dose on both days. Fourteen students exceeded 100% dose during large ensemble rehearsals and eight students exceeded 100% dose during individual practice sessions. Approximately, half of the student musicians exceeded 100% noise dose on a typical college schedule. This finding indicates that a large proportion of collegiate student musicians are at risk of developing noise-induced hearing loss due to hazardous sound levels. Considering the current finding, there is a need to conduct hearing conservation programs in all music schools, and to educate student musicians about the use and importance of hearing protection devices for their hearing.

Student's music exposure: Full-day personal dose measurements

PubMed Central

Washnik, Nilesh Jeevandas; Phillips, Susan L.; Teglas, Sandra

2016-01-01

Previous studies have shown that collegiate level music students are exposed to potentially hazardous sound levels. Compared to professional musicians, collegiate level music students typically do not perform as frequently, but they are exposed to intense sounds during practice and rehearsal sessions. The purpose of the study was to determine the full-day exposure dose including individual practice and ensemble rehearsals for collegiate student musicians. Sixty-seven college students of classical music were recruited representing 17 primary instruments. Of these students, 57 completed 2 days of noise dose measurements using Cirrus doseBadge programed according to the National Institute for Occupational Safety and Health criterion. Sound exposure was measured for 2 days from morning to evening, ranging from 7 to 9 h. Twenty-eight out of 57 (49%) student musicians exceeded a 100% daily noise dose on at least 1 day of the two measurement days. Eleven student musicians (19%) exceeded 100% daily noise dose on both days. Fourteen students exceeded 100% dose during large ensemble rehearsals and eight students exceeded 100% dose during individual practice sessions. Approximately, half of the student musicians exceeded 100% noise dose on a typical college schedule. This finding indicates that a large proportion of collegiate student musicians are at risk of developing noise-induced hearing loss due to hazardous sound levels. Considering the current finding, there is a need to conduct hearing conservation programs in all music schools, and to educate student musicians about the use and importance of hearing protection devices for their hearing. PMID:26960787

The effect of methylmercury exposure on behavior and cerebellar granule cell physiology in aged mice.

PubMed

Bellum, Sairam; Thuett, Kerry A; Bawa, Bhupinder; Abbott, Louise C

2013-09-01

Epidemiology studies have clearly documented that the central nervous system is highly susceptible to methylmercury toxicity, and exposure to this neurotoxicant in humans primarily results from consumption of contaminated fish. While the effects of methylmercury exposure have been studied in great detail, comparatively little is known about the effects of moderate to low dose methylmercury toxicity in the aging central nervous system. We examined the toxic effects of a moderate dose of methylmercury on the aging mouse cerebellum. Male and female C57BL/6 mice at 16-20 months of age were exposed to methylmercury by feeding a total dose of 5.0 mg kg(-1) body weight and assessed using four behavioral tests. Methylmercury-treated aged mice performed significantly worse in open field, footprint analysis and the vertical pole test compared with age-matched control mice. Isolated cerebellar granule cells from methylmercury-treated aged mice exhibited higher levels of reactive oxygen species and reduced mitochondrial membrane potentials, but no differences in basal intracellular calcium ion levels compared with age-matched control mice. When aged mice were exposed to a moderate dose of methylmercury, they exhibited a similar degree of impairment when compared with young adult mice exposed to the same moderate dose of methylmercury, as reported in earlier studies from this laboratory. Thus, at least in mice, exposure of the aged brain to moderate concentrations methylmercury does not pose greater risk compared with the young adult brain exposed to similar concentrations of methylmercury. Copyright © 2012 John Wiley & Sons, Ltd.

WE-D-18A-04: How Iterative Reconstruction Algorithms Affect the MTFs of Variable-Contrast Targets in CT Images

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

Dodge, C.T.; Rong, J.; Dodge, C.W.

2014-06-15

Purpose: To determine how filtered back-projection (FBP), adaptive statistical (ASiR), and model based (MBIR) iterative reconstruction algorithms affect the measured modulation transfer functions (MTFs) of variable-contrast targets over a wide range of clinically applicable dose levels. Methods: The Catphan 600 CTP401 module, surrounded by an oval, fat-equivalent ring to mimic patient size/shape, was scanned on a GE HD750 CT scanner at 1, 2, 3, 6, 12 and 24 mGy CTDIvol levels with typical patient scan parameters: 120kVp, 0.8s, 40mm beam width, large SFOV, 2.5mm thickness, 0.984 pitch. The images were reconstructed using GE's Standard kernel with FBP; 20%, 40% andmore » 70% ASiR; and MBIR. A task-based MTF (MTFtask) was computed for six cylindrical targets: 2 low-contrast (Polystyrene, LDPE), 2 medium-contrast (Delrin, PMP), and 2 high-contrast (Teflon, air). MTFtask was used to compare the performance of reconstruction algorithms with decreasing CTDIvol from 24mGy, which is currently used in the clinic. Results: For the air target and 75% dose savings (6 mGy), MBIR MTFtask at 5 lp/cm measured 0.24, compared to 0.20 for 70% ASiR and 0.11 for FBP. Overall, for both high-contrast targets, MBIR MTFtask improved with increasing CTDIvol and consistently outperformed ASiR and FBP near the system's Nyquist frequency. Conversely, for Polystyrene at 6 mGy, MBIR (0.10) and 70% ASiR (0.07) MTFtask was lower than for FBP (0.18). For medium and low-contrast targets, FBP remains the best overall algorithm for improved resolution at low CTDIvol (1–6 mGy) levels, whereas MBIR is comparable at higher dose levels (12–24 mGy). Conclusion: MBIR improved the MTF of small, high-contrast targets compared to FBP and ASiR at doses of 50%–12.5% of those currently used in the clinic. However, for imaging low- and mediumcontrast targets, FBP performed the best across all dose levels. For assessing MTF from different reconstruction algorithms, task-based MTF measurements are necessary.« less

New patient-controlled abdominal compression method in radiography: radiation dose and image quality.

PubMed

Piippo-Huotari, Oili; Norrman, Eva; Anderzén-Carlsson, Agneta; Geijer, Håkan

2018-05-01

The radiation dose for patients can be reduced with many methods and one way is to use abdominal compression. In this study, the radiation dose and image quality for a new patient-controlled compression device were compared with conventional compression and compression in the prone position . To compare radiation dose and image quality of patient-controlled compression compared with conventional and prone compression in general radiography. An experimental design with quantitative approach. After obtaining the approval of the ethics committee, a consecutive sample of 48 patients was examined with the standard clinical urography protocol. The radiation doses were measured as dose-area product and analyzed with a paired t-test. The image quality was evaluated by visual grading analysis. Four radiologists evaluated each image individually by scoring nine criteria modified from the European quality criteria for diagnostic radiographic images. There was no significant difference in radiation dose or image quality between conventional and patient-controlled compression. Prone position resulted in both higher dose and inferior image quality. Patient-controlled compression gave similar dose levels as conventional compression and lower than prone compression. Image quality was similar with both patient-controlled and conventional compression and was judged to be better than in the prone position.

Low kV versus dual-energy virtual monoenergetic CT imaging for proven liver lesions: what are the advantages and trade-offs in conspicuity and image quality? A pilot study.

PubMed

Hanson, G Jay; Michalak, Gregory J; Childs, Robert; McCollough, Brian; Kurup, Anil N; Hough, David M; Frye, Judson M; Fidler, Jeff L; Venkatesh, Sudhakar K; Leng, Shuai; Yu, Lifeng; Halaweish, Ahmed F; Harmsen, W Scott; McCollough, Cynthia H; Fletcher, J G

2018-06-01

Single-energy low tube potential (SE-LTP) and dual-energy virtual monoenergetic (DE-VM) CT images both increase the conspicuity of hepatic lesions by increasing iodine signal. Our purpose was to compare the conspicuity of proven liver lesions, artifacts, and radiologist preferences in dose-matched SE-LTP and DE-VM images. Thirty-one patients with 72 proven liver lesions (21 benign, 51 malignant) underwent full-dose contrast-enhanced dual-energy CT (DECT). Half-dose images were obtained using single tube reconstruction of the dual-source SE-LTP projection data (80 or 100 kV), and by inserting noise into dual-energy projection data, with DE-VM images reconstructed from 40 to 70 keV. Three blinded gastrointestinal radiologists evaluated half-dose SE-LTP and DE-VM images, ranking and grading liver lesion conspicuity and diagnostic confidence (4-point scale) on a per-lesion basis. Image quality (noise, artifacts, sharpness) was evaluated, and overall image preference was ranked on per-patient basis. Lesion-to-liver contrast-to-noise ratio (CNR) was compared between techniques. Mean lesion size was 1.5 ± 1.2 cm. Across the readers, the mean conspicuity ratings for 40, 45, and 50 keV half-dose DE-VM images were superior compared to other half-dose image sets (p < 0.0001). Per-lesion diagnostic confidence was similar between half-dose SE-LTP compared to half-dose DE-VM images (p ≥ 0.05; 1.19 vs. 1.24-1.32). However, SE-LTP images had less noise and artifacts and were sharper compared to DE-VM images less than 70 keV (p < 0.05). On a per-patient basis, radiologists preferred SE-LTP images the most and preferred 40-50 keV the least (p < 0.0001). Lesion CNR was also higher in SE-LTP images than DE-VM images (p < 0.01). For the same applied dose level, liver lesions were more conspicuous using DE-VM compared to SE-LTP; however, SE-LTP images were preferred more than any single DE-VM energy level, likely due to lower noise and artifacts.

Radiation exposure levels within timber industries in Calabar, Nigeria

PubMed Central

Inyang, S. O.; Inyang, I. S.; Egbe, N. O.

2009-01-01

The UNSCEAR (2000) observed that there could be some exposure at work which would require regulatory control but is not really considered. This study was, therefore, set up to evaluate the effective dose in timber industries in Calabar, Nigeria to determine if the evaluated dose levels could lead to any radiological health effect in the workers, and also determine if the industries require regulatory control. The gamma ray exposure at four timber industries measured using an exposure meter were converted to effective dose and compared with the public and occupational values. The evaluated effective dose values in the timber industries were below public and occupational exposure limits and may not necessarily result in any radiological health hazard. Therefore, they may not require regulatory control. PMID:20098544

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

Seitz, R.R.; Rittmann, P.D.; Wood, M.I.

The US Department of Energy Headquarters established a performance assessment task team (PATT) to integrate the activities of DOE sites that are preparing performance assessments for the disposal of newly generated low-level waste. The PATT chartered a subteam with the task of comparing computer codes and exposure scenarios used for dose calculations in performance assessments. This report documents the efforts of the subteam. Computer codes considered in the comparison include GENII, PATHRAE-EPA, MICROSHIELD, and ISOSHLD. Calculations were also conducted using spreadsheets to provide a comparison at the most fundamental level. Calculations and modeling approaches are compared for unit radionuclide concentrationsmore » in water and soil for the ingestion, inhalation, and external dose pathways. Over 30 tables comparing inputs and results are provided.« less

Diethylene glycol in health products sold over-the-counter and imported from Asian countries.

PubMed

Schier, Joshua G; Barr, Dana B; Li, Zheng; Wolkin, Amy F; Baker, Samuel E; Lewis, Lauren S; McGeehin, Michael A

2011-03-01

Diethylene glycol (DEG), a chemical that has been implicated in multiple medication-associated mass poisonings, can result in renal and neurological toxicity if ingested. Three previous such mass poisonings implicated Chinese manufacturers as the origin of contaminated ingredients. No literature exists on potential DEG or triethylene glycol (TEG), a related compound, contamination of health products imported from Asian countries to the USA. Our primary objective was to quantitatively assess the amount of DEG present in a convenience sampling of these health products. The study's secondary objectives were to: (1) evaluate for, and quantify TEG levels in these samples; (2) compare DEG and TEG levels in these products directly to levels in medications implicated in previous similar mass poisonings; and (3) to estimate DEG dose (in mg/kg) based on the manufacturer's instructions and compare these values to toxic doses from past mass poisonings and the literature. A quantitative assessment of DEG and TEG was performed in a convenience sampling of over-the-counter health products imported from Asian countries. Results were converted to volume to volume (v/v) % and compared with DEG levels in medications implicated in previous mass poisonings. Estimated doses (based on the manufacturer's instructions) of each product with detectable levels of DEG for a 70 kg adult were compared to toxic doses of DEG reported in the literature. Seventeen of 85 (20%) samples were not able to be analyzed for DEG or TEG due to technical reasons. Fifteen of 68 (22%) samples successfully tested had detectable levels of DEG (mean, 18.8 μg/ml; range, 0.791-110.1 μg/ml; and volume to volume (v/v) range, 0.00007-0.01%). Two of 68 (3%) samples had TEG levels of 12.8 and 20.2 μg/ml or 0.0012% and 0.0018% TEG v/v. The product with the highest DEG% by v/v was 810 times less than the product involved in the Panama DEG mass poisoning (8.1%). The lowest reported toxic dose from a past DEG mass poisoning (14 mg/kg) was more than 150 times higher than the highest daily dose estimated in our study (0.09 mg/kg). Sixty-eight of 85 (80%) samples were able to be successfully analyzed for DEG and TEG. DEG and TEG were detectable in 15/68 (22%) and 2/68 (3%) samples, respectively. Based on current standards, these levels probably do not represent an acute public health threat. Additional research focusing on why DEG is found in these products and on the minimum amount of DEG needed to result in toxicity is needed. © American College of Medical Toxicology 2010

Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

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

Maier, Joscha, E-mail: joscha.maier@dkfz.de; Sawall, Stefan; Kachelrieß, Marc

2014-05-15

Purpose: Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levelsmore » from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Methods: Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Results: Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the best performance. At 50 mGy, the deviation from the reference obtained at 500 mGy were less than 4%. Also the LDPC algorithm provides reasonable results with deviation less than 10% at 50 mGy while PCF and MKB reconstruction show larger deviations even at higher dose levels. Conclusions: LDPC and HDTV increase CNR and allow for quantitative evaluations even at dose levels as low as 50 mGy. The left ventricular volumes exemplarily illustrate that cardiac parameters can be accurately estimated at lowest dose levels if sophisticated algorithms are used. This allows to reduce dose by a factor of 10 compared to today's gold standard and opens new options for longitudinal studies of the heart.« less

Evaluation of the use of automatic exposure control and automatic tube potential selection in low-dose cerebrospinal fluid shunt head CT.

PubMed

Wallace, Adam N; Vyhmeister, Ross; Bagade, Swapnil; Chatterjee, Arindam; Hicks, Brandon; Ramirez-Giraldo, Juan Carlos; McKinstry, Robert C

2015-06-01

Cerebrospinal fluid shunts are primarily used for the treatment of hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT scans resulting in potentially high levels of radiation dose starting at an early age. A new head CT protocol using automatic exposure control and automated tube potential selection has been implemented at our institution to reduce radiation exposure. The purpose of this study was to evaluate the reduction in radiation dose achieved by this protocol compared with a protocol with fixed parameters. A retrospective sample of 60 non-contrast head CT scans assessing for cerebrospinal fluid shunt malfunction was identified, 30 of which were performed with each protocol. The radiation doses of the two protocols were compared using the volume CT dose index and dose length product. The diagnostic acceptability and quality of each scan were evaluated by three independent readers. The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P < 0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans with comparable image quality to the fixed parameter protocol. A pediatric shunt non-contrast head CT protocol using automatic exposure control and automated tube potential selection reduced patient radiation dose compared with a fixed parameter protocol while producing diagnostic images of comparable quality.

The adaptive statistical iterative reconstruction-V technique for radiation dose reduction in abdominal CT: comparison with the adaptive statistical iterative reconstruction technique.

PubMed

Kwon, Heejin; Cho, Jinhan; Oh, Jongyeong; Kim, Dongwon; Cho, Junghyun; Kim, Sanghyun; Lee, Sangyun; Lee, Jihyun

2015-10-01

To investigate whether reduced radiation dose abdominal CT images reconstructed with adaptive statistical iterative reconstruction V (ASIR-V) compromise the depiction of clinically competent features when compared with the currently used routine radiation dose CT images reconstructed with ASIR. 27 consecutive patients (mean body mass index: 23.55 kg m(-2) underwent CT of the abdomen at two time points. At the first time point, abdominal CT was scanned at 21.45 noise index levels of automatic current modulation at 120 kV. Images were reconstructed with 40% ASIR, the routine protocol of Dong-A University Hospital. At the second time point, follow-up scans were performed at 30 noise index levels. Images were reconstructed with filtered back projection (FBP), 40% ASIR, 30% ASIR-V, 50% ASIR-V and 70% ASIR-V for the reduced radiation dose. Both quantitative and qualitative analyses of image quality were conducted. The CT dose index was also recorded. At the follow-up study, the mean dose reduction relative to the currently used common radiation dose was 35.37% (range: 19-49%). The overall subjective image quality and diagnostic acceptability of the 50% ASIR-V scores at the reduced radiation dose were nearly identical to those recorded when using the initial routine-dose CT with 40% ASIR. Subjective ratings of the qualitative analysis revealed that of all reduced radiation dose CT series reconstructed, 30% ASIR-V and 50% ASIR-V were associated with higher image quality with lower noise and artefacts as well as good sharpness when compared with 40% ASIR and FBP. However, the sharpness score at 70% ASIR-V was considered to be worse than that at 40% ASIR. Objective image noise for 50% ASIR-V was 34.24% and 46.34% which was lower than 40% ASIR and FBP. Abdominal CT images reconstructed with ASIR-V facilitate radiation dose reductions of to 35% when compared with the ASIR. This study represents the first clinical research experiment to use ASIR-V, the newest version of iterative reconstruction. Use of the ASIR-V algorithm decreased image noise and increased image quality when compared with the ASIR and FBP methods. These results suggest that high-quality low-dose CT may represent a new clinical option.

The adaptive statistical iterative reconstruction-V technique for radiation dose reduction in abdominal CT: comparison with the adaptive statistical iterative reconstruction technique

PubMed Central

Cho, Jinhan; Oh, Jongyeong; Kim, Dongwon; Cho, Junghyun; Kim, Sanghyun; Lee, Sangyun; Lee, Jihyun

2015-01-01

Objective: To investigate whether reduced radiation dose abdominal CT images reconstructed with adaptive statistical iterative reconstruction V (ASIR-V) compromise the depiction of clinically competent features when compared with the currently used routine radiation dose CT images reconstructed with ASIR. Methods: 27 consecutive patients (mean body mass index: 23.55 kg m−2 underwent CT of the abdomen at two time points. At the first time point, abdominal CT was scanned at 21.45 noise index levels of automatic current modulation at 120 kV. Images were reconstructed with 40% ASIR, the routine protocol of Dong-A University Hospital. At the second time point, follow-up scans were performed at 30 noise index levels. Images were reconstructed with filtered back projection (FBP), 40% ASIR, 30% ASIR-V, 50% ASIR-V and 70% ASIR-V for the reduced radiation dose. Both quantitative and qualitative analyses of image quality were conducted. The CT dose index was also recorded. Results: At the follow-up study, the mean dose reduction relative to the currently used common radiation dose was 35.37% (range: 19–49%). The overall subjective image quality and diagnostic acceptability of the 50% ASIR-V scores at the reduced radiation dose were nearly identical to those recorded when using the initial routine-dose CT with 40% ASIR. Subjective ratings of the qualitative analysis revealed that of all reduced radiation dose CT series reconstructed, 30% ASIR-V and 50% ASIR-V were associated with higher image quality with lower noise and artefacts as well as good sharpness when compared with 40% ASIR and FBP. However, the sharpness score at 70% ASIR-V was considered to be worse than that at 40% ASIR. Objective image noise for 50% ASIR-V was 34.24% and 46.34% which was lower than 40% ASIR and FBP. Conclusion: Abdominal CT images reconstructed with ASIR-V facilitate radiation dose reductions of to 35% when compared with the ASIR. Advances in knowledge: This study represents the first clinical research experiment to use ASIR-V, the newest version of iterative reconstruction. Use of the ASIR-V algorithm decreased image noise and increased image quality when compared with the ASIR and FBP methods. These results suggest that high-quality low-dose CT may represent a new clinical option. PMID:26234823

Vitamin C modulates lead excretion in rats.

PubMed

Lihm, Hoseob; Kim, Hyun; Chang, Heekyung; Yoon, Myunghee; Lee, Kayoung; Choi, Jongsoon

2013-12-01

Lead, one of the most toxic heavy metals, takes longer time to be excreted from the body than other heavy metals. The purpose of this study is, by measuring lead excretion via urine and feces, to find out the effect of vitamin C in lead chelation. Thirty-six rats were randomly assorted into four groups. All 33 rats except for the control group were administered with lead, before orally administered with different doses of vitamin C per kilogram of body weight. The lead excretion levels in urine and feces as well as the survival rate were then measured for each group. The rats with lead administrations (10/13, 76.9%) with lead administrations only, 10/11 rats (90.9%) with lead administrations and low dose of vitamin C, 9/9 rats (100%) with lead administrations and high dose of vitamin C survived. Among the 29 surviving rats, low vitamin C intake group exhibited higher urinary excretion than the lead only group. The urinary excretion level in high dose vitamin C intakegroup was significantly higher than the lead only group. In addition, fecal lead excretion seemed to be increased in the high dose vitamin C intake group, compared to the group with lead administrations only with statistical significance. Through animal experiment, it was found out that administrating high dose of vitamin C accelerated the excretion of lead in body compared to low dose of vitamin C.

Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with acute coronary syndrome: A systematic review and meta-analysis

PubMed Central

Su, Qiang; Guo, Wenqin; Dai, Weiran; Li, Hongqing; Yang, Huafeng; Li, Lang

2017-01-01

Background Acute coronary syndrome (ACS) is an important disease threatening human life and health. Many studies have shown that the loading dose of atorvastatin can significantly improve the prognosis of patients with ACS, and reduce the mortality. However, this conclusion is not consistent. Thus, we aimed to evaluate the effect of high-dose rosuvastatin loading before percutaneous coronary intervention (PCI) in Chinese patients with ACS using a meta-analysis based on a systematic review of published articles. Methods We systematically reviewed published studies, evaluating the effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with ACS. The retrieval time is limited from inception to 2 November 2016, and the retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database and the Wang Fang database. Two researchers independently assessed the quality of the included studies and then extracted the data. Stata 11.0 was used for data analysis. Results In total, 11 articles, which included 802 patients, were included in our meta-analysis. Among these patients, 398 patients were in the high-dose group (20 mg/day) and 404 patients were in the conventional dose group (10 mg/day). Meta-analysis results showed that compared with the conventional dose group: 1) The loading dose of rosuvastatin can significantly reduce the hs-CRP level after PCI, including at 24 hours (SMD = -0.65, 95%CI -0.84 ~ -0.47, P = 0.000), 48 hours (SMD = -0.40, 95%CI -0.68 ~ -0.11, P = 0.006), and four weeks (SMD = -1.64, 95%CI -2.01 ~ -1.26, P = 0.000). 2) The loading dose of rosuvastatin can significantly reduce the levels of LDL-C and cTnT, including the level of LDL-C at 30 d after PCI (SMD = -0.89, 95%CI -1.10 ~ -0.69, P = 0.000), and the level of cTnT at 24 h after PCI (SMD = -1.93, 95%CI -2.28 ~ -1.59, P = 0.000), and increase the level of HDL-C at 48 h after PCI (SMD = 0.61, 95%CI 0.34 ~ 0.88, P = 0.000). 3) The loading dose of rosuvastatin can significantly reduce the levels of TG and TC, including the level of TG at 30 d after PCI (SMD = -0.94, 95%CI -1.17 ~ -0.71, P = 0.000), the level of TC at 48 h after PCI (SMD = -0.35, 95%CI -0.68 ~ -0.01, P = 0.043), and the level of TC at 30 d after PCI (SMD = -0.77, 95%CI -0.98 ~ -0.56, P = 0.000). Conclusions Our systematic review and meta-analysis showed that, compared with the conventional dose, the loading dose of rosuvastatin was more beneficial to patients with ACS in China and is suitable for clinical application. Due to the limitations of the quality and quantity of included articles, this conclusion still needs to be confirmed by multicenter clinical trials. PMID:28231287

The evaluation of different treatment protocols for trauma-induced lung injury in rats

PubMed Central

Güzel, Aygül; Katı, Celal; Duran, Latif; Alaçam, Hasan; Gacar, Ayhan; Güvenç, Tolga; Murat, Naci; Şişman, Bülent

2014-01-01

Background Lung contusion is an important factor that affects mortality and morbidity of lung injury after blunt chest trauma (BCT). The present study aims to evaluate the effectiveness of different treatment regimens on BCT-induced lung injury. Methods A total of 35 Sprague Dawley rats were divided into five experimental groups (n=7): sham, control; BCT; BCT + MP, BCT group treated with methylprednisolone (MP; 30 mg/kg on first day and 3 mg/kg/d on the following days); BCT + Q, BCT group treated with quercetin (Q; 50 mg/kg/d for seven days); and BCT + MP + Q, BCT group treated with the same doses of MP and Q. Serum Clara Cell Protein-16 (CC-16), thiobarbituric acid reactive substances (TBARS), and superoxide dismutase (SOD) levels were analyzed to determine histopathological changes in the lung tissues. Results Elevated serum CC-16 and TBARS levels and reduced serum SOD levels were found in the BCT group compared to the Sham group. There was a significant change in the serum CC-16 levels in the BCT + MP group compared to the Sham group. Serum TBARS levels were significantly lower in the BCT + MP and BCT + Q group compared to the BCT group. The combined therapy regimen yielded significantly decreased CC-16 levels and increased serum SOD levels compared to the individual treatment groups. Serum TBARS levels did not significantly differ between the BCT + MP + Q group and the other treatment groups. Compared to the BCT + MP + Q group, the BCT + MP group showed significantly lower alveolar edema (AED) and alveolar exudate (AEX) scores, while the BCT + Q group showed significantly lower peribronchial inflammatory cell infiltration (PICI) and AED scores. Conclusions The combined usage of quercetin and low dose MP treatment after initial high dose MP at the early stage of lung injury after BCT is more effective. PMID:24605218

Long-term mesalamine maintenance in ulcerative colitis: which is more important? Adherence or daily dose.

PubMed

Khan, Nabeel; Abbas, Ali M; Koleva, Yordanka N; Bazzano, Lydia A

2013-05-01

There are limited data about the long-term follow-up of patients with ulcerative colitis (UC) maintained on high versus low doses of mesalamine. We evaluated the best long-term average daily dose that would keep the disease in remission. Nationwide ulcerative colitis data were obtained from the Veterans Affairs health care system for the period 2001 to 2011. Those who started mesalamine maintenance during this period were included. Average daily dose and the level of adherence were assessed for the period between the first mesalamine dispense and the date of first flare defined as the first filling of 40 mg/day or more of oral prednisone or any dose of intravenous steroids. Patients with ulcerative colitis maintained on an average daily dose 2.4 to 2.8 g/day (low dose) were compared with 4.4 to 4.8 g/day (high dose). Adherence was assessed using continuous single interval medication availability indicator. We included 4452 patients with a median follow-up of 6 years. There was no significant reduction in the risk of flares when comparing high versus low average mesalamine dose among patients with high [hazard ratio = 0.96, P = 0.8)] and medium (hazard ratio = 0.74, P = 0.17) adherence. However, there was a significant reduction in the risk of flares with high dose of mesalamine among patients with low adherence (hazard ratio = 0.28, P = 0.003). Our data show that when starting a patient on mesalamine, there is no difference in the long-term flare risk between low versus high average daily dose as long as the patients have a high to moderate level of adherence.

Estimation of low-level neutron dose-equivalent rate by using extrapolation method for a curie level Am-Be neutron source.

PubMed

Li, Gang; Xu, Jiayun; Zhang, Jie

2015-01-01

Neutron radiation protection is an important research area because of the strong radiation biological effect of neutron field. The radiation dose of neutron is closely related to the neutron energy, and the connected relationship is a complex function of energy. For the low-level neutron radiation field (e.g. the Am-Be source), the commonly used commercial neutron dosimeter cannot always reflect the low-level dose rate, which is restricted by its own sensitivity limit and measuring range. In this paper, the intensity distribution of neutron field caused by a curie level Am-Be neutron source was investigated by measuring the count rates obtained through a 3 He proportional counter at different locations around the source. The results indicate that the count rates outside of the source room are negligible compared with the count rates measured in the source room. In the source room, 3 He proportional counter and neutron dosimeter were used to measure the count rates and dose rates respectively at different distances to the source. The results indicate that both the count rates and dose rates decrease exponentially with the increasing distance, and the dose rates measured by a commercial dosimeter are in good agreement with the results calculated by the Geant4 simulation within the inherent errors recommended by ICRP and IEC. Further studies presented in this paper indicate that the low-level neutron dose equivalent rates in the source room increase exponentially with the increasing low-energy neutron count rates when the source is lifted from the shield with different radiation intensities. Based on this relationship as well as the count rates measured at larger distance to the source, the dose rates can be calculated approximately by the extrapolation method. This principle can be used to estimate the low level neutron dose values in the source room which cannot be measured directly by a commercial dosimeter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vitamin D supplementation in nursing home patients: randomized controlled trial of standard daily dose versus individualized loading dose regimen.

PubMed

Wijnen, Hugo; Salemink, Dayenne; Roovers, Lian; Taekema, Diana; de Boer, Hans

2015-05-01

Supplementation of cholecalciferol 800 IU daily appears to be insufficient to raise vitamin D levels to >75 nmol/l in nursing home (NH) patients. Our objective was to compare the efficacy of an individualized cholecalciferol loading dose (LD) regimen and a daily dose (DD) regimen of cholecalciferol 800 IU in reaching 25-OH vitamin D (25OHD) levels >75 nmol/l. A total of 30 NH patients with 25OHD levels <50 nmol/l were included. Patients were randomized using the minimization method in the LD or DD group. The cholecalciferol LD, calculated with an algorithm based on serum 25OHD level and body weight, was administered in divided doses of 50,000 IU twice a week, followed by a monthly maintenance dose of either 50,000 or 25,000 IU. The DD regimen consisted of cholecalciferol 800 IU daily for 26 weeks. Serum 25OHD, calcium, creatinine, phosphate, and parathyroid hormone were measured, and 2-minute walking test, handgrip strength, and timed get up and go test were assessed at baseline (T 0), after 5 weeks (T 5), 12 weeks (T 12), and 26 weeks (T 26). The primary endpoint was the percentage of patients with 25OHD levels >75 nmol/l at T 5. Secondary endpoints were the proportion of patients with 25OHD levels >75 nmol/l at T 26, safety of LD regimen, and improvement of performance tests with normalization of vitamin D levels. Median baseline 25OHD levels (interquartile range) were comparable between the 14 DD and 16 LD patients: 20.9 (15.9-29.6) and 21.7 (16.4-32.8) nmol/l, respectively. Levels of 25OHD >75 nmol/l at T 5 were reached in 79 % of the 14 LD patients, but in none of the 13 DD patients (p < 0.001). At T 26, 25OHD levels >75 nmol/l were reached in 83 % of the 12 LD patients and in 30 % of the ten DD patients (p < 0.05). Side effects or hypercalcemia were not observed. No improvement of performance tests was observed. In NH patients with severe 25OHD deficiency, an individualized calculated cholecalciferol LD is likely to be superior to a DD of cholecalciferol 800 IU in terms of the ability to rapidly normalize vitamin D levels.

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

PubMed

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

2012-05-15

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

Evaluation of a new very low dose imaging protocol: feasibility and impact on X-ray dose levels in electrophysiology procedures

PubMed Central

Bourier, Felix; Reents, Tilko; Ammar-Busch, Sonia; Buiatti, Alessandra; Kottmaier, Marc; Semmler, Verena; Telishevska, Marta; Brkic, Amir; Grebmer, Christian; Lennerz, Carsten; Kolb, Christof; Hessling, Gabriele; Deisenhofer, Isabel

2016-01-01

Aims This study presents and evaluates the impact of a new lowest-dose fluoroscopy protocol (Siemens AG), especially designed for electrophysiology (EP) procedures, on X-ray dose levels. Methods and results From October 2014 to March 2015, 140 patients underwent an EP study on an Artis zee angiography system. The standard low-dose protocol was operated at 23 nGy (fluoroscopy) and at 120 nGy (cine-loop), the new lowest-dose protocol was operated at 8 nGy (fluoroscopy) and at 36 nGy (cine-loop). Procedural data, X-ray times, and doses were analysed in 100 complex left atrial and in 40 standard EP procedures. The resulting dose–area products were 877.9 ± 624.7 µGym² (n = 50 complex procedures, standard low dose), 199 ± 159.6 µGym² (n = 50 complex procedures, lowest dose), 387.7 ± 36.0 µGym² (n = 20 standard procedures, standard low dose), and 90.7 ± 62.3 µGym² (n = 20 standard procedures, lowest dose), P < 0.01. In the low-dose and lowest-dose groups, procedure times were 132.6 ± 35.7 vs. 126.7 ± 34.7 min (P = 0.40, complex procedures) and 72.3 ± 20.9 vs. 85.2 ± 44.1 min (P = 0.24, standard procedures), radiofrequency (RF) times were 53.8 ± 26.1 vs. 50.4 ± 29.4 min (P = 0.54, complex procedures) and 10.1 ± 9.9 vs. 12.2 ± 14.7 min (P = 0.60, standard procedures). One complication occurred in the standard low-dose and lowest-dose groups (P = 1.0). Conclusion The new lowest-dose imaging protocol reduces X-ray dose levels by 77% compared with the currently available standard low-dose protocol. From an operator standpoint, lowest X-ray dose levels create a different, reduced image quality. The new image quality did not significantly affect procedure or RF times and did not result in higher complication rates. Regarding radiological protection, operating at lowest-dose settings should become standard in EP procedures. PMID:26589627

Diagnostic reference levels of paediatric computed tomography examinations performed at a dedicated Australian paediatric hospital.

PubMed

Bibbo, Giovanni; Brown, Scott; Linke, Rebecca

2016-08-01

Diagnostic Reference Levels (DRL) of procedures involving ionizing radiation are important tools to optimizing radiation doses delivered to patients and in identifying cases where the levels of doses are unusually high. This is particularly important for paediatric patients undergoing computed tomography (CT) examinations as these examinations are associated with relatively high-dose. Paediatric CT studies, performed at our institution from January 2010 to March 2014, have been retrospectively analysed to determine the 75th and 95th percentiles of both the volume computed tomography dose index (CTDIvol ) and dose-length product (DLP) for the most commonly performed studies to: establish local diagnostic reference levels for paediatric computed tomography examinations performed at our institution, benchmark our DRL with national and international published paediatric values, and determine the compliance of CT radiographer with established protocols. The derived local 75th percentile DRL have been found to be acceptable when compared with those published by the Australian National Radiation Dose Register and two national children's hospitals, and at the international level with the National Reference Doses for the UK. The 95th percentiles of CTDIvol for the various CT examinations have been found to be acceptable values for the CT scanner Dose-Check Notification. Benchmarking CT radiographers shows that they follow the set protocols for the various examinations without significant variations in the machine setting factors. The derivation of DRL has given us the tool to evaluate and improve the performance of our CT service by improved compliance and a reduction in radiation dose to our paediatric patients. We have also been able to benchmark our performance with similar national and international institutions. © 2016 The Royal Australian and New Zealand College of Radiologists.

Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite level dependent effects?

PubMed

Gilissen, L P L; Derijks, L J J; Driessen, A; Bos, L P; Hooymans, P M; Stockbrügger, R W; Engels, L G J B

2007-02-01

6-Thioguanine is used in inflammatory bowel disease since 2001, with promising short-term results. In 2003, liver histology of some 6-thioguanine treated patients showed nodular regenerative hyperplasia. Recently, magnetic resonance imaging revealed nodular regenerative hyperplasia in patients with normal histology. Investigating the presence of nodular regenerative hyperplasia in long-term 6-thioguanine treated patients. Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months, were asked to undergo liver biopsy and magnetic resonance imaging. Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6-thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels were: 36 months, 18.8 mg (0.28 mg/kg) and 705 pmol/8x10(8) erythrocytes, respectively. Liver histology and magnetic resonance imaging showed no nodular regenerative hyperplasia. Liver biopsy and magnetic resonance imaging showed no nodular regenerative hyperplasia in these long-term 6-thioguanine treated inflammatory bowel disease patients. 6-thioguanine dose and metabolite levels were lower compared with previous nodular regenerative hyperplasia reports, suggesting dose or metabolite level-dependent effects. Otherwise, nodular regenerative hyperplasia is related with inflammatory bowel disease itself and immunosuppressives, including azathioprine and 6-mercaptopurine. 6-Thioguanine is debated due to nodular regenerative hyperplasia. We found no nodular regenerative hyperplasia in inflammatory bowel disease patients with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent effects. Therefore, 6-thioguanine still seems useful, but in selected patients, intolerant for other immunosuppressives, low dosed and under close surveillance of metabolite levels and hepatotoxity.

TU-EF-204-08: Dose Efficiency of Added Beam-Shaping Filter with Varied Attenuation Levels in Lung-Cancer Screening CT

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

Ma, C; Yu, L; Vrieze, T

Purpose: Added filtration such as tin filter has the potential to improve dose efficiency of x-ray beam in lung-cancer screening CT. However, dose efficiency with added beam filtration is highly dependent on patient attenuation level. In this phantom study, we evaluated the image quality at different tube voltages with and without added tin filter when attenuation level varies. Methods: A 30 x 20 cm anthropomorphic thorax phantom with three added extension rings were used to simulate small (S), medium (M), large (L), and extra-large (XL) adult patients. These phantoms were scanned on a 192-slice CT scanner (Force, Siemens) at 100more » and 120kV without tin filtration, and 100 and 150 kV with tin filtration (100Sn and 150Sn), at multiple dose levels at each kV. Images were reconstructed using iterative reconstruction (ADMIRE, Siemens). Radiation dose was measured with a 0.6 cc ion chamber in the middle and peripheral areas of the phantom. Image quality was assessed using mean image noise at uniform areas in the central region and lung. Radiation dose that is required for each kV to match the noise in a routine lung-cancer CT screening technique (120kV, 25 quality reference mAs) was calculated. Results: At each of the four phantom sizes, 100Sn had the lowest noise in both soft tissue and lung. Compared with 120 kV, 100Sn saved 39%–60% dose for the same noise, depending on phantom size. For the XL phantom (50 by 40 cm), 150Sn provided images with the least beam-hardening artifact in peripheral region. Conclusion: For thoracic CT, added tin filtration can provide considerable dose reduction compared with 120 kV. 100Sn provides better dose efficiencies for all phantom sizes, while 150Sn provides better image quality in peripheral region for extra-large patients. Drs.Joel G. Fletcher and Cynthia H. McCollough receive research support from Siemens Healthcare.« less

Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

PubMed Central

Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

2016-01-01

Purpose Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results Both intravenously and EP-administered neostigmine (0.2–66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. PMID:27274203

Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP).

PubMed

Liu, Albert Y; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P; Greenblatt, Ruth M; Gandhi, Monica

2014-01-01

Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60-93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also facilitate adherence measurement in real-world settings and merit further investigation in upcoming PrEP implementation studies and programs. ClinicalTrials.gov NCT00903084.

Strong Relationship between Oral Dose and Tenofovir Hair Levels in a Randomized Trial: Hair as a Potential Adherence Measure for Pre-Exposure Prophylaxis (PrEP)

PubMed Central

Liu, Albert Y.; Yang, Qiyun; Huang, Yong; Bacchetti, Peter; Anderson, Peter L.; Jin, Chengshi; Goggin, Kathy; Stojanovski, Kristefer; Grant, Robert; Buchbinder, Susan P.; Greenblatt, Ruth M.; Gandhi, Monica

2014-01-01

Background Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults. Methods A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs). Results Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60–93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair. Conclusions This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also facilitate adherence measurement in real-world settings and merit further investigation in upcoming PrEP implementation studies and programs. Trial Registration ClinicalTrials.gov +NCT00903084. PMID:24421901

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

Heintz, P; Heintz, B; Sandoval, D

Purpose: Computerized radiation therapy treatment planning is performed on almost all patients today. However it is seldom used for laboratory irradiations. The first objective is to assess whether modern radiation therapy treatment planning (RTP) systems accurately predict the subject dose by comparing in vivo and decedent dose measurements to calculated doses. The other objective is determine the importance of using a RTP system for laboratory irradiations. Methods: 5 MOSFET radiation dosimeters were placed enterically in each subject (2 sedated Rhesus Macaques) to measure the absorbed dose at 5 levels (carina, lung, heart, liver and rectum) during whole body irradiation. Themore » subjects were treated with large opposed lateral fields and extended distances to cover the entire subject using a Varian 600C linac. CT simulation was performed ante-mortem (AM) and post-mortem (PM). To compare AM and PM doses, calculation points were placed at the location of each dosimeter in the treatment plan. The measured results were compared to the results using Varian Eclipse and Prowess Panther RTP systems. Results: The Varian and Prowess treatment planning system agreed to within in +1.5% for both subjects. However there were significant differences between the measured and calculated doses. For both animals the calculated central axis dose was higher than prescribed by 3–5%. This was caused in part by inaccurate measurement of animal thickness at the time of irradiation. For one subject the doses ranged from 4% to 7% high and the other subject the doses ranged 7% to 14% high when compared to the RTP doses. Conclusions: Our results suggest that using proper CT RTP system can more accurately deliver the prescribed dose to laboratory subjects. It also shows that there is significant dose variation in such subjects when inhomogeneities are not considered in the planning process.« less

Effect of different doses of nandrolone decanoate on lipid peroxidation, DNA fragmentation, sperm abnormality and histopathology of testes of male Wister rats.

PubMed

Mohamed, Hanaa Mahmoud; Mohamed, Manal Abdul-Hamid

2015-01-01

The present study aims of to investigate the effects of low and high doses of nandrolone decanoate (ND) on histopathology and apoptosis of the spermatogenic cells as well as lipid peroxidation, antioxidant enzyme activities, sperm abnormality and DNA fragmentation. Eighteen animals were divided into three groups each group contain six animals. The rats were divided into three groups as following: Group 1 was administered saline (control). Group 2, received nandrolone decanoate (3 mg/kg/weekly) (low dose) with intramuscular injection. Group 3, received intramuscular injection dose of nandrolone decanoate (10 mg/kg/weekly) (high dose). After 8 weeks, caspase-3 assay was used to determine the apoptotic cells. The sperm parameters, lipid peroxidation, antioxidant enzyme activities and testosterone concentration were also investigated in the experimental groups of both low and high dose compared to the control groups. Treated group with high dose showed degenerated germinal epithelial cells sloughed in the lumina of seminiferous tubules, where almost seminiferous tubules were devoid of spermatids and spermatozoa compared to control and group treated with low dose. Also, a significant increase of lipid peroxidation levels and heat shock proteins was observed in two groups administrated with two different doses of ND while, antioxidant enzyme activities, and testosterone concentration was significantly decreased in two treated group when compared with control. Administration of ND at high and low doses leads to deteriorated sperm parameters, DNA fragmentation and testicular apoptosis. In conclusion, the administration ND at high doses more effective on lipid peroxidation, antioxidant enzyme activities, sperm abnormality, histopathology, apoptotic and DNA changes compared to low dose group and to control group. Published by Elsevier GmbH.

Subnormal and waning immunity to tetanus toxoid in previously vaccinated HIV-infected children and response to booster doses of the vaccine.

PubMed

Choudhury, Shahana A; Matin, Fazle

2013-12-01

Little is known regarding waning immunity to tetanus toxoid (TT) in HIV-infected children and the need for booster doses before the recommended interval of 5-10 years. Anti-tetanus antibodies were assessed by ELISA in 24 HIV-infected and 24 control children. A protective level (>0.1 IU/ml) of TT antibodies was observed in 62% of HIV-infected children and in 100% of controls. HIV-infected children with five doses had a significantly (p=0.01) lower prevalence of protective immunity compared to controls. Follow-up anti-TT antibody levels in nine HIV-infected children declined from 1.27 to 0.26 IU/ml, but levels did not decline in the seven controls; five of the seven (71%) children with a non-protective level of antibodies responded with a level>0.16 IU/ml following one booster dose of the vaccine. HIV-infected children may need TT boosters before the recommended 5-10 years. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Influence of radiation dose and reconstruction algorithm in MDCT assessment of airway wall thickness: A phantom study

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

Gomez-Cardona, Daniel; Nagle, Scott K.; Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Avenue, Madison, Wisconsin 53792

Purpose: Wall thickness (WT) is an airway feature of great interest for the assessment of morphological changes in the lung parenchyma. Multidetector computed tomography (MDCT) has recently been used to evaluate airway WT, but the potential risk of radiation-induced carcinogenesis—particularly in younger patients—might limit a wider use of this imaging method in clinical practice. The recent commercial implementation of the statistical model-based iterative reconstruction (MBIR) algorithm, instead of the conventional filtered back projection (FBP) algorithm, has enabled considerable radiation dose reduction in many other clinical applications of MDCT. The purpose of this work was to study the impact of radiationmore » dose and MBIR in the MDCT assessment of airway WT. Methods: An airway phantom was scanned using a clinical MDCT system (Discovery CT750 HD, GE Healthcare) at 4 kV levels and 5 mAs levels. Both FBP and a commercial implementation of MBIR (Veo{sup TM}, GE Healthcare) were used to reconstruct CT images of the airways. For each kV–mAs combination and each reconstruction algorithm, the contrast-to-noise ratio (CNR) of the airways was measured, and the WT of each airway was measured and compared with the nominal value; the relative bias and the angular standard deviation in the measured WT were calculated. For each airway and reconstruction algorithm, the overall performance of WT quantification across all of the 20 kV–mAs combinations was quantified by the sum of squares (SSQs) of the difference between the measured and nominal WT values. Finally, the particular kV–mAs combination and reconstruction algorithm that minimized radiation dose while still achieving a reference WT quantification accuracy level was chosen as the optimal acquisition and reconstruction settings. Results: The wall thicknesses of seven airways of different sizes were analyzed in the study. Compared with FBP, MBIR improved the CNR of the airways, particularly at low radiation dose levels. For FBP, the relative bias and the angular standard deviation of the measured WT increased steeply with decreasing radiation dose. Except for the smallest airway, MBIR enabled significant reduction in both the relative bias and angular standard deviation of the WT, particularly at low radiation dose levels; the SSQ was reduced by 50%–96% by using MBIR. The optimal reconstruction algorithm was found to be MBIR for the seven airways being assessed, and the combined use of MBIR and optimal kV–mAs selection resulted in a radiation dose reduction of 37%–83% compared with a reference scan protocol with a dose level of 1 mGy. Conclusions: The quantification accuracy of airway WT is strongly influenced by radiation dose and reconstruction algorithm. The MBIR algorithm potentially allows the desired WT quantification accuracy to be achieved with reduced radiation dose, which may enable a wider clinical use of MDCT for the assessment of airway WT, particularly for younger patients who may be more sensitive to exposures with ionizing radiation.« less

Dose rate effects on array CCDs exposed by Co-60 γ rays induce saturation output degradation and annealing tests

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Chen, Wei; He, Baoping

The experimental tests of dose rate and annealing effects on array charge-coupled devices (CCDs) are presented. The saturation output voltage (V{sub S}) versus the total dose at the dose rates of 0.01, 0.1, 1.0, 10.0 and 50 rad(Si)/s are compared. Annealing tests are performed to eliminate the time-dependent effects. The V{sub S} degradation levels depend on the dose rates. The V{sub S} degradation mechanism induced by dose rate and annealing effects is analyzed. The V{sub S} at 20 krad(Si) with the dose rate of 0.03 rad(Si)/s are supplemented to assure the degradation curves between the dose rates of 0.1 andmore » 0.01 rad(Si)/s. The CCDs are divided into two groups, with one group biased and the other unbiased during {sup 60}Co γ radiation. The V{sub S} degradation levels of the biased CCDs during radiation are more severe than that of the unbiased CCDs.« less

The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Śliwka, Przemysław W; Puła, Bartosz; Karwowski, Bolesław; Merecz-Sadowska, Anna; Dedecjus, Marek; Lewiński, Andrzej

2017-06-15

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131 I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake-the phenomenon called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131 I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations ( p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131 I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.

PubMed

Dellinger, Ryan W; Santos, Santiago Roel; Morris, Mark; Evans, Mal; Alminana, Dan; Guarente, Leonard; Marcotulli, Eric

2017-01-01

NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD +) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks. Analysis of NAD + in whole blood demonstrated that NRPT significantly increases the concentration of NAD + in a dose-dependent manner. NAD + levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. Furthermore, this significant increase in NAD + levels was sustained throughout the entire 8-week trial. NAD + levels did not increase for the placebo group during the trial. No serious adverse events were reported in this study. This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD + levels sustainably.

Volumetric modulated arc radiotherapy for esophageal cancer.

PubMed

Vivekanandan, Nagarajan; Sriram, Padmanaban; Kumar, S A Syam; Bhuvaneswari, Narayanan; Saranya, Kamalakannan

2012-01-01

A treatment planning study was performed to evaluate the performance of volumetric arc modulation with RapidArc (RA) against 3D conformal radiation therapy (3D-CRT) and conventional intensity-modulated radiation therapy (IMRT) techniques for esophageal cancer. Computed tomgraphy scans of 10 patients were included in the study. 3D-CRT, 4-field IMRT, and single-arc and double-arc RA plans were generated with the aim to spare organs at risk (OAR) and healthy tissue while enforcing highly conformal target coverage. The planning objective was to deliver 54 Gy to the planning target volume (PTV) in 30 fractions. Plans were evaluated based on target conformity and dose-volume histograms of organs at risk (lung, spinal cord, and heart). The monitor unit (MU) and treatment delivery time were also evaluated to measure the treatment efficiency. The IMRT plan improves target conformity and spares OAR when compared with 3D-CRT. Target conformity improved with RA plans compared with IMRT. The mean lung dose was similar in all techniques. However, RA plans showed a reduction in the volume of the lung irradiated at V(₂₀Gy) and V(₃₀Gy) dose levels (range, 4.62-17.98%) compared with IMRT plans. The mean dose and D(₃₅%) of heart for the RA plans were better than the IMRT by 0.5-5.8%. Mean V(₁₀Gy) and integral dose to healthy tissue were almost similar in all techniques. But RA plans resulted in a reduced low-level dose bath (15-20 Gy) in the range of 14-16% compared with IMRT plans. The average MU needed to deliver the prescribed dose by RA technique was reduced by 20-25% compared with IMRT technique. The preliminary study on RA for esophageal cancers showed improvements in sparing OAR and healthy tissue with reduced beam-on time, whereas only double-arc RA offered improved target coverage compared with IMRT and 3D-CRT plans. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Adaptive intensity modulated radiotherapy for advanced prostate cancer

NASA Astrophysics Data System (ADS)

Ludlum, Erica Marie

The purpose of this research is to develop and evaluate improvements in intensity modulated radiotherapy (IMRT) for concurrent treatment of prostate and pelvic lymph nodes. The first objective is to decrease delivery time while maintaining treatment quality, and evaluate the effectiveness and efficiency of novel one-step optimization compared to conventional two-step optimization. Both planning methods are examined at multiple levels of complexity by comparing the number of beam apertures, or segments, the amount of radiation delivered as measured by monitor units (MUs), and delivery time. One-step optimization is demonstrated to simplify IMRT planning and reduce segments (from 160 to 40), MUs (from 911 to 746), and delivery time (from 22 to 7 min) with comparable plan quality. The second objective is to examine the capability of three commercial dose calculation engines employing different levels of accuracy and efficiency to handle high--Z materials, such as metallic hip prostheses, included in the treatment field. Pencil beam, convolution superposition, and Monte Carlo dose calculation engines are compared by examining the dose differences for patient plans with unilateral and bilateral hip prostheses, and for phantom plans with a metal insert for comparison with film measurements. Convolution superposition and Monte Carlo methods calculate doses that are 1.3% and 34.5% less than the pencil beam method, respectively. Film results demonstrate that Monte Carlo most closely represents actual radiation delivery, but none of the three engines accurately predict the dose distribution when high-Z heterogeneities exist in the treatment fields. The final objective is to improve the accuracy of IMRT delivery by accounting for independent organ motion during concurrent treatment of the prostate and pelvic lymph nodes. A leaf-shifting algorithm is developed to track daily prostate position without requiring online dose calculation. Compared to conventional methods of adjusting patient position, adjusting the multileaf collimator (MLC) leaves associated with the prostate in each segment significantly improves lymph node dose coverage (maintains 45 Gy compared to 42.7, 38.3, and 34.0 Gy for iso-shifts of 0.5, 1 and 1.5 cm). Altering the MLC portal shape is demonstrated as a new and effective solution to independent prostate movement during concurrent treatment.

Oral hypoglycemic activity of culinary-medicinal mushrooms Pleurotus ostreatus and P. cystidiosus (higher basidiomycetes) in normal and alloxan-induced diabetic Wistar rats.

PubMed

Jayasuriya, W J A B; Suresh, T S; Abeytunga, D; Fernando, G H; Wanigatunga, C A

2012-01-01

This study investigates the oral hypoglycemic activity of Pleurotus ostreatus (P.o.) and P. cystidiosus (P.c.) mushrooms on normal and alloxan-induced diabetic Wistar rats. Different doses (250, 500, 750, 1000, and 1250 mg/kg/body weight) of suspensions of freeze-dried and powdered (SFDP) P.o. and P.c. were administered to normal rats, and postprandial serum glucose levels were measured. Optimal time of activity was investigated using the dose 500 mg/kg. Hypoglycemic effect of a single dose of SFDP P.o. and P.c. (500 mg/kg) were investigated using diabetic male and female rats at different stages of estrous cycle and compared with metformin and glibenclamide. Chronic hypoglycemic activity of SFDP P.o. and P.c. (500 mg/kg) was studied using serum glucose levels and glycosylated hemoglobin levels. Maximally effective dose of SFDP P.o. and P.c. was 500 mg/kg. The highest reduction in the serum glucose level was observed 120 minutes after administration of mushrooms. A single dose of P.o. and P.c. significantly (P < 0.05) reduced the serum glucose levels of male diabetic rats. The hypoglycemic activity in female rats was highest in proestrous stage. The hypoglycemic effect of P.o. and P.c. is comparable with metformin and glibenclamide. Daily single administrations of P.o. and P.c. to diabetic rats exert apparent control on the homeostasis of blood glucose. SFDP P.o. and P.c. possessed marked and significant oral hypoglycemic activity. This study suggests the consumption of P.o. and P.c. mushrooms might bring health benefits to mankind as it shows hypoglycemic activity in rats.

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

PubMed Central

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

2004-01-01

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

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma: radiation dose to the testes

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

Hattori, Naoya; Gopal, Ajay K.; Shields, Andrew T.

Purpose: To investigate radiation doses to the testes delivered by a radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. Materials and methods: Testicular uptake and retention of 131I-tositumomab were measured, and testicular absorbed doses were calculated for 67 male patients (54+/-11 years of age) with non-Hodgkin's lymphoma who had undergone myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging studies. In a subset of patients, male sex hormones were measured before and 1 year after the therapy. Results: The absorbed dose to the testes showed considerablemore » variability (range=4.4-70.2 Gy). Pretherapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction [4.6+/-1.8 nmol/l (pre-RIT) vs. 3.8+/-2.9 nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the testes (>=25 Gy) showed a greater reduction [4.7+/-1.6 nmol/l (pre-RIT) vs. 3.3+/-2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower doses (<25 Gy), who showed no significant change in total testosterone levels. Conclusion: The testicular radiation absorbed dose varied highly among individual patients. Finally, patients receiving higher doses to the testes were more likely to show post-RIT suppression of testosterone levels.« less

Experimental study of radiation dose rate at different strategic points of the BAEC TRIGA Research Reactor.

PubMed

Ajijul Hoq, M; Malek Soner, M A; Salam, M A; Haque, M M; Khanom, Salma; Fahad, S M

2017-12-01

The 3MW TRIGA Mark-II Research Reactor of Bangladesh Atomic Energy Commission (BAEC) has been under operation for about thirty years since its commissioning at 1986. In accordance with the demand of fundamental nuclear research works, the reactor has to operate at different power levels by utilizing a number of experimental facilities. Regarding the enquiry for safety of reactor operating personnel and radiation workers, it is necessary to know the radiation level at different strategic points of the reactor where they are often worked. In the present study, neutron, beta and gamma radiation dose rate at different strategic points of the reactor facility with reactor power level of 2.4MW was measured to estimate the rising level of radiation due to its operational activities. From the obtained results high radiation dose is observed at the measurement position of the piercing beam port which is caused by neutron leakage and accordingly, dose rate at the stated position with different reactor power levels was measured. This study also deals with the gamma dose rate measurements at a fixed position of the reactor pool top surface for different reactor power levels under both Natural Convection Cooling Mode (NCCM) and Forced Convection Cooling Mode (FCCM). Results show that, radiation dose rate is higher for NCCM in compared with FCCM and increasing with the increase of reactor power. Thus, concerning the radiological safety issues for working personnel and the general public, the radiation dose level monitoring and the experimental analysis performed within this paper is so much effective and the result of this work can be utilized for base line data and code verification of the nuclear reactor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

PubMed

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

A comparison of the convolution and TMR10 treatment planning algorithms for Gamma Knife® radiosurgery

PubMed Central

Wright, Gavin; Harrold, Natalie; Bownes, Peter

2018-01-01

Aims To compare the accuracies of the convolution and TMR10 Gamma Knife treatment planning algorithms, and assess the impact upon clinical practice of implementing convolution-based treatment planning. Methods Doses calculated by both algorithms were compared against ionisation chamber measurements in homogeneous and heterogeneous phantoms. Relative dose distributions calculated by both algorithms were compared against film-derived 2D isodose plots in a heterogeneous phantom, with distance-to-agreement (DTA) measured at the 80%, 50% and 20% isodose levels. A retrospective planning study compared 19 clinically acceptable metastasis convolution plans against TMR10 plans with matched shot times, allowing novel comparison of true dosimetric parameters rather than total beam-on-time. Gamma analysis and dose-difference analysis were performed on each pair of dose distributions. Results Both algorithms matched point dose measurement within ±1.1% in homogeneous conditions. Convolution provided superior point-dose accuracy in the heterogeneous phantom (-1.1% v 4.0%), with no discernible differences in relative dose distribution accuracy. In our study convolution-calculated plans yielded D99% 6.4% (95% CI:5.5%-7.3%,p<0.001) less than shot matched TMR10 plans. For gamma passing criteria 1%/1mm, 16% of targets had passing rates >95%. The range of dose differences in the targets was 0.2-4.6Gy. Conclusions Convolution provides superior accuracy versus TMR10 in heterogeneous conditions. Implementing convolution would result in increased target doses therefore its implementation may require a revaluation of prescription doses. PMID:29657896

Very low-dose (0.15 mGy) chest CT protocols using the COPDGene 2 test object and a third-generation dual-source CT scanner with corresponding third-generation iterative reconstruction software.

PubMed

Newell, John D; Fuld, Matthew K; Allmendinger, Thomas; Sieren, Jered P; Chan, Kung-Sik; Guo, Junfeng; Hoffman, Eric A

2015-01-01

The purpose of this study was to evaluate the impact of ultralow radiation dose single-energy computed tomographic (CT) acquisitions with Sn prefiltration and third-generation iterative reconstruction on density-based quantitative measures of growing interest in phenotyping pulmonary disease. The effects of both decreasing dose and different body habitus on the accuracy of the mean CT attenuation measurements and the level of image noise (SD) were evaluated using the COPDGene 2 test object, containing 8 different materials of interest ranging from air to acrylic and including various density foams. A third-generation dual-source multidetector CT scanner (Siemens SOMATOM FORCE; Siemens Healthcare AG, Erlangen, Germany) running advanced modeled iterative reconstruction (ADMIRE) software (Siemens Healthcare AG) was used.We used normal and very large body habitus rings at dose levels varying from 1.5 to 0.15 mGy using a spectral-shaped (0.6-mm Sn) tube output of 100 kV(p). Three CT scans were obtained at each dose level using both rings. Regions of interest for each material in the test object scans were automatically extracted. The Hounsfield unit values of each material using weighted filtered back projection (WFBP) at 1.5 mGy was used as the reference value to evaluate shifts in CT attenuation at lower dose levels using either WFBP or ADMIRE. Statistical analysis included basic statistics, Welch t tests, multivariable covariant model using the F test to assess the significance of the explanatory (independent) variables on the response (dependent) variable, and CT mean attenuation, in the multivariable covariant model including reconstruction method. Multivariable regression analysis of the mean CT attenuation values showed a significant difference with decreasing dose between ADMIRE and WFBP. The ADMIRE has reduced noise and more stable CT attenuation compared with WFBP. There was a strong effect on the mean CT attenuation values of the scanned materials for ring size (P < 0.0001) and dose level (P < 0.0001). The number of voxels in the region of interest for the particular material studied did not demonstrate a significant effect (P > 0.05). The SD was lower with ADMIRE compared with WFBP at all dose levels and ring sizes (P < 0.05). The third-generation dual-source CT scanners using third-generation iterative reconstruction methods can acquire accurate quantitative CT images with acceptable image noise at very low-dose levels (0.15 mGy). This opens up new diagnostic and research opportunities in CT phenotyping of the lung for developing new treatments and increased understanding of pulmonary disease.

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

PubMed

Ozyigit, Filiz; Kucuk, Aysegul; Akcer, Sezer; Tosun, Murat; Kocak, Fatma Emel; Kocak, Cengiz; Kocak, Ahmet; Metineren, Hasan; Genc, Osman

2015-08-26

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (p<0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (p<0.01, p<0.05, respectively), and increased SOD, GPx, and CAT activities (p<0.001, p<0.01, p<0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (p<0.01, p<0.05, p<0.001) and MDA and NO levels (p<0.05, p<0.01) and decreased SOD, GPx, and CAT activities (p<0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

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

PubMed Central

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

2013-01-01

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

MO-FG-204-04: How Iterative Reconstruction Algorithms Affect the NPS of CT Images

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

Li, G; Liu, X; Dodge, C

2015-06-15

Purpose: To evaluate how the third generation model based iterative reconstruction (MBIR) compares with filtered back-projection (FBP), adaptive statistical iterative reconstruction (ASiR), and the second generation MBIR based on noise power spectrum (NPS) analysis over a wide range of clinically applicable dose levels. Methods: The Catphan 600 CTP515 module, surrounded by an oval, fat-equivalent ring to mimic patient size/shape, was scanned on a GE HD750 CT scanner at 1, 2, 3, 6, 12 and 19mGy CTDIvol levels with typical patient scan parameters: 120kVp, 0.8s, 40mm beam width, large SFOV, 0.984 pitch and reconstructed thickness 2.5mm (VEO3.0: Abd/Pelvis with Texture andmore » NR05). At each CTDIvol level, 10 repeated scans were acquired for achieving sufficient data sampling. The images were reconstructed using Standard kernel with FBP; 20%, 40% and 70% ASiR; and two versions of MBIR (VEO2.0 and 3.0). For evaluating the effect of the ROI spatial location to the Result of NPS, 4 ROI groups were categorized based on their distances from the center of the phantom. Results: VEO3.0 performed inferiorly comparing to VEO2.0 over all dose levels. On the other hand, at low dose levels (less than 3 mGy), it clearly outperformed ASiR and FBP, in NPS values. Therefore, the lower the dose level, the relative performance of MBIR improves. However, the shapes of the NPS show substantial differences in horizontal and vertical sampling dimensions. These differences may determine the characteristics of the noise/texture features in images, and hence, play an important role in image interpretation. Conclusion: The third generation MBIR did not improve over the second generation MBIR in term of NPS analysis. The overall performance of both versions of MBIR improved as compared to other reconstruction algorithms when dose was reduced. The shapes of the NPS curves provided additional value for future characterization of the image noise/texture features.« less

Brief Report: The Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen Does Not Impact the Ovarian Reserve, as Measured by Serum Levels of Anti-Müllerian Hormone.

PubMed

Tamirou, Farah; Husson, Séverine Nieuwland; Gruson, Damien; Debiève, Frédéric; Lauwerys, Bernard R; Houssiau, Frédéric A

2017-06-01

The Euro-Lupus regimen of low-dose intravenous cyclophosphamide (IV CYC) (cumulative dose of 3 gm) was developed to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum titers of anti-Müllerian hormone (AMH) in patients with systemic lupus erythematosus (SLE) treated with the Euro-Lupus regimen and compared them with those measured in patients who were treated with higher doses of IV CYC or were never treated with IV CYC. Serum AMH levels were measured by enzyme-linked immunosorbent assay in a cohort of 155 premenopausal SLE patients; 30 of these patients had been treated with the Euro-Lupus regimen, and 24 had received higher doses of IV CYC. None had received oral CYC. AMH levels were age-adjusted using a slope computed from levels measured across the group of SLE patients who had not been treated with IV CYC. Demographic and clinical data were collected. Serum titers of AMH measured in SLE patients treated with the Euro-Lupus IV CYC regimen (median dose 1.46 ng/ml) did not differ from those measured in patients never treated with the cytotoxic drug (median 1.85 ng/ml). As expected, patients given >6 gm of IV CYC had significantly lower serum titers of AMH (median 0.83 ng/ml) compared with those never treated with IV CYC (P = 0.047). Median serum AMH titers did not change before (1.24 ng/ml) and after (2.50 ng/ml) treatment with the Euro-Lupus IV CYC regimen in the subset of patients for whom paired samples could be tested (P = 0.43). The Euro-Lupus regimen of low-dose IV CYC does not impact the ovarian reserve of SLE patients and can therefore be proposed as treatment in patients seeking to become pregnant. © 2017, American College of Rheumatology.

Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey.

PubMed

Knight-Jones, T J D; Bulut, A N; Gubbins, S; Stärk, K D C; Pfeiffer, D U; Sumption, K J; Paton, D J

2015-02-04

Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the relationship between antibody titre and protection. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Viability of primary osteoblasts after treatment with tenofovir alafenamide: Lack of cytotoxicity at clinically relevant drug concentrations

PubMed Central

Callebaut, Christian; Liu, Yang; Babusis, Darius; Ray, Adrian; Miller, Michael; Kitrinos, Kathryn

2017-01-01

Tenofovir alafenamide (TAF) is a phosphonoamidate prodrug of the nucleotide HIV reverse transcriptase inhibitor tenofovir (TFV). TAF is approved for the treatment of HIV-1 infection as part of the single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF. When dosed once-daily, TAF results in approximately 90% lower levels of plasma TFV and a 4-fold increase in intracellular TFV-diphosphate (TFV-DP) in PBMCs compared with the TFV prodrug tenofovir disoproxil fumarate (TDF). Several antiretrovirals, including TDF, have been associated with bone mineral density decreases in patients; the effect of clinically relevant TAF concentrations on primary osteoblast viability was therefore assessed in vitro. Studies in PBMCs determined that a 2-hour TAF exposure at concentrations similar to human plasma Cmax achieved intracellular TFV-DP levels comparable to those observed after the maximum recommended human dose of 25 mg TAF. Comparable intracellular TFV-DP levels were achieved in primary osteoblasts with 2-hour TAF exposure daily for 3 days at concentrations similar to those used for PBMCs (100–400 nM). No change in cell viability was observed in either primary osteoblasts or PBMCs. The mean TAF CC50 in primary osteoblasts after 3 days of daily 2-hour pulses was >500 μM, which is >1033 times higher than the TAF maximum recommended human dose plasma Cmax. In summary, primary osteoblasts were not preferentially loaded by TAF compared with PBMCs, with comparable TFV-DP levels achieved in both cell types. Furthermore, there was no impact on osteoblast cell viability at clinically relevant TAF concentrations. PMID:28182625

Viability of primary osteoblasts after treatment with tenofovir alafenamide: Lack of cytotoxicity at clinically relevant drug concentrations.

PubMed

Callebaut, Christian; Liu, Yang; Babusis, Darius; Ray, Adrian; Miller, Michael; Kitrinos, Kathryn

2017-01-01

Tenofovir alafenamide (TAF) is a phosphonoamidate prodrug of the nucleotide HIV reverse transcriptase inhibitor tenofovir (TFV). TAF is approved for the treatment of HIV-1 infection as part of the single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF. When dosed once-daily, TAF results in approximately 90% lower levels of plasma TFV and a 4-fold increase in intracellular TFV-diphosphate (TFV-DP) in PBMCs compared with the TFV prodrug tenofovir disoproxil fumarate (TDF). Several antiretrovirals, including TDF, have been associated with bone mineral density decreases in patients; the effect of clinically relevant TAF concentrations on primary osteoblast viability was therefore assessed in vitro. Studies in PBMCs determined that a 2-hour TAF exposure at concentrations similar to human plasma Cmax achieved intracellular TFV-DP levels comparable to those observed after the maximum recommended human dose of 25 mg TAF. Comparable intracellular TFV-DP levels were achieved in primary osteoblasts with 2-hour TAF exposure daily for 3 days at concentrations similar to those used for PBMCs (100-400 nM). No change in cell viability was observed in either primary osteoblasts or PBMCs. The mean TAF CC50 in primary osteoblasts after 3 days of daily 2-hour pulses was >500 μM, which is >1033 times higher than the TAF maximum recommended human dose plasma Cmax. In summary, primary osteoblasts were not preferentially loaded by TAF compared with PBMCs, with comparable TFV-DP levels achieved in both cell types. Furthermore, there was no impact on osteoblast cell viability at clinically relevant TAF concentrations.

Relationship Between Physical Activity, Body Mass Index, and Risk of Heart Failure

PubMed Central

Pandey, Ambarish; LaMonte, Michael; Klein, Liviu; Ayers, Colby; Psaty, Bruce; Eaton, Charles; Allen, Norrina; de Lemos, James A.; Carnethon, Mercedes; Greenland, Philip; Berry, Jarett D.

2018-01-01

Background Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Objective This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes. Methods Individual-level data from 3 cohort studies (WHI, MESA, and CHS) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction [EF] ≥45%) and HFrEF (EF <45%) were assessed used multivariable adjusted Cox models and restricted cubic splines. Results The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, 1,014 missing EF). In adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 metabolic equivalents of task [MET]-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (HR: 0.81; 95% CI: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥ 25 kg/m2) was associated with greater increase in risk of HFpEF than HFrEF. Conclusion Our study findings demonstrate strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF. PMID:28254175

Bayesian Dose-Response Modeling in Sparse Data

NASA Astrophysics Data System (ADS)

Kim, Steven B.

This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a wrong parametric assumption. In this regard, we consider a robust experimental design which does not require any parametric assumption.

Weight-adapted iodinated contrast media administration in abdomino-pelvic CT: Can image quality be maintained?

PubMed

Perrin, E; Jackson, M; Grant, R; Lloyd, C; Chinaka, F; Goh, V

2018-02-01

In many centres, a fixed method of contrast-media administration is used for CT regardless of patient body habitus. The aim of this trial was to assess contrast enhancement of the aorta, portal vein, liver and spleen during abdomino-pelvic CT imaging using a weight-adapted contrast media protocol compared to the current fixed dose method. Thirty-nine oncology patients, who had previously undergone CT abdomino-pelvic imaging at the institution using a fixed contrast media dose, were prospectively imaged using a weight-adapted contrast media dose (1.4 ml/kg). The two sets of images were assessed for contrast enhancement levels (HU) at locations in the liver, aorta, portal vein and spleen during portal-venous enhancement phase. The t-test was used to compare the difference in results using a non-inferiority margin of 10 HU. When the contrast dose was tailored to patient weight, contrast enhancement levels were shown to be non-inferior to the fixed dose method (liver p < 0.001; portal vein p = 0.003; aorta p = 0.001; spleen p = 0.001). As a group, patients received a total contrast dose reduction of 165 ml using the weight-adapted method compared to the fixed dose method, with a mean cost per patient of £6.81 and £7.19 respectively. Using a weight-adapted method of contrast media administration was shown to be non-inferior to a fixed dose method of contrast media administration. Patients weighing 76 kg, or less, received a lower contrast dose which may have associated cost savings. A weight-adapted contrast media protocol should be implemented for portal-venous phase abdomino-pelvic CT for oncology patients with adequate renal function (>70 ml/min/1.73 m 2 ). Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Olive leaf down-regulates the oxidative stress and immune dysregulation in streptozotocin-induced diabetic mice.

PubMed

Park, Jung-Hyun; Jung, Ji-Hye; Yang, Jin-Young; Kim, Hyun-Sook

2013-11-01

Type 1 diabetes is an endocrinologic disorder characterized by uncontrolled glucose regulation and oxidative stress. Olive leaves have been studied extensively for their antioxidant activity and capacity to improve immune function. We hypothesized that olive leaf powder supplementation will be effective in inhibiting the oxidative stress and immune dysregulation in streptozotocin (STZ)-induced diabetic mice. Mice were assigned to 1 of 5 groups: control (C), STZ-induced diabetes (D), and STZ-induced diabetes supplemented with very low dose (VLOL), low dose (LOL), or high dose of olive leaf powder (HOL). Blood glucose in the VLOL and LOL groups was lower than that in the D group (P < .05). Insulin levels were increased in all experimental groups in comparison with that in the D group, (P < .05). Superoxide dismutase, glutathione peroxidase, and catalase activities were shown to decrease in the D group, whereas these were increased in the VLOL and LOL groups. Nitric oxide levels decreased in the VLOL and LOL groups, as compared with the D group. The messenger RNA expression levels of inducible nitric oxide synthase were significantly decreased in the VLOL and HOL groups, and interferon-γ levels were significantly decreased in the liver of the VLOL, LOL, and HOL groups compared with the levels in the D group. Interleukin-17 levels were significantly decreased in the VLOL and HOL groups. Th1 and Th17 cytokine levels were increased in the D group but decreased in all the experimental groups. Th2 cytokine levels were increased in all olive leaf-supplemented groups compared with those in the D group. These results indicate a reduction in the levels of proinflammatory cytokines, suggesting that olive leaves have the potential to provide therapeutic inhibition of diabetic complications. © 2013.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

[Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level].

PubMed

Yan, Ling; Ye, Lu; Wang, Kun; Zhou, Jie; Zhu, Chunjia

2016-05-25

Objective: To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels. Methods: One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed. Results: Serum uric acid levels were decreased after treatment in both groups (all P <0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level ( P <0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group ( P <0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups ( P >0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels ( P <0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid ( P <0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI ( OR =1.01, 95% CI :1.01-1.11, P <0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) ( P <0.01). Conclusion: High dose atorvastatin can decrease serum uric acid levels and improve reflow after PCI in patients with STEMI.

High-dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of relation between serum methotrexate concentration and creatinine clearance.

PubMed

Joannon, Pilar; Oviedo, Iris; Campbell, Myriam; Tordecilla, Juan

2004-07-01

The objectives of this study were: (1) to analyze the relation of serum methotrexate (MTX) concentration with creatinine clearance, (2) to compare the leucovorin rescue dose administered to the patients based on creatinine clearance, with the one calculated according to serum MTX levels, and (3) to determine MTX-related toxicity. Thirty children with high-risk non-B acute lymphoblastic leukemia (ALL) treated according to the national protocol (PINDA 92) based on ALL BFM 90, were randomized to receive consolidation with four doses of either 1 or 2 g/m(2) MTX as a 24-hr infusion, at 2-week intervals (group M1 and M2, respectively). Serum MTX concentrations were measured at 24, 42, and 48 hr after beginning the infusion and were analyzed retrospectively. The creatinine clearance was calculated after 12-hr intravenous hydration prior to each MTX dose. Leucovorin dosage was adjusted according to creatinine clearance. Serum MTX concentrations at 24, 42, and 48 hr after starting the infusion were not related to creatinine clearance in both treatment groups. Leucovorin rescue administered according to creatinine clearance was excessive in 43% in group M1 and in 51% in group M2, as compared to the dose calculated according to serum MTX levels. No serious clinical complications were observed. These results suggest that creatinine clearance is not a good parameter to calculate leucovorin rescue. MTX-related toxicity in this group of patients receiving a dose of 1 or 2 g/m(2) and rescued with leucovorin without monitoring serum MTX levels was acceptable. Copyright 2004 Wiley-Liss, Inc.

210Po, 210Pb, 40K and 137Cs in edible wild berries and mushrooms and ingestion doses to man from high consumption rates of these wild foods.

PubMed

Gwynn, Justin P; Nalbandyan, Anna; Rudolfsen, Geir

2013-02-01

This paper discusses activity concentrations of (210)Po, (210)Pb, (40)K and (137)Cs in edible wild berries and mushrooms collected from Øvre Dividalen national park, Northern Norway and derives committed effective ingestion doses to man based on high consumption rates of these wild foods. Edible wild berries and mushrooms accumulated similar levels of (210)Pb, but mushrooms accumulated higher levels of (210)Po and (40)K than berries. There appears to be a clear difference in the ability of Leccinum spp. of fungi to accumulate (210)Po and/or translocate (210)Po to mushrooms compared to Russula spp. of fungi. Activity concentrations of (137)Cs in edible wild berries and mushrooms from Øvre Dividalen national park reflected the lower levels of fallout of this radionuclide in Northern Norway compared to more central areas following the Chernobyl accident. For mushrooms, ingestion doses are dominated by (210)Po, while for berries, (40)K is typically the main contributor to dose. Based on high consumption rates, ingestion doses arising from the combination of (210)Po, (210)Pb and (40)K were up to 0.05 mSv/a for berries and 0.50 mSv/a for mushrooms. Consumption of such wild foods may result in a significant contribution to total annual doses when consumed in large quantities, particularly when selecting mushrooms species that accumulate high activity concentrations of (210)Po. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

External doses of residents near Semipalatinsk nuclear test site.

PubMed

Takada, J; Hoshi, M; Nagatomo, T; Yamamoto, M; Endo, S; Takatsuji, T; Yoshikawa, I; Gusev, B I; Sakerbaev, A K; Tchaijunusova, N J

1999-12-01

Accumulated external radiation doses of residents near the Semipalatinsk nuclear test site of the former USSR are presented as a results of study by the thermoluminescence technique for bricks sampled at several settlements in 1995 and 1996. The external doses that we evaluated from exposed bricks were up to about 100 cGy for resident. The external doses at several points in the center of Semipalatinsk City ranged from a background level to 60 cGy, which was remarkably high compared with the previously reported values based on military data.

Dosimetric analysis of testicular doses in prostate intensity-modulated and volumetric-modulated arc radiation therapy at different energy levels

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

Onal, Cem, E-mail: hcemonal@hotmail.com; Arslan, Gungor; Dolek, Yemliha

2016-01-01

The aim of this study is to evaluate the incidental testicular doses during prostate radiation therapy with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) at different energies. Dosimetric data of 15 patients with intermediate-risk prostate cancer who were treated with radiotherapy were analyzed. The prescribed dose was 78 Gy in 39 fractions. Dosimetric analysis compared testicular doses generated by 7-field intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy with a single arc at 6, 10, and 15 MV energy levels. Testicular doses calculated from the treatment planning system and doses measured from the detectors were analyzed. Mean testicular doses from themore » intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy per fraction calculated in the treatment planning system were 16.3 ± 10.3 cGy vs 21.5 ± 11.2 cGy (p = 0.03) at 6 MV, 13.4 ± 10.4 cGy vs 17.8 ± 10.7 cGy (p = 0.04) at 10 MV, and 10.6 ± 8.5 cGy vs 14.5 ± 8.6 cGy (p = 0.03) at 15 MV, respectively. Mean scattered testicular doses in the phantom measurements were 99.5 ± 17.2 cGy, 118.7 ± 16.4 cGy, and 193.9 ± 14.5 cGy at 6, 10, and 15 MV, respectively, in the intensity-modulated radiotherapy plans. In the volumetric-modulated arc radiotherapy plans, corresponding testicular doses per course were 90.4 ± 16.3 cGy, 103.6 ± 16.4 cGy, and 139.3 ± 14.6 cGy at 6, 10, and 15 MV, respectively. In conclusions, this study was the first to measure the incidental testicular doses by intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy plans at different energy levels during prostate-only irradiation. Higher photon energy and volumetric-modulated arc radiotherapy plans resulted in higher incidental testicular doses compared with lower photon energy and intensity-modulated radiotherapy plans.« less

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

PubMed

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

2015-07-01

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

Improvements to image quality using hybrid and model-based iterative reconstructions: a phantom study.

PubMed

Aurumskjöld, Marie-Louise; Ydström, Kristina; Tingberg, Anders; Söderberg, Marcus

2017-01-01

The number of computed tomography (CT) examinations is increasing and leading to an increase in total patient exposure. It is therefore important to optimize CT scan imaging conditions in order to reduce the radiation dose. The introduction of iterative reconstruction methods has enabled an improvement in image quality and a reduction in radiation dose. To investigate how image quality depends on reconstruction method and to discuss patient dose reduction resulting from the use of hybrid and model-based iterative reconstruction. An image quality phantom (Catphan® 600) and an anthropomorphic torso phantom were examined on a Philips Brilliance iCT. The image quality was evaluated in terms of CT numbers, noise, noise power spectra (NPS), contrast-to-noise ratio (CNR), low-contrast resolution, and spatial resolution for different scan parameters and dose levels. The images were reconstructed using filtered back projection (FBP) and different settings of hybrid (iDose 4 ) and model-based (IMR) iterative reconstruction methods. iDose 4 decreased the noise by 15-45% compared with FBP depending on the level of iDose 4 . The IMR reduced the noise even further, by 60-75% compared to FBP. The results are independent of dose. The NPS showed changes in the noise distribution for different reconstruction methods. The low-contrast resolution and CNR were improved with iDose 4 , and the improvement was even greater with IMR. There is great potential to reduce noise and thereby improve image quality by using hybrid or, in particular, model-based iterative reconstruction methods, or to lower radiation dose and maintain image quality. © The Foundation Acta Radiologica 2016.

[Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].

PubMed

Ding, Xiao-shuang; Liang, Ai-hua; Wang, Jin-hua; Xiao, Yong-qing; Wu, Zi-lun; Li, Chun-ying; Li, Li; He, Rong; Hui, Lian-qiang; Liu, Bao-yan

2005-07-01

The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA. GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.

Dose escalation study to evaluate safety, tolerability and efficacy of intravenous etoposide phosphate administration in 27 dogs with multicentric lymphoma

PubMed Central

Hordeaux, Juliette; Bouchaert, Emmanuel; Gomes, Bruno

2017-01-01

Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies. This work was part of a comparative oncology project assessing a new, clinical-stage topoisomerase II inhibitor and comparing it with etoposide in dogs with spontaneous lymphoma with the objective to translate findings from dogs to humans. Etoposide is a topoisomerase II inhibitor widely used in various humans’ solid and hematopoietic cancer, but little data is available concerning its potential antitumor efficacy in dogs. Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to be better tolerated in dogs. The objectives of this study were to assess the safety, the tolerability and the efficacy of intravenous etoposide phosphate in dogs with multicentric lymphoma. Seven dose levels were evaluated in a traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade multicentric lymphoma were enrolled and treated with three cycles of etoposide phosphate IV injections every 2 weeks. Adverse effects were graded according to the Veterinary Cooperative Oncology Group criteria. A complete end-staging was realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no hypersensitivity reaction were reported at this dose level. Beyond the characterization of etoposide clinical efficacy in dogs, this study underlined the clinical and therapeutic homologies between dog and human lymphomas. PMID:28505195

Bone cancer occurrence among beagles given 239Pu as young adults.

PubMed

Lloyd, R D; Taylor, G N; Angus, W; Bruenger, F W; Miller, S C

1993-01-01

The occurrence of skeletal malignancies has been documented among 234 young adult beagles given single intravenous injections of monomeric 239Pu citrate. Occurrence has also been documented among 132 comparable control group animals surviving the minimum latent time period of 2.79 y for radiation-induced bone cancer, who were maintained for lifespan observation. Injected amounts ranged from about 0.02-106 kBq kg-1 body mass with factors of 2 or 3 between dose levels. There were 84 radiographically apparent bone tumors in 76 plutonium-injected dogs and one tumor in a control group dog. Most of these were osteosarcomas except for seven chondrosarcomas, one liposarcoma, and one plasma cell myeloma of bone. The relationship between percent of dogs at any dose level with bone malignancy and average skeletal dose at the presumed time of tumor initiation of 1 y before death appeared to be linear below about 1.3 Gy average skeletal dose. The observed data can be approximated by the expression A = 0.76 + 75 D, where A = percent of dogs with bone cancer at any dose level, D = average skeletal dose in Gy (for doses up to 1.3 Gy) at tumor initiation, and 0.76 represents the percent tumor response in the control animals not given plutonium. Similar analysis of our corresponding data for beagles given 226Ra, excluding the two highest dose levels (approximately 100% occurrence), yielded the expression A = 0.76 + 4.7 D, where D = the average skeletal dose in Gy (for doses up to 20 Gy) at 1 y before death. The ratio of coefficients indicates the effectiveness for bone cancer induction of 239Pu relative to 226Ra, or [(75 +/- 22.5)(4.7 +/- 0.47)-1] = 16 +/- 5 for a single, brief intake of either nuclide into blood.

The Effect of Route, Vehicle, and Divided Doses on the Pharmacokinetics of Chlorpyrifos and its Metabolite Trichloropyridinol in Neonatal Sprague-Dawley Rats

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

Marty, M. S.; Domoradzki, J. Y.; Hansen, S. C.

2007-12-01

There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single vs. divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol (TCP), were measured at multiple times through 24 h. Groups included: single gavage bolus vs. divided gavage doses in corn oil (1 vs 3 times in 24 h), single gavage bolus vs. divided gavage doses in rat milk, and subcutaneous administration in DMSO. These data were compared with lactationalmore » exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for four weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g, and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered chlorpyrifos. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose and frequency of administration result in different systemic exposure to the test chemical and its metabolites.« less

SU-E-P-57: Radiation Doses Assessment to Paediatric Patients for Some Digital Diagnostic Radiology Examination in Emergency Department in Qatar

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

Abdallah, I; Aly, A; Al Naemi, H

Purpose: The aim of this study was to evaluate radiation doses to pediatric patients undergoing standard radiographic examinations using Direct Digital Radiography (DDR) in Paediatric emergency center of Hamad General Hospital (HGH) in state of Qatar and compared with regional and international Dose Reference Levels (DRLs). Methods: Entrance Skin Dose (ESD) was measured for 2739 patients for two common X-ray examinations namely: Chest AP/PA, Abdomen. Exposure factors such as kV, mAs and Focal to Skin Distance (FSD) were recorded for each patient. Tube Output was measured for a range of selected kV values. ESD for each individual patient was calculatedmore » using the tube output and the technical exposure factors for each examination. The ESD values were compared with the some international Dose Reference Levels (DRL) for all types of examinations. Results: The most performed procedure during the time of this study was chest PA/PA (85%). The mean ESD values obtained from AP chest, PA chest and AP abdomen ranged 91–120, 80–84 and 209 – 659 µGy per radiograph for different age’s groups respectively. Two protocols have been used for chest AP and PA using different radiological parameters, and the different of ESD values for chest PA and were 41% for 1 years old child, 57% for 5 years old for chest AP. Conclusion: The mean ESD were compared with those found in literature and were found to be comparable. The radiation dose can be reduced more for Chest AP and PA examination by optimization of each investigation and hence more studies are required for this task. The results presented will serve as a baseline data needed for deriving local reference doses for pediatric X-ray examinations in this local department and hence it can be applied in the whole Qatar.« less

Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method

NASA Astrophysics Data System (ADS)

McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A.; Purdie, Thomas G.

2017-08-01

Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment planning and can be readily applied to different treatment sites and modalities.

Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method.

PubMed

McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A; Purdie, Thomas G

2017-07-06

Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment planning and can be readily applied to different treatment sites and modalities.

Extended-interval Dosing of Gentamicin in Premature Neonates Born at <32 Weeks' Gestation and >7 Days of age.

PubMed

Sundaram, Arun; Alshaikh, Belal; Dersch-Mills, Deonne; Dobry, Jenna; Akierman, Albert R; Yusuf, Kamran

2017-06-01

Extended-interval dosing (EID) regimens of gentamicin have been validated for treating confirmed or suspected early- and late-onset sepsis in preterm infants in the first week of life. Despite the marked changes in volume of distribution and renal clearance in preterm infants after the first few days of life, few studies have validated EID regimens of gentamicin in this population. The objective of the study was to evaluate an EID regimen of gentamicin in infants born at <32 weeks' gestational age and aged >7 days. This observational study of an EID regimen was conducted in 39 infants. Dosing interval was based on the serum drug concentration at 22 hours after the administration of the first dose of 5 mg/kg. Gentamicin peak (5-12 µg/mL) and trough (<2 µg/mL) levels were compared to those in a historical control group of 39 infants who received traditional-interval dosing (TID) of 2.5 mg/kg of gentamicin with dosing intervals of 8, 12, or 24 hours. There were no differences in birthweight, gestational age at birth, postmenstrual age, weight at the start of gentamicin administration, postnatal age, small for gestational age status, antenatal corticosteroid use, or postnatal indomethacin exposure between the 2 groups. In the EID group, dosing intervals were 24 hours in 30 infants, 36 hours in 6 infants, and 48 hours in 3 infants. Compared with the TID group (n = 39), the EID group had a significantly higher peak level (median, 9.0 vs 4.7 µg/mL) and a significantly lower trough level (median, 0.7 vs 1.1 µg/mL) (both, P < 0.001). On regression analysis, the postmenstrual age was correlated significantly with trough levels in the EID group. There was no adverse effect on renal function in either group. On follow-up, 1 infant in the EID group and 2 infants in the TID group had evidence of sensorineural hearing loss. In infants born at <32 weeks' gestation and >7 days of age, an EID gentamicin regimen, with a dosing interval based on a single concentration measurement at 22 hours after the administration of the first dose, achieved therapeutic peak and trough levels and performed significantly better than did a TID regimen in reaching target peak and trough levels. Larger-scale trials are needed for assessing the clinical efficacy (treatment failure/success) of these regimens. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

A New Dual-purpose Quality Control Dosimetry Protocol for Diagnostic Reference-level Determination in Computed Tomography.

PubMed

Sohrabi, Mehdi; Parsi, Masoumeh; Sina, Sedigheh

2018-05-17

A diagnostic reference level is an advisory dose level set by a regulatory authority in a country as an efficient criterion for protection of patients from unwanted medical exposure. In computed tomography, the direct dose measurement and data collection methods are commonly applied for determination of diagnostic reference levels. Recently, a new quality-control-based dose survey method was proposed by the authors to simplify the diagnostic reference-level determination using a retrospective quality control database usually available at a regulatory authority in a country. In line with such a development, a prospective dual-purpose quality control dosimetry protocol is proposed for determination of diagnostic reference levels in a country, which can be simply applied by quality control service providers. This new proposed method was applied to five computed tomography scanners in Shiraz, Iran, and diagnostic reference levels for head, abdomen/pelvis, sinus, chest, and lumbar spine examinations were determined. The results were compared to those obtained by the data collection and quality-control-based dose survey methods, carried out in parallel in this study, and were found to agree well within approximately 6%. This is highly acceptable for quality-control-based methods according to International Atomic Energy Agency tolerance levels (±20%).

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

PubMed

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

2015-03-01

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

Effects of compound Shenhua tablet on renal tubular Na+-K+-ATPase in rats with acute ischemic reperfusion injury.

PubMed

Yang, Yue; Wei, Ri-bao; Zheng, Xiao-yong; Qiu, Qiang; Cui, Shao-yuan; Yin, Zhong; Shi, Suo-zhu; Chen, Xiang-mei

2014-03-01

To observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI). Fifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope. Compared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a superior effect as compared with the astragaloside group and the SHT low-dose group. The SHT effectively alleviated RIRI caused by ischemic reperfusion, promoted the recovery of the polarity of renal tubular epithelial cells, and protected the renal tubules. The therapeutic effects of SHT were superior to those of astragaloside as a single agent.

Use of a channelized Hotelling observer to assess CT image quality and optimize dose reduction for iteratively reconstructed images.

PubMed

Favazza, Christopher P; Ferrero, Andrea; Yu, Lifeng; Leng, Shuai; McMillan, Kyle L; McCollough, Cynthia H

2017-07-01

The use of iterative reconstruction (IR) algorithms in CT generally decreases image noise and enables dose reduction. However, the amount of dose reduction possible using IR without sacrificing diagnostic performance is difficult to assess with conventional image quality metrics. Through this investigation, achievable dose reduction using a commercially available IR algorithm without loss of low contrast spatial resolution was determined with a channelized Hotelling observer (CHO) model and used to optimize a clinical abdomen/pelvis exam protocol. A phantom containing 21 low contrast disks-three different contrast levels and seven different diameters-was imaged at different dose levels. Images were created with filtered backprojection (FBP) and IR. The CHO was tasked with detecting the low contrast disks. CHO performance indicated dose could be reduced by 22% to 25% without compromising low contrast detectability (as compared to full-dose FBP images) whereas 50% or more dose reduction significantly reduced detection performance. Importantly, default settings for the scanner and protocol investigated reduced dose by upward of 75%. Subsequently, CHO-based protocol changes to the default protocol yielded images of higher quality and doses more consistent with values from a larger, dose-optimized scanner fleet. CHO assessment provided objective data to successfully optimize a clinical CT acquisition protocol.

Benzo(a)pyrene-induced cytochrome p4501A expression of four freshwater fishes (Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus).

PubMed

Lee, Jin Wuk; Yoon, Hong-Gil; Lee, Sung Kyu

2015-05-01

Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus are useful indicator species for CYP1A biomarker studies; however, comparative studies have not been performed. To compare susceptibility, dose- and time-dependent CYP1A induction at the mRNA and protein levels in response to benzo(a)pyrene (BaP) exposure was analyzed. At the mRNA level, a statistically significant difference was found among the four species; however, such was not observed at the protein level. C. carpio showed the highest CYP1A induction level and the steepest slope in the dose-response curve. To assess susceptibility, the difference in CYP1A mRNA induction among species must be considered, and C. carpio was the most sensitive species of the four evaluated in terms of CYP1A expression. Copyright © 2015 Elsevier B.V. All rights reserved.

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice.

PubMed

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Diabetes mellitus is the most rampant metabolic pandemic of the 21(st) century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14(th) and 28(th) day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine in combination with subtherapeutic dose of metformin also showed better effect than therapeutic dose of metformin. Piperine, thus shows potential to be used as bioenhancer in combination with metformin.

Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study.

PubMed

Peechakara, Seenia; Bena, James; Clarke, Nigel J; McPhaul, Michael J; Reitz, Richard E; Weil, Robert J; Recinos, Pablo; Kennedy, Laurence; Hamrahian, Amir H

2017-09-01

The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard. The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12). All tests were done in random order. Sensitivity and specificity were calculated for total cortisol and serum free cortisol cut-off levels during cosyntropin stimulation tests. The median (range) age and F/M sex ratios for patients and controls were 54 years (23-62), 2/8, and 33 years (21-51), 6/6, respectively. The best total cortisol cut-off during low dose cosyntropin test, medium dose cosyntropin test, 30 min and 60 min standard dose cosyntropin test were 14.6 μg/dL (100% sensitivity & specificity), 18.7 μg/dL (100% sensitivity, 88% specificity), 16.1 (100% sensitivity & specificity), and 19.5 μg/dL (100% sensitivity & specificity), respectively. There was no difference in the ROC curve for cortisol values between the cosyntropin stimulation tests (p  > 0.41). Using a cortisol cut-off of 18 μg/dL during cosyntropin stimulation tests, only cortisol level at 30 min during standard dose cosyntropin test provided discrimination similar to insulin tolerance test. The best peak free cortisol cut-off levels were 1 μg/dL for insulin tolerance test, 0.9 μg/dL for low dose cosyntropin test, 0.9 μg/dL for medium dose cosyntropin test, and 0.9 μg/dL and 1.3 μg/dL for 30 min and 60 min standard dose cosyntropin test, respectively. All cosyntropin stimulation tests had excellent correlations with insulin tolerance test, when appropriate cut-offs were used. This pilot study does not suggest an advantage in using 25 μg cosyntropin dose during the cosyntropin stimulation test. A serum free cortisol cut-off of 0.9 μg/dL may be used as pass criterion during low dose cosyntropin test, standard dose cosyntropin test cosyntropin test, and 30 min standard dose cosyntropin test.

[Comparison of planning quality and delivery efficiency between volumetric modulated arc therapy and dynamic intensity modulated radiation therapy for nasopharyngeal carcinoma with more than 4 prescribed dose levels].

PubMed

Jia, Pengfei; Xu, Jun; Zhou, Xiaoxi; Chen, Jian; Tang, Lemin

2017-12-01

The aim of this study is to compare the planning quality and delivery efficiency between dynamic intensity modulated radiation therapy (d-IMRT) and dual arc volumetric modulated arc therapy (VMAT) systematically for nasopharyngeal carcinoma (NPC) patients with multi-prescribed dose levels, and to analyze the correlations between target volumes and plan qualities. A total of 20 patients of NPC with 4-5 prescribed dose levels to achieve simultaneous integrated boost (SIB) treated by sliding window d-IMRT in our department from 2014 to 2015 were re-planned with dual arc VMAT. All optimization objectives for each VMAT plan were as the same as the corresponding d-IMRT plan. The dose parameters for targets and organ at risk (OAR), the delivery time and monitor units (MU) in two sets of plans were compared respectively. The treatment accuracy was tested by three dimensional dose validation system. Finally, the correlations between the difference of planning quality and the volume of targets were discussed. The conform indexes (CIs) of planning target volumes (PTVs) in VMAT plans were obviously high than those in d-IMRT plans ( P < 0.05), but no significant correlations between the difference of CIs and the volume of targets were discovered ( P > 0.05). The target coverage and heterogeneity indexes (HIs) of PTV 1 and PGTV nd and PTV 3 in two sets of plans were consistent. The doses of PTV 2 decreased and HIs were worse in VMAT plans. VMAT could provide better spinal cord and brainstem sparing, but increase mean dose of parotids. The average number of MUs and delivery time for d-IMRT were 3.32 and 2.19 times of that for VMAT. The γ-index (3 mm, 3%) analysis for each plans was more than 97% in COMPASS ® measurement for quality assurance (QA). The results show that target dose coverages in d-IMRT and VMAT plans are similar for NPC with multi-prescribed dose levels. VMAT could improve the the CIs of targets, but reduce the dose to the target volume in neck except for PGTV nd . The biggest advantages of VMAT over d-IMRT are delivery efficiency and QA.

A comparison study of size-specific dose estimate calculation methods.

PubMed

Parikh, Roshni A; Wien, Michael A; Novak, Ronald D; Jordan, David W; Klahr, Paul; Soriano, Stephanie; Ciancibello, Leslie; Berlin, Sheila C

2018-01-01

The size-specific dose estimate (SSDE) has emerged as an improved metric for use by medical physicists and radiologists for estimating individual patient dose. Several methods of calculating SSDE have been described, ranging from patient thickness or attenuation-based (automated and manual) measurements to weight-based techniques. To compare the accuracy of thickness vs. weight measurement of body size to allow for the calculation of the size-specific dose estimate (SSDE) in pediatric body CT. We retrospectively identified 109 pediatric body CT examinations for SSDE calculation. We examined two automated methods measuring a series of level-specific diameters of the patient's body: method A used the effective diameter and method B used the water-equivalent diameter. Two manual methods measured patient diameter at two predetermined levels: the superior endplate of L2, where body width is typically most thin, and the superior femoral head or iliac crest (for scans that did not include the pelvis), where body width is typically most thick; method C averaged lateral measurements at these two levels from the CT projection scan, and method D averaged lateral and anteroposterior measurements at the same two levels from the axial CT images. Finally, we used body weight to characterize patient size, method E, and compared this with the various other measurement methods. Methods were compared across the entire population as well as by subgroup based on body width. Concordance correlation (ρ c ) between each of the SSDE calculation methods (methods A-E) was greater than 0.92 across the entire population, although the range was wider when analyzed by subgroup (0.42-0.99). When we compared each SSDE measurement method with CTDI vol, there was poor correlation, ρ c <0.77, with percentage differences between 20.8% and 51.0%. Automated computer algorithms are accurate and efficient in the calculation of SSDE. Manual methods based on patient thickness provide acceptable dose estimates for pediatric patients <30 cm in body width. Body weight provides a quick and practical method to identify conversion factors that can be used to estimate SSDE with reasonable accuracy in pediatric patients with body width ≥20 cm.

Immunological mechanism of low-dose priming radiation resistance in walker-256 tumor model mice

PubMed Central

Feng, Li; Qin, Ling; Guo, Dan; Deng, Daping; Lu, Feng; Li, Hailiang; Bao, Narisu; Yang, Xiting; Ding, Hongyu; Li, Jianguo

2017-01-01

The aim of the present study was to investigate whether low-dose priming radiation induces antitumor immunity that can be augmented by the modulation of natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker-256 cells were injected into the right flank of male BALB/c mice. At 7 days after inoculation, mice were divided into three groups, including group 1,2,3. In group 1 the mice were without radiation, in group 2 the mice were received 2 Gy radiation only, and in group 3 the mice were radiated with a priming dose of 75 mGy followed by 2 Gy radiation after 24 h. On day 21 following the radiation, the tumors were removed and the tumor index (tumor weight as a percentage of body weight) was calculated. At 1, 7, 14 and 21 days following the 2 Gy radiation, mouse splenocytes were isolated to analyze the NK activity and measure the production of the cytokines interleukin-1β, interferon-γ and tumor necrosis factor-α by ELISA. Apoptosis was also measured by flow cytometry. The results demonstrated that priming radiation significantly delayed the tumor growth and prolonged the median survival time to 38 days compared with the 31-day survival in the 2 Gy radiation group. The percentage of apoptotic cells was significantly higher in the mice that received 75 mGy + 2 Gy radiation compared with that in the mice that received 2 Gy alone; by contrast, mice that were not irradiated exhibited a relatively low level of apoptosis. The primed mice had a higher level of NK activity as compared with the mice exposed to 2 Gy radiation only or mice that were not irradiated. Furthermore, cytokine expression remained at a higher level in mice receiving priming dose of radiation compared that in the mice receiving only 2 Gy radiation. In conclusion, the results indicated that low-dose priming X-ray radiation may enhance the NK activity and the levels of cytokines, and that the immune response serves an important role in anticancer therapy, including radiotherapy. PMID:29042994

Mechanism of nonylphenol-induced neurotoxicity in F1 rats during sexual maturity.

PubMed

Jie, Yu; Xuefeng, Yang; Mengxue, Yang; Xuesong, Yang; Jing, Yang; Yin, Tang; Jie, Xu

2016-06-01

The purpose of this study was to examine whether gestational and lactational exposure to environmental endocrine disrupting chemical, nonylphenol (NP), in pregnant dams would lead to the alterations in hormone levels in the body, apoptosis and glial fibrillary acidic protein (GFAP) in hippocampus during weaning and sexual maturity periods in pups of rats. Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 6 to postnatal day (PND) 21. At PND 21, serum testosterone (TT) level significantly decreased in the 50, 100 mg/kg NP-treated groups compared with the control (p < 0.01). Serum estradiol (E2) level was increased with the increase in the NP concentration; a dose-effect relationship was revealed (r = 0.462, p < 0.01). At both PND 21 and PND 60, pups exposed to 100 mg/kg/day NP had an obviously higher apoptotic rate than control did. We observed a significant positive correlation between the dose of NP and the apoptotic rate (r = 0.836, p < 0.05). The number of GFAP-positive cells in rat hippocampus and integral optical density (IOD) of 100 mg/kg/day NP-treated group were much higher than the control group. GFAP mRNA expressions increased at high dose (100 mg/kg/day) (p < 0.05), and positive correlations between the GFAP mRNA expressions and NP level was observed (r = 0.586, 0.737, p < 0.05). Both the number of growth-associated protein (GAP)-43 positive cells and IOD were much lower at high dose (100 mg/kg/day) than the control at both PND 21 and PND 60 (p < 0.05). The number of GAP-43 positive cells was negatively correlated with the NP exposure dose (r = - 0.562, - 0.649, p < 0.05) at these two time points. GAP-43 mRNA expressions in the hippocampus of pups decreased dramatically at high dose (100 mg/kg/day) at both PND 21 and PND 60 compared with the control (p < 0.05). High exposure to NP might inhibit neuronal development and differentiation as indicated by the reduction of the neurotrophic factor GAP-43.

Validation of self-reported cannabis dose and potency: an ecological study.

PubMed

van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

2013-10-01

To assess the reliability and validity of self-reported cannabis dose and potency measures. Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Ecological study with assessments at participants' homes or in a coffee shop. Young adult frequent cannabis users (n = 106) from the Dutch Cannabis Dependence (CanDep) study. The objectively measured amount of cannabis per joint (dose in grams) was compared with self-reported estimates using a prompt card and average number of joints made from 1 g of cannabis. In addition, objectively assessed THC concentration in the participant's cannabis was compared with self-reported level of intoxication, subjective estimate of cannabis potency and price per gram of cannabis. Objective estimates of doses per joint (0.07-0.88 g/joint) and cannabis potency (1.1-24.7%) varied widely. Self-reported measures of dose were imprecise, but at group level, average dose per joint was estimated accurately with the number of joints made from 1 g [limit of agreement (LOA) = -0.02 g, 95% confidence interval (CI) = -0.29; 0.26], whereas the prompt card resulted in serious underestimation (LOA = 0.14 g, 95% CI = -0.10; 0.37). THC concentration in cannabis was associated with subjective potency ['average' 3.77% (P = 0.002) and '(very) strong' 5.13% more THC (P < 0.001) than '(very) mild' cannabis] and with cannabis price (about 1% increase in THC concentration per euro spent on 1 g of cannabis, P < 0.001), but not with level of intoxication. Self-report measures relating to cannabis use appear at best to be associated weakly with objective measures. Of the self-report measures, number of joints per gram, cannabis price and subjective potency have at least some validity. © 2013 Society for the Study of Addiction.

Upgrade to iterative image reconstruction (IR) in MDCT imaging: a clinical study for detailed parameter optimization beyond vendor recommendations using the adaptive statistical iterative reconstruction environment (ASIR) Part2: The chest.

PubMed

Mueck, F G; Michael, L; Deak, Z; Scherr, M K; Maxien, D; Geyer, L L; Reiser, M; Wirth, S

2013-07-01

To compare the image quality in dose-reduced 64-row CT of the chest at different levels of adaptive statistical iterative reconstruction (ASIR) to full-dose baseline examinations reconstructed solely with filtered back projection (FBP) in a realistic upgrade scenario. A waiver of consent was granted by the institutional review board (IRB). The noise index (NI) relates to the standard deviation of Hounsfield units in a water phantom. Baseline exams of the chest (NI = 29; LightSpeed VCT XT, GE Healthcare) were intra-individually compared to follow-up studies on a CT with ASIR after system upgrade (NI = 45; Discovery HD750, GE Healthcare), n = 46. Images were calculated in slice and volume mode with ASIR levels of 0 - 100 % in the standard and lung kernel. Three radiologists independently compared the image quality to the corresponding full-dose baseline examinations (-2: diagnostically inferior, -1: inferior, 0: equal, + 1: superior, + 2: diagnostically superior). Statistical analysis used Wilcoxon's test, Mann-Whitney U test and the intraclass correlation coefficient (ICC). The mean CTDIvol decreased by 53 % from the FBP baseline to 8.0 ± 2.3 mGy for ASIR follow-ups; p < 0.001. The ICC was 0.70. Regarding the standard kernel, the image quality in dose-reduced studies was comparable to the baseline at ASIR 70 % in volume mode (-0.07 ± 0.29, p = 0.29). Concerning the lung kernel, every ASIR level outperformed the baseline image quality (p < 0.001), with ASIR 30 % rated best (slice: 0.70 ± 0.6, volume: 0.74 ± 0.61). Vendors' recommendation of 50 % ASIR is fair. In detail, the ASIR 70 % in volume mode for the standard kernel and ASIR 30 % for the lung kernel performed best, allowing for a dose reduction of approximately 50 %. © Georg Thieme Verlag KG Stuttgart · New York.

Differences in fecundity of Eimeria maxima strains exhibiting different levels of pathogenicity in its avian host.

PubMed

Jenkins, Mark C; Dubey, J P; Miska, Katarzyna; Fetterer, Raymond

2017-03-15

Eimeria maxima is one of the most pathogenic species of avian coccidia, yet it is unknown why different E. maxima strains differ in the pathogenic effects they cause in chickens. The purpose of this study was to determine if a more pathogenic E. maxima strain (APU1) was also more fecund than a less pathogenic E. maxima strain (APU2). At identical doses, E. maxima APU1 always produces greater intestinal lesions and lower weight gain compared to E. maxima APU2. Using a dose response study, median and mean intestinal lesion scores in E. maxima APU1-infected chickens were greater by a score of 1-1.5 compared to chickens infected with E. maxima APU2. Likewise, weight gain depression in E. maxima APU1-infected chickens was 20-25% greater (equivalent to 110-130g body weight) than in E. maxima APU2-infected chickens. In order to understand the underlying cause of these observed clinical effects, 120 broiler chicks (5 oocyst levels, 6 replicates/level) were inoculated with various doses of E. maxima APU1 or APU2 oocysts. The dynamics of oocyst shedding was investigated by collecting fecal material every 12h from 114 to 210h post-inoculation (p.i.) and every 24h thereafter from 210 to 306h, and then processed for measuring E. maxima oocyst output. Oocysts were first observed at 138h p.i., and time of peak oocyst production was nearly identical for both E. maxima APU1 and APU2 around 150-162h. Total oocyst production was 1.1-2.6 fold higher at all dose levels for E. maxima APU1 compared to E. maxima APU2, being significantly higher (P<0.05) at the log 1.5 dose level. Other groups of chickens were infected with higher doses of E. maxima APU1 or APU2 oocysts, and intestinal lesions were assessed by histology at 72, 96, 120, and 144h p.i. Although schizonts, gamonts, and oocysts were observed at expected time-points, no obvious differences were noted in lesions induced by the two E. maxima strains. This study showed that the greater fecundity of E. maxima APU1 compared to E. maxima APU2 explains in part the observed differences in pathogenicity of the two E. maxima strains, but that other factors may contribute to differences in observed clinical effects. Published by Elsevier B.V.

Conformity of commercial oral single solid unit dose packages in hospital pharmacy practice.

PubMed

Thibault, Maxime; Prot-Labarthe, Sonia; Bussières, Jean-François; Lebel, Denis

2008-06-01

There are limited published data on the labelling of single unit dose packages in hospitals. The study was conducted in three large hospitals (two adult and one paediatric) in the metropolitan Montreal area, Quebec, Canada. The objective is to evaluate the labelling of commercial oral single solid unit dose packages available in Canadian urban hospital pharmacy practice. The study endpoint was the labelling conformity of each unit dose package for each criterion and overall for each manufacturer. Complete labelling of unit dose packages should include the following information: (1) brand name, (2) international non-proprietary name or generic name, (3) dosage, (4) pharmaceutical form, (5) manufacturer's name, (6) expiry date, (7) batch number and (8) drug identification number. We also evaluated the ease with which a single unit dose package is detached from a multiple unit dose package for quick, easy and safe use by pharmacy staff. Conformity levels were compared between brand-name and generic packages. A total of 124 different unit dose packages were evaluated. The level of conformity of each criterion varied between 19 and 50%. Only 43% of unit dose packages provided an easy-to-detach system for single doses. Among the 14 manufacturers with three or more unit dose packages evaluated, eight (57%) had a conformity level less than 50%. This study describes the conformity of commercial oral single solid unit dose packages in hospital pharmacy practice in Quebec. A large proportion of unit dose packages do not conform to a set of nine criteria set out in the guidelines of the American Society of Health-System Pharmacists and the Canadian Society of Hospital Pharmacists.

Locomotor activity and tissue levels following acute ...

EPA Pesticide Factsheets

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administ

Locomotor activating effects of cocaine and scopolamine combinations in rats: isobolographic analysis

PubMed Central

Thomsen, Morgane

2014-01-01

Muscarinic cholinergic receptors are receiving renewed interest as viable targets for treating various psychiatric disorders. Dopaminergic and muscarinic systems interact in complex ways. The goal of this study was to quantify the interaction of a systemically administered psychomotor stimulant and muscarinic antagonist at the behavioral level. Using isobolographic analysis of locomotor activity data, we assessed the effects of three cocaine/scopolamine mixtures in terms of deviation from simple dose addition (additivity), at four effect levels. All three mixtures produced some more-than-additive (synergistic) effects, as lower doses were needed to produce given effects relative to the calculated effect of additive doses. A mixture with comparable contributions from cocaine and scopolamine produced significantly more-than-additive effects at all but the lowest effect level examined. A mostly-cocaine mixture was more-than-additive at low effect levels only, while a mostly-scopolamine mixture produced effects more consistent with additivity, with only the highest effect level barely reaching significant synergism. Our study confirms and quantifies previous findings that suggested synergistic effects of stimulants and muscarinic antagonists. The synergism implies that cocaine and scopolamine stimulate locomotor activity through non-identical pathways, and was most pronounced for a mixture containing cocaine and scopolamine in comparable proportions. PMID:24769455

Effects of Unripe Musa Paradisiaca on the Histochemistry of the Testis and Testosterone Levels in Adult Albino Rats.

PubMed

Alabi, A S; Omotosho, G O; Tagoe, C N B; Akinola, O B; Enaibe, B U

2017-06-30

This study was aimed at determining the effects of the unripe fruit of Musa paradisiaca on the testis andtestosterone levels in male Wistar rats. The animals were grouped into three, comprising a control, and 2 treatment groupsadministered with different doses (500 mg/kg and 1000 mg/kg) daily of the fruit flour over 28 days. Histochemical evaluationof the testes was done using Haematoxylin and Eosin, Periodic acid Schiff's (PAS) and Feulgen staining techniques, whilethe serum and homogenised testicular tissue were evaluated for testosterone levels using Accu-Bind ELISA Kit. The testisof the treated groups showed more rapidly dividing cells and more population of sperm cells compared to the control group,and also showed more positivity for Feulgen staining and PAS reaction. Both serum and testicular testosterone levels werehowever reduced. Serum testosterone was significantly lowered in the animals given the low dose (0.67 ± 0.03 ng/ml),compared to those given high dose (0.85 ± 0.02 ng/ml) and the control animals (1.88 ± 0.15 ng/ml) (p < 0.05). Changes intesticular testosterone were not statistically significant. The study suggests that M. paradisiaca fruit has reproductiveenhancing potential when consumed moderately, but this benefit may not be related to testosterone levels.

Effects of traditional chinese medicine on endotoxin and its receptors in rats with non-alcoholic steatohepatitis.

PubMed

Gao, Yuan; Song, Lin-Xuan; Jiang, Miao-Na; Ge, Guang-Yan; Jia, Yu-Jie

2008-04-01

The aim of this research is to study the effects of traditional Chinese medicine on endotoxin and its receptors in rats with nonalcoholic steatohepatitis (NASH). Fifty-six SD rats were divided into seven groups. All the animals were fed high fatty diet for 12 weeks. Rats with non-alcoholic steatohepatitis (NASH) were treated with traditional Chinese medicine according to low-dose, middle-dose, high-dose and Lipitor from fifth week. All rats were killed at the end of 12th week. The liver pathology changes were observed under light microscope. The levels of serum lipoid, alanine aminotransferase (ALT), endotoxin (ET), tumor necrosis factor-alpha (TNF-alpha) and interleukine-1beta (IL-1beta) were determined. The expressions of CD14 and nuclear transcriptional factor kappaB (NF-kappaB) were observed by immunohistochemistry. The expressions of lipopolysaccharide binding protein (LBP), toll-like receptor-4 (TLR-4), myeloid differentiation-2 (MD-2) and induced nitric oxide synthase (iNOS) mRNA were detected by the reverse transcription polymerase chain reaction (RT-PCR). The levels of serum endotoxin in the middle dose group (0.0225 +/- 0.0112 EU/l) were lower than those in high fatty diet model group (0.2249 +/- 0.0982 EU/l) at 12th week, the difference was significant (P < 0.01). In the middle dose group, mean values of serum TNF-alpha and IL-1beta levels decreased dramatically (1.604 +/- 0.302 ng/ml and 0.052 +/- 0.024 ng/ml) compared with those in the high fatty diet model group (4.029 +/- 1.180 ng/ml and 14.944 +/- 0.491 ng/ml; P < 0.01 and P < 0.01). The expressions of CD14 and NF-kappaB in the middle dose group decreased compared with those in the high fatty diet model group. The expressions of LBP mRNA (0.284 +/- 0.105) and TLR-4 mRNA (0.290 +/- 0.123) in the middle dose group down regulated compared with those in the high fatty diet model group (1.060 +/- 0.158 and 1.261 +/- 0.368; P < 0.01 and P < 0.01). In the middle dose group MD-2 and iNOS gene expressions were 0.132 +/- 0.058 and 0.164 +/- 0.061, respectively, which were significantly lower compared with the high fatty diet model group (0.795 +/- 0.294 and 1.029 +/- 0.388; P < 0.01 and P < 0.01). The mechanism of non-alcoholic steatohepatitis (NASH) maybe related to increasing the levels of serum endotoxin, upregulating endotoxin receptors of hepatic tissue and enhancing liver inflammatory injury. Traditional Chinese medicine is a good treatment for non-alcoholic steatohepatitis (NASH). It can produce a marked effect via relieving LPS-induced liver injury.

In vitro dermal disposition of abamectin (avermectin B(1)) in livestock.

PubMed

Baynes, Ronald E

2004-06-01

Many avermectins are approved for topical application in domestic animals. However, extralabel use may result in significant dermal absorption and consequently the potential for adverse effects or violative residues. The primary aim of this study was to assess dermal disposition of abamectin in vitro in bovine, caprine, ovine, and porcine skin dosed in 100% isopropanol, commercial alcohol-based (Ivomec), or oil-based (Eprinex) formulations. Skin sections were perfused in a flow-through diffusion cell system for 8 h, and the disposition of radiolabel abamectin was determined from perfusate and skin samples. Abamectin absorption ranged from 0.09% to 0.20% dose and there were no significant differences between formulations in each species. Isopropanol significantly increased skin deposition in all species when compared to the oil formulation. Absorption was significantly greater in bovine skin than in porcine skin for the isopropanol-containing formulations, but there were no significant species differences for the oil formulation. While significant levels (11.69-50.23% dose) remained on the skin surface, the highest levels deposited in viable skin were observed in caprine skin (28.09% dose) and the lowest levels were in porcine skin (1.50% dose) which could lead to systemic absorption. In summary, these 8-h experiments demonstrated that the alcohol-based formulations compared to oil-based formulations enhanced abamectin absorption and skin deposition in several animal species, and this effect is more likely to be observed in ruminant species than in porcine species.

Evaluation of a new very low dose imaging protocol: feasibility and impact on X-ray dose levels in electrophysiology procedures.

PubMed

Bourier, Felix; Reents, Tilko; Ammar-Busch, Sonia; Buiatti, Alessandra; Kottmaier, Marc; Semmler, Verena; Telishevska, Marta; Brkic, Amir; Grebmer, Christian; Lennerz, Carsten; Kolb, Christof; Hessling, Gabriele; Deisenhofer, Isabel

2016-09-01

This study presents and evaluates the impact of a new lowest-dose fluoroscopy protocol (Siemens AG), especially designed for electrophysiology (EP) procedures, on X-ray dose levels. From October 2014 to March 2015, 140 patients underwent an EP study on an Artis zee angiography system. The standard low-dose protocol was operated at 23 nGy (fluoroscopy) and at 120 nGy (cine-loop), the new lowest-dose protocol was operated at 8 nGy (fluoroscopy) and at 36 nGy (cine-loop). Procedural data, X-ray times, and doses were analysed in 100 complex left atrial and in 40 standard EP procedures. The resulting dose-area products were 877.9 ± 624.7 µGym² (n = 50 complex procedures, standard low dose), 199 ± 159.6 µGym² (n = 50 complex procedures, lowest dose), 387.7 ± 36.0 µGym² (n = 20 standard procedures, standard low dose), and 90.7 ± 62.3 µGym² (n = 20 standard procedures, lowest dose), P < 0.01. In the low-dose and lowest-dose groups, procedure times were 132.6 ± 35.7 vs. 126.7 ± 34.7 min (P = 0.40, complex procedures) and 72.3 ± 20.9 vs. 85.2 ± 44.1 min (P = 0.24, standard procedures), radiofrequency (RF) times were 53.8 ± 26.1 vs. 50.4 ± 29.4 min (P = 0.54, complex procedures) and 10.1 ± 9.9 vs. 12.2 ± 14.7 min (P = 0.60, standard procedures). One complication occurred in the standard low-dose and lowest-dose groups (P = 1.0). The new lowest-dose imaging protocol reduces X-ray dose levels by 77% compared with the currently available standard low-dose protocol. From an operator standpoint, lowest X-ray dose levels create a different, reduced image quality. The new image quality did not significantly affect procedure or RF times and did not result in higher complication rates. Regarding radiological protection, operating at lowest-dose settings should become standard in EP procedures. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Implications of the 2013 ACC/AHA cholesterol guidelines on contemporary clinical practice for patients with atherosclerotic coronary and peripheral arterial disease.

PubMed

Gunasekaran, Prasad; Jeevanantham, Vinodh; Sharma, Suresh; Thapa, Rashmi; Gupta, Kamal

Cholesterol management guidelines from the American College of Cardiology/American Heart Association (ACC/AHA-2013) recommend fixed statin dosing (dose depends on age ≤ or >75years) compared to the earlier adult treatment panel III (ATPIII) guidelines which recommended specific low-density lipoprotein-cholesterol (LDL-C) targets. Clinical implications of this recommendation are not known. We retrospectively compared cholesterol levels and statin utilization across cohorts with coronary artery disease (CAD) (n=9563), peripheral arterial disease (PAD) (n=596) and CAD+PAD (n=975) by applying both guidelines. The percentage of patients who achieved guideline-specific targets using 2013 ACC/AHA (use of moderate/high intensity statins) or ATPIII guidelines (LDL-C<100mg/dl) was compared between all groups. Using both guidelines, the PAD only group demonstrated lower utilization and lower statin doses than the CAD or CAD+PAD groups. When applying the ACC/AHA guidelines, more patients in the CAD only group (age ≤75 years) were considered at goal as compared to the ATPIII guidelines (92.2% vs. 75%), primarily driven by the group placed on moderate/high intensity statins but had an LDL-C level >100mg/dl. Application of the ACC/AHA guidelines results in a higher percentage of patients considered to be 'at goal' when compared to the ATP III guidelines without changes in clinical practice. This is due to patients ≤75 years old on adequate statin doses but still have LDL-C levels >100mg/dl, thereby raising concerns that physicians may not pursue alternate LDL reduction strategies since they are now considered at goal despite LDL-C >100mg/dl. Lipid management of PAD patients remains sub-optimal as compared to CAD and CAD+PAD. Copyright © 2017. Published by Elsevier B.V.

Acute effects of ethanol and acetate on glucose kinetics in normal subjects

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

Yki-Jaervinen, H.; Koivisto, V.A.; Ylikahri, R.

1988-02-01

The authors compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low or moderate ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited basal glucose production. The decrease in R{sub a} was matched by a comparable decrease in glucose utilization (R{sub d}), resulting in maintenance of normoglycemia. During hyperinsulinemia glucose disposal was lower in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level wasmore » comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, (1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on R{sub a} is counterbalanced by equal inhibition of R{sub d}; (2) basal R{sub a} and R{sub d} are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and (3) acetate is not the mediator of ethanol-induced insulin resistance.« less

Effects of Phonation Time and Magnitude Dose on Vocal Fold Epithelial Genes, Barrier Integrity, and Function

PubMed Central

Kojima, Tsuyoshi; Valenzuela, Carla V.; Novaleski, Carolyn K.; Van Deusen, Mark; Mitchell, Joshua R.; Garrett, C. Gaelyn; Sivasankar, M. Preeti; Rousseau, Bernard

2014-01-01

Objective To investigate the effects of increasing time and magnitude doses of vibration exposure on transcription of the vocal fold's junctional proteins, structural alterations, and functional tissue outcomes. Study Design Animal study. Methods 100 New Zealand White breeder rabbits were studied. Dependent variables were measured in response to increasing time doses (30, 60, or 120 minutes) and magnitude doses (control, modal intensity, and raised intensity) of vibration exposure. Messenger RNA expression of occludin, zonula occluden-1 (ZO-1), E-cadherin, β-catenin, interleukin 1β (IL-1β), cyclooxygenase-2 (COX-2), transforming growth factor β-1 (TGFβ1), and fibronectin were measured. Tissue structural alterations were assessed using transmission electron microscopy (TEM). Transepithelial resistance was used to measure functional tissue outcomes. Results Occludin gene expression was downregulated in vocal folds exposed to 120 minute time doses of raised intensity phonation, relative to control, and modal intensity phonation. ZO-1 gene expression was upregulated following a 120 minute time dose of modal intensity phonation, compared to control, and downregulated after a 120 minute time dose of raised intensity phonation, compared to modal intensity phonation. E-cadherin gene expression was downregulated after a120 minute time dose of raised intensity phonation, compared to control and modal intensity phonation. TEM revealed extensive desquamation of the stratified squamous epithelial cells with increasing time and magnitude doses of vibration exposure. A general observation of lower transepithelial resistance measures was made in tissues exposed to raised intensity phonation, compared to all other groups. Conclusions This study provides evidence of vocal fold tissue responses to varying time and magnitude doses of vibration exposure. Level of Evidence N/A PMID:25073715

Pharmacokinetic interactions of efavirenz and voriconazole in healthy volunteers

PubMed Central

Damle, Bharat; LaBadie, Robert; Crownover, Penelope; Glue, Paul

2008-01-01

AIMS Co-administration of standard-dose voriconazole and efavirenz results in a substantial decrease in voriconazole levels, while concurrently increasing efavirenz levels. Hence, concomitant use of standard doses of these drugs was initially contraindicated. This study assessed different dose combinations of efavirenz and voriconazole, with the goal of attaining a dose combination that provides systemic exposures similar to standard-dose monotherapy with each drug. METHODS This was an open-label, four-treatment, multiple-dose, fixed-sequence study in 16 healthy males. Steady-state pharmacokinetics were assessed following two test treatments (voriconazole 300 mg q12 h + efavirenz 300 mg q24 h and voriconazole 400 mg q12 h + efavirenz 300 mg q24 h) and compared with standard-dose monotherapy (voriconazole 200 mg q12 h or efavirenz 600 mg q24 h). RESULTS Dose adjustment to voriconazole 300 mg q12 h with efavirenz 300 mg q24 h decreased voriconazole area under the concentration–time curve (AUCτ) and maximum concentration (Cmax), with changes of −55% [90% confidence interval (CI) −62, −45] and −36% (90% CI −49, −21), respectively, when compared with monotherapy. Voriconazole 400 mg q12 h plus efavirenz 300 mg q24 h decreased voriconazole AUCτ (−7%; 90% CI −23, 13) and increased Cmax (23%; 90% CI −1, 53), while increasing efavirenz AUCτ (17%; 90% CI 6, 29) and not changing Cmax when compared with the respective monotherapy regimens. No serious adverse events were observed with voriconazole plus efavirenz. CONCLUSIONS When co-administered, voriconazole dose should be increased to 400 mg q12 h and efavirenz dose decreased to 300 mg q24 h in order to provide systemic exposures similar to standard-dose monotherapy. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Efavirenz 400 mg q24 h reduces exposure to voriconazole 200 mg q12 h when the two drugs are co-administered.Furthermore, voriconazole increases the systemic exposure of efavirenz.Co-administration was therefore initially contraindicated. WHAT THIS STUDY ADDS The doses of efavirenz and voriconazole can be adjusted to provide adequate exposure to both drugs when the two are co-administered, without compromising safety.Appropriate adjustment of doses for both drugs may thus represent an alternative to a mere contraindication. PMID:18294336

A comprehensive toxicity study of zinc oxide nanoparticles versus their bulk in Wistar rats: Toxicity study of zinc oxide nanoparticles.

PubMed

Srivastav, Anurag Kumar; Kumar, Mahadeo; Ansari, Nasreen Ghazi; Jain, Abhishek Kumar; Shankar, Jai; Arjaria, Nidhi; Jagdale, Pankaj; Singh, Dhirendra

2016-12-01

The purpose of this study was to characterize the zinc oxide nanoparticles (ZnO-NPs) and their bulk counterpart in suspensions and to access the impact of their acute oral toxicity at doses of 300 and 2000 mg/kg in healthy female Wistar rats. The hematological, biochemical, and urine parameters were accessed at 24 and 48 h and 14 days posttreatment. The histopathological evaluations of tissues were also performed. The distribution of zinc content in liver, kidney, spleen, plasma, and excretory materials (feces and urine) at 24 and 48 h and 14 days posttreatment were accessed after a single exposure at dose of 2000 mg/kg body weight. The elevated level of alanine amino transferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were observed in ZnO-NPs at a dose of 2000 mg/kg at all time points. There was a decrease in iron levels in all the treated groups at 24 h posttreatment as compared to control groups but returned to their normal level at 14 days posttreatment. The hematological parameters red blood cells, hemoglobin, hematocrit, platelets, and haptoglobin were reduced at 48 h posttreatment at a dose of 2000 mg/kg ZnO-NPs and showed hemolytic condition. All the treated groups were comparable to control group at the end of 14 days posttreatment. The zinc concentration in the kidney, liver, plasma, feces, and urine showed a significant increase in both groups as compared to control. This study explained that ZnO-NPs produced more toxicological effect as compared to their bulk particles as evidenced through alteration in some hemato-biochemical parameters and with few histopathological lesions in liver and kidney tissues. © The Author(s) 2016.

Skin entrance dose with and without lead apron in digital panoramic radiography for selected sensitive body regions.

PubMed

Schulze, Ralf Kurt Willy; Cremers, Catrin; Karle, Heiko; de Las Heras Gala, Hugo

2017-05-01

The aim of this study was to compare the dose at skin level at five significant anatomical regions for panoramic radiography devices with and without lead apron by means of a highly sensitive dosimeter. A female RANDO-phantom was exposed in five different digital panoramic radiography systems, and the dose at skin level was assessed tenfold for each measurement region by means of a highly sensitive solid-state-dosimeter. The five measurement regions selected were the thyroid, both female breasts, the gonads, and a central region in the back of the phantom. For each panoramic machine, the measurements were performed in two modes: with and without a commercial lead apron specifically designed for panoramic radiography. Reproducibility of the measurements was expressed by absolute differences and the coefficient of variation. Values between shielded and unshielded doses were pooled for each region and compared by means of the paired Wilcoxon tests (p ≤ 0.05). Reproducibility as represented by the mean CV was 22 ± 52 % (median 2.3 %) with larger variations for small dose values. Doses at skin level ranged between 0.00 μGy at the gonads and 85.39 μGy at the unshielded thyroid (mean ± SD 15 ± 24 μGy). Except for the gonads, the dose in all the other regions was significantly lower (p < 0.001) when a lead apron was applied. Unshielded doses were between 1.02-fold (thyroid) and 112-fold (at the right breast) higher than those with lead apron shielding (mean: 14-fold ± 18-fold). Although the doses were entirely very low, we observed a significant increase in dose in the radiation-sensitive female breast region when no lead apron was used. Future discussions on shielding requirements for panoramic radiography should focus on these differences in the light of the linear non-threshold (LNT) theory which is generally adopted in medical imaging.

Estradiol promotes the rewarding effects of nicotine in female rats.

PubMed

Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

2016-07-01

It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2. Copyright © 2016 Elsevier B.V. All rights reserved.

Fukushima radionuclides in the NW Pacific, and assessment of doses for Japanese and world population from ingestion of seafood

PubMed Central

Povinec, Pavel P.; Hirose, Katsumi

2015-01-01

Variations of Fukushima-derived radionuclides (90Sr, 134Cs and 137Cs) in seawater and biota offshore Fukushima and in the NW Pacific Ocean were investigated and radiation doses to the Japanese and world population from ingestion of seafood contaminated by Fukushima radionuclides were estimated and compared with those from other sources of anthropogenic and natural radionuclides. The total effective dose commitment from ingestion of radionuclides in fish, shellfish and seaweed caught in coastal waters off Fukushima was estimated to be 0.6 ± 0.4 mSv/y. The individual effective dose commitment from consumption of radioactive-contaminated fish caught in the open Pacific Ocean was estimated to be 0.07 ± 0.05 mSv/y. These doses are comparable or much lower than doses delivered from the consumption of natural 210Po in fish and in shellfish (0.7 mSv/y). The estimated individual doses have been below the levels when any health damage of the Japanese and world population could be expected. PMID:25761420

Fukushima radionuclides in the NW Pacific, and assessment of doses for Japanese and world population from ingestion of seafood.

PubMed

Povinec, Pavel P; Hirose, Katsumi

2015-03-12

Variations of Fukushima-derived radionuclides ((90)Sr, (134)Cs and (137)Cs) in seawater and biota offshore Fukushima and in the NW Pacific Ocean were investigated and radiation doses to the Japanese and world population from ingestion of seafood contaminated by Fukushima radionuclides were estimated and compared with those from other sources of anthropogenic and natural radionuclides. The total effective dose commitment from ingestion of radionuclides in fish, shellfish and seaweed caught in coastal waters off Fukushima was estimated to be 0.6 ± 0.4 mSv/y. The individual effective dose commitment from consumption of radioactive-contaminated fish caught in the open Pacific Ocean was estimated to be 0.07 ± 0.05 mSv/y. These doses are comparable or much lower than doses delivered from the consumption of natural (210)Po in fish and in shellfish (0.7 mSv/y). The estimated individual doses have been below the levels when any health damage of the Japanese and world population could be expected.

[Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

PubMed

Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

2016-01-01

To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Reduction of radiation exposure while maintaining high-quality fluoroscopic images during interventional cardiology using novel x-ray tube technology with extra beam filtering.

PubMed

den Boer, A; de Feyter, P J; Hummel, W A; Keane, D; Roelandt, J R

1994-06-01

Radiographic technology plays an integral role in interventional cardiology. The number of interventions continues to increase, and the associated radiation exposure to patients and personnel is of major concern. This study was undertaken to determine whether a newly developed x-ray tube deploying grid-switched pulsed fluoroscopy and extra beam filtering can achieve a reduction in radiation exposure while maintaining fluoroscopic images of high quality. Three fluoroscopic techniques were compared: continuous fluoroscopy, pulsed fluoroscopy, and a newly developed high-output pulsed fluoroscopy with extra filtering. To ascertain differences in the quality of images and to determine differences in patient entrance and investigator radiation exposure, the radiated volume curve was measured to determine the required high voltage levels (kVpeak) for different object sizes for each fluoroscopic mode. The fluoroscopic data of 124 patient procedures were combined. The data were analyzed for radiographic projections, image intensifier field size, and x-ray tube kilovoltage levels (kVpeak). On the basis of this analysis, a reference procedure was constructed. The reference procedure was tested on a phantom or dummy patient by all three fluoroscopic modes. The phantom was so designed that the kilovoltage requirements for each projection were comparable to those needed for the average patient. Radiation exposure of the operator and patient was measured during each mode. The patient entrance dose was measured in air, and the operator dose was measured by 18 dosimeters on a dummy operator. Pulsed compared with continuous fluoroscopy could be performed with improved image quality at lower kilovoltages. The patient entrance dose was reduced by 21% and the operator dose by 54%. High-output pulsed fluoroscopy with extra beam filtering compared with continuous fluoroscopy improved the image quality, lowered the kilovoltage requirements, and reduced the patient entrance dose by 55% and the operator dose by 69%. High-output pulsed fluoroscopy with a grid-switched tube and extra filtering improves the image quality and significantly reduces both the operator dose and patient dose.

Everolimus with reduced-dose cyclosporine in de novo renal transplant recipients: Philippine experience.

PubMed

Li, J T; Danguilan, R A; Cabanayan-Casasola, C B; Talusan-Tomacruz, Y; Ona, E T

2008-09-01

The objective of this study was to describe the appropriate dose of everolimus to achieve target trough concentrations in standard-risk Filipino kidney transplant recipients. We reviewed all kidney transplant recipients from December 1, 2006 to June 15, 2007 who were given everolimus (1.5 mg/d) in combination with low-dose cyclosporine (5 mg/kg/d) and prednisone but without induction therapy for their immunosuppressive doses, trough levels, as well as hematologic and blood chemistry profiles. Target everolimus trough concentration was 3-8 ng/mL and C2 level was 1000-1400 ng/mL for the first 3 months. Among 148 patients who underwent transplantation during the study period, 26 comprised the study population but only 15 patients completed the 3-month follow-up and are the subject of this report. Their mean age was 33 years, average PRA 2%, and mean HLA mismatches 3. All were from living donors. At 7 days posttransplantation, all patients achieved or exceeded the target everolimus trough and cyclosporine C2 level. At 1 and 3 months posttransplantation the mean everolimus dose was 1.17 and 0.78 mg/d, respectively, whereas the cyclosporine dose was 195 and 148 mg/d, respectively. Three patients showed elevated alanine aminotransferase (ALT) and all patients had hypercholesterolemia after 1 month, which improved with everolimus dose reduction (half required statins). One patient experienced a Banff Grade IA acute rejection episode at 2 months posttransplantation with a serum creatinine value of 2 mg/dL after steroid pulsing. Most standard-risk Filipino kidney transplant recipients required a maintenance everolimus dose of 1 mg/d at 1 month. The cyclosporine dose requirement was also lower. A larger sample size is needed to provide a level of significance compared with other populations.

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

PubMed

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

2002-02-01

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

Comparative plasma salicylate and urine salicylurate levels following administration of aspirin, magnesium salicylate, and choline magnesium trisalicylate.

PubMed

Mason, W D

1980-11-01

Eighteen healthy volunteers were administered single doses of commercially available solid dosage forms of aspirin, magnesium salicylate (I), and choline magnesium trisalicylate (II), equivalent to approximately 500 mg of salicylic acid, in a randomized, complete crossover design. Plasma salicylate and urine salicylurate levels were measured by high-pressure liquid chromatography at frequent intervals following dosing; the resultant profiles, areas under the curve (AUC), and percentages of dose excreted as salicylurate were statistically analyzed by an analysis of variance. The plasma salicylate levels following the two dosage forms containing I and II were virtually identical when corrected for small differences in the dose. The plasma salicylic acid level following aspirin was approximately 10% lower during the 1.5--3.0-hr interval due to a portion of unhydrolyzed aspirin, but the dose-corrected AUC for the products tested did not differ significantly (p < 0.05). During the 24 hr following dosing, 66.5 +/- 12.1 68.4 +/- 7.1, and 60.9 +/- 14.1% of the salicylic acid were excreted as urine salicylurate for aspirin, I, and II, respectively, with no significant difference (p < 0.05). Based on this study, there are no significant differences in the rate and extent of absorption of salicylate following the three dosage forms tested, and the elimination kinetics of salicylic acid are not altered by these dosage forms.

TH-AB-207A-12: CT Lung Cancer Screening and the Effects of Further Dose Reduction On CAD Performance

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

Young, S; Lo, P; Hoffman, J

Purpose: CT lung screening is already performed at low doses. In this study, we investigated the effects of further dose reduction on a lung-nodule CAD detection algorithm. Methods: The original raw CT data and images from 348 patients were obtained from our local database of National Lung Screening Trial (NLST) cases. 61 patients (17.5%) had at least one nodule reported on the NLST reader forms. All scans were acquired with fixed mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare). All images were reconstructed with 1-mm slice thickness, B50 kernel. Based onmore » a previously-published technique, we added noise to the raw data to simulate reduced-dose versions of each case at 50% and 25% of the original NLST dose (i.e. approximately 1.0 and 0.5 mGy CTDIvol). For each case at each dose level, a CAD detection algorithm was run and nodules greater than 4 mm in diameter were reported. These CAD results were compared to “truth”, defined as the approximate nodule centroids from the NLST forms. Sensitivities and false-positive rates (FPR) were calculated for each dose level, with a sub-analysis by nodule LungRADS category. Results: For larger category 4 nodules, median sensitivities were 100% at all three dose levels, and mean sensitivity decreased with dose. For the more challenging category 2 and 3 nodules, the dose dependence was less obvious. Overall, mean subject-level sensitivity varied from 38.5% at 100% dose to 40.4% at 50% dose, a difference of only 1.9%. However, median FPR quadrupled from 1 per case at 100% dose to 4 per case at 25% dose. Conclusions: Dose reduction affected nodule detectability differently depending on the LungRADS category, and FPR was very sensitive at sub-screening levels. Care should be taken to adapt CAD for the very challenging noise characteristics of screening. Funding support: NIH U01 CA181156; Disclosures (McNitt-Gray): Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

An analysis of collegiate band directors' exposure to sound pressure levels

NASA Astrophysics Data System (ADS)

Roebuck, Nikole Moore

Noise-induced hearing loss (NIHL) is a significant but unfortunate common occupational hazard. The purpose of the current study was to measure the magnitude of sound pressure levels generated within a collegiate band room and determine if those sound pressure levels are of a magnitude that exceeds the policy standards and recommendations of the Occupational Safety and Health Administration (OSHA), and the National Institute of Occupational Safety and Health (NIOSH). In addition, reverberation times were measured and analyzed in order to determine the appropriateness of acoustical conditions for the band rehearsal environment. Sound pressure measurements were taken from the rehearsal of seven collegiate marching bands. Single sample t test were conducted to compare the sound pressure levels of all bands to the noise exposure standards of OSHA and NIOSH. Multiple regression analysis were conducted and analyzed in order to determine the effect of the band room's conditions on the sound pressure levels and reverberation times. Time weighted averages (TWA), noise percentage doses, and peak levels were also collected. The mean Leq for all band directors was 90.5 dBA. The total accumulated noise percentage dose for all band directors was 77.6% of the maximum allowable daily noise dose under the OSHA standard. The total calculated TWA for all band directors was 88.2% of the maximum allowable daily noise dose under the OSHA standard. The total accumulated noise percentage dose for all band directors was 152.1% of the maximum allowable daily noise dose under the NIOSH standards, and the total calculated TWA for all band directors was 93dBA of the maximum allowable daily noise dose under the NIOSH standard. Multiple regression analysis revealed that the room volume, the level of acoustical treatment and the mean room reverberation time predicted 80% of the variance in sound pressure levels in this study.

Type 2 Diabetic Rats on Diet Supplemented With Chromium Malate Show Improved Glycometabolism, Glycometabolism-Related Enzyme Levels and Lipid Metabolism

PubMed Central

Feng, Weiwei; Zhao, Ting; Mao, Guanghua; Wang, Wei; Feng, Yun; Li, Fang; Zheng, Daheng; Wu, Huiyu; Jin, Dun; Yang, Liuqing; Wu, Xiangyang

2015-01-01

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model group, chromium picolinate group and chromium trichloride group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, Glut4, phosphor-AMPKβ1 and Akt levels in the high dose group were significantly higher than those of the model, chromium picolinate and chromium trichloride groups. Chromium malate in a high dose group can significantly increase high density lipoprotein cholesterol level while decreasing the total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared with chromium picolinate and chromium trichloride. The serum chromium content in chromium malate and chromium picolinate group is significantly higher than that of the chromium trichloride group. The results indicated that the curative effects of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism changes are better than those of chromium picolinate and chromium trichloride. Chromium malate contributes to glucose uptake and transport in order to improved glycometabolism and glycometabolism-related enzymes. PMID:25942313

Type 2 diabetic rats on diet supplemented with chromium malate show improved glycometabolism, glycometabolism-related enzyme levels and lipid metabolism.

PubMed

Feng, Weiwei; Zhao, Ting; Mao, Guanghua; Wang, Wei; Feng, Yun; Li, Fang; Zheng, Daheng; Wu, Huiyu; Jin, Dun; Yang, Liuqing; Wu, Xiangyang

2015-01-01

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model group, chromium picolinate group and chromium trichloride group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, Glut4, phosphor-AMPKβ1 and Akt levels in the high dose group were significantly higher than those of the model, chromium picolinate and chromium trichloride groups. Chromium malate in a high dose group can significantly increase high density lipoprotein cholesterol level while decreasing the total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared with chromium picolinate and chromium trichloride. The serum chromium content in chromium malate and chromium picolinate group is significantly higher than that of the chromium trichloride group. The results indicated that the curative effects of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism changes are better than those of chromium picolinate and chromium trichloride. Chromium malate contributes to glucose uptake and transport in order to improved glycometabolism and glycometabolism-related enzymes.

Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

NASA Astrophysics Data System (ADS)

Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

2014-03-01

We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

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

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

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

2006-10-01

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

Effect of rosuvastatin dose-loading on serum sLox-1, hs-CRP, and postoperative prognosis in diabetic patients with acute coronary syndromes undergoing selected percutaneous coronary intervention (PCI).

PubMed

Jiao, Yungen; Hu, Feng; Zhang, Zhengang; Gong, Kaizheng; Sun, Xiaoning; Li, Aihua; Liu, Naifeng

2015-01-01

To investigate the effect of rosuvastatin dose-loading on serum levels of lectin-like oxidized low-density lipoprotein receptor-1 (Lox-1) and high-sensitivity c-reactive protein (hs-CRP) and postoperative prognosis in patients with diabetes and non-ST segment elevation acute coronary syndromes (NSTEACS) undergoing selected percutaneous coronary intervention (PCI). A total of 72 patients with diabetes and NSTEACS were randomized to either the group treated with 20 mg rosuvastatin 12 hours prior to PCI with a second dose administered just before PCI (n = 33), or a control group treated with standard method according guideline (n = 39). Serum levels of sLox-1, hs-CRP, CK-MB, and cTnI were measured prior to PCI, and at 24 hours and 30 days after PCI. The 30-day incidence of major adverse cardiac events (MACE) was recorded in both groups. Compared to pre-PCI, serum levels of sLox-1 and hs-CRP of the two groups were increased at 24 hours after PCI (P < 0.05); the levels of CK-MB and cTnI were also improved (P < 0.01); however, the ascended values of sLox-1, hs-CRP, CK-MB, and cTnI were significantly lower in the loading-dose rosuvastatin-treated group than in the control-treated group. Serum levels of sLox-1 and hs-CRP were higher in the loading-dose rosuvastatin-treated group than in the control-treated group at 30 days after PCI (P < 0.05); compared to pre-PCI, the levels of TC and LDL-C were not changed at 24 hours after PCI (P > 0.05) until 30 days after PCI (P < 0.05), but there were no difference between the two groups. The levels of ALT and Scr had no significant difference between the two groups before and after PCI; the 30-day incidence of MACE occurred in 6.06% of patients in the loading-dose rosuvastatin-treated group and in 23.08% of patients in the control-treated group (P < 0.05). The therapy of dose-loading rosuvastatin for patients with diabetes and non-ST segment elevation acute coronary syndromes undergoing selected percutaneous coronary intervention can attenuate the increase of serum levels of sLox-1, reduce myocardial injury and inflammatory reaction caused by PCI, and also reduce the occurrence of MACE 30 days after PCI.

Accuracy and Injection Force of the Gla-300 Injection Device Compared With Other Commercialized Disposable Insulin Pens.

PubMed

Klonoff, David; Nayberg, Irina; Thonius, Marissa; See, Florian; Abdel-Tawab, Mona; Erbstein, Frank; Haak, Thomas

2015-08-26

To deliver insulin glargine 300 U/mL (Gla-300), the widely used SoloSTAR(®) pen has been modified to allow for accurate and precise delivery of required insulin units in one-third of the volume compared with insulin glargine 100 U/mL, while improving usability. Here we compare the accuracy and injection force of 3 disposable insulin pens: Gla-300 SoloSTAR(®), FlexPen(®), and KwikPen™. For the accuracy assessment, 60 of each of the 3 tested devices were used for the delivery of 3 different doses (1 U, half-maximal dose, and maximal dose), which were measured gravimetrically. For the injection force assessment, 20 pens of each of the 3 types were tested twice at half-maximal and once at maximal dose, at an injection speed of 6 U/s. All tested pens met the International Organization for Standardization (ISO) requirements for dosing accuracy, with Gla-300 SoloSTAR showing the lowest between-dose variation (greatest reproducibility) at all dose levels. Mean injection force was significantly lower for Gla-300 SoloSTAR than for the other 2 pens at both half maximal and maximal doses (P < .0271). All tested pens were accurate according to ISO criteria, and the Gla-300 SoloSTAR pen displayed the greatest reproducibility and lowest injection force of any of the 3 tested devices. © 2015 Diabetes Technology Society.

The antagonistic effects of atipamezole and yohimbine on stress-related neurohormonal and metabolic responses induced by medetomidine in dogs

PubMed Central

Ambrisko, T. D.; Hikasa, Y.

2003-01-01

This study aimed to compare the antagonistic effects of atipamezole (40, 120, and 320 μg/kg, IM), yohimbine (110 μg/kg, IM), and saline on neurohormonal and metabolic responses induced by medetomidine (20 μg/kg, IM). Five beagle dogs were used in each of the 5 experimental groups in randomized order. Blood samples were taken for 6 h. Medetomidine significantly decreased norepinephrine, epinephrine, insulin, and nonesterified fatty acid levels, and increased plasma glucose levels. Both atipamezole and yohimbine antagonized these effects. The reversal effect of atipamezole was dose-dependency, except on epinephrine. Yohimbine caused prolonged increases in plasma norepinephrine and insulin levels compared to atipamezole, possibly because of its longer half-life elimination. Only yohimbine increased the cortisol levels. Neither glucagon nor lactate levels changed significantly. Based on these findings, when medetomidine-induced sedation is antagonized in dogs, we recommend using atipamezole IM, from 2- to 6-fold the dose of medetomidine, unless otherwise indicated. PMID:12528832

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

PubMed Central

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Results Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 μg.mL-1 and 16.81 μg.mL-1, respectively, for ibuprofen from the combination, compared with 0.58 μg.mL-1 and 9.00 μg.mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 μg.mL-1 and 14.54 μg.mL-1, respectively, for the combination compared with 0.33 μg.mL-1 and 9.19 μg.mL-1, respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily. Conclusions Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing. PMID:20602760

The effect of low dose rate on metabolomic response to radiation in mice

PubMed Central

Goudarzi, Maryam; Mak, Tytus D.; Chen, Congju; Smilenov, Lubomir B.; Brenner, David J.

2014-01-01

Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual's exposure in a radiobiological event and thus would have utility for both triage and injury assessment. PMID:25047638

Species differences in susceptibility to 1,3-dinitrobenzene-induced testicular toxicity and methemoglobinemia.

PubMed

Obasaju, M F; Katz, D F; Miller, M G

1991-02-01

The testicular toxicity and methemoglobinemia induced by 1,3-dinitrobenzene (1,3-DNB) was compared in two species, the Sprague-Dawley rat and the golden Syrian hamster. A marked difference in susceptibility to both endpoints of toxicity was observed. The hamster showed no testicular lesions at dose levels up to 50 mg/kg whereas, as previously reported by others, damage to rat testicular tubules in later stages of spermatogenesis was readily apparent at a 25 mg/kg dose level. Similarly, administration of 1,3-DNB induced substantially less methemoglobinemia in the hamster than in the rat. For example, at the 25 mg/kg dose level peak levels of methemoglobin in the hamster were 15% compared with 80% in the rat. Mortality in the rat also occurred at lower doses than in the hamster (50 vs 100 mg/kg, respectively). In in vitro studies, the capacity of 1,3-DNB and 1,3-DNB metabolites (nitroaniline, nitroacetanilide, aminoacetanilide, diacetamidobenzene) to induce methemoglobinemia was examined in suspensions of red blood cells obtained from both species. Only 1,3-DNB caused the formation of methemoglobin and rat red blood cells were twice as sensitive as hamster red blood cells. The species difference in susceptibility to both methemoglobinemia and testicular toxicity could indicate differences in 1,3-DNB clearance and/or formation of toxic metabolites. Additional metabolic work is under way. This study demonstrates that the hamster is more resistant than the rat to the testicular lesion and methemoglobinemia induced by 1,3-DNB.

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

PubMed

Johnson, Daniel J; Johnson, Christine C; Goobie, Susan M; Nami, Nina; Wetzler, Joshua A; Sponseller, Paul D; Frank, Steven M

2017-12-01

Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Level-III, retrospective cohort study.

In vivo Investigation of Anti-diabetic Properties of Ripe Onion Juice in Normal and Streptozotocin-induced Diabetic Rats

PubMed Central

Lee, Chul-Won; Lee, Hyung-Seok; Cha, Yong-Jun; Joo, Woo-Hong; Kang, Dae-Ook; Moon, Ja-Young

2013-01-01

The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is “Black Onion Extract”) were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyper-glycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product “Black Onion Extract” may possess anti-hyperglycemic potential in diabetes. PMID:24471128

Image Quality of 3rd Generation Spiral Cranial Dual-Source CT in Combination with an Advanced Model Iterative Reconstruction Technique: A Prospective Intra-Individual Comparison Study to Standard Sequential Cranial CT Using Identical Radiation Dose

PubMed Central

Wenz, Holger; Maros, Máté E.; Meyer, Mathias; Förster, Alex; Haubenreisser, Holger; Kurth, Stefan; Schoenberg, Stefan O.; Flohr, Thomas; Leidecker, Christianne; Groden, Christoph; Scharf, Johann; Henzler, Thomas

2015-01-01

Objectives To prospectively intra-individually compare image quality of a 3rd generation Dual-Source-CT (DSCT) spiral cranial CT (cCT) to a sequential 4-slice Multi-Slice-CT (MSCT) while maintaining identical intra-individual radiation dose levels. Methods 35 patients, who had a non-contrast enhanced sequential cCT examination on a 4-slice MDCT within the past 12 months, underwent a spiral cCT scan on a 3rd generation DSCT. CTDIvol identical to initial 4-slice MDCT was applied. Data was reconstructed using filtered backward projection (FBP) and 3rd-generation iterative reconstruction (IR) algorithm at 5 different IR strength levels. Two neuroradiologists independently evaluated subjective image quality using a 4-point Likert-scale and objective image quality was assessed in white matter and nucleus caudatus with signal-to-noise ratios (SNR) being subsequently calculated. Results Subjective image quality of all spiral cCT datasets was rated significantly higher compared to the 4-slice MDCT sequential acquisitions (p<0.05). Mean SNR was significantly higher in all spiral compared to sequential cCT datasets with mean SNR improvement of 61.65% (p*Bonferroni0.05<0.0024). Subjective image quality improved with increasing IR levels. Conclusion Combination of 3rd-generation DSCT spiral cCT with an advanced model IR technique significantly improves subjective and objective image quality compared to a standard sequential cCT acquisition acquired at identical dose levels. PMID:26288186

Image Quality of 3rd Generation Spiral Cranial Dual-Source CT in Combination with an Advanced Model Iterative Reconstruction Technique: A Prospective Intra-Individual Comparison Study to Standard Sequential Cranial CT Using Identical Radiation Dose.

PubMed

Wenz, Holger; Maros, Máté E; Meyer, Mathias; Förster, Alex; Haubenreisser, Holger; Kurth, Stefan; Schoenberg, Stefan O; Flohr, Thomas; Leidecker, Christianne; Groden, Christoph; Scharf, Johann; Henzler, Thomas

2015-01-01

To prospectively intra-individually compare image quality of a 3rd generation Dual-Source-CT (DSCT) spiral cranial CT (cCT) to a sequential 4-slice Multi-Slice-CT (MSCT) while maintaining identical intra-individual radiation dose levels. 35 patients, who had a non-contrast enhanced sequential cCT examination on a 4-slice MDCT within the past 12 months, underwent a spiral cCT scan on a 3rd generation DSCT. CTDIvol identical to initial 4-slice MDCT was applied. Data was reconstructed using filtered backward projection (FBP) and 3rd-generation iterative reconstruction (IR) algorithm at 5 different IR strength levels. Two neuroradiologists independently evaluated subjective image quality using a 4-point Likert-scale and objective image quality was assessed in white matter and nucleus caudatus with signal-to-noise ratios (SNR) being subsequently calculated. Subjective image quality of all spiral cCT datasets was rated significantly higher compared to the 4-slice MDCT sequential acquisitions (p<0.05). Mean SNR was significantly higher in all spiral compared to sequential cCT datasets with mean SNR improvement of 61.65% (p*Bonferroni0.05<0.0024). Subjective image quality improved with increasing IR levels. Combination of 3rd-generation DSCT spiral cCT with an advanced model IR technique significantly improves subjective and objective image quality compared to a standard sequential cCT acquisition acquired at identical dose levels.

Does a history of psychoactive substances abuse play a role in the level of pain of the patient with severe trauma?

PubMed

López-López, C; Arranz-Esteban, A; Martinez-Ureta, M V; Sánchez-Rascón, M C; Morales-Sánchez, C; Chico-Fernández, M

To analyse the influence of psychotropic substance use on the level of pain in patients with severe trauma. Longitudinal analytical study. Intensive Care Unit (ICU) of Trauma and Emergencies. severe trauma, non-communicative and mechanical ventilation >48hours. Two groups of patients were created: users and non-users of psychotropic substances according to medical records. Measurement of pain level at baseline and during mobilization, using the Pain Indicator Behaviour Scale. demographic characteristics, pain score, sedation level and type and dose of analgesia and sedation. Sample of 84 patients, 42 in each group. The pain level in both groups, during mobilisation, showed significant differences p=0.011, with a mean of 3.11(2.40) for the user group and 1.83(2.14) for the non-user group. A relative risk of 2.5 CI (1,014-6,163) was found to have moderate / severe pain in the user group compared to the non-user group. The mean dose of analgesia and continuous sedation was significantly higher in the user group: P=.032 and P=.004 respectively. There was no difference in bolus dose of analgesia and sedation with P=.624 and P=.690 respectively. Patients with a history of consumption of psychoactive substances show higher levels of pain and experience a higher risk of this being moderate/severe compared to non-users despite receiving higher doses of analgesia and sedation infusion. Key words: pain, multiple trauma, drug users. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

SU-E-I-33: Initial Evaluation of Model-Based Iterative CT Reconstruction Using Standard Image Quality Phantoms

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

Gingold, E; Dave, J

2014-06-01

Purpose: The purpose of this study was to compare a new model-based iterative reconstruction with existing reconstruction methods (filtered backprojection and basic iterative reconstruction) using quantitative analysis of standard image quality phantom images. Methods: An ACR accreditation phantom (Gammex 464) and a CATPHAN600 phantom were scanned using 3 routine clinical acquisition protocols (adult axial brain, adult abdomen, and pediatric abdomen) on a Philips iCT system. Each scan was acquired using default conditions and 75%, 50% and 25% dose levels. Images were reconstructed using standard filtered backprojection (FBP), conventional iterative reconstruction (iDose4) and a prototype model-based iterative reconstruction (IMR). Phantom measurementsmore » included CT number accuracy, contrast to noise ratio (CNR), modulation transfer function (MTF), low contrast detectability (LCD), and noise power spectrum (NPS). Results: The choice of reconstruction method had no effect on CT number accuracy, or MTF (p<0.01). The CNR of a 6 HU contrast target was improved by 1–67% with iDose4 relative to FBP, while IMR improved CNR by 145–367% across all protocols and dose levels. Within each scan protocol, the CNR improvement from IMR vs FBP showed a general trend of greater improvement at lower dose levels. NPS magnitude was greatest for FBP and lowest for IMR. The NPS of the IMR reconstruction showed a pronounced decrease with increasing spatial frequency, consistent with the unusual noise texture seen in IMR images. Conclusion: Iterative Model Reconstruction reduces noise and improves contrast-to-noise ratio without sacrificing spatial resolution in CT phantom images. This offers the possibility of radiation dose reduction and improved low contrast detectability compared with filtered backprojection or conventional iterative reconstruction.« less

One and three doses of propranolol a day in hypertension.

PubMed

van den Brink, G; Boer, P; van Asten, P; Dorhout Mees, E J; Geyskes, G G

1980-01-01

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

Half-dose non-contrast CT in the investigation of urolithiasis: image quality improvement with third-generation integrated circuit CT detectors.

PubMed

Wang, Jun; Kang, Tony; Arepalli, Chesnal; Barrett, Sarah; O'Connell, Tim; Louis, Luck; Nicolaou, Savvakis; McLaughlin, Patrick

2015-06-01

The objective of this study is to establish the effect of third-generation integrated circuit (IC) CT detector on objective image quality in full- and half-dose non-contrast CT of the urinary tract. 51 consecutive patients with acute renal colic underwent non-contrast CT of the urinary tract using a 128-slice dual-source CT before (n = 24) and after (n = 27) the installation of third-generation IC detectors. Half-dose images were generated using projections from detector A using the dual-source RAW data. Objective image noise in the liver, spleen, right renal cortex, and right psoas muscle was compared between DC and IC cohorts for full-dose and half-dose images reconstructed with FBP and IR algorithms using 1 cm(2) regions of interest. Presence and size of obstructing ureteric calculi were also compared for full-dose and half-dose reconstructions using DC and IC detectors. No statistical difference in age and lateral body size was found between patients in the IC and DC cohorts. Radiation dose, as measured by size-specific dose estimates, did not differ significantly either between the two cohorts (10.02 ± 4.54 mGy IC vs. 12.28 ± 7.03 mGy DC). At full dose, objective image noise was not significantly lower in the IC cohort as compared to the DC cohort for the liver, spleen, and right psoas muscle. At half dose, objective image noise was lower in the IC cohort as compared to DC cohort at the liver (21.32 IC vs. 24.99 DC, 14.7% decrease, p < 0.001), spleen (19.33 IC vs. 20.83 DC, 7.20% decrease, p = 0.02), and right renal cortex (20.28 IC vs. 22.98 DC, 11.7% decrease, p = 0.005). Mean obstructing ureteric calculi size was not significantly different when comparison was made between full-dose and half-dose images, regardless of detector type (p > 0.05 for all comparisons). Third-generation IC detectors result in lower objective image noise at full- and half-radiation dose levels as compared with traditional DC detectors. The magnitude of noise reduction was greater at half-radiation dose indicating that the benefits of using novel IC detectors are greater in low and ultra-low-dose CT imaging.

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

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

Chen, Y; Souri, S; Gill, G

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

Comparing probabilistic and descriptive analyses of time–dose–toxicity relationship for determining no-observed-adverse-effect level in drug development

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

Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder

The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; andmore » then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. - Highlights: • Simulations revealed issues with NOAEL concept, determination and application. • Probabilistic modelling was used to address these issues. • The model integrated time-dose-toxicity data from multiple studies. • The approach uses data efficiently and may allow more meaningful human translation.« less

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

PubMed

Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

2017-08-15

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017. Published by Elsevier B.V.

Pharmacokinetic equivalence of a levothyroxine sodium soft capsule manufactured using the new food and drug administration potency guidelines in healthy volunteers under fasting conditions.

PubMed

Colucci, Philippe; D'Angelo, Pina; Mautone, Giuseppe; Scarsi, Claudia; Ducharme, Murray P

2011-06-01

To assess the pharmacokinetic equivalence of a new soft capsule formulation of levothyroxine versus a marketed reference product and to assess the soft capsule formulated with stricter potency guidelines versus the capsule before the implementation of the new potency rule. Two single-dose randomized two-way crossover pharmacokinetic equivalence studies and one dosage form proportionality single-dose study comparing low, medium, and high strengths of the new formulation. All three studies were performed in a clinical setting. Participants were healthy male and female adult subjects with normal levothyroxine levels. A total of 90 subjects participated in the three studies. Pharmacokinetic parameters were calculated on baseline- adjusted concentrations. The first pharmacokinetic equivalence study compared the levothyroxine sodium soft capsule formulation (Tirosint) with the reference Synthroid tablets and the two products were considered bioequivalent. The dosage form proportionality study compared the 50-, 100-, and 150-μg test capsules strengths dosed at the same level (600 μg) and all three strengths were considered equivalent when given at the same dosage. The last study compared the test capsule used in the first two studies with a new capsule formulation following the new potency guideline (±5%) set forward by the Food and Drug Administration and the two capsules were considered bioequivalent. Doses were well tolerated by subjects in all three studies with no serious adverse events reported. The levothyroxine soft capsule formulated with the stricter new potency guideline set forward by the Food and Drug Administration met equivalence criteria in terms of rate and extent of exposure under fasting conditions to the reference tablet formulation. Clinical doses of the capsule formulation can be given using any combination of the commercialized strengths.

A Randomized Phase 2 Study of Long-Acting TransCon GH vs Daily GH in Childhood GH Deficiency.

PubMed

Chatelain, Pierre; Malievskiy, Oleg; Radziuk, Klaudziya; Senatorova, Ganna; Abdou, Magdy O; Vlachopapadopoulou, Elpis; Skorodok, Yulia; Peterkova, Valentina; Leff, Jonathan A; Beckert, Michael

2017-05-01

TransCon Growth Hormone (GH) (Ascendis Pharma) is a long-acting recombinant sustained-release human GH prodrug in development for children with GH deficiency (GHD). To compare the pharmacokinetics, pharmacodynamics, safety, and efficacy of weekly TransCon GH to that of daily GH in prepubertal children with GHD. Randomized, open-label, active-controlled study of three doses of weekly TransCon GH versus daily Genotropin (Pfizer). Thirty-eight centers in 14 European countries and Egypt. Prepubertal male and female treatment-naïve children with GHD (n = 53). Subjects received one of three TransCon GH doses (0.14, 0.21, or 0.30 mg GH/kg/wk) or Genotropin 0.03 mg GH/kg/d for 26 weeks. GH and insulinlike growth factor-1 (IGF-1) levels, growth, adverse events, and immunogenicity. Both GH maximum concentration and area under the curve were similar following TransCon GH or Genotropin administration at comparable doses. A dose response was observed, with IGF-1 standard deviation scores increasing into the normal range for all three TransCon GH doses. Annualized mean height velocity for the three TransCon GH doses ranged from 11.9 cm to 13.9 cm, which was not statistically different from 11.6 cm for Genotropin. Adverse events were mild to moderate, and most were unrelated to the study drug. Injection site tolerance was good. One TransCon GH subject developed a low-titer, nonneutralizing antibody response to GH. The results suggest that long-acting TransCon GH is comparable to daily Genotropin for GH (pharmacokinetics) and IGF-1 (pharmacodynamics) levels, safety, and efficacy and support advancement into phase 3 development. Copyright © 2017 Endocrine Society

A bone marrow toxicity model for 223Ra alpha-emitter radiopharmaceutical therapy

NASA Astrophysics Data System (ADS)

Hobbs, Robert F.; Song, Hong; Watchman, Christopher J.; Bolch, Wesley E.; Aksnes, Anne-Kirsti; Ramdahl, Thomas; Flux, Glenn D.; Sgouros, George

2012-05-01

Ra-223, an α-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metastases of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histogram results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e. the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 to 20 Gy. The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the absorbed fraction method of dose calculation.

TU-G-204-09: The Effects of Reduced- Dose Lung Cancer Screening CT On Lung Nodule Detection Using a CAD Algorithm

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

Young, S; Lo, P; Kim, G

2015-06-15

Purpose: While Lung Cancer Screening CT is being performed at low doses, the purpose of this study was to investigate the effects of further reducing dose on the performance of a CAD nodule-detection algorithm. Methods: We selected 50 cases from our local database of National Lung Screening Trial (NLST) patients for which we had both the image series and the raw CT data from the original scans. All scans were acquired with fixed mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare). All images were reconstructed with 1-mm slice thickness, B50 kernel.more » 10 of the cases had at least one nodule reported on the NLST reader forms. Based on a previously-published technique, we added noise to the raw data to simulate reduced-dose versions of each case at 50% and 25% of the original NLST dose (i.e. approximately 1.0 and 0.5 mGy CTDIvol). For each case at each dose level, the CAD detection algorithm was run and nodules greater than 4 mm in diameter were reported. These CAD results were compared to “truth”, defined as the approximate nodule centroids from the NLST reports. Subject-level mean sensitivities and false-positive rates were calculated for each dose level. Results: The mean sensitivities of the CAD algorithm were 35% at the original dose, 20% at 50% dose, and 42.5% at 25% dose. The false-positive rates, in decreasing-dose order, were 3.7, 2.9, and 10 per case. In certain cases, particularly in larger patients, there were severe photon-starvation artifacts, especially in the apical region due to the high-attenuating shoulders. Conclusion: The detection task was challenging for the CAD algorithm at all dose levels, including the original NLST dose. However, the false-positive rate at 25% dose approximately tripled, suggesting a loss of CAD robustness somewhere between 0.5 and 1.0 mGy. NCI grant U01 CA181156 (Quantitative Imaging Network); Tobacco Related Disease Research Project grant 22RT-0131.« less

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter

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

Ricketts, Kate, E-mail: k.ricketts@ucl.ac.uk; Department of Radiotherapy Physics, Royal Berkshire NHS Foundation Trust, Reading; Navarro, Clara

2016-08-01

Purpose: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Methods and Materials: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. Themore » deviation of the results was used to inform future action levels. Results: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of Δ{sub D} of 0 ± 5 cGy or %Δ{sub D} of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (−2 ± 5 cGy) or summed field percentage dose difference (−6% ± 7%). Conclusions: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups.« less

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter.

PubMed

Ricketts, Kate; Navarro, Clara; Lane, Katherine; Blowfield, Claire; Cotten, Gary; Tomala, Dee; Lord, Christine; Jones, Joanne; Adeyemi, Abiodun

2016-08-01

To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. The deviation of the results was used to inform future action levels. Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of ΔD of 0 ± 5 cGy or %ΔD of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (-2 ± 5 cGy) or summed field percentage dose difference (-6% ± 7%). The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative assessment of onion and garlic extracts on endogenous hepatic and renal antioxidant status in rat.

PubMed

Suru, Stephen M; Ugwu, Chidiebere E

2015-07-01

Despite growing claims of functional health benefits in folkloric medicine, the safety of chronic/elevated intakes of onion and garlic cannot be assumed. Therefore, this study assesses oral administration of varied doses of onion and garlic on some biomarkers of hepatic and renal functions in rats. Animals were divided into five groups: control group received vehicle and extract-treated groups received varied doses of onion or garlic extract (0.5 mL and 1.0 mL/100 g bwt/day) for 6 weeks. Both doses of onion caused marked (p<0.05) increase in hepatic and renal levels of glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and marked (p<0.05) decrease in malondialdehyde (MDA). Treatment with low dose of garlic elicited similar trend except in hepatic CAT, renal SOD and GST levels. A high dose of garlic only caused marked (p<0.05) increase in hepatic GST, renal GST, and SOD. Both doses of onion and low dose of garlic significantly (p<0.05) enhanced renal Na+/K+-ATPase activity. Only a high dose of onion caused significant (p<0.05) increase in hepatic aspartate transaminase (AST), alkaline phosphatase (ALP), and decrease in plasma AST activities. These findings suggest antioxidant enhancing capability for both doses of onion and low dose of garlic, while high dose of garlic elicited pro-oxidant conditions.

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

Commentary on "randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and Ki67 labeling in prostate cancer patients." Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R, Department of Nutritional Sciences, University of Toronto, Ontario, Canada.: J Clin Endocrinol Metab 2013;98(4):1498-507 [Epub 2013 Mar 5].

PubMed

Olumi, Aria F

2014-02-01

Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol. Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue. We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada. PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol. Vitamin D3 (400, 10000, or 40000 IU/d) was orally administered before radical prostatectomy. We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed. Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P<.03) and were significantly higher in the 40000-IU/d group than in every other dose group (P<.03). Prostate vitamin D metabolites correlated positively with serum levels (P<.0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P<.05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P< .02). Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research. Copyright © 2014 Elsevier Inc. All rights reserved.

Real-time dosimetry in radiotherapy using tailored optical fibers

NASA Astrophysics Data System (ADS)

Rahman, A. K. M. Mizanur; Zubair, H. T.; Begum, Mahfuza; Abdul-Rashid, H. A.; Yusoff, Z.; Omar, Nasr Y. M.; Ung, N. M.; Mat-Sharif, K. A.; Bradley, D. A.

2016-05-01

Real-time dosimetry plays an important role for accurate patient-dose measurement during radiotherapy. A tiny piece of laboratory fabricated Ge-doped optical fiber has been investigated as a radioluminescence (RL) sensor for real-time dosimetry over the dose range from 1 Gy to 8 Gy under 6 MV photon beam by LINAC. Fiber-coupled software-based RL prototype system was used to assess essential dosimetric characteristics including dose response linearity, dose rate dependency, sensitivity, repeatability and output dependence on field sizes. The consistency level of RL photon counts versus dose rate was also compared with that of standard Al2O3:C chips. Sensitivity of Ge-doped fiber were found to be sufficiently sensitive for practical use and also provided linear dose responses for various dose rates from 100 cGy/min to 600 cGy/min using both 6 MV photon and 6 MeV electron beams. SEM-EDX analysis was performed to identify Ge-dopant concentration level within the optical fiber RL material. Accumulated doses were also estimated using simple integral technique and the error was found to be around less than 1% under dissimilar dose rates or repeat measurements. The evaluation of the Ge-doped optical fiber based RL dosimeter system indicates its potential in medical dosimetry.

[Effects of Salvianolate on Myosin Heavy Chain in Cardiomyocytes of Congestive Heart Failure Rats].

PubMed

Chen, Cheng; Zou, Xiang-gu; Qiu, Shan-dong; Chen, Hui; Chen, Yong-zhong; Lin, Xiu-ming

2015-07-01

To explore the effect of Salvianolate on myosin heavy chain (MHC) in cardiomyocytes of congestive heart failure (CHF) rats. Sixty male SD rats were divided into 6 groups according to random digit table, i.e., the normal control group (NCG), the model group, the Captopril group (CAG), the low dose Salvianolate group (LSG), the high dose Salvianolate group (HSG), the Captopril and high dose Salvianolate group (CSG), 10 in each group. CHF rat model was established with peritoneal injection of adriamycin in all rats except those in the NCG. Equal volume of normal saline was peritoneally injected to rats in the NCG, once per week for 6 successive weeks. Corresponding medication was started from the 5th week of injecting adriamycin. Rats in the CAG were administered with Captopril solution at the daily dose of 10 mg/kg by gastrogavage. Rats in the LSG and the HSG were administered with Salvianolate solution at the daily dose of 24.219 mg/kg and 48.438 mg/kg respectively by gastrogavage. Salvianolate was dissolved in 2 mL 5% glucose solution and administered by peritoneal injection. Rats in the CSG were peritoneally injected with high dose Salvianolate solution and administered with Captopril solution by gastrogavage. Two mL normal saline was peritoneally injected to rats in the model group, once per day for 8 successive weeks. Eight weeks later, the cardiac function and myocardial hypertrophy indices were detected by biological signal collecting and processing system. mRNA expression levels of alpha-MHC and beta-MHC in cardiac muscle were detected by fluorescence quantitative PCR. Expressions of protein kinase C (PKC) in cardiac muscle were detected by Western blot. Compared with the normal control group, heart mass index (HMI) and left ventricular mass index (LVMI) obviously increased in the model group (P < 0.01). Compared with the model group, HMI and LVMI decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). It was more obviously lowered in the CSG group than in the CAG group (P < 0.05). Compared with the NCG, the mRNA expression level of alpha-MHC in cardiac muscle decreased, the mRNA expression level of p-MHC and the expression of PKC in cardiac muscle increased in the model group (P < 0.01). Compared with the model group, the mRNA expression level of alpha-MHC in cardiac muscle was increased, and the mRNA expression level of beta-MHC and the expression of PKC in cardiac muscle were decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). There was statistical difference between the CSG group and the CAG group (P < 0.05). Salvianolate could up-regulate the mRNA expression level of alpha-MHC, and down-regulate the mRNA expression level of beta-MHC in cardiac muscle. Its mechanism might be related to decreasing the expression of PKC.

Effective radiation dose of ProMax 3D cone-beam computerized tomography scanner with different dental protocols.

PubMed

Qu, Xing-min; Li, Gang; Ludlow, John B; Zhang, Zu-yan; Ma, Xu-chen

2010-12-01

The aim of this study was to compare effective doses resulting from different scan protocols for cone-beam computerized tomography (CBCT) using International Commission on Radiological Protection (ICRP) 1990 and 2007 calculations of dose. Average tissue-absorbed dose, equivalent dose, and effective dose for a ProMax 3D CBCT with different dental protocols were calculated using thermoluminescent dosimeter chips in a human equivalent phantom. Effective doses were derived using ICRP 1990 and the superseding 2007 recommendations. Effective doses (ICRP 2007) for default patient sizes from small to large ranged from 102 to 298 μSv. The coefficient of determination (R(2)) between tube current and effective dose (ICRP 2007) was 0.90. When scanning with lower resolution settings, the effective doses were reduced significantly (P < .05). ProMax 3D can provide a wide range of radiation dose levels. Reduction in radiation dose can be achieved when using lower settings of exposure parameters. Copyright © 2010 Mosby, Inc. All rights reserved.

Icariin Improves Cognitive Impairment after Traumatic Brain Injury by Enhancing Hippocampal Acetylation.

PubMed

Zhang, Zi-Gang; Wang, Xin; Zai, Jin-Hai; Sun, Cai-Hua; Yan, Bing-Chun

2018-05-01

To examine the effect of icariin (ICA) on the cognitive impairment induced by traumatic brain injury (TBI) in mice and the underlying mechanisms related to changes in hippocampal acetylation level. The modifified free-fall method was used to establish the TBI mouse model. Mice with post-TBI cognitive impairment were randomly divided into 3 groups using the randomised block method (n=7): TBI (vehicle-treated), low-dose (75 mg/kg) and high-dose (150 mg/kg) of ICA groups. An additional sham-operated group (vehicle-treated) was employed. The vehicle or ICA was administrated by gavage for 28 consecutive days. The Morris water maze (MWM) test was conducted. Acetylcholine (ACh) content, mRNA and protein levels of choline acetyltransferase (ChAT), and protein levels of acetylated H3 (Ac-H3) and Ac-H4 were detected in the hippocampus. Compared with the sham-operated group, the MWM performance, hippocampal ACh content, mRNA and protein levels of ChAT, and protein levels of Ac-H3 and Ac-H4 were signifificantly decreased in the TBI group (P<0.05). High-dose of ICA signifificantly ameliorated the TBI-induced weak MWM performance, increased hippocampal ACh content, and mRNA and protein levels of ChAT, as well as Ac-H3 protein level compared with the TBI group (P<0.05). ICA improved post-TBI cognitive impairment in mice by enhancing hippocampal acetylation, which improved hippocampal cholinergic function and ultimately improved cognition.

Prospective Evaluation of a Model-Based Dosing Regimen for Amikacin in Preterm and Term Neonates in Clinical Practice

PubMed Central

De Cock, R. F. W.; Allegaert, K.; Vanhaesebrouck, S.; Danhof, M.; Knibbe, C. A. J.

2015-01-01

Based on a previously derived population pharmacokinetic model, a novel neonatal amikacin dosing regimen was developed. The aim of the current study was to prospectively evaluate this dosing regimen. First, early (before and after second dose) therapeutic drug monitoring (TDM) observations were evaluated for achieving target trough (<3 mg/liter) and peak (>24 mg/liter) levels. Second, all observed TDM concentrations were compared with model-predicted concentrations, whereby the results of a normalized prediction distribution error (NPDE) were considered. Subsequently, Monte Carlo simulations were performed. Finally, remaining causes limiting amikacin predictability (i.e., prescription errors and disease characteristics of outliers) were explored. In 579 neonates (median birth body weight, 2,285 [range, 420 to 4,850] g; postnatal age 2 days [range, 1 to 30 days]; gestational age, 34 weeks [range, 24 to 41 weeks]), 90.5% of the observed early peak levels reached 24 mg/liter, and 60.2% of the trough levels were <3 mg/liter (93.4% ≤5 mg/liter). Observations were accurately predicted by the model without bias, which was confirmed by the NPDE. Monte Carlo simulations showed that peak concentrations of >24 mg/liter were reached at steady state in almost all patients. Trough values of <3 mg/liter at steady state were documented in 78% to 100% and 45% to 96% of simulated cases with and without ibuprofen coadministration, respectively; suboptimal trough levels were found in patients with postnatal age <14 days and current weight of >2,000 g. Prospective evaluation of a model-based neonatal amikacin dosing regimen resulted in optimized peak and trough concentrations in almost all patients. Slightly adapted dosing for patient subgroups with suboptimal trough levels was proposed. This model-based approach improves neonatal dosing individualization. PMID:26248375

Urinary Cotinine Levels Among Latino Tobacco Farmworkers in North Carolina Compared to Latinos Not Employed in Agriculture.

PubMed

Arcury, Thomas A; Laurienti, Paul J; Talton, Jennifer W; Chen, Haiying; Howard, Timothy D; Summers, Phillip; Quandt, Sara A

2016-06-01

This analysis describes urinary cotinine levels of North Carolina Latino farmworkers, compares cotinine levels of farmworkers to those of Latinos non-farmworkers, determines factors associated with farmworker cotinine levels, and determines if differences in farmworker and non-farmworker cotinine levels are associated with smoking. Data are from 63 farmworkers and 44 non-farmworkers who participated in a larger study of occupational exposures. Questionnaire data and urine samples collected in 2012 and 2013 are analyzed. Farmworkers had urinary cotinine levels that were far greater than the non-farmworker group. Geometric mean (GM) urinary cotinine levels for farmworkers were 1808.22ng/ml in 2012, and 396.03ng/ml in 2013; corresponding GM levels for non-farmworkers were 4.68ng/ml and 9.03ng/ml. Farmworker GM cotinine levels were associated with harvesting tobacco (1242.77ng/ml vs. 471.26ng/ml; P = .0048), and working in wet shoes (1356.41ng/ml vs. 596.93ng/ml; P = .0148). Smoking did not account for cotinine level differences; the GM cotinine level for farmworkers who did not smoke was 541.31ng/ml; it was 199.40ng/ml for non-farmworkers who did smoke. North Carolina farmworkers experience large nicotine doses. The long-term health effects of these doses are not known. Although procedures to reduce occupational nicotine exposure are known, no changes in work practices or in policies to protect workers have been implemented. Research on the health effects of occupational nicotine exposure must become a priority. Current knowledge of occupational transdermal nicotine exposure must be used to improve occupational safety practice and policy for tobacco workers. This study documents the heavy burden of nicotine exposure and dose experienced by tobacco workers in North Carolina. Hundreds of thousands of farmworkers and farmers in the United States and Canada, as well as agricultural workers around the world, share this burden of nicotine exposure and dose. These results support the need to change work practices and regulations to protect workers. They also document the need to delineate the health effects of long-term exposure to high transdermal nicotine doses. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

PubMed

Yokoyama, Shota; Tsuji, Hideyuki; Hiraoka, Sachiko; Nishihara, Masayuki

2016-01-01

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

[The effect of aluminum adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine].

PubMed

Wang, Fang; Zhang, Ming; Xie, Bing-Feng; Cao, Han; Tong, Shao-Yong; Wang, Jun-Rong; Yu, Xiao-Ping; Tang, Yang; Yang, Jing-Ran; Sun, Ming-Bo

2013-04-01

To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine. Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay. The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant. Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.

Comparative dose levels between CT-scanner and slot-scanning device (EOS system) in pregnant women pelvimetry.

PubMed

Ben Abdennebi, A; Aubry, S; Ounalli, L; Fayache, M S; Delabrousse, E; Petegnief, Y

2017-01-01

To estimate fetal absorbed doses for pregnant women pelvimetry, a comparative study between EOS imaging system and low-dose spiral CT-scanner was carried out. For this purpose three different studies were investigated: in vivo, in vitro and Monte Carlo calculations. In vivo dosimetry was performed, using OSL NanoDot dosimeters, to determine the dose to the skin of twenty pregnant women. In vitro studies were established by using a cubic phantom of water, in order to estimate the out of field doses. In the latter study, OSLDs were placed at depths corresponding to the lowest, average and highest position of the uterus. Monte Carlo calculations of effective doses to high radio-sensitive organs were established, using PCXMC and CTExpo software suites for EOS imaging system and CT-scanner, respectively. The EOS imaging system reduces radiation exposure 4 to 8 times compared to the CT-scanner. The entrance skin doses were 74% (p-values <0.01) higher with the CT-scanner than with the EOS system. In the out of field region, the measured doses of the EOS system were reduced by 80% (p-values <0.02). Monte Carlo calculations confirmed that effective doses to organs are less accentuated for EOS than for CT pelvimetry. The EOS system is less irradiating than the CT exam. The out-of-field dose which is significant, is lower in the EOS than in the CT-scanner and could be reduced even further by optimizing the time used for image acquisition. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dose Assessment of Los Alamos National Laboratory-Derived Residual Radionuclides in Soils within Tract A-18-2 for Land Conveyance and Transfer Decisions

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

Ruedig, Elizabeth; Whicker, Jeffrey Jay

In 2017, soil sampling for radiological materials was conducted within Tract A-18-2 at Los Alamos National Laboratory (LANL) for land conveyance decisions. Measurements of radionuclides in soil samples were evaluated against a recreational use scenario, and all measurements were below screening action levels for each radionuclide. The total estimated dose was less than 1 mrem/yr (<10 μSv/yr) for a hypothetical recreational user (compared with a dose limit of 25 mrem/yr [250 μSv/yr]). Dose estimates were based on the 95% upper confidence levels for radionuclide concentrations within the Tract. Dose estimates less than 3 mrem/yr are considered to be as lowmore » as reasonably achievable (ALARA), therefore no follow-up analysis was conducted. Release of this property is consistent with the requirements of DOE Order 458.1 (DOE 2013) and Policy 412 (LANL 2014).« less

Effect of strawberry (Fragaria x ananasa) as antidepresant activity on mice induced by stress

NASA Astrophysics Data System (ADS)

Hazar, Siti; Fitri, Lulu L.

2015-09-01

Depression is a physiological disorder on the brain and may induce the reduction levels of monoamine neurotransmitters, serotonin and the increased levels of stress hormone, corticosterone. The use of antidepressant drugs causing side effect, therefore natural agents are used as alternative therapy. The objectives of this study are to determine the effect of strawberries in the murine experiments in increasing serotonin level as well as decreasing in the immobility time of mice on Forced Swimming Task (FST). Forty-eight male outbreed of 4 weeks old mice strain Swiss Webster with average body weight of 18-22 grams were divided into six groups of eight mice, as follows: (1) non-stressed, (2) Chronic Mild Stressed (CMS), (3) strawberry extract (with dose of 464.1 mg/kg) and CMS, (4) strawberry extract (with dose of 928.2 mg/kg) and CMS, (5) fisetin (with a dose of 10 mg/kg) and CMS, and (6) amitriptyline (an antidepressant, with a dose of 3.25 mg/kg) and CMS as a comparison group. Chronic Mild Stress (CMS) method were used as induction of stress consisted of seven different stressors and assigned randomly for 35 days. Provision of treatment was made during the 14 days preparations on day 22 to day 35. At the end of treatments, all mice were assigned on FST test for immobility time measurements. Next, all mice were decapitated and the brains were isolated. Serotonin levels were measured using High Performance Liquid Chromatography (HPLC) with UV-visible light detector. The results showed that the immobility time of group mice which were given by the strawberries (928.2 mg/kg) and fisetin had shorter duration than the positive control group. Furthermore, the level of serotonin in the test group increased compared to CMS group. Corticosterone levels of treatment mice were increased significantly compared to non-stressed mice. Therefore, it can be concluded that strawberries are able to improve depressive symptoms by decreasing immobility time and increasing levels of serotonin compared with CMS group.

A Third-Generation Adaptive Statistical Iterative Reconstruction Technique: Phantom Study of Image Noise, Spatial Resolution, Lesion Detectability, and Dose Reduction Potential.

PubMed

Euler, André; Solomon, Justin; Marin, Daniele; Nelson, Rendon C; Samei, Ehsan

2018-06-01

The purpose of this study was to assess image noise, spatial resolution, lesion detectability, and the dose reduction potential of a proprietary third-generation adaptive statistical iterative reconstruction (ASIR-V) technique. A phantom representing five different body sizes (12-37 cm) and a contrast-detail phantom containing lesions of five low-contrast levels (5-20 HU) and three sizes (2-6 mm) were deployed. Both phantoms were scanned on a 256-MDCT scanner at six different radiation doses (1.25-10 mGy). Images were reconstructed with filtered back projection (FBP), ASIR-V with 50% blending with FBP (ASIR-V 50%), and ASIR-V without blending (ASIR-V 100%). In the first phantom, noise properties were assessed by noise power spectrum analysis. Spatial resolution properties were measured by use of task transfer functions for objects of different contrasts. Noise magnitude, noise texture, and resolution were compared between the three groups. In the second phantom, low-contrast detectability was assessed by nine human readers independently for each condition. The dose reduction potential of ASIR-V was estimated on the basis of a generalized linear statistical regression model. On average, image noise was reduced 37.3% with ASIR-V 50% and 71.5% with ASIR-V 100% compared with FBP. ASIR-V shifted the noise power spectrum toward lower frequencies compared with FBP. The spatial resolution of ASIR-V was equivalent or slightly superior to that of FBP, except for the low-contrast object, which had lower resolution. Lesion detection significantly increased with both ASIR-V levels (p = 0.001), with an estimated radiation dose reduction potential of 15% ± 5% (SD) for ASIR-V 50% and 31% ± 9% for ASIR-V 100%. ASIR-V reduced image noise and improved lesion detection compared with FBP and had potential for radiation dose reduction while preserving low-contrast detectability.

Ovarian activity in obese and nonobese women treated with three transdermal contraceptive patches delivering three different doses of ethinyl estradiol and levonorgestrel.

PubMed

Foegh, Marie; Archer, David F; Stanczyk, Frank Z; Rubin, Arkady; Mishell, Daniel R

2013-02-01

The effect of obesity on ovarian follicular suppression in women using low-estrogen dose contraceptive patches has not been determined. A Phase II, parallel-group, multicenter, three-cycle study evaluated three patches containing different ethinyl estradiol (EE) and levonorgestrel (LNG) doses. Serum levels of EE, LNG, sex hormone-binding globulin and progesterone were compared in 41 obese [body mass index (BMI) ≥30] and 75 nonobese (BMI <30) women. Suppression of ovulation during the luteal phase was dose dependent, with the highest dose (AG200-15) preventing progesterone increases in all women (cycles 2-3). In the follicular phase, the lowest-dose patch had the highest rate of increased progesterone in nonobese subjects. Progesterone levels ≥3.0 ng/mL in the follicular phase were more common in obese than nonobese women. AG200-15 suppresses ovulation in obese and nonobese women. All three patches found increased progesterone in the follicular phase, albeit more in obese versus nonobese women. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of medetomidine on serum glucose in cattle calves.

PubMed

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

2016-05-01

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

Efficacy of topotecan treatment on antioxidant enzymes and TBA-RS levels in submandibular glands of rabbits: an experimental study.

PubMed

Muluk, Nuray Bayar; Kisa, Uçler; Kaçmaz, Murat; Apan, Alpaslan; Koç, Can

2005-01-01

The aim of this study was to investigate the effects of topotecan (Hycamtin), a topoisomerase I inhibiting anticancer agent, on antioxidant enzymes (SOD, CAT, and GSH-Px) and TBA-RS values of the submandibular glands of the rabbits. The study was conveyed in two groups (Group I, II) and control with a total of 24 rabbits. Eight rabbits in group I received intravenous (i.v.) topotecan (0.25 mg/kg once daily) for 3 days. Eight rabbits in group II received i.v. topotecan (0.5 mg/kg once daily) for 3 days. On the 15th day after administration of topotecan, submandibular glands were removed and levels of the SOD, CAT, and GSH-Px and the TBA-RS in the submandibular glands of the rabbits were examined. SOD, CAT, and GSH-Px values were significantly higher in high-dose topotecan group compared to control group (P < 0.05). SOD and TBA-RS values were significantly higher in high-dose topotecan group compared to low-dose topotecan group (P < 0.05). It was concluded that, to prevent the hazardous effects of oxygen free radicals due to topotecan, antioxidant enzymes SOD, CAT, and GSH-Px were increased. The higher levels of the TBA-RS values in group II showed that permanent damage was present because of high-dose topotecan administration in the submandibular glands of the rabbits.

Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis.

PubMed

Ai, Si; Zheng, Jian; Chu, Ke-Dan; Zhang, Hong-Sheng

2015-06-01

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side-effects.However,the effects of Xingbi gel for the treatment of AR was investigated. We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p <0.01). Treatments with low-dose Xingbi gel, high-dose Xingbi gel, and budesonide significantly reduced the ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts as compared to untreated AR model guinea pigs (p <0.01). Xingbi gel alleviates AR in part through inhibiting LTE4 and IgE production and reducing eosinophilia in the nasal mucosa.

The Effects of Eucheuma cottonii on Signaling Pathway Inducing Mucin Synthesis in Rat Lungs Chronically Exposed to Particulate Matter 10 (PM10) Coal Dust

PubMed Central

Kania, Nia; Mayangsari, Elly; Tony, Frans; Wahyuni, Endang Sri; Widodo, M. Aris

2013-01-01

This study was aimed at investigating the effects of Eucheuma cottonii (EC) in oxidative stress and the signaling for mucin synthesis in rat lungs chronically exposed to coal dust. Coal dust with concomitant oral administration of ethanolic extract of EC at doses of 150 (EC150) or 300 mg/kg BW (EC300) compared to exposed to PM10 coal dust at doses of 6.25 (CD6.25), 12.5 (CD12.5), or 25 mg/m3 (CD25) (an hour daily for 6 months) and nonexposure group (control). The malondialdehyde (MDA), epidermal growth factor (EGF), transforming growth factor (TGF)-α, epidermal growth factor receptor (EGFR), and MUC5AC levels were determined in the lung. The administration of EC300 significantly (p < 0.05) reduced the MDA levels in groups exposed to all doses of coal dust compared to the respective coal dust-exposed nonsupplemented groups. Although not statistically significant,EC reduced the EGF levels and EGFR expressions in CD12.5 and CD25 groups and decreased the TGF-α, level and MUC5AC expression in CD25 group compared to the respective coal dust-exposed nonsupplemented groups. EC was able to decrease oxidative stress and was also able to decrease signaling for mucin synthesis, at least a part, via reducing the ligand in chronic coal dust exposure. PMID:24228027

Use of Explicit Instruction and Double-Dosing to Teach Ratios, Proportions, and Percentages to At-Risk Middle School Students

ERIC Educational Resources Information Center

Piper, Lisa; Marchand-Martella, Nancy; Martella, Ronald

2010-01-01

The purpose of this action research was to determine the level of improvement of middle school students who were low performers in a mathematics class (N = 8) and who received "explicit instruction" with "double dosing" compared to their peer group who received normal instruction (N = 49). Results showed that at-risk…

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

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

Low-dose Norfloxacin-treated leptospires induce less IL-1β release in J774A.1 cells following discrepant leptospiral gene expression.

PubMed

Cao, Yongguo; Xie, Xufeng; Zhang, Wenlong; Wu, Dianjun; Tu, Changchun

2018-06-01

Currently, accumulating evidence is challenging subtherapeutic therapy. Low-dose Norfloxacin (Nor) has been reported to suppress the immune response and worsen leptospirosis. In this study, we investigated the influence of low-dose Nor (0.03 μg/ml, 0.06 μg/ml, 0.125 μg/ml) on leptospiral gene expression and analyzed the immunomodulatory effects of low-dose Nor-treated leptospires in J774A.1 cells. To study the expression profiles of low-dose Nor-treated leptospires, we chose LipL71/LipL21 as reference genes determined by the geNorm applet in this experiment. The results showed that low-dose Nor up-regulated the expression of FlaB and inhibited the expression of 16S rRNA, LipL32, LipL41, Loa22, KdpA, and KdpB compared with the untreated leptospires. These results indicated that low-dose Nor could regulate leptospiral gene expression. Using RT-PCR, the gene expression of IL-1β and TNF-α in J774A.1 cells was detected. Nor-treated leptospires induced higher expression levels of both IL-1β and TNF-α. However, when analyzed by ELISA, the release of mature IL-1β was reduced compared with that observed in cells induced with no Nor-treated leptospires, although the TNF-α protein level showed no significant change. Our study indicated that the gene expression of leptospires could be modulated by low-dose Nor, which induced less IL-1β release in J774A.1 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

A longitudinal study of depression among middle-aged and senior patients initiating chronic opioid therapy.

PubMed

Von Korff, Michael; Shortreed, Susan M; LeResche, Linda; Saunders, Kathleen; Thielke, Stephen; Thakral, Manu; Rosenberg, Dori; Turner, Judith A

2017-03-15

Improved understanding how depressive symptoms change with sustained opioid use is needed. We prospectively assessed patients 45 years or older initiating chronic opioid therapy (COT) at baseline and at 4 and 12 months, differentiating recent COT initiators (n=748) and continuing users (n=468). Level of opioid use before 12-month follow-up was classified as regular/higher-dose, intermittent/lower-dose, or minimal/no use. Depressive symptoms were assessed using the Patient Health Questionnaire-8 (PHQ-8). Depressive symptoms decreased, on average, from baseline to 12 months regardless of level of opioid use. COT patients with regular/higher-dose compared to those with intermittent/lower-dose opioid use (who had similar pain outcomes) did not differ in PHQ-8 scores at 12 months (adjusted mean difference -0.14, 95% CI, -1.07, 0.78 for COT initiators). At 12 months, COT patients with intermittent/lower-dose use had higher adjusted PHQ-8 scores than did those with minimal/no opioid use (adjusted mean difference 0.77, 95% CI, 0.03-1.52 for COT initiators). However, 77% of patients who discontinued opioids cited improved pain as a reason for discontinuation, while 21% cited negative emotional effects of opioids as a reason for discontinuation. Discontinuation was more common among persons who, at baseline, attributed 3 or more depressive symptoms to opioid use. Results are relevant to older COT patients receiving low to moderate opioid doses. Depressive symptoms did not increase with sustained opioid use. Depressive symptoms were not higher with regular/higher-dose compared to intermittent/lower-dose use. Persons who perceived negative effects of opioids on emotions more often discontinued their use. Copyright © 2017. Published by Elsevier B.V.

Assessment of potential advantages of relevant ions for particle therapy: a model based study.

PubMed

Grün, Rebecca; Friedrich, Thomas; Krämer, Michael; Zink, Klemens; Durante, Marco; Engenhart-Cabillic, Rita; Scholz, Michael

2015-02-01

Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ((12)C), helium ((4)He), and protons ((1)H) for different treatment scenarios. A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratio (PER) was determined for the physical dose (PERPHY S), the RBE (PERRBE), and the RBE-weighted dose (PERBIO) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PERRBE for the analyzed configurations. Due to the fact that protons show a somewhat better PERPHY S compared to helium and carbon ions whereas helium shows a higher PERRBE compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PERRBE with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PERBIO is observed when using an orthogonal field configuration for carbon ions as compared to opposing fields. In contrast, for protons, the PERBIO is almost independent on the field configuration. Concerning the artificial lateral OAR, the volume receiving 20% of the prescribed RBE-weighted dose (V20) was reduced by over 35% using helium ions and by over 40% using carbon ions compared to protons. The analysis of the patient plan showed that protons, helium, and carbon ions are similar in terms of target coverage whereas the dose to the surrounding tissue is increasing from carbon ions toward protons. The mean dose to the brain stem can be reduced by more than 55% when using helium ions and by further 25% when using carbon ions instead of protons. The comparison of the PERRBE and PERPHY S of the three ion types suggests a strong dependence of the advantages of the three ions on the dose-level, tissue type, and field configuration. In terms of conformity, i.e., dose to the normal tissue, a clear gain is expected using carbon or helium ions compared to protons.

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.

Dosimetric Comparison of Bone Marrow-Sparing Intensity-Modulated Radiotherapy Versus Conventional Techniques for Treatment of Cervical Cancer

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

Mell, Loren K.; Tiryaki, Hanifi; Ahn, Kang-Hyun

2008-08-01

Purpose: To compare bone marrow-sparing intensity-modulated pelvic radiotherapy (BMS-IMRT) with conventional (four-field box and anteroposterior-posteroanterior [AP-PA]) techniques in the treatment of cervical cancer. Methods and Materials: The data from 7 cervical cancer patients treated with concurrent chemotherapy and IMRT without BMS were analyzed and compared with data using four-field box and AP-PA techniques. All plans were normalized to cover the planning target volume with the 99% isodose line. The clinical target volume consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprisedmore » the lumbosacral spine and ilium and the ischium, pubis, and proximal femora (lower pelvis bone marrow). Dose-volume histograms for the planning target volume and normal tissues were compared for BMS-IMRT vs. four-field box and AP-PA plans. Results: BMS-IMRT was superior to the four-field box technique in reducing the dose to the PBM, small bowel, rectum, and bladder. Compared with AP-PA plans, BMS-IMRT reduced the PBM volume receiving a dose >16.4 Gy. BMS-IMRT reduced the volume of ilium, lower pelvis bone marrow, and bowel receiving a dose >27.7, >18.7, and >21.1 Gy, respectively, but increased dose below these thresholds compared with the AP-PA plans. BMS-IMRT reduced the volume of lumbosacral spine bone marrow, rectum, small bowel, and bladder at all dose levels in all 7 patients. Conclusion: BMS-IMRT reduced irradiation of PBM compared with the four-field box technique. Compared with the AP-PA technique, BMS-IMRT reduced lumbosacral spine bone marrow irradiation and reduced the volume of PBM irradiated to high doses. Therefore BMS-IMRT might reduce acute hematologic toxicity compared with conventional techniques.« less

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

PubMed Central

Midgley, John E M; Larisch, Rolf; Dietrich, Johannes W; Hoermann, Rudolf

2015-01-01

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4–T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23–29 and >29 nmol/s revealed an increasing FT3–FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3–TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases. PMID:26335522

WE-FG-207B-07: Feasibility of Low Dose Lung Cancer Screening with a Whole-Body Photon Counting CT: First Human Results

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

Symons, R; Cork, T; Folio, L

2016-06-15

Purpose: To evaluate the feasibility of using a whole-body photon counting detector (PCD) CT scanner for low dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Methods: Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom and 2 human volunteers were acquired. Phantom images were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp), while human images were acquired at vendor recommended low-dose lung cancer screening settings. EID and PCD images were compared for quantitative Hounsfield unit accuracy, noise levels, and contrast-to-noisemore » ratios (CNR) for detection of ground-glass nodules (GGNs) and emphysema. Results: The PCD Hounsfield unit accuracy was better for water at all scan parameters, and for lung, GGN and emphysema equivalent regions of interest (ROIs) at 1.5 and 0.75 mGy. PCD attenuation accuracy was more consistent for all scan parameters (all P<0.01), while Hounsfield units for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P<0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2±0.3 vs 15.8±0.2, P=0.03; 16.1±0.3 vs 18.0±0.4, P=0.003; and 16.1±0.3 vs 17.9±0.3, P=0.001, respectively), resulting in superior CNR for the detection of GGNs and emphysema at 100 and 80 kVp. Significantly lower PCD noise levels were confirmed in volunteer images. Conclusion: PCD provided better Hounsfield unit accuracy for lung, ground-glass, and emphysema-equivalent foams at 1.5 and 0.75 mGy with less variability than EID. Additionally, PCD showed less noise, and higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.« less

SU-F-T-195: Systematic Constraining of Contralateral Parotid Gland Led to Improved Dosimetric Outcomes for Multi-Field Optimization with Scanning Beam Proton Therapy: Promising Results From a Pilot Study in Patients with Base of Tongue Carcinoma

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

Wu, R; Liu, A; Poenisch, F

Purpose: Treatment planning for Intensity Modulated Proton Therapy (IMPT) for head and neck cancer is time-consuming due to the large number of organs-at-risk (OAR) to be considered. As there are many competing objectives and also wide range of acceptable OAR constraints, the final approved plan may not be most optimal for the given structures. We evaluated the dose reduction to the contralateral parotid by implementing standardized constraints during optimization for scanning beam proton therapy planning. Methods: Twenty-four (24) consecutive patients previously treated for base of tongue carcinoma were retrospectively selected. The doses were 70Gy, 63Gy and 57Gy (SIB in 33more » fractions) for high-, intermediate-, and standard-risk clinical target volumes (CTV), respectively; the treatment included bilateral neck. Scanning beams using MFO with standardized bilateral anterior oblique and PA fields were applied. New plans where then developed and optimized by employing additional contralateral parotid constraints at multiple defined dose levels. Using a step-wise iterative process, the volume-based constraints at each level were then further reduced until known target coverages were compromised. The newly developed plans were then compared to the original clinically approved plans using paired student t-testing. Results: All 24 newly optimized treatment plans maintained initial plan quality as compared to the approved plans, and the 98% prescription dose coverage to the CTV’s were not compromised. Representative DVH comparison is shown in FIGURE 1. The contralateral parotid doses were reduced at all levels of interest when systematic constraints were applied to V10, V20, V30 and V40Gy (All P<0.0001; TABLE 1). Overall, the mean contralateral parotid doses were reduced by 2.26 Gy on average, a ∼13% relative improvement. Conclusion: Applying systematic and volume-based contralateral parotid constraints for IMPT planning significantly reduced the dose at all dosimetric levels for patients with base of tongue cancer.« less

Monte Carlo simulations of the dose from imaging with GE eXplore 120 micro-CT using GATE

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

Bretin, Florian; Bahri, Mohamed Ali; Luxen, André

Purpose: Small animals are increasingly used as translational models in preclinical imaging studies involving microCT, during which the subjects can be exposed to large amounts of radiation. While the radiation levels are generally sublethal, studies have shown that low-level radiation can change physiological parameters in mice. In order to rule out any influence of radiation on the outcome of such experiments, or resulting deterministic effects in the subjects, the levels of radiation involved need to be addressed. The aim of this study was to investigate the radiation dose delivered by the GE eXplore 120 microCT non-invasively using Monte Carlo simulationsmore » in GATE and to compare results to previously obtained experimental values. Methods: Tungsten X-ray spectra were simulated at 70, 80, and 97 kVp using an analytical tool and their half-value layers were simulated for spectra validation against experimentally measured values of the physical X-ray tube. A Monte Carlo model of the microCT system was set up and four protocols that are regularly applied to live animal scanning were implemented. The computed tomography dose index (CTDI) inside a PMMA phantom was derived and multiple field of view acquisitions were simulated using the PMMA phantom, a representative mouse and rat. Results: Simulated half-value layers agreed with experimentally obtained results within a 7% error window. The CTDI ranged from 20 to 56 mGy and closely matched experimental values. Derived organ doses in mice reached 459 mGy in bones and up to 200 mGy in soft tissue organs using the highest energy protocol. Dose levels in rats were lower due to the increased mass of the animal compared to mice. The uncertainty of all dose simulations was below 14%. Conclusions: Monte Carlo simulations proved a valuable tool to investigate the 3D dose distribution in animals from microCT. Small animals, especially mice (due to their small volume), receive large amounts of radiation from the GE eXplore 120 microCT, which might alter physiological parameters in a longitudinal study setup.« less

SU-E-T-48: A Multi-Institutional Study of Independent Dose Verification for Conventional, SRS and SBRT

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

Takahashi, R; Kamima, T; Tachibana, H

2015-06-15

Purpose: To show the results of a multi-institutional study of the independent dose verification for conventional, Stereotactic radiosurgery and body radiotherapy (SRS and SBRT) plans based on the action level of AAPM TG-114. Methods: This study was performed at 12 institutions in Japan. To eliminate the bias of independent dose verification program (Indp), all of the institutions used the same CT-based independent dose verification software (Simple MU Analysis, Triangle Products, JP) with the Clarkson-based algorithm. Eclipse (AAA, PBC), Pinnacle{sup 3} (Adaptive Convolve) and Xio (Superposition) were used as treatment planning system (TPS). The confidence limits (CL, Mean±2SD) for 18 sitesmore » (head, breast, lung, pelvis, etc.) were evaluated in comparison in dose between the TPS and the Indp. Results: A retrospective analysis of 6352 treatment fields was conducted. The CLs for conventional, SRS and SBRT were 1.0±3.7 %, 2.0±2.5 % and 6.2±4.4 %, respectively. In conventional plans, most of the sites showed within 5 % of TG-114 action level. However, there were the systematic difference (4.0±4.0 % and 2.5±5.8 % for breast and lung, respectively). In SRS plans, our results showed good agreement compared to the action level. In SBRT plans, the discrepancy between the Indp was variable depending on dose calculation algorithms of TPS. Conclusion: The impact of dose calculation algorithms for the TPS and the Indp affects the action level. It is effective to set the site-specific tolerances, especially for the site where inhomogeneous correction can affect dose distribution strongly.« less

Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test

PubMed Central

Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen

2013-01-01

Introduction Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Methods Forty male Wistar rats weighing 180–220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Results Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) Conclusion The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats. PMID:22970723

Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test.

PubMed

Yang, Chun; Hu, Yi-Min; Zhou, Zhi-Qiang; Zhang, Guang-Fen; Yang, Jian-Jun

2013-03-01

Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR). Forty male Wistar rats weighing 180-220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels. Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses) The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats.

Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure

PubMed Central

Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.; Smith, Martyn T.

2014-01-01

Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. PMID:24786086

Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

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

Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov; Herman, Eugene H.; Moland, Carrie L.

2013-01-01

Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F{sub 1} mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively.more » Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F{sub 1} mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.« less

TH-A-19A-06: Site-Specific Comparison of Analytical and Monte Carlo Based Dose Calculations

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

Schuemann, J; Grassberger, C; Paganetti, H

2014-06-15

Purpose: To investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict dose distributions and to verify currently used uncertainty margins in proton therapy. Methods: Dose distributions predicted by an analytical pencilbeam algorithm were compared with Monte Carlo simulations (MCS) using TOPAS. 79 complete patient treatment plans were investigated for 7 disease sites (liver, prostate, breast, medulloblastoma spine and whole brain, lung and head and neck). A total of 508 individual passively scattered treatment fields were analyzed for field specific properties. Comparisons based on target coverage indices (EUD, D95, D90 and D50)more » were performed. Range differences were estimated for the distal position of the 90% dose level (R90) and the 50% dose level (R50). Two-dimensional distal dose surfaces were calculated and the root mean square differences (RMSD), average range difference (ARD) and average distal dose degradation (ADD), the distance between the distal position of the 80% and 20% dose levels (R80- R20), were analyzed. Results: We found target coverage indices calculated by TOPAS to generally be around 1–2% lower than predicted by the analytical algorithm. Differences in R90 predicted by TOPAS and the planning system can be larger than currently applied range margins in proton therapy for small regions distal to the target volume. We estimate new site-specific range margins (R90) for analytical dose calculations considering total range uncertainties and uncertainties from dose calculation alone based on the RMSD. Our results demonstrate that a reduction of currently used uncertainty margins is feasible for liver, prostate and whole brain fields even without introducing MC dose calculations. Conclusion: Analytical dose calculation algorithms predict dose distributions within clinical limits for more homogeneous patients sites (liver, prostate, whole brain). However, we recommend treatment plan verification using Monte Carlo simulations for patients with complex geometries.« less

[Experimental study on avascular necrosis of femoral head in chickens induced by different glucocorticoides].

PubMed

Xiao, Chun-Sheng; Lin, Na; Lin, Shi-Fu; Wan, Rong; Chen, Wei-Heng

2010-03-01

To study the effects of Methylprednisolone and Dexamethasone on the avascular necrosis of femoral head in chickens. Thirty-six chickens were randomly divided into 6 groups (n = 6): control group (group A), Methylprednisolone low dose group (group B), Methylprednisolone large dose group (group C), small dose Dexamethasone and horse serum group (group D), middle dose Dexamethasone and horse serum group (group E), and Dexamethasone large dose group (group F). On the 6th and 12th weeks, blood samples were obtained to determine the level of total cholesterol triglyeride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL). On the 12th week, femoral heads were taken off. Paraffin tissue sections were prepared to detect histopathologic change with hematoxylin and eosin staining. On the 6th week, compared with group A, the level of CHO increased significantly in group C and group F (P < 0.05), and TG increased in group B, C and group E, while HDL decreased in group B, C and group E. On the 12th week, the level of TG and CHO increased in group B, C, E and group F, and HDL decreased in group C, D and group E (P < 0.05). LDL was not detected in most chickens. The ratio of empty lacuna was higher in group C and group E compared with those of the control group (P < 0.05). Methylprednisolone is easier to induce osteonecrosis of femoral head than Dexamethasone. The condition of metabolic disorder in blood may be the basic pathomechanism of steroid-induced necrosis of femoral head.

Accelerated hematopoietic syndrome after radiation doses bridging hematopoietic (H-ARS) and gastrointestinal (GI-ARS) acute radiation syndrome: early hematological changes and systemic inflammatory response syndrome in minipig.

PubMed

Moroni, Maria; Elliott, Thomas B; Deutz, Nicolaas E; Olsen, Cara H; Owens, Rossitsa; Christensen, Christine; Lombardini, Eric D; Whitnall, Mark H

2014-05-01

To characterize acute radiation syndrome (ARS) sequelae at doses intermediate between the bone marrow (H-ARS) and full gastrointestinal (GI-ARS) syndrome. Male minipigs, approximately 5 months old, 9-12 kg in weight, were irradiated with Cobalt-60 (total body, bilateral gamma irradiation, 0.6 Gy/min). Endpoints were 10-day survival, gastrointestinal histology, plasma citrulline, bacterial translocation, vomiting, diarrhea, vital signs, systemic inflammatory response syndrome (SIRS), febrile neutropenia (FN). We exposed animals to doses (2.2-5.0 Gy) above those causing H-ARS (1.6-2.0 Gy), and evaluated development of ARS. Compared to what was observed during H-ARS (historical data: Moroni et al. 2011a , 2011c ), doses above 2 Gy produced signs of increasingly severe pulmonary damage, faster deterioration of clinical conditions, and faster increases in levels of C-reactive protein (CRP). In the range of 4.6-5.0 Gy, animals died by day 9-10; signs of the classic GI syndrome, as measured by diarrhea, vomiting and bacterial translocation, did not occur. At doses above 2 Gy we observed transient reduction in circulating citrulline levels, and animals exhibited earlier depletion of blood elements and faster onset of SIRS and FN. An accelerated hematopoietic subsyndrome (AH-ARS) is observed at radiation doses between those producing H-ARS and GI-ARS. It is characterized by early onset of SIRS and FN, and greater lung damage, compared to H-ARS.

Evidence of dose saving in routine CT practice using iterative reconstruction derived from a national diagnostic reference level survey.

PubMed

Thomas, P; Hayton, A; Beveridge, T; Marks, P; Wallace, A

2015-09-01

To assess the influence and significance of the use of iterative reconstruction (IR) algorithms on patient dose in CT in Australia. We examined survey data submitted to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) National Diagnostic Reference Level Service (NDRLS) during 2013 and 2014. We compared median survey dose metrics with categorization by scan region and use of IR. The use of IR results in a reduction in volume CT dose index of between 17% and 44% and a reduction in dose-length product of between 14% and 34% depending on the specific scan region. The reduction was highly significant (p < 0.001, Wilcoxon rank-sum test) for all six scan regions included in the NDRLS. Overall, 69% (806/1167) of surveys included in the analysis used IR. The use of IR in CT is achieving dose savings of 20-30% in routine practice in Australia. IR appears to be widely used by participants in the ARPANSA NDRLS with approximately 70% of surveys submitted employing this technique. This study examines the impact of the use of IR on patient dose in CT on a national scale.

High dynamic range CMOS-based mammography detector for FFDM and DBT

NASA Astrophysics Data System (ADS)

Peters, Inge M.; Smit, Chiel; Miller, James J.; Lomako, Andrey

2016-03-01

Digital Breast Tomosynthesis (DBT) requires excellent image quality in a dynamic mode at very low dose levels while Full Field Digital Mammography (FFDM) is a static imaging modality that requires high saturation dose levels. These opposing requirements can only be met by a dynamic detector with a high dynamic range. This paper will discuss a wafer-scale CMOS-based mammography detector with 49.5 μm pixels and a CsI scintillator. Excellent image quality is obtained for FFDM as well as DBT applications, comparing favorably with a-Se detectors that dominate the X-ray mammography market today. The typical dynamic range of a mammography detector is not high enough to accommodate both the low noise and the high saturation dose requirements for DBT and FFDM applications, respectively. An approach based on gain switching does not provide the signal-to-noise benefits in the low-dose DBT conditions. The solution to this is to add frame summing functionality to the detector. In one X-ray pulse several image frames will be acquired and summed. The requirements to implement this into a detector are low noise levels, high frame rates and low lag performance, all of which are unique characteristics of CMOS detectors. Results are presented to prove that excellent image quality is achieved, using a single detector for both DBT as well as FFDM dose conditions. This method of frame summing gave the opportunity to optimize the detector noise and saturation level for DBT applications, to achieve high DQE level at low dose, without compromising the FFDM performance.

Assessment of eye lens doses for workers during interventional radiology procedures.

PubMed

Urboniene, A; Sadzeviciene, E; Ziliukas, J

2015-07-01

The assessment of eye lens doses for workers during interventional radiology (IR) procedures was performed using a new eye lens dosemeter. In parallel, the results of routine individual monitoring were analysed and compared with the results obtained from measurements with a new eye lens dosemeter. The eye lens doses were assessed using Hp(3) measured at the level of the eyes and were compared with Hp(10) measured with the whole-body dosemeter above the lead collar. The information about use of protective measures, the number of performed interventional procedures per month and their fluoroscopy time was also collected. The assessment of doses to the lens of the eye was done for 50 IR workers at 9 Lithuanian hospitals for the period of 2012-2013. If the use of lead glasses is not taken into account, the estimated maximum annual dose equivalent to the lens of the eye was 82 mSv. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Is ICRP guidance on the use of reference levels consistent?

PubMed

Hedemann-Jensen, Per; McEwan, Andrew C

2011-12-01

In ICRP 103, which has replaced ICRP 60, it is stated that no fundamental changes have been introduced compared with ICRP 60. This is true except that the application of reference levels in emergency and existing exposure situations seems to be applied inconsistently, and also in the related publications ICRP 109 and ICRP 111. ICRP 103 emphasises that focus should be on the residual doses after the implementation of protection strategies in emergency and existing exposure situations. If possible, the result of an optimised protection strategy should bring the residual dose below the reference level. Thus the reference level represents the maximum acceptable residual dose after an optimised protection strategy has been implemented. It is not an 'off-the-shelf item' that can be set free of the prevailing situation. It should be determined as part of the process of optimising the protection strategy. If not, protection would be sub-optimised. However, in ICRP 103 some inconsistent concepts have been introduced, e.g. in paragraph 279 which states: 'All exposures above or below the reference level should be subject to optimisation of protection, and particular attention should be given to exposures above the reference level'. If, in fact, all exposures above and below reference levels are subject to the process of optimisation, reference levels appear superfluous. It could be considered that if optimisation of protection below a fixed reference level is necessary, then the reference level has been set too high at the outset. Up until the last phase of the preparation of ICRP 103 the concept of a dose constraint was recommended to constrain the optimisation of protection in all types of exposure situations. In the final phase, the term 'dose constraint' was changed to 'reference level' for emergency and existing exposure situations. However, it seems as if in ICRP 103 it was not fully recognised that dose constraints and reference levels are conceptually different. The use of reference levels in radiological protection is reviewed. It is concluded that the recommendations in ICRP 103 and related ICRP publications seem to be inconsistent regarding the use of reference levels in existing and emergency exposure situations.

Early diagnosis and treatment of steroid-induced diabetes mellitus in patients with rheumatoid arthritis and other connective tissue diseases.

PubMed

Ito, Satoshi; Ogishima, Hiroshi; Kondo, Yuya; Sugihara, Makoto; Hayashi, Taichi; Chino, Yusuke; Goto, Daisuke; Matsumoto, Isao; Sumida, Takayuki

2014-01-01

To reveal how often patients with rheumatoid arthritis (RA) or any of other connective tissue diseases (CTDs) who take prednisolone (PSL) manifest postprandial hyperglycemia, and to evaluate the effects of divided daily dose administration of PSL, and of acarbose and nateglinide, on RA patients. The blood sugar (BS) levels of the patients were measured after meals. For in-patients who showed postprandial hyperglycemia, the daily dose of PSL was divided and nateglinide and/or acarbose were/was added if their BS levels did not improve sufficiently. The patients with BS levels that were well controlled for three months were compared with the patients with poorly controlled BS levels. The BS levels of 78 patients, including 16 patients with diabetes mellitus (DM), were measured after meals, and 27 of them were newly diagnosed with DM. Five of 14 patients who took a steady dose of PSL showed high BS levels after lunch (over 200 mg/dl) without elevated HbA1c. The combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia significantly. The period from the start of PSL administration to intervention was significantly longer in patients with good control at three months than the corresponding period in those with poor control. The prevalence of postprandial hyperglycemia was high in patients with RA/CTD taking PSL; accordingly, measurement of the BS level after each meal was valuable. Combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia.

Image perception by expert readers as a function of patient skin entrance dose levels in digital radiography

NASA Astrophysics Data System (ADS)

Lehnert, T.; Korkusuz, H.; Khan, F.; Vogl, T. J.; Mack, M. G.

2008-03-01

In this study, image quality was based on required clinical criteria, in order to investigate to what degree entrance dose could be lowered and what kind of added filtration can be used without impinging on radiologist confidence levels in diagnosing. Images were taken of extremities from a cadaver using stepwise decreasing dose levels and variation of added filtration (no filtration, aluminum, aluminum/copper) under digital projection radiography (Kodak DirectView DR7500). The starting point dose level for all body parts imaged was the current x-ray technique. Two experienced and two resident radiologists were presented the images in a blinded fashion and rated each with an image quality score from 1 to 9 indicated very satisfied and 1 as very unsatisfied indicating loss of diagnostic value. The readers were not aware of which dose level and added filtration corresponded to which image. Dose levels considered were 100%, 75%, 50% and 25% of the normal and customary x-ray techniques used for the particular body part and projection. Images were reviewed on a clinical diagnostic workstation with no time limits imposed. Readers were also able to change the image presentation by adjusting the window width and level. Without added filtration image quality mean score was rated with 6.3 (dose level 100%), 6.2 (dose level 75%), 5.3 (dose level 50%) and with 4.4 (dose level 25%). An added aluminum filtration induced an image quality mean score of 6.3 (dose level 100%), 6.0 (dose level 75%), 5.1 (dose level 50%) and of 4.2 (dose level 25%). Using aluminum/copper filtration image quality mean score was rated with 6.0 (dose level 100%), 6.1 (dose level 75%), 5.0 (dose level 50%) and with 3.8 (dose level 25%). Regardless of the added filtration a differentiation between dose levels 100% and 75% was possible in 38.9%, between dose levels 75% and 50% in 66.7%, and between dose levels 50% and 25% in 70.0% of the cases. It is possible, in the case of extremities, to lower entrance doses up to 75 % of the normal value, a reduction of 25% in dose, under simultaneous use of added aluminum or aluminum/copper filtration, without comprising the diagnostic value required.

Randomized comparison of operator radiation exposure comparing transradial and transfemoral approach for percutaneous coronary procedures: rationale and design of the minimizing adverse haemorrhagic events by TRansradial access site and systemic implementation of angioX - RAdiation Dose study (RAD-MATRIX).

PubMed

Sciahbasi, Alessandro; Calabrò, Paolo; Sarandrea, Alessandro; Rigattieri, Stefano; Tomassini, Francesco; Sardella, Gennaro; Zavalloni, Dennis; Cortese, Bernardo; Limbruno, Ugo; Tebaldi, Matteo; Gagnor, Andrea; Rubartelli, Paolo; Zingarelli, Antonio; Valgimigli, Marco

2014-06-01

Radiation absorbed by interventional cardiologists is a frequently under-evaluated important issue. Aim is to compare radiation dose absorbed by interventional cardiologists during percutaneous coronary procedures for acute coronary syndromes comparing transradial and transfemoral access. The randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial has been designed to compare the clinical outcome of patients with acute coronary syndromes treated invasively according to the access site (transfemoral vs. transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected experienced interventional cardiologists involved in this study have been equipped with dedicated thermoluminescent dosimeters to evaluate the radiation dose absorbed during transfemoral or right transradial or left transradial access. For each access we evaluate the radiation dose absorbed at wrist, at thorax and at eye level. Consequently the operator is equipped with three sets (transfemoral, right transradial or left transradial access) of three different dosimeters (wrist, thorax and eye dosimeter). Primary end-point of the study is the procedural radiation dose absorbed by operators at thorax. An important secondary end-point is the procedural radiation dose absorbed by operators comparing the right or left radial approach. Patient randomization is performed according to the MATRIX protocol for the femoral or radial approach. A further randomization for the radial approach is performed to compare right and left transradial access. The RAD-MATRIX study will probably consent to clarify the radiation issue for interventional cardiologist comparing transradial and transfemoral access in the setting of acute coronary syndromes. Copyright © 2014 Elsevier Inc. All rights reserved.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

PubMed

Ludvigsson, Johnny; Krisky, David; Casas, Rosaura; Battelino, Tadej; Castaño, Luis; Greening, James; Kordonouri, Olga; Otonkoski, Timo; Pozzilli, Paolo; Robert, Jean-Jacques; Veeze, Henk J; Palmer, Jerry; Samuelsson, Ulf; Elding Larsson, Helena; Åman, Jan; Kärdell, Gunilla; Neiderud Helsingborg, Jan; Lundström, Göran; Albinsson, Eva; Carlsson, Annelie; Nordvall, Maria; Fors, Hans; Arvidsson, Carl-Göran; Edvardson, Stig; Hanås, Ragnar; Larsson, Karin; Rathsman, Björn; Forsgren, Henrik; Desaix, Helena; Forsander, Gun; Nilsson, Nils-Östen; Åkesson, Carl-Göran; Keskinen, Päivi; Veijola, Riitta; Talvitie, Timo; Raile, Klemens; Kapellen, Thomas; Burger, Walter; Neu, Andreas; Engelsberger, Ilse; Heidtmann, Bettina; Bechtold, Suzanne; Leslie, David; Chiarelli, Francesco; Cicognani, Alesandro; Chiumello, Giuseppe; Cerutti, Franco; Zuccotti, Gian Vincenzo; Gomez Gila, Ana; Rica, Itxaso; Barrio, Raquel; Clemente, Maria; López Garcia, Maria José; Rodriguez, Mercedes; Gonzalez, Isabel; Lopez, Juan Pedro; Oyarzabal, Mirentxu; Reeser, H M; Nuboer, Roos; Stouthart, Pauline; Bratina, Natasa; Bratanic, Nina; de Kerdanet, Marc; Weill, Jacques; Ser, Nicole; Barat, Pascal; Bertrand, Anne Marie; Carel, Jean-Claude; Reynaud, Rachel; Coutant, Regis; Baron, Sabine

2012-02-02

The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).

The flame-retardant BDE-99 dose-dependently affects viral replication in CVB3-infected mice.

PubMed

Lundgren, Magnus; Darnerud, Per Ola; Ilbäck, Nils-Gunnar

2013-06-01

The flame retardant component 2,2',4,4',5-penta-BDE (BDE-99) is found in the environment and in human tissues and fluids. In mice the common human coxsackievirus B3 (CVB3) infection has been shown to change the tissue distribution of BDE-99. We now investigate how CVB3 infection in mice affects liver uptake of (14)C at two doses of radiolabelled BDE-99, and whether increased tissue levels are related to changed virus replication and gene expression of the proinflammatory chemokine monocyte chemoattractant protein-1 (MCP-1). Mice were infected on day 0, orally treated either with 200μg or 20mg (14)C-BDE-99/kgbw on day 1, and euthanised on day 3. Serum and liver levels of (14)C-BDE-99, as well as virus levels and gene expressions of MCP-1 in the liver, were measured. In non-infected mice, there was a dose-dependent uptake of BDE-99 in both liver and serum, and in infected animals the liver BDE-99 levels was further increased. When comparing infected mice exposed to the two BDE-99 doses, the higher BDE dose resulted in increased virus amounts in the liver, and decreased infection-induced expression of MCP-1. Consequently, a high enough dose/tissue concentration of BDE-99 may result in a disturbed mobilisation of immune cells into infected tissues that could explain higher virus titres and a possibly altered clinical course of the disease. Moreover, the fact that CVB3 infection increased the BDE-99 levels in liver but not in serum may impair the risk assessment of polybrominated diphenyl ethers (PBDEs) in subclinical and clinically infected individuals, as serum levels is the common marker of exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reference dosimetry using radiochromic film

PubMed Central

Girard, Frédéric; Bouchard, Hugo

2012-01-01

The objectives of this study are to identify and quantify factors that influence radiochromic film dose response and to determine whether such films are suitable for reference dosimetry. The influence of several parameters that may introduce systematic dose errors when performing reference dose measurements were investigated. The effect of the film storage temperature was determined by comparing the performance of three lots of GAFCHROMIC EBT2 films stored at either 4°C or room temperature. The effect of high (>80%) or low (<20%) relative humidity was also determined. Doses measured in optimal conditions with EBT and EBT2 films were then compared with an A12 ionization chamber measurement. Intensity‐modulated radiation therapy quality controls using EBT2 films were also performed in reference dose. The results obtained using reference dose measurements were compared with those obtained using relative dose measurements. Storing the film at 4°C improves the stability of the film over time, but does not eliminate the noncatalytic film development, seen as a rise in optical density over time in the absence of radiation. Relative humidity variations ranging from 80% to 20% have a strong impact on the optical density and could introduce dose errors of up to 15% if the humidity were not controlled during the film storage period. During the scanning procedure, the film temperature influences the optical density that is measured. When controlling for these three parameters, the dose differences between EBT or EBT2 and the A12 chamber are found to be within ±4% (2σ level) over a dose range of 20–350 cGy. Our results also demonstrate the limitation of the Anisotropic Analytical Algorithm for dose calculation of highly modulated treatment plans. PACS numbers: 87.55.Qr; 87.56.Fc PMID:23149793

Round-robin study of arsenic implant dose measurement in silicon by SIMS

NASA Astrophysics Data System (ADS)

Simons, D.; Kim, K.; Benbalagh, R.; Bennett, J.; Chew, A.; Gehre, D.; Hasegawa, T.; Hitzman, C.; Ko, J.; Lindstrom, R.; MacDonald, B.; Magee, C.; Montgomery, N.; Peres, P.; Ronsheim, P.; Yoshikawa, S.; Schuhmacher, M.; Stockwell, W.; Sykes, D.; Tomita, M.; Toujou, F.; Won, J.

2006-07-01

An international round-robin study was undertaken under the auspices of ISO TC201/SC6 to determine the best analytical conditions and the level of interlaboratory agreement for the determination of the implantation dose of arsenic in silicon by secondary ion mass spectrometry (SIMS). Fifteen SIMS laboratories, as well as two laboratories that performed low energy electron-induced X-ray emission spectrometry (LEXES) and one that made measurements by instrumental neutron activation analysis (INAA) were asked to determine the implanted arsenic doses in three unknown samples using as a comparator NIST Standard Reference Material ® 2134. The use of a common reference material by all laboratories resulted in better interlaboratory agreement than was seen in a previous round-robin that lacked a common comparator. The relative standard deviation among laboratories was less than 4% for the medium-dose sample, but several percent larger for the low- and high-dose samples. The high-dose sample showed a significant difference between point-by-point and average matrix normalization because the matrix signal decreased in the vicinity of the implant peak, as observed in a previous study. The dose from point-by-point normalization was in close agreement with that determined by INAA. No clear difference in measurement repeatability was seen when comparing Si 2- and Si 3- as matrix references with AsSi -.

Intermittent minodronic acid treatment with sufficient bone resorption inhibition prevents reduction in bone mass and strength in ovariectomized rats with established osteopenia comparable with daily treatment.

PubMed

Kimoto, Aishi; Tanaka, Makoto; Nozaki, Kazutoshi; Mori, Masamichi; Fukushima, Shinji; Mori, Hiroshi; Shiroya, Tsutomu; Nakamura, Toshitaka

2013-07-01

This study examined and compared the effects of four-week intermittent and daily administrations of minodronic acid, a highly potent nitrogen-containing bisphosphonate, on bone mineral density (BMD), bone strength, bone turnover, and histomorphometry on established osteopenia in ovariectomized (OVX) rats. Fourteen-week-old female F344 rats were OVX or sham-operated. At 12 weeks post surgery, minodronic acid was orally administered once every 4 weeks at 0.2, 1, and 5 mg/kg and once daily at 0.006, 0.03, and 0.15 mg/kg for 12 months. The total dosing amount was comparable between the two dosing regimens. The levels of urinary deoxypyridinoline and serum osteocalcin were measured to assess bone turnover. BMD as assessed via dual-energy X-ray absorptiometry, bone structure and dynamical changes in vertebral trabecula and biomechanical properties were measured ex vivo at 12 months to assess bone content and material properties. Minodronic acid dose-dependently ameliorated the decrease in BMD of lumbar vertebrae and the femur in both treatment regimens similarly. Minodronic acid suppressed elevated urinary levels of deoxypyridinoline, a bone resorption marker, and reduced the serum levels of osteocalcin, a bone formation marker. In the mechanical test at 12 months of treatment, minodronic acid dose-dependently ameliorated the reduction in bone strength in femur and vertebral body. There is no significant difference in parameters between the two regimens except maximal load of lower doses in lumbar vertebral body and absorption energy of middle doses in femur. With these parameters with significant differences, values of the intermittent regimen were significantly lower than that of daily repeated regimen. Bone histomorphometric analysis of the lumbar vertebral body showed that minodronic acid significantly ameliorated the decrease in bone mass, trabecular thickness and number, and the increase in trabecular separation, bone resorption indices (Oc.S/BS and N.Oc/BS), and bone formation indices (BFR/BS, MAR and OV/BV) in both regimens. Minodronic acid suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, thereby improving the deterioration of bone quality under osteoporotic disease conditions regardless of the regimen. In conclusion, a four-week intermittent treatment of minodronic acid suppressed increased bone resorption as daily treatment when considering the total administered dose in OVX rats with established osteopenia. The improvement of microarchitectural destruction in low dose of intermittent treatment was weaker than that observed in a daily repeated regimen; however the effects of high and middle doses of intermittent treatment were equivalent to that observed in daily repeated regimen accompanied by sufficient bone resorption inhibition in rats. These findings suggest that minodronic acid at an appropriate dose in an intermittent regimen may be as clinically useful in osteoporosis therapy as in daily treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : A retrospective cohort study.

PubMed

De Vecchis, R; Ariano, C; Di Biase, G; Noutsias, M

2018-03-08

In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.

Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults.

PubMed

Pettersen, Jacqueline A

2017-04-01

Insufficiency of 25-hydroxyvitamin D [25(OH)D] has been associated with dementia and cognitive decline. However, the effects of vitamin D supplementation on cognition are unclear. It was hypothesized that high dose vitamin D3 supplementation would result in enhanced cognitive functioning, particularly among adults whose 25(OH)D levels were insufficient (<75nmol/L) at baseline. Healthy adults (n=82) from northern British Columbia, Canada (54° north latitude) with baseline 25(OH)D levels ≤100nmol/L were randomized and blinded to High Dose (4000IU/d) versus Low Dose (400IU/d) vitamin D3 (cholecalciferol) for 18weeks. Baseline and follow-up serum 25(OH)D and cognitive performance were assessed and the latter consisted of: Symbol Digit Modalities Test, verbal (phonemic) fluency, digit span, and the CANTAB® computerized battery. There were no significant baseline differences between Low (n=40) and High (n=42) dose groups. Serum 25(OH)D increased significantly more in the High Dose (from 67.2±20 to 130.6±26nmol/L) than the Low Dose group (60.5±22 to 85.9±16nmol/L), p=0.0001. Performance improved in the High Dose group on nonverbal (visual) memory, as assessed by the Pattern Recognition Memory task (PRM), from 84.1±14.9 to 88.3±13.2, p=0.043 (d=0.3) and Paired Associates Learning Task, (PAL) number of stages completed, from 4.86±0.35 to 4.95±0.22, p=0.044 (d=0.5), but not in the Low Dose Group. Mixed effects modeling controlling for age, education, sex and baseline performance revealed that the degree of improvement was comparatively greater in the High Dose Group for these tasks, approaching significance: PRM, p=0.11 (d=0.4), PAL, p=0.058 (d=0.4). Among those who had insufficient 25(OH)D (<75nmol/L) at baseline, the High Dose group (n=23) improved significantly (p=0.005, d=0.7) and to a comparatively greater degree on the PRM (p=0.025, d=0.6). Nonverbal (visual) memory seems to benefit from higher doses of vitamin D supplementation, particularly among those who are insufficient (<75nmol/L) at baseline, while verbal memory and other cognitive domains do not. These findings are consistent with recent cross-sectional and longitudinal studies, which have demonstrated significant positive associations between 25(OH)D levels and nonverbal, but not verbal, memory. While our findings require confirmation, they suggest that higher 25(OH)D is particularly important for higher level cognitive functioning, specifically nonverbal (visual) memory, which also utilizes executive functioning processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Dose estimation and dating of pottery from Turkey

NASA Astrophysics Data System (ADS)

Altay Atlıhan, M.; Şahiner, Eren; Soykal Alanyalı, Feriştah

2012-06-01

The luminescence method is a widely used technique for environmental dosimetry and dating archaeological, geological materials. In this study, equivalent dose (ED) and annual dose rate (AD) of an archaeological sample were measured. The age of the material was calculated by means of equivalent dose divided by the annual dose rate. The archaeological sample was taken from Antalya, Turkey. Samples were prepared by the fine grain technique and equivalent dose was found using multiple-aliquot-additive-dose (MAAD) and single aliquot regeneration (SAR) techniques. Also the short shine normalization-MAAD and long shine normalization-MAAD were applied and the results of the methods were compared with each other. The optimal preheat temperature was found to be 200 °C for 10 min. The annual doses of concentrations of the major radioactive isotopes were determined using a high-purity germanium detector and a low-level alpha counter. The age of the sample was found to be 510±40 years.

Prescribing patterns and the use of therapeutic drug monitoring of psychotropic medication in a psychiatric high-security unit.

PubMed

Castberg, Ingrid; Spigset, Olav

2008-10-01

The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two patients were admitted in the period from January 2000 to December 2005. All available samples were used when comparing serum concentrations and doses with the recommended ranges. For the comparison of doses and serum concentration-to-dose (C:D) ratios with the control group only 1 sample from each patient was used. A total of 459 analyses of 27 different drugs in samples from 8 women and 73 men were included. The median number of therapeutic drug monitoring analyses per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine, quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the recommended. The serum levels were frequently above those recommended for clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol. The serum levels were significantly higher in the study group than in the control group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose was significantly higher in the study group than in the control group for clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower in the study group than in the control group for olanzapine but higher for quetiapine. The non-evidence based practice of high-dose polypharmacy with several antipsychotics is widely used in this unit. The use of higher doses in the study group than in the control group was not due to differences in metabolism or adherence to treatment between the 2 groups. The frequent use of therapeutic drug monitoring did not seem to have a great impact on the prescribed doses.

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

Evaluation of the Effectiveness of Two Morphine Protocols to Treat Neonatal Abstinence Syndrome in a Level II Nursery in a Community Hospital.

PubMed

DeAtley, Heather N; Burton, Amanda; Fraley, Michelle DeLuca; Haltom, Joan

2017-07-01

The authors sought to evaluate the impact on length of hospital stay and treatment duration of morphine after implementation of a change in the institutional protocol for managing neonatal abstinence syndrome (NAS) in an effort to improve patient outcomes. A single-center, retrospective chart review was conducted at a Level II nursery in a community hospital in Kentucky. Fifty-nine neonates born between January 1, 2014, and December 31, 2015, who were diagnosed with NAS and received morphine for treatment were included. The protocol 1 group consisted of 33 neonates who received an initial dose of morphine 0.04 mg/kg/dose administered orally every 4 hours (January 1-December 31, 2014), and the protocol 2 group consisted of 26 neonates who received an initial dose of morphine 0.06 mg/kg/dose administered orally every 3 hours (January 1-November 30, 2015), after a change in the protocol for managing NAS was implemented on January 1, 2015. Data were reviewed and compared between the two protocol groups to determine the impact that the dosage change had on length of hospital stay and morphine treatment duration. The average length of stay decreased by 7 days in the protocol 2 group compared with the protocol 1 group (21 vs 28.65 days). The average duration of treatment decreased by 7 days in the protocol 2 group compared with the protocol 1 group (18.3 vs 25.4 days). These differences between groups were not statistically significant, however, because the population size was not large enough to achieve adequate power. These results indicate that protocol 2 displayed the potential to decrease length of stay and duration of treatment compared with protocol 1 at this facility; however, balancing higher starting doses with the risk of oversedation will continue to challenge the health care team. Concern for oversedation when using the higher starting dose in protocol 2 has prompted further research (e.g., protocol 3, initial morphine 0.05 mg/kg/dose every 3 hrs). Continued research is also necessary with larger patient populations to enable generalizability to other institutions. © 2017 Pharmacotherapy Publications, Inc.

Leflunomide is equally efficacious and safe compared to low dose rituximab in refractory rheumatoid arthritis given in combination with methotrexate: results from a randomized double blind controlled clinical trial.

PubMed

Wijesinghe, Harindu; Galappatthy, Priyadharshini; de Silva, Rajiva; Seneviratne, Suranjith L; Saravanamuttu, Ushagowry; Udagama, Preethi; Hart, Melanie; Kelleher, Peter; Senerath, Upul; Fernandopulle, Rohini; Weerasekera, Lilani P; Wijayaratne, Lalith S

2017-07-19

The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination. Patients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly assigned to rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. Sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, tetanus and pneumococcal antibody levels were secondary end points. Baseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84% (p = 0.93), ACR50 was 60% vs. 64% (p = 0.79) and ACR70 was 35% vs 32% (P = 0.84), in rituximab and in leflunomide groups respectively. Serious adverse events were similar. With rituximab there was significant reduction in B cells (p < 0.001), memory B cells (p < 0.001) and pneumococcal antibody levels (P < 0.05) without significant changes in T cells (p = 0.835) and tetanus antibody levels (p = 0.424) at 24 weeks. With leflunomide, significant reduction in memory B cells (p < 0.01) and pneumococcal antibody levels (p < 0.01) occurred without significant changes in B cells (P > 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05). Leflunomide-methotrexate combination is as efficacious as low-dose rituximab-methotrexate combination at 24 weeks, in RA patient's refractory to initial DMARDs. The high responses seen in both groups have favorable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterization. The trial was registered with the Sri Lanka Clinical Trials Registry (SLCTR), a publicly accessible primary registry linked to the registry network of the International Clinical Trials Registry Platform of the WHO (WHO-ICTRP) (registration number: SLCTR/2008/008 dated 16th May 2008).

Differential toxic effects of Carbofuran and Diazinon on time of flight in pigeons (Columba livia): Potential for pesticide effects on migration

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

Brasel, Jeffrey M.; Environmental Sciences and Health Graduate Program, University of Nevada, Reno, NV 89557; Collier, Abby C.

Cholinesterase inhibiting compounds such as carbamates and organophosphate insecticides have been widely used in agriculture since the ban on organochlorines in the 1970s. Carbofuran, a carbamate, and diazinon, an organophosphate, are among the most commonly implicated cholinesterase inhibitors in episodes of accidental avian toxicity and mortality. Despite the apparent effects of these compounds, little work has been done to study effects of low-level, environmentally relevant doses at the population level in migratory bird species. In this study, homing pigeons were used as surrogate species to assess the differences in the effect of incrementally low doses (0.0, 0.25, 0.5, and 1.0more » mg/kg) of carbofuran and diazinon on time of flight and determine whether there was a threshold dose of either or both xenobiotics when orally administered at these levels. The results indicate that there is a significant dose-dependent increase in flight time in pigeons dosed with carbofuran while diazinon exposed pigeons showed little effect. More profound effects were noted with carbofuran with pigeons falling off the pace of the flock and a dose for highly significant increase in flight time elucidated between 0.5 and 1.0 mg/kg. The results of the studies validate the homing pigeon as a good subject for comparative studies of cholinesterase inhibitors in birds and the need for further research on repeated low-level exposures on populations of avian species.« less

A Methodology to Compare Insulin Dosing Recommendations in Real-Life Settings.

PubMed

Groat, Danielle; Grando, Maria A; Thompson, Bithika; Neto, Pedro; Soni, Hiral; Boyle, Mary E; Bailey, Marilyn; Cook, Curtiss B

2017-11-01

We propose a methodology to analyze complex real-life glucose data in insulin pump users. Patients with type 1 diabetes (T1D) on insulin pumps were recruited from an academic endocrinology practice. Glucose data, insulin bolus (IB) amounts, and self-reported alcohol consumption and exercise events were collected for 30 days. Rules were developed to retrospectively compare IB recommendations from the insulin pump bolus calculator (IPBC) against recommendations from a proposed decision aid (PDA) and for assessing the PDA's recommendation for exercise and alcohol. Data from 15 participants were analyzed. When considering instances where glucose was below target, the PDA recommended a smaller dose in 14%, but a larger dose in 13% and an equivalent IB in 73%. For glucose levels at target, the PDA suggested an equivalent IB in 58% compared to the subject's IPBC, but higher doses in 20% and lower in 22%. In events where postprandial glucose was higher than target, the PDA suggested higher doses in 25%, lower doses in 13%, and equivalent doses in 62%. In 64% of all alcohol events the PDA would have provided appropriate advice. In 75% of exercise events, the PDA appropriately advised an IB, a carbohydrate snack, or neither. This study provides a methodology to systematically analyze real-life data generated by insulin pumps and allowed a preliminary analysis of the performance of the PDA for insulin dosing. Further testing of the methodological approach in a broader diabetes population and prospective testing of the PDA are needed.

Green tea (Camellia sinensis) administration induces expression of immune relevant genes and biochemical parameters in rainbow trout (Oncorhynchus mykiss).

PubMed

Nootash, Shahab; Sheikhzadeh, Najmeh; Baradaran, Behzad; Oushani, Ali Khani; Maleki Moghadam, Mohammad Reza; Nofouzi, Katayoon; Monfaredan, Amir; Aghebati, Leili; Zare, Fatemeh; Shabanzadeh, Sadigheh

2013-12-01

Present study elucidates the efficacy of green tea (Camellia sinensis) on growth performance, immune and antioxidant systems and cytokine gene expression in rainbow trout tissues. Green tea was supplemented at 20, 100, and 500 mg kg(-1) diet and fed to fish (average weight: 23.5 g) for 35 days. No remarkable changes in growth performance were observed among all test groups. Lower lipid peroxidation product and higher superoxide dismutase activity were noted in fish received the medium dose of green tea. Significant increase in serum bactericidal activity and total protein were recorded in all treatment groups. All doses of green tea up-regulated Interleukin-1β transcription in the spleen, while Interleukin-1β mRNA level decreased significantly in the kidney of low dose of green tea. Interleukin-6 mRNA level was up-regulated in the spleen of high dose of green tea and liver of middle and high doses of green tea. High dose and medium dose of green tea up-regulated the interleukin-8 transcription in the kidney and liver, respectively. Meanwhile, green tea inhibited the production of interleukin-10 in all treatment groups compared with control group. Medium dose of green tea up-regulated tumor necrosis factor-α transcription in all fish tissues, while high dose and low dose of green tea enhanced tumor necrosis factor-α mRNA levels in the kidney and spleen, respectively. Present study suggests that green tea especially at 100 mg kg(-1) feed may effectively enhance the antioxidant system and immune system in rainbow trout. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of different glucocorticoid regimens in the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

PubMed

Ajish, T P; Praveen, V P; Nisha, B; Kumar, Harish

2014-11-01

There are recommendations regarding the total dose of hydrocortisone to be administered in the treatment of classical congenital adrenal hyperplasia (CAH) to achieve the twin objectives of glucocorticoid replacement and control of hyperandrogenism. However, there is evidence gap regarding the breakup, timing and type of the steroid regimen. Efficacy of three different glucocorticoid regimens having the same total dose of steroid, differing in either the timing or type of evening steroid administered, in achieving biochemical control of the disease was assessed. The study was done in 13 prepubertal children with classical CAH over a 6-month period with 2 months devoted to each regimen. We used a prospective cross-over design using 10-15 mg/m(2) total dose of hydrocortisone. Two-fifths of the total dose of hydrocortisone was administered in the morning and one-fifth of the total dose was administered at noon in all the regimens. The regimens differed in the timing of the evening dose of hydrocortisone, 06.00-07.00 pm in regimen 1 and 09.00-10.00 pm in regimen 2. The third regimen had the evening dose of hydrocortisone replaced by an equivalent dose of prednisolone suspension which was administered at 10.00 pm. Serum 17-hydroxyprogesterone and testosterone levels were compared to assess the efficacy of treatment regimens. The three different regimens were found to be similar in their ability to control 17-hydroxyprogesterone and testosterone levels. The percentage of patients with predefined criteria for biochemically controlled disease was similar in all the three regimens. However, there was a trend toward better control of 17-hydroxyprogesterone levels in patients receiving evening dose of prednisolone. There is no significant advantage in administering the hydrocortisone dose late at night in patients with classical CAH.

Microdose-induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

PubMed Central

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; Lin, Tzu-yin; Malfatti, Michael; Haack, Kurt; Ognibene, Ted; Yang, Hongyuan; Airhart, Susan; Turteltaub, Kenneth W.; Cimino, George D.; Tepper, Clifford G.; Drakaki, Alexandra; Chamie, Karim; de Vere White, Ralph; Pan, Chong-xian; Henderson, Paul T.

2017-01-01

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry (AMS) in blood and tumor samples collected within 24 hours, and compared to subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [14C]carboplatin or [14C]gemcitabine and the resulting drug-DNA adduct levels were compared to tumor response to chemotherapy. At least one of the drugs had to induce high drug-DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug-DNA adducts as predictive biomarkers. PMID:27903751

Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea.

PubMed

Lindahl, Magnus S; Olovsson, Matts; Nyberg, Sigrid; Thorsen, Kim; Olsson, Tommy; Sundström Poromaa, Inger

2007-01-01

To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls. Cross-sectional study. Umeå University Hospital, Umeå, Sweden. Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls. None. We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer. Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels. The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.

Effect of rosuvastatin monotherapy and in combination with fenofibrate or omega-3 fatty acids on serum vitamin D levels.

PubMed

Makariou, Stefania E; Liberopoulos, Evangelos N; Agouridis, Aris P; Challa, Anna; Elisaf, Moses

2012-12-01

Low levels of 25(OH) vitamin D [25(OH)VitD] have been recognized as a new cardiovascular disease (CVD) risk factor. Statins seem to increase 25(OH)VitD concentration. To investigate whether combined treatment with the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids would increase 25(OH)VitD levels compared with the high-dose rosuvastatin monotherapy in participants with mixed dislipidemia. We randomly allocated 60 patients with mixed dyslipidemia (low-density lipoprotein cholesterol: >160 mg/dL plus triglycerides: >200 mg/dL) to receive rosuvastatin 40 mg (n = 22), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 21), or rosuvastatin 10 mg plus omega-3 fatty acids 2 g (n = 17) daily for 3 months. Our primary end point was changes in the levels of serum 25(OH)VitD. Rosuvastatin monotherapy was associated with a 53% increase in 25(OH)VitD (from 14.6 [1.0-38.0] to 17.8 [5.3-49.6] ng/mL; P = .000). Rosuvastatin plus micronized fenofibrate and rosuvastatin plus omega-3 fatty acids were associated with increases of 64% (from 14.1 [1.0-48.0] to 18.4 [6.7-52.4] ng/mL, P = .001) and 61% (from 10.4 [6.6-38.4] to 14.0 [9.6-37.6] ng/mL, P = .04), respectively. The changes in 25(OH)VitD after treatment were comparable in the 3 groups. High-dose rosuvastatin monotherapy and the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids are associated with significant and similar increases in the 25(OH)VitD levels. This increase may be relevant in terms of CVD risk prevention.

An in vitro evaluation of anti-aging effect of guluronic acid (G2013) based on enzymatic oxidative stress gene expression using healthy individuals PBMCs.

PubMed

Taeb, Mahsa; Mortazavi-Jahromi, Seyed Shahabeddin; Jafarzadeh, Abdollah; Mirzaei, Mohammad Reza; Mirshafiey, Abbas

2017-06-01

Aging is usually associated with increased levels of oxidants, and may result in damages caused by oxidative stress. There is a direct relationship between aging and increased incidence of inflammatory diseases. The present research intended to study the anti-aging and anti-inflammatory effects of the drug G2013 (guluronic acid) at low and high doses on the genes expression of a number of enzymes involved in oxidative stress (including SOD2, GPX1, CAT, GST, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy individuals under in vitro conditions. Venous blood samples were taken from 20 healthy individuals, the PBMCs were isolated and their RNAs extracted and their cDNAs were synthesized, and the genes expression levels were measured using the qRT-PCR technique. Our results indicated that this drug could, at both low and high doses, significantly reduce the expression of the genes for SOD2, GPX1, CAT, and GST compared to the LPS group (p<0.0001). Moreover, it was noticed that the drug is able to significantly reduce gene expression levels at the high dose and at both doses (low and high), for iNOS and MPO compared to the LPS group (p<0.0001), respectively. The present research showed that G2013, as a novel NSAID drug with immunomodulatory properties, could modulate the expression levels of the genes for SOD2, GPX1, CAT, GST, iNOS, and MPO, to the level of healthy gene expression, and possibly it might reduce the pathological process of aging and age-related inflammatory diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2017-06-01

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

Pediatric susceptibility to 18 industrial chemicals: a comparative analysis of newborn with young animals.

PubMed

Hasegawa, R; Hirata-Koizumi, M; Dourson, M; Parker, A; Hirose, A; Nakai, S; Kamata, E; Ema, M

2007-04-01

We comprehensively re-analyzed the toxicity data for 18 industrial chemicals from repeated oral exposures in newborn and young rats, which were previously published. Two new toxicity endpoints specific to this comparative analysis were identified, the first, the presumed no observed adverse effect level (pNOAEL) was estimated based on results of both main and dose-finding studies, and the second, the presumed unequivocally toxic level (pUETL) was defined as a clear toxic dose giving similar severity in both newborn and young rats. Based on the analyses of both pNOAEL and pUETL ratios between the different ages, newborn rats demonstrated greater susceptibility (at most 8-fold) to nearly two thirds of these 18 chemicals (mostly phenolic substances), and less or nearly equal sensitivity to the other chemicals. Exceptionally one chemical only showed toxicity in newborn rats. In addition, Benchmark Dose Lower Bound (BMDL) estimates were calculated as an alternative endpoint. Most BMDLs were comparable to their corresponding pNOAELs and the overall correlation coefficient was 0.904. We discussed how our results can be incorporated into chemical risk assessment approaches to protect pediatric health from direct oral exposure to chemicals.

De novo use of generic tacrolimus in liver transplantation - a single center experience with one-yr follow-up.

PubMed

Dannhorn, E; Cheung, M; Rodrigues, S; Cooper, H; Thorburn, D; Patch, D; Burroughs, A K; O'Beirne, J

2014-12-01

Use of generic tacrolimus in liver transplantation (LT) could result in cost savings. Generic tacrolimus has been shown to be bioequivalent to innovator tacrolimus in healthy volunteers and renal transplant patients. There are limited data on the de novo use of generic tacrolimus in LT. This study aimed to determine whether the de novo use of generic tacrolimus (Adoport, Sandoz,UK) was associated with differences in outcomes, safety, and cost compared with innovator tacrolimus (Prograf, Astellas, Japan). Patients were studied before and after a programmatic change from de novo IS with Prograf to Adoport. Outcomes, tacrolimus levels, doses, and costs were compared for the first-yr post-LT. Ninety-four patients were studied, 46 Prograf, 48 Adoport. No significant differences in rejection, cytomegalovirus infection, acute kidney injury, sepsis, or graft loss were observed between groups. Tacrolimus costs were significantly reduced with the de novo use of Adoport. Day 14 dose normalized levels in Adoport patients showed significant variation but at the day 30 and one yr, there were no significant differences in the doses or levels of tacrolimus between groups. Adoport is safe and effective compared to Prograf when used de novo in LT patients. Tacrolimus costs were significantly reduced by the use of Adoport. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice

PubMed Central

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Background: Diabetes mellitus is the most rampant metabolic pandemic of the 21st century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. Objective: To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Materials and Methods: Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). Results: The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14th and 28th day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Conclusion: Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. SUMMARY Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine in combination with subtherapeutic dose of metformin also showed better effect than therapeutic dose of metformin. Piperine, thus shows potential to be used as bioenhancer in combination with metformin. PMID:26941537

Efficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: preliminary indications from a secondary analysis of the COMACS study data.

PubMed

Sonuga-Barke, Edmund J S; Swanson, James M; Coghill, David; DeCory, Heleen H; Hatch, Simon J

2004-09-30

Methylphenidate (MPH) is commonly prescribed in the treatment of Attention-Deficit/Hyperactivity Disorder or ADHD. Concerta and Metadate CD are once-daily formulations of MPH using different delivery mechanisms resulting in different pharmacokinetic profiles. A recent study (COMACS) showed that for near-milligram (mg) equivalent daily doses, Metadate CD provides greater symptom control in the morning (1.5 through 4.5 hours post-dose), while Concerta provides greater control in the early evening (12 hours post-dose). Non-inferential comparison of effects for different dose levels of the two formulations suggested that equivalent levels of morning symptom control could be obtained with lower daily doses of Metadate CD than Concerta; the situation being reversed in the evening. The current paper presents a secondary analysis that provides a statistical test of these observations. The COMACS study was a multi-center, double-blind crossover study of Metadate CD, Concerta and placebo with each treatment administered for 1 week. Children were assigned on the basis of their pre-trial dosage to either high (Metadate CD 60 mg; Concerta 54 mg), medium (Metadate CD 40 mg; Concerta 36 mg) or low doses (Metadate CD 20 mg; Concerta 18 mg) of MPH, and attended a laboratory school on the 7th day for assessment at 7 sessions across the day. For the post-hoc comparisons across dose levels presented here, total SKAMP scores with the active treatments (adjusted for placebo response) were analyzed using an analysis of covariance, with a combined measure modeling placebo response across all time period as the covariate. Symptom control from 1.5 through 6.0 hours post-dose was as good with lower doses of Metadate CD (20 and 40 mg) as with higher doses of Concerta (36 and 54 mg, respectively). Lower daily doses of Concerta (18 and 36 mg) and higher doses of Metadate CD (40 and 60 mg, respectively) gave equivalent control at 7.5 and 12 hours with Metadate CD giving better control from1.5 through 6.0 hours post-dose. Different delivery profiles of Metadate CD and Concerta can be exploited to limit total daily exposure to MPH while at the same targeting a specific, especially clinically significant, period of the day. These results need to be confirmed in a study in which children are randomly allocated to different dose levels of the two formulations and plasma MPH concentrations are assessed simultaneously.

In vitro analysis of low-level laser irradiation on human osteoblast-like cells proliferation

NASA Astrophysics Data System (ADS)

Bloise, Nora; Saino, Enrica; Bragheri, Francesca; Minzioni, Paolo; Cristiani, Ilaria; Imbriani, Marcello; Visai, Livia

2011-07-01

The objective of this study was to examine the in vitro effect of a single or a multiple doses of low-level laser irradiation (LLLI) on proliferation of the human osteosarcoma cell line, SAOS-2. SAOS-2 cells were divided in five groups and exposed to LLLI (659 nm diode laser; 11 mW power output): group I as a control (dark), group II exposed to a single laser dose of 1 J/cm2, group III irradiated with a single dose of 3 J/cm2, and group IV and V exposed for three consecutive days to 1 or 3 J/cm², respectively. Cellular proliferation was assessed daily up to 7 days of culturing. The obtained results showed an increase in proliferative capacity of SAOS-2 cells during the first 96 h of culturing time in once-irradiated cells, as compared to control cells. Furthermore, a significantly higher proliferation in the group IV and V was detected if compared to a single dose or to control group after 96 h and 7 days. In conclusion, the effect of the single dose on cell proliferation was transitory and repeated irradiations were necessary to observe a strong enhancement of SAOS-2 growth. As a future perspective, we would like to determine the potential of LLLI as a new approach for promoting bone regeneration onto biomaterials.

Aspirin administered to women at 100 mg every other day produces less platelet inhibition than aspirin administered at 81 mg per day: implications for interpreting the women's health study.

PubMed

Swaim, Lisa; Hillman, Robert S

2009-07-01

We aimed to determine the relative level of platelet inhibition achieved with low-dose aspirin (81 mg daily) compared with a very low-dose (100 mg every other day). The Womens Health Study (WHS) found that a dose of 100 mg every other day of aspirin provided protection against stroke as primary prophylaxis, but not myocardial infarction. In the United States, the most commonly prescribed dose of aspirin for primary prophylaxis is 81 mg per day. As a result, it is important to know whether these doses are equivalent before extrapolating the results of the WHS to women in the U.S. To achieve this goal, we have studied the effects of these two dosing regimens on platelet function in healthy women meeting the WHS inclusion criteria using a randomized design. We enrolled 49 healthy female volunteers and used a sequential, crossover design to compare the two regimens. The participants received a 17-day course of each aspirin-dosing regimen separated by a 7-day washout period. The degree of platelet inhibition was measured on days 14-17 of each dosing regimen using a point-of-care platelet function assay utilizing arachidonic acid to activate platelets (VerifyNow-Aspirin). Participants platelet response, expressed as Aspirin Response Unit (ARU) attained a significantly greater level of platelet inhibition on days 14-17 while taking aspirin 81 mg daily compared to aspirin 100 mg every other day (31.3% vs. 12.7%, P < 0.0001) with mean +/- SD ARU values of 445 +/- 50 and 570 +/- 68, P < 0.0001. Significantly more daily readings in participants were >or=550 ARU, a value correlated with clinical outcomes in several studies, with the 100 mg every other day regimen (72.0% vs. 6.4% with 81 mg daily, P < 0.0001), and this alternate-day regimen also resulted in more day-to-day variability in platelet function (P = 0.0002). We found significantly less inhibition of platelet function with the dose used in the WHS than the usual U.S. dose. We observed that the degree of platelet inhibition was significantly less with aspirin 100 mg every other day compared with aspirin 81 mg daily, suggesting that results of the Women's Health Study may have underestimated both the efficacy and toxicity of aspirin as it is commonly administered. These data need to be considered when developing recommendations about the use of aspirin in the primary prevention of cardiovascular disease in women.

A dose comparison survey in CT departments of dedicated paediatric hospitals in Australia and Saudi Arabia

PubMed Central

Mohiy, Hussain Al; Sim, Jenny; Seeram, Euclid; Annabell, Nathan; Geso, Moshi; Mandarano, Giovanni; Davidson, Rob

2012-01-01

AIM: To measure and compare computed tomography (CT) radiation doses delivered to patients in public paediatric hospitals in Australia and Saudi Arabia. METHODS: Doses were measured for routine CT scans of the head, chest and abdomen/pelvis for children aged 3-6 years in all dedicated public paediatric hospitals in Australia and Saudi Arabia using a CT phantom measurement cylinder. RESULTS: CT doses, using the departments’ protocols for 3-6 year old, varied considerably between hospitals. Measured head doses varied from 137.6 to 528.0 mGy·cm, chest doses from 21.9 to 92.5 mGy·cm, and abdomen/pelvis doses from 24.9 to 118.0 mGy·cm. Mean head and abdomen/pelvis doses delivered in Saudi Arabian paediatric CT departments were significantly higher than those in their Australian equivalents. CONCLUSION: CT dose varies substantially across Australian and Saudi Arabian paediatric hospitals. Therefore, diagnostic reference levels should be established for major anatomical regions to standardise dose. PMID:23150767

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

NASA Astrophysics Data System (ADS)

Li, X. Allen; Wang, Jian Z.; Stewart, Robert D.; Di Biase, Steven J.

2003-09-01

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

Clinical and genetic factors affecting tacrolimus trough levels and drug-related outcomes in Korean kidney transplant recipients.

PubMed

Kim, In-Wha; Moon, Yoo Jin; Ji, Eunhee; Kim, Kyung Im; Han, Nayoung; Kim, Sung Ju; Shin, Wan Gyoon; Ha, Jongwon; Yoon, Jeong-Hyun; Lee, Hye Suk; Oh, Jung Mi

2012-05-01

The purpose of this study was to characterize the effects of clinical and genetic variables on the pharmacokinetics and complications of tacrolimus during the first year after kidney transplantation. One hundred and thirty-two Korean kidney recipients who received tacrolimus were genotyped for ABCB1 (exons 12, 21, and 26) and CYP3A5 (intron 3). Tacrolimus trough levels, dose, or dose-adjusted trough levels and complications were compared among patients during the early stage (3, 7, 14, 30, and 90 days) and up to 1 year according to the genotypes. A donor source-adjusted linear mixed model with multilevel analysis adjusting for age, body weight, hematocrit, and serum creatinine showed that CYP3A5 genotype is associated with dose-adjusted level of tacrolimus (p < 0.001). The influence of ABCB1 polymorphisms on the pharmacokinetics or complications of tacrolimus was less certain in our study. The incidence of acute rejections was significantly higher in recipients of cadaveric donor kidney (p < 0.05). A generalized estimating equation model analysis showed that alopecia and hyperlipidemia were associated with dose-adjusted level of tacrolimus (p < 0.001). Genotype of CYP3A5 variants along with significant clinical covariates may be useful in individualizing tacrolimus therapy in kidney transplantation patients.

Whole-body voxel-based personalized dosimetry: Multiple voxel S-value approach for heterogeneous media with non-uniform activity distributions.

PubMed

Lee, Min Sun; Kim, Joong Hyun; Paeng, Jin Chul; Kang, Keon Wook; Jeong, Jae Min; Lee, Dong Soo; Lee, Jae Sung

2017-12-14

Personalized dosimetry with high accuracy is becoming more important because of the growing interests in personalized medicine and targeted radionuclide therapy. Voxel-based dosimetry using dose point kernel or voxel S-value (VSV) convolution is available. However, these approaches do not consider medium heterogeneity. Here, we propose a new method for whole-body voxel-based personalized dosimetry for heterogeneous media with non-uniform activity distributions, which is referred to as the multiple VSV approach. Methods: The multiple numbers (N) of VSVs for media with different densities covering the whole-body density ranges were used instead of using only a single VSV for water. The VSVs were pre-calculated using GATE Monte Carlo simulation; those were convoluted with the time-integrated activity to generate density-specific dose maps. Computed tomography-based segmentation was conducted to generate binary maps for each density region. The final dose map was acquired by the summation of N segmented density-specific dose maps. We tested several sets of VSVs with different densities: N = 1 (single water VSV), 4, 6, 8, 10, and 20. To validate the proposed method, phantom and patient studies were conducted and compared with direct Monte Carlo, which was considered the ground truth. Finally, patient dosimetry (10 subjects) was conducted using the multiple VSV approach and compared with the single VSV and organ-based dosimetry approaches. Errors at the voxel- and organ-levels were reported for eight organs. Results: In the phantom and patient studies, the multiple VSV approach showed significant improvements regarding voxel-level errors, especially for the lung and bone regions. As N increased, voxel-level errors decreased, although some overestimations were observed at lung boundaries. In the case of multiple VSVs ( N = 8), we achieved voxel-level errors of 2.06%. In the dosimetry study, our proposed method showed much improved results compared to the single VSV and organ-based dosimetry. Errors at the organ-level were -6.71%, 2.17%, and 227.46% for the single VSV, multiple VSV, and organ-based dosimetry, respectively. Conclusion: The multiple VSV approach for heterogeneous media with non-uniform activity distributions offers fast personalized dosimetry at whole-body level, yielding results comparable to those of the direct Monte Carlo approach. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

First-in-human study of the toxicity, pharmacokinetics, and pharmacodynamics of CG200745, a pan-HDAC inhibitor, in patients with refractory solid malignancies.

PubMed

Kim, Kyu-pyo; Park, Seong Joon; Kim, Jeong-Eun; Hong, Yong Sang; Lee, Jae-Lyun; Bae, Kyun-Seop; Cha, Hyunju; Kwon, Sool-Ki; Ro, Seonggu; Cho, JoongMyung; Kim, Tae Won

2015-10-01

The aim of the present study was to assess the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and efficacy of single and multiple doses of intravenous CG200745, a novel histone deacetylase (HDAC) inhibitor, in patients with advanced solid malignancies. Two to six patients received intravenous CG200745 according to the 2 + 4 dose-escalating method. This first-in-human trial was comprised of two parts: Part 1 was a single ascending dose, and Part 2 was multiple ascending doses weekly for 3 weeks, and then 1 week off. For the first cycle, pharmacokinetic sampling for CG200745 and pharmacodynamic sampling for acetylated histone H4 in peripheral blood mononuclear cells (PBMCs) were performed on day 1 for Part 1 and on days 1 and 15 for Part 2. Examination of acetylated histone H4 in pre- and post-biopsy samples was performed in accessible patients. In all, 28 patients were treated at 13 dose levels (1.8-250 mg/m(2)) and received a total of 71 cycles of CG200745. Hematologic toxicities included grade 3/4 neutropenia (22.2 %) that did not last a week and non-hematologic toxicities included fatigue (22.2 %) and anorexia (16.7 %) that did not exceed grade 2. No dose-limiting toxic effects were noted. Dose proportionality was observed for both the maximum concentration and area under the curve. The elimination half-life was 5.67 ± 2.69 h (mean ± standard deviation). An increase in PBMC acetylated histone H4 was observed at dose levels up to 51 mg/m(2), which plateaued at higher dose levels. At 24 h, 75 % of patients (6/8) showed higher relative acetylation in tumor tissue compared to PBMCs. Although there was no partial or complete response, 57.1 % of patients (16/28) had stable disease that lasted at least 6 weeks. CG200745 can be safely administered at effective dose levels that inhibit HDAC in PBMCs and tumor tissue. Although MTD was not reached, further escalation was not performed because acetylated histone H4 plateaued at dose levels higher than 51 mg/m(2). Additional phase II trials are recommended at 250 mg/m(2).

Apollo mission experience

NASA Technical Reports Server (NTRS)

Schaefer, H. J.

1972-01-01

Dosimetric implications for manned space flight are evaluated by analyzing the radiation field behind the heavy shielding of a manned space vehicle on a near-earth orbital mission and how it compares with actual exposure levels recorded on Apollo missions. Emphasis shifts from flux densities and energy spectra to incident radiation and absorbed doses and dose equivalents as they are recorded within the ship at locations close to crew members.

Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

PubMed

Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

2010-12-01

The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p < 0.001) mainly owing to the significantly higher CT-related cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p < 0.001). Overall, CT accounted for 86% of the total cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection.

PubMed

Melgaço, Juliana Gil; Morgado, Lucas Nóbrega; Santiago, Marta Almeida; Oliveira, Jaqueline Mendes de; Lewis-Ximenez, Lia Laura; Hasselmann, Bárbara; Cruz, Oswaldo Gonçalves; Pinto, Marcelo Alves; Vitral, Claudia Lamarca

2015-07-31

Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-07-01

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

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study.

PubMed

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

2009-10-20

The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels. The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are required to confirm and further define the benefits of this juice. The juice was administered safely. ISRCTN9300027.

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study

PubMed Central

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

2009-01-01

Background The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels. Methods The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice™: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. Results One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. Conclusion In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice™) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are required to confirm and further define the benefits of this juice. The juice was administered safely. Trial Registration ISRCTN9300027 PMID:19843321

OUT-OF-FIELD DOSES IN CHILDREN TREATED FOR LARGE ARTERIOVENOUS MALFORMATIONS USING HYPOFRACTIONATED GAMMA KNIFE RADIOSURGERY AND INTENSITY-MODULATED RADIATION THERAPY.

PubMed

De Saint-Hubert, Marijke; Majer, Marija; Hršak, Hrvoje; Heinrich, Zdravko; Kneževic, Željka; Miljanic, Saveta; Porwol, Paulina; Stolarczyk, Liliana; Vanhavere, Filip; Harrison, Roger M

2018-01-17

The purpose of this study was to measure out-of-field organ doses in two anthropomorphic child phantoms for the treatment of large brain arteriovenous malformations (AVMs) using hypofractionated gamma knife (GK) radiosurgery and to compare these with an alternative treatment using intensity-modulated radiation therapy (IMRT). Target volume was identical in size and shape in all cases. Radiophotoluminescent (RPL), thermoluminescent (TL) and optically stimulated luminescent (OSL) dosimeters were used for out-of-field dosimetry during GK treatment and a good agreement within 1-2% between results was shown. In addition, the use of multiple dosimetry systems strengthens the reliability of the findings. The number of GK isocentres was confirmed to be important for the magnitude of out-of-field doses. Measured GK doses for the same distance from the target, when expressed per target dose and isocentre, were comparable in both phantoms. GK out-of-field doses averaged for both phantoms were evaluated to be 120 mGy/Gy for eyes then sharply reduced to 20 mGy/Gy for mandible and slowly reduced up to 0.8 mGy/Gy for testes. Taking into account the fractionation regimen used to treat AVM patients, the total treatment organ doses to the out-of-field organs were calculated and compared with IMRT. The eyes were better spared with GK whilst for more distant organs doses were up to a factor of 2.8 and 4 times larger for GK compared to IMRT in 5-year and 10-year old phantoms, respectively. Presented out-of-field dose values are specific for the investigated AVM case, phantoms and treatment plans used for GK and IMRT, but provide useful information about out-of-field dose levels and emphasise their importance. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Efficacy of an extract from garlic, Allium sativum, against infection with the furunculosis bacterium, Aeromonas salmonicida, in rainbow trout, Oncorhynchus mykiss

USGS Publications Warehouse

Breyer, Kate E.; Getchell, Rodman G.; Cornwell, Emily R.; Wooster, Gregory A.; Ketola, H. George; Bowser, Paul R.

2015-01-01

Juvenile rainbow trout, Oncorhynchus mykiss, were fed diets containing 0, 0.5, 1.0, and 2.0% of a garlic extract, challenged with a modified 50% lethal dose of Aeromonas salmonicida and monitored for 28 d. There were significant increases in survival of trout fed 0.5 and 1.0% garlic extract as compared to the control and 2.0% garlic extract groups. A target animal safety study was performed at varying increments using the target dose of 0.5% garlic extract at 0× (0% garlic extract), 1× (0.5% garlic extract), 3× (1.5% garlic extract), and 5× (2.5% garlic extract) for 3× (6 wk) the duration of the original study. There was a significant increase in the level of circulating lymphocytes and a significant decrease in the level of circulating monocytes. The latter correlated to an increased level of pigment-containing macrophage centers within the renal tissue as garlic extract dosing increased, denoting a potential deleterious inflammatory effect as macrophage infiltration became severe at the highest dose. These studies suggest that feeding low-dose (0.5% or 1.0%) garlic extract improves survivability in rainbow trout when challenged with A. salmonicida and appears safe; however, higher levels do not appear to be effective and may cause deleterious effects on health.

Effect of fat on serum 25-hydroxyvitamin D levels after a single oral dose of vitamin D in young healthy adults: a double-blind randomized placebo-controlled study.

PubMed

Raimundo, Fabiana Viegas; Lang, Maria Augusta Britto; Scopel, Luciano; Marcondes, Natália Aydos; Araújo, Mirna Griselda Anocibar; Faulhaber, Gustavo Adolpho Moreira; Furlanetto, Tania Weber

2015-04-01

This double-blind placebo-controlled trial evaluated serum 25-hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of cholecalciferol during one of the three meals, containing different amounts of fat or placebo. Sixty-four healthy medical residents or students of a university hospital in Porto Alegre, latitude 30° S, Brazil, were divided into four groups. Three groups received a single 50,000 IU oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group 2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin, magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D levels were low in all groups. Vitamin D given during breakfast increased the mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the intake of fat with vitamin D increased the mean change of serum 25(OH)D levels. A single oral dose of vitamin D given with food increased mean serum 25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal had at least 15 g of fat. These findings can have important implications to oral vitamin D supplementation.

De novo kidney transplant recipients need higher doses of Advagraf compared with Prograf to get therapeutic levels.

PubMed

Crespo, M; Mir, M; Marin, M; Hurtado, S; Estadella, C; Gurí, X; Rap, O; Moral, R; Puig, J M; Lloveras, J

2009-01-01

Advagraf is a new modified-release once-daily formulation of tacrolimus with a similar efficacy and safety profile to twice-daily tacrolimus (Prograf) according to clinical trials. Few data are published about its use in clinical practice, outside of sponsored clinical trials. We compared efficacy and basic pharmacokinetics of once-daily and twice-daily tacrolimus in de novo renal transplantation. The Advagraf group included 26 de novo renal cases who had received initial immunosuppression with once-daily tacrolimus (0.2 mg/kg from day 1 posttransplantation) combined with mycophenolic acid, steroids, and anti-CD25 monoclonal antibodies (2 doses). We compared them with a Prograf group of 26 transplants performed immediately before, who received equivalent immunosuppression with twice-daily tacrolimus (0.2 mg/kg from day 1). We did not observe significant differences between groups in demographics, efficacy, and basic pharmacokinetics, namely, tacrolimus trough levels at 7, 15, 30, 60, or 90 days. We found that recipients on Advagraf needed significantly higher tacrolimus doses per kg up to 6 months post-transplantation than those on Prograf: 0.16 vs 0.11; 0.14 vs 0.08; and 0.12 vs 0.08 mg/kg at 1, 3, and 6 months. No patient suffered severe liver dysfunction. There were no differences between groups in the administration of drugs interacting with CYP3A4 or prokinetics, which could alter tacrolimus pharmacokinetics. Among de novo renal cases, the new once-daily formulation of tacrolimus offered a similar short-term efficacy profile as the twice-daily tacrolimus. But it was necessary to use up to a 50% higher dose of Advagraf than Prograf to achieve similar trough levels during the first 6 months.

Estimated fluoride doses from toothpastes should be based on total soluble fluoride.

PubMed

Oliveira, Maria José L; Martins, Carolina C; Paiva, Saul M; Tenuta, Livia M A; Cury, Jaime A

2013-11-01

The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride-TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children's toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children's toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p < 0.05), no difference between types of toothpaste was found regarding the ingested dose based on TSF (0.039 ± 0.005 and 0.039 ± 0.005 mg F/day/Kg, respectively; p > 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children's toothpaste is used.

Estimated Fluoride Doses from Toothpastes Should be Based on Total Soluble Fluoride

PubMed Central

Oliveira, Maria José L.; Martins, Carolina C.; Paiva, Saul M.; Tenuta, Livia M. A.; Cury, Jaime A.

2013-01-01

The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride—TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children’s toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children’s toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p < 0.05), no difference between types of toothpaste was found regarding the ingested dose based on TSF (0.039 ± 0.005 and 0.039 ± 0.005 mg F/day/Kg, respectively; p > 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children’s toothpaste is used. PMID:24189183

Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin.

PubMed

Vanky, E; Salvesen, K A; Carlsen, S M

2004-03-01

The purpose of this study was to investigate the effect of low-dose dexamethasone on androgen levels in women with polycystic ovary syndrome (PCOS) treated with diet and lifestyle counselling, and metformin. A prospective, randomized, double blind, placebo-controlled study was carried out. Thirty-eight women with PCOS were randomized to either dexamethasone 0.25 mg daily or placebo for 26 weeks. All received diet and lifestyle counselling at inclusion and metformin 850 mg three times daily during the whole study. Main outcome measures were: androgen levels, body mass index (BMI), insulin c-peptide, fasting glucose and serum lipids. Two-tailed t-tests and Pearson's statistics were used. Compared with the placebo, dexamethasone reduced testosterone by 27%, androstenedione by 21%, dehydroepiandrosterone sulphate by 46% and free testosterone index by 50% in women with PCOS treated with diet and lifestyle advice, and metformin. BMI, fasting glucose, insulin c-peptide and serum lipid levels were unaffected. Six-month, low-dose dexamethasone treatment further reduces androgen levels in metformin-treated PCOS women.

Radiologic Monitoring of Faculty and Staff in an Electrophysiology Lab Using a Real-Time Dose Monitoring System

NASA Astrophysics Data System (ADS)

Chardenet, Kathleen A.

Purpose: A real-time dose management system was used to determine if radiation exposure levels would decrease when providers were privy to their real-time radiation exposure levels. Six aggregate categories of providers were first blinded (phase 1) and subsequently made aware of their radiation exposure levels during electrophysiology procedures (phase 2). Methods: A primary, quantitative crossover study of faculty and staff working in an electrophysiology lab at the University of Michigan Hospitals setting occurred. Participants in the control group was first blinded in phase 1 to their radiation exposure over an 10-week time period. The same group subsequently became the treatment group in phase 2 when over a second 10-week period real-time exposure levels were made available to them. Power analysis, using a 40% decrease in exposure, was calculated using a variance of radiation exposure equal to the mean radiation exposure with 80% power and alpha = .05. Calculations revealed 102 subjects in each treatment and control group were necessary. Results: Using the mixed effect linear model, a significant decrease in radiation levels occurred in phase 2 as compared to phase 1 for the operator role represented by the combined electrophysiologist-fellow role with a P value of .025. Exposure levels in all other provider groups for phase 1 or 2 failed to reach statistical significance. All dose values were low and well below the US maximum allowable yearly dose of 5,000 mrem per year. Conclusion: A real-time radiation dose monitoring system during electrophysiology procedures may significantly lower occupational radiation exposure in health care workers.

Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians.

PubMed

Meor Anuar Shuhaili, Meor Fairuz Rizal; Samsudin, Intan Nureslyna; Stanslas, Johnson; Hasan, Shariful; Thambiah, Subashini C

2017-04-01

The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians. PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles. CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group. The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

Comparison of Diagnostic Accuracy of Radiation Dose-Equivalent Radiography, Multidetector Computed Tomography and Cone Beam Computed Tomography for Fractures of Adult Cadaveric Wrists

PubMed Central

Neubauer, Jakob; Benndorf, Matthias; Reidelbach, Carolin; Krauß, Tobias; Lampert, Florian; Zajonc, Horst; Kotter, Elmar; Langer, Mathias; Fiebich, Martin; Goerke, Sebastian M.

2016-01-01

Purpose To compare the diagnostic accuracy of radiography, to radiography equivalent dose multidetector computed tomography (RED-MDCT) and to radiography equivalent dose cone beam computed tomography (RED-CBCT) for wrist fractures. Methods As study subjects we obtained 10 cadaveric human hands from body donors. Distal radius, distal ulna and carpal bones (n = 100) were artificially fractured in random order in a controlled experimental setting. We performed radiation dose equivalent radiography (settings as in standard clinical care), RED-MDCT in a 320 row MDCT with single shot mode and RED-CBCT in a device dedicated to musculoskeletal imaging. Three raters independently evaluated the resulting images for fractures and the level of confidence for each finding. Gold standard was evaluated by consensus reading of a high-dose MDCT. Results Pooled sensitivity was higher in RED-MDCT with 0.89 and RED-MDCT with 0.81 compared to radiography with 0.54 (P = < .004). No significant differences were detected concerning the modalities’ specificities (with values between P = .98). Raters' confidence was higher in RED-MDCT and RED-CBCT compared to radiography (P < .001). Conclusion The diagnostic accuracy of RED-MDCT and RED-CBCT for wrist fractures proved to be similar and in some parts even higher compared to radiography. Readers are more confident in their reporting with the cross sectional modalities. Dose equivalent cross sectional computed tomography of the wrist could replace plain radiography for fracture diagnosis in the long run. PMID:27788215

A placebo-controlled trial of dextromethorphan as an adjunct in opioid-dependent patients undergoing methadone maintenance treatment.

PubMed

Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Chen, Shih-Heng; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2015-02-25

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. We provide evidence-decreased concomitant heroin use-of low-dose add-on DM's efficacy for treating opioid-dependent patients undergoing MMT. © The Author 2015. Published by Oxford University Press on behalf of CINP.

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

PubMed Central

Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Chen, Shih-Heng; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong

2015-01-01

Background: Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Methods: Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Results: After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. Conclusions: We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT. PMID:25716777

Patient dosimetry audit for establishing local diagnostic reference levels for nuclear medicine CT.

PubMed

Gardner, Matthew; Katsidzira, Ngonidzashe M; Ross, Erin; Larkin, Elizabeth A

2017-03-01

To establish a system for patient dosimetry audit and setting of local diagnostic reference levels (LDRLs) for nuclear medicine (NM) CT. Computed radiological information system (CRIS) data were matched with NM paper records, which provided the body region and dose mode for NMCT carried out at a large UK hospital. It was necessary to divide data in terms of the NM examination type, body region and dose mode. The mean and standard deviation dose-length products (DLPs) for common NMCT examinations were then calculated and compared with the proposed National Diagnostic Reference Levels (NDRLs). Only procedures which have 10 or more patients will be used to suggest LDRLs. For most examinations, the mean DLPs do not exceed the proposed NDRLs. The bone single-photon emission CT/CT lumbar spine data clearly show the need to divide data according to the purpose of the scan (dose mode), with mean (±standard error) DLPs ranging from 51 ± 5 mGy cm (low dose) to 1086 ± 124 mGy cm (metal dose). A system for NMCT patient dose audit has been developed, but there are non-trivial challenges which make the process labour intensive. These include limited information provided by CRIS downloads, dependence on paper records and limited number of examinations available owing to the need to subdivide data. Advances in knowledge: This article demonstrates that a system can be developed for NMCT patient dose audit, but also highlights the challenges associated with such audit, which may not be encountered with more routine audit of radiology CT.

Effect of fluconazole on fungicidal activity of flucytosine in murine cryptococcal meningitis.

PubMed Central

Larsen, R A; Bauer, M; Weiner, J M; Diamond, D M; Leal, M E; Ding, J C; Rinaldi, M G; Graybill, J R

1996-01-01

Both animal and in vitro studies have demonstrated that combinations of flucytosine with amphotericin B and with fluconazole have significantly improved activity against cryptococcal meningitis compared with the activity of each drug used alone. However, very few dose levels of these agents have been tested in combination. This study evaluated the efficacy of fluconazole plus flucytosine in a murine model of cryptococcal meningitis over a broad range of dose combinations (fluconazole, 0 to 40 micrograms/g of body weight per day; flucytosine, 0 to 200 micrograms/g/day). Both drugs were dissolved in drinking water, with treatment on days 2 to 11. In this highly reproducible model, fluconazole had a dramatic effect on the fungicidal activity of flucytosine. Flucytosine at dose levels of as much as 200 micrograms/g/day alone or in combination with low doses of fluconazole had minimal fungicidal activity, whereas in combination with fluconazole at 24 to 40 micrograms/g/day, flucytosine showed fungicidal activity in the range of 45 to 65% of the animals treated at doses of 40 to 100 micrograms/g/day. This striking effect of fluconazole is consistent with the results of both in vitro and clinical studies. In the clinic, the use of flucytosine is often limited by severe toxicity, while toxicity is rarely observed with fluconazole. These results suggest that when flucytosine is given with higher doses of fluconazole, the maximum therapeutic effect of the former in the clinic may be observed at dose levels that are far less than the doses commonly employed (150 micrograms/g daily). PMID:8878602

Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction

NASA Astrophysics Data System (ADS)

Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

2015-03-01

Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene

PubMed Central

Yoo, Hong Sik; Cichocki, Joseph A.; Kim, Sungkyoon; Venkatratnam, Abhishek; Iwata, Yasuhiro; Kosyk, Oksana; Bodnar, Wanda; Sweet, Stephen; Knap, Anthony; Wade, Terry; Campbell, Jerry; Clewell, Harvey J.; Melnyk, Stepan B.; Chiu, Weihsueh A.; Rusyn, Ivan

2015-01-01

Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARα) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARα to alter TCE toxicokinetics, which may lead to differences in TCA internal doses and hence confound inferences as to the role of PPARα in TCE toxicity. To address this gap, male and female wild type (129S1/SvImJ), Pparα-null, and humanized PPARα (hPPARα) mice were exposed intragastrically to 400 mg/kg TCE in single-dose (2, 5 and 12 h) and repeat-dose (5 days/week, 4 weeks) studies. Interestingly, following either a single- or repeat-dose exposure to TCE, levels of TCA in liver and kidney were lower in Pparα-null and hPPARα mice as compared with those in wild type mice. Levels of trichloroethanol (TCOH) were similar in all strains. TCE-exposed male mice consistently had higher levels of TCA and TCOH in all tissues compared with females. Additionally, in both single- and repeat-dose studies, a similar degree of induction of PPARα-responsive genes was observed in liver and kidney of hPPARα and wild type mice, despite the difference in hepatic and renal TCA levels. Additional sex- and strain-dependent effects were observed in the liver, including hepatocyte proliferation and oxidative stress, which were not dependent on TCA or TCOH levels. These data demonstrate that PPARα status affects the levels of the putative PPARα agonist TCA following TCE exposure. Therefore, interpretations of studies using Pparα-null and hPPARα mice need to consider the potential contribution of genotype-dependent toxicokinetics to observed differences in toxicity, rather than attributing such differences only to receptor-mediated toxicodynamic effects. PMID:26136231

The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene.

PubMed

Yoo, Hong Sik; Cichocki, Joseph A; Kim, Sungkyoon; Venkatratnam, Abhishek; Iwata, Yasuhiro; Kosyk, Oksana; Bodnar, Wanda; Sweet, Stephen; Knap, Anthony; Wade, Terry; Campbell, Jerry; Clewell, Harvey J; Melnyk, Stepan B; Chiu, Weihsueh A; Rusyn, Ivan

2015-10-01

Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARα) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARα to alter TCE toxicokinetics, which may lead to differences in TCA internal doses and hence confound inferences as to the role of PPARα in TCE toxicity. To address this gap, male and female wild type (129S1/SvImJ), Pparα-null, and humanized PPARα (hPPARα) mice were exposed intragastrically to 400 mg/kg TCE in single-dose (2, 5 and 12 h) and repeat-dose (5 days/week, 4 weeks) studies. Interestingly, following either a single- or repeat-dose exposure to TCE, levels of TCA in liver and kidney were lower in Pparα-null and hPPARα mice as compared with those in wild type mice. Levels of trichloroethanol (TCOH) were similar in all strains. TCE-exposed male mice consistently had higher levels of TCA and TCOH in all tissues compared with females. Additionally, in both single- and repeat-dose studies, a similar degree of induction of PPARα-responsive genes was observed in liver and kidney of hPPARα and wild type mice, despite the difference in hepatic and renal TCA levels. Additional sex- and strain-dependent effects were observed in the liver, including hepatocyte proliferation and oxidative stress, which were not dependent on TCA or TCOH levels. These data demonstrate that PPARα status affects the levels of the putative PPARα agonist TCA following TCE exposure. Therefore, interpretations of studies using Pparα-null and hPPARα mice need to consider the potential contribution of genotype-dependent toxicokinetics to observed differences in toxicity, rather than attributing such differences only to receptor-mediated toxicodynamic effects. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Life-stage-, sex-, and dose-dependent dietary toxicokinetics and relationship to toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats: implications for toxicity test dose selection, design, and interpretation.

PubMed

Saghir, Shakil A; Marty, Mary S; Zablotny, Carol L; Passage, Julie K; Perala, Adam W; Neal, Barbara H; Hammond, Larry; Bus, James S

2013-12-01

Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥ 1200 ppm (63 mg/kg/day) for P1 males and between 200 and 400 ppm (14-27 mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21-35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies.

Life-Stage-, Sex-, and Dose-Dependent Dietary Toxicokinetics and Relationship to Toxicity of 2,4-Dichlorophenoxyacetic Acid (2,4-D) in Rats: Implications for Toxicity Test Dose Selection, Design, and Interpretation

PubMed Central

Marty, Mary S.

2013-01-01

Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥1200 ppm (63mg/kg/day) for P1 males and between 200 and 400 ppm (14–27mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21–35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies. PMID:24105888

A dose-up of ursodeoxycholic acid decreases transaminases in hepatitis C patients

PubMed Central

Sato, Shuichi; Miyake, Tatsuya; Tobita, Hiroshi; Oshima, Naoki; Ishine, Junichi; Hanaoka, Takuya; Amano, Yuji; Kinoshita, Yoshikazu

2009-01-01

AIM: To examine whether a dose-up to 900 mg of ursodeoxycholic acid (UDCA) decreases transaminases in hepatitis C patients. METHODS: From January to December 2007, patients with chronic hepatitis C or compensated liver cirrhosis with hepatitis C virus (HCV) (43-80 years old) showing positive serum HCV-RNA who had already taken 600 mg/d of UDCA were recruited into this study. Blood parameters were examined at 4, 8 and 24 wk after increasing the dose of oral UDCA from 600 to 900 mg/d. RESULTS: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) levels were significantly decreased following the administration of 900 mg/d as compared to 600 mg/d. The decrease in ALT from immediately before the dose-up of UDCA to 8 wk after the dose-up was 14.3 IU/L, while that for AST was 10.5 IU/L and for GGT was 9.8 IU/L. Platelet count tended to increase after the dose-up of UDCA, although it did not show a statistically significant level (P = 0.05). Minor adverse events were observed in 3 cases, although no drop-outs from the study occurred. CONCLUSION: Oral administration of 900 mg/d of UDCA was more effective than 600 mg/d for reducing ALT, AST, and GGT levels in patients with HCV-related chronic liver disease. PMID:19522030

WE-G-17A-07: Investigation of the Influence of the Electron Return Effect (ERE) On the Dose Distribution in Rectal Cancer Patients On a 1.5T MR-Linac

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

Uilkema, S; Heide, U; Nijkamp, J

Purpose: The purpose of this planning study is to investigate the influence of the ERE on the day-to-day dose distribution in rectal cancer patients, where changes in gas-pockets frequently occur. Methods: Daily CT scans of 5 patients treated neo-adjuvant with 5x5Gy for rectal cancer were used. We optimized two plans on the planning CT (Monaco, 1 mm3 dosegrid), a conventional 7-field 6MV IMRT plan (Dconv) and a plan in the presence of a 1.5T field (Dmrl). We recalculated the plans on all repeat-CT scans and evaluated under/over-dosage of the daily CTVs. Changes of more than 1% were considered significant. Inmore » the bowel area, we investigated the relative dose changes due to the ERE, where the contribution of the ERE was separated from other effects such as attenuation. Results: Both plans were comparable and compliant with ICRU 62 for all patients. For 2 fractions in one patient under-dosage in the CTV was significant, due to a disappearing gas-pocket. Here the V95 was 96.82 and 97.36% in in Dmrl compared to 98.85 and 98.66% in Dconv, respectively. For 3 fractions in another patient appearing gas-pockets resulted in significant over-dosage of the CTV. In these fractions the V107 was 1.88–2.68% in Dmrl compared to 0.33–1.27% in Dconv. In the bowel area the dose changes attributable to the ERE were approximately ± 5% in 1cc, at low dose levels. Conclusion: We were able to calculate acceptable treatment plans with and without a magnetic field. The ERE was present in the Dmrl, but the volumetric effect within the CTV was limited. Outside the CTV relative dose differences were similar, but on small volumes at lower, less relevant dose levels. This suggests that there is no clinical relevant ERE on dose distributions in rectal cancer patients on a 1.5T MR-Linac.« less

Virtual Colonoscopy Screening With Ultra Low-Dose CT and Less-Stressful Bowel Preparation: A Computer Simulation Study

NASA Astrophysics Data System (ADS)

Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong

2008-10-01

Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.

A hospital-based cost minimization study of the potential financial impact on the UK health care system of introduction of iron isomaltoside 1000.

PubMed

Bhandari, Sunil

2011-01-01

The clinical need to be able to administer high doses of intravenous iron conveniently in a single rapid infusion has been addressed by the recent introduction of ferric carboxymaltose and subsequently iron isomaltoside 1000. Neither requires a test dose. Ferric carboxymaltose can be administered at 15 mg/kg body weight to a maximum dose of 1000 mg, whereas iron isomaltoside 1000 can be administered at 20 mg/kg body weight. The ability to give high doses of iron is important in the context of managing iron deficiency anemia in a number of clinical conditions where demands for iron are high (including chronic blood loss associated with inflammatory bowel disease, menorrhagia, and chronic kidney disease). It is also an important component in the strategy as an alternative to a blood transfusion. Affordability is a key issue for health services. This study was a comparative analysis of the costs of administering the newly available intravenous iron formulations against standard practice (blood transfusion, intravenous iron sucrose) by considering the cost of this treatment option plus nursing costs associated with administration, equipment for administration, and patient transportation in the secondary care (hospital) setting across three dosage levels (600 mg, 1000 mg, and 1600 mg). The analysis indicates that the use of iron isomaltoside 1000 results in a net saving when compared with iron sucrose, blood, and ferric carboxymaltose. At 600 mg and 1000 mg doses, it is cheaper than low-molecular-weight iron dextran but more expensive at a dose of 1600 mg. However, it takes six hours to administer low-molecular-weight iron dextran at this dose level, which is inconvenient and reduces patient throughput (productivity).

Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study.

PubMed

Coelingh Bennink, Herjan J T; Verhoeven, Carole; Zimmerman, Yvette; Visser, Monique; Foidart, Jean-Michel; Gemzell-Danielsson, Kristina

2017-06-01

Estetrol (E4) is an estrogen produced exclusively by the human fetal liver during pregnancy. In this study the pharmacodynamic effects of escalating doses of E4 in postmenopausal women were investigated. This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women. Participants were randomized to receive either 2 mg E4 or 2 mg estradiol-valerate (E2 V) for 28 days. Subsequent dose-escalation groups were (non-randomized): 10, 20 and 40 mg E4. Blood samples were collected regularly for measuring endocrine and hemostasis variables, lipids and lipoproteins, fasting glucose and bone turnover markers. Estetrol treatment resulted in a decrease of follicle-stimulating hormone and luteinizing hormone and an increase of sex-hormone binding globulin. Changes in hemostasis variables were small. A lowering effect on low-density lipoprotein cholesterol was accompanied with an increase in high-density lipoprotein cholesterol and no or minimal changes in triglycerides. The considerable decrease in osteocalcin levels in the three highest E4 dose groups and the small decrease in C-telopeptide levels were comparable to the E2 V control group and suggest a preventive effect on bone loss. All changes observed were dose-dependent. In this study, estetrol treatment showed dose-dependent estrogenic effects on endocrine parameters, bone turnover markers, and lipids and lipoproteins. The effect on triglycerides was small as were the effects on hemostatic variables. These results support the further investigation of estetrol as a candidate for hormone therapy. Quantitatively, the effects of 10 mg estetrol were similar to the study comparator 2 mg estradiol valerate.

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

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

Zhang, Q; Lei, Y; Zheng, D

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

Ten-year oral toxicity study with Norlestrin in rhesus monkeys.

PubMed

Fitzgerald, J; de la Iglesia, F; Goldenthal, E I

1982-12-01

The long term effects of the oral contraceptive, Norlestrin, were evaluated in sexually mature female rhesus (Macaca mulatta) monkeys over a 10 year period. Norlestrin, a combination of norethindrone acetate and ethinylestradiol (50:1) was given orally on a continuous cyclic regimen of 21 d of dosing followed by 7 d without treatment. Groups of 16 monkeys each received the drug at dose levels of 0.05, 0.51, and 2.55 mg/kg representing multiples of 1, 10, and 50 times the human dose, respectively. A comparable group of 16 animals remained untreated and served as controls. Selected clinical and laboratory parameters were monitored throughout the study and all animals were necropsied and evaluated for gross and histopathologic changes. All dose levels were well tolerated and survival was not affected. There were no consistent treatment-related alterations in coagulation or other clinical laboratory parameters. Ophthalmologically, macular pigmentary anomalies were observed in all groups. Treatment-associated pathologic findings, representing exaggerated pharmacological responses with superimposed senile changes, including ovarian and uterine atrophy and dilatation of acini and ducts in the mammary gland. Periodic vaginal cytologic examination and mammary gland palpation did not demonstrate drug related changes. A small number of neoplasms was seen in all groups and a granulosa cell carcinoma of the ovary occurred in a control animal. The benign tumors consisted of three cutaneous papillomas: one in a low dose and one in a high dose animal, a uterine leiomyoma in one high dose animal, and a pancreatic duct adenoma in one low dose animal. The results of this study indicate that Norlestrin had no significant toxic manifestations or tumorigenic potential when administered on a cyclic regimen to female rhesus monkeys at levels up to 50 times the human dose for ten yr.

SU-E-T-50: A Multi-Institutional Study of Independent Dose Verification Software Program for Lung SBRT

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

Kawai, D; Takahashi, R; Kamima, T

2015-06-15

Purpose: The accuracy of dose distribution depends on treatment planning system especially in heterogeneity-region. The tolerance level (TL) of the secondary check using the independent dose verification may be variable in lung SBRT plans. We conducted a multi-institutional study to evaluate the tolerance level of lung SBRT plans shown in the AAPM TG114. Methods: Five institutes in Japan participated in this study. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU, Triangle Product, Ishikawa, JP), which is Clarkson-based and CT images were used to compute radiological path length. Analytical Anisotropic Algorithm (AAA), Pencilmore » Beam Convolution with modified Batho-method (PBC-B) and Adaptive Convolve (AC) were used for lung SBRT planning. A measurement using an ion-chamber was performed in a heterogeneous phantom to compare doses from the three different algorithms and the SMU to the measured dose. In addition to it, a retrospective analysis using clinical lung SBRT plans (547 beams from 77 patients) was conducted to evaluate the confidence limit (CL, Average±2SD) in dose between the three algorithms and the SMU. Results: Compared to the measurement, the AAA showed the larger systematic dose error of 2.9±3.2% than PBC-B and AC. The Clarkson-based SMU showed larger error of 5.8±3.8%. The CLs for clinical plans were 7.7±6.0 % (AAA), 5.3±3.3 % (AC), 5.7±3.4 % (PBC -B), respectively. Conclusion: The TLs from the CLs were evaluated. A Clarkson-based system shows a large systematic variation because of inhomogeneous correction. The AAA showed a significant variation. Thus, we must consider the difference of inhomogeneous correction as well as the dependence of dose calculation engine.« less

Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies.

PubMed

Paranjpe, Madhav G; Belich, Jessica; Vidmar, Tom J; Elbekai, Reem H; McKeon, Marie; Brown, Caren

Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

PubMed

Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

2017-10-01

Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHD<20ng/ml (50nmol/L). A history of falls was collected at baseline and fall events were collected every 3 months. Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

L.Soholt; G.Gonzales; P.Fresquez

2003-03-01

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

Phase I Trial of the Combination of Docetaxel, Prednisone, and Pasireotide in Metastatic Castrate-Resistant Prostate Cancer.

PubMed

Thakur, Manish K; Heilbrun, Lance; Dobson, Kimberlee; Boerner, Julie; Stark, Karri; Li, Jing; Smith, Daryn; Heath, Elisabeth; Fontana, Joseph; Vaishampayan, Ulka

2018-06-01

Pasireotide (SOM230; Novartis Inc, Basel, Switzerland) is a multitargeted somatostatin receptor analogue likely to treat the neuroendocrine, and docetaxel resistant components within metastatic castrate-resistant prostate cancer (mCRPC). This phase I trial tested the combination of pasireotide, docetaxel, and prednisone in pretreated mCRPC. Chemotherapy naive mCRPC patients received docetaxel 75 mg/m 2 intravenously every 21 days and pasireotide intramuscularly every 28 days at escalating dose levels of 40, 60, and 80 mg. Maximum tolerated dose and recommended phase II dose (RP2D) were assessed. Eighteen patients were enrolled with a median age of 65 (range, 49-75) years, and pretherapy prostate-specific antigen of 259.9 ng/mL. The dose-limiting toxicities were Grade 4 hyperglycemia unresponsive to therapy and Grade 4 neutropenia lasting for > 7 days in 1 patient each occurring at the 80-mg dose level of pasireotide. The RP2D was determined at 60 mg every 28 days. Four patients at the 60 mg dose had Grade 3 or 4 hyperglycemia, which responded adequately to therapy. Median time to progression and survival were 7.2 and 18.3 months, respectively. Three of 6 patients with circulating tumor cells ≥5 converted to circulating tumor cells < 5 post therapy. The insulin like growth factor-1 levels revealed a median 51% decrease after therapy. The neuron-specific enolase and chromogranin did not show any marked change. The addition of pasireotide to docetaxel and prednisone is clinically feasible at a dose level of 60 mg every 28 days. The combination showed potential for clinical efficacy but needs to be compared with the standard docetaxel and prednisone regimen. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypoglycemic and hypolipidemic effects of Bersama engleriana leaves in nicotinamide/streptozotocin-induced type 2 diabetic rats

PubMed Central

2012-01-01

Background The present investigation was aimed at evaluating the hypoglycemic and hypolipidemic properties of the aqueous and methanolic extracts from Bersama engleriana leaves in streptozotocin/nicotinamide (STZ-NA)-induced type 2 diabetic rats. Methods Animals were orally treated for 4 consecutive weeks with Bersama engleriana extracts at doses of 300 or 600 mg/kg. The anti-diabetic effect was examined by measuring blood glucose (BG) at 0, 1, 14 and 28 days after STZ-NA treatment and, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels at sacrifice (day 29). Glibenclamide (0.25 mg/kg) was used for comparison. Results STZ-NA-induced diabetic rats showed moderate to significant increases in the levels of BG, TG, TC, LDL-C while body weight, HDL-C levels and relative weights of liver and pancreas were decreased compared to controls (non diabetic rats). Administration of the plant extracts to STZ-NA diabetic rats resulted in a significant decrease in BG, TG, TC and LDL-C and the dose 600 mg/kg of the methanolic extract was the most effective; HDL-C level was markedly increased after four weeks compared to untreated diabetic rats. A dose-dependent increase in the relative weights of the diabetogenic organs was observed in the Bersama engleriana groups. It can be also noticed that the methanolic extract, especially the dose 600 mg/kg (p<0.001), produced more effects than glibenclamide and aqueous extract. Rats treated with glibenclamide (0.25 mg/kg) generally gave lower results compared to groups treated with plant extracts. Conclusion Results of the present study showed that Bersama engleriana extracts and especially its methanolic extract possess antidiabetogenic properties and beneficial effects on diabetic hyperlipidemia. All these effects could be due to the bioactive components revealed in the Bersama engleriana extracts such as triterpenes and phenols and which could justify its ethnomedical use. PMID:23267560

Continuous spinal anaesthesia versus single dosing. A comparative study.

PubMed

De Andrés, J A; Febré, E; Bellver, J; Bolinches, R

1995-03-01

Continuous and single dose spinal anaesthesia were compared in a prospective randomized fashion in 108 patients undergoing orthopaedic surgery. Continuous spinal anaesthesia was via a 20 gauge polyamide multiperforated catheter introduced through an 18 gauge Tuohy needle. Single-dose spinal anaesthesia was performed with a 24 guage x 103 mm Sprotte spinal needle. The mean local anaesthetic dose for the continuous technique was 38.4 (SD 16.5) mg as hyperbaric lignocaine 5%, and for the single-dose spinal anaesthesia 10.8 (SD 2.2) mg as hyperbaric bupivacaine 0.5%. Segmental levels reached with the initial dose did not differ significantly between the two groups. Mean time required to perform continuous spinal anaesthesia was 6.7 (SD 3.9) min, which was longer than for single dose 4.9 (SD 2.8) min (P < 0.05). The onset time and efficacy of anaesthesia, and the duration of the operation were similar in the two groups. Analgesia was inadequate in six patients who received continuous spinal anaesthesia (11%) and one patient who received single dose (2%) (P = 0.18). Hypotension was more frequent in those receiving single doses (P < 0.05). Caudal rotation of the outlet needle orifice to advance the catheter correlated with inadequate analgesia (P < 0.01, r = 0.38). There were no significant differences in the incidence of post-operative complications.

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels

PubMed Central

Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Background: Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Materials and Methods: Forty male rats were randomly allocated to five different groups (n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results: Results revealed that chronic stress had a significantly (P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly (P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly (P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly (P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. Conclusions: It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain. PMID:29387668

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.

PubMed

Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Forty male rats were randomly allocated to five different groups ( n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results revealed that chronic stress had a significantly ( P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly ( P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly ( P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly ( P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.

Evaluation of anti-fatigue property of the extruded product of cereal grains mixed with Cordyceps militaris on mice.

PubMed

Zhong, Lei; Zhao, Liyan; Yang, Fangmei; Yang, Wenjian; Sun, Yong; Hu, Qiuhui

2017-01-01

Fatigue is a biological phenomenon that involves a feeling of extreme physical or mental tiredness that could potentially cause some severe chronic diseases. Recently, diet therapy has provided a new alternative to alleviate physical fatigue. In our previous study, addition of Cordyceps militaris ( C. militaris ) into an extruded product was shown to provide high nutrition and unique flavors; however, little is known whether this product has some scientific evidence regarding anti-fatigue property. The purpose of this study was to evaluate the anti-fatigue effects of extruded products of cereal grains (EC) and EC mixed with C. militaris (ECC). The mice were divided into seven groups: one group received distilled water (Control group, n  = 20), and the other groups received different dosages of EC (5, 10 and 20 g/kg body weight, n  = 20 per group) or of ECC (5, 10 and 20 g/kg body weight, n  = 20 per group) solution in water. All of the mice were administered with distilled water, EC or ECC continuously for 30 days by gavage and the anti-fatigue activity was evaluated using a weight-loaded swimming test, along with assessments of fatigue-related indicators. The mode of fighting fatigue was investigated by determining changes in exercise endurance and biochemical markers, including exhaustive swimming time, lactate dehydrogenase (LDH), blood lactic acid (BLA), creatine kinase (CK), blood urea nitrogen (BUN), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and hepatic and muscle glycogen levels. EC and ECC prolonged the swimming endurance time of mice compared to the control. The content of BLA at high dose of ECC group (20 g/kg) was significantly lower than that in the negative control group. CK, BUN and MDA levels were significantly reduced by treatment with EC and ECC compared to the negative control, while the low and middle dose of EC had no significant effect on MDA levels. Additionally, only the middle and high dose of EC (10, 20 g/kg) could significantly decrease the BUN level. EC and ECC treatments increased glycogen, LDH, SOD, CAT and GSH-Px levels. Low and middle dose of EC had no significant effects on muscle glycogen. Moreover, low dose of EC could increase the level of SOD but it was not statistically significant. Compared to the EC treatment groups, ECC demonstrated the efficacy of anti-fatigue potential, particularly at a high dose of ECC, the best performance in relieving fatigue. These results suggest that EC and ECC could prevent exercise-induced fatigue in mice and ECC provided a better effect. In addition, C. militaris in ECC might play a crucial role in the anti-fatigue activity of ECC.

Selective toxin effects on faster and slower growing individuals in the formation of hormesis at the population level - A case study with Lactuca sativa and PCIB.

PubMed

Belz, Regina G; Sinkkonen, Aki

2016-10-01

Natural plant populations have large phenotypic plasticity that enhances acclimation to local stress factors such as toxin exposures. While consequences of high toxin exposures are well addressed, effects of low-dose toxin exposures on plant populations are seldom investigated. In particular, the importance of 'selective low-dose toxicity' and hormesis, i.e. stimulatory effects, has not been studied simultaneously. Since selective toxicity can change the size distribution of populations, we assumed that hormesis alters the size distribution at the population level, and investigated whether and how these two low-dose phenomena coexist. The study was conducted with Lactuca sativa L. exposed to the auxin-inhibitor 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB) in vitro. In two separate experiments, L. sativa was exposed to 12 PCIB doses in 24 replicates (50 plants/replicate). Shoot/root growth responses at the population level were compared to the fast-growing (≥90% percentile) and the slow-growing subpopulations (≤10% percentile) by Mann-Whitney U testing and dose-response modelling. In the formation of pronounced PCIB hormesis at the population level, low-dose effects proved selective, but widely stimulatory which seems to counteract low-dose selective toxicity. The selectivity of hormesis was dose- and growth rate-dependent. Stimulation occurred at lower concentrations and stimulation percentage was higher among slow-growing individuals, but partly or entirely masked at the population level by moderate or negligible stimulation among the faster growing individuals. We conclude that the hormetic effect up to the maximum stimulation may be primarily facilitated by an increase in size of the most slow-growing individuals, while thereafter it seems that mainly the fast-growing individuals contributed to the observed hormesis at the population level. As size distribution within a population is related to survival, our study hints that selective effects on slow- and fast-growing individuals may change population dynamics, providing that similar effects can be repeated under field conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

TH-A-9A-01: Active Optical Flow Model: Predicting Voxel-Level Dose Prediction in Spine SBRT

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

Liu, J; Wu, Q.J.; Yin, F

2014-06-15

Purpose: To predict voxel-level dose distribution and enable effective evaluation of cord dose sparing in spine SBRT. Methods: We present an active optical flow model (AOFM) to statistically describe cord dose variations and train a predictive model to represent correlations between AOFM and PTV contours. Thirty clinically accepted spine SBRT plans are evenly divided into training and testing datasets. The development of predictive model consists of 1) collecting a sequence of dose maps including PTV and OAR (spinal cord) as well as a set of associated PTV contours adjacent to OAR from the training dataset, 2) classifying data into fivemore » groups based on PTV's locations relative to OAR, two “Top”s, “Left”, “Right”, and “Bottom”, 3) randomly selecting a dose map as the reference in each group and applying rigid registration and optical flow deformation to match all other maps to the reference, 4) building AOFM by importing optical flow vectors and dose values into the principal component analysis (PCA), 5) applying another PCA to features of PTV and OAR contours to generate an active shape model (ASM), and 6) computing a linear regression model of correlations between AOFM and ASM.When predicting dose distribution of a new case in the testing dataset, the PTV is first assigned to a group based on its contour characteristics. Contour features are then transformed into ASM's principal coordinates of the selected group. Finally, voxel-level dose distribution is determined by mapping from the ASM space to the AOFM space using the predictive model. Results: The DVHs predicted by the AOFM-based model and those in clinical plans are comparable in training and testing datasets. At 2% volume the dose difference between predicted and clinical plans is 4.2±4.4% and 3.3±3.5% in the training and testing datasets, respectively. Conclusion: The AOFM is effective in predicting voxel-level dose distribution for spine SBRT. Partially supported by NIH/NCI under grant #R21CA161389 and a master research grant by Varian Medical System.« less

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies

PubMed Central

Feldstein, Leora R.; Matrajt, Laura; Halloran, M. Elizabeth; Keitel, Wendy A.; Longini, Ira M.

2016-01-01

Influenza A virus subtype H5N1 has been a public health concern for almost 20 years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: 1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and 2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48–0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32–0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15 mcg had the highest estimated theoretical vaccine efficacy: Dose 1) 45% (95%CI: 36–57%), 53% (95%CI: 42–63%) and 55% (95%CI: 44–64%), respectively and Dose 2) 93% (95%CI: 89–96%), 97% (95%CI: 95–98%) and 97% (95%CI: 96–100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals against a potential avian influenza pandemic. PMID:27268778

Effect of oral tolerance in a mouse model of allergic rhinitis.

PubMed

Shin, Ji-Hyeon; Kang, Jun Myung; Kim, Sung Won; Cho, Jin-Hee; Park, Yong Jin; Kim, Soo Whan

2010-03-01

Induction of oral tolerance (OT) is known to prevent allergic inflammation in models of asthma. This study investigated the preventive effect of OT and airway remodeling in a mouse model of allergic rhinitis (AR). An in vivo study using an animal model. Catholic Research Institutes of Medical Science. Forty six-week-old, female BALB/c mice were divided into four groups: control, AR, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/aluminum hydroxide, 1 mg for six days in the low-dose OT group and a 25 mg single dose in the high-dose OT group. Mice in the AR group were fed phosphate-buffered saline. After sensitization followed by challenges with OVA during six weeks, nasal behaviors, interleukin (IL)-13 and interferon gamma (IFN-gamma) levels in nasal lavage (NAL) fluids, as well as OVA-specific IgE levels in serum, were measured. The degree of goblet cell hyperplasia and thickness of lamina propria were observed in nasal tissues by periodic acid-Schiff and Masson's trichrome stain. A P value < 0.05 was accepted as statistically significant. Both OT groups showed a significant decrease in inflammatory cells, IL-13 and IFN-gamma in NAL fluids, as well as OVA-specific IgE levels in serum compared with the AR group. In addition, the degree of goblet cell hyperplasia and thickness of lamina propria were attenuated in both OT groups compared with the AR group. Further, these alterations did not differ significantly between the two OT groups. These results suggest that OT may effectively reduce allergic inflammation as well as airway remodeling in a mouse model of AR. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Evaluation of Larynx-Sparing Techniques With IMRT When Treating the Head and Neck

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

Webster, Gareth J.; Rowbottom, Carl G.; Ho, Kean F.

2008-10-01

Purpose: Concern exists that widespread implementation of whole-field intensity-modulated radiotherapy (IMRT) for the treatment of head-and-neck cancer has resulted in increased levels of dysphagia relative to those seen with conventional planning. Other investigators have suggested an alternative junctioned-IMRT (J-IMRT) method, which matches an IMRT plan to a centrally blocked neck field to restrict the laryngeal dose and reduce dysphagia. The effect on target coverage and sparing of organs at risk, including laryngeal sparing, in the optimization was evaluated and compared with that achieved using a J-IMRT technique. Methods and Materials: A total of 13 oropharyngeal cancer whole-field IMRT plans weremore » planned with and without including laryngeal sparing in the optimization. A comparison of the target coverage and sparing of organs at risk was made using the resulting dose-volume histograms and dose distribution. The nine plans with disease located superior to the level of the larynx were replanned using a series of J-IMRT techniques to compare the two laryngeal-sparing techniques. Results: An average mean larynx dose of 29.1 Gy was achieved if disease did not extend to the level of the larynx, with 38.8 Gy for disease extending inferiorly and close to the larynx (reduced from 46.2 and 47.7 Gy, respectively, without laryngeal sparing). Additional laryngeal sparing could be achieved with J-IMRT (mean dose 24.4 Gy), although often at the expense of significantly reduced coverage of the target volume and with no improvement to other areas of the IMRT plan. Conclusion: The benefits of J-IMRT can be achieved with whole-field IMRT if laryngeal sparing is incorporated into the class solution. Inclusion of laryngeal sparing had no effect on other parameters in the plan.« less

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

PubMed

Damla, Nevzat; Aldemir, Kamuran

2014-06-01

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

Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity

NASA Technical Reports Server (NTRS)

Heathcote, D. G.; Bircher, B. W.; Brown, A. H. (Principal Investigator)

1987-01-01

The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

Oral MSG administration alters hepatic expression of genes for lipid and nitrogen metabolism in suckling piglets.

PubMed

Chen, Gang; Zhang, Jun; Zhang, Yuzhe; Liao, Peng; Li, Tiejun; Chen, Lixiang; Yin, Yulong; Wang, Jinquan; Wu, Guoyao

2014-01-01

This experiment was conducted to investigate the effects of oral administration of monosodium glutamate (MSG) on expression of genes for hepatic lipid and nitrogen metabolism in piglets. A total of 24 newborn pigs were assigned randomly into one of four treatments (n = 6/group). The doses of oral MSG administration, given at 8:00 and 18:00 to sow-reared piglets between 0 and 21 days of age, were 0 (control), 0.06 (low dose), 0.5 (intermediate dose), and 1 (high dose) g/kg body weight/day. At the end of the 3-week treatment, serum concentrations of total protein and high-density lipoprotein cholesterol in the intermediate dose group were elevated than those in the control group (P < 0.05). Hepatic mRNA levels for fatty acid synthase, acetyl-coA carboxylase, insulin-like growth factor-1, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were higher in the middle-dose group (P < 0.05), compared with the control group. MSG administration did not affect hepatic mRNA levels for hormone-sensitive lipase or carnitine palmitoyl transferase-1. We conclude that oral MSG administration alters hepatic expression of certain genes for lipid and nitrogen metabolism in suckling piglets.

Transfer of Low Dose Aspirin Into Human Milk.

PubMed

Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

2017-05-01

Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.

PubMed

Bloemen-van Gurp, Esther J; Murrer, Lars H P; Haanstra, Björk K C; van Gils, Francis C J M; Dekker, Andre L A J; Mijnheer, Ben J; Lambin, Philippe

2009-01-01

In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

Assessment of potential advantages of relevant ions for particle therapy: A model based study

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

Grün, Rebecca, E-mail: r.gruen@gsi.de; Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390; Medical Faculty of Philipps-University Marburg, Marburg 35032

2015-02-15

Purpose: Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ({sup 12}C), helium ({sup 4}He), and protons ({sup 1}H) for different treatment scenarios. Methods: A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratiomore » (PER) was determined for the physical dose (PER{sub PHY} {sub S}), the RBE (PER{sub RBE}), and the RBE-weighted dose (PER{sub BIO}) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. Results: The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PER{sub RBE} for the analyzed configurations. Due to the fact that protons show a somewhat better PER{sub PHY} {sub S} compared to helium and carbon ions whereas helium shows a higher PER{sub RBE} compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PER{sub RBE} with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PER{sub BIO} is observed when using an orthogonal field configuration for carbon ions as compared to opposing fields. In contrast, for protons, the PER{sub BIO} is almost independent on the field configuration. Concerning the artificial lateral OAR, the volume receiving 20% of the prescribed RBE-weighted dose (V20) was reduced by over 35% using helium ions and by over 40% using carbon ions compared to protons. The analysis of the patient plan showed that protons, helium, and carbon ions are similar in terms of target coverage whereas the dose to the surrounding tissue is increasing from carbon ions toward protons. The mean dose to the brain stem can be reduced by more than 55% when using helium ions and by further 25% when using carbon ions instead of protons. Conclusions: The comparison of the PER{sub RBE} and PER{sub PHY} {sub S} of the three ion types suggests a strong dependence of the advantages of the three ions on the dose-level, tissue type, and field configuration. In terms of conformity, i.e., dose to the normal tissue, a clear gain is expected using carbon or helium ions compared to protons.« less

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2018-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("standard") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2017-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level (“standard”) support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282 PMID:29020861

Monte Carlo calculation of the radiation field at aircraft altitudes.

PubMed

Roesler, S; Heinrich, W; Schraube, H

2002-01-01

Energy spectra of secondary cosmic rays are calculated for aircraft altitudes and a discrete set of solar modulation parameters and rigidity cut-off values covering all possible conditions. The calculations are based on the Monte Carlo code FLUKA and on the most recent information on the interstellar cosmic ray flux including a detailed model of solar modulation. Results are compared to a large variety of experimental data obtained on the ground and aboard aircraft and balloons, such as neutron, proton, and muon spectra and yields of charged particles. Furthermore, particle fluence is converted into ambient dose equivalent and effective dose and the dependence of these quantities on height above sea level, solar modulation, and geographical location is studied. Finally, calculated dose equivalent is compared to results of comprehensive measurements performed aboard aircraft.

A randomized clinical trial of the efficacy of single versus double-daily dose of oral iron for prevention of iron deficiency anemia in women with twin gestations.

PubMed

Ali, Mohammed K; Abbas, Ahmed M; Abdelmagied, Ahmed M; Mohammed, Ghada E; Abdalmageed, Osama S

2017-12-01

The study aims to assess the efficacy of single versus double-daily oral iron dose on prevention of iron deficiency anemia in women with twin gestations. A randomized controlled trial (NCT02858505) conducted at Woman's Health Hospital, Assiut, Egypt, between August 2015 and June 2016 included 120 non-anemic pregnant women with twin gestations in the first trimester. Women were randomly assigned to either group I (27 mg elemental iron) or group II (54 mg elemental iron) daily starting from 12 weeks of pregnancy till 36 weeks. The primary outcomes included the mean level of hemoglobin, hematocrit and serum ferritin at 36 weeks' gestation. Both iron doses maintained the mean hemoglobin and hematocrit within the normal level from 12 weeks to 36 weeks (p = 0.378 and p = 0.244, respectively). However, the mean serum ferritin level was higher in group II than group I (p = 0.000) at 36 weeks' gestation. Moreover, women in group II reported more side effects than group I at 36 weeks' gestation. Doubling the prophylactic iron dose is comparable to single dose in the prevention of iron deficiency anemia among women with twin gestations with more side effects.

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 Home-Based Constraint-Induced Therapy versus Dose-Matched Control Intervention on Functional Outcomes and Caregiver Well-Being in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Lin, Keh-chung; Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Chang, Kai-chieh; Lin, Yu-chan; Chen, Yi-ju

2011-01-01

This study compared home-based constraint-induced therapy (CIT) with a dose-matched home-based control intervention for children with cerebral palsy (CP). The differences in unilateral and bilateral motor performance, daily functions, and quality of parental well-being (i.e., the stress level of their parents) were evaluated. The study included 21…

Key parameters and practices controlling pesticide degradation efficiency of biobed substrates.

PubMed

Karanasios, Evangelos; Karpouzas, Dimitrios G; Tsiropoulos, Nikolaos G

2012-01-01

We studied the contribution of each of the components of a compost-based biomixture (BX), commonly used in Europe, on pesticide degradation. The impact of other key parameters including pesticide dose, temperature and repeated applications on the degradation of eight pesticides, applied as a mixture, in a BX and a peat-based biomixture (OBX) was compared and contrasted to their degradation in soil. Incubation studies showed that straw was essential in maintaining a high pesticide degradation capacity of the biomixture, whereas compost, when mixed with soil, retarded pesticide degradation. The highest rates of degradation were shown in the biomixture composed of soil/compost/straw suggesting that all three components are essential for maximum biobed performance. Increasing doses prolonged the persistence of most pesticides with biomixtures showing a higher tolerance to high pesticide dose levels compared to soil. Increasing the incubation temperature from 15 °C to 25 °C resulted in lower t(1/2) values, with biomixtures performing better than soil at the lower temperature. Repeated applications led to a decrease in the degradation rates of most pesticides in all the substrates, with the exception of iprodione and metalaxyl. Overall, our results stress the ability of biomixtures to perform better than soil under unfavorable conditions and extreme pesticide dose levels. Copyright © Taylor & Francis Group, LLC

Microglial disruption in young mice with early chronic lead exposure☆

PubMed Central

Sobin, Christina; Montoya, Mayra Gisel Flores; Parisi, Natali; Schaub, Tanner; Cervantes, Miguel; Armijos, Rodrigo X.

2013-01-01

The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2.66 to 20.31 μg/dL. Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent. Microglia cell body number also differed between groups and reductions were dose-dependent. As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low- and high-dose animals were reduced. The results did not support a model of increased neuroinflammation. Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals. PMID:23598043

Adaptive statistical iterative reconstruction use for radiation dose reduction in pediatric lower-extremity CT: impact on diagnostic image quality.

PubMed

Shah, Amisha; Rees, Mitchell; Kar, Erica; Bolton, Kimberly; Lee, Vincent; Panigrahy, Ashok

2018-06-01

For the past several years, increased levels of imaging radiation and cumulative radiation to children has been a significant concern. Although several measures have been taken to reduce radiation dose during computed tomography (CT) scan, the newer dose reduction software adaptive statistical iterative reconstruction (ASIR) has been an effective technique in reducing radiation dose. To our knowledge, no studies are published that assess the effect of ASIR on extremity CT scans in children. To compare radiation dose, image noise, and subjective image quality in pediatric lower extremity CT scans acquired with and without ASIR. The study group consisted of 53 patients imaged on a CT scanner equipped with ASIR software. The control group consisted of 37 patients whose CT images were acquired without ASIR. Image noise, Computed Tomography Dose Index (CTDI) and dose length product (DLP) were measured. Two pediatric radiologists rated the studies in subjective categories: image sharpness, noise, diagnostic acceptability, and artifacts. The CTDI (p value = 0.0184) and DLP (p value <0.0002) were significantly decreased with the use of ASIR compared with non-ASIR studies. However, the subjective ratings for sharpness (p < 0.0001) and diagnostic acceptability of the ASIR images (p < 0.0128) were decreased compared with standard, non-ASIR CT studies. Adaptive statistical iterative reconstruction reduces radiation dose for lower extremity CTs in children, but at the expense of diagnostic imaging quality. Further studies are warranted to determine the specific utility of ASIR for pediatric musculoskeletal CT imaging.

Nevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single-Dose Nevirapine

PubMed Central

Micek, Mark A.; Blanco, Ana Judith; Beck, Ingrid A.; Dross, Sandra; Matunha, Laurinda; Montoya, Pablo; Seidel, Kristy; Gantt, Soren; Matediane, Eduardo; Jamisse, Lilia; Gloyd, Stephen; Frenkel, Lisa M.

2011-01-01

Background In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection. Methods We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time. Results Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P =.006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P =.001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P =.017, compared with established in utero infection). Conclusions The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals. PMID:20384494

[Influence of n-hexane on vascular endothelial active substances in brain tissue in mice].

PubMed

Lin, L; Zhang, Z Q; Zhang, C Z

2017-01-20

Objective: To investigate the influence of n - hexane on vascular endothelial active substances in brain tissue in mice and its significance. Methods: A total of 48 healthy Kunming mice were randomly divided into high - dose exposure group, middle - dose exposure group, low - dose exposure group, and control group, with 12 mice in each group. All groups except the control group were exposed to n - hexane via static inhalation (0.035 g/L, 0.018 g/L, and 0.009 g/L for the high - , middle - , and low - dose exposure groups, respectively) 4 hours a day for 21 days. the mice in the control groups were not exposed to n - hexane. After the exposure, the lev-els of endothelin - 1 (ET - 1) , nitric oxide (NO) , and angiotensin II (Ang II) in brain tissue were measured in all groups. Results: There were significant differences in the levels of ET - 1, NO, and Ang II between the three ex-posure groups and the control group ( P <0.05). Compared with the control group, the high - and middle - dose expo-sure group had significant increases in the levels of ET - 1 and Ang II and the high - dose exposure group had a sig-nificant reduction in the level of NO ( P <0.05 or P <0.01). Conclusion: n - Hexane can affect the vascular endothe-lial active substances in brain tissue in mice, and the changes and imbalance in vascular endothelial active sub-stances may be one of the reasons for central nervous system impairment caused by n - hexane.

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

PubMed

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

2016-01-01

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

TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

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

Wu, V; Epelman, M; Feng, M

2014-06-15

Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUDmore » (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD and satisfying dose limits to critical structures. This project is funded by MCubed and grant R01-CA132834.« less

Influence of Ultra-Low-Dose and Iterative Reconstructions on the Visualization of Orbital Soft Tissues on Maxillofacial CT.

PubMed

Widmann, G; Juranek, D; Waldenberger, F; Schullian, P; Dennhardt, A; Hoermann, R; Steurer, M; Gassner, E-M; Puelacher, W

2017-08-01

Dose reduction on CT scans for surgical planning and postoperative evaluation of midface and orbital fractures is an important concern. The purpose of this study was to evaluate the variability of various low-dose and iterative reconstruction techniques on the visualization of orbital soft tissues. Contrast-to-noise ratios of the optic nerve and inferior rectus muscle and subjective scores of a human cadaver were calculated from CT with a reference dose protocol (CT dose index volume = 36.69 mGy) and a subsequent series of low-dose protocols (LDPs I-4: CT dose index volume = 4.18, 2.64, 0.99, and 0.53 mGy) with filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR)-50, ASIR-100, and model-based iterative reconstruction. The Dunn Multiple Comparison Test was used to compare each combination of protocols (α = .05). Compared with the reference dose protocol with FBP, the following statistically significant differences in contrast-to-noise ratios were shown (all, P ≤ .012) for the following: 1) optic nerve: LDP-I with FBP; LDP-II with FBP and ASIR-50; LDP-III with FBP, ASIR-50, and ASIR-100; and LDP-IV with FBP, ASIR-50, and ASIR-100; and 2) inferior rectus muscle: LDP-II with FBP, LDP-III with FBP and ASIR-50, and LDP-IV with FBP, ASIR-50, and ASIR-100. Model-based iterative reconstruction showed the best contrast-to-noise ratio in all images and provided similar subjective scores for LDP-II. ASIR-50 had no remarkable effect, and ASIR-100, a small effect on subjective scores. Compared with a reference dose protocol with FBP, model-based iterative reconstruction may show similar diagnostic visibility of orbital soft tissues at a CT dose index volume of 2.64 mGy. Low-dose technology and iterative reconstruction technology may redefine current reference dose levels in maxillofacial CT. © 2017 by American Journal of Neuroradiology.

SU-F-I-41: Calibration-Free Material Decomposition for Dual-Energy CT

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

Zhao, W; Xing, L; Zhang, Q

2016-06-15

Purpose: To eliminate tedious phantom calibration or manually region of interest (ROI) selection as required in dual-energy CT material decomposition, we establish a new projection-domain material decomposition framework with incorporation of energy spectrum. Methods: Similar to the case of dual-energy CT, the integral of the basis material image in our model is expressed as a linear combination of basis functions, which are the polynomials of high- and low-energy raw projection data. To yield the unknown coefficients of the linear combination, the proposed algorithm minimizes the quadratic error between the high- and low-energy raw projection data and the projection calculated usingmore » material images. We evaluate the algorithm with an iodine concentration numerical phantom at different dose and iodine concentration levels. The x-ray energy spectra of the high and low energy are estimated using an indirect transmission method. The derived monochromatic images are compared with the high- and low-energy CT images to demonstrate beam hardening artifacts reduction. Quantitative results were measured and compared to the true values. Results: The differences between the true density value used for simulation and that were obtained from the monochromatic images, are 1.8%, 1.3%, 2.3%, and 2.9% for the dose levels from standard dose to 1/8 dose, and are 0.4%, 0.7%, 1.5%, and 1.8% for the four iodine concentration levels from 6 mg/mL to 24 mg/mL. For all of the cases, beam hardening artifacts, especially streaks shown between dense inserts, are almost completely removed in the monochromatic images. Conclusion: The proposed algorithm provides an effective way to yield material images and artifacts-free monochromatic images at different dose levels without the need for phantom calibration or ROI selection. Furthermore, the approach also yields accurate results when the concentration of the iodine concentrate insert is very low, suggesting the algorithm is robust with respect to the low-contrast scenario.« less

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure.

PubMed

Tucker, Deirdre K; Macon, Madisa B; Strynar, Mark J; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E

2015-07-01

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. Published by Elsevier Inc.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

PubMed Central

Tucker, Deirdre K.; Macon, Madisa B.; Strynar, Mark J.; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E.

2015-01-01

Perfluorooctanoic acid (PFOA) is a known developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg), however, has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Mouse pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in exposed female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. In contrast, an evaluation of serum hormone levels and pubertal timing onset in the same offspring revealed no effects of PFOA compared to controls in either strain. Therefore, our data suggest that the mammary gland is more sensitive to the effects of early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. PMID:25499722

Influence of Sinogram-Affirmed Iterative Reconstruction on Computed Tomography-Based Lung Volumetry and Quantification of Pulmonary Emphysema.

PubMed

Baumueller, Stephan; Hilty, Regina; Nguyen, Thi Dan Linh; Weder, Walter; Alkadhi, Hatem; Frauenfelder, Thomas

2016-01-01

The purpose of this study was to evaluate the influence of sinogram-affirmed iterative reconstruction (SAFIRE) on quantification of lung volume and pulmonary emphysema in low-dose chest computed tomography compared with filtered back projection (FBP). Enhanced or nonenhanced low-dose chest computed tomography was performed in 20 patients with chronic obstructive pulmonary disease (group A) and in 20 patients without lung disease (group B). Data sets were reconstructed with FBP and SAFIRE strength levels 3 to 5. Two readers semiautomatically evaluated lung volumes and automatically quantified pulmonary emphysema, and another assessed image quality. Radiation dose parameters were recorded. Lung volume between FBP and SAFIRE 3 to 5 was not significantly different among both groups (all P > 0.05). When compared with those of FBP, total emphysema volume was significantly lower among reconstructions with SAFIRE 4 and 5 (mean difference, 0.56 and 0.79 L; all P < 0.001). There was no nondiagnostic image quality. Sinogram-affirmed iterative reconstruction does not alter lung volume measurements, although quantification of lung emphysema is affected at higher strength levels.

Task-based image quality evaluation of iterative reconstruction methods for low dose CT using computer simulations

NASA Astrophysics Data System (ADS)

Xu, Jingyan; Fuld, Matthew K.; Fung, George S. K.; Tsui, Benjamin M. W.

2015-04-01

Iterative reconstruction (IR) methods for x-ray CT is a promising approach to improve image quality or reduce radiation dose to patients. The goal of this work was to use task based image quality measures and the channelized Hotelling observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT applications. We performed realistic computer simulations at five radiation dose levels, from a clinical reference low dose D0 to 25% D0. A fixed size and contrast lesion was inserted at different locations into the liver of the XCAT phantom to simulate a weak signal. The simulated data were reconstructed on a commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany) using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The reconstructed images were analyzed by CHOs with both rotationally symmetric (RS) and rotationally oriented (RO) channels, and with different numbers of lesion locations (5, 10, and 20) in a signal known exactly (SKE), background known exactly but variable (BKEV) detection task. The area under the receiver operating characteristic curve (AUC) was used as a summary measure to compare the IR and analytic methods; the AUC was also used as the equal performance criterion to derive the potential dose reduction factor of IR. In general, there was a good agreement in the relative AUC values of different reconstruction methods using CHOs with RS and RO channels, although the CHO with RO channels achieved higher AUCs than RS channels. The improvement of IR over analytic methods depends on the dose level. The reference dose level D0 was based on a clinical low dose protocol, lower than the standard dose due to the use of IR methods. At 75% D0, the performance improvement was statistically significant (p < 0.05). The potential dose reduction factor also depended on the detection task. For the SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25% from D0 was achieved.

Laparoscopic cholecystectomy under spinal anesthesia: comparative study between conventional-dose and low-dose hyperbaric bupivacaine

PubMed Central

Imbelloni, Luiz Eduardo; Sant’Anna, Raphael; Fornasari, Marcos; Fialho, José Carlos

2011-01-01

Background Laparoscopic cholecystectomy has the advantages of causing less postoperative pain and requiring a short hospital stay, and therefore is the treatment of choice for cholelithiasis. This study was designed to compare spinal anesthesia using hyperbaric bupivacaine given as a conventional dose by lumbar puncture or as a low-dose by thoracic puncture. Methods A total of 140 patients with symptomatic gallstone disease were randomized to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia using either conventional lumbar spinal anesthesia (hyperbaric bupivacaine 15 mg and fentanyl 20 mg) or low-dose thoracic spinal anesthesia (hyperbaric bupivacaine 7.5 mg and fentanyl 20 μg). Intraoperative parameters, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two treatment groups. Results All procedures were completed under spinal anesthesia, with no cases needing conversion to general anesthesia. Values for time for block to reach the T3 dermatomal level, duration of motor and sensory block, and hypotensive events were significantly lower with low-dose bupivacaine. Postoperative pain was higher for low-dose hyperbaric bupivacaine at 6 and 12 hours. All patients were discharged after 24 hours. Follow-up 1 week postoperatively showed all patients to be satisfied and to be keen advocates of spinal anesthesia. Conclusion Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia. A small dose of hyperbaric bupivacaine 7.5 mg and 20 μg fentanyl provides adequate spinal anesthesia for laparoscopy and, in comparison with hyperbaric bupivacaine 15% and fentanyl 20 μg, causes markedly less hypotension. The low-dose strategy may have an advantage in ambulatory patients because of the earlier recovery of motor and sensory function and earlier discharge. PMID:22915892

Image quality and radiation dose on digital chest imaging: comparison of amorphous silicon and amorphous selenium flat-panel systems.

PubMed

Bacher, Klaus; Smeets, Peter; Vereecken, Ludo; De Hauwere, An; Duyck, Philippe; De Man, Robert; Verstraete, Koenraad; Thierens, Hubert

2006-09-01

The aim of this study was to compare the image quality and radiation dose in chest imaging using an amorphous silicon flat-panel detector system and an amorphous selenium flat-panel detector system. In addition, the low-contrast performance of both systems with standard and low radiation doses was compared. In two groups of 100 patients each, digital chest radiographs were acquired with either an amorphous silicon or an amorphous selenium flat-panel system. The effective dose of the examination was measured using thermoluminescent dosimeters placed in an anthropomorphic Rando phantom. The image quality of the digital chest radiographs was assessed by five experienced radiologists using the European Guidelines on Quality Criteria for Diagnostic Radiographic Images. In addition, a contrast-detail phantom study was set up to assess the low-contrast performance of both systems at different radiation dose levels. Differences between the two groups were tested for significance using the two-tailed Mann-Whitney test. The amorphous silicon flat-panel system allowed an important and significant reduction in effective dose in comparison with the amorphous selenium flat-panel system (p < 0.0001) for both the posteroanterior and lateral views. In addition, clinical image quality analysis showed that the dose reduction was not detrimental to image quality. Compared with the amorphous selenium flat-panel detector system, the amorphous silicon flat-panel detector system performed significantly better in the low-contrast phantom study, with phantom entrance dose values of up to 135 muGy. Chest radiographs can be acquired with a significantly lower patient radiation dose using an amorphous silicon flat-panel system than using an amorphous selenium flat-panel system, thereby producing images that are equal or even superior in quality to those of the amorphous selenium flat-panel detector system.

Mealtime Insulin Dosing by Carbohydrate Counting in Hospitalized Cardiology Patients: A Retrospective Cohort Study.

PubMed

Thurber, Kristina M; Dierkhising, Ross A; Reiland, Sarah A; Pearson, Kristina K; Smith, Steven A; O'Meara, John G

2016-01-01

Carbohydrate counting may improve glycemic control in hospitalized cardiology patients by providing individualized insulin doses tailored to meal consumption. The purpose of this study was to compare glycemic outcomes with mealtime insulin dosed by carbohydrate counting versus fixed dosing in the inpatient setting. This single-center retrospective cohort study included 225 adult medical cardiology patients who received mealtime, basal, and correction-scale insulin concurrently for at least 72 h and up to 7 days in the interval March 1, 2010-November 7, 2013. Mealtime insulin was dosed by carbohydrate counting or with fixed doses determined prior to meal intake. An inpatient diabetes consult service was responsible for insulin management. Exclusion criteria included receipt of an insulin infusion. The primary end point compared mean daily postprandial glucose values, whereas secondary end points included comparison of preprandial glucose values and mean daily rates of hypoglycemia. Mean postprandial glucose level on Day 7 was 204 and 183 mg/dL in the carbohydrate counting and fixed mealtime dose groups, respectively (unadjusted P=0.04, adjusted P=0.12). There were no statistical differences between groups on Days 2-6. Greater rates of preprandial hypoglycemia were observed in the carbohydrate counting cohort on Day 5 (8.6% vs. 1.5%, P=0.02), Day 6 (1.7% vs. 0%, P=0.01), and Day 7 (7.1% vs. 0%, P=0.008). No differences in postprandial hypoglycemia were seen. Mealtime insulin dosing by carbohydrate counting was associated with similar glycemic outcomes as fixed mealtime insulin dosing, except for a greater incidence of preprandial hypoglycemia. Additional comparative studies that include hospital outcomes are needed.

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study

PubMed Central

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-01-01

Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21–64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140–187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30–120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0–2 h (AUC0–2 h) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe. PMID:27882216

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

PubMed

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-11-01

Kale ( Brassica oleracea var. acephala ), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (C max ; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0-2 h (AUC 0-2 h ) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

Transforming growth factor-beta-1 is a serum biomarker of radiation-induced pneumonitis in esophageal cancer patients treated with thoracic radiotherapy: preliminary results of a prospective study.

PubMed

Li, Jingxia; Mu, Shuangfeng; Mu, Lixiang; Zhang, Xiaohui; Pang, Ranran; Gao, Shegan

2015-01-01

To examine the relationship between cytokine levels of transforming growth factor-beta-1 (TGF-β1), interleukin-1 beta (IL-1β), and angiotensin-converting enzyme (ACE) in the plasma of esophageal carcinoma patients and radiation-induced pneumonitis (RP). Sixty-three patients with esophageal carcinoma were treated with three-dimensional conformal radiotherapy (RT) using the Elekta Precise treatment planning system with a prescribed dose of 50-70 Gy. Dose-volume histograms were collected from three-dimensional conformal RT to determine the volume percentage of the lung received V5, V10, V20, and the normal tissue complication probability. RP was diagnosed based on computed tomography imaging, respiratory symptoms, and signs. The severity of radiation-induced lung toxicity was determined using the Lent-Soma scale defined by the Radiation Therapy Oncology Group. Plasma samples obtained before RT, during RT (at 40 Gy), and at 1 day, 1 month, and 3 months after RT were assayed for TGF-β1, IL-1β, and ACE levels by enzyme-linked immunosorbent assay. From the 63 patients, 17 (27%) developed RP, and 13 (21%) had RP of grade I and four (6%) had grade II or higher. We found plasma TGF-β1 levels were elevated in the patients that had RP when compared with the other 46 patients who did not have RP. The plasma IL-1β levels were not changed. The ACE levels were significantly lower in the 17 patients with RP compared to the 46 patients without RP throughout the RT. As expected, RP is associated with a higher dose of irradiation (>60 Gy); no other factors, including dose-volume histogram, age, sex, smoking status, location of tumor, and methods of treatment, are associated with RP. Elevated plasma TGF-β1 levels can be used as a marker for RP.

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity

PubMed Central

Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka; Heldrup, Jesper; Harila-Saari, Arja; Jonsson, Olafur G.; Bechensteen, Anne Grete; Abrahamsson, Jonas; Lausen, Birgitte; Frandsen, Thomas L.; Weinshilboum, Richard M.; Schmiegelow, Kjeld

2015-01-01

Purpose Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides (6TGN), the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Methods Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. Results The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However, since TPMTIA had lower blood counts at initiation of HD-MTX compared to TPMTHA patients (median WBC 2.8 vs. 3.3 ×109/L, P=0.01; median ANC 1.4 vs. 1.7 ×109/L, P=0.02), TPMTIA continued to have lower WBC and ANC levels compared to TPMTHA during all 28 days after HD-MTX (relative difference: 9% (95% CI: 2-17%), P=0.02 and 21% (95% CI: 6-39%), P=0.005). Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMTIA and TPMTHA patients (P=0.47 and P=0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P<0.001 for all analyses). Conclusion For both TPMTIA and TPMTHA patients dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity. PMID:25347948

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity.

PubMed

Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka; Heldrup, Jesper; Harila-Saari, Arja; Jonsson, Olafur G; Bechensteen, Anne Grete; Abrahamsson, Jonas; Lausen, Birgitte; Frandsen, Thomas L; Weinshilboum, Richard M; Schmiegelow, Kjeld

2015-01-01

Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMT(IA)) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. The degree of myelosuppression following HD-MTX was similar for patients with TPMT(IA) and patients with high TPMT activity (TPMT(HA)), when HD-MTX started with same blood counts and 6MP doses. However, since TPMT(IA) had lower blood counts at initiation of HD-MTX compared with TPMT(HA) patients (median WBC 2.8 vs. 3.3 × 10⁹/L, P = 0.01; median ANC 1.4 vs. 1.7 × 10⁹/L, P = 0.02), TPMT(IA) continued to have lower WBC and ANC levels compared with TPMT(HA) during all 28 days after HD-MTX [relative difference 9 % (95 % CI 2-17), P = 0.02 and 21 % (95 % CI 6-39), P = 0.005]. Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMT(IA) and TPMT(HA) patients (P = 0.47; P = 0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P < 0.001 for all analyses). For both TPMT(IA) and TPMT(HA) patients, dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity.

Effects of Radiation Exposure From Cardiac Imaging: How Good Are the Data?

PubMed Central

Einstein, Andrew J.

2012-01-01

Concerns about medical exposure to ionizing radiation have become heightened in recent years due to rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This article summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, I address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac-dose-level studies, albeit with exceptions. Using risk projection models developed by the US National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared to benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. PMID:22300689

A method for deriving a 4D-interpolated balanced planning target for mobile tumor radiotherapy.

PubMed

Roland, Teboh; Hales, Russell; McNutt, Todd; Wong, John; Simari, Patricio; Tryggestad, Erik

2012-01-01

Tumor control and normal tissue toxicity are strongly correlated to the tumor and normal tissue volumes receiving high prescribed dose levels in the course of radiotherapy. Planning target definition is, therefore, crucial to ensure favorable clinical outcomes. This is especially important for stereotactic body radiation therapy of lung cancers, characterized by high fractional doses and steep dose gradients. The shift in recent years from population-based to patient-specific treatment margins, as facilitated by the emergence of 4D medical imaging capabilities, is a major improvement. The commonly used motion-encompassing, or internal-target volume (ITV), target definition approach provides a high likelihood of coverage for the mobile tumor but inevitably exposes healthy tissue to high prescribed dose levels. The goal of this work was to generate an interpolated balanced planning target that takes into account both tumor coverage and normal tissue sparing from high prescribed dose levels, thereby improving on the ITV approach. For each 4DCT dataset, 4D deformable image registration was used to derive two bounding targets, namely, a 4D-intersection and a 4D-composite target which minimized normal tissue exposure to high prescribed dose levels and maximized tumor coverage, respectively. Through definition of an "effective overlap volume histogram" the authors derived an "interpolated balanced planning target" intended to balance normal tissue sparing from prescribed doses with tumor coverage. To demonstrate the dosimetric efficacy of the interpolated balanced planning target, the authors performed 4D treatment planning based on deformable image registration of 4D-CT data for five previously treated lung cancer patients. Two 4D plans were generated per patient, one based on the interpolated balanced planning target and the other based on the conventional ITV target. Plans were compared for tumor coverage and the degree of normal tissue sparing resulting from the new approach was quantified. Analysis of the 4D dose distributions from all five patients showed that while achieving tumor coverage comparable to the ITV approach, the new planning target definition resulted in reductions of lung V(10), V(20), and V(30) of 6.3% ± 1.7%, 10.6% ± 3.9%, and 12.9% ± 5.5%, respectively, as well as reductions in mean lung dose, mean dose to the GTV-ring and mean heart dose of 8.8% ± 2.5%, 7.2% ± 2.5%, and 10.6% ± 3.6%, respectively. The authors have developed a simple and systematic approach to generate a 4D-interpolated balanced planning target volume that implicitly incorporates the dynamics of respiratory-organ motion without requiring 4D-dose computation or optimization. Preliminary results based on 4D-CT data of five previously treated lung patients showed that this new planning target approach may improve normal tissue sparing without sacrificing tumor coverage.

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

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

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

2010-01-01

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

Fabrication of topical metered dose film forming sprays for pain management.

PubMed

Ranade, Sneha; Bajaj, Amrita; Londhe, Vaishali; Babul, Najib; Kao, Danny

2017-03-30

Topical film-forming metered dose spray formulations were designed for management of pain. Ropivacaine, a local anesthetic is explored for its topical efficacy in alleviating pain. Metered dose spray containers, organic solvents, film forming polymers and permeation enhancers were utilized to fabricate the Metered Dose topical spray. Factors like viscosity, spray pattern, spray angle, volume of actuation, droplet size distribution of the metered dose spray formulation and drying time, flexibility and wash-ability of the film formed after spraying were assessed. Permeation of the drug into the porcine skin was observed based on ex-vivo diffusion studies and confocal microscopy. The results indicated a high level of drug concentration in the skin layers. Anti-nociceptive efficacy of the formulations was assessed on Wistar rats by hot plate and tail flick tests, based on the response to pain perception. The results were comparable to the conventional lidocaine gel. Topical film forming sprays have the ability to provide an accurate, long lasting and patient compliant delivery of drugs on the skin as compared to conventional gels. Copyright © 2017 Elsevier B.V. All rights reserved.

Patient doses from CT examinations in Turkey.

PubMed

Ataç, Gökçe Kaan; Parmaksız, Aydın; İnal, Tolga; Bulur, Emine; Bulgurlu, Figen; Öncü, Tolga; Gündoğdu, Sadi

2015-01-01

We aimed to establish the first diagnostic reference levels (DRLs) for computed tomography (CT) examinations in adult and pediatric patients in Turkey and compare these with international DRLs. CT performance information and examination parameters (for head, chest, high-resolution CT of the chest [HRCT-chest], abdominal, and pelvic protocols) from 1607 hospitals were collected via a survey. Dose length products and effective doses for standard patient sizes were calculated from the reported volume CT dose index (CTDIvol). The median number of protocols reported from the 167 responding hospitals (10% response rate) was 102 across five different age groups. Third quartile CTDIvol values for adult pelvic and all pediatric body protocols were higher than the European Commission standards but were comparable to studies conducted in other countries. The radiation dose indicators for adult patients were similar to those reported in the literature, except for those associated with head protocols. CT protocol optimization is necessary for adult head and pediatric chest, HRCT-chest, abdominal, and pelvic protocols. The findings from this study are recommended for use as national DRLs in Turkey.

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.

[Experimental and clinical studies of BRL 25000 (clavulanic acid-amoxicillin) granules in the field of pediatrics].

PubMed

Minamitani, M; Hachimori, K; Kaneda, K

1985-02-01

BRL 25000 granules, a formulation consisting of amoxicillin (AMPC) and clavulanic acid (CVA), was evaluated in the field of pediatrics. In a pharmacokinetic study, serum concentrations were determined in a patient after oral administration of BRL 25000 granules in the non-fasting state at a dose of 11.76 mg/kg. The serum levels of amoxicillin (AMPC) and clavulanic acid (CVA) 1 hour after administration were 7.76 micrograms/ml and 6.64 micrograms/ml, with biological half-lives of 0.86 hour and 0.88 hour respectively. The serum concentration profile at a dose of 31.58 mg/kg showed almost the same tendency as at 11.76 mg/kg, although the peak level and biological half-life of the serum concentrations were not obtained. These serum levels and their peak levels were considered reasonable compared with those obtained in adults at similar dose levels. In clinical studies, 34 patients were evaluated including 8 patients with acute pharyngitis or acute tonsillitis, 1 patient with acute bronchitis, 1 patient with bronchopneumonia, 23 patients with scarlet fever and 1 patient with pertussis. BRL 25000 granules were administered orally 3-4 times per day for 4-8 days to 2 patients at doses of 20 approximately less than 30 mg/kg/day, to 18 patients at doses of 30 approximately less than 40 mg/kg/day, to 11 patients at doses of 40 less than approximately 50 mg/kg/day, and to 3 patients at doses of 50-60 mg/kg/day. The clinical response was assessed excellent in 13 cases and good in 21 cases giving an overall clinical efficacy rate of 100% (34/34). The causative organisms were isolated in 17 cases and included 12 strains of Streptococcus group A, 2 S. pneumoniae, 3 H. influenzae and 1 H. parainfluenzae.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of dose and DNA damages in individuals exposed to low dose and low dose rate ionizing radiations during computed tomography imaging.

PubMed

Kanagaraj, Karthik; Abdul Syed Basheerudeen, Safa; Tamizh Selvan, G; Jose, M T; Ozhimuthu, Annalakshmi; Panneer Selvam, S; Pattan, Sudha; Perumal, Venkatachalam

2015-08-01

Computed tomography (CT) is a frequently used imaging modality that contributes to a tenfold increase in radiation exposure to the public when compared to other medical imaging modalities. The use of radiation for therapeutic need is always rationalized on the basis of risk versus benefit thereby increasing concerns on the dose received by patients undergoing CT imaging. Therefore, it was of interest to us to investigate the effects of low dose and low dose-rate X-irradiation in patients who underwent CT imaging by recording the doses received by the eye, forehead and thyroid, and to study the levels of damages in the lymphocytes in vivo. Lithium manganese borate doped with terbium (LMB:Tb) thermo luminescence dosimeters (TLD) were used to record the doses in the patient's (n = 27) eye, forehead, and thyroid and compared with the dose length product (DLP) values. The in vivo DNA damages measured were compared before and after CT imaging using chromosomal aberration (CA) and micronucleus (MN) assays. The overall measured organ dose ranged between 2 ± 0.29 and 520 ± 41.63 mGy for the eye, 0.84 ± 0.29 and 210 ± 20.50 mGy for the forehead, and 1.79 ± 0.43 and 185 ± 0.70 mGy for the thyroid. The in vivo damages measured from the blood lymphocytes of the subjects showed an extremely significant (p < 0.0001) increase in CA frequency and significant (p < 0.001) increase in MN frequency after exposure, compared to before exposure. The results suggest that CT imaging delivers a considerable amount of radiation dose to the eye, forehead, and thyroid, and the observed increase in the CA and MN frequencies show low dose radiation effects calling for protective regulatory measures to increase patient's safety. This study is the first attempt to indicate the trend of doses received by the patient's eye, forehead and thyroid and measured directly in contrast to earlier values obtained by extrapolation from phantoms, and to assess the in vivo low dose effects in an Indian patient population undergoing CT procedures. Copyright © 2015 Elsevier B.V. All rights reserved.

[Comparative study on the tolerance and efficacy of high doses of metoclopramide and clebopride in vomiting induced by cisplatin].

PubMed

Martín, M; Díaz-Rubio, E

1989-06-10

Forty-one patients treated with cisplatin (100-120 mg/m2), alone or associated with vindesine (3 mg/m2), were included in a randomized crossover pilot study which compared 3 different doses of intravenous clebopride with intravenous metoclopramide. The patients were randomly assigned to receive clebopride in the first chemotherapy course in one of the three dose levels used (0.5 mg/kg, 21 patients; 0.75 mg/kg, 11 patients; 1 mg/kg, 10 patients) or metoclopramide (10 mg/kg). In the second course of the same chemotherapy the patients received the alternative antiemetic, and thus each patient was his own control. The total dose of both antiemetic drugs was infused in 5 intravenous fractions given every 2 hours. The antiemetic activity of clebopride was moderately lower to that of metoclopramide with the first two tested doses (overall doses of 0.5 and 0.75 mg/kg) and similar with the last dose (1 mg/kg). Clebopride was reasonably well tolerated at the used dosages, inducing sedation in 20% of cases (versus 24% with metoclopramide) and diarrhea in 37% (versus 20% with metoclopramide). Extrapyramidal reactions developed in 17% of the courses which included metoclopramide and in none including clebopride. This difference was statistically significant.

Serial betamethasone administration: effect on maternal salivary estriol levels.

PubMed

Hendershott, C M; Dullien, V; Goodwin, T M

1999-01-01

Maternal salivary estriol levels are an indirect measure of fetal adrenal activity, which may be affected by administration of betamethasone. The objective was to compare sequential salivary estriol levels in patients receiving serial betamethasone therapy with those of healthy pregnant patients. Ten patients at high risk for preterm delivery were asked to obtain salivary specimens before and 1 to 2 days after each administration of weekly betamethasone treatments between 24 and 32 weeks' gestation. These values were compared with those of specimens obtained throughout gestation in healthy women who were not delivered preterm. Unconjugated salivary estriol was measured with a sensitive and specific enzyme-linked immunoassay (Biex, Inc, Dublin, Calif). The effect of betamethasone on salivary estriol levels did not change with time, showing an average of 23.1% drop from pretreatment to posttreatment levels but rebounding to the same starting level before the next dose. When weekly pretreatment values were looked at across time, the geometric mean of the individual patients' slopes did not differ significantly from no change. The same was true of the posttreatment values. The rate of change with advancing gestation was compared between 182 control subjects and the 10 study subjects. The average change was +8.8% per week in the control subjects and -1.3% per week in the study patients (P =.003). Maternal administration of betamethasone significantly suppressed salivary estriol levels. These levels returned to pretreatment values each week before the next dose; however, the rise normally associated with advancing gestational age was not observed.

NovaSil clay does not affect the concentrations of vitamins A and E and nutrient minerals in serum samples from Ghanaians at high risk for aflatoxicosis.

PubMed

Afriyie-Gyawu, E; Wang, Z; Ankrah, N-A; Xu, L; Johnson, N M; Tang, L; Guan, H; Huebner, H J; Jolly, P E; Ellis, W O; Taylor, R; Brattin, B; Ofori-Adjei, D; Williams, J H; Wang, J-S; Phillips, T D

2008-07-01

To assess the potential interference of NovaSil (NS) clay with micronutrients in humans, vitamins A and E and minerals (15 nutrient and 15 non-nutrient minerals) were measured in serum samples from a 3-month intervention trial with NS. Participants (n = 177) were randomly divided into three groups that received 3.0 g NS day(-1) (high dose, HD), 1.5 g NS day(-1) (low dose, LD), or placebo (PL). Levels of vitamins A and E in serum were comparable among the three study groups at baseline, 1 month and 3 months of NS intervention. Gender-stratified non-parametric mixed-effect model analysis showed no significant effects of dose and dose-time interaction for levels of vitamins A and E. A significant time effect was detected; however, it was limited to an increase in vitamin E in the male participants over the course of the study. No significant differences were found in levels of the nutrient and non-nutrient minerals between the HD and PL groups at baseline and 3 months of NS intervention, except for strontium levels. Strontium was significantly increased (p < 0.001) in the HD group (male = 113.65 +/- 28.00 microg l(-1); female = 116.40 +/- 24.26 microg l(-1)) compared with the PL group (male = 83.55 +/- 39.90 microg l(-1); female = 90.47 +/- 25.68 microg l(-1)) following the 3-month intervention with NS. These results, combined with safety and efficacy data, confirm that NS clay is highly effective in reducing aflatoxin exposure and acts as a selective enterosorbent that does not affect the serum concentrations of important vitamins and nutrient minerals in humans.

Beneficial Effects of Pentoxifylline Plus Losartan Dual Therapy in Type 2 Diabetes with Nephropathy.

PubMed

Rabizadeh, Soghra; Dehghani Firouzabadi, Fatemeh; Noshad, Sina; Esteghamati, Sadaf; Afarideh, Mohsen; Ghajar, Alireza; Ganji, Morsaleh; Saadat, Mohammad; Heidari, Behnam; Najafi, Mohammad Taghi; Nakhjavani, Manouchehr; Esteghamati, Alireza

2018-05-01

This study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy. In an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400mg plus daily dose of losartan 50mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50mg (losartan arm) during a 12-week follow-up period. Serum NT-proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT-proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P < 0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively). Circulating NT-proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-01-01

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

Taxonomic and developmental aspects of radiosensitivity

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

Harrison, F.L.; Anderson, S.L.

1996-11-01

Considerable information is available on the effects of radioactivity on adult and early life stages of organisms. The preponderance of data is on mortality after a single irradiation with relatively high doses. Unfortunately, because experiments were carried out under different conditions and for different time periods, the validity of comparing the results from different laxonomic groups is questionable. In general, the conclusions are that there is a relationship (1) between radioresistance to high doses of acute radiation and taxonomy of the organism, primitive forms being more radioresistant than complex vertebrates and (2) between radiosensitivity and developmental stage, early life stagesmore » being more sensitive than later stages. The first conclusion may be related to the capability of the organism to repopulate cells and to differentiate and redifferentiate them; the second to the rate of cellular division and to the degree of differentiation. In question, however, is the relevance of the responses from high levels of acute radiation to that of the responses to long-term exposure to low levels of radiation, which are ecologically of more interest. Data from studies of the effects of acute and chronic exposure on development of gametes and zygotes indicate that, for some fishes and invertebrates, responses at the cellular and molecular levels show effect levels comparable to those observed in some mammals. Acute doses between 0,05 and 0.5Cy and dose rates between 0.02 to 0.2mCy/h appear to define critical ranges in which detrimental effects on fertility are first observed in a variety of radiosensitive organisms. To better understand inherent radiosensitivity, we need more information on the ability of cells to repopulate and differentiate and to prevent or repair damage to biological critical molecules, such as DNA, because these factors may alter significantly organisms` responses to radiation.« less

Cumulative effective radiation dose received by blunt trauma patients arriving to a military level I trauma center from point of injury and interhospital transfers.

PubMed

Van Arnem, Kerri A; Supinski, David P; Tucker, Jonathan E; Varney, Shawn

2016-12-01

Trauma patients sustaining blunt injuries are exposed to multiple radiologic studies. Evidence indicates that the risk of cancer from exposure to ionizing radiation rises in direct proportion to the cumulative effective dose (CED) received. The purpose of this study is to quantify the amount of ionizing radiation accumulated when arriving directly from point of injury to San Antonio Military Medical Center (SAMMC), a level I trauma center, compared with those transferred from other facilities. A retrospective record review was conducted from 1st January 2010 through 31st December 2012. The SAMMC trauma registry, electronic medical records, and the digital radiology imaging system were searched for possible candidates. The medical records were then analyzed for sex, age, mechanism of injury, received directly from point of injury (direct group), transfer from another medical facility (transfer group), computed tomographic scans received, dose-length product, CED of radiation, and injury severity score. A diagnostic imaging physicist then calculated the estimated CED each subject received based on the dose-length product of each computed tomographic scan. A total of 300 patients were analyzed, with 150 patients in the direct group and 150 patients in the transfer group. Both groups were similar in age and sex. Patients in the transfer group received a significantly greater CED of radiation compared with the direct group (mean, 37.6 mSv vs 28 mSv; P=.001). The radiation received in the direct group correlates with a lifetime attributable risk (LAR) of 1 in 357 compared with the transfer group with an increase in LAR to 1 in 266. Patients transferred to our facility received a 34% increase in ionizing radiation compared with patients brought directly from the injury scene. This increased dose of ionizing radiation contributes to the LAR of cancer and needs to be considered before repeating imaging studies. III. Published by Elsevier Inc.

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

PubMed

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

2016-11-01

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

Characterization of a developmental toxicity dose-response model.

PubMed Central

Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A

1989-01-01

The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose. PMID:2707204

Association between an Alzheimer's Disease-Related Index and APOE ε4 Gene Dose.

PubMed

Schraml, Frank; Chen, Kewei; Ayutyanont, Napatkamon; Auttawut, Roontiva; Langbaum, Jessica B S; Lee, Wendy; Liu, Xiaofen; Bandy, Dan; Reeder, Stephanie Q; Alexander, Gene E; Caselli, Richard J; Fleisher, Adam S; Reiman, Eric M

2013-01-01

We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person's fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer's disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers. An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers. These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001). The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.

Terrestrial gamma radiation dose (TGRD) levels in northern zone of Jos Plateau, Nigeria: Statistical relationship between dose rates and geological formations

NASA Astrophysics Data System (ADS)

Abba, Habu Tela; Hassan, Wan Muhamad Saridan Wan; Saleh, Muneer Aziz; Aliyu, Abubakar Sadiq; Ramli, Ahmad Termizi

2017-11-01

In- situ measurement of terrestrial gamma radiation dose rates (TGRD) was conducted in northern zone of Jos Plateau and a statistical relationship between the TGRD and the underlying geological formations was investigated. The TGRD rates in all the measurements ranged from 40 to 1265 nGy h-1 with a mean value of 250 nGy h-1. The maximum TGDR was recorded on geological type G8 (Younger Granites) at Bisitchi, and the lowest TGDR was recorded on G6 (Basaltic rocks) at Gabia. One way analysis of variance (ANOVA) statistical test was used to compared the data. Significantly, the results of this study inferred a strong relationship between TGRD levels with geological structures of a place. An isodose map was plotted to represent exposure rates due to TGRD. The results of this investigation could be useful for multiple public interest such as evaluating public dose for the area.

Teratogenic effects of retinoic acid on neurulation in mice embryos.

PubMed

Nobakht, M; Zirak, A; Mehdizadeh, M; Tabatabaeei, P

2006-02-21

Retinoic acids (RA) are natural chemicals that exert a hormone-like activity and a variety of biological effects on early development of mouse. In this study, the probable teratogenic effects of RA on CNS have been investigated in pregnant mice (n = 20) divided into four groups: (1) untreated controls, (2) controls which received a single dose of DMSO, (3) a group that received 40 mg/kg, and (4) a group that received 60 mg/kg of all-trans RA in DMSO, respectively on the eighth day of gestation. Embryos whose dams had received 40 and 60 mg/kg doses of RA, showed malformations and decreased size. At 40 mg/kg dosage level, 50% of the embryos had closed neural tubes while at 60 mg/kg dosage level the neural tube failed to close. The neuroblast mantle layers were disorganized in the 40 mg/kg and even more in the 60 mg/kg exposed group compared to the controls. In mitosis, the density of chromatin was increased in the 60 mg/kg dose group. Compared to controls the 40 and 60 mg/kg dose groups of RA treated dams decreases in the luminal longitudinal and internal measures were observed. Also the thickness of ventricular, mantle and marginal layers was smaller. Wide intercellular spaces due to the degenerated cells at high doses of RA as well as an accumulation of intercellular fluid were observed. Therefore, the wedge shape of neuroepithelium was abolished, preventing the elevation of the neural wall.

Effects of reduced natural background radiation on Drosophila melanogaster growth and development as revealed by the FLYINGLOW program.

PubMed

Morciano, Patrizia; Iorio, Roberto; Iovino, Daniela; Cipressa, Francesca; Esposito, Giuseppe; Porrazzo, Antonella; Satta, Luigi; Alesse, Edoardo; Tabocchini, Maria Antonella; Cenci, Giovanni

2018-01-01

Natural background radiation of Earth and cosmic rays played a relevant role during the evolution of living organisms. However, how chronic low doses of radiation can affect biological processes is still unclear. Previous data have indicated that cells grown at the Gran Sasso Underground Laboratory (LNGS, L'Aquila) of National Institute of Nuclear Physics (INFN) of Italy, where the dose rate of cosmic rays and neutrons is significantly reduced with respect to the external environment, elicited an impaired response against endogenous damage as compared to cells grown outside LNGS. This suggests that environmental radiation contributes to the development of defense mechanisms at cellular level. To further understand how environmental radiation affects metabolism of living organisms, we have recently launched the FLYINGLOW program that aims at exploiting Drosophila melanogaster as a model for evaluating the effects of low doses/dose rates of radiation at the organismal level. Here, we will present a comparative data set on lifespan, motility and fertility from different Drosophila strains grown in parallel at LNGS and in a reference laboratory at the University of L'Aquila. Our data suggest the reduced radiation environment can influence Drosophila development and, depending on the genetic background, may affect viability for several generations even when flies are moved back to normal background radiation. As flies are considered a valuable model for human biology, our results might shed some light on understanding the effect of low dose radiation also in humans. © 2017 Wiley Periodicals, Inc.

In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

PubMed

Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

2018-04-15

The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

Simulation study of natural UV-B radiation on Catla catla and its impact on physiology, oxidative stress, Hsp 70 and DNA fragmentation.

PubMed

Singh, Moirangthem Kameshwor; Sharma, Jai Gopal; Chakrabarti, Rina

2015-08-01

UV-B radiation is a potential stressor to the aquacultural species. Catla catla, catla larvae (1.08±0.065g) were exposed to different doses of UV-B radiation, 0 (control), 504, 1008, 1512 and 2016mJ/cm(2) at a mean radiant energy of 80μW/cm(2) for 21days. The dose of UV-B radiation was selected on the basis of the field study conducted in Lake Naini, Delhi, India (Latitude: 28°41'26″N and Longitude: 77°12″37″E). Significantly (P<0.05) lower survival, average weight and specific growth rate were found in UV-B irradiated larvae compared to the control one. Food conversion ratio was 1.5-4-fold higher in UV-B treated larvae compared to the control one. The carbonyl protein (CP), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) levels were significantly (P <0.05) higher in UV-B irradiated larvae compared to the control group. Among the treated larvae, CP and SOD were significantly (P <0.05) higher in larvae exposed at 1512mJ/cm(2) UV-B. A correlation was found between the CP and SOD (R(2)=0.834). Highest TBARS level was found in 2016mJ/cm(2) UV-B exposed catla. Nitric oxide synthase level was significantly (P <0.05) lower in UV-B exposed larvae compared to the control one. A 3-fold increased Hsp 70 level was recorded in UV-B irradiated catla compared to the control larvae. Comet assay analysis indicated that UV-B irradiation enhanced DNA fragmentation. Tail extent moment and the olive tail moment were significantly (P <0.05) higher in 2016mJ/cm(2) UV-B exposed catla compared to others. The tail length was significantly (P <0.05) higher in 1512 and 2016mJ/cm(2) UV-B exposed larvae compared to the other doses. The present study suggests that the catla is a useful species for the biomonitoring of stress in the aquatic environment. Copyright © 2015 Elsevier B.V. All rights reserved.

Unenhanced 320-row multidetector computed tomography of the brain in children: comparison of image quality and radiation dose among wide-volume, one-shot volume, and helical scan modes.

PubMed

Jeon, Sun Kyung; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun; Cho, Yeon Jin; Ha, Ji Young; Lee, Seung Hyun; Hyun, Hyejin; Kim, In-One

2018-04-01

The 320-row multidetector computed tomography (CT) scanner has multiple scan modes, including volumetric modes. To compare the image quality and radiation dose of 320-row CT in three acquisition modes - helical, one-shot volume, and wide-volume scan - at pediatric brain imaging. Fifty-seven children underwent unenhanced brain CT using one of three scan modes (helical scan, n=21; one-shot volume scan, n=17; wide-volume scan, n=19). For qualitative analysis, two reviewers evaluated overall image quality and image noise using a 5-point grading system. For quantitative analysis, signal-to-noise ratio, image noise and posterior fossa artifact index were calculated. To measure the radiation dose, adjusted CT dose index per unit volume (CTDI adj ) and dose length product (DLP) were compared. Qualitatively, the wide-volume scan showed significantly less image noise than the helical scan (P=0.009), and less streak artifact than the one-shot volume scan (P=0.001). The helical mode showed significantly lower signal-to-noise ratio, with a higher image noise level compared with the one-shot volume and wide-volume modes (all P<0.05). The CTDI adj and DLP were significantly lower in the one-shot volume and wide-volume modes compared with those in the helical scan mode (all P<0.05). For pediatric unenhanced brain CT, both the wide-volume and one-shot volume scans reduced radiation dose compared to the helical scan mode, while the wide-volume scan mode showed fewer streak artifacts in the skull vertex and posterior fossa than the one-shot volume scan.

Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The aim of the present study was to investigate the protective role of Ginkgo biloba L. leaf extract against the active agent of Roundup® herbicide (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided into six groups, with each group consisting of six animals: Group I (control) received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only), Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50 mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body weight). The single dose of glyphosate was given intraperitoneally. Animals from all the groups were sacrificed at the end of 72 hours, and their blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and glutathione (GSH) levels and the presence of micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The results indicated that serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with glyphosate alone compared with the other groups (P<.05). Besides, glyphosate-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of the liver and kidney tissues. Moreover, glyphosate alone-treated mice presented higher frequencies of CAs, MNs, and abnormal metaphases compared with the controls (P<.05). These mice also displayed a lower mean mitotic index than the controls (P<.05). Treatment with G. biloba produced amelioration in indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to Group II. Each dose of G. biloba provided significant protection against glyphosate-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is a potent protector against glyphosate-induced toxicity, and its protective role is dose-dependent.

Analysis of Flow Cytometry DNA Damage Response Protein Activation Kinetics Following X-rays and High Energy Iron Nuclei Exposure

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

Universities Space Research Association; Chappell, Lori J.; Whalen, Mary K.

2010-12-15

We developed a mathematical method to analyze flow cytometry data to describe the kinetics of {gamma}H2AX and pATF2 phosphorylations ensuing various qualities of low dose radiation in normal human fibroblast cells. Previously reported flow cytometry kinetic results for these DSB repair phospho-proteins revealed that distributions of intensity were highly skewed, severely limiting the detection of differences in the very low dose range. Distributional analysis reveals significant differences between control and low dose samples when distributions are compared using the Kolmogorov-Smirnov test. Radiation quality differences are found in the distribution shapes and when a nonlinear model is used to relate dosemore » and time to the decay of the mean ratio of phosphoprotein intensities of irradiated samples to controls. We analyzed cell cycle phase and radiation quality dependent characteristic repair times and residual phospho-protein levels with these methods. Characteristic repair times for {gamma}H2AX were higher following Fe nuclei as compared to X-rays in G1 cells (4.5 {+-} 0.46 h vs 3.26 {+-} 0.76 h, respectively), and in S/G2 cells (5.51 {+-} 2.94 h vs 2.87 {+-} 0.45 h, respectively). The RBE in G1 cells for Fe nuclei relative to X-rays for {gamma}H2AX was 2.05 {+-} 0.61 and 5.02 {+-} 3.47, at 2 h and 24-h postirradiation, respectively. For pATF2, a saturation effect is observed with reduced expression at high doses, especially for Fe nuclei, with much slower characteristic repair times (>7 h) compared to X-rays. RBEs for pATF2 were 0.66 {+-} 0.13 and 1.66 {+-} 0.46 at 2 h and 24 h, respectively. Significant differences in {gamma}H2AX and pATF2 levels comparing irradiated samples to control were noted even at the lowest dose analyzed (0.05 Gy) using these methods of analysis. These results reveal that mathematical models can be applied to flow cytometry data to uncover important and subtle differences following exposure to various qualities of low dose radiation.« less

[Effects of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin-resistant adipocytes].

PubMed

Tu, Jun; Luo, Xin-Xin; Li, Bing-Tao; Li, Yu; Xu, Guo-Liang

2016-06-01

Adipocytokines are closely associated with insulin resistance (IR) in adipose tissues, and they are more and more seriously taken in the study of the development of diabetes. This experiment was mainly to study the effect of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin resistant adipocytes, and investigate the molecular mechanism of berberine in enhancing insulin sensitization and application advantages of droplet digital PCR (ddPCR). ddPCR absolute quantification analysis was taken in this experiment to simply and intuitively determine the appropriate reference genes. ddPCR and quantitative Real-time PCR (qPCR) were used to compare the effect of different doses of berberine (10, 20, 50, 100 μmol•L⁻¹) on mRNA expression levels of PPARγ, adiponectin, resistin and leptin in IR 3T3-L1adipocytes. Antagonist GW9662 was added to study the inherent correlation between PPARγ and adiponectin mRNA expression levels. ddPCR results showed that the expression level of β-actin in adipocytes was stable, and suitable as reference gene for normalization of quantitative PCR data. Both of ddPCR and qPCR results showed that, as compared with IR models, the mRNA expression levels of adiponectin were decreased in the treatment with berberine (10, 20, 50, 100 μmol•L⁻¹) in a dose-dependent manner (P<0.01); the expression of PPARγ was decreased by 20, 50, 100 μmol•L⁻¹ berberine in a dose-dependent manner in qPCR assay (P<0.01) and decreased only by 50 and 100 μmol•L⁻¹ berberine in ddPCR assay (P<0.05). PPARγ specific antagonist GW9662 intervention experiment showed that adiponectin gene expression was directly relevant with PPARγ (P<0.05). ddPCR probe assay showed that various doses of berberine could significantly reduce mRNA expression levels of resistin and leptin (P<0.01) in a dose-dependent manner. In conclusion, berberine enhanced insulin sensitization effect not by up-regulating adiponect in expression of transcriptional level in PPARγ-dependent manner, but may by the elevated multimerization of adiponectin in the posttranslational regulation level. Berberine down-regulated the resistin and leptin expression levels, which could alleviate lipolysis and improve IR in adipocytes. ddPCR provided better sensitivity and linear range than qPCR, with obvious technical advantages for the detection of low abundance expression of target genes. Copyright© by the Chinese Pharmaceutical Association.

Effects of fenfluramine on plasma homovanillic acid in healthy subjects.

PubMed

Hollander, E; Stein, D J; Saoud, J B; DeCaria, C M; Cooper, T B; Islam, M N; Liebowitz, M R; Stanley, M

1992-01-01

The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose l-fenfluramine show increases in striatal levels of the dopamine metabolite homovanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.

Prepubertal subchronic exposure to soy milk and glyphosate leads to endocrine disruption.

PubMed

Nardi, Jessica; Moras, Patricia Bonamigo; Koeppe, Carina; Dallegrave, Eliane; Leal, Mirna Bainy; Rossato-Grando, Luciana Grazziotin

2017-02-01

Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing dairy milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Success rates of single-dose methotrexate and additional dose requirements among women with first and previous ectopic pregnancies.

PubMed

Cirik, Derya Akdag; Kinay, Tugba; Keskin, Ugur; Ozden, Eda; Altay, Metin; Gelisen, Orhan

2016-04-01

To compare the success of the single-dose methotrexate regimen and the requirement for a second or third dose of methotrexate between women with their first ectopic pregnancy (EP) and those with previous EP. In a retrospective cohort study, data were analyzed from women treated for EP by single-dose methotrexate at a Turkish tertiary referral center between January 2010 and December 2013. Data were compared between women with at least one previous EP and those with their first EP. The success rate of the protocol in the first and previous EP groups was similar: 93.0% (320/344) and 87.3% (48/55), respectively. History of previous EP was not a predictor of treatment failure. However, the requirement for additional methotrexate doses was significantly higher in the previous EP group (16/48 [33.4%]) than in the first EP group (55/320 [17.2%]; P=0.03). Multivariate analysis showed that history of tubal surgery (P=0.006) and initial levels of the β-subunit of human chorionic gonadotropin (P=0.001) were significant predictors of treatment failure. Although the single-dose regimen had similar success rates in the previous EP and first EP groups, additional doses of methotrexate were more frequently required in the previous EP group. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Dietary Aloe Vera Supplementation Improves Facial Wrinkles and Elasticity and It Increases the Type I Procollagen Gene Expression in Human Skin in vivo

PubMed Central

Cho, Soyun; Lee, Serah; Lee, Min-Jung; Lee, Dong Hun; Won, Chong-Hyun; Kim, Sang Min

2009-01-01

Background No studies have yet been undertaken to determine the effect of aloe gel on the clinical signs and biochemical changes of aging skin. Objective We wanted to determine whether dietary aloe vera gel has anti-aging properties on the skin. Methods Thirty healthy female subjects over the age of 45 were recruited and they received 2 different doses (low-dose: 1,200 mg/d, high-dose: 3,600 mg/d) of aloe vera gel supplementation for 90 days. Their baseline status was used as a control. At baseline and at completion of the study, facial wrinkles were measured using a skin replica, and facial elasticity was measured by an in vivo suction skin elasticity meter. Skin samples were taken before and after aloe intake to compare the type I procollagen and matrix metalloproteinase 1 (MMP-1) mRNA levels by performing real-time RT-PCR. Results After aloe gel intake, the facial wrinkles improved significantly (p<0.05) in both groups, and facial elasticity improved in the lower-dose group. In the photoprotected skin, the type I procollagen mRNA levels were increased in both groups, albeit without significance; the MMP-1 mRNA levels were significantly decreased in the higher-dose group. Type I procollagen immunostaining was substantially increased throughout the dermis in both groups. Conclusion Aloe gel significantly improves wrinkles and elasticity in photoaged human skin, with an increase in collagen production in the photoprotected skin and a decrease in the collagen-degrading MMP-1 gene expression. However, no dose-response relationship was found between the low-dose and high-dose groups. PMID:20548848

Comparison of low-dose spinal anesthesia and single-shot femoral block combination with conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair.

PubMed

Turhan, K S Cakar; Akmese, R; Ozkan, F; Okten, F F

2015-04-01

In the current prospective, randomized study, we aimed to compare the effects of low dose selective spinal anesthesia with 5 mg of hyperbaric bupivacaine and single-shot femoral nerve block combination with conventional dose selective spinal anesthesia in terms of intraoperative anesthesia characteristics, block recovery characteristics, and postoperative analgesic consumption. After obtaining institutional Ethics Committee approval, 52 ASA I-II patients aged 25-65, undergoing arthroscopic meniscus repair were randomly assigned to Group S (conventional dose selective spinal anesthesia with 10 mg bupivacaine) and Group FS (low-dose selective spinal anesthesia with 5mg bupivacaine +single-shot femoral block with 0.25% bupivacaine). Primary endpoints were time to reach T12 sensory block level, L2 regression, and complete motor block regression. Secondary endpoints were maximum sensory block level (MSBL); time to reach MSBL, time to first urination, time to first analgesic consumption and pain severity at the time of first mobilization. Demographic characteristics were similar in both groups (p > 0.05). MSBL and time to reach T12 sensory level were similar in both groups (p > 0.05). Time to reach L2 regression, complete motor block regression, and time to first micturition were significantly shorter; time to first analgesic consumption was significantly longer; and total analgesic consumption and severity of pain at time of first mobilization were significantly lower in Group FS (p < 0.05). The findings of the current study suggest that addition of single-shot femoral block to low dose spinal anesthesia could be an alternative to conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair. NCT02322372.

Measurement of skin dose from cone-beam computed tomography imaging.

PubMed

Akyalcin, Sercan; English, Jeryl D; Abramovitch, Kenneth M; Rong, Xiujiang J

2013-10-09

To measure surface skin dose from various cone-beam computed tomography (CBCT) scanners using point-dosimeters. A head anthropomorphic phantom was used with nanoDOT optically stimulated luminescence (OSL) dosimeters (Landauer Corp., Glenwood, IL) attached to various anatomic landmarks. The phantom was scanned using multiple exposure protocols for craniofacial evaluations in three different CBCT units and a conventional x-ray imaging system. The dosimeters were calibrated for each of the scan protocols on the different imaging systems. Peak skin dose and surface doses at the eye lens, thyroid, submandibular and parotid gland levels were measured. The measured skin doses ranged from 0.09 to 4.62 mGy depending on dosimeter positions and imaging systems. The average surface doses to the lens locations were ~4.0 mGy, well below the threshold for cataractogenesis (500 mGy). The results changed accordingly with x-ray tube output (mAs and kV) and also were sensitive to scan field of view (SFOV). As compared to the conventional panoramic and cephalometric imaging system, doses from all three CBCT systems were at least an order of magnitude higher. Peak skin dose and surface doses at the eye lens, thyroid, and salivary gland levels measured from the CBCT imaging systems were lower than the thresholds to induce deterministic effects. However, our findings do not justify the routine use of CBCT imaging in orthodontics considering the lifetime-attributable risk to the individual.

Measurement of skin dose from cone-beam computed tomography imaging

PubMed Central

2013-01-01

Objective To measure surface skin dose from various cone-beam computed tomography (CBCT) scanners using point-dosimeters. Materials & methods A head anthropomorphic phantom was used with nanoDOT optically stimulated luminescence (OSL) dosimeters (Landauer Corp., Glenwood, IL) attached to various anatomic landmarks. The phantom was scanned using multiple exposure protocols for craniofacial evaluations in three different CBCT units and a conventional x-ray imaging system. The dosimeters were calibrated for each of the scan protocols on the different imaging systems. Peak skin dose and surface doses at the eye lens, thyroid, submandibular and parotid gland levels were measured. Results The measured skin doses ranged from 0.09 to 4.62 mGy depending on dosimeter positions and imaging systems. The average surface doses to the lens locations were ~4.0 mGy, well below the threshold for cataractogenesis (500 mGy). The results changed accordingly with x-ray tube output (mAs and kV) and also were sensitive to scan field of view (SFOV). As compared to the conventional panoramic and cephalometric imaging system, doses from all three CBCT systems were at least an order of magnitude higher. Conclusions Peak skin dose and surface doses at the eye lens, thyroid, and salivary gland levels measured from the CBCT imaging systems were lower than the thresholds to induce deterministic effects. However, our findings do not justify the routine use of CBCT imaging in orthodontics considering the lifetime-attributable risk to the individual. PMID:24192155

Evaluation of Radiation Doses Due to Consumption of Contaminated Food Items and Calculation of Food Class-Specific Derived Intervention Levels

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

Heinzelman, K M; Mansfield, W G

This document evaluates the expected radiation dose due to the consumption of several specific food classes (dairy, meat, produce, etc.) contaminated with specific radionuclides, and relates concentration levels in food to the detection abilities of typical aboratory analysis/measurement methods. The attached charts present the limiting organ dose as a function of the radionuclide concentration in a particular food class, and allow the user to compare these concentrations and doses to typical analytical detection apabilities. The expected radiation dose depends on several factors: the age of the individual; the radionuclide present in the food; the concentration of the radionuclide in themore » food; and the amount of food consumed. Food consumption rates for individuals of various ges were taken from the 1998 United States Food and Drug Administration (FDA) document, Accidental Radioactive Contamination of HUman Food and Animal Feeds: Recommendations for State and Local Agencies. In that document, the FDA defines the erived Intervention Level (DIL), which is the concentration of a particular radionuclide in food that if consumed could result in an individual receiving a radiation dose exceeding the Protection Action Guide (PAG) thresholds for intervention. This document also resents odified, food class specific DIL, which is calculated using a somewhat modified version of the FDA's procedure. This document begins with an overview of the FDA's DIL calculation, followed by a description of the food class specific DIL calculations, and finally charts of the radiation dose per radioactivity concentration for several food class/radionuclide combinations.« less

Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

DOE PAGES

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; ...

2016-11-30

Here, we report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice weremore » dosed with [ 14C]carboplatin or [ 14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers.« less

Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

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

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong

Here, we report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice weremore » dosed with [ 14C]carboplatin or [ 14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers.« less

Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice.

PubMed

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; Lin, Tzu-Yin; Malfatti, Michael; Haack, Kurt; Ognibene, Ted; Yang, Hongyuan; Airhart, Susan; Turteltaub, Kenneth W; Cimino, George D; Tepper, Clifford G; Drakaki, Alexandra; Chamie, Karim; de Vere White, Ralph; Pan, Chong-Xian; Henderson, Paul T

2017-02-01

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14 C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [ 14 C]carboplatin or [ 14 C]gemcitabine and the resulting drug-DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug-DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug-DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376-87. ©2016 AACR. ©2016 American Association for Cancer Research.