Dosimetry study of diagnostic X-ray using doped iodide normoxic polymer gels

NASA Astrophysics Data System (ADS)

Huang, Y. R.; Chang, Y. J.; Hsieh, L. L.; Liu, M. H.; Liu, J. S.; Chu, C. H.; Hsieh, B. T.

2014-11-01

In radiotherapy, polymer gel dosimeters are used for three-dimensional (3D) dose distribution. However, the doses are within the Gy range. In this study, we attempted to develop a low-dose 3D dosimeter within the mGy range for diagnostic radiology. The effect of the iodinated compound was used as a dose enhancement sensitizer to enhance the dose sensitivity of normoxic polymer gel dosimeters. This study aims to use N-isopropylacrylamide(NIPAM)-based and methacrylic acid (MAGAT)-based gels to evaluate the potential dose enhancement sensitizer, as well as to compare two gels that may be suitable for measuring diagnostic radiation doses. The suitable formulation of NIPAM gel [5% (w/w) gelatin, 5% (w/w) NIPAM, 3% (w/w) N,N‧-methylenebisacrylamide (BIS), 5 mM tetrakis (hydroxymethyl) phosphonium chloride (THPC), and 87% (w/w) deionized distilled water] and MAGAT gel (4% MAA, 9% gelatin, 87% deionized water, and 10 mM THPC) were used and loaded with clinical iodinated contrast medium agent (Iobitridol, Xenetix® 350). Irradiation was conducted using X-ray computed tomography. The irradiation doses ranged from 0 mGy to 80 mGy. Optical computed tomography was the employed gel measurement system. The results indicate that the iodinated contrast agent yields a quantifiable dose enhancement ratio. The dose enhancement ratios of NIPAM and MAGAT gels are 3.35±0.6 and 1.36±0.3, respectively. The developed NIPAM gel in this study could be suitable for measuring diagnostic radiation doses.

Oral desmopressin in central diabetes insipidus.

PubMed Central

Westgren, U; Wittström, C; Harris, A S

1986-01-01

Seven paediatric patients with central diabetes insipidus were studied in an open dose ranging study in hospital followed by a six month study on an outpatient basis to assess the efficacy and safety of peroral administration of DDAVP (desmopressin) tablets. In the dose ranging study a dose dependent antidiuretic response was observed. The response to 12.5-50 mcg was, however, less effective in correcting baseline polyuria than were doses of 100 mcg and above. Patients were discharged from hospital on a preliminary dosage regimen ranging from 100 to 400 mcg three times daily. After an initial adjustment in dosage in three patients at one week follow up, all patients were stabilised on treatment with tablets and reported an adequate water turnover at six months. As with the intranasal route of administration dosage requirements varied from patient to patient, and a dose range rather than standard doses were required. A significant correlation, however, was found for the relation between previous intranasal and present oral daily dosage. No adverse reactions were reported. No clinically significant changes were noted in blood chemistry and urinalysis. All patients expressed a preference for the oral over existing intranasal treatment. Treatment with tablets offers a beneficial alternative to the intranasal route, particularly in patients with chronic rhinitis or impaired vision. PMID:3963868

An end-to-end assessment of range uncertainty in proton therapy using animal tissues.

PubMed

Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

2016-11-21

Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams' superior dose advantage over conventional photon-based radiation therapy.

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

PubMed

KuKanich, Butch; Warner, Matt; Hahn, Kevin

2017-02-01

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

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

Viel, Francis; Duzenli, Cheryl; British Columbia Cancer Agency, Department of Medical Physics, Vancouver Centre

2014-08-15

Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data andmore » a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.« less

A dose ranging study of ibuprofen suspension as an antipyretic.

PubMed Central

Marriott, S C; Stephenson, T J; Hull, D; Pownall, R; Smith, C M; Butler, A

1991-01-01

A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic. PMID:1929509

Study of the Phototransference in GR-200 Dosimetric Material and its Convenience for Dose Re-estimation

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

Baly, L.; Otazo, M. R.; Molina, D.

2006-09-08

A study of the phototransference of charges from deep to dosimetric traps in GR-200 material is presented and its convenience for dose re-estimation in the dose range between 2 and 100mSv is also analyzed. The recovering coefficient (RC) defined as the ratio between the phototransferred thermoluminescence (PTTL) and the original thermoluminescence (TL) of the dosimetric trap was used to evaluate the ratio of phototransferred charges from deep traps and the original charges in the dosimetric traps. The results show the convenience of this method for dose re-estimation for this material in the selected range of doses.

Reduction of the unnecessary dose from the over-range area with a spiral dynamic z-collimator: comparison of beam pitch and detector coverage with 128-detector row CT.

PubMed

Shirasaka, Takashi; Funama, Yoshinori; Hayashi, Mutsukazu; Awamoto, Shinichi; Kondo, Masatoshi; Nakamura, Yasuhiko; Hatakenaka, Masamitsu; Honda, Hiroshi

2012-01-01

Our purpose in this study was to assess the radiation dose reduction and the actual exposed scan length of over-range areas using a spiral dynamic z-collimator at different beam pitches and detector coverage. Using glass rod dosimeters, we measured the unilateral over-range scan dose between the beginning of the planned scan range and the beginning of the actual exposed scan range. Scanning was performed at detector coverage of 80.0 and 40.0 mm, with and without the spiral dynamic z-collimator. The dose-saving ratio was calculated as the ratio of the unnecessary over-range dose, with and without the spiral dynamic z-collimator. In 80.0 mm detector coverage without the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 108, 120, and 126 mm, corresponding to a beam pitch of 0.60, 0.80, and 0.99, respectively. With the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 48, 66, and 84 mm with a beam pitch of 0.60, 0.80, and 0.99, respectively. The dose-saving ratios with and without the spiral dynamic z-collimator for a beam pitch of 0.60, 0.80, and 0.99 were 35.07, 24.76, and 13.51%, respectively. With 40.0 mm detector coverage, the dose-saving ratios with and without the spiral dynamic z-collimator had the highest value of 27.23% with a low beam pitch of 0.60. The spiral dynamic z-collimator is important for a reduction in the unnecessary over-range dose and makes it possible to reduce the unnecessary dose by means of a lower beam pitch.

SU-E-T-396: Dosimetric Accuracy of Proton Therapy for Patients with Metal Implants in CT Scans Using Metal Deletion Technique (MDT) Artifacts Reduction

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

Li, X; Kantor, M; Zhu, X

2014-06-01

Purpose: To evaluate the dosimetric accuracy for proton therapy patients with metal implants in CT using metal deletion technique (MDT) artifacts reduction. Methods: Proton dose accuracies under CT metal artifacts were first evaluated using a water phantom with cylindrical inserts of different materials (titanium and steel). Ranges and dose profiles along different beam angles were calculated using treatment planning system (Eclipse version 8.9) on uncorrected CT, MDT CT, and manually-corrected CT, where true Hounsfield units (water) were assigned to the streak artifacts. In patient studies, the treatment plans were developed on manually-corrected CTs, then recalculated on MDT and uncorrected CTs.more » DVH indices were compared between the dose distributions on all the CTs. Results: For water phantom study with 1/2 inch titanium insert, the proton range differences estimated by MDT CT were with 1% for all beam angles, while the range error can be up to 2.6% for uncorrected CT. For the study with 1 inch stainless steel insert, the maximum range error calculated by MDT CT was 1.09% among all the beam angles compared with maximum range error with 4.7% for uncorrected CT. The dose profiles calculated on MDT CTs for both titanium and steel inserts showed very good agreements with the ones calculated on manually-corrected CTs, while large dose discrepancies calculated using uncorrected CTs were observed in the distal end region of the proton beam. The patient study showed similar dose distribution and DVHs for organs near the metal artifacts recalculated on MDT CT compared with the ones calculated on manually-corrected CT, while the differences between uncorrected and corrected CTs were much pronounced. Conclusion: In proton therapy, large dose error could occur due to metal artifact. The MDT CT can be used for proton dose calculation to achieve similar dose accuracy as the current clinical practice using manual correction.« less

Radiation dose and magnification in pelvic X-ray: EOS™ imaging system versus plain radiographs.

PubMed

Chiron, P; Demoulin, L; Wytrykowski, K; Cavaignac, E; Reina, N; Murgier, J

2017-12-01

In plain pelvic X-ray, magnification makes measurement unreliable. The EOS™ (EOS Imaging, Paris France) imaging system is reputed to reproduce patient anatomy exactly, with a lower radiation dose. This, however, has not been assessed according to patient weight, although both magnification and irradiation are known to vary with weight. We therefore conducted a prospective comparative study, to compare: (1) image magnification and (2) radiation dose between the EOS imaging system and plain X-ray. The EOS imaging system reproduces patient anatomy exactly, regardless of weight, unlike plain X-ray. A single-center comparative study of plain pelvic X-ray and 2D EOS radiography was performed in 183 patients: 186 arthroplasties; 104 male, 81 female; mean age 61.3±13.7years (range, 24-87years). Magnification and radiation dose (dose-area product [DAP]) were compared between the two systems in 186 hips in patients with a mean body-mass index (BMI) of 27.1±5.3kg/m 2 (range, 17.6-42.3kg/m 2 ), including 7 with morbid obesity. Mean magnification was zero using the EOS system, regardless of patient weight, compared to 1.15±0.05 (range, 1-1.32) on plain X-ray (P<10 -5 ). In patients with BMI<25, mean magnification on plain X-ray was 1.15±0.05 (range, 1-1.25) and, in patients with morbid obesity, 1.22±0.06 (range, 1.18-1.32). The mean radiation dose was 8.19±2.63dGy/cm 2 (range, 1.77-14.24) with the EOS system, versus 19.38±12.37dGy/cm 2 (range, 4.77-81.75) with plain X-ray (P<10 -4 ). For BMI >40, mean radiation dose was 9.36±2.57dGy/cm 2 (range, 7.4-14.2) with the EOS system, versus 44.76±22.21 (range, 25.2-81.7) with plain X-ray. Radiation dose increased by 0.20dGy with each extra BMI point for the EOS system, versus 0.74dGy for plain X-ray. Magnification did not vary with patient weight using the EOS system, unlike plain X-ray, and radiation dose was 2.5-fold lower. 3, prospective case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Range-Finding Risk Assessment of Inhalation Exposure to Nanodiamonds in a Laboratory Environment

PubMed Central

Koivisto, Antti J.; Palomäki, Jaana E.; Viitanen, Anna-Kaisa; Siivola, Kirsi M.; Koponen, Ismo K.; Yu, Mingzhou; Kanerva, Tomi S.; Norppa, Hannu; Alenius, Harri T.; Hussein, Tareq; Savolainen, Kai M.; Hämeri, Kaarle J.

2014-01-01

This study considers fundamental methods in occupational risk assessment of exposure to airborne engineered nanomaterials. We discuss characterization of particle emissions, exposure assessment, hazard assessment with in vitro studies, and risk range characterization using calculated inhaled doses and dose-response translated to humans from in vitro studies. Here, the methods were utilized to assess workers’ risk range of inhalation exposure to nanodiamonds (NDs) during handling and sieving of ND powder. NDs were agglomerated to over 500 nm particles, and mean exposure levels of different work tasks varied from 0.24 to 4.96 µg·m−3 (0.08 to 0.74 cm−3). In vitro-experiments suggested that ND exposure may cause a risk for activation of inflammatory cascade. However, risk range characterization based on in vitro dose-response was not performed because accurate assessment of delivered (settled) dose on the cells was not possible. Comparison of ND exposure with common pollutants revealed that ND exposure was below 5 μg·m−3, which is one of the proposed exposure limits for diesel particulate matter, and the workers’ calculated dose of NDs during the measurement day was 74 ng which corresponded to 0.02% of the modeled daily (24 h) dose of submicrometer urban air particles. PMID:24840353

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

PubMed

Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

2013-01-15

We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

PubMed Central

2013-01-01

Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

EPR TOOTH DOSIMETRY OF SNTS AREA INHABITANTS.

PubMed

Sholom, Sergey; Desrosiers, Marc; Bouville, André; Luckyanov, Nicholas; Chumak, Vadim; Simon, Steven L

2007-07-01

The determination of external dose to teeth of inhabitants of settlements near the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry technique to assess radiation doses associated with exposure to radioactive fallout from the test site. In this study, tooth doses have been reconstructed for 103 persons with all studied teeth having been formed before the first nuclear test in 1949. Doses above those received from natural background radiation, termed "accident doses", were found to lie in the range from zero to approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk city was approximately 9 Gy. The variability of reconstructed doses within each of the settlements demonstrated heterogeneity of the deposited fallout as well as variations in lifestyle. The village mean external gamma doses for residents of nine[ settlements were in the range from a few tens of mGy to approximately 100 mGy.

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs

PubMed Central

Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-01-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day. PMID:25874036

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs.

PubMed

Nam, Chunja; Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-03-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

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

Moore, Bria M.; Brady, Samuel L., E-mail: samuel.brady@stjude.org; Kaufman, Robert A.

Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (CF{sub SSDE}{sup organ}) were then multiplied by patient-specific SSDE to estimate patient organ dose. Themore » CF{sub SSDE}{sup organ} were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. IndividualCF{sub SSDE}{sup organ} were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and CF{sub SSDE}{sup organ}, was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusions: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ±10%. In addition, this study provides a complete list of organ dose correlation factors (CF{sub SSDE}{sup organ}) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE.« less

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

PubMed

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

2014-04-01

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

Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

PubMed

Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

2010-08-01

The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

PubMed

Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

2007-05-01

Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

NASA Astrophysics Data System (ADS)

Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

2014-08-01

The purpose of this study was to assess the possibility of introducing site-specific range margins to replace current generic margins in proton therapy. Further, the goal was to study the potential of reducing margins with current analytical dose calculations methods. For this purpose we investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo (MC) simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for seven disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head and neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and MC algorithms to obtain the average range differences and root mean square deviation for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing MC dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head and neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be needed for breast, lung and head and neck treatments. We conclude that the currently used generic range uncertainty margins in proton therapy should be redefined site specific and that complex geometries may require a field specific adjustment. Routine verifications of treatment plans using MC simulations are recommended for patients with heterogeneous geometries.

Quantifying the effect of air gap, depth, and range shifter thickness on TPS dosimetric accuracy in superficial PBS proton therapy.

PubMed

Shirey, Robert J; Wu, Hsinshun Terry

2018-01-01

This study quantifies the dosimetric accuracy of a commercial treatment planning system as functions of treatment depth, air gap, and range shifter thickness for superficial pencil beam scanning proton therapy treatments. The RayStation 6 pencil beam and Monte Carlo dose engines were each used to calculate the dose distributions for a single treatment plan with varying range shifter air gaps. Central axis dose values extracted from each of the calculated plans were compared to dose values measured with a calibrated PTW Markus chamber at various depths in RW3 solid water. Dose was measured at 12 depths, ranging from the surface to 5 cm, for each of the 18 different air gaps, which ranged from 0.5 to 28 cm. TPS dosimetric accuracy, defined as the ratio of calculated dose relative to the measured dose, was plotted as functions of depth and air gap for the pencil beam and Monte Carlo dose algorithms. The accuracy of the TPS pencil beam dose algorithm was found to be clinically unacceptable at depths shallower than 3 cm with air gaps wider than 10 cm, and increased range shifter thickness only added to the dosimetric inaccuracy of the pencil beam algorithm. Each configuration calculated with Monte Carlo was determined to be clinically acceptable. Further comparisons of the Monte Carlo dose algorithm to the measured spread-out Bragg Peaks of multiple fields used during machine commissioning verified the dosimetric accuracy of Monte Carlo in a variety of beam energies and field sizes. Discrepancies between measured and TPS calculated dose values can mainly be attributed to the ability (or lack thereof) of the TPS pencil beam dose algorithm to properly model secondary proton scatter generated in the range shifter. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Genetic effects of radiotherapy for childhood cancer: gonadal dose reconstruction.

PubMed

Stovall, Marilyn; Donaldson, Sarah S; Weathers, Rita E; Robison, Leslie L; Mertens, Ann C; Winther, Jeanette Falck; Olsen, Jorgen H; Boice, John D

2004-10-01

To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death. The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account. Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy. Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.

Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

PubMed Central

Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

2012-01-01

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

Estimation of organ and effective doses from newborn radiography of the chest and abdomen.

PubMed

Ma, Hillgan; Elbakri, Idris A; Reed, Martin

2013-09-01

Neonatal intensive care patients undergo frequent chest and abdomen radiographic imaging. In this study, the organ doses and the effective dose resulting from combined chest-abdomen radiography of the newborn child are determined. These values are calculated using the Monte Carlo simulation software PCXCM 2.0 and compared with direct dose measurements obtained from thermoluminescent detectors (TLDs) in a physical phantom. The effective dose obtained from PCXMC is 21.2 ± 0.7 μSv and that obtained from TLD measurements is 22.0 ± 0.5 μSv. While the two methods are in close agreement with regard to the effective dose, there is a wide range of variation in organ doses, ranging from 85 % difference for the testes to 1.4 % for the lungs. Large organ dose variations are attributed to organs at the edge of the field of view, or organs with large experimental error or simulation uncertainty. This study suggests that PCXMC can be used to estimate organ and effective doses for newborn patients.

Dosimetry in differentiated thyroid carcinoma (12-1402R)

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

Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier

2013-01-15

Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. Withmore » those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose-effect correlation could be determined.« less

EPR TOOTH DOSIMETRY OF SNTS AREA INHABITANTS

PubMed Central

Sholom, Sergey; Desrosiers, Marc; Bouville, André; Luckyanov, Nicholas; Chumak, Vadim

2009-01-01

The determination of external dose to teeth of inhabitants of settlements near the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry technique to assess radiation doses associated with exposure to radioactive fallout from the test site. In this study, tooth doses have been reconstructed for 103 persons with all studied teeth having been formed before the first nuclear test in 1949. Doses above those received from natural background radiation, termed “accident doses”, were found to lie in the range from zero to approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk city was approximately 9 Gy. The variability of reconstructed doses within each of the settlements demonstrated heterogeneity of the deposited fallout as well as variations in lifestyle. The village mean external gamma doses for residents of nine[ settlements were in the range from a few tens of mGy to approximately 100 mGy. PMID:19590746

Cytogenetic effect of low dose gamma-radiation in Hordeum vulgare seedlings: non-linear dose-effect relationship.

PubMed

Geras'kin, Stanislav A; Oudalova, Alla A; Kim, Jin Kyu; Dikarev, Vladimir G; Dikareva, Nina S

2007-03-01

The induction of chromosome aberrations in Hordeum vulgare germinated seeds was studied after ionizing irradiation with doses in the range of 10-1,000 mGy. The relationship between the frequency of aberrant cells and the absorbed dose was found to be nonlinear. A dose-independent plateau in the dose range from about 50 to 500 mGy was observed, where the level of cytogenetic damage was significantly different from the spontaneous level. The comparison of the goodness of the experimental data fitting with mathematical models of different complexity, using the most common quantitative criteria, demonstrated the advantage of a piecewise linear model over linear and polynomial models in approximating the frequency of cytogenetical disturbances. The results of the study support the hypothesis of indirect mechanisms of mutagenesis induced by low doses. Fundamental and applied implications of these findings are discussed.

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

PubMed

Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses.

Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure to inorganic arsenic.

PubMed

Gentry, P R; Yager, J W; Clewell, R A; Clewell, H J

2014-10-01

In the recent National Research Council report on conducting a dose-response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose-response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose-response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose-response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations <100 ppb in epidemiological studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

PubMed

Karlsson, Kristin; Nyman, Jan; Baumann, Pia; Wersäll, Peter; Drugge, Ninni; Gagliardi, Giovanna; Johansson, Karl-Axel; Persson, Jan-Olov; Rutkowska, Eva; Tullgren, Owe; Lax, Ingmar

2013-11-01

To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D(0.1cm3)) was used for further analysis. The median value of D(0.1cm3) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of processor temperature on film dosimetry

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

Srivastava, Shiv P.; Das, Indra J., E-mail: idas@iupui.edu

2012-07-01

Optical density (OD) of a radiographic film plays an important role in radiation dosimetry, which depends on various parameters, including beam energy, depth, field size, film batch, dose, dose rate, air film interface, postexposure processing time, and temperature of the processor. Most of these parameters have been studied for Kodak XV and extended dose range (EDR) films used in radiation oncology. There is very limited information on processor temperature, which is investigated in this study. Multiple XV and EDR films were exposed in the reference condition (d{sub max.}, 10 Multiplication-Sign 10 cm{sup 2}, 100 cm) to a given dose. Anmore » automatic film processor (X-Omat 5000) was used for processing films. The temperature of the processor was adjusted manually with increasing temperature. At each temperature, a set of films was processed to evaluate OD at a given dose. For both films, OD is a linear function of processor temperature in the range of 29.4-40.6 Degree-Sign C (85-105 Degree-Sign F) for various dose ranges. The changes in processor temperature are directly related to the dose by a quadratic function. A simple linear equation is provided for the changes in OD vs. processor temperature, which could be used for correcting dose in radiation dosimetry when film is used.« less

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

NASA Astrophysics Data System (ADS)

Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O'Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

2017-04-01

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

DSC studies on gamma irradiated poly(vinylidene fluoride) applied to high gamma dose dosimetry

NASA Astrophysics Data System (ADS)

Batista, Adriana S. M.; Faria, Luiz O.

2017-11-01

Poly(vinylidene fluoride) homopolymer (PVDF) was investigated for use on high gamma dose dosimetry. Samples were irradiated with gamma doses ranging from 100 kGy to 3000 kGy. Differential scanning calorimetry (DSC) was used to construct an unambiguous relationship between the melting transition latent heat (LM) and the absorbed dose (D). DSC thermograms were taken immediately, 1, 2 and 8 months after the irradiation process revealing that the LMx D relationship presented no change for doses ranging from 100 to 2750 kGy. FTIR and UV-Vis spectroscopy data revealed the radio-induction of C˭O and C˭C bonds. These radio-induced bonds were responsible by the chain stiffening and chain oxidation, respectively. SEM microscopy demonstrates that the spherulitic large crystalline structures present in pristine PVDF are destroyed with doses as low as 100 kGy. The DRX analysis revealed that the main effect of high gamma doses in the crystalline structure of PVDF is to provoke a change from the pristine PVDF α-phase to the γ-phase. Both the ability to detect gamma doses in a large dose range and the low fading features make PVDF homopolymers good candidates to be investigated as high gamma dose dosimeters.

Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

PubMed Central

Ron, Elaine; Brenner, Alina

2013-01-01

Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

High dose-per-pulse electron beam dosimetry: Usability and dose-rate independence of EBT3 Gafchromic films.

PubMed

Jaccard, Maud; Petersson, Kristoffer; Buchillier, Thierry; Germond, Jean-François; Durán, Maria Teresa; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François O; Bailat, Claude

2017-02-01

The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose-per-pulse linear accelerator (linac), capable of delivering electron beams with a mean dose-rate (Ḋ m ) ranging from 0.07 to 3000 Gy/s and a dose-rate in pulse (Ḋ p ) of up to 8 × 10 6 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose-rate dependence of their response. Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋ m dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Ḋ m between 0.55 and 4.40 Gy/min, while Ḋ p dependence was probed at the prototype machine for Ḋ p ranging from 7 × 10 3 to 8 × 10 6 Gy/s. Ḋ p dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo-luminescent dosimeters (TLD) that have been reported as being dose-rate independent up to such high dose-rates. We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋ m dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋ p range attainable at the prototype linac confirming the absence of any dose-rate dependence within the investigated range (7 × 10 3 to 8 × 10 6 Gy/s). This aspect was further corroborated by the linear relationship between the dose-per-pulse (D p ) measured by films and the charge per pulse (C p ) measured at the prototype linac exit. Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose-rate and energy independent. © 2016 American Association of Physicists in Medicine.

Assessment of pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers.

PubMed

Lim, Mi-sun; Seong, Sook Jin; Park, Jeonghyeon; Seo, Jeong Ju; Lee, Joomi; Yu, Kyung-Sang; Lee, Hae Won; Yoon, Young-Ran

2012-04-01

Levofloxacin and cyclosporine show different pharmacokinetic properties, but are known to be dose proportional within the therapeutic range. The authors evaluated the pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two independent, randomized, crossover studies were performed. For levofloxacin, eight volunteers were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or intravenously, followed by a 1-week washout period and administration via the alternate route. After another 1-week washout period, a therapeutic dose (750 mg) was administered to all eight subjects. For cyclosporine, another eight volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with a 1-week washout period. Drug concentrations were determined by LC-MS/MS. For levofloxacin, the mean values for dose-normalized C(max) and AUC(last) with the two doses were as follows: therapeutic dose, 15.2 ± 4.6 ng/ml/mg and 103.6 ± 15.5 ng·h/ml/mg, respectively; low dose, 17.1 ± 6.5 ng/ml/mg and 72.6 ± 8.7 ng·h/ml/mg, respectively. For cyclosporine, the mean values for dose-normalized C(max) and AUC(last) were as follows: therapeutic dose, 4.9 ± 1.5 ng/ml/mg and 15.4 ± 4.9 ng·h/ml/mg, respectively; low dose, 1.6 ± 0.6 ng/ml/mg and 9.3 ± 7.3 ng·h/ml/mg, respectively. In this study levofloxacin, which is completely absorbed and primarily eliminated renally without modification, showed better pharmacokinetic proportionality than cyclosporine, which is poorly absorbed and extensively metabolized.

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women
.

PubMed

Schultze-Mosgau, Marcus-Hillert; Schuett, Barbara; Hafner, Frank-Thorsten; Zollmann, Frank; Kaiser, Andreas; Hoechel, Joachim; Rohde, Beate

2017-01-01

Vilaprisan is a novel, potent, and highly selective progesterone receptor modulator, which might offer a promising option for the treatment of uterine fibroids. In this randomized, placebo-controlled, parallel-group phase 1 study, the pharmacokinetics and safety of vilaprisan were investigated in healthy postmenopausal women. Subjects received a single oral dose of vilaprisan (1, 5, 15, or 30 mg) or placebo and - after a wash-out period - daily doses of the same strength over 28 days. Safety assessments included vital signs, ECGs, clinical laboratory tests, and adverse events. Blood samples for pharmacokinetic (PK) profiles were collected over 14 days after single dose (sd) and multiple dose (md; day 28). Vilaprisan was well tolerated. Mild to moderate adverse events occurred with similar frequency at all dose levels. Following single dose, maximum vilaprisan concentrations were observed 1 - 2 hours post-dose. Terminal half-lives ranged from 31 to 38 hours. Maximum concentrations of vilaprisan (Cmax) and exposure to vilaprisan (AUC) increased roughly dose-proportionally from 3.74 µg/L (1 mg) to 68.6 µg/L (30 mg) and 58.5 µg×h/L to 1,590 µg×h/L, respectively. With daily dosing, accumulation consistent with the long terminal half-life was observed (AUC(0-24)md/AUC(0-24)sd ratios: 1.9 to 3.2). The ratio AUC(0-24)md/AUCsd increased with dose from ~ 1 (1 mg) to 1.5 (30 mg). Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range.
.

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

Poplawski, L; Li, T; Chino, J

Purpose: In brachytherapy, structures surrounding the target have the potential to move between treatments and receive unknown dose. Deformable image registration could overcome challenges through dose accumulation. This study uses two possible deformable dose summation techniques and compares the results to point dose summation currently performed in clinic. Methods: Data for ten patients treated with a Syed template was imported into the MIM software (Cleveland, OH). The deformable registration was applied to structures by masking other image data to a single intensity. The registration flow consisted of the following steps: 1) mask CTs so that each of the structures-of-interest hadmore » one unique intensity; 2) perform applicator — based rigid registration; 3) Perform deformable registration; 4) Refine registration by changing local alignments manually; 5) Repeat steps 1 to 3 until desired structure adequately deformed; 5) Transfer each deformed contours to the first CT. The deformed structure accuracy was determined by a dice similarity coefficient (DSC) comparison with the first fraction. Two dose summation techniques were investigated: a deformation and recalculation on the structure; and a dose deformation and accumulation method. Point doses were used as a comparison value. Results: The Syed deformations have DSC ranging from 0.53 to 0.97 and 0.75 and 0.95 for the bladder and rectum, respectively. For the bladder, contour deformation addition ranged from −34.8% to 0.98% and dose deformation accumulation ranged from −35% to 29.3% difference from clinical calculations. For the rectum, contour deformation addition ranged from −5.2% to 16.9% and the dose deformation accumulation ranged from −29.1% to 15.3% change. Conclusion: Deforming dose for summation leads to different volumetric doses than when dose is recalculated on deformed structures, raising concerns about the accuracy of the deformed dose. DSC alone cannot be used to establish the accuracy of a deformation for brachy dose summation purpose.« less

SU-F-BRD-05: Robustness of Dose Painting by Numbers in Proton Therapy

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

Montero, A Barragan; Sterpin, E; Lee, J

Purpose: Proton range uncertainties may cause important dose perturbations within the target volume, especially when steep dose gradients are present as in dose painting. The aim of this study is to assess the robustness against setup and range errors for high heterogeneous dose prescriptions (i.e., dose painting by numbers), delivered by proton pencil beam scanning. Methods: An automatic workflow, based on MATLAB functions, was implemented through scripting in RayStation (RaySearch Laboratories). It performs a gradient-based segmentation of the dose painting volume from 18FDG-PET images (GTVPET), and calculates the dose prescription as a linear function of the FDG-uptake value on eachmore » voxel. The workflow was applied to two patients with head and neck cancer. Robustness against setup and range errors of the conventional PTV margin strategy (prescription dilated by 2.5 mm) versus CTV-based (minimax) robust optimization (2.5 mm setup, 3% range error) was assessed by comparing the prescription with the planned dose for a set of error scenarios. Results: In order to ensure dose coverage above 95% of the prescribed dose in more than 95% of the GTVPET voxels while compensating for the uncertainties, the plans with a PTV generated a high overdose. For the nominal case, up to 35% of the GTVPET received doses 5% beyond prescription. For the worst of the evaluated error scenarios, the volume with 5% overdose increased to 50%. In contrast, for CTV-based plans this 5% overdose was present only in a small fraction of the GTVPET, which ranged from 7% in the nominal case to 15% in the worst of the evaluated scenarios. Conclusion: The use of a PTV leads to non-robust dose distributions with excessive overdose in the painted volume. In contrast, robust optimization yields robust dose distributions with limited overdose. RaySearch Laboratories is sincerely acknowledged for providing us with RayStation treatment planning system and for the support provided.« less

Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film.

PubMed

Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

2016-01-01

Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were -32.336 and -33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range.

Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film

PubMed Central

Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

2016-01-01

Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were −32.336 and −33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range. PMID:28144120

SU-F-I-33: Estimating Radiation Dose in Abdominal Fat Quantitative CT

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

Li, X; Yang, K; Liu, B

Purpose: To compare size-specific dose estimate (SSDE) in abdominal fat quantitative CT with another dose estimate D{sub size,L} that also takes into account scan length. Methods: This study complied with the requirements of the Health Insurance Portability and Accountability Act. At our institution, abdominal fat CT is performed with scan length = 1 cm and CTDI{sub vol} = 4.66 mGy (referenced to body CTDI phantom). A previously developed CT simulation program was used to simulate single rotation axial scans of 6–55 cm diameter water cylinders, and dose integral of the longitudinal dose profile over the central 1 cm length wasmore » used to predict the dose at the center of one-cm scan range. SSDE and D{sub size,L} were assessed for 182 consecutive abdominal fat CT examinations with mean water-equivalent diameter (WED) of 27.8 cm ± 6.0 (range, 17.9 - 42.2 cm). Patient age ranged from 18 to 75 years, and weight ranged from 39 to 163 kg. Results: Mean SSDE was 6.37 mGy ± 1.33 (range, 3.67–8.95 mGy); mean D{sub size,L} was 2.99 mGy ± 0.85 (range, 1.48 - 4.88 mGy); and mean D{sub size,L}/SSDE ratio was 0.46 ± 0.04 (range, 0.40 - 0.55). Conclusion: The conversion factors for size-specific dose estimate in AAPM Report No. 204 were generated using 15 - 30 cm scan lengths. One needs to be cautious in applying SSDE to small length CT scans. For abdominal fat CT, SSDE was 80–150% higher than the dose of 1 cm scan length.« less

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.

Psychopharmacology of theobromine in healthy volunteers.

PubMed

Baggott, Matthew J; Childs, Emma; Hart, Amy B; de Bruin, Eveline; Palmer, Abraham A; Wilkinson, Joy E; de Wit, Harriet

2013-07-01

Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.

Psychopharmacology of theobromine in healthy volunteers

PubMed Central

Baggott, Matthew J.; Childs, Emma; Hart, Amy B.; de Bruin, Eveline; Palmer, Abraham A.; Wilkinson, Joy E.; de Wit, Harriet

2013-01-01

Background Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, currently evidence for this is limited. Objectives We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Results Caffeine had the expected effects on mood including feelings of alertness, and cardiovascular parameters. Theobromine responses differed according to dose: it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses we also examined individual differences in the drugs' effects in relation to genes related to their target receptors, but few associations were detected. Conclusions This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes effects become negative. PMID:23420115

Dose-response relationship in the treatment of gastrointestinal disorders.

PubMed

Weihrauch, T R; Demol, P

1989-08-01

Numerous clinical studies have been performed to establish efficacy and safety of drugs in gastroenterological disorders. Only in a few if any of these studies, however, the rationale for the optimal dose and the dose regimens, respectively, have been addressed. Adequate and well-controlled dose finding studies play a key role in the clinical assessment of new drugs and in the evaluation of new indications. Hereby the range from the minimal effective dose to the maximal effective and well tolerated dose can be assessed and thus the optimal dose-range and dosage regimen be determined. Meaningful pharmacodynamic studies can be performed in the gastrointestinal tract also in healthy volunteers provided that a method with a high predictability for the desired therapeutic effect is available such as measurement of gastric acid secretion and its inhibition by a drug. Dose finding studies in gastroenterology can be carried out under two main aspects: First, to assess the pharmacodynamic and therapeutic effect of a compound on the gastrointestinal tract (e.g. anti-ulcer drug). Second, to evaluate the side effects of a drug on the gastrointestinal tract (e.g. gastric mucosal damage by non-steroidal anti-inflammatory drugs). For the evaluation of new drugs in gastrointestinal therapy a number of methods are available which yield accurate and reproducible data. While careful clinical-pharmacological dose-response studies using these methods have been carried out already more than a decade ago, it is surprising that therapeutic dose finding studies have become available only during the past few years. For scientific as well as for ethical reasons more trials which determine the optimal therapeutic dose are warranted.

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

Patient-specific dose calculations for pediatric CT of the chest, abdomen and pelvis

PubMed Central

Fraser, Nicholas D.; Carver, Diana E.; Pickens, David R.; Price, Ronald R.; Hernanz-Schulman, Marta; Stabin, Michael G.

2015-01-01

Background Organ dose is essential for accurate estimates of patient dose from CT. Objective To determine organ doses from a broad range of pediatric patients undergoing diagnostic chest–abdomen–pelvis CT and investigate how these relate to patient size. Materials and methods We used a previously validated Monte Carlo simulation model of a Philips Brilliance 64 multi-detector CT scanner (Philips Healthcare, Best, The Netherlands) to calculate organ doses for 40 pediatric patients (M:F=21:19; range 0.6–17 years). Organ volumes and positions were determined from the images using standard segmentation techniques. Non-linear regression was performed to determine the relationship between volume CT dose index (CTDIvol)-normalized organ doses and abdominopelvic diameter. We then compared results with values obtained from independent studies. Results We found that CTDIvol-normalized organ dose correlated strongly with exponentially decreasing abdominopelvic diameter (R2>0.8 for most organs). A similar relationship was determined for effective dose when normalized by dose-length product (R2=0.95). Our results agreed with previous studies within 12% using similar scan parameters (i.e. bowtie filter size, beam collimation); however results varied up to 25% when compared to studies using different bowtie filters. Conclusion Our study determined that organ doses can be estimated from measurements of patient size, namely body diameter, and CTDIvol prior to CT examination. This information provides an improved method for patient dose estimation. PMID:26142256

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

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

Moteabbed, M; Trofimov, A; Testa, M

2014-06-01

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

Peak skin and eye lens radiation dose from brain perfusion CT based on Monte Carlo simulation.

PubMed

Zhang, Di; Cagnon, Chris H; Villablanca, J Pablo; McCollough, Cynthia H; Cody, Dianna D; Stevens, Donna M; Zankl, Maria; Demarco, John J; Turner, Adam C; Khatonabadi, Maryam; McNitt-Gray, Michael F

2012-02-01

The purpose of our study was to accurately estimate the radiation dose to skin and the eye lens from clinical CT brain perfusion studies, investigate how well scanner output (expressed as volume CT dose index [CTDI(vol)]) matches these estimated doses, and investigate the efficacy of eye lens dose reduction techniques. Peak skin dose and eye lens dose were estimated using Monte Carlo simulation methods on a voxelized patient model and 64-MDCT scanners from four major manufacturers. A range of clinical protocols was evaluated. CTDI(vol) for each scanner was obtained from the scanner console. Dose reduction to the eye lens was evaluated for various gantry tilt angles as well as scan locations. Peak skin dose and eye lens dose ranged from 81 mGy to 348 mGy, depending on the scanner and protocol used. Peak skin dose and eye lens dose were observed to be 66-79% and 59-63%, respectively, of the CTDI(vol) values reported by the scanners. The eye lens dose was significantly reduced when the eye lenses were not directly irradiated. CTDI(vol) should not be interpreted as patient dose; this study has shown it to overestimate dose to the skin or eye lens. These results may be used to provide more accurate estimates of actual dose to ensure that protocols are operated safely below thresholds. Tilting the gantry or moving the scanning region further away from the eyes are effective for reducing lens dose in clinical practice. These actions should be considered when they are consistent with the clinical task and patient anatomy.

Safety and pharmacokinetics of the oral iron chelator SP-420 in β-thalassemia.

PubMed

Taher, Ali T; Saliba, Antoine N; Kuo, Kevin H; Giardina, Patricia J; Cohen, Alan R; Neufeld, Ellis J; Aydinok, Yesim; Kwiatkowski, Janet L; Jeglinski, Brenda I; Pietropaolo, Keith; Berk, Gregory; Viprakasit, Vip

2017-12-01

Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for C max and AUC 0-τ over the dose range evaluated. The median t max ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug. © 2017 Wiley Periodicals, Inc.

SU-F-T-587: Quality Assurance of Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) for Patient Specific Plans: A Comparison Between MATRIXX and Delta4 QA Devices

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

Tsai, YC; Lu, SH; Chen, LH

2016-06-15

Purpose: Patient-specific quality assurance (QA) is necessary to accurately deliver high dose radiation to the target, especially for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). Unlike previous 2 dimensional (D) array QA devices, Delta{sup 4} can verify the dose delivery in 3D. In this study, the difference between calculated and measured dose distribution was compared with two QA devices (MATRIXX and Delta{sup 4}) to evaluate the delivery accuracy. Methods: Twenty-seven SRS/SBRT plans with VMAT were verified with point-dose and dose-map analysis. We use an ion chamber (A1SL, 0.053cc) for point-dose measurement. For verification of the dose map, themore » differences between the calculated and measured doses were analyzed with a gamma index using MATRIXX and Delta{sup 4} devices. The passing criteria for gamma evaluation were set at 3 mm for distance-to-agreement (DTA) and 3% for dose-difference. A gamma index less than 1 was defined as the verification passing the criteria and satisfying at least 95% of the points. Results: The mean prescribed dose and fraction was 40 ± 14.41 Gy (range: 16–60) and 10 ± 2.35 fractions (range: 1–8), respectively. In point dose analysis, the differences between the calculated and measured doses were all less than 5% (mean: 2.12 ± 1.13%; range: −0.55% to 4.45%). In dose-map analysis, the average passing rates were 99.38 ± 0.96% (range: 95.31–100%) and 100 ± 0.12% (range: 99.5%–100%) for MATRIXX and Delta{sup 4}, respectively. Even using criteria of 2%/2 mm, the passing rate of Delta{sup 4} was still more than 95% (mean: 99 ± 1.08%; range: 95.6%–100%). Conclusion: Both MATRIXX and Delta{sup 4} offer accurate and efficient verification for SRS/SBRT plans. The results measured by MATRIXX and Delta{sup 4} dosimetry systems are similar for SRS/SBRT performed with the VMAT technique.« less

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

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

Damilakis, J; Stratakis, J; Solomou, G

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

Automated estimation of abdominal effective diameter for body size normalization of CT dose.

PubMed

Cheng, Phillip M

2013-06-01

Most CT dose data aggregation methods do not currently adjust dose values for patient size. This work proposes a simple heuristic for reliably computing an effective diameter of a patient from an abdominal CT image. Evaluation of this method on 106 patients scanned on Philips Brilliance 64 and Brilliance Big Bore scanners demonstrates close correspondence between computed and manually measured patient effective diameters, with a mean absolute error of 1.0 cm (error range +2.2 to -0.4 cm). This level of correspondence was also demonstrated for 60 patients on Siemens, General Electric, and Toshiba scanners. A calculated effective diameter in the middle slice of an abdominal CT study was found to be a close approximation of the mean calculated effective diameter for the study, with a mean absolute error of approximately 1.0 cm (error range +3.5 to -2.2 cm). Furthermore, the mean absolute error for an adjusted mean volume computed tomography dose index (CTDIvol) using a mid-study calculated effective diameter, versus a mean per-slice adjusted CTDIvol based on the calculated effective diameter of each slice, was 0.59 mGy (error range 1.64 to -3.12 mGy). These results are used to calculate approximate normalized dose length product values in an abdominal CT dose database of 12,506 studies.

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

Zhang, J; Zhang, W; Lu, J

Purpose: To investigate the accuracy and feasibility of dose calculations using kilovoltage cone beam computed tomography in cervical cancer radiotherapy using a correction algorithm. Methods: The Hounsfield units (HU) and electron density (HU-density) curve was obtained for both planning CT (pCT) and kilovoltage cone beam CT (CBCT) using a CIRS-062 calibration phantom. The pCT and kV-CBCT images have different HU values, and if the HU-density curve of CBCT was directly used to calculate dose in CBCT images may have a deviation on dose distribution. It is necessary to normalize the different HU values between pCT and CBCT. A HU correctionmore » algorithm was used for CBCT images (cCBCT). Fifteen intensity-modulated radiation therapy (IMRT) plans of cervical cancer were chosen, and the plans were transferred to the pCT and cCBCT data sets without any changes for dose calculations. Phantom and patient studies were carried out. The dose differences and dose distributions were compared between cCBCT plan and pCT plan. Results: The HU number of CBCT was measured by several times, and the maximum change was less than 2%. To compare with pCT, the CBCT and cCBCT has a discrepancy, the dose differences in CBCT and cCBCT images were 2.48%±0.65% (range: 1.3%∼3.8%) and 0.48%±0.21% (range: 0.1%∼0.82%) for phantom study, respectively. For dose calculation in patient images, the dose differences were 2.25%±0.43% (range: 1.4%∼3.4%) and 0.63%±0.35% (range: 0.13%∼0.97%), respectively. And for the dose distributions, the passing rate of cCBCT was higher than the CBCTs. Conclusion: The CBCT image for dose calculation is feasible in cervical cancer radiotherapy, and the correction algorithm offers acceptable accuracy. It will become a useful tool for adaptive radiation therapy.« less

Performance of Al2O3:C optically stimulated luminescence dosimeters for clinical radiation therapy applications.

PubMed

Hu, B; Wang, Y; Zealey, W

2009-12-01

A commercial Optical Stimulated Luminescence (OSL) dosimetry system developed by Landauer was tested to analyse the possibility of using OSL dosimetry for external beam radiotherapy planning checks. Experiments were performed to determine signal sensitivity, dose response range, beam type/energy dependency, reproducibility and linearity. Optical annealing processes to test OSL material reusability were also studied. In each case the measurements were converted into absorbed dose. The experimental results show that OSL dosimetry provides a wide dose response range, good linearity and reproducibility for the doses up to 800cGy. The OSL output is linear with dose up to 600cGy range showing a maximum deviation from linearity of 2.0% for the doses above 600cGy. The standard deviation in response of 20 dosimeters was 3.0%. After optical annealing using incandescent light, the readout intensity decreased by approximately 98% in the first 30 minutes. The readout intensity, I, decreased after repeated optical annealing as a power law, given by I infinity t (-1.3). This study concludes that OSL dosimetry can provide an alternative dosimetry technique for use in in-vivo dosimetry if rigorous measurement protocols are established.

Dosimetric characteristics of a MOSFET dosimeter for clinical electron beams.

PubMed

Manigandan, D; Bharanidharan, G; Aruna, P; Devan, K; Elangovan, D; Patil, Vikram; Tamilarasan, R; Vasanthan, S; Ganesan, S

2009-09-01

The fundamental dosimetric characteristics of commercially available metal oxide semiconductor field effect transistor (MOSFET) detectors were studied for clinical electron beam irradiations. MOSFET showed excellent linearity against doses measured using an ion chamber in the dose range of 20-630cGy. MOSFET reproducibility is better at high doses compared to low doses. The output factors measured with the MOSFET were within +/-3% when compared with those measured with a parallel plate chamber. From 4 to 12MeV, MOSFETs showed a large angular dependence in the tilt directions and less in the axial directions. MOSFETs do not show any dose-rate dependence between 100 and 600MU/min. However, MOSFETs have shown under-response when the dose per pulse of the beam is decreased. No measurable effect in MOSFET response was observed in the temperature range of 23-40 degrees C. The energy dependence of a MOSFET dosimeter was within +/-3.0% for 6-18MeV electron beams and 5.5% for 4MeV ones. This study shows that MOSFET detectors are suitable for dosimetry of electron beams in the energy range of 4-18MeV.

Digital radiography can reduce scoliosis x-ray exposure

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

Kling, T.F. Jr.; Cohen, M.J.; Lindseth, R.E.

1990-09-01

Digital radiology is a new computerized system of acquiring x-rays in a digital (electronic) format. It possesses a greatly expanded dose response curve that allows a very broad range of x-ray dose to produce a diagnostic image. Potential advantages include significantly reduced radiation exposure without loss of image quality, acquisition of images of constant density irrespective of under or over exposure, and reduced repeat rates for unsatisfactory films. The authors prospectively studied 30 adolescents with scoliosis who had both conventional (full dose) and digital (full, one-half, or one-third dose) x-rays. They found digital made AP and lateral image with allmore » anatomic areas clearly depicted at full and one-half dose. Digital laterals were better at full dose and equal to conventional at one-half dose. Cobb angles were easily measured on all one-third dose AP and on 8 of 10 one-third dose digital laterals. Digital clearly depicted the Risser sign at one-half and one-third dose and the repeat rate was nil in this study, indicating digital compensates well for exposure errors. The study indicates that digital does allow radiation dose to be reduced by at least one-half in scoliosis patients and that it does have improved image quality with good contrast over a wide range of x-ray exposure.« less

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

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

2005-07-01

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

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

Islam, M; Ahmad, S; Jin, H

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

Flat Ge-doped optical fibres for food irradiation dosimetry

NASA Astrophysics Data System (ADS)

Noor, N. Mohd; Jusoh, M. A.; Razis, A. F. Abdull; Alawiah, A.; Bradley, D. A.

2015-04-01

Exposing food to radiation can improve hygiene quality, germination control, retard sprouting, and enhance physical attributes of the food product. To provide for food safety, radiation dosimetry in irradiated food is required. Herein, fabricated germanium doped (Ge-doped) optical fibres have been used. The fibres have been irradiated using a gamma source irradiator, doses in the range 1 kGy to 10 kGy being delivered. Using Ge-doped optical fibres of variable size, type and dopant concentration, study has been made of linearity, reproducibility, and fading. The thermoluminescence (TL) yield of the fibres were obtained and compared. The fibres exhibit a linear dose response over the investigated range of doses, with mean reproducibility to within 2.69 % to 8.77 %, exceeding the dose range of all commercial dosimeters used in evaluating high doses for the food irradiation industry. TL fading of the Ge-doped flat fibres has been found to be < 13%.

Prospective study of direct radiation exposure measurements for family members living with patients with prostate (125)I seed implantation: Evidence of radiation safety.

PubMed

Hanada, Takashi; Yorozu, Atsunori; Shinya, Yukiko; Kuroiwa, Nobuko; Ohashi, Toshio; Saito, Shiro; Shigematsu, Naoyuki

2016-01-01

To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to (125)I seed implantation. Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent (125)I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. Our study demonstrated low radiation exposures to family members of patients undergoing (125)I prostate implantation. It was clear that (125)I seed implantation did not pose a threat to the safety of family members. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

PubMed Central

Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses. PMID:28235009

Dosimetric characterization of a single crystal diamond detector in X-ray beams for preclinical research.

PubMed

Kampfer, Severin; Cho, Nathan; Combs, Stephanie E; Wilkens, Jan J

2018-05-29

The aim of this study was to investigate a single crystal diamond detector, the microDiamond detector from PTW (PTW-Freiburg, Freiburg, Germany), concerning the particular requirements in the set-up and energy range used in small animal radiotherapy (RT) research (around 220kV). We tested it to find out the minimal required pre-irradiation dose, the dose linearity, dose rate dependency and the angular response as well as usability in the small animal radiation research platform, SARRP (Xstrahl Ltd., Camberley, UK). For a stable signal in the range of energies used in the study, we found a required pre-irradiation dose of 10Gy. The dose linearity and dose rate dependence measurements showed a very good performance of the microDiamond detector. Regarding the effect of angular dependency, the variation of the response signal is less than 0.5% within the first 15° of the polar angle. In the azimuthal angle, however, there are differences in detector response up to 20%, depending on the range of energies used in the study. In addition, we compared the detector to a radiosensitive film for a profile measurement of a 5×5mm 2 irradiation field. Both methods showed a good accordance with the field size, however, the film has a steeper dose gradient in the penumbra region but also a higher noise than the microDiamond detector. We demonstrated that the microDiamond detector is a useful measurement tool for small animal RT research due to its small size. Nevertheless, it seems to be very important to verify the response of the detector in the given set-up and energy range. Copyright © 2018. Published by Elsevier GmbH.

Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

PubMed Central

Lao, Victoria; Ramos, Courtney L.; Ong, Voon S.; Turteltaub, Kenneth W.

2014-01-01

Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a 14C-labeled microdose versus a 14C-labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng · h/ml and 1,336 ng · h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng · h/ml for the microdose and 418.2 ng · h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals. PMID:25136019

A Monte Carlo study on quantifying the amount of dose reduction by shielding the superficial organs of an Iranian 11-year-old boy

PubMed Central

Akhlaghi, Parisa; Hoseinian-Azghadi, Elie; Miri-Hakimabad, Hashem; Rafat-Motavalli, Laleh

2016-01-01

A method for minimizing organ dose during computed tomography examinations is the use of shielding to protect superficial organs. There are some scientific reports that usage of shielding technique reduces the surface dose to patients with no appreciable loss in diagnostic quality. Therefore, in this Monte Carlo study based on the phantom of a 11-year-old Iranian boy, the effect of using an optimized shield on dose reduction to body organs was quantified. Based on the impact of shield on image quality, lead shields with thicknesses of 0.2 and 0.4 mm were considered for organs exposed directly and indirectly in the scan range, respectively. The results showed that there is 50%–62% reduction in amounts of dose for organs located fully or partly in the scan range at different tube voltages and modeling the true location of all organs in human anatomy, especially the ones located at the border of the scan, range affects the results up to 49%. PMID:28144117

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

PubMed

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

Radiation hardness study of semi-insulating GaAs detectors against 5 MeV electrons

NASA Astrophysics Data System (ADS)

Šagátová, A.; Zaťko, B.; Nečas, V.; Sedlačková, K.; Boháček, P.; Fülöp, M.; Pavlovič, M.

2018-01-01

A radiation hardness study of Semi-Insulating (SI) GaAs detectors against 5 MeV electrons is described in this paper. The influence of two parameters, the accumulative absorbed dose (from 1 to 200 kGy) and the applied dose rate (20, 40 or 80 kGy/h), on detector spectrometric properties were studied. The accumulative dose has influenced all evaluated spectrometric properties and also negatively affected the detector CCE (Charge Collection Efficiency). We have observed its systematic reduction from an initial 79% before irradiation down to about 51% at maximum dose of 200 kGy. Relative energy resolution was also influenced by electron irradiation. Its degradation was obvious in the range of doses from 24 up to a maximum dose of 200 kGy, where an increase from 19% up to 31% at 200 V reverse voltage was noticed. On the other hand, a global increase of detection efficiency with accumulative absorbed dose was observed for all samples. Concerning the actual detector degradation we can assume that the tested SI GaAs detectors will be able to operate up to a dose of 300 kGy at least, when irradiated by 5 MeV electrons. The second investigated parameter of irradiation, the dose rate of chosen ranges, did not greatly alter the spectrometric properties of studied detectors.

Childhood leukemia incidence and exposure to indoor radon, terrestrial and cosmic gamma radiation.

PubMed

Evrard, Anne-Sophie; Hémon, Denis; Billon, Solenne; Laurier, Dominique; Jougla, Eric; Tirmarche, Margot; Clavel, Jacqueline

2006-06-01

This study was undertaken to evaluate the ecological association between terrestrial and cosmic gamma radiation, indoor radon, and acute leukemia incidence among children under 15 y of age. From 1990 to 2001, 5,330 cases of acute leukemia were registered by the French National Registry of Childhood Leukemia and Lymphoma. Exposure to terrestrial gamma radiation was based on measurements, using thermoluminescent dosimeters, at about 1,000 sites covering all the "Départements." In addition, 8,737 indoor terrestrial gamma dose rate measurements covering 62% of the "Départements" and 13,240 indoor radon concentration measurements covering all the "Départements" were made during a national campaign. Cosmic ray doses were estimated in each of the 36,363 "Communes" of France. There was no evidence of an ecological association between terrestrial gamma dose (range: 0.22-0.90 mSv y) or total gamma dose (range: 0.49-1.28 mSv y) and childhood acute leukemia incidence, for acute myeloid leukemia (AML) or for acute lymphoblastic leukemia (ALL), in univariate or multivariate regression analyses including indoor radon. A significant positive association between indoor radon (range: 22-262 Bq m) and AML incidence among children was observed and remained significant in multivariate regression analyses including either terrestrial gamma dose [SIR per 100 Bq m = 1.29 (1.09-1.53)] or total gamma dose [SIR per 100 Bq m = 1.29 (1.09-1.53)]. The study showed no ecological association between terrestrial gamma radiation and childhood leukemia for the range of variation in gamma dose rates observed in France. The moderate ecological association between childhood AML incidence and indoor radon does not appear to be confounded by terrestrial gamma dose.

Organ doses for reference adult male and female undergoing computed tomography estimated by Monte Carlo simulations

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

Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel

2011-03-15

Purpose: To develop a computed tomography (CT) organ dose estimation method designed to readily provide organ doses in a reference adult male and female for different scan ranges to investigate the degree to which existing commercial programs can reasonably match organ doses defined in these more anatomically realistic adult hybrid phantomsMethods: The x-ray fan beam in the SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code MCNPX2.6. The simulated CT scanner model was validated through comparison with experimentally measured lateral free-in-air dose profiles and computed tomography dose index (CTDI) values. The reference adult malemore » and female hybrid phantoms were coupled with the established CT scanner model following arm removal to simulate clinical head and other body region scans. A set of organ dose matrices were calculated for a series of consecutive axial scans ranging from the top of the head to the bottom of the phantoms with a beam thickness of 10 mm and the tube potentials of 80, 100, and 120 kVp. The organ doses for head, chest, and abdomen/pelvis examinations were calculated based on the organ dose matrices and compared to those obtained from two commercial programs, CT-EXPO and CTDOSIMETRY. Organ dose calculations were repeated for an adult stylized phantom by using the same simulation method used for the adult hybrid phantom. Results: Comparisons of both lateral free-in-air dose profiles and CTDI values through experimental measurement with the Monte Carlo simulations showed good agreement to within 9%. Organ doses for head, chest, and abdomen/pelvis scans reported in the commercial programs exceeded those from the Monte Carlo calculations in both the hybrid and stylized phantoms in this study, sometimes by orders of magnitude. Conclusions: The organ dose estimation method and dose matrices established in this study readily provides organ doses for a reference adult male and female for different CT scan ranges and technical parameters. Organ doses from existing commercial programs do not reasonably match organ doses calculated for the hybrid phantoms due to differences in phantom anatomy, as well as differences in organ dose scaling parameters. The organ dose matrices developed in this study will be extended to cover different technical parameters, CT scanner models, and various age groups.« less

Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe.

PubMed

Fahlman, A; Loveridge, A; Wenham, C; Foggin, C; Arnemo, J M; Nyman, G

2005-12-01

The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32 mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepam-tiletamine doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.

Aripiprazole Lauroxil

PubMed Central

Hard, Marjie L.; Mills, Richard J.; Sadler, Brian M.; Turncliff, Ryan Z.; Citrome, Leslie

2017-01-01

Abstract Background Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Methods Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. Findings The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441–882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. Conclusions This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice. PMID:28350572

Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement

PubMed Central

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

Objective To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. Methods We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. Results A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. Conclusions All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement. PMID:24728385

Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement.

PubMed

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88-4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.

Patient-specific dose estimation for pediatric abdomen-pelvis CT

NASA Astrophysics Data System (ADS)

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

2009-02-01

The purpose of this study is to develop a method for estimating patient-specific dose from abdomen-pelvis CT examinations and to investigate dose variation across patients in the same weight group. Our study consisted of seven pediatric patients in the same weight/protocol group, for whom full-body computer models were previously created based on the patients' CT data obtained for clinical indications. Organ and effective dose of these patients from an abdomen-pelvis scan protocol (LightSpeed VCT scanner, 120-kVp, 85-90 mA, 0.4-s gantry rotation period, 1.375-pitch, 40-mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated for the same CT system. The seven patients had effective dose of 2.4-2.8 mSv, corresponding to normalized effective dose of 6.6-8.3 mSv/100mAs (coefficient of variation: 7.6%). Dose variations across the patients were small for large organs in the scan coverage (mean: 6.6%; range: 4.9%-9.2%), larger for small organs in the scan coverage (mean: 10.3%; range: 1.4%-15.6%), and the largest for organs partially or completely outside the scan coverage (mean: 14.8%; range: 5.7%-27.7%). Normalized effective dose correlated strongly with body weight (correlation coefficient: r = -0.94). Normalized dose to the kidney and the adrenal gland correlated strongly with mid-liver equivalent diameter (kidney: r = -0.97; adrenal glands: r = -0.98). Normalized dose to the small intestine correlated strongly with mid-intestine equivalent diameter (r = -0.97). These strong correlations suggest that patient-specific dose may be estimated for any other child in the same size group who undergoes the abdomen-pelvis scan.

Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree

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

Karlsson, Kristin, E-mail: kristin.karlsson@karolinska.se; Department of Oncology-Pathology, Karolinska Institute, Stockholm; Nyman, Jan

2013-11-01

Purpose: To evaluate the dose–response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm{sup 3} up to 2.0 cm{sup 3}]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showedmore » a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm{sup 3} (D{sub 0.1cm3}) was used for further analysis. The median value of D{sub 0.1cm3} (α/β = 3 Gy) was EQD{sub 2,LQ} = 147 Gy{sub 3} (range, 20-293 Gy{sub 3}). For patients who developed atelectasis the median value was EQD{sub 2,LQ} = 210 Gy{sub 3}, and for patients who did not develop atelectasis, EQD{sub 2,LQ} = 105 Gy{sub 3}. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose–response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.« less

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

PubMed

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

2011-06-01

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

Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements

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

Bentefour, El H., E-mail: hassan.bentefour@iba-group.com; Prieels, Damien; Tang, Shikui

Purpose: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. Methods: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification inmore » the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. Results: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. Conclusions: Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.« less

SU-F-T-185: Study of the Robustness of a Proton Arc Technique Based On PBS Beams

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

Wang, Z; Zheng, Y

Purpose: One potential technique to realize proton arc is through using PBS beams from many directions to form overlaid Bragg peak (OBP) spots and placing these OBP spots throughout the target volume to achieve desired dose distribution. In this study, we analyzed the robustness of this proton arc technique. Methods: We used a cylindrical water phantom of 20 cm in radius in our robustness analysis. To study the range uncertainty effect, we changed the density of the phantom by ±3%. To study the setup uncertainty effect, we shifted the phantom by 3 & 5 mm. We also combined the rangemore » and setup uncertainties (3mm/±3%). For each test plan, we performed dose calculation for the nominal and 6 disturbed scenarios. Two test plans were used, one with single OBP spot and the other consisting of 121 OBP spots covering a 10×10cm{sup 2} area. We compared the dose profiles between the nominal and disturbed scenarios to estimate the impact of the uncertainties. Dose calculation was performed with Gate/GEANT based Monte Carlo software in cloud computing environment. Results: For each of the 7 scenarios, we simulated 100k & 10M events for plans consisting of single OBP spot and 121 OBP spots respectively. For single OBP spot, the setup uncertainty had minimum impact on the spot’s dose profile while range uncertainty had significant impact on the dose profile. For plan consisting of 121 OBP spots, similar effect was observed but the extent of disturbance was much less compared to single OBP spot. Conclusion: For PBS arc technique, range uncertainty has significantly more impact than setup uncertainty. Although single OBP spot can be severely disturbed by the range uncertainty, the overall effect is much less when a large number of OBP spots are used. Robustness optimization for PBS arc technique should consider range uncertainty with priority.« less

Accuracy of micro powder dosing via a vibratory sieve-chute system.

PubMed

Besenhard, M O; Faulhammer, E; Fathollahi, S; Reif, G; Calzolari, V; Biserni, S; Ferrari, A; Lawrence, S M; Llusa, M; Khinast, J G

2015-08-01

This paper describes a powder dosing system with a vibratory sieve mounted on a chute that doses particles into a capsule. Vertical vibration occurred with a broad range of frequencies and amplitudes. During dosing events, the fill weight was accurately recorded via a capacitance sensor, covering the capsules and making it possible to analyze filling characteristics, that is, the fill rates and their robustness. The range of frequencies and amplitudes was screened for settings that facilitated reasonable (no blocking, no spilling) fill rates for three lactose powders. The filling characteristics were studied within this operating space. The results reveal similar operating spaces for all investigated powders. The fill rate robustness varied distinctly in the operating space, which is of prime importance for selecting the settings for continuous feeding applications. In addition, we present accurate dosing studies utilizing the knowledge about the filling characteristics of each powder. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

PubMed

Batschinski, K; Dervisis, N G; Kitchell, B E

2014-12-01

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

The impact of different algorithms for ideal body weight on screening for hydroxychloroquine retinopathy in women.

PubMed

Browning, David J; Lee, Chong; Rotberg, David

2014-01-01

To determine how algorithms for ideal body weight (IBW) affect hydroxychloroquine dosing in women. This was a retrospective study of 520 patients screened for hydroxychloroquine retinopathy. Charts were reviewed for sex, height, weight, and daily dose. The outcome measures were ranges of IBW across algorithms; rates of potentially toxic dosing; height thresholds below which 400 mg/d dosing is potentially toxic; and rates for which actual body weight (ABW) was less than IBW. Women made up 474 (91%) of the patients. The IBWs for a height varied from 30-34 pounds (13.6-15.5 kg) across algorithms. The threshold heights below which toxic dosing occurred varied from 62-70 inches (157.5-177.8 cm). Different algorithms placed 16%-98% of women in the toxic dosing range. The proportion for whom dosing should have been based on ABW rather than IBW ranged from 5%-31% across algorithms. Although hydroxychloroquine dosing should be based on the lesser of ABW and IBW, there is no consensus about the definition of IBW. The Michaelides algorithm is associated with the most frequent need to adjust dosing; the Metropolitan Life Insurance, large frame, mean value table with the least frequent need. No evidence indicates that one algorithm is superior to others.

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

PubMed Central

2013-01-01

Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that associated with the label dose of toceranib. This lower dose range of toceranib should be considered for future use in dogs with cancer. PMID:24079884

Hormesis as a biological hypothesis.

PubMed Central

Calabrese, E J; Baldwin, L A

1998-01-01

A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer database searches by using various key word descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential environmental relevance. Numerous biological end points were assessed; growth responses were the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude. The average low-dose maximum stimulation was approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude, with the upper end of the hormetic curve approaching the estimated no observable effect level for the particular end point. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of > 6 doses; with > 3 doses in the hormetic zone. The present analysis suggests that chemical hormesis is a reproducible and relatively common biological phenomenon. A quantitative scheme is presented for future application to the database. PMID:9539030

A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis.

PubMed

Moustafa, Moustafa; Lehrner, Lawrence; Al-Saghir, Fahd; Smith, Mark; Goyal, Sunita; Dillon, Maureen; Hunter, John; Holmes-Farley, Randy

2014-01-01

Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in vitro competitive phosphate binding assay, Genz-644470 bound significantly more phosphate per gram than sevelamer. As a consequence, this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo. Because three different fixed doses of Genz-644470 and sevelamer carbonate were used, phosphate-lowering dose-responses of each agent were also analyzed. A randomized, double-blind, dose-ranging study was conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum phosphorus >5.5 mg/dL) hemodialysis patients were randomized to one of seven fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz-644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day, or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks. The change in serum phosphorus during the treatment period and its dose-response patterns were assessed. Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment. Genz-644470 did not show any advantage in phosphorus lowering per gram of binder compared with sevelamer carbonate. Overall toler-ability was similar between active treatment groups. The tolerability of sevelamer carbonate was consistent with prior studies and with the established safety profile of sevelamer. Both Genz-644470 and sevelamer carbonate effectively lowered serum phosphate levels in a dose-dependent fashion in patients with chronic kidney disease on hemodialysis. However, Genz-644470 did not provide any advantage over sevelamer carbonate in phosphate lowering in vivo, as had been demonstrated in vitro.

A comprehensive study on the relationship between the image quality and imaging dose in low-dose cone beam CT

NASA Astrophysics Data System (ADS)

Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B.

2012-04-01

While compressed sensing (CS)-based algorithms have been developed for the low-dose cone beam CT (CBCT) reconstruction, a clear understanding of the relationship between the image quality and imaging dose at low-dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of the number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding of the tradeoff between the image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image-guided radiation therapy (IGRT). Main findings of this work include (1) under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40-100 total mAs, depending on the specific IGRT applications. (2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with the projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. (3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. (4) The clinically acceptable lowest imaging dose level is task dependent. In our study, 72.8 mAs is a safe dose level for visualizing low-contrast objects, while 12.2 total mAs is sufficient for detecting high-contrast objects of diameter greater than 3 mm.

SU-F-T-613: Multi-Lesion Cranial SRS VMAT Plan Quality

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

Ballangrud, A; Kuo, L; Happersett, L

Purpose: Cranial SRS VMAT plans must have steep dose gradient around each target to reduce dose to normal brain. This study reports on the correlation between gradient index (GI=V50%/V100%), target size and target dose heterogeneity index (HI=PTV Dmax/prescription dose) for multi-lesion cranial SRS VMAT plans. Methods: VMAT plans for 10 cranial cases with 3 to 6 lesions (total 39 lesions) generated in Varian Eclipse V11.0.47 with a fine-tuned AAA beam model and 0.125 cm dose grid were analyzed. One or two iso centers were used depending on the spatial distribution of lesions. Two to nine coplanar and non-coplanar arcs weremore » used per isocenter. Conformity index (CI= V100%/VPTV), HI, and GI were determined for each lesion. Dose to critical structures were recorded. Results: Lesion size ranged from 0.05–11.00 cm3. HI ranged from 1.2–1.4, CI ranged from 1.0–2.8 and GI from 3.1–8.4. Maximum dose to brainstem, chiasm, lenses, optic nerves and eyes ranged from 120–1946 cGy, 47–463 cGy, 9–121 cGy, 14–512 cGy, and 17–294 cGy, respectively. Brain minus PTV (Brain-PTV) V7Gy was in the range 1.1–6.5%, and Brain-PTV Dmean was in the range 94–324 cGy. Conclusion: This work shows that a GI < 5 can be achieved for lesions > 0.4cc. For smaller lesions, GI increases rapidly. GI is lower when HI is increased. Based on this study, recommend HI is 1.4, and recommended GI is for volumes <0.1cc GI<9, 0.1–0.4cc GI<6, 0.4–0.1.0cc GI<5, and for volumes >1.0cc GI<4. CI is < 1.3 for all lesions except for targets < 0.1cc. Cranial SRS VMAT plans must be optimized to lower the GI to reduce the dose to normal brain tissue.« less

Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers.

PubMed

Martin, David E; Blum, Robert; Doto, Judy; Galbraith, Hal; Ballow, Charles

2007-01-01

Bevirimat [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] is a novel inhibitor of HIV-1 maturation. This study was performed to investigate the pharmacokinetics and safety of bevirimat during repeated dosing in healthy volunteers. The study was a 10-day, randomised, double-blind, placebo-controlled, dose escalation study. A total of 48 healthy male volunteers, aged 19-54 years, took part in the study. Treatment was administered for 10 days in six escalating dose cohorts (n = 8 in each cohort; 6 bevirimat, 2 placebo). The doses of bevirimat given in each successive cohort were 25 mg, 50 mg, 75 mg (with 150 mg loading dose), 100 mg, 150 mg and 200mg. Safety follow-up was performed 28 days after the first dose. PHARMACOKINETIC AND STATISTICAL ANALYSIS: Plasma bevirimat levels were measured from blood samples collected pre-dose on days 1-10 and then at approximately 48-hour intervals until 21 days after dosing started. On days 1 and 10, further blood samples were obtained at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours after dosing. Urine samples were collected in the morning on days 1, 5 and 11 and at the end of the study for the measurement of cortisol and 6beta-hydroxycortisol. The pharmacokinetic parameters of bevirimat were estimated using non-compartmental methods. Dose proportionality of exposure to bevirimat, assessed by the maximum plasma concentration and the area under the plasma concentration-time curve. The mean terminal elimination half-life of bevirimat ranged from 56.3 to 69.5 hours, and the mean clearance ranged from 173.9 to 185.8 mL/hour. Bevirimat showed approximately 4-fold greater accumulation on day 10 compared with day 1, and the degree of accumulation was similar with all doses. Maximum plasma concentrations ranged from 8 to 58 microg/mL at day 10. Testing for dose-proportionality showed that exposure to bevirimat was proportional to the dose, both after a single dose and after repeat dosing for 10 days. Measurement of the urinary 6beta-hydroxycortisol/cortisol ratio indicated that bevirimat did not affect cytochrome P450 3A activity. Repeated dosing with bevirimat for 10 days was well tolerated. There was no increase in adverse events observed for bevirimat compared with placebo, and no serious adverse events occurred. No clinically relevant changes in vital signs, physical examination or clinical laboratory evaluations were observed. Bevirimat shows dose-proportional pharmacokinetics during repeated dosing for 10 days. Its accumulation is approximately 4-fold greater on day 10 compared with day 1. Repeated dosing with bevirimat is well tolerated. These properties make bevirimat potentially suitable for inclusion in highly active antiretroviral therapy regimens.

Spatial Prediction of Coxiella burnetii Outbreak Exposure via Notified Case Counts in a Dose-Response Model.

PubMed

Brooke, Russell J; Kretzschmar, Mirjam E E; Hackert, Volker; Hoebe, Christian J P A; Teunis, Peter F M; Waller, Lance A

2017-01-01

We develop a novel approach to study an outbreak of Q fever in 2009 in the Netherlands by combining a human dose-response model with geostatistics prediction to relate probability of infection and associated probability of illness to an effective dose of Coxiella burnetii. The spatial distribution of the 220 notified cases in the at-risk population are translated into a smooth spatial field of dose. Based on these symptomatic cases, the dose-response model predicts a median of 611 asymptomatic infections (95% range: 410, 1,084) for the 220 reported symptomatic cases in the at-risk population; 2.78 (95% range: 1.86, 4.93) asymptomatic infections for each reported case. The low attack rates observed during the outbreak range from (Equation is included in full-text article.)to (Equation is included in full-text article.). The estimated peak levels of exposure extend to the north-east from the point source with an increasing proportion of asymptomatic infections further from the source. Our work combines established methodology from model-based geostatistics and dose-response modeling allowing for a novel approach to study outbreaks. Unobserved infections and the spatially varying effective dose can be predicted using the flexible framework without assuming any underlying spatial structure of the outbreak process. Such predictions are important for targeting interventions during an outbreak, estimating future disease burden, and determining acceptable risk levels.

Cumulative doses analysis in young trauma patients: a single-centre experience.

PubMed

Salerno, Sergio; Marrale, Maurizio; Geraci, Claudia; Caruso, Giuseppe; Lo Re, Giuseppe; Lo Casto, Antonio; Midiri, Massimo

2016-02-01

Multidetector computed tomography (MDCT) represents the main source of radiation exposure in trauma patients. The radiation exposure of young patients is a matter of considerable medical concern due to possible long-term effects. Multiple MDCT studies have been observed in the young trauma population with an increase in radiation exposure. We have identified 249 young adult patients (178 men and 71 women; age range 14-40 years) who had received more than one MDCT study between June 2010 and June 2014. According to the International Commission on Radiological Protection publication, we have calculated the cumulative organ dose tissue-weighting factors by using CT-EXPO software(®). We have observed a mean cumulative dose of about 27 mSv (range from 3 to 297 mSv). The distribution analysis is characterised by low effective dose, below 20 mSv, in the majority of the patients. However, in 29 patients, the effective dose was found to be higher than 20 mSv. Dose distribution for the various organs analysed (breasts, ovaries, testicles, heart and eye lenses) shows an intense peak for lower doses, but in some cases high doses were recorded. Even though cumulative doses may have long-term effects, which are still under debate, high doses are observed in this specific group of young patients.

Radiation Dose Index of Renal Colic Protocol CT Studies in the United States

PubMed Central

Lukasiewicz, Adam; Bhargavan-Chatfield, Mythreyi; Coombs, Laura; Ghita, Monica; Weinreb, Jeffrey; Gunabushanam, Gowthaman; Moore, Christopher L.

2016-01-01

Purpose To determine radiation dose indexes for computed tomography (CT) performed with renal colic protocols in the United States, including frequency of reduced-dose technique usage and any institutional-level factors associated with high or low dose indexes. Materials and Methods The Dose Imaging Registry (DIR) collects deidentified CT data, including examination type and dose indexes, for CT performed at participating institutions; thus, the DIR portion of the study was exempt from institutional review board approval and was HIPAA compliant. CT dose indexes were examined at the institutional level for CT performed with a renal colic protocol at institutions that contributed at least 10 studies to the registry as of January 2013. Additionally, patients undergoing CT for renal colic at a single institution (with institutional review board approval and informed consent from prospective subjects and waiver of consent from retrospective subjects) were studied to examine individual renal colic CT dose index patterns and explore relationships between patient habitus, demographics, and dose indexes. Descriptive statistics were used to analyze dose indexes, and linear regression and Spearman correlations were used to examine relationships between dose indexes and institutional factors. Results There were 49 903 renal colic protocol CT examinations conducted at 93 institutions between May 2011 and January 2013. Mean age ± standard deviation was 49 years ± 18, and 53.9% of patients were female. Institutions contributed a median of 268 (interquartile range, 77–699) CT studies. Overall mean institutional dose-length product (DLP) was 746 mGy · cm (effective dose, 11.2 mSv), with a range of 307–1497 mGy · cm (effective dose, 4.6–22.5 mSv) for mean DLPs. Only 2% of studies were conducted with a DLP of 200 mGy · cm or lower (a “reduced dose”) (effective dose, 3 mSv), and only 10% of institutions kept DLP at 400 mGy · cm (effective dose, 6 mSv) or less in at least 50% of patients. Conclusion Reduced-dose renal protocol CT is used infrequently in the United States. Mean dose index is higher than reported previously, and institutional variation is substantial. PMID:24484064

SU-E-T-129: Dosimetric Evaluation of the Impact of Density Correction On Dose Calculation of Breast Cancer Treatment: A Study Based On RTOG 1005 Cases

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

Li, J; Yu, Y

Purpose: RTOG 1005 requires density correction in the dose calculation of breast cancer radiation treatment. The aim of the study was to evaluate the impact of density correction on the dose calculation. Methods: Eight cases were studied, which were planned on an XiO treatment planning system with pixel-by-pixel density correction using a superposition algorithm, following RTOG 1005 protocol requirements. Four were protocol Arm 1 (standard whole breast irradiation with sequential boost) cases and four were Arm 2 (hypofractionated whole breast irradiation with concurrent boost) cases. The plans were recalculated with the same monitor units without density correction. Dose calculations withmore » and without density correction were compared. Results: Results of Arm 1 and Arm 2 cases showed similar trends in the comparison. The average differences between the calculations with and without density correction (difference = Without - With) among all the cases were: -0.82 Gy (range: -2.65∼−0.18 Gy) in breast PTV Eval D95, −0.75 Gy (range: −1.23∼0.26 Gy) in breast PTV Eval D90, −1.00 Gy (range: −2.46∼−0.29 Gy) in lumpectomy PTV Eval D95, −0.78 Gy (range: −1.30∼0.11 Gy) in lumpectomy PTV Eval D90, −0.43% (range: −0.95∼−0.14%) in ipsilateral lung V20, −0.81% (range: −1.62∼−0.26%) in V16, −1.95% (range: −4.13∼−0.84%) in V10, −2.64% (−5.55∼−1.04%) in V8, −4.19% (range: −6.92∼−1.81%) in V5, and −4.95% (range: −7.49∼−2.01%) in V4, respectively. The differences in other normal tissues were minimal. Conclusion: The effect of density correction was observed in breast target doses (an average increase of ∼1 Gy in D95 and D90, compared to the calculation without density correction) and exposed ipsilateral lung volumes in low dose region (average increases of ∼4% and ∼5% in V5 and V4, respectively)« less

Reconstruction of paediatric organ doses from axial CT scans performed in the 1990s - range of doses as input to uncertainty estimates.

PubMed

Olerud, Hilde M; Toft, Benthe; Flatabø, Silje; Jahnen, Andreas; Lee, Choonsik; Thierry-Chef, Isabelle

2016-09-01

To assess the range of doses in paediatric CT scans conducted in the 1990s in Norway as input to an international epidemiology study: the EPI-CT study, http://epi-ct.iarc.fr/ . National Cancer Institute dosimetry system for Computed Tomography (NCICT) program based on pre-calculated organ dose conversion coefficients was used to convert CT Dose Index to organ doses in paediatric CT in the 1990s. Protocols reported from local hospitals in a previous Norwegian CT survey were used as input, presuming these were used without optimization for paediatric patients. Large variations in doses between different scanner models and local scan parameter settings are demonstrated. Small children will receive a factor of 2-3 times higher doses compared with adults if the protocols are not optimized for them. For common CT examinations, the doses to the active bone marrow, breast tissue and brain may have exceeded 30 mGy, 60 mGy and 100 mGy respectively, for the youngest children in the 1990s. The doses children received from non-optimised CT examinations during the 1990s are of such magnitude that they may provide statistically significant effects in the EPI-CT study, but probably do not reflect current practice. • Some organ doses from paediatric CT in the 1990s may have exceeded 100 mGy. • Small children may have received doses 2-3 times higher compared with adults. • Different scanner models varied by a factor of 2-3 in dose to patients. • Different local scan parameter settings gave dose variations of a factor 2-3. • Modern CTs and age-adjusted protocols will give much lower paediatric doses.

Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics

DTIC Science & Technology

2008-05-01

in non-human primates. a. Study behavioral effects of ultra- low doses of intrathecal N/OFQ over a wide dose range using a warm water tail...threshold of monkeys. Figure 1 compares the effects of ultra- low doses of intrathecal N/OFQ (i.e., 1 fmol and 1 pmol) with those of a mu opioid...findings indicate that ultra- low doses of intrathecal N/OFQ did not change the monkey’s thermal nociceptive threshold (Figure 1, middle panels

SU-E-J-11: Measurement of Eye Lens Dose for Varian On-Board Imaging with Different CBCT Acquisition Techniques

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

Deshpande, S; Dhote, D; Kumar, R

Purpose: To measure actual patient eye lens dose for different cone beam computed tomography (CBCT) acquisition protocol of Varian’s On Board Imagining (OBI) system using Optically Stimulated Luminescence (OSL) dosimeter and study the eye lens dose with patient geometry and distance of isocenter to the eye lens Methods: OSL dosimeter was used to measure eye lens dose of patient. OSL dosimeter was placed on patient forehead center during CBCT image acquisition to measure eye lens dose. For three different cone beam acquisition protocol (standard dose head, low dose head and high quality head) of Varian On-Board Imaging, eye lens dosesmore » were measured. Measured doses were correlated with patient geometry and distance between isocenter to eye lens. Results: Measured eye lens dose for standard dose head was in the range of 1.8 mGy to 3.2 mGy, for high quality head protocol dose was in range of 4.5mGy to 9.9 mGy whereas for low dose head was in the range of 0.3mGy to 0.7mGy. Dose to eye lens is depends upon position of isocenter. For posterioraly located tumor eye lens dose is less. Conclusion: From measured doses it can be concluded that by proper selection of imagining protocol and frequency of imaging, it is possible to restrict the eye lens dose below the new limit set by ICRP. However, undoubted advantages of imaging system should be counter balanced by careful consideration of imaging protocol especially for very intense imaging sequences for Adoptive Radiotherapy or IMRT.« less

Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice

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

Sailer, Anna M., E-mail: karmanna@stanford.edu; Paulis, Leonie, E-mail: leonie.paulis@mumc.nl; Vergoossen, Laura

PurposeKnowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.Materials and MethodsAll interventional radiologists, vascular surgeons, and technicians wore personal dose meters (PDMs, DoseAware, Philips Healthcare). The dose monitoring system simultaneously registered for each procedure dose-related data as the dose area product (DAP) and effective staff dose (E) from PDMs. Use and type of shielding were recorded separately. All procedures were analyzed according to proceduremore » type; these included among others cerebral interventions (n = 112), iliac and/or caval venous recanalization procedures (n = 68), endovascular aortic repair procedures (n = 63), biliary duct interventions (n = 58), and percutaneous gastrostomy procedure (n = 28).ResultsMedian (±IQR) DAP doses ranged from 2.0 (0.8–3.1) (percutaneous gastrostomy) to 84 (53–147) Gy cm{sup 2} (aortic repair procedures). Median (±IQR) first operator doses ranged from 1.6 (1.1–5.0) μSv to 33.4 (12.1–125.0) for these procedures, respectively. The relative exposure, determined as first operator dose normalized to procedural DAP, ranged from 1.9 in biliary interventions to 0.1 μSv/Gy cm{sup 2} in cerebral interventions, indicating large variation in staff dose per unit DAP among the procedure types.ConclusionReal-time dose monitoring was able to identify the types of interventions with either an absolute or relatively high staff dose, and may allow for specific optimization of radiation protection.« less

Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: Results of a double-blind randomized clinical trial

PubMed Central

Flanigan, Kevin M.; Voit, Thomas; Rosales, Xiomara Q.; Servais, Laurent; Kraus, John E.; Wardell, Claire; Morgan, Allison; Dorricott, Susie; Nakielny, Joanna; Quarcoo, Naashika; Liefaard, Lia; Drury, Tom; Campion, Giles; Wright, Padraig

2014-01-01

Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2′-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after a single subcutaneous administration in non-ambulatory subjects. Eligible subjects were non-ambulant boys aged ≥9 years, in wheelchairs for ≥1 to ≤4 years, with a diagnosis of DMD resulting from a mutation correctable by drisapersen treatment. Four dose cohorts were planned (3, 6, 9 and 12 mg/kg), but study objectives were met with the 9 mg/kg dose. Less than proportional increase in exposure was demonstrated over the 3–9 mg/kg dose range, though post hoc analysis showed dose proportionality was more feasible over the 3–6 mg/kg range. Single doses of drisapersen at 3 and 6 mg/kg did not result in significant safety or tolerability concerns; however, at the 9 mg/kg dose, pyrexia and transient elevations in inflammatory parameters were seen. The maximum tolerated dose of 6 mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population. PMID:24321374

Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma

PubMed Central

Khare, Shruti; Lila, Anurag R.; Patil, Rishikesh; Phadke, Milind; Kerkar, Prafulla; Bandgar, Tushar; Shah, Nalini S.

2017-01-01

Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. Results: Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16–58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12–155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26–1196 mg; interquartile range: 104–416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3–4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves. Conclusion: Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure. PMID:28217516

The Impact of Azilsartan Medoxomil Treatment (Capsule Formulation) at Doses Ranging From 10 to 80 mg: Significant, Rapid Reductions in Clinic Diastolic and Systolic Blood Pressure.

PubMed

Perez, Alfonso; Cao, Charlie

2017-03-01

In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d. ©2016 Wiley Periodicals, Inc.

A swinging seesaw as a novel model mechanism for time-dependent hormesis under dose-dependent stimulatory and inhibitory effects: A case study on the toxicity of antibacterial chemicals to Aliivibrio fischeri.

PubMed

Sun, Haoyu; Calabrese, Edward J; Zheng, Min; Wang, Dali; Pan, Yongzheng; Lin, Zhifen; Liu, Ying

2018-08-01

Hormesis occurs frequently in broadly ranging biological areas (e.g. plant biology, microbiology, biogerontology), toxicology, pharmacology and medicine. While numerous mechanisms (e.g. receptor and pathway mediated pathway responses) account for stimulatory and inhibitory features of hormetic dose responses, the vast majority emphasizes the inclusion of many doses but only one timepoint or use of a single optimized dose that is assessed over a broad range of timepoints. In this paper, a toxicity study was designed using a large number of properly spaced doses with responses determined over a large number of timepoints, which could help us reveal the underlying mechanism of hormesis. We present the results of a dose-time-response study on hormesis using five antibacterial chemicals on the bioluminescence of Aliivibrio fischeri, measuring expression of protein mRNA based on quorum sensing, simulating bioluminescent reaction and analyzing toxic actions of test chemicals. The findings show dose-time-dependent responses conforming to the hormetic dose-response model, while revealing unique response dynamics between agent induced stimulatory and inhibitory effects within bacterial growth phase dynamics. These dynamic dose-time features reveal a type of biological seesaw model that integrates stimulatory and inhibitory responses within unique growth phase, dose and time features, which has faultlessly explained the time-dependent hormetic phenomenon induced by five antibacterial chemicals (characterized by low-dose stimulation and high-dose inhibition). This study offers advances in understanding cellular dynamics, the biological integration of diverse and opposing responses and their role in evolutionary adaptive strategies to chemicals, which can provide new insight into the mechanistic investigation of hormesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Age- and gender-specific estimates of cumulative CT dose over 5 years using real radiation dose tracking data in children.

PubMed

Lee, Eunsol; Goo, Hyun Woo; Lee, Jae-Yeong

2015-08-01

It is necessary to develop a mechanism to estimate and analyze cumulative radiation risks from multiple CT exams in various clinical scenarios in children. To identify major contributors to high cumulative CT dose estimates using actual dose-length product values collected for 5 years in children. Between August 2006 and July 2011 we reviewed 26,937 CT exams in 13,803 children. Among them, we included 931 children (median age 3.5 years, age range 0 days-15 years; M:F = 533:398) who had 5,339 CT exams. Each child underwent at least three CT scans and had accessible radiation dose reports. Dose-length product values were automatically extracted from DICOM files and we used recently updated conversion factors for age, gender, anatomical region and tube voltage to estimate CT radiation dose. We tracked the calculated CT dose estimates to obtain a 5-year cumulative value for each child. The study population was divided into three groups according to the cumulative CT dose estimates: high, ≥30 mSv; moderate, 10-30 mSv; and low, <10 mSv. We reviewed clinical data and CT protocols to identify major contributors to high and moderate cumulative CT dose estimates. Median cumulative CT dose estimate was 5.4 mSv (range 0.5-71.1 mSv), and median number of CT scans was 4 (range 3-36). High cumulative CT dose estimates were most common in children with malignant tumors (57.9%, 11/19). High frequency of CT scans was attributed to high cumulative CT dose estimates in children with ventriculoperitoneal shunt (35 in 1 child) and malignant tumors (range 18-49). Moreover, high-dose CT protocols, such as multiphase abdomen CT (median 4.7 mSv) contributed to high cumulative CT dose estimates even in children with a low number of CT scans. Disease group, number of CT scans, and high-dose CT protocols are major contributors to higher cumulative CT dose estimates in children.

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry.

PubMed

González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

2016-05-01

This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dose ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

PubMed

Mourad, Waleed F; Young, Brett M; Young, Rebekah; Blakaj, Dukagjin M; Ohri, Nitin; Shourbaji, Rania A; Manolidis, Spiros; Gámez, Mauricio; Kumar, Mahesh; Khorsandi, Azita; Khan, Majid A; Shasha, Daniel; Blakaj, Adriana; Glanzman, Jonathan; Garg, Madhur K; Hu, Kenneth S; Kalnicki, Shalom; Harrison, Louis B

2013-09-01

Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. Published by Elsevier Ltd.

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

Battum, LJ van; Heukelom, S

Purpose This study investigates the origin of lateral optical density (OD) variation for Gafchromic film (EBT and EBT2) scanned in transmission mode with Epson flatbed scanners (1680 Expression Pro and 10000XL). Effects investigated are: cross talk, optical path length and polarization. Methods Cross talk has been examined with triangular shaped light-transmission sheets with OD ranging from 0 to opaque. Optical path length has been studied with absorptive and reflective OD-filters (OD range 0.2 to 2.0). Dependency on light-polarization on the scanner read out has been investigated using linear polarizer sheets. All experiments have been performed at centre scanner position (normmore » point) and at several lateral scan positions, without and with (un)irradiated EBT-film. Dose values used ranged between 0.2 to 9 Gy, yielding an OD-range between 0.25 to 1.1. Results The lateral OD variation is dose dependent and increases up to 14% at most lateral position for dose up to 9 Gy. Cross talk effect contributes to 0.5% in clinical used OD ranges but equals 2% for extreme high dose gradients. Film induced optical path length will effect the lateral OD variation up to 3% at most lateral points. Light polarization is inherent present in these scanners due to multiple reflection on mirrors. In addition film induced polarization is the most important effect generating the observed lateral OD variation. Both Gafchromic film base and sensitive layer have polarizing capabilities; for the sensitive layer its influence is dose dependent. Conclusions Lateral OD variation origins from optical physics (i.e. polarization and reflection) related to scanner and film construction. Cross talk can be ignored in film dosimetry for clinical used dose values and gradients. Therefore it is recommended to determine the lateral OD variation per film type and scanner.« less

A multicenter study of plasma use in the United States

PubMed Central

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

2016-01-01

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

Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

PubMed

Hard, Marjie L; Mills, Richard J; Sadler, Brian M; Turncliff, Ryan Z; Citrome, Leslie

2017-06-01

Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441-882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.

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

Mead, H; St. Jude Children’s Research Hospital, Memphis, TN; Brady, S

Purpose: To discover if a previously published methodology for estimating patient-specific organ dose in a pediatric population (5–55kg) is translatable to the adult sized patient population (> 55 kg). Methods: An adult male anthropomorphic phantom was scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations in the chest and abdominopelvic regions to determine absolute organ dose. Organ-dose-to-SSDE correlation factors were developed by dividing individual phantom organ doses by SSDE of the phantom; where SSDE was calculated at the center of the scan volume of the chest and abdomen/pelvis separately. Organ dose correlation factors developedmore » in phantom were multiplied by 28 chest and 22 abdominopelvic patient SSDE values to estimate organ dose. The median patient weight from the CT examinations was 68.9 kg (range 57–87 kg) and median age was 17 years (range 13–28 years). Calculated organ dose estimates were compared to published Monte Carlo simulated patient and phantom results. Results: Organ-dose-to-SSDE correlation was determined for a total of 23 organs in the chest and abdominopelvic regions. For organs fully covered by the scan volume, correlation in the chest (median 1.3; range 1.1–1.5) and abdominopelvic (median 0.9; range 0.7–1.0) was 1.0 ± 10%. For organs that extended beyond the scan volume (i.e. skin bone marrow and bone surface) correlation was determined to be a median of 0.3 (range 0.1–0.4). Calculated patient organ dose using patient SSDE agreed to better than 6% (chest) and 15% (abdominopelvic) to published values. Conclusion: This study demonstrated that our previous published methodology for calculating organ dose using patient-specific SSDE for the chest and abdominopelvic regions is translatable to adult sized patients for organs fully covered by the scan volume.« less

First clinical implementation of the Capri applicator

PubMed Central

2014-01-01

This study was to assess the Capri applicator for patients with endometrial cancer undergoing high‐radiation dose treatments following external‐beam radiation therapy. The Capri applicator is an inflatable vaginal cylinder with multiple channels. It is used to tailor the dose distribution to an asymmetric vaginal disease, and better spare organs at risk. Five patients with high‐risk endometrial cancer were selected for this study. The patients were treated with a high dose of radiation using the Capri applicator: daily fraction of 7 Gy was prescribed for a total dose of 21 Gy. The treatment plans included radiobiological parameters such as equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and tumor control probability (TCP). Based on the dose‐volume histograms (DVH), we also calculated four quality factors: conformity index (CI), dose homogeneity index (DHI), dose nonuniformity index (DNR), and overdose index (OI). The TCP values range from 82.26% to 95.92%. Very low values of NTCP were observed for the bladder and rectum. The EUDs to organs at risk ranged from 4.65 Gy to 18.22 Gy for the bladder, and from 3.41 Gy from to 6.56 Gy for the rectum. The mean CI was 1.05(SD=0.0008). The mean DNR was 0.10(range0.0−0.295,SD=0.100). The mean OI was 0.019(SD=0.028). The DHIs were in the range of 1.0−0.754(mean0.886,SD=0.116). The use of a multichannel vaginal cylinder may not only help cover extensive vaginal disease, but also reduce the dose to the rectum. This dosimetric analysis shows that rectal doses could be reduced using a multichannel cylinder. However, the dose delivered to the bladder based on EUD calculation may be higher than that obtained with other methods. Each patient must be evaluated independently to determine if a multichannel treatment is appropriate. Clinical followup will show whether this rectal dose sparing translates into a real toxicity improvement. PACS number: 3.6.96.0 PMID:24423857

Population Pharmacokinetics of Rifapentine and Desacetyl Rifapentine in Healthy Volunteers: Nonlinearities in Clearance and Bioavailability

PubMed Central

Lu, Yanhui; Bliven-Sizemore, Erin; Weiner, Marc; Nuermberger, Eric; Burman, William; Dorman, Susan E.; Dooley, Kelly E.

2014-01-01

Rifapentine is under active investigation as a potent drug that may help shorten the tuberculosis (TB) treatment duration. A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine. This study aimed to assess the effects of increasing doses on rifapentine absorption and bioavailability and to evaluate the clearance changes over 14 days. A population analysis was performed with nonlinear mixed-effects modeling. Absorption, time-varying clearance, bioavailability, and empirical and semimechanistic autoinduction models were investigated. A one-compartment model linked to a transit compartment absorption model best described the data. The bioavailability of rifapentine decreased linearly by 2.5% for each 100-mg increase in dose. The autoinduction model suggested a dose-independent linear increase in clearance of the parent drug and metabolite over time from 1.2 and 3.1 liters · h−1, respectively, after a single dose to 2.2 and 5.0 liters · h−1, respectively, after 14 once-daily doses, with no plateau being reached by day 14. In clinical trial simulations using the final model, rifapentine demonstrated less-than-dose-proportional pharmacokinetics, but there was no plateau in exposures over the dose range tested (450 to 1,800 mg), and divided dosing increased exposures significantly. Thus, the proposed compartmental model incorporating daily dosing of rifapentine over a wide range of doses and time-related changes in bioavailability and clearance provides a useful tool for estimation of drug exposure that can be used to optimize rifapentine dosing for TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01162486.) PMID:24614383

Evaluation of various approaches for assessing dose indicators and patient organ doses resulting from radiotherapy cone-beam CT

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

Rampado, Osvaldo, E-mail: orampado@cittadellasalute.to.it; Giglioli, Francesca Romana; Rossetti, Veronica

Purpose: The aim of this study was to evaluate various approaches for assessing patient organ doses resulting from radiotherapy cone-beam CT (CBCT), by the use of thermoluminescent dosimeter (TLD) measurements in anthropomorphic phantoms, a Monte Carlo based dose calculation software, and different dose indicators as presently defined. Methods: Dose evaluations were performed on a CBCT Elekta XVI (Elekta, Crawley, UK) for different protocols and anatomical regions. The first part of the study focuses on using PCXMC software (PCXMC 2.0, STUK, Helsinki, Finland) for calculating organ doses, adapting the input parameters to simulate the exposure geometry, and beam dose distribution inmore » an appropriate way. The calculated doses were compared to readouts of TLDs placed in an anthropomorphic Rando phantom. After this validation, the software was used for analyzing organ dose variability associated with patients’ differences in size and gender. At the same time, various dose indicators were evaluated: kerma area product (KAP), cumulative air-kerma at the isocenter (K{sub air}), cone-beam dose index, and central cumulative dose. The latter was evaluated in a single phantom and in a stack of three adjacent computed tomography dose index phantoms. Based on the different dose indicators, a set of coefficients was calculated to estimate organ doses for a range of patient morphologies, using their equivalent diameters. Results: Maximum organ doses were about 1 mGy for head and neck and 25 mGy for chest and pelvis protocols. The differences between PCXMC and TLDs doses were generally below 10% for organs within the field of view and approximately 15% for organs at the boundaries of the radiation beam. When considering patient size and gender variability, differences in organ doses up to 40% were observed especially in the pelvic region; for the organs in the thorax, the maximum differences ranged between 20% and 30%. Phantom dose indexes provided better correlation with organ doses than K{sub air} and KAP, with average ratios ranging between 0.9 and 1.1 and variations for different organs and protocols below 20%. The triple phantom setup allowed us to take into account scatter dose contributions, but nonetheless, the correlation with the evaluated organ doses was not improved with this method. Conclusions: The simulation of rotational geometry and of asymmetric beam distribution by means of PCXMC 2.0 enabled us to determine patient organ doses depending on weight, height and gender. Alternatively, the measurement of an in phantom dose indicator combined with proper correction coefficients can be a useful tool for a first dose estimation of in-field organs. The data and coefficients provided in this study can be applied to any patient undergoing a scan by an Elekta XVI equipment.« less

Fast, epithermal and thermal photoneutron dosimetry in air and in tissue equivalent phantom for a high-energy X-ray medical accelerator.

PubMed

Sohrabi, Mehdi; Hakimi, Amir

2018-02-01

Photoneutron (PN) dosimetry in fast, epithermal and thermal energy ranges originated from the beam and albedo neutrons in high-energy X-ray medical accelerators is highly important from scientific, technical, radiation protection and medical physics points of view. Detailed dose equivalents in the fast, epithermal and thermal PN energy ranges in air up to 2m as well as at 35 positions from the central axis of 12 cross sections of the phantom at different depths were determined in 18MV X-ray beams of a Siemens ONCOR accelerator. A novel dosimetry method based on polycarbonate track dosimeters (PCTD)/ 10 B (with/without cadmium cover) was used to determine and separate different PN dose equivalents in air and in a multilayer polyethylene phantom. Dose equivalent distributions of PNs, as originated from the main beam and/or albedo PNs, on cross-plane, in-plane and diagonal axes in 10cm×10cm fields are reported. PN dose equivalent distributions on the 3 axes have their maxima at the isocenter. Epithermal and thermal PN depth dose equivalent distributions in the phantom for different positions studied peak at ∼3cm depth. The neutron dosimeters used for the first time in such studies are highly effective for separating dose equivalents of PNs in the studied energy ranges (beam and/or albedo). The PN dose equivalent data matrix made available in this paper is highly essential for detailed patient dosimetry in general and for estimating secondary cancer risks in particular. Copyright © 2017. Published by Elsevier GmbH.

RECONSTRUCTION OF RADIATION DOSES IN A CASE-CONTROL STUDY OF THYROID CANCER FOLLOWING THE CHERNOBYL ACCIDENT

PubMed Central

Drozdovitch, Vladimir; Khrouch, Valeri; Maceika, Evaldas; Zvonova, Irina; Vlasov, Oleg; Bratilova, Angelica; Gavrilin, Yury; Goulko, Guennadi; Hoshi, Masaharu; Kesminiene, Ausrele; Shinkarev, Sergey; Tenet, Vanessa; Cardis, Elisabeth; Bouville, Andre

2010-01-01

A population-based case-control study of thyroid cancer was carried out in contaminated regions of Belarus and Russia among persons who were exposed during childhood and adolescence to fallout from the Chernobyl accident. For each study subject, individual thyroid doses were reconstructed for the following pathways of exposure: (1) intake of 131I via inhalation and ingestion; (2) intake of short-lived radioiodines (132I, 133I, and 135I) and radiotelluriums (131mTe, 132Te) via inhalation and ingestion; (3) external dose from radionuclides deposited on the ground; and (4) ingestion of 134Cs and 137Cs. A series of intercomparison exercises validated the models used for reconstruction of average doses to populations of specific age groups as well as of individual doses. Median thyroid doses from all factors for study subjects were estimated to be 0.37 and 0.034 Gy in Belarus and Russia, respectively. The highest individual thyroid doses among the subjects were 10.2 Gy in Belarus and 5.3 Gy in Russia. Iodine-131 intake was the main pathway for thyroid exposure. Estimated doses from short-lived radioiodines and radiotelluriums ranged up to 0.53 Gy. Reconstructed individual thyroid doses from external exposure ranged up to 0.1 Gy, while those from internal exposure due to ingested cesium did not exceed 0.05 Gy. The uncertainty of the reconstructed individual thyroid doses, characterized by the geometric standard deviation, varies from 1.7 to 4.0 with a median of 2.2. PMID:20539120

The nonuniformity of antibody distribution in the kidney and its influence on dosimetry.

PubMed

Flynn, Aiden A; Pedley, R Barbara; Green, Alan J; Dearling, Jason L; El-Emir, Ethaar; Boxer, Geoffrey M; Boden, Robert; Begent, Richard H J

2003-02-01

The therapeutic efficacy of radiolabeled antibody fragments can be limited by nephrotoxicity, particularly when the kidney is the major route of extraction from the circulation. Conventional dose estimates in kidney assume uniform dose deposition, but we have shown increased antibody localization in the cortex after glomerular filtration. The purpose of this study was to measure the radioactivity in cortex relative to medulla for a range of antibodies and to assess the validity of the assumption of uniformity of dose deposition in the whole kidney and in the cortex for these antibodies with a range of radionuclides. Storage phosphor plate technology (radioluminography) was used to acquire images of the distributions of a range of antibodies of various sizes, labeled with 125I, in kidney sections. This allowed the calculation of the antibody concentration in the cortex relative to the medulla. Beta-particle point dose kernels were then used to generate the dose-rate distributions from 14C, 131I, 186Re, 32P and 90Y. The correlation between the actual dose-rate distribution and the corresponding distribution calculated assuming uniform antibody distribution throughout the kidney was used to test the validity of estimating dose by assuming uniformity in the kidney and in the cortex. There was a strong inverse relationship between the ratio of the radioactivity in the cortex relative to that in the medulla and the antibody size. The nonuniformity of dose deposition was greatest with the smallest antibody fragments but became more uniform as the range of the emissions from the radionuclide increased. Furthermore, there was a strong correlation between the actual dose-rate distribution and the distribution when assuming a uniform source in the kidney for intact antibodies along with medium- to long-range radionuclides, but there was no correlation for small antibody fragments with any radioisotope or for short-range radionuclides with any antibody. However, when the cortex was separated from the whole kidney, the correlation between the actual dose-rate distribution and the assumed dose-rate distribution, if the source was uniform, increased significantly. During radioimmunotherapy, the extent of nonuniformity of dose deposition in the kidney depends on the properties of the antibody and radionuclide. For dosimetry estimates, the cortex should be taken as a separate source region when the radiopharmaceutical is small enough to be filtered by the glomerulus.

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

SU-C-12A-05: Radiation Dose in High-Pitch Pediatric Cardiac CTA: Correlation Between Lung Dose and CTDIvol, DLP, and Size Specific Dose Estimates (SSDE)

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

Wang, J; Kino, A; Newman, B

2014-06-01

Purpose: To investigate the radiation dose for pediatric high pitch cardiac CTA Methods: A total of 14 cases were included in this study, with mean age of 6.2 years (ranges from 2 months to 15 years). Cardiac CTA was performed using a dual-source CT system (Definition Flash, Siemens). Tube voltage (70, 80 and 100kV) was chosen based on patient weight. All patients were scanned using a high-pitch spiral mode (pitch ranges from 2.5 to 3) with tube current modulation technique (CareDose4D, Siemens). For each case, the three dimensional dose distributions were calculated using a Monte Carlo software package (IMPACT-MC, CTmore » Image GmbH). Scanning parameters of each exam, including tube voltage, tube current, beamshaping filters, beam collimation, were defined in the Monte Carlo calculation. Tube current profile along projection angles was obtained from projection data of each tube, which included data within the over-scanning range along z direction. The volume of lungs was segmented out with CT images (3DSlicer). Lung doses of all patients were calculated and compared with CTDIvol, DLP, and SSDE. Results: The average (range) of CTDIvol, DLP and SSDE of all patients was 1.19 mGy (0.58 to 3.12mGy), 31.54 mGy*cm (12.56 to 99 mGy*cm), 2.26 mGy (1.19 to 6.24 mGy), respectively. Radiation dose to the lungs ranged from 0.83 to 4.18 mGy. Lung doses correlated with CTDIvol, DLP and SSDE with correlation coefficients(k) at 0.98, 0.93, and 0.99. However, for the cases with CTDIvol less than 1mGy, only SSDE preserved a strong correlation with lung doses (k=0.83), while much weaker correlations were found for CTDIvol (k=0.29) and DLP (k=-0.47). Conclusion: Lung doses to pediatric patients during Cardiac CTA were estimated. SSDE showed the most robust correlation with lung doses in contrast to CTDIvol and DLP.« less

Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature.

PubMed

Kaster, Tyler S; Yaremko, Brian; Palma, David A; Rodrigues, George B

2015-03-01

To identify survival and toxicity characteristics associated with radical-intent hypofractionated radiotherapy for the treatment of stage III non-small-cell lung cancer (NSCLC). Relevant studies were identified from a systematic PubMed search of articles published between January 1990 and January 2014. All studies were peer reviewed and included both retrospective and prospective studies of NSCLC patients being treated with radical hypofractionated radiotherapy. Data on overall survival (OS) and toxicity were extracted from each of the studies where available. Of 685 studies initially identified by the search, a total of 33 studies were found to be relevant and were included in this systematic review. The number of fractions ranged from 15 to 35, the dose per fraction ranged from 2.3 to 3.5 Gy, and the delivered dose ranged from 45.0 to 85.5 Gy. Fifteen of the studies included concurrent chemotherapy, while 18 did not. OS was found to be associated with tumor biological effective dose, with the Pearson correlation coefficient ranging from 0.34 to 0.48. For both concurrent and nonconcurrent chemoradiotherapy acute pulmonary, late esophageal and late pulmonary incidences of toxicity ranged from 1.2% to 12.2%, but had 95% confidence intervals that included zero. The greatest incidence of toxicity was acute esophageal toxicity at 14.9% (95% confidence interval, 0.7%, 29.1%). There is a moderate linear relationship between biological effective dose and OS, and greater acute esophageal toxicity with concurrent chemotherapy. Improving outcomes in stage III NSCLC may involve some form of hypofractionation in the context of systemic concurrent therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

Han, C; Schultheiss, T

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

SU-F-J-197: A Novel Intra-Beam Range Detection and Adaptation Strategy for Particle Therapy

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

Chen, M; Jiang, S; Shao, Y

2016-06-15

Purpose: In-vivo range detection/verification is crucial in particle therapy for effective and safe delivery. The state-of-art techniques are not sufficient for in-vivo on-line range verification due to conflicts among patient dose, signal statistics and imaging time. We propose a novel intra-beam range detection and adaptation strategy for particle therapy. Methods: This strategy uses the planned mid-range spots as probing beams without adding extra radiation to patients. Such choice of probing beams ensures the Bragg peaks to remain inside the tumor even with significant range variation from the plan. It offers sufficient signal statistics for in-beam positron emission tomography (PET) duemore » to high positron activity of therapeutic dose. The probing beam signal can be acquired and reconstructed using in-beam PET that allows for delineation of the Bragg peaks and detection of range shift with ease of detection enabled by single-layered spots. If the detected range shift is within a pre-defined tolerance, the remaining spots will be delivered as the original plan. Otherwise, a fast re-optimization using range-shifted beamlets and accounting for the probing beam dose is applied to consider the tradeoffs posed by the online anatomy. Simulated planning and delivery studies were used to demonstrate the effectiveness of the proposed techniques. Results: Simulations with online range variations due to shifts of various foreign objects into the beam path showed successful delineation of the Bragg peaks as a result of delivering probing beams. Without on-line delivery adaptation, dose distribution was significantly distorted. In contrast, delivery adaptation incorporating detected range shift recovered well the planned dose. Conclusion: The proposed intra-beam range detection and adaptation utilizing the planned mid-range spots as probing beams, which illuminate the beam range with strong and accurate PET signals, is a safe, practical, yet effective approach to address range uncertainty issues in particle therapy.« less

Radiosurgery for Para-IAC Meningiomas: The Effect of Radiation Dose to the Cochlea on Hearing Outcome

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

Kim, Young-Hoon; Department of Neurosurgery, Seoul National University College of Medicine, Seoul; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr

2012-11-01

Purpose: This study was performed to assess the radiosurgical results of meningiomas extending into the internal acoustic canal (para-IAC meningiomas), with a particular focus on the effect of radiation dose to the cochlea on hearing outcome. Methods and Materials: A total of 50 patients who underwent radiosurgery for para-IAC meningiomas between 1998 and 2009, which were followed for 2 years, were enrolled. The mean age was 55.8 years (range, 15-75). The mean tumor volume was 6.1 cm{sup 3} (range, 1.0-19.0), the mean tumor length in the IAC was 6.9 mm (range, 1.3-13.3), and the mean prescribed marginal dose was 13.1more » Gy (range, 10-15) at an isodose line of 50%. The mean follow-up duration was 46 months (range, 24-122). Results: Eight (16.0%) patients had nonserviceable hearing at the time of surgery. At the last follow-up, the tumor control rate was 94%; unchanged in 17 patients, decreased in 30 patients, and increased in 3 patients. Among 42 patients with serviceable hearing at the time of radiosurgery, it was preserved in 41 (97.6%) patients at the last follow-up. The maximal and mean radiation doses to the cochleae of these 41 patients were 5.8 Gy {+-} 0.3 (range, 3.1-11.5) and 4.3 Gy {+-} 0.2 (range, 2.2-7.5), respectively. The maximal dose to the cochlea of the patient who lost hearing after radiosurgery was 4.7 Gy. Conclusions: The radiation dose to the cochlea may have the minimal toxic effect on the hearing outcome in patients who undergo radiosurgery for para-IAC meningiomas.« less

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning.

PubMed

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A

2016-05-01

Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose-volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Estimation of annual occupational effective doses from external ionizing radiation at medical institutions in Kenya

NASA Astrophysics Data System (ADS)

Korir, Geoffrey; Wambani, Jeska; Korir, Ian

2011-04-01

This study details the distribution and trends of doses due to occupational radiation exposure among radiation workers from participating medical institutions in Kenya, where monthly dose measurements were collected for a period of one year ranging from January to December in 2007. A total of 367 medical radiation workers were monitored using thermoluminescent dosemeters. They included radiologists (27%), oncologists (2%), dentists (4%), Physicists (5%), technologists (45%), nurses (4%), film processor technicians (3%), auxiliary staff (4%), and radiology office staff (5%). The average annual effective dose of all categories of staff was found to range from 1.19 to 2.52 mSv. This study formed the initiation stage of wider, comprehensive and more frequent monitoring of occupational radiation exposures and long-term investigations into its accumulation patterns in our country.

A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study.

PubMed

Buller, Harry R; Lensing, Anthonie W A; Prins, Martin H; Agnelli, Giancarlo; Cohen, Alexander; Gallus, Alexander S; Misselwitz, Frank; Raskob, Gary; Schellong, Sebastian; Segers, Annelise

2008-09-15

We performed a randomized dose-ranging study, double-blind for rivaroxaban doses and open-label for the comparator (low-molecular-weight heparin followed by vitamin K antagonists) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator. Treatment lasted for 84 days. The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline. The main safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding. A total of 449 (83%) of the 543 patients could be included in the per-protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and 6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 9.9% of those receiving standard therapy. The main safety outcome occurred in 5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 8.8% of those receiving standard therapy. These results with simple fixed-dose oral regimens justify phase 3 evaluations (www.ClinicalTrials.gov no.NCT00395772).

The dose-response of Harshaw TLD-700H.

PubMed

Velbeck, K J; Luo, L Z; Ramlo, M J; Rotunda, J E

2006-01-01

Harshaw TLD-700H (7LiF:Mg,Cu,P) was previously characterised for low- to high-dose ranges from 1 microGy to 20 Gy. This paper describes the studies and results of dose-response and linearity at much higher doses. TLD-700H is a near perfect dosimetric material with near tissue equivalence, flat energy response, and the ability to measure beta, gamma and X rays. These new results extend the applicability of Harshaw TLD-700H into more dosimetric measurement environments. The simple glow curve structure provides insignificant fade, eliminating special oven preparation methods experienced by other materials. The work presented in this paper quantifies the performance of Harshaw TLD-700H in extended ranges.

Organ dose assessment in pediatric fluoroscopy and CT via a tomographic computational phantom of the newborn patient

NASA Astrophysics Data System (ADS)

Staton, Robert J.

Of the various types of imaging modalities used in pediatric radiology, fluoroscopy and computed tomography (CT) have the highest associated radiation dose. While these examinations are commonly used for pediatric patients, little data exists on the magnitude of the organ and effective dose values for these procedures. Calculation of these dose values is necessary because of children's increased sensitivity to radiation and their long life expectancy for which to express radiation's latent effects. In this study, a newborn tomographic phantom has been implemented in a radiation transport code to evaluate organ and effective doses for newborn patients in commonly performed fluoroscopy and CT examinations. Organ doses were evaluated for voiding cystourethrogram (VCUG) fluoroscopy studies of infant patients. Time-sequence analysis was performed for videotaped VCUG studies of five different patients. Organ dose values were then estimated for each patient through Monte Carlo (MC) simulations. The effective dose values of the VCUG examination for five patients ranged from 0.6 mSv to 3.2 mSv, with a mean of 1.8 +/- 0.9 mSv. Organ doses were also assessed for infant upper gastrointestinal (UGI) fluoroscopy exams. The effective dose values of the UGI examinations for five patients ranged from 1.05 mSv to 5.92 mSv, with a mean of 2.90 +/- 1.97 mSv. MC simulations of helical multislice CT (MSCT) exams were also completed using, the newborn tomographic phantom and a stylized newborn phantom. The helical path of the source, beam shaping filter, beam profile, patient table, were all included in the MC simulations of the helical MSCT scanner. Organ doses and effective doses and their dependence on scan parameters were evaluated for newborn patients. For all CT scans, the effective dose was found to range approximately 1-13 mSv, with the largest values occurring for CAP scans. Tube current modulation strategies to reduce patient dose were also evaluated for newborn patients. Overall, utilization of the newborn tomographic phantom in MC simulations has shown the need for and usefulness of pediatric tomographic phantoms. The newborn tomographic model has shown more versatility and realistic anatomical modeling when compared to the existing stylized newborn phantom. This work has provided important organ dose data for infant patients in common examinations in pediatric radiology.

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique.

PubMed

Gandhi, Diksha; Crotty, Dominic J; Stevens, Grant M; Schmidt, Taly Gilat

2015-11-01

This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%-20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.

Tolerability and pharmacokinetic profile of a sunitinib powder formulation in pediatric patients with refractory solid tumors: a Children's Oncology Group study.

PubMed

DuBois, Steven G; Shusterman, Suzanne; Reid, Joel M; Ingle, Ashish M; Ahern, Charlotte H; Baruchel, Sylvain; Glade-Bender, Julia; Ivy, Percy; Adamson, Peter C; Blaney, Susan M

2012-04-01

Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m(2)/day. This study was conducted to evaluate sunitinib given as a powder formulation. Sunitinib 15 mg/m(2) was administered orally daily for 4 weeks on/2 weeks off to patients <21 years old with refractory solid tumors. Sunitinib capsules were opened, and the powder sprinkled onto applesauce or yogurt. Plasma levels of sunitinib and an active metabolite, SU12662, were measured, and pharmacokinetic parameters were estimated. 12 patients, median age 13 (range 4-21) years, were treated. The most common first-cycle toxicities were leucopenia (n = 6), fatigue (n = 5), neutropenia (n = 4), and hypertension (n = 4). Three patients had dose-limiting toxicities (DLTs) in cycle 1 (dizziness/back pain, hand-foot syndrome, and intratumoral hemorrhage/hypoxia). A median peak plasma sunitinib concentration of 21 (range 6-36) ng/ml was reached at a median of 4 (range 4-8) h after the first dose. The median exposure (AUC(0-48)) was 585 (range 196-1,059) h ng/l. The median half-life was 23 (range 13-36) h. The median trough concentration measured before day 14 dosing was 32 (range 12-58) ng/ml. The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules. The powder formulation allows patients unable to swallow capsules to receive sunitinib.

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

Moore, B; Brady, S; Kaufman, R

Purpose: Investigate the correlation of SSDE with organ dose in a pediatric population. Methods: Four anthropomorphic phantoms, representing a range of pediatric body habitus, were scanned with MOSFET dosimeters placed at 23 organ locations to determine absolute organ dosimetry. Phantom organ dosimetry was divided by phantom SSDE to determine correlation between organ dose and SSDE. Correlation factors were then multiplied by patient SSDE to estimate patient organ dose. Patient demographics consisted of 352 chest and 241 abdominopelvic CT examinations, 22 ± 15 kg (range 5−55 kg) mean weight, and 6 ± 5 years (range 4 mon to 23 years) meanmore » age. Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm. 23 organ correlation factors were determined in the chest and abdominopelvic region across nine pediatric weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7−1.4) and abdominopelvic (average 0.9; range 0.7−1.3) was near unity. For organs that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1−0.4) for both the chest and abdominopelvic regions, respectively. Pediatric organ dosimetry was compared to published values and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusion: Average correlation of SSDE and organ dosimetry was found to be better than ± 10% for fully covered organs within the scan volume. This study provides a list of organ dose correlation factors for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE.« less

The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review.

PubMed

Gebremedhn, Endale Gebreegziabher; Shortland, Peter John; Mahns, David Anthony

2018-04-12

Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle. A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy. Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1-4) was the most common event with prevalence ranging from 4-98%, followed by haematological (1.4-81%) and gastrointestinal (1.2-67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m 2 ) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase. Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.

Traditional medicine and gastroprotective crude drugs.

PubMed

Schmeda-Hirschmann, Guillermo; Yesilada, Erdem

2005-08-22

A frequent question when dealing with the search for gastroprotective compounds from natural sources is how far or close are both the plant preparations and extract amounts from the doses recommended in traditional medicine and what should be considered realistic levels for experimental studies. The administration way is oral and therefore extracts and products should be administered by gavage when looking for validation of ethnopharmacological uses. Suggestions of doses for both crude extracts and pure compounds are presented and discussed. For plant extracts prepared from single herbs and herbal mixtures, dose-response studies in the range between 100 and 300 mg/kg are suggested, with more than a single gastric ulcer model either in rats or mice. A suitable reference compound should be used according to the ulcer model and in doses resembling those used for human patients. For pure compounds and structure-activity studies or trends, dose-response results should be provided for at least a parent compound in order to select a reasonable dose for comparison purposes. We suggest an evaluation of the activity of the parent compound in the 50-300 mg/kg range and to look for structural modification leading to derivatives with similar or higher gastroprotective effects than the reference antiulcer compounds.

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

NASA Technical Reports Server (NTRS)

Hada, M.; George, Kerry; Cucinotta, Francis A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

Flat Ge-doped optical fibres for food irradiation dosimetry

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

Noor, N. Mohd; Jusoh, M. A.; Razis, A. F. Abdull

Exposing food to radiation can improve hygiene quality, germination control, retard sprouting, and enhance physical attributes of the food product. To provide for food safety, radiation dosimetry in irradiated food is required. Herein, fabricated germanium doped (Ge-doped) optical fibres have been used. The fibres have been irradiated using a gamma source irradiator, doses in the range 1 kGy to 10 kGy being delivered. Using Ge-doped optical fibres of variable size, type and dopant concentration, study has been made of linearity, reproducibility, and fading. The thermoluminescence (TL) yield of the fibres were obtained and compared. The fibres exhibit a linear dosemore » response over the investigated range of doses, with mean reproducibility to within 2.69 % to 8.77 %, exceeding the dose range of all commercial dosimeters used in evaluating high doses for the food irradiation industry. TL fading of the Ge-doped flat fibres has been found to be < 13%.« less

SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

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

Bichay, T; Mayville, A

2016-06-15

Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fractionmore » and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.« less

SU-E-T-115: Dose Perturbation Study of Self-Expandable Metal and Polyester Esophageal Stents in Proton Therapy Beams

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

Lee, S; Li, Z; Jalaj, S

2014-06-01

Purpose: This work investigates dose perturbations due to Self-expandable metal and polyester esophageal stents undergoing proton radiotherapy for esophageal cancer. Methods: Five commercially available esophageal stents made of nitinol (Evolution, Wallflex and Ultraflex), stainless steel (Z-Stent) and polyester (Polyflex) were tested. Radiochromic film (GafChromic EBT3 film, Ashland, Covington, KY) wrapped around a stent and a 12cc syringe was irradiated with 2CGE (Cobalt Gray Equivalent) of proton beam in a custom fabricated acrylic phantom. An air-hollow syringe simulates the esophagus. Results: The Z-stent created the largest dose perturbations ranges from -14.5% to 6.1% due to the steel composition. The WallFlex, Evolutionmore » and Ultraflex stents produced the dose perturbation ranges of (−9.2%∼8.6%), (−6.8%∼5.7%) and (−6.2%∼6.2%), respectively. The PolyFlex stent contains the radiopaque tungsten markers located top, middle and bottom portions. When the focal cold spots induced by the markers were excluded in the analysis, the dose perturbation range was changed from (−11.6%∼6.4%) to (−0.6%∼5.0%). Conclusion: The magnitude of dose perturbation is related to material of a metallic stent. The non-metallic stent such as PolyFlex shows relatively lower dose perturbation than metallic stents except a radiopaque marker region. Overall Evolution and Ultraflex stent appear to be less dose perturbations. The largest dose perturbations (cold spots) were located at both edges of stents in distal area for the single proton beam irradiation study. The analysis of more than two proton beam which is more typical clinical beam arrangement would be necessary to minimize the doe perturbation effect in proton ratiotherapy.« less

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

Size-specific dose estimate (SSDE) provides a simple method to calculate organ dose for pediatric CT examinations

PubMed Central

Moore, Bria M.; Brady, Samuel L.; Mirro, Amy E.; Kaufman, Robert A.

2014-01-01

Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) were then multiplied by patient-specific SSDE to estimate patient organ dose. The \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. Individual\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ , was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusions: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ±10%. In addition, this study provides a complete list of organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE. PMID:24989395

Study on the Dose Uncertainties in the Lung during Passive Proton Irradiation with a Proton Beam Range Compensator

NASA Astrophysics Data System (ADS)

Yoo, Seung Hoon; Son, Jae Man; Yoon, Myonggeun; Park, Sung Yong; Shin, Dongho; Min, Byung Jun

2018-06-01

A moving phantom is manufactured for mimicking lung model to study the dose uncertainty from CT number-stopping power conversion and dose calculation in the soft tissue, light lung tissue and bone regions during passive proton irradiation with compensator smearing value. The phantom is scanned with a CT system, and a proton beam irradiation plan is carried out with the use of a treatment planning system (Eclipse). In the case of the moving phantom, a RPM system is used for respiratory gating. The uncertainties in the dose distribution between the measured data and the planned data are investigated by a gamma analysis with 3%-3 mm acceptance criteria. To investigate smearing effect, three smearing values (0.3 cm, 0.7 cm, 1.2 cm) are used to for fixed and moving phantom system. For both fixed and moving phantom, uncertainties in the light lung tissue are severe than those in soft tissue region in which the dose uncertainties are within clinically tolerable ranges. As the smearing value increases, the uncertainty in the proton dose distribution decreases.

A rule-based, dose-finding design for use in stroke rehabilitation research: methodological development.

PubMed

Colucci, E; Clark, A; Lang, C E; Pomeroy, V M

2017-12-01

Dose-optimisation studies as precursors to clinical trials are rare in stroke rehabilitation. To develop a rule-based, dose-finding design for stroke rehabilitation research. 3+3 rule-based, dose-finding study. Dose escalation/de-escalation was undertaken according to preset rules and a mathematical sequence (modified Fibonacci sequence). The target starting daily dose was 50 repetitions for the first cohort. Adherence was recorded by an electronic counter. At the end of the 2-week training period, the adherence record indicated dose tolerability (adherence to target dose) and the outcome measure indicated dose benefit (10% increase in motor function). The preset increment/decrease and checking rules were then applied to set the dose for the subsequent cohort. The process was repeated until preset stopping rules were met. Participants had a mean age of 68 (range 48 to 81) years, and were a mean of 70 (range 9 to 289) months post stroke with moderate upper limb paresis. A custom-built model of exercise-based training to enhance ability to open the paretic hand. Repetitions per minute of extension/flexion of paretic digits against resistance. Usability of the preset rules and whether the maximally tolerated dose was identifiable. Five cohorts of three participants were involved. Discernibly different doses were set for each subsequent cohort (i.e. 50, 100, 167, 251 and 209 repetitions/day). The maximally tolerated dose for the model training task was 209 repetitions/day. This dose-finding design is a feasible method for use in stroke rehabilitation research. Copyright © 2017 Chartered Society of Physiotherapy. All rights reserved.

Safety and pharmacokinetics of NXN-188 after single and multiple doses in five phase I, randomized, double-blind, parallel studies in healthy adult volunteers.

PubMed

Vaughan, David; Speed, Joanne; Medve, Robert; Andrews, John S

2010-01-01

NXN-188 is a dual-action oral therapeutic being developed for the treatment of acute migraine. The mechanism of action of NXN-188 involves inhibition of both the neuronal nitric oxide synthase enzyme isoform and affinity for serotonin (5-hydroxytryptamine1B/D) receptors. The aims of the initial Phase I clinical studies were to compare the pharmacokinetic (PK) properties of NXN-188 administered as a single dose or multiple twice-daily doses to healthy adult volunteers and to determine the tolerability of NXN-188 in these individuals. Healthy adult male and female subjects were enrolled in 5 Phase I, randomized, double-blind studies, all of which (except for a fed/fasted trial) were placebo controlled. In the 4 single-dose studies, which differed with respect to feeding status and the formulation used (capsules or solution), subjects received NXN-188 at doses of 2 to 800 mg (0.027-11.2 mg/kg). In the repeat-dose study, subjects received 50-mg (0.71 mg/kg) doses twice daily for 4 days. Serum samples were analyzed for NXN-188 using validated HPLC-MS/MS methods. Standard clinical laboratory analyses (chemistry, hematology, and urinalysis) and measurements of serum creatine kinase and myoglobin levels were conducted at screening, admission, discharge, and follow-up. Baseline and postexposure values were compared to assess tolerability. Electrocardiography and physical examination were conducted at screening and at discharge and follow-up if any negative change occurred from the previous findings. Vital signs (heart rate, blood pressure, respiration), including assessment for orthostatic changes, were measured at screening, check-in, and follow-up visits (1 hour before dosing, every 30 minutes for the first 4 hours, then every hour for the next 4 hours, then every 4 hours for the remainder of the 24-hour study). Adverse events were recorded, reviewed, and monitored throughout the study. Two hundred three subjects (102 women, 101 men) 18 to 50 years of age were enrolled in the 5 studies; 168 subjects received NXN-188 and 35 received placebo. Most (91%) of the subjects were white; weight ranged from 69.3 to 71.8 kg (body mass index, 24.5-25.8 kg/m(2)). The initial absorption phase of orally administered NXN-188 peaked at approximately 1 hour, followed by a second absorption phase with a T(max) of approximately 4 to 5 hours. Exposure (C(max) and AUC) increased in a slightly greater than dose-proportional manner across a dose range of 2 to 800 mg (0.027-11.2 mg/kg). Elimination was multiexponential, with an initial rapid plasma drug elimination (plasma concentrations decreased approximately 70%-90% from Cmax within 24 hours after dosing), followed by a prolonged clearance phase of very low NXN-188 concentrations ( approximately 1%-5% of Cmax) that persisted for several weeks. Clearance ranged from 70 to 130 L/h, and the NXN-188 halflife ranged from 11 to 178 hours. Neither food nor gender had any measurable effect on the PK properties of NXN-188. Overall, dizziness was reported more often in the NXN-188 groups than in the placebo groups (6.3% vs 2.9%, respectively). Frequently reported adverse events that occurred more often in the placebo groups than in the NXN-188 groups were somnolence (11.4% vs 6.3%, respectively), and headache (8.6% vs 6.9%). Incidences of orthostatic hypotension (6.3% vs 5.7%) and postural (orthostatic) tachycardia syndrome (6.3% vs 5.7%) were comparable in the NXN-188 and placebo groups, respectively. No serious adverse events were reported at any dose of NXN-188 up to the current maximum dose (800 mg or 11.2 mg/kg). NXN-188 exhibited linear pharmaco-kinetics over the dose range studied and appeared to be well tolerated in these healthy volunteers.

Pharmacokinetics and pharmacodynamics of SCT800, a new recombinant FVIII, in hemophilia A mice

PubMed Central

Gu, Ruo-lan; Liu, Liang; Xie, Liang-zhi; Gai, Wen-lin; Cao, Si-shuo; Meng, Zhi-yun; Gan, Hui; Wu, Zhuo-na; Li, Jian; Zheng, Ying; Zhu, Xiao-xia; Dou, Gui-fang

2016-01-01

Aim: SCT800 is a new third-generation recombinant FVIII agent that is undergoing promising preclinical study. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles of SCT800 in hemophilia A mice. Methods: After hemophilia A mice were intravenously injected with single dose of SCT800 (80, 180, and 280 IU/kg) or the commercially available product Xyntha (280 IU/kg), pharmacokinetics profiles were evaluated based on measuring plasma FVIII: C. For pharmacodynamics study, dose-response curves of SCT800 and Xyntha (1–200 IU/kg) were constructed using a tail bleeding model monitoring both bleeding time and blood loss. Results: Pharmacokinetics profile analysis showed a dose independency of SCT800 ranging from 80 to 280 IU/kg and comparable pharmacokinetic profiles between SCT800 and Xyntha at the doses tested. Pharmacodynamics study revealed comparable ED50 values of SCT800 and Xyntha in the tail bleeding model: 14.78 and 15.81 IU/kg for bleeding time, respectively; 13.50 and 13.58 IU/kg for blood loss, respectively. Moreover, at the doses tested, the accompanying dose-related safety evaluation in the tail bleeding model showed lower hypercoagulable tendency and wider dosage range potential for SCT800 than Xyntha. Conclusion: In hemophilia A mice, SCT800 shows comparable pharmacokinetics and pharmacodynamics to Xyntha at the doses tested, and possibly with better safety properties. PMID:26806305

Characterization of commercial MOSFET detectors and their feasibility for in-vivo HDR brachytherapy.

PubMed

Phurailatpam, Reena; Upreti, Rituraj; Nojin Paul, Siji; Jamema, Swamidas V; Deshpande, Deepak D

2016-01-01

The present study was to investigate the use of MOSFET as an vivo dosimeter for the application of Ir-192 HDR brachytherapy treatments. MOSFET was characterized for dose linearity in the range of 50-1000 cGy, depth dose dependence from 2 to 7 cm, angular dependence. Signal fading was checked for two weeks. Dose linearity was found to be within 2% in the dose range (50-1000 cGy). The response varied within 8.07% for detector-source distance of 2-7 cm. The response of MOSFET with the epoxy side facing the source (0 degree) is the highest and the lowest response was observed at 90 and 270 degrees. Signal was stable during the study period. The detector showed high dose linearity and insignificant fading. But due to angular and depth dependence, care should be taken and corrections must be applied for clinical dosimetry. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.

PubMed

Tanaka, Jun; Kasai, Hidefumi; Shimizu, Kenji; Shimasaki, Shigeki; Kumagai, Yuji

2013-03-01

We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10-20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.

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.

Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia.

PubMed

Jakubowski, Joseph A; Hoppe, Carolyn C; Zhou, Chunmei; Smith, Brendan E; Brown, Patricia B; Heath, Lori E; Inusa, Baba; Rees, David C; Small, David S; Gupta, Neehar; Yao, Suqin; Heeney, Matthew; Kanter, Julie

2017-02-28

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients' P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12 ® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136-231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136-231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8  ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.

Dose-dependent establishment of Trichuris suis larvae in Göttingen minipigs.

PubMed

Vejzagić, Nermina; Roepstorff, Allan; Kringel, Helene; Thamsborg, Stig Milan; Nielsen, Mads Pårup; Kapel, Christian M O

2015-03-15

Embryonated eggs of the pig whipworm Trichuris suis (TSOee) constitute the active pharmaceutical ingredient (API) in a medicinal product explored in human clinical trials against several immune-mediated diseases. The measurement of TSO biological potency (hatchability and infectivity) is a requirement for the assessment of TSO's pharmacological potency in human clinical trials. The present study aims to validate the dose-dependent establishment of T. suis larvae in Göttingen minipigs and eventual clinical implication of a dose range (1000-10,000 TSO). Four groups of 5 minipigs were inoculated with doses of 1000, 2500, 7500, and 10,000 TSOee, respectively, to evaluate a range of concentrations of TSOee in a minipig infectivity model. Unembryonated eggs (TSOue) were added to keep the total egg number in the inoculum constant at 10,000 eggs. Two groups received 2500 and 7500 TSOee per pig without the addition of TSOue as controls. The intestinal larval establishment at 21 days post inoculation (dpi) demonstrated a clear positive linear dose-response relationship between numbers of inoculated TSOee and recovered larvae. There was a low level of variation in larval counts in all study groups. Thus, the infectivity model in minipigs within the tested dose range offers a reliable, sensitive and accurate assay for testing biological potency of TSO. Copyright © 2015 Elsevier B.V. All rights reserved.

PHOTODYNAMIC THERAPY (PDT) USING HPPH FOR THE TREATMENT OF PRECANCEROUS LESIONS ASSOCIATED WITH BARRETT’S ESOPHAGUS

PubMed Central

Nava, Hector R; Allamaneni, Shyam S; Dougherty, Thomas J; Cooper, Michele T; Tan, Wei; Wilding, Gregory; Henderson, Barbara W

2011-01-01

Background and Objectives Photodynamic therapy (PDT) with porfimer sodium, FDA approved to treat premalignant lesions in Barrett’s esophagus, causes photosensitivity for 6-8 weeks. HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) shows minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. We also want to know the efficacy of one time treatment with HPPH-PDT. Study Design/Materials and Methods Two nonrandomized dose escalation studies were performed (18 patients each) with biopsy-proven high grade dysplasia or early intramucosal adenocarcinoma of esophagus. HPPH doses ranged from 3 to 6 mg/m2. At 24 or 48 hours after HPPH administration the lesions received one endoscopic exposure to 150, 175 or 200 J/cm of 665 nm light. Results Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Six patients experienced Grade 3 & 4 adverse events (16.6%). Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the drug dose ranging study (light dose of 150 J/cm at 48 h), 3 and 4 mg/m2 of HPPH emerged as most effective. In the light dose ranging study (3 or 4 mg/m2 HPPH, light at 24 h), complete response rates (disappearance of high grade dysplasia and early carcinoma) of 72% were achieved at 1 year, with all patients treated with 3 mg/m2 HPPH plus 175 J/cm and 4 mg/m2 HPPH plus 150 J/cm showing complete responses at 1 year. Conclusions HPPH-PDT for precancerous lesions in Barrett’s esophagus appears to be safe and showing promising efficacy. Further clinical studies are required to establish the use of HPPH-PDT. PMID:22057498

Radiation Dose to the Lens of the Eye from Computed Tomography Scans of the Head

NASA Astrophysics Data System (ADS)

Januzis, Natalie Ann

While it is well known that exposure to radiation can result in cataract formation, questions still remain about the presence of a dose threshold in radiation cataractogenesis. Since the exposure history from diagnostic CT exams is well documented in a patient's medical record, the population of patients chronically exposed to radiation from head CT exams may be an interesting area to explore for further research in this area. However, there are some challenges in estimating lens dose from head CT exams. An accurate lens dosimetry model would have to account for differences in imaging protocols, differences in head size, and the use of any dose reduction methods. The overall objective of this dissertation was to develop a comprehensive method to estimate radiation dose to the lens of the eye for patients receiving CT scans of the head. This research is comprised of a physics component, in which a lens dosimetry model was derived for head CT, and a clinical component, which involved the application of that dosimetry model to patient data. The physics component includes experiments related to the physical measurement of the radiation dose to the lens by various types of dosimeters placed within anthropomorphic phantoms. These dosimeters include high-sensitivity MOSFETs, TLDs, and radiochromic film. The six anthropomorphic phantoms used in these experiments range in age from newborn to adult. First, the lens dose from five clinically relevant head CT protocols was measured in the anthropomorphic phantoms with MOSFET dosimeters on two state-of-the-art CT scanners. The volume CT dose index (CTDIvol), which is a standard CT output index, was compared to the measured lens doses. Phantom age-specific CTDIvol-to-lens dose conversion factors were derived using linear regression analysis. Since head size can vary among individuals of the same age, a method was derived to estimate the CTDIvol-to-lens dose conversion factor using the effective head diameter. These conversion factors were derived for each scanner individually, but also were derived with the combined data from the two scanners as a means to investigate the feasibility of a scanner-independent method. Using the scanner-independent method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter, most of the fitted lens dose values fell within 10-15% of the measured values from the phantom study, suggesting that this is a fairly accurate method of estimating lens dose from the CTDIvol with knowledge of the patient's head size. Second, the dose reduction potential of organ-based tube current modulation (OB-TCM) and its effect on the CTDIvol-to-lens dose estimation method was investigated. The lens dose was measured with MOSFET dosimeters placed within the same six anthropomorphic phantoms. The phantoms were scanned with the five clinical head CT protocols with OB-TCM enabled on the one scanner model at our institution equipped with this software. The average decrease in lens dose with OB-TCM ranged from 13.5 to 26.0%. Using the size-specific method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter for protocols with OB-TCM, the majority of the fitted lens dose values fell within 15-18% of the measured values from the phantom study. Third, the effect of gantry angulation on lens dose was investigated by measuring the lens dose with TLDs placed within the six anthropomorphic phantoms. The 2-dimensional spatial distribution of dose within the areas of the phantoms containing the orbit was measured with radiochromic film. A method was derived to determine the CTDIvol-to-lens dose conversion factor based upon distance from the primary beam scan range to the lens. The average dose to the lens region decreased substantially for almost all the phantoms (ranging from 67 to 92%) when the orbit was exposed to scattered radiation compared to the primary beam. The effectiveness of this method to reduce lens dose is highly dependent upon the shape and size of the head, which influences whether or not the angled scan range coverage can include the entire brain volume and still avoid the orbit. The clinical component of this dissertation involved performing retrospective patient studies in the pediatric and adult populations, and reconstructing the lens doses from head CT examinations with the methods derived in the physics component. The cumulative lens doses in the patients selected for the retrospective study ranged from 40 to 1020 mGy in the pediatric group, and 53 to 2900 mGy in the adult group. This dissertation represents a comprehensive approach to lens of the eye dosimetry in CT imaging of the head. The collected data and derived formulas can be used in future studies on radiation-induced cataracts from repeated CT imaging of the head. Additionally, it can be used in the areas of personalized patient dose management, and protocol optimization and clinician training.

Energy spectrum control for modulated proton beams.

PubMed

Hsi, Wen C; Moyers, Michael F; Nichiporov, Dmitri; Anferov, Vladimir; Wolanski, Mark; Allgower, Chris E; Farr, Jonathan B; Mascia, Anthony E; Schreuder, Andries N

2009-06-01

In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.

Clinical Decision Support Improves Initial Dosing and Monitoring of Tobramycin and Amikacin

PubMed Central

Cox, Zachary L.; Nelsen, Cori L.; Waitman, Lemuel R.; McCoy, Jacob A.; Peterson, Josh F.

2010-01-01

Purpose Clinical decision support (CDS) systems could be valuable tools in reducing aminoglycoside prescribing errors. We evaluated the impact of CDS on initial dosing, interval, and pharmacokinetic outcomes of amikacin and tobramycin therapy. Methods A complex CDS advisor to provide guidance on initial dosing and monitoring, using both traditional and extended interval dosing strategies, was integrated into computerized provider order entry (CPOE) and compared to a control group which featured close pharmacy monitoring of all aminoglycoside orders. A random sample of 118 patients from an academic, tertiary care medical center prescribed amikacin and tobramycin prior to advisor implementation was compared to 98 patients admitted following advisor implementation. Primary outcome was an initial dose within 10% of a dose calculated to be adherent to published dose guidelines. Secondary outcomes were a guideline-adherent interval, trough and peak concentrations in goal range, and incidence of nephrotoxicity. Results Of 216 patients studied, 97 were prescribed amikacin and 119 were prescribed tobramycin. The primary outcome of initial dosing consistent with guideline-based care increased from 40% in the pre-advisor arm to 80% in the post-advisor arm (p<0.001), with a number needed to treat of 3 patients to prevent one incorrect dose. Correct initial interval based on renal function also increased from 63% to 87% (p<0.001). The changes in initial dosing and interval resulted in an increase of trough concentrations in the goal range from 59% pre-advisor to 89% post-advisor implementation (p=0.0004). There was no significant difference in peak concentrations in goal range or incidence of nephrotoxicity (25% vs. 17%, p=0.2). Conclusion An advisor for aminoglycoside dosing and monitoring integrated into CPOE significantly improves initial dosing, selection of interval, and trough concentrations at goal compared to unassisted physician dosing. PMID:21411805

Reduction of radiation dose during facet joint injection using the new image guidance system SabreSource™: a prospective study in 60 patients

PubMed Central

Proschek, Dirk; Kafchitsas, K.; Rauschmann, M. A.; Kurth, A. A.; Vogl, T. J.

2008-01-01

Interventional procedures are associated with high radiation doses for both patients and surgeons. To reduce the risk from ionizing radiation, it is essential to minimize radiation dose. This prospective study was performed to evaluate the effectiveness in reducing radiation dose during facet joint injection in the lumbar spine and to evaluate the feasibility and possibilities of the new real time image guidance system SabreSource™. A total of 60 patients, treated with a standardized injection therapy of the facet joints L4–L5 or L5–S1, were included in this study. A total of 30 patients were treated by fluoroscopy guidance alone, the following 30 patients were treated using the new SabreSource™ system. Thus a total of 120 injections to the facet joints were performed. Pain, according to the visual analogue scale (VAS), was documented before and 6 h after the intervention. Radiation dose, time of radiation and the number of exposures needed to place the needle were recorded. No significant differences concerning age (mean age 60.5 years, range 51–69), body mass index (mean BMI 26.2, range 22.2–29.9) and preoperative pain (VAS 7.9, range 6–10) were found between the two groups. There was no difference in pain reduction between the two groups (60 vs. 61.5%; P = 0.001) but the radiation dose was significantly smaller with the new SabreSource™ system (reduction of radiation dose 32.7%, P = 0.01; reduction of mean entrance surface dose 32.3%, P = 0.01). The SabreSource™ System significantly reduced the radiation dose received during the injection therapy of the lumbar facet joints. With minimal effort for the setup at the beginning of a session, the system is easy to handle and can be helpful for other injection therapies (e.g. nerve root block therapies). PMID:19082641

The incidence of the different sources of noise on the uncertainty in radiochromic film dosimetry using single channel and multichannel methods

NASA Astrophysics Data System (ADS)

González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

2017-11-01

The influence of the various sources of noise on the uncertainty in radiochromic film (RCF) dosimetry using single channel and multichannel methods is investigated in this work. These sources of noise are extracted from pixel value (PV) readings and dose maps. Pieces of an RCF were each irradiated to different uniform doses, ranging from 0 to 1092 cGy. Then, the pieces were read at two resolutions (72 and 150 ppp) with two flatbed scanners: Epson 10000XL and Epson V800, representing two states of technology. Noise was extracted as described in ISO 15739 (2013), separating its distinct constituents: random noise and fixed pattern (FP) noise. Regarding the PV maps, FP noise is the main source of noise for both models of digitizer. Also, the standard deviation of the random noise in the 10000XL model is almost twice that of the V800 model. In the dose maps, the FP noise is smaller in the multichannel method than in the single channel ones. However, random noise is higher in this method, throughout the dose range. In the multichannel method, FP noise is reduced, as a consequence of this method’s ability to eliminate channel independent perturbations. However, the random noise increases, because the dose is calculated as a linear combination of the doses obtained by the single channel methods. The values of the coefficients of this linear combination are obtained in the present study, and the root of the sum of their squares is shown to range between 0.9 and 1.9 over the dose range studied. These results indicate the random noise to play a fundamental role in the uncertainty of RCF dosimetry: low levels of random noise are required in the digitizer to fully exploit the advantages of the multichannel dosimetry method. This is particularly important for measuring high doses at high spatial resolutions.

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

PubMed

von Tresckow, Bastian; Morschhauser, Franck; Ribrag, Vincent; Topp, Max S; Chien, Caly; Seetharam, Shobha; Aquino, Regina; Kotoulek, Sonja; de Boer, Carla J; Engert, Andreas

2015-04-15

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL). Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics. Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing). JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL. ©2015 American Association for Cancer Research.

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview

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

Calabrese, Edward J.; Blain, Robyn

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying amore » broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.« less

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview.

PubMed

Calabrese, Edward J; Blain, Robyn

2005-02-01

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.

Acute effects of THC on time perception in frequent and infrequent cannabis users.

PubMed

Sewell, R Andrew; Schnakenberg, Ashley; Elander, Jacqueline; Radhakrishnan, Rajiv; Williams, Ashley; Skosnik, Patrick D; Pittman, Brian; Ranganathan, Mohini; D'Souza, D Cyril

2013-03-01

Cannabinoids have been shown to alter time perception, but existing literature has several limitations. Few studies have included both time estimation and production tasks, few control for subvocal counting, most had small sample sizes, some did not record subjects' cannabis use, many tested only one dose, and used either oral or inhaled administration of Δ⁹-tetrahydrocannabinol (THC), leading to variable pharmacokinetics, and some used whole-plant cannabis containing cannabinoids other than THC. Our study attempted to address these limitations. This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception. THC was hypothesized to produce transient, dose-related time overestimation and underproduction. Frequent cannabis smokers were hypothesized to show blunted responses to these alterations. IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind, randomized, counterbalanced, crossover, placebo-controlled studies. Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day. All doses induced time overestimation and underproduction. Chronic cannabis use had no effect on baseline time perception. While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses, frequent cannabis users showed no differences. THC effects on time perception were not dose related. A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction. This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception.

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

PubMed

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

2016-01-01

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

Evaluation of dose-area product of common radiographic examinations towards establishing a preliminary diagnostic reference levels (PDRLs) in Southwestern Nigeria.

PubMed

Jibiri, Nnamdi N; Olowookere, Christopher J

2016-11-08

In Nigeria, a large number of radiographic examinations are conducted yearly for various diagnostic purposes. However, most examinations carried out do not have records of doses received by the patients, and the employed exposure parameters used are not documented; therefore, adequate radiation dose management is hin-dered. The aim of the present study was to estimate the dose-area product (DAP) of patients examined in Nigeria, and to propose regional reference dose levels for nine common examinations (chest PA, abdomen AP, pelvis AP, lumbar AP, skull AP, leg AP, knee AP, hand AP, and thigh AP) undertaken in Nigeria. Measurement of entrance surface dose (ESD) was carried out using thermoluminescent dosimeter (TLD). Measured ESDS were converted into DAP using the beam area of patients in 12 purposely selected hospitals. Results of the study show that the maximum/ minimum ratio ranged from 3 for thigh AP to 57 in abdomen AP. The range of determined mean and 75th percentile DAPs were 0.18-17.16, and 0.25-28.59 Gy cm2, respectively. Data available for comparison show that 75th percentile DAPs in this study (in chest PA, abdomen AP, pelvis AP, lumbar AP) are higher than NRPB-HPE reference values. The DAP in this study is higher by factor of 31.4 (chest PA), 9.9 (abdomen AP), 2.2 (pelvis AP), and 2.1 (lumbar AP) than NRPB-HPE values. The relative higher dose found in this study shows nonoptimization of practice in Nigeria. It is expected that regular dose auditing and dose optimization implementation in Nigeria would lead to lower DAP value, especially in abdomen AP. The 75th percentile DAP distribution reported in this study could be taken as regional diagnostic reference level in the Southwestern Nigeria; however, a more extensive nationwide dose survey is required to establish national reference dose. © 2016 The Authors.

Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients.

PubMed

Belldina, Eric B; Huang, Mei Y; Schneider, Jerry A; Brundage, Richard C; Tracy, Timothy S

2003-11-01

Cysteamine is used to reduce tissue cystine content in patients suffering from nephropathic cystinosis. The objectives of the current study were to investigate pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young adults with nephropathic cystinosis. Cysteamine bitartrate was administered to 11 cystinosis patients at their regular dose level in a single-dose, open-label, steady-state study. Blood samples were collected and analysed for plasma cysteamine and white blood cell cystine content and pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using a linked pharmacokinetic-pharmacodynamic model. Cysteamine was rapidly cleared from the plasma (mean CL/F = 32.3 ml min(-1) kg(-1), range = 17.3-52.2), appeared to be extensively distributed (mean Vss/F = 15.1 l, range 2.7-32.3) and exhibited a mean Tmax of 1.4 h. White blood cell cystine content post-dosing was significantly decreased compared with pre- and post-dose values (average decrement approximately 47%). A counter-clockwise hysteresis was noted in all patients, suggestive of a lag time (mean Tlag = 0.44 h, range 0.22-0.92) between drug concentration and effect. The results of this study establish that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing interval adequately maintains white blood cell cystine content below the target of 1 nmol cystine per mg protein.

A Multi-Compartment, Single and Multiple Dose Pharmacokinetic Study of the Vaginal Candidate Microbicide 1% Tenofovir Gel

PubMed Central

Schwartz, Jill L.; Rountree, Wes; Kashuba, Angela D. M.; Brache, Vivian; Creinin, Mitchell D.; Poindexter, Alfred; Kearney, Brian P.

2011-01-01

Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496 PMID:22039430

Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

PubMed

Craven, Meghan; Frank, Graeme R

2018-06-27

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 μg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. This study is a retrospective chart review of infants with CH between 2002 and 2012. Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 μg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 μg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 μg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 μg/kg/day (p=0.007). Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.

Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)

USGS Publications Warehouse

McKenney, Douglas; Kurath, Gael; Wargo, Andrew

2016-01-01

The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

Oseltamivir Pharmacokinetics, Dosing, and Resistance Among Children Aged <2 Years With Influenza

PubMed Central

Kimberlin, David W.; Acosta, Edward P.; Prichard, Mark N.; Sánchez, Pablo J.; Ampofo, Krow; Lang, David; Ashouri, Negar; Vanchiere, John A.; Abzug, Mark J.; Abughali, Nazha; Caserta, Mary T.; Englund, Janet A.; Sood, Sunil K.; Spigarelli, Michael G.; Bradley, John S.; Lew, Judy; Michaels, Marian G.; Wan, Wen; Cloud, Gretchen; Jester, Penelope; Lakeman, Fred D.; Whitley, Richard J.; Giles, Dusty; Cotton, Bari; Judy, Sharon; Cowie, Margaret; Francis, Jeanne; Evans, Candice; O'Donnell, Nan; Shiraishi, Ofelia Vargas; Latiolais, Lisa; Aymami, Valeri; Dole, Ken; Gaultier, Julie; Lofthus, Gerry; Kinnunen, Diane; Lacombe, Kirsten; Stellato, Nancy; Denlinger, Julie; Hingtgen, Sara; Mason, Christina; Jeffrey, Noreen

2013-01-01

Background. Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown. Methods. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age–de-escalation, adaptive design with a targeted systemic exposure. Results. From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0–8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9–11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12–23 months receiving the Food and Drug Administration–approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment. Conclusions. The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9–11 months old is 3.5 mg/kg. Clinical Trials Registration. NCT00391768. PMID:23230059

80 MeV C{sup 6+} ion irradiation effects on the DC electrical characteristics of silicon NPN power transistors

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

Bharathi, M. N.; Vinayakprasanna, N. H.; Prakash, A. P. Gnana, E-mail: gnanaprakash@physics.uni-mysore.ac.in

The total dose effects of 80 MeV C{sup 6+} ions on the DC electrical characteristics of Silicon NPN rf power transistors have been studied in the dose range of 100 krad to 100 Mrad. The SRIM simulation was used to understand the energy loss and range of the ions in the transistor structure. The different electrical parameters such as Gummel characteristics, excess base current (ΔI{sub B} = I{sub Bpost} - I{sub Bpre}), dc forward current gain (h{sub FE}), transconductance (g{sub m}), displacement damage factor (K) and output characteristics (V{sub CE}-I{sub C}) were studied systematically before and after irradiation. The significantmore » degradation in base current (I{sub B}) and h{sub FE} was observed after irradiation. Isochronal annealing study was conducted on the irradiated transistors to analyze the recovery in different electrical parameters. These results were compared with {sup 60}C0 gamma irradiation results in the same dose range.« less

Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT

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

Tol-Geerdink, Julia J. van; Stalmeier, Peep F.M.; Department of Medical Technology Assessment, Radboud University Nijmegen Medical Center, Nijmegen

Purpose: A higher radiation dose is believed to result in a larger probability of tumor control and a higher risk of side effects. To make an evidence-based choice of dose, the relation between dose and outcome needs to be known. This study focuses on the dose-response relation for prostate cancer. Methods and Materials: A systematic review was carried out on the literature from 1990 to 2003. From the selected studies, the radiation dose, the associated 5-year survival, 5-year bNED (biochemical no evidence of disease), acute and late gastrointestinal (GI) and genitourinary (GU) morbidity Grade 2 or more, and sexual dysfunctionmore » were extracted. With logistic regression models, the relation between dose and outcome was described. Results: Thirty-eight studies met our criteria, describing 87 subgroups and involving up to 3000 patients per outcome measure. Between the (equivalent) dose of 70 and 80 Gy, various models estimated an increase in 5-year survival (ranging from 10% to 11%), 5-year bNED for low-risk patients (5-7%), late GI complications (12-16%), late GU complications (8-10%), and erectile dysfunction (19-24%). Only for the overall 5-year bNED, results were inconclusive (range, 0-18%). Conclusions: The data suggest a relationship between dose and outcome measures, including survival. However, the strength of these conclusions is limited by the sometimes small number of studies, the incompleteness of the data, and above all, the correlational nature of the data. Unambiguous proof for the dose-response relationships can, therefore, only be obtained by conducting randomized trials.« less

Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

PubMed Central

Booth, J. C.; Rweyemamu, M. M.; Pay, T. W.

1978-01-01

Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection. PMID:202650

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study

PubMed Central

Schlesinger, Naomi; Mysler, Eduardo; Lin, Hsiao-Yi; De Meulemeester, Marc; Rovensky, Jozef; Arulmani, Udayasankar; Balfour, Alison; Krammer, Gerhard; Sallstig, Peter; So, Alexander

2011-01-01

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28–0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28–0.36, p≤0.05). The incidence of adverse events was similar across treatment groups. Conclusions Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg. PMID:21540198

Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants.

PubMed

Lee, Sun Ku; Xing, Jun; Catlett, Ian M; Adamczyk, Robert; Griffies, Amber; Liu, Ang; Murthy, Bindu; Nowak, Miroslawa

2017-06-01

BMS-986142 is an oral, small-molecule reversible inhibitor of Bruton's tyrosine kinase. The main objectives of our phase I studies were to characterize the safety and tolerability, pharmacokinetics, and pharmacodynamics of BMS-986142 in healthy participants, and to investigate the potential for the effect of BMS-986142 on the PK of methotrexate (MTX) in combination. In a combined single ascending dose and multiple ascending dose study, the safety, pharmacokinetics, and pharmacodynamics of BMS-986142 were assessed in healthy non-Japanese participants following administration of a single dose (5-900 mg) or multiple doses (25-350 mg, once daily for 14 days). In a drug-drug interaction study, the effect of BMS-986142 (350 mg, once daily for 5 days) on the single-dose pharmacokinetics of MTX (7.5 mg) was assessed in healthy participants. BMS-986142 was generally well tolerated, alone and in combination with MTX. BMS-986142 was rapidly absorbed with peak concentrations occurring within 2 h, and was eliminated with a mean half-life ranging from 7 to 11 h. Exposure of BMS-986142 appeared dose proportional within the dose ranges tested. A dose- and concentration-dependent inhibition of CD69 expression was observed following administration of BMS-986142. BMS-986142 did not affect the pharmacokinetics of MTX. BMS-986142 was well tolerated at the doses tested, had pharmacokinetic and pharmacodynamic profiles which support once-daily dosing, and can be coadministered with MTX without the pharmacokinetic interaction of BMS-986142 on MTX.

The plasma free amino acid dose-response technique: A proposed methodology for determining lysine relative bioavailability of rumen-protected lysine supplements.

PubMed

Whitehouse, N L; Schwab, C G; Brito, A F

2017-12-01

Estimates of Lys bioavailability of rumen-protected Lys (RP-Lys) supplements are often obtained using in vitro or 2-step in situ techniques, with little to no data determining efficacy and bioavailability in vivo. The objective of this study was to further evaluate and refine the use of the plasma free AA dose-response technique as a method for determining Lys relative bioavailability of RP-Lys supplements. Thirteen dose-response Latin square studies using 87 lactating, ruminally cannulated multiparous Holstein cows (days in milk from 55 to 315 and milk yield from 12 to 62 kg/d at the start of the studies) were conducted to measure the relative bioavailability of RP-Lys supplements. Intestinal (1 study) and abomasal (12 studies) infusions of Lys ranged from 0 to 84 g/d, and experimental periods ranged from 4 to 21 d. Basal diets were formulated to be adequate in metabolizable Met, but varied in predicted metabolizable Lys (5.04 to 6.81% of metabolizable protein). One to 4 daily blood samples were taken from the coccygeal vessels for 1 to 3 consecutive days in each period. Plasma Lys concentration in cows assigned to the control treatment (0 g/d Lys) ranged from 1.83 to 5.21% of total plasma AA, whereas that from cows duodenally or abomasally infused with Lys ranged from 2.53 to 7.51% of total plasma AA. Results from studies involving more than 2 amounts of infused Lys confirmed linearity of response. The following variables were regressed against the plasma Lys dose-response slopes generated from the Lys infusion treatments to examine their effects on the magnitude of the slopes: plasma Lys concentration of the control diet, plasma Lys concentration at the greatest amount of infused Lys, net energy of lactation and metabolizable protein balances, metabolizable protein supply, days in milk, milk yield, milk concentrations of fat, true protein, and lactose, milk true protein yield, and dry matter intake. The variable having the greatest effect on the magnitude of the dose-response slope was the plasma Lys concentration at the greatest amount infused. The relative bioavailability of evaluated RP-Lys supplements using the plasma free AA dose-response technique ranged from 5 to 87%. It was concluded that plasma free Lys increases in a linear fashion to increasing amounts of absorbed Lys and that the dose-response technique is an appropriate technique for evaluating RP-Lys supplements. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Nuclear accident dosimetry intercomparison studies

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

Sims, C.S.

1989-09-01

Twenty-two nuclear accident dosimetry intercomparison studies utilizing the fast-pulse Health Physics Research Reactor at the Oak Ridge National Laboratory have been conducted since 1965. These studies have provided a total of 62 different organizations a forum for discussion of criticality accident dosimetry, an opportunity to test their neutron and gamma-ray dosimetry systems under a variety of simulated criticality accident conditions, and the experience of comparing results with reference dose values as well as with the measured results obtained by others making measurements under identical conditions. Sixty-nine nuclear accidents (27 with unmoderated neutron energy spectra and 42 with eight different shieldedmore » spectra) have been simulated in the studies. Neutron doses were in the 0.2-8.5 Gy range and gamma doses in the 0.1-2.0 Gy range. A total of 2,289 dose measurements (1,311 neutron, 978 gamma) were made during the intercomparisons. The primary methods of neutron dosimetry were activation foils, thermoluminescent dosimeters, and blood sodium activation. The main methods of gamma dose measurement were thermoluminescent dosimeters, radiophotoluminescent glass, and film. About 68% of the neutron measurements met the accuracy guidelines (+/- 25%) and about 52% of the gamma measurements met the accuracy criterion (+/- 20%) for accident dosimetry.« less

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

Modern dosimetric tools for 60Co irradiation at high containment laboratories

PubMed Central

Twardoski, Barri; Feldmann, Heinz; Bloom, Marshall E.; Ward, Joe

2011-01-01

Purpose To evaluate an innovative photo-fluorescent film as a routine dosimetric tool during 60Co irradiations at a high containment biological research laboratory, and to investigate whether manufacturer-provided chamber exposure rates can be used to accurately administer a prescribed dose to biological specimens. Materials and methods Photo-fluorescent, lithium fluoride film dosimeters and National Institutes of Standards and Technology (NIST) transfer dosimeters were co-located in a self-shielded 60Co irradiator and exposed to γ-radiation with doses ranging from 5–85 kGy. Film dose-response relationships were developed for varying temperatures simulating conditions present when irradiating infectious biological specimens. Dose measurement results from NIST transfer dosimeters were compared to doses predicted using manufacturer-provided irradiator chamber exposure rates. Results The film dosimeter exhibited a photo-fluorescent response signal that was consistent and nearly linear in relationship to γ-radiation exposure over a wide dose range. The dosimeter response also showed negligible effects from dose fractionization and humidity. Significant disparities existed between manufacturer-provided chamber exposure rates and actual doses administered. Conclusion This study demonstrates the merit of utilizing dosimetric tools to validate the process of exposing dangerous and exotic biological agents to γ-radiation at high containment laboratories. The film dosimeter used in this study can be utilized to eliminate potential for improperly administering γ-radiation doses. PMID:21961968

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

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

Warren, Samantha, E-mail: samantha.warren@oncology.ox.ac.uk; Partridge, Mike; Bolsi, Alessandra

Purpose: Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods andmore » Materials: For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV){sub 50Gy} or PTV{sub 62.5Gy} (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results: SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D{sub 98} was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D{sub 98} was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D{sub 98} was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D{sub 98} was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions: The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial.« less

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

PubMed Central

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J.; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

2016-01-01

Purpose Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods and Materials For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. PMID:27084641

Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation.

PubMed

Tran, Van; Little, Mark P

2017-11-01

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and non-malignant, show downward curvature in the dose response, and for most endpoints this is statistically significant (p < 0.05). Associated with this, the low-dose extrapolation factor associated with neutron exposure is generally statistically significantly less than 1 for most malignant and non-malignant endpoints, with central estimates mostly in the range 0.1-0.9. In contrast to the situation at higher dose rates, there are statistically non-significant decreases of risk per unit dose at gamma dose rates of less than or equal to 5 mGy/h for most malignant endpoints, and generally non-significant increases in risk per unit dose at gamma dose rates ≤5 mGy/h for most non-malignant endpoints. Associated with this, the dose-rate extrapolation factor, the ratio of high dose-rate to low dose-rate (≤5 mGy/h) gamma dose response slopes, for many tumour sites is in the range 1.2-2.3, albeit not statistically significantly elevated from 1, while for most non-malignant endpoints the gamma dose-rate extrapolation factor is less than 1, with most estimates in the range 0.2-0.8. After neutron exposure there are non-significant indications of lower risk per unit dose at dose rates ≤5 mGy/h compared to higher dose rates for most malignant endpoints, and for all tumours (p = 0.001), and respiratory tumours (p = 0.007) this reduction is conventionally statistically significant; for most non-malignant outcomes risks per unit dose non-significantly increase at lower dose rates. Associated with this, the neutron dose-rate extrapolation factor is less than 1 for most malignant and non-malignant endpoints, in many cases statistically significantly so, with central estimates mostly in the range 0.0-0.2.

Optimization and Dose Estimation of Aerosol Delivery to Non-Human Primates.

PubMed

MacLoughlin, Ronan J; van Amerongen, Geert; Fink, James B; Janssens, Hettie M; Duprex, W Paul; de Swart, Rik L

2016-06-01

In pre-clinical animal studies, the uniformity of dosing across subjects and routes of administration is a crucial requirement. In preparation for a study in which aerosolized live-attenuated measles virus vaccine was administered to cynomolgus monkeys (Macaca fascicularis) by inhalation, we assessed the percentage of a nebulized dose inhaled under varying conditions. Drug delivery varies with breathing parameters. Therefore we determined macaque breathing patterns (tidal volume, breathing frequency, and inspiratory to expiratory (I:E) ratio) across a range of 3.3-6.5 kg body weight, using a pediatric pneumotachometer interfaced either with an endotracheal tube or a facemask. Subsequently, these breathing patterns were reproduced using a breathing simulator attached to a filter to collect the inhaled dose. Albuterol was nebulized using a vibrating mesh nebulizer and the percentage inhaled dose was determined by extraction of drug from the filter and subsequent quantification. Tidal volumes ranged from 24 to 46 mL, breathing frequencies from 19 to 31 breaths per minute and I:E ratios from 0.7 to 1.6. A small pediatric resuscitation mask was identified as the best fitting interface between animal and pneumotachometer. The average efficiency of inhaled dose delivery was 32.1% (standard deviation 7.5, range 24%-48%), with variation in tidal volumes as the most important determinant. Studies in non-human primates aimed at comparing aerosol delivery with other routes of administration should take both the inter-subject variation and relatively low efficiency of delivery to these low body weight mammals into account.

Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women undergoing Mammography (1960 to the Present)

PubMed Central

Thierry-Chef, Isabelle; Simon, Steven L.; Weinstock, Robert M.; Kwon, Deukwoo; Linet, Martha S.

2013-01-01

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters including imaging protocols, x-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum, and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations which can be used in epidemiologic studies of breast cancer. PMID:21988547

Isotretinoin kinetics after 80 to 320 mg oral doses.

PubMed

Colburn, W A; Gibson, D M

1985-04-01

Twelve healthy male subjects received 80, 160, 240, and 320 mg doses of oral isotretinoin as multiples of 40 mg capsules separated by 2-week washout periods in a randomized, crossover design. Blood samples were drawn at specific times over a 72-hour period after dosing. Blood concentrations of isotretinoin as well as its major metabolite, 4-oxo-isotretinoin, were determined by a specific HPLC method. In addition to the normal laboratory battery of tests, serum triglyceride levels were determined before the first dose and again 72 hours after each of the four doses. Mean (+/- SD) maximum concentrations after 80 to 320 mg doses were 366 +/- 159, 820 +/- 474, 1056 +/- 547, and 981 +/- 381 ng/ml, whereas the respective AUC0-infinity values were 3690 +/- 1280, 7030 +/- 4140, 9780 +/- 6080, and 9040 +/- 2900 ng X hr/ml. The observed apparent elimination t1/2 remained approximately the same (14.7 hours) for each dose. The maximum concentration and AUC values for isotretinoin appear to be dose proportional from 80 to 240 mg but plateau at the 320 mg dose level. Therefore, because isotretinoin blood concentrations may not increase with higher doses in the fasting state, single, oral doses in excess of 240 mg should be used with caution. The data also suggest that elevated triglyceride levels are not a simple function of isotretinoin blood concentrations across the entire study population and dose range studied, but that in subjects with triglyceride levels in excess of the normal range triglyceride levels were positively related to isotretinoin blood concentrations.

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

PubMed

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

2012-02-29

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

Tolerability and pharmacokinetic profile of a sunitinib powder formulation in pediatric patients with refractory solid tumors: a Children’s Oncology Group study

PubMed Central

Shusterman, Suzanne; Reid, Joel M.; Ingle, Ashish M.; Ahern, Charlotte H.; Baruchel, Sylvain; Glade-Bender, Julia; Ivy, Percy; Adamson, Peter C.; Blaney, Susan M.

2012-01-01

Purpose Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m2/day. This study was conducted to evaluate sunitinib given as a powder formulation. Methods Sunitinib 15 mg/m2 was administered orally daily for 4 weeks on/2 weeks off to patients <21 years old with refractory solid tumors. Sunitinib capsules were opened, and the powder sprinkled onto applesauce or yogurt. Plasma levels of sunitinib and an active metabolite, SU12662, were measured, and pharmacokinetic parameters were estimated. Results 12 patients, median age 13 (range 4–21) years, were treated. The most common first-cycle toxicities were leucopenia (n = 6), fatigue (n = 5), neutropenia (n = 4), and hypertension (n = 4). Three patients had dose-limiting toxicities (DLTs) in cycle 1 (dizziness/back pain, hand–foot syndrome, and intratumoral hemorrhage/hypoxia). A median peak plasma sunitinib concentration of 21 (range 6–36) ng/ml was reached at a median of 4 (range 4–8) h after the first dose. The median exposure (AUC0–48) was 585 (range 196–1,059) h ng/l. The median half-life was 23 (range 13–36) h. The median trough concentration measured before day 14 dosing was 32 (range 12–58) ng/ml. Conclusions The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules. The powder formulation allows patients unable to swallow capsules to receive sunitinib. PMID:22179104

Risperidone Dosing in Children and Adolescents with Autistic Disorder: A Double-Blind, Placebo-Controlled Study

ERIC Educational Resources Information Center

Kent, Justine M.; Kushner, Stuart; Ning, Xiaoping; Karcher, Keith; Ness, Seth; Aman, Michael; Singh, Jaskaran; Hough, David

2013-01-01

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change…

Estimation of the total effective dose from low-dose CT scans and radiopharmaceutical administrations delivered to patients undergoing SPECT/CT explorations.

PubMed

Montes, Carlos; Tamayo, Pilar; Hernandez, Jorge; Gomez-Caminero, Felipe; García, Sofia; Martín, Carlos; Rosero, Angela

2013-08-01

Hybrid imaging, such as SPECT/CT, is used in routine clinical practice, allowing coregistered images of the functional and structural information provided by the two imaging modalities. However, this multimodality imaging may mean that patients are exposed to a higher radiation dose than those receiving SPECT alone. The study aimed to determine the radiation exposure of patients who had undergone SPECT/CT examinations and to relate this to the Background Equivalent Radiation Time (BERT). 145 SPECT/CT studies were used to estimate the total effective dose to patients due to both radiopharmaceutical administrations and low-dose CT scans. The CT contribution was estimated by the Dose-Length Product method. Specific conversion coefficients were calculated for SPECT explorations. The radiation dose from low-dose CTs ranged between 0.6 mSv for head and neck CT and 2.6 mSv for whole body CT scan, representing a maximum of 1 year of background radiation exposure. These values represent a decrease of 80-85% with respect to the radiation dose from diagnostic CT. The radiation exposure from radiopharmaceutical administration varied from 2.1 mSv for stress myocardial perfusion SPECT to 26 mSv for gallium SPECT in patients with lymphoma. The BERT ranged from 1 to 11 years. The contribution of low-dose CT scans to the total radiation dose to patients undergoing SPECT/CT examinations is relatively low compared with the effective dose from radiopharmaceutical administration. When a CT scan is only acquired for anatomical localization and attenuation correction, low-dose CT scan is justified on the basis of its lower dose.

Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects.

PubMed

Chandra, Kumar P; Shiwalkar, Ajay; Kotecha, Jignesh; Thakkar, Purav; Srivastava, Ambrish; Chauthaiwale, Vijay; Sharma, Sanjay K; Cross, Maurice R; Dutt, Chaitanya

2009-01-01

Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic complications through a variety of mechanisms including endothelial dysfunction and structural abnormalities in the vasculature and myocardium. Reducing the AGEs burden and their ensuing pro-inflammatory, pro-oxidative and pro-coagulant effect with associated dysfunctional proteins in various target tissues may retard the progression of and even reverse diabetic macro- and microvascular complications. Pyridinium, 3-[[2-(methylsulfonyl) hydrazino] carbonyl]-1-[2-oxo-2-2-thienyl) ethyl]-chloride (TRC4186) has demonstrated AGE-breaking activities in in vitro experiments and improvement in the endothelial and myocardial function in animal models of diabetes mellitus with reduction of AGEs accumulation in tissues over time. The safety of TRC4186 has been established in in vitro and in vivo preclinical studies. Thus, this drug is being developed for the treatment of complications associated with diabetes. This investigation set out to evaluate the safety, tolerability and pharmacokinetics of TRC4186 in healthy human subjects after single and multiple ascending doses, fixed doses in elderly male and female subjects, and with food and different formulations of the compound. Four studies were conducted during phase I clinical development of TRC4186. These were: (i) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in healthy male subjects with doses of TRC4186 ranging from 250 to 2500 mg administered as an oral solution (total six doses); (ii) a randomized, double-blind, placebo-controlled, multiple-dose, dose-ascending study in healthy male subjects with three doses of TRC4186 ranging from 500 to 2000 mg twice daily for 6 days with a final single dose on day 7; (iii) a randomized, open-label, three-way crossover study to assess the effect of food (fasted vs fed) and formulation (solution vs tablet) with TRC4186 500 mg; (iv) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in elderly male and female subjects at a dose of TRC4186 500 mg followed by TRC4186 1000 mg after a 7-day washout period. The safety and tolerability of TRC4186 were assessed by considering adverse events (AEs), ECG findings, vital signs and laboratory investigation results. TRC4186 was rapidly absorbed, with maximum plasma concentrations (C(max)) attained within 1-4 hours. C(max) and area under the plasma concentration-time curve (AUC) were dose proportional over the range 250-2500 mg for a single dose and 500-2000 mg for multiple doses with twice-daily administration. Steady-state conditions were attained within 6 days at different dose levels. C(max) and AUC were not affected by age, sex, race or type of formulation. The tablet formulation of TRC4186 was bioequivalent with the solution form of the drug under fasting conditions and systemic availability of the tablet formulation was reduced by 40% when administered under fed conditions. Terminal elimination and renal clearance in the elderly male (age 69.1 +/- 6.0 years) were not significantly different compared with younger subjects (age 31 +/- 8.6 years). TRC4186 was safe and well tolerated when administered orally with either a single or multiple doses across the different ages, sexes, races and formulations studied. A dose-proportional increase in plasma TRC4186 concentration was seen, with steady state being achieved within 6 days.

Proton therapy of prostate cancer by anterior-oblique beams: implications of setup and anatomy variations

NASA Astrophysics Data System (ADS)

Moteabbed, M.; Trofimov, A.; Sharp, G. C.; Wang, Y.; Zietman, A. L.; Efstathiou, J. A.; Lu, H.-M.

2017-03-01

Proton therapy of prostate by anterior beams could offer an attractive option for treating patients with hip prosthesis and limiting the high-dose exposure to the rectum. We investigated the impact of setup and anatomy variations on the anterior-oblique (AO) proton plan dose, and strategies to manage these effects via range verification and adaptive delivery. Ten patients treated by bilateral (BL) passive-scattering proton therapy (79.2 Gy in 44 fractions) who underwent weekly verification CT scans were selected. Plans with AO beams were additionally created. To isolate the effect of daily variations, initial AO plans did not include range uncertainty margins. The use of fixed planning margins and adaptive range adjustments to manage these effects was investigated. For each case, the planned dose was recalculated on weekly CTs, and accumulated on the simulation CT using deformable registration to approximate the delivered dose. Planned and accumulated doses were compared for each scenario to quantify dose deviations induced by variations. The possibility of estimating the necessary range adjustments before each treatment was explored by simulating the procedure of a diode-based in vivo range verification technique, which would potentially be used clinically. The average planned rectum, penile bulb and femoral heads mean doses were smaller for initial AO compared to BL plans (by 8.3, 16.1 and 25.9 Gy, respectively). After considering interfractional variations in AO plans, the target coverage was substantially reduced. The maximum reduction of V 79.2/D 95/D mean/EUD for AO (without distal margins) (25.3%/10.7/1.6/4.9 Gy, respectively) was considerably larger than BL plans. The loss of coverage was mainly related to changes in water equivalent path length of the prostate after fiducial-based setup, caused by discrepancies in patient anterior surface and bony-anatomy alignment. Target coverage was recovered partially when using fixed planning margins, and fully when applying adaptive range adjustments. The accumulated organs-at-risk dose for AO beams after range adjustment demonstrated full sparing of femoral heads and superior sparing of penile bulb and rectum compared to the conventional BL cases. Our study indicates that using AO beams makes prostate treatment more susceptible to target underdose induced by interfractional variations. Adaptive range verification/adjustment may facilitate the use of anterior beam approaches, and ensure adequate target coverage in every fraction of the treatment.

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

SU-G-IeP2-10: Lens Dose Reduction by Patient Position Modification During Neck CT Exams

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

Mosher, E; Lee, C; Butman, J

Purpose: Irradiation of the lens during a neck CT may increase a patient’s risk of developing cataracts later in life. Radiologists and technologists at the National Institutes of Health Clinical Center (NIHCC) have developed new CT imaging protocols that include a reduction in scan range and modifying neck positioning using a head tilt. This study will evaluate the efficacy of this protocol in the reduction of lens dose. Methods: We retrieved CT images of five male patients who had two sets of CT images: before and after the implementation of the new protocol. The lens doses before the new protocolmore » were calculated using an in-house CT dose calculator, National Cancer Institute dosimetry system for CT (NCICT), where computational human phantoms with no head tilt are included. We also calculated the lens dose for the patient CT conducted after the new protocol by using an adult male computational phantom with the neck position deformed to match the angle of the head tilt. We also calculated the doses to other radiosensitive organs including the globes of the eye, brain, pituitary gland and salivary glands before and after head tilt. Results: Our dose calculations demonstrated that modifying neck position reduced dose to the lens by 89% on average (range: 86–96%). Globe, brain, pituitary and salivary gland doses also decreased by an average of 65% (51–95%), 38% (−8–66%), 34% (−43–84%) and 14% (13–14%), respectively. The new protocol resulted in a nearly ten-fold decrease in lens dose. Conclusion: The use of a head tilt and scan range reduction is an easy and effective method to reduce radiation exposure to the lens and other radiosensitive organs, while still allowing for the inclusion of critical neck structures in the CT image. We are expanding our study to a total of 10 males and 10 females.« less

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells.

PubMed

Li, Ming-juan; Wang, Wei-wei; Chen, Shi-wei; Shen, Qian; Min, Rui

2011-10-01

The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles. Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR). Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2-8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges. The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.

A novel approach for estimating ingested dose associated with paracetamol overdose

PubMed Central

Zurlinden, Todd J.; Heard, Kennon

2015-01-01

Aim In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue‐specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow‐up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. Methods The core component of the computational framework was a physiologically‐based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter‐study variability, and facilitating the calculation of uncertainty in model outputs. Results Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Conclusions Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow‐up plan. PMID:26441245

A novel approach for estimating ingested dose associated with paracetamol overdose.

PubMed

Zurlinden, Todd J; Heard, Kennon; Reisfeld, Brad

2016-04-01

In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Simulations of paracetamol time course concentrations in the blood were in close agreement with experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement with a large collection of clinical and emergency setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan. © 2015 The British Pharmacological Society.

Object Kinetic Monte Carlo Simulations of Radiation Damage In Bulk Tungsten

NASA Astrophysics Data System (ADS)

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard; Roche, Kenneth; Kurtz, Richard; Wirth, Brian

2015-11-01

Results are presented for the evolution of radiation damage in bulk tungsten investigated using the object KMC simulation tool, KSOME, as a function of dose, dose rate and primary knock-on atom (PKA) energies in the range of 10 to 100 keV, at temperatures of 300, 1025 and 2050 K. At 300 K, the number density of vacancies changes minimally with dose rate while the number density of vacancy clusters slightly decreases with dose rate indicating that larger clusters are formed at higher dose rates. Although the average vacancy cluster size increases slightly, the vast majority exists as mono-vacancies. At 1025 K void lattice formation was observed at all dose rates for cascades below 60 keV and at lower dose rates for higher PKA energies. After the appearance of initial features of the void lattice, vacancy cluster density increased minimally while the average vacancy cluster size increases rapidly with dose. At 2050 K, no accumulation of defects was observed over a broad range of dose rates for all PKA energies studied in this work. Further comparisons of results of irradiation simulations at various dose rates and PKA spectra, representative of the High Flux Isotope Reactor and future fusion relevant irradiation facilities will be discussed. The U.S. Department of Energy, Office of Fusion Energy Sciences (FES) and Office of Advanced Scientific Computing Research (ASCR) has supported this study through the SciDAC-3 program.

Degradation of the Bragg peak due to inhomogeneities.

PubMed

Urie, M; Goitein, M; Holley, W R; Chen, G T

1986-01-01

The rapid fall-off of dose at the end of range of heavy charged particle beams has the potential in therapeutic applications of sparing critical structures just distal to the target volume. Here we explored the effects of highly inhomogeneous regions on this desirable depth-dose characteristic. The proton depth-dose distribution behind a lucite-air interface parallel to the beam was bimodal, indicating the presence of two groups of protons with different residual ranges, creating a step-like depth-dose distribution at the end of range. The residual ranges became more spread out as the interface was angled at 3 degrees, and still more at 6 degrees, to the direction of the beam. A second experiment showed little significant effect on the distal depth-dose of protons having passed through a mosaic of teflon and lucite. Anatomic studies demonstrated significant effects of complex fine inhomogeneities on the end of range characteristics. Monoenergetic protons passing through the petrous ridges and mastoid air cells in the base of skull showed a dramatic degradation of the distal Bragg peak. In beams with spread out Bragg peaks passing through regions of the base of skull, the distal fall-off from 90 to 20% dose was increased from its nominal 6 to well over 32 mm. Heavy ions showed a corresponding degradation in their ends of range. In the worst case in the base of skull region, a monoenergetic neon beam showed a broadening of the full width at half maximum of the Bragg peak to over 15 mm (compared with 4 mm in a homogeneous unit density medium). A similar effect was found with carbon ions in the abdomen, where the full width at half maximum of the Bragg peak (nominally 5.5 mm) was found to be greater than 25 mm behind gas-soft-tissue interfaces. We address the implications of these data for dose computation with heavy charged particles.

SU-E-T-638: Evaluation and Comparison of Landauer Microstar (OSLD) Readers

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

Souri, S; Ahmed, Y; Cao, Y

2014-06-15

Purpose: To evaluate and compare characteristic performance of a new Landauer nanodot Reader with the previous model. Methods: In order to calibrate and test the reader, a set of nanodots were irradiated using a Varian Truebeam Linac. Solid water slabs and bolus were used in the process of irradiation. Calibration sets of nanodots were irradiated for radiation dose ranges: 0 to 10 and 20 to 1000 cGy, using 6MV photons. Additionally, three sets of nanodots were each irradiated using 6MV, 10MV and 15MV beams. For each beam energy, and selected dose in the range of 3 to 1000 cGy, amore » pair of nanodots was irradiated and three readings were obtained with both readers. Results: The analysis shows that for 3 photon beam energies and selected ranges of dose, the calculated absorbed dose agrees well with the expected value. The results illustrate that the new Microstar II reader is a highly consistent system and that the repeated readings provide results with a reasonably small standard deviation. For all practical purposes, the response of system is linear for all radiation beam energies. Conclusion: The Microstar II nanodot reader is consistent, accurate, and reliable. The new hardware design and corresponding software contain several advantages over the previous model. The automatic repeat reading mechanism, that helps improve reproducibility and reduce processing time, and the smaller unit size that renders ease of transport, are two of such features. Present study shows that for high dose ranges a polynomial calibration equation provides more consistent results. A 3rd order polynomial calibration curve was used to analyze the readings of dosimeters exposed to high dose range radiation. It was observed that the results show less error compared to those calculated by using linear calibration curves, as provided by Landauer system software for all dose ranges.« less

Evaluation of cytotoxicity and radiation enhancement using 1.9 nm gold particles: potential application for cancer therapy

PubMed Central

Butterworth, K T; Coulter, J A; Jain, S; Forker, J; McMahon, S J; Schettino, G; Prise, K M; Currell, F J; Hirst, D G

2010-01-01

High atomic number (Z) materials such as gold preferentially absorb kilovoltage x-rays compared to soft tissue and may be used to achieve local dose enhancement in tumours during treatment with ionizing radiation. Gold nanoparticles have been demonstrated as radiation dose enhancing agents in vivo and in vitro. In the present study, we used multiple endpoints to characterize the cellular cytotoxic response of a range of cell lines to 1.9 nm gold particles and measured dose modifying effects following transient exposure at low concentrations. Gold nanoparticles caused significant levels of cell type specific cytotoxicity, apoptosis and increased oxidative stress. When used as dose modifying agents, dose enhancement factors varied between the cell lines investigated with the highest enhancement being 1.9 in AGO-1522B cells at a nanoparticle concentration of 100 μg ml−1. This study shows exposure to 1.9 nm gold particles to induce a range of cell line specific responses including decreased clonogenic survival, increased apoptosis and induction of DNA damage which may be mediated through the production of reactive oxygen species. This is the first study involving 1.9 nm nanometre sized particles to report multiple cellular responses which impact on the radiation dose modifying effect. The findings highlight the need for extensive characterization of responses to gold nanoparticles when assessing dose enhancing potential in cancer therapy. PMID:20601762

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.

PubMed

Andrews, Louise M; de Winter, Brenda C M; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H N; Koch, Birgit C P; van Gelder, Teun; Hesselink, Dennis A

2017-02-01

Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients.

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique

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

Gandhi, Diksha; Schmidt, Taly Gilat, E-mail: taly.gilat-schmidt@marquette.edu; Crotty, Dominic J.

Purpose: This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods: Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings.more » Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results: ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions: ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.« less

Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants.

PubMed

Tekgündüz, Kadir Şerafettin; Ceviz, Naci; Caner, İbrahim; Olgun, Haşim; Demirelli, Yaşar; Yolcu, Canan; Şahin, İrfan Oğuz; Kara, Mustafa

2015-08-01

Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.

Feasibility of MR-only proton dose calculations for prostate cancer radiotherapy using a commercial pseudo-CT generation method

NASA Astrophysics Data System (ADS)

Maspero, Matteo; van den Berg, Cornelis A. T.; Landry, Guillaume; Belka, Claus; Parodi, Katia; Seevinck, Peter R.; Raaymakers, Bas W.; Kurz, Christopher

2017-12-01

A magnetic resonance (MR)-only radiotherapy workflow can reduce cost, radiation exposure and uncertainties introduced by CT-MRI registration. A crucial prerequisite is generating the so called pseudo-CT (pCT) images for accurate dose calculation and planning. Many pCT generation methods have been proposed in the scope of photon radiotherapy. This work aims at verifying for the first time whether a commercially available photon-oriented pCT generation method can be employed for accurate intensity-modulated proton therapy (IMPT) dose calculation. A retrospective study was conducted on ten prostate cancer patients. For pCT generation from MR images, a commercial solution for creating bulk-assigned pCTs, called MR for Attenuation Correction (MRCAT), was employed. The assigned pseudo-Hounsfield Unit (HU) values were adapted to yield an increased agreement to the reference CT in terms of proton range. Internal air cavities were copied from the CT to minimise inter-scan differences. CT- and MRCAT-based dose calculations for opposing beam IMPT plans were compared by gamma analysis and evaluation of clinically relevant target and organ at risk dose volume histogram (DVH) parameters. The proton range in beam’s eye view (BEV) was compared using single field uniform dose (SFUD) plans. On average, a (2%, 2 mm) gamma pass rate of 98.4% was obtained using a 10% dose threshold after adaptation of the pseudo-HU values. Mean differences between CT- and MRCAT-based dose in the DVH parameters were below 1 Gy (<1.5% ). The median proton range difference was 0.1 mm, with on average 96% of all BEV dose profiles showing a range agreement better than 3 mm. Results suggest that accurate MR-based proton dose calculation using an automatic commercial bulk-assignment pCT generation method, originally designed for photon radiotherapy, is feasible following adaptation of the assigned pseudo-HU values.

Dosing of Milrinone in Preterm Neonates to Prevent Postligation Cardiac Syndrome: Simulation Study Suggests Need for Bolus Infusion.

PubMed

Hallik, Maarja; Tasa, Tõnis; Starkopf, Joel; Metsvaht, Tuuli

2017-01-01

Milrinone has been suggested as a possible first-line therapy for preterm neonates to prevent postligation cardiac syndrome (PLCS) through decreasing systemic vascular resistance and increasing cardiac contractility. The optimal dosing regimen, however, is not known. To model the dosing of milrinone in preterm infants for prevention of PLCS after surgical closure of patent ductus arteriosus (PDA). Milrinone time-concentration profiles were simulated for 1,000 subjects using the volume of distribution and clearance estimates based on one compartmental population pharmacokinetic model by Paradisis et al. [Arch Dis Child Fetal Neonatal Ed 2007;92:F204-F209]. Dose optimization was based on retrospectively collected demographic data from neonates undergoing PDA ligation in Estonian PICUs between 2012 and 2014 and existing pharmacodynamic data. The target plasma concentration was set at 150-200 ng/ml. The simulation study used demographic data from 31 neonates who underwent PDA ligation. The median postnatal age was 13 days (range: 3-29) and weight was 760 g (range: 500-2,351). With continuous infusion of milrinone 0.33 μg/kg/min, the proportion of subjects within the desired concentration range was 0% by 3 h, 36% by 6 h, and 61% by 8 h; 99% of subjects exceeded the range by 18 h. The maximum proportion of total simulated concentrations in the target range was attained with a bolus infusion of 0.73 μg/kg/min for 3 h followed by a 0.16-μg/kg/min maintenance infusion. Mathematical simulations suggest that in preterm neonates the plasma time-concentration profile of milrinone can be optimized with a slow loading dose followed by maintenance infusion. © 2016 S. Karger AG, Basel.

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry

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

González-López, Antonio, E-mail: antonio.gonzalez7@carm.es; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

Purpose: This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Methods: Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dosemore » ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. Results: For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Conclusions: Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.« less

SU-F-T-22: Clinical Implications When Using TG-186 (ACE) Heterogeneity Software

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

Likhacheva, A; Grade, E; Sadeghi, A

Purpose: The purpose of this study is to compare dosimetric calculations using traditional TG-43 formalism and Oncentra Brachy Advanced Collapsed cone Engine (ACE) TG-186 calculation algorithm in clinical setting. Methods: We analyzed dosimetry of four patients treated with accelerated partial breast irradiation using a multi-channel intracavitary device (SAVI). All patients were treated to 34 Gy in 10 fractions using a high-dose-rate (192) Ir source. The plans were designed and treated using the TG-43 model. ACE was used to assess the effect heterogeneity correction on various dosimetric parameters. Mass density was estimated using Hounsfield units. Results: Compared to TG-43 formalism, ACEmore » estimated lower doses to targets and organs at risk. The mean difference was 19.8% (range 15.3–24.1%) for PTV-eval V200, 12.0% (range 9.7–17.7%) for PTV-eval V150, 4.3% (range 3.3–6.5%) for PTV-eval D95, 3.3% (range 1.4–5.4%) for PTV-eval D90, 5.4% (range 2.9–9.9%) for maximum rib dose, and 5.7% (2.4–7.4%) for maximum skin dose. There was no correlation between the magnitude of the difference and the PTV-eval volume, air volume, or tissue-applicator conformance. Conclusion: Based on our preliminary study, the TG-43 algorithm appears to overestimate the dose to targets and organs at risk when compared to the ACE TG-186 software. We hypothesize that air adjacent to the SAVI struts contributes to lack of scatter thereby contributing a significant difference in dose calculation when using ACE. We believe that ACE calculation provides a more realistic isodose distribution than TG-43. We plan to further investigate the impact of heterogeneity correction on brachytherapy planning for a wide variety of clinical scenarios, include skin, cervix/uterus, prostate, and lung.« less

Estimation of breast dose reduction potential for organ-based tube current modulated CT with wide dose reduction arc

NASA Astrophysics Data System (ADS)

Fu, Wanyi; Sturgeon, Gregory M.; Agasthya, Greeshma; Segars, W. Paul; Kapadia, Anuj J.; Samei, Ehsan

2017-03-01

This study aimed to estimate the organ dose reduction potential for organ-dose-based tube current modulated (ODM) thoracic CT with wide dose reduction arc. Twenty-one computational anthropomorphic phantoms (XCAT, age range: 27- 75 years, weight range: 52.0-105.8 kg) were used to create a virtual patient population with clinical anatomic variations. For each phantom, two breast tissue compositions were simulated: 50/50 and 20/80 (glandular-to-adipose ratio). A validated Monte Carlo program was used to estimate the organ dose for standard tube current modulation (TCM) (SmartmA, GE Healthcare) and ODM (GE Healthcare) for a commercial CT scanner (Revolution, GE Healthcare) with explicitly modeled tube current modulation profile, scanner geometry, bowtie filtration, and source spectrum. Organ dose was determined using a typical clinical thoracic CT protocol. Both organ dose and CTDIvol-to-organ dose conversion coefficients (h factors) were compared between TCM and ODM. ODM significantly reduced all radiosensitive organ doses (p<0.01). The breast dose was reduced by 30+/-2%. For h factors, organs in the anterior region (e.g. thyroid, stomach) exhibited substantial decreases, and the medial, distributed, and posterior region either saw an increase or no significant change. The organ-dose-based tube current modulation significantly reduced organ doses especially for radiosensitive superficial anterior organs such as the breasts.

Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

PubMed

Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

2013-12-02

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

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

Olson, J.J.; Friedman, R.; Orr, K.

1990-05-01

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose,more » a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.« less

Optimal sensitometric curves of Kodak EDR2 film for dynamic intensity modulated radiation therapy verification

PubMed Central

Suriyapee, S; Pitaxtarnin, N; Oonsiri, S; Jumpangern, C; Israngkul Na Ayuthaya, I

2008-01-01

Purpose: To investigate the optimal sensitometric curves of extended dose range (EDR2) radiographic film in terms of depth, field size, dose range and processing conditions for dynamic intensity modulated radiation therapy (IMRT) dosimetry verification with 6 MV X-ray beams. Materials and methods: A Varian Clinac 23 EX linear accelerator with 6 MV X-ray beam was used to study the response of Kodak EDR2 film. Measurements were performed at depths of 5, 10 and 15 cm in MedTec virtual water phantom and with field sizes of 2x2, 3x3, 10x10 and 15x15 cm2. Doses ranging from 20 to 450 cGy were used. The film was developed with the Kodak RP X-OMAT Model M6B automatic film processor. Film response was measured with the Vidar model VXR-16 scanner. Sensitometric curves were applied to the dose profiles measured with film at 5 cm in the virtual water phantom with field sizes of 2x2 and 10x10 cm2 and compared with ion chamber data. Scanditronix/Wellhofer OmniProTM IMRT software was used for the evaluation of the IMRT plan calculated by Eclipse treatment planning. Results: Investigation of the reproducibility and accuracy of the film responses, which depend mainly on the film processor, was carried out by irradiating one film nine times with doses of 20 to 450 cGy. A maximum standard deviation of 4.9% was found which decreased to 1.9% for doses between 20 and 200 cGy. The sensitometric curves for various field sizes at fixed depth showed a maximum difference of 4.2% between 2x2 and 15x15 cm2 at 5 cm depth with a dose of 450 cGy. The shallow depth tended to show a greater effect of field size responses than the deeper depths. The sensitometric curves for various depths at fixed field size showed slightly different film responses; the difference due to depth was within 1.8% for all field sizes studied. Both field size and depth effect were reduced when the doses were lower than 450 cGy. The difference was within 2.5% in the dose range from 20 to 300 cGy for all field sizes and depths studied. Dose profiles measured with EDR2 film were consistent with those measured with an ion chamber. The optimal sensitometric curve was acquired by irradiating film at a depth of 5 cm with doses ranging from 20 to 450 cGy with a 3×3 cm2 multileaf collimator. The optimal sensitometric curve allowed accurate determination of the absolute dose distribution. In almost 200 cases of dynamic IMRT plan verification with EDR2 film, the difference between measured and calculated dose was generally less than 3% and with 3 mm distance to agreement when using gamma value verification. Conclusion: EDR2 film can be used for accurate verification of composite isodose distributions of dynamic IMRT when the optimal sensitometric curve has been established. PMID:21614315

Optimal sensitometric curves of Kodak EDR2 film for dynamic intensity modulated radiation therapy verification.

PubMed

Suriyapee, S; Pitaxtarnin, N; Oonsiri, S; Jumpangern, C; Israngkul Na Ayuthaya, I

2008-01-01

To investigate the optimal sensitometric curves of extended dose range (EDR2) radiographic film in terms of depth, field size, dose range and processing conditions for dynamic intensity modulated radiation therapy (IMRT) dosimetry verification with 6 MV X-ray beams. A Varian Clinac 23 EX linear accelerator with 6 MV X-ray beam was used to study the response of Kodak EDR2 film. Measurements were performed at depths of 5, 10 and 15 cm in MedTec virtual water phantom and with field sizes of 2x2, 3x3, 10x10 and 15x15 cm(2). Doses ranging from 20 to 450 cGy were used. The film was developed with the Kodak RP X-OMAT Model M6B automatic film processor. Film response was measured with the Vidar model VXR-16 scanner. Sensitometric curves were applied to the dose profiles measured with film at 5 cm in the virtual water phantom with field sizes of 2x2 and 10x10 cm(2) and compared with ion chamber data. Scanditronix/Wellhofer OmniPro(TM) IMRT software was used for the evaluation of the IMRT plan calculated by Eclipse treatment planning. Investigation of the reproducibility and accuracy of the film responses, which depend mainly on the film processor, was carried out by irradiating one film nine times with doses of 20 to 450 cGy. A maximum standard deviation of 4.9% was found which decreased to 1.9% for doses between 20 and 200 cGy. The sensitometric curves for various field sizes at fixed depth showed a maximum difference of 4.2% between 2x2 and 15x15 cm(2) at 5 cm depth with a dose of 450 cGy. The shallow depth tended to show a greater effect of field size responses than the deeper depths. The sensitometric curves for various depths at fixed field size showed slightly different film responses; the difference due to depth was within 1.8% for all field sizes studied. Both field size and depth effect were reduced when the doses were lower than 450 cGy. The difference was within 2.5% in the dose range from 20 to 300 cGy for all field sizes and depths studied. Dose profiles measured with EDR2 film were consistent with those measured with an ion chamber. The optimal sensitometric curve was acquired by irradiating film at a depth of 5 cm with doses ranging from 20 to 450 cGy with a 3×3 cm(2) multileaf collimator. The optimal sensitometric curve allowed accurate determination of the absolute dose distribution. In almost 200 cases of dynamic IMRT plan verification with EDR2 film, the difference between measured and calculated dose was generally less than 3% and with 3 mm distance to agreement when using gamma value verification. EDR2 film can be used for accurate verification of composite isodose distributions of dynamic IMRT when the optimal sensitometric curve has been established.

Characterization of Thymol blue Radiochromic dosimeters for high dose applications

NASA Astrophysics Data System (ADS)

Aldweri, Feras M.; Abuzayed, Manar H.; Al-Ajaleen, Musab S.; Rabaeh, Khalid A.

2018-03-01

Thymol blue (TB) solutions and Thymol blue Polyvinyl Alcohol (TB-PVA) films have been introduced as Radiochromic dosimeter for high dose applications. The dosimeters were irradiated with gamma ray (60Co source) from 5 to 30 kGy for film, and from 0.150 kGy to 4 kGy for solution. The optical density of unirradiated and irradiated TB solution as well as TB-PVA film dosimeters were studied in terms of absorbance at 434 nm using UV/VIS spectrophotometer. The effects of scan temperature, light pre-gamma irradiation, dose rate, relative humidity and stability of the absorbance of solutions and films after irradiation were investigated. We found the dose sensitivity of TB solution and TB-PVA film dosimeters increases significantly with increases of the absorbed dose as well as with the increases of TB dye concentrations. The useful dose range of developed TB solutions and TB-PVA films dosimeters is in the range 0.125-1 kGy and of 5-20 kGy, respectively.

The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

PubMed

Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

2016-04-01

Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of Antivenom Dosing Strategies for Rattlesnake Envenomation.

PubMed

Spyres, Meghan B; Skolnik, Aaron B; Moore, Elizabeth C; Gerkin, Richard D; Padilla-Jones, Angela; Ruha, Anne-Michelle

2018-06-01

This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation. This is a retrospective cohort study of adult rattlesnake envenomations treated at a regional toxicology center. Data on demographics, envenomation details, antivenom administration, length of stay, and laboratory and clinical outcomes were compared between the PRN and maintenance groups. Primary outcomes were hospital length of stay and total antivenom used, with a hypothesis of no difference between the two dosing strategies. A single regional toxicology center PATIENTS:: Three-hundred ten adult patients envenomated by rattlesnakes between 2007 and 2014 were included. Patients were excluded if no antivenom was administered or for receiving an antivenom other than Crofab (BTG International, West Conshohocken, PA). This is a retrospective study of rattlesnake envenomations treated with and without maintenance antivenom dosing. One-hundred forty-eight in the maintenance group and 162 in the PRN group were included. There was no difference in demographics or baseline envenomation severity or hemotoxicity (32.7% vs 40.5%; respectively; p = 0.158) between the two groups. Comparing the PRN with the maintenance group, less antivenom was used (8 [interquartile range, 6-12] vs 16 [interquartile range, 12-18] vials, respectively; p < 0.001), and hospital length of stay was shorter (27 hr [interquartile range, 20-44 hr] vs 34 hr [interquartile range, 24-43 hr], respectively; p = 0.014). There were no differences in follow-up outcomes of readmission, retreatment, or bleeding and surgical complications. Hospital length of stay was shorter, and less antivenom was used in patients receiving a PRN antivenom dosing strategy after rattlesnake envenomation.

High-temperature thermoluminescence of anion-deficient alumina and possibilities of its application in high-dose dosimetry

NASA Astrophysics Data System (ADS)

Surdo, A. I.; Milman, I. I.; Abashev, R. M.; Vlasov, M. I.

2014-12-01

Results of studies of the thermoluminescence (TL) of anion-deficient alumina (α-Al2O3 - δ) single crystals and based on them TLD-500 detectors exposed to pulsed X-ray and electron radiation in a wide range of doses D, pulsed dose rates P p , and temperatures are described. The TL responses of α-Al2O3 - δ for continuous and pulsed X-ray irradiation at D = 0.05-150 Gy are compared. Unlike continuous irradiation, in the case of pulsed irradiation at P p ≥ 6 × 106 Gy/s, a linear increase in the TL response as a function of D is registered in the main and "chromium" peaks at 450 and 580 K, respectively, with a decrease in the slope of the dose dependence at D > 2 Gy for the peak at 450 K. It is found that high-dose irradiation (>60 Gy) leads to the formation of a new TL peak at 830 K and the preferential redistribution of the stored light sums into this peak. The dose dependence for the TL peak at 830 K is studied. It is established that it is linear in a super-high dose range of 104 to 6 × 106 Gy at P p = 2.6 × 1011 Gy/s.

IMRT and RapidArc commissioning of a TrueBeam linear accelerator using TG-119 protocol cases.

PubMed

Wen, Ning; Zhao, Bo; Kim, Jinkoo; Chin-Snyder, Karen; Bellon, Maria; Glide-Hurst, Carri; Barton, Kenneth; Chen, Daiquan; Chetty, Indrin J

2014-09-08

The purpose of this study is to evaluate the overall accuracy of intensity-modulated radiation therapy (IMRT) and RapidArc delivery using both flattening filter (FF) and flattening filter-free (FFF) modalities based on test cases developed by AAPM Task Group 119. Institutional confidence limits (CLs) were established as the baseline for patient specific treatment plan quality assurance (QA). The effects of gantry range, gantry speed, leaf speed, dose rate, as well as the capability to capture intentional errors, were evaluated by measuring a series of Picket Fence (PF) tests using the electronic portal imaging device (EPID) and EBT3 films. Both IMRT and RapidArc plans were created in a Solid Water phantom (30 × 30 × 15 cm3) for the TG-119 test cases representative of normal clinical treatment sites for all five photon energies (6X, 10X, 15X, 6X-FFF, 10X-FFF) and the Exact IGRT couch was included in the dose calculation. One high-dose point in the PTV and one low-dose point in the avoidance structure were measured with an ion chamber in each case for each energy. Similarly, two GAFCHROMIC EBT3 films were placed in the coronal planes to measure planar dose distributions in both high- and low-dose regions. The confidence limit was set to have 95% of the measured data fall within the tolerance. The mean of the absolute dose deviation for variable dose rate and gantry speed during RapidArc delivery was within 0.5% for all energies. The corresponding results for leaf speed tests were all within 0.4%. The combinations of dynamic leaf gap (DLG) and MLC transmission factor were optimized based on the ion chamber measurement results of RapidArc delivery for each energy. The average 95% CLs for the high-dose point in the PTV were 0.030 ± 0.007 (range, 0.022-0.038) for the IMRT plans and 0.029 ± 0.011 (range, 0.016-0.043) for the RapidArc plans. For low-point dose in the avoidance structures, the CLs were 0.029 ± 0.006 (range, 0.024-0.039) for the IMRT plans and 0.027 ± 0.013 (range, 0.017-0.047) for the RapidArc plans. The average 95% CLs using 3%/3 mm gamma criteria in the high-dose region were 5.9 ± 2.7 (range, 1.4-8.6) and 3.9 ± 2.9 (range, 1.5-8.8) for IMRT and RapidArc plans, respectively. The average 95% CLs in the low-dose region were 5.3 ± 2.6 (range, 1.2-7.4) and 3.7 ± 2.8 (range, 1.8-8.3) for IMRT and RapidArc plans, respectively. Based on ion chamber, as well as film measurements, we have established CLs values to ensure the high precision of IMRT and RapidArc delivery for both FF and FFF modalities.

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

2016-06-01

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

[Comparison of Organ Dose Calculation Using Monte Carlo Simulation and In-phantom Dosimetry in CT Examination].

PubMed

Iriuchijima, Akiko; Fukushima, Yasuhiro; Ogura, Akio

Direct measurement of each patient organ dose from computed tomography (CT) is not possible. Most methods to estimate patient organ dose is using Monte Carlo simulation with dedicated software. However, the method and the relative differences between organ dose simulation and measurement is unclear. The purpose of this study was to compare organ doses evaluated by Monte Carlo simulation with doses evaluated by in-phantom dosimetry. The simulation software Radimetrics (Bayer) was used for the calculation of organ dose. Measurement was performed with radio-photoluminescence glass dosimeter (RPLD) set at various organ positions within RANDO phantom. To evaluate difference of CT scanner, two different CT scanners were used in this study. Angular dependence of RPLD and measurement of effective energy were performed for each scanner. The comparison of simulation and measurement was evaluated by relative differences. In the results, angular dependence of RPLD at two scanners was 31.6±0.45 mGy for SOMATOM Definition Flash and 29.2±0.18 mGy for LightSpeed VCT. The organ dose was 42.2 mGy (range, 29.9-52.7 mGy) by measurements and 37.7 mGy (range, 27.9-48.1 mGy) by simulations. The relative differences of organ dose between measurement and simulation were 13%, excluding of breast's 42%. We found that organ dose by simulation was lower than by measurement. In conclusion, the results of relative differences will be useful for evaluating organ doses for individual patients by simulation software Radimetrics.

Micro-Dose Calibrator for Pre-clinical Radiotracer Assays | NCI Technology Transfer Center | TTC

Cancer.gov

Pre-clinical radiotracer biomedical research involves the use of compounds labeled with radioisotopes, including cell binding studies, immune cell labeling techniques, and radio-ligand bio-distribution studies. Before this Micro-Dose Calibrator, measurement of pre-clinical level dosage for small animal studies was inaccurate and unreliable. This dose calibrator is a prototype ready for manufacturing. It is designed to accurately measure radioactive doses in the range of 50 nCi (1.8 kBq) to 100 µCi (3.7 MBq) with 1% precision. The NCI seeks co-development or licensing to commercialize it. Alternative uses will be considered.

Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

PubMed

Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

2016-02-01

To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Peripheral doses from pediatric IMRT

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

Klein, Eric E.; Maserang, Beth; Wood, Roy

Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 tomore » 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged from 0.47-0.94) doses {approx}[0.4-1.8 cGy]/[0.9-2.9 cGy]/fraction, respectively. Prior phantom reports are for fields 10 cm or greater, while pediatric central nervous system fields range from 4 to 7 cm, and effectively much smaller for IMRT (2-6 cm). Peripheral dose in close proximity (<10 cm from the field edge) is dominated by internal scatter; therefore, field-size differences overwhelm phantom size affects and increased MU. Distant peripheral dose, dominated by head leakage, was higher than predicted, even when accounting for MUs ({approx}factor of 3) likely due to the pediatric phantom size. The ratio of the testes dose ranged from 3.3-5.3 for IMRT/conventional. PD to OAR for pediatric IMRT cannot be predicted from large-field full phantom studies. For regional OAR, doses are likely lower than predicted by existing ''large field'' data, while the distant PD is higher.« less

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2015-07-01

High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).

PubMed

Maze, Ian S; Wright, Geraldine A; Mustard, Julie A

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.

Point-of-use chlorination of turbid water: results from a field study in Tanzania.

PubMed

Mohamed, Hussein; Brown, Joe; Njee, Robert M; Clasen, Thomas; Malebo, Hamisi M; Mbuligwe, Steven

2015-06-01

Household-based chlorine disinfection is widely effective against waterborne bacteria and viruses, and may be among the most inexpensive and accessible options for household water treatment. The microbiological effectiveness of chlorine is limited, however, by turbidity. In Tanzania, there are no guidelines on water chlorination at household level, and limited data on whether dosing guidelines for higher turbidity waters are sufficient to produce potable water. This study was designed to assess the effectiveness of chlorination across a range of turbidities found in rural water sources, following local dosing guidelines that recommend a 'double dose' for water that is visibly turbid. We chlorinated water from 43 sources representing a range of turbidities using two locally available chlorine-based disinfectants: WaterGuard and Aquatabs. We determined free available chlorine at 30 min and 24 h contact time. Our data suggest that water chlorination with WaterGuard or Aquatabs can be effective using both single and double doses up to 20 nephelometric turbidity units (NTU), or using a double dose of Aquatabs up to 100 NTU, but neither was effective at turbidities greater than 100 NTU.

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.

The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range

PubMed Central

Kalliokoski, Annikka; Neuvonen, Mikko; Neuvonen, Pertti J; Niemi, Mikko

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTOrganic anion transporting polypeptide 1B1 is an influx transporter expressed on the basolateral membrane of hepatocytes.A common single nucleotide polymorphism, c.521T→C (p.Val174Ala), of the SLCO1B1 gene has been associated with increased plasma repaglinide concentrations in healthy volunteers.Previous studies at low repaglinide doses have suggested that the effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide could be dose-dependent. WHAT THIS STUDY ADDSRepaglinide peak plasma concentration and area under the plasma concentration–time curve increased linearly along with repaglinide dose ranging from 0.25 to 2 mg in both the predominant c.521TT and rare c.521CC genotype group.The effect of SLCO1B1 c.521T→C polymorphism on repaglinide pharmacokinetics persists over a wide dose range. AIMS To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T→C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose-dependent. METHODS Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25-, 0.5-, 1- or 2-mg dose of repaglinide in a dose-escalation study with a wash-out period of ≥1 week. RESULTS The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P ≤ 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC0–∞ increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype. CONCLUSIONS The effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range. PMID:18823304

TU-H-CAMPUS-JeP1-05: Dose Deformation Error Associated with Deformable Image Registration Pathways

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

Surucu, M; Woerner, A; Roeske, J

Purpose: To evaluate errors associated with using different deformable image registration (DIR) pathways to deform dose from planning CT (pCT) to cone-beam CT (CBCT). Methods: Deforming dose is controversial because of the lack of quality assurance tools. We previously proposed a novel metric to evaluate dose deformation error (DDE) by warping dose information using two methods, via dose and contour deformation. First, isodose lines of the pCT were converted into structures and then deformed to the CBCT using an image based deformation map (dose/structure/deform). Alternatively, the dose matrix from the pCT was deformed to CBCT using the same deformation map,more » and then the same isodose lines of the deformed dose were converted into structures (dose/deform/structure). The doses corresponding to each structure were queried from the deformed dose and full-width-half-maximums were used to evaluate the dose dispersion. The difference between the FWHM of each isodose level structure is defined as the DDE. Three head-and-neck cancer patients were identified. For each patient, two DIRs were performed between the pCT and CBCT, either deforming pCT-to-CBCT or CBCT-to-pCT. We evaluated the errors associated by using either of these pathways to deform dose. A commercially available, Demons based DIR was used for this study, and 10 isodose levels (20% to 105%) were used to evaluate the errors in various dose levels. Results: The prescription dose for all patients was 70 Gy. The mean DDE for CT-to-CBCT deformation was 1.0 Gy (range: 0.3–2.0 Gy) and this was increased to 4.3 Gy (range: 1.5–6.4 Gy) for CBCT-to-CT deformation. The mean increase in DDE between the two deformations was 3.3 Gy (range: 1.0–5.4 Gy). Conclusion: The proposed DDF was used to quantitatively estimate dose deformation errors caused by different pathways to perform DIR. Deforming dose using CBCT-to-CT deformation produced greater error than CT-to-CBCT deformation.« less

Application of commercial MOSFET detectors for in vivo dosimetry in the therapeutic x-ray range from 80 kV to 250 kV

NASA Astrophysics Data System (ADS)

Ehringfeld, Christian; Schmid, Susanne; Poljanc, Karin; Kirisits, Christian; Aiginger, Hannes; Georg, Dietmar

2005-01-01

The purpose of this study was to investigate the dosimetric characteristics (energy dependence, linearity, fading, reproducibility, etc) of MOSFET detectors for in vivo dosimetry in the kV x-ray range. The experience of MOSFET in vivo dosimetry in a pre-clinical study using the Alderson phantom and in clinical practice is also reported. All measurements were performed with a Gulmay D3300 kV unit and TN-502RDI MOSFET detectors. For the determination of correction factors different solid phantoms and a calibrated Farmer-type chamber were used. The MOSFET signal was linear with applied dose in the range from 0.2 to 2 Gy for all energies. Due to fading it is recommended to read the MOSFET signal during the first 15 min after irradiation. For long time intervals between irradiation and readout the fading can vary largely with the detector. The temperature dependence of the detector signal was small (0.3% °C-1) in the temperature range between 22 and 40 °C. The variation of the measuring signal with beam incidence amounts to ±5% and should be considered in clinical applications. Finally, for entrance dose measurements energy-dependent calibration factors, correction factors for field size and irradiated cable length were applied. The overall accuracy, for all measurements, was dominated by reproducibility as a function of applied dose. During the pre-clinical in vivo study, the agreement between MOSFET and TLD measurements was well within 3%. The results of MOSFET measurements, to determine the dosimetric characteristics as well as clinical applications, showed that MOSFET detectors are suitable for in vivo dosimetry in the kV range. However, some energy-dependent dosimetry effects need to be considered and corrected for. Due to reproducibility effects at low dose levels accurate in vivo measurements are only possible if the applied dose is equal to or larger than 2 Gy.

Application of commercial MOSFET detectors for in vivo dosimetry in the therapeutic x-ray range from 80 kV to 250 kV.

PubMed

Ehringfeld, Christian; Schmid, Susanne; Poljanc, Karin; Kirisits, Christian; Aiginger, Hannes; Georg, Dietmar

2005-01-21

The purpose of this study was to investigate the dosimetric characteristics (energy dependence, linearity, fading, reproducibility, etc) of MOSFET detectors for in vivo dosimetry in the kV x-ray range. The experience of MOSFET in vivo dosimetry in a pre-clinical study using the Alderson phantom and in clinical practice is also reported. All measurements were performed with a Gulmay D3300 kV unit and TN-502RDI MOSFET detectors. For the determination of correction factors different solid phantoms and a calibrated Farmer-type chamber were used. The MOSFET signal was linear with applied dose in the range from 0.2 to 2 Gy for all energies. Due to fading it is recommended to read the MOSFET signal during the first 15 min after irradiation. For long time intervals between irradiation and readout the fading can vary largely with the detector. The temperature dependence of the detector signal was small (0.3% degrees C(-1)) in the temperature range between 22 and 40 degrees C. The variation of the measuring signal with beam incidence amounts to +/-5% and should be considered in clinical applications. Finally, for entrance dose measurements energy-dependent calibration factors, correction factors for field size and irradiated cable length were applied. The overall accuracy, for all measurements, was dominated by reproducibility as a function of applied dose. During the pre-clinical in vivo study, the agreement between MOSFET and TLD measurements was well within 3%. The results of MOSFET measurements, to determine the dosimetric characteristics as well as clinical applications, showed that MOSFET detectors are suitable for in vivo dosimetry in the kV range. However, some energy-dependent dosimetry effects need to be considered and corrected for. Due to reproducibility effects at low dose levels accurate in vivo measurements are only possible if the applied dose is equal to or larger than 2 Gy.

Systemic levels of local anaesthetic after intra-peritoneal application--a systematic review.

PubMed

Kahokehr, A; Sammour, T; Vather, R; Taylor, M; Stapelberg, F; Hill, A G

2010-07-01

There is a lack of cohesive reports on the systemic levels of local anaesthetic after intraperitoneal application. A comprehensive systematic review with no language restriction was conducted. Eighteen suitable articles were identified. Data were compiled and presented according to local anaesthetic agent. Intraperitoneal local anaesthetic has been studied in many different procedures, including open and laparoscopic surgery. A total of 415 patients were included for analysis. There were no cases of clinical toxicity. There were 11 (2.7%) cases with a systemic level above or close to a safe threshold (as determined by the report authors) in three trials utilising intraperitoneal local anaesthetic after laparoscopic cholecystectomy. Intraperitoneal lignocaine doses varied from 100 to 1000 mg, mean Cmax ranged from 1.01 to 4.32 microg/ml and mean Tmax ranged from 15 to 40 minutes. Intraperitoneal bupivacaine doses varied from 50 to 150 mg (weight based doses also reported), mean Cmax ranged from 0.29 to 1.14 microg/ml and mean Tmax ranged from 15 to 60 minutes. Intraperitoneal ropivacaine doses varied from 100 to 300 mg, mean Cmax ranged from 0.66 to 3.76 microg/ml and mean Tmax ranged from 15 to 35 minutes. The addition of adrenaline to intraperitoneal local anaesthetic almost halves systemic levels and prolongs Tmax. Intraperitoneal local anaesthetic results in detectable systemic levels in the perioperative setting. Despite a lack of clinical toxicity, careful attention to dose is still required to prevent potential systemic toxic levels. Clinicians should also consider the addition of adrenaline to intraperitoneal local anaesthetic solutions to further add to the systemic safety profile.

Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.

PubMed

Sarashina, Akiko; Koiwai, Kazuki; Seman, Leo J; Yamamura, Norio; Taniguchi, Atsushi; Negishi, Takahiro; Sesoko, Shogo; Woerle, Hans J; Dugi, Klaus A

2013-01-01

This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

Dose uniformity of budesonide Easyhaler® under simulated real-life conditions and with low inspiration flow rates.

PubMed

Haikarainen, Jussi; Rytilä, Paula; Roos, Sirkku; Metsärinne, Sirpa; Happonen, Anita

2017-01-01

Budesonide Easyhaler® multidose dry powder inhaler is approved for the treatment of asthma. Objectives were to determine the delivered dose (DD) uniformity of budesonide Easyhaler® in simulated real-world conditions and with different inspiration flow rates (IFRs). Three dose delivery studies were performed using 100, 200, and 400 µg/dose strengths of budesonide. Dose uniformity was assessed during in-use periods of 4-6 months after exposure to high temperature (30°C) and humidity (60% relative humidity) and after dropping and vibration testing. The influence of various IFRs (31, 43, and 54 L/min) on the DD was also investigated. Acceptable dose uniformity was declared when mean DD were within 80-120% of expected dose; all data reported descriptively. DD was constant (range: 93-109% of expected dose) at all in-use periods and after exposure to high temperature and humidity for a duration of up to 6 months. DD post-dropping and -vibration were unaffected (range 98-105% of expected dose). Similarly, DD was constant and within 10% of expected dose across all IFRs. Results indicate that budesonide Easyhaler® delivers consistently accurate doses in various real-life conditions. Budesonide Easyhaler® can be expected to consistently deliver a uniform dose and improve asthma control regardless of high temperature and humidity or varying IFR.

Dosimetric evaluation of the OneDoseTM MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures.

PubMed

Ding, George X; Coffey, Charles W

2010-09-01

The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model

PubMed Central

2011-01-01

Background Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. Methods We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. Results Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. Conclusions The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child. PMID:21635774

Acute changes in the central nervous system of monkeys exposed to protons.

NASA Technical Reports Server (NTRS)

Haymaker, W.; Ibrahim, M. Z. M.; Miquel, J.; Call, N.; Noden, P.; Ashley, W.; Ballinger, E. R.; Ghidoni, J.; Lindsay, I. R.; Behar, A. J.

1972-01-01

Study of the changes occurring in simian brain exposed to protons of varied energy, given in wide dose and dose-rate ranges. Results show that inflammatory reaction and glycogen accumulation in astrocytes occurred practically in all animals. Cerebral cortical necrosis, granule cell pyknosis, and inflammatory reaction occurred at doses far lower than effective for high-energy gamma radiation given other series of monkeys at comparable dose rates. Metallic impregnation, carried out in virtually all the animals tested, revealed a wide variation in glial response even at equal doses and dose rates in the same proton energy series. Proton energy effect, dose effect, dose-time effect, and dose-rate effect were evident in the various morphological categories investigated, but inconsistencies were encountered.

Proposed linear energy transfer areal detector for protons using radiochromic film.

PubMed

Mayer, Rulon; Lin, Liyong; Fager, Marcus; Douglas, Dan; McDonough, James; Carabe, Alejandro

2015-04-01

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

Capstone Depleted Uranium Aerosol Biokinetics, Concentrations, and Doses

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

Guilmette, Raymond A.; Miller, Guthrie; Parkhurst, MaryAnn

2009-02-26

One of the principal goals of the Capstone Depleted Uranium (DU) Aerosol Study was to quantify and characterize DU aerosols generated inside armored vehicles by perforation with a DU penetrator. This study consequently produced a database in which the DU aerosol source terms were specified both physically and chemically for a variety of penetrator-impact geometries and conditions. These source terms were used to calculate radiation doses and uranium concentrations for various scenarios as part of the Capstone DU Human Health Risk Assessment (HHRA). This paper describes the scenario-related biokinetics of uranium, and summarizes intakes, chemical concentrations to the organs, andmore » E(50) and HT(50) for organs and tissues based on exposure scenarios for personnel in vehicles at the time of perforation as well as for first responders. For a given exposure scenario (duration time and breathing rates), the range of DU intakes among the target vehicles and shots was not large, about a factor of 10, with the lowest being from a ventilated operational Abrams tank and the highest being for an unventilated Abrams with DU penetrator perforating DU armor. The ranges of committed effective doses were more scenario-dependent than were intakes. For example, the largest range, a factor of 20, was shown for scenario A, a 1-min exposure, whereas, the range was only a factor of two for the first-responder scenario (E). In general, the committed effective doses were found to be in the tens of mSv. The risks ascribed to these doses are discussed separately.« less

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

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

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

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

LiF TLD-100 as a Dosimeter in High Energy Proton Beam Therapy-Can It Yield Accurate Results?

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

Zullo, John R.; Kudchadker, Rajat J.; Zhu, X. Ronald

In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly inmore » the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within {+-}5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within {+-} 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy.« less

Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

PubMed

Palmsten, Kristin; Rolland, Matthieu; Hebert, Mary F; Clowse, Megan E B; Schatz, Michael; Xu, Ronghui; Chambers, Christina D

2018-04-01

To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose. Copyright © 2018 John Wiley & Sons, Ltd.

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

PubMed

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

2014-06-01

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

Estimating the effective radiation dose imparted to patients by intraoperative cone-beam computed tomography in thoracolumbar spinal surgery.

PubMed

Lange, Jeffrey; Karellas, Andrew; Street, John; Eck, Jason C; Lapinsky, Anthony; Connolly, Patrick J; Dipaola, Christian P

2013-03-01

Observational. To estimate the radiation dose imparted to patients during typical thoracolumbar spinal surgical scenarios. Minimally invasive techniques continue to become more common in spine surgery. Computer-assisted navigation systems coupled with intraoperative cone-beam computed tomography (CT) represent one such method used to aid in instrumented spinal procedures. Some studies indicate that cone-beam CT technology delivers a relatively low dose of radiation to patients compared with other x-ray-based imaging modalities. The goal of this study was to estimate the radiation exposure to the patient imparted during typical posterior thoracolumbar instrumented spinal procedures, using intraoperative cone-beam CT and to place these values in the context of standard CT doses. Cone-beam CT scans were obtained using Medtronic O-arm (Medtronic, Minneapolis, MN). Thermoluminescence dosimeters were placed in a linear array on a foam-plastic thoracolumbar spine model centered above the radiation source for O-arm presets of lumbar scans for small or large patients. In-air dosimeter measurements were converted to skin surface measurements, using published conversion factors. Dose-length product was calculated from these values. Effective dose was estimated using published effective dose to dose-length product conversion factors. Calculated dosages for many full-length procedures using the small-patient setting fell within the range of published effective doses of abdominal CT scans (1-31 mSv). Calculated dosages for many full-length procedures using the large-patient setting fell within the range of published effective doses of abdominal CT scans when the number of scans did not exceed 3. We have demonstrated that single cone-beam CT scans and most full-length posterior instrumented spinal procedures using O-arm in standard mode would likely impart a radiation dose within the range of those imparted by a single standard CT scan of the abdomen. Radiation dose increases with patient size, and the radiation dose received by larger patients as a result of more than 3 O-arm scans in standard mode may exceed the dose received during standard CT of the abdomen. Understanding radiation imparted to patients by cone-beam CT is important for assessing risks and benefits of this technology, especially when spinal surgical procedures require multiple intraoperative scans.

Evaluation of dose‐area product of common radiographic examinations towards establishing a preliminary diagnostic reference levels (PDRLs) in Southwestern Nigeria

PubMed Central

Jibiri, Nnamdi N.

2016-01-01

In Nigeria, a large number of radiographic examinations are conducted yearly for various diagnostic purposes. However, most examinations carried out do not have records of doses received by the patients, and the employed exposure parameters used are not documented; therefore, adequate radiation dose management is hindered. The aim of the present study was to estimate the dose‐area product (DAP) of patients examined in Nigeria, and to propose regional reference dose levels for nine common examinations (chest PA, abdomen AP, pelvis AP, lumbar AP, skull AP, leg AP, knee AP, hand AP, and thigh AP) undertaken in Nigeria. Measurement of entrance surface dose (ESD) was carried out using thermoluminescent dosimeter (TLD). Measured ESDS were converted into DAP using the beam area of patients in 12 purposely selected hospitals. Results of the study show that the maximum/minimum ratio ranged from 3 for thigh AP to 57 in abdomen AP. The range of determined mean and 75th percentile DAPs were 0.18–17.16, and 0.25–28.59 Gy cm2, respectively. Data available for comparison show that 75th percentile DAPs in this study (in chest PA, abdomen AP, pelvis AP, lumbar AP) are higher than NRPB‐HPE reference values. The DAP in this study is higher by factor of 31.4 (chest PA), 9.9 (abdomen AP), 2.2 (pelvis AP), and 2.1 (lumbar AP) than NRPB‐HPE values. The relative higher dose found in this study shows nonoptimization of practice in Nigeria. It is expected that regular dose auditing and dose optimization implementation in Nigeria would lead to lower DAP value, especially in abdomen AP. The 75th percentile DAP distribution reported in this study could be taken as regional diagnostic reference level in the Southwestern Nigeria; however, a more extensive nationwide dose survey is required to establish national reference dose. PACS number(s): 87.53.Bn, 87.59.B PMID:27929511

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances.

PubMed

Orito, Kensuke; Kawarai-Shimamura, Asako; Ogawa, Atsushi; Nakamura, Atsushi

2017-12-22

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20-50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25-50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26-370 sec), median duration of emesis was 151.5 sec (range, 30-780 sec), and median number of emesis episodes was 2 (range, 1-8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting.

Pharmacokinetics and Safety of MP-376 (Levofloxacin Inhalation Solution) in Cystic Fibrosis Subjects▿

PubMed Central

Geller, David E.; Flume, Patrick A.; Griffith, David C.; Morgan, Elizabeth; White, Dan; Loutit, Jeffery S.; Dudley, Michael N.

2011-01-01

The pharmacokinetics and tolerability of nebulized MP-376 (levofloxacin inhalation solution [Aeroquin]) were determined in cystic fibrosis (CF) subjects. Ten CF subjects received single 180-mg doses of two formulations of MP-376, followed by a multiple-dose phase of 240 mg once daily for 7 days. Serum and expectorated-sputum samples were assayed for levofloxacin content. Safety was evaluated following the single- and multiple-dose study phases. Nebulized MP-376 produced high concentrations of levofloxacin in sputum. The mean maximum plasma concentration (Cmax) ranged between 2,563 and 2,932 mg/liter for 180-mg doses of the 50- and 100-mg/ml formulations, respectively. After 7 days of dosing, the mean Cmax for the 240-mg dose was 4,691 mg/liter. The mean serum levofloxacin Cmax ranged between 0.95 and 1.28 for the 180-mg doses and was 1.71 for the 240-mg dose. MP-376 was well tolerated. Nebulized MP-376 produces high sputum and low serum levofloxacin concentrations. The pharmacokinetics, safety, and tolerability were similar for the two formulations. MP-376 240 mg (100 mg/ml) is being advanced into late-stage clinical development. PMID:21444699

SU-E-J-08: Comparison of Unintended Radiation Doses to Organs at Risk Resulting From the Out-Of-Field Therapeutic Beams and From Image-Guidance X-Ray Procedures

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

Ding, G; Wang, L

Purpose: The unintended radiation dose to organs at risk (OAR) can be contributed from imaging guidance procedures as well as from leakage and scatter of therapeutic beams. This study compares the imaging dose with the unintended out-of-field therapeutic dose to patient sensitive organs. Methods: The Monte Carlo EGSnrc user codes, BEAMnrc and DOSXYZnrc, were used to simulate kV X-ray sources from imaging devices as well as the therapeutic IMRT/VMAT beams and to calculate doses to target and OARs on patient treatment planning CT images. The accuracy of the Monte Carlo simulations was benchmarked against measurements in phantoms. The dose-volume histogrammore » was utilized in analyzing the patient organ doses. Results: The dose resulting from Standard Head kV-CBCT scans to bone and soft tissues ranges from 0.7 to 1.1 cGy and from 0.03 to 0.3 cGy, respectively. The dose resulting from Thorax scans on the chest to bone and soft tissues ranges from 1.1 to 1.8 cGy and from 0.3 to 0.6 cGy, respectively. The dose resulting from Pelvis scans on the abdomen to bone and soft tissues range from 3.2 to 4.2 cGy and from 1.2 to 2.2 cGy, respectively. The out-of-field doses to OAR are sensitive to the distance between the treated target and the OAR. For a typical Head-and-Neck IMRT/VMAT treatment the out-of-field doses to eyes are 1–3% of the target dose, or 2–6 cGy per fraction. Conclusion: The imaging doses to OAR are predictable based on the imaging protocols used when OARs are within the imaged volume and can be estimated and accounted for by using tabulated values. The unintended out-of-field doses are proportional to the target dose, strongly depend on the distance between the treated target and OAR, and are generally higher comparing to the imaging dose. This work was partially supported by Varian research grant VUMC40590.« less

SU-G-IeP3-13: Real-Time Patient and Staff Dose Monitoring in Fluoroscopy Guided Interventions

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

Vergoossen, L; Sailer, A; Paulis, L

Purpose: Interventional radiology procedures involve the use of X-rays, which can pose a large radiation burden on both patients and staff. Although some reports on radiation dose are available, most studies focus on limited types of procedures and only report patient dose. In our cathlabs a dedicated real-time patient and staff monitoring system was installed in November 2015. The aim of this study was to investigate the patient and staff dose exposure for different types of interventions. Methods: Radiologists involved in fluoroscopy guided interventional radiology procedures wore personal dose meters (PDM, DoseAware, Philips) on their lead-apron that measured the personalmore » dose equivalent Hp(10), a measure for the effective dose (E). Furthermore, reference PDMs were installed in the C-arms of the fluoroscopy system (Allura XPer, Philips). Patient dose-area-product (DAP) and PDM doses were retrieved from the monitoring system (DoseWise, Philips) for each procedure. A total of 399 procedures performed between November 2015 and February 2016 were analyzed with respect to the type of intervention. Interventions were grouped by anatomy and radiologist position. Results: The mean DAP for the different types of interventions ranged from 2.86±2.96 Gycm{sup 2} (percutaneous gastrostomy) to 147±178 Gycm{sup 2} (aortic repair procedures). The radiologist dose (E) ranged from 5.39±7.38 µSv (cerebral interventions) to 84.7±106 µSv (abdominal interventions) and strongly correlated with DAP (R{sup 2}=0.83). The E normalized to DAP showed that the relative radiologist dose was higher for interventions in larger body parts (e.g. abdomen) compared to smaller body parts (e.g. head). Conclusion: Using a real-time dose monitoring system we were able to assess the staff and patient dose revealing that the relative staff dose strongly depended on the type of procedure and patient anatomy. This could be explained by the position of the radiologist with respect to the patient and X-ray tube. To facilitate this study L Vergoossen received a scholarship from Philips Medical Systems.« less

Radiotherapy dose verification on a customised head and neck perspex phantom

NASA Astrophysics Data System (ADS)

Eng, K. Y.; Kandaiya, S.; Yahaya, N. Z.

2017-05-01

IMRT dose planned for head and neck radiotherapy was verified using a customised acrylic head-and-neck phantom. The dosimeters used were calibrated Gafchromic EBT2 film and metal-oxide-semiconductor-field-effect-transistor (MOSFET). Target volumes (TV) and organs-at-risk (OAR) which were previously contoured by an oncologist on selected nasopharynx (NPC) patients were transferred to this phantom by an image fusion procedure. Three radiotherapy plans were done: Plan1 with 7-fields intensity-modulated radiotherapy (IMRT) of prescribed dose 70 Gy using 33 fractions; Plan2 with 7-fields IMRT plan at 70 Gy and 35 fractions; and Plan3 which was a mid-plane-dose (MPD) plan of 66 Gy at 33 fractions. The dose maps were first verified using MapCheck2 by SNC-PatientTM software. The passing rates from gamma analysis were 97.7% (Plan1), 93.1% (Plan2) and 100% (Plan3). Percentage difference between Treatment Planning System (TPS) calculated dose and MOSFET measured dose was comparatively higher than those from EBT2. Calculated dose and EBT2 measured doses showed differences of within the range of ±3% for TV and <±10% for OARs. However MOSFET had differences of within the range of ±6% for TV and within the range of ±10% for OARs between measured and planned doses. An overdose treatment may occur as TPS calculated doses were lower than the measured doses in these plans. This may be due to the effects of leaf leakage, leaf scatter and photon backscatter into the measuring tools (Pawlicki et al., 1999 and Ma et al., 2000). More IMRT plans have to be studied to validate this conclusion. However, the dose measurements were still within the 10% tolerance (AAPM Task Group 119). In conclusion, both GafchromicEBT2 film and MOSFET are suitable for IMRT radiotherapy dosimetry.

Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms.

PubMed

Koivisto, Juha H; Wolff, Jan E; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-07-08

The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50-90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point-dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k = 2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low-dose limit. The sensitivity was 3.09 ± 0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was -8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD-comparable low-dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low.

Calculation of organ doses from breast cancer radiotherapy: a Monte Carlo study

PubMed Central

Berris, T.; Mazonakis, M.; Stratakis, J.; Tzedakis, A.; Fasoulaki, A.

2013-01-01

The current study aimed to: a) utilize Monte Carlo simulation methods for the assessment of radiation doses imparted to all organs at risk to develop secondary radiation induced cancer, for patients undergoing radiotherapy for breast cancer; and b) evaluate the effect of breast size on dose to organs outside the irradiation field. A simulated linear accelerator model was generated. The in‐field accuracy of the simulated photon beam properties was verified against percentage depth dose (PDD) and dose profile measurements on an actual water phantom. Off‐axis dose calculations were verified with thermoluminescent dosimetry (TLD) measurements on a humanoid physical phantom. An anthropomorphic mathematical phantom was used to simulate breast cancer radiotherapy with medial and lateral fields. The effect of breast size on the calculated organ dose was investigated. Local differences between measured and calculated PDDs and dose profiles did not exceed 2% for the points at depths beyond the depth of maximum dose and the plateau region of the profile, respectively. For the penumbral regions of the dose profiles, the distance to agreement (DTA) did not exceed 2 mm. The mean difference between calculated out‐of‐field doses and TLD measurements was 11.4%±5.9%. The calculated doses to peripheral organs ranged from 2.32 cGy up to 161.41 cGy depending on breast size and thus the field dimensions applied, as well as the proximity of the organs to the primary beam. An increase to the therapeutic field area by 50% to account for the large breast led to a mean organ dose elevation by up to 85.2% for lateral exposure. The contralateral breast dose ranged between 1.4% and 1.6% of the prescribed dose to the tumor. Breast size affects dose deposition substantially. PACS numbers: 87.10.rt, 87.56.bd, 87.53.Bn, 87.55.K‐, 87.55.ne, 87.56.jf, 87.56.J‐ PMID:23318389

Total target volume is a better predictor of whole brain dose from gamma stereotactic radiosurgery than the number, shape, or location of the lesions

PubMed Central

Narayanasamy, Ganesh; Smith, Adam; Van Meter, Emily; McGarry, Ronald; Molloy, Janelle A.

2013-01-01

Purpose: To assess the hypothesis that the volume of whole brain that receives a certain dose level is primarily dependent on the treated volume rather than on the number, shape, or location of the lesions. This would help a physician validate the suitability of GammaKnife® based stereotactic radiosurgery (GKSR) prior to treatment. Methods: Simulation studies were performed to establish the hypothesis for both oblong and spherical shaped lesions of various numbers and sizes. Forty patients who underwent GKSR [mean age of 54 years (range 7–80), mean number of lesions of 2.5 (range 1–6), and mean lesion volume of 4.4 cm3 (range 0.02–22.2 cm3)] were also studied retrospectively. Following recommendations of QUANTEC, the volume of brain irradiated by the 12 Gy (VB12) isodose line was measured and a power-law based relation is proposed here for estimating VB12 from the known tumor volume and the prescription dose. Results: In the simulation study on oblong, spherical, and multiple lesions, the volume of brain irradiated by 50%, 10%, and 1% of maximum dose was found to have linear, linear, and exponentially increasing dependence on the volume of the treated region, respectively. In the retrospective study on 40 GKSR patients, a similar relationship was found to predict the brain dose with a Spearman correlation coefficient >0.9. In both the studies, the volume of brain irradiated by a certain dose level does not have a statistically significant relationship (p ≥ 0.05) with the number, shape, or position of the lesions. The measured VB12 agrees with calculation to within 1.7%. Conclusions: The results from the simulation and the retrospective clinical studies indicate that the volume of whole brain that receives a certain percentage of the maximum dose is primarily dependent on the treated volume and less on the number, shape, and location of the lesions. PMID:24007147

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

Lucconi, G; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Bentefour, E

Purpose: The clinical commissioning of a workflow for pre-treatment range verification/adjustment for the head treatment of pediatric medulloblastoma patients, including dose monitoring during treatment. Methods: An array of Si-diodes (DIODES Incorporated) is placed on the patient skin on the opposite side to the beam entrance. A “scout” SOBP beam, with a longer beam range to cover the diodes in its plateau, is delivered; the measured signal is analyzed and the extracted water equivalent path lengths (WEPL) are compared to the expected values, revealing if a range correction is needed. Diodes stay in place during treatment to measure dose. The workflowmore » was tested in solid water and head phantoms and validated against independent WEPL measurements. Both measured WEPL and skin doses were compared to computed values from the TPS (XiO); a Markus chamber was used for reference dose measurements. Results: The WEPL accuracy of the method was verified by comparing it with the dose extinction method. It resulted, for both solid water and head phantom, in the sub-millimeter range, with a deviation less than 1% to the value extracted from the TPS. The accuracy of dose measurements in the fall-off part of the dose profile was validated against the Markus chamber. The entire range verification workflow was successfully tested for the mock-treatment of head phantom with the standard delivery of 90 cGy per field per fraction. The WEPL measurement revealed no need for range correction. The dose measurements agreed to better than 4% with the prescription dose. The robustness of the method and workflow, including detector array, hardware set and software functions, was successfully stress-tested with multiple repetitions. Conclusion: The performance of the in-vivo range verification system and related workflow meet the clinical requirements in terms of the needed WEPL accuracy for pretreatment range verification with acceptable dose to the patient.« less

Phase I study of 6-diazo-5-oxo-L-norleucine (DON).

PubMed

Sklaroff, R B; Casper, E S; Magill, G B; Young, C W

1980-01-01

We conducted a phase I study of 6-diazo-5-oxo-L-norleucine given iv on a twice weekly schedule. Twenty-six evaluable patients received 31 courses of the drug. Doses ranged from 100 to 500 mg/m2. Nausea with vomiting was the dose-limiting toxic effect, transient thrombocytopenia was seen frequently, and mucositis occurred in 39% of the patients. No definite therapeutic responses were observed in 18 patients with measurable lesions. The recommended dose for phase II studies is 200-300 mg/m2 iv twice weekly.

Oral and Inactivated Poliovirus Vaccines in the Newborn: A review

PubMed Central

Mateen, Farrah J.; Shinohara, Russell T.; Sutter, Roland W.

2015-01-01

Background Oral poliovirus vaccine (OPV) remains the vaccine-of-choice for routine immunization and supplemental immunization activities (SIAs) to eradicate poliomyelitis globally. Recent data from India suggested lowerthanexpected immunogenicity of an OPV birth dose, prompting a review of the immunogenicity of OPV or inactivated poliovirus vaccine (IPV) when administered at birth. Methods We evaluated the seroconversion and reported adverse events among infants given a single birth dose (given ≤7 days of life) of OPV or IPV through a systematic review of published articles and conference abstracts from 1959-2011 in any language found on PubMed, Google Scholar, or reference lists of selected articles. Results 25 articles from 13 countries published between1959 and 2011 documented seroconversion rates in newborns following an OPV dose given within the first seven days of life. There were 10 studies that measured seroconversion rates between 4 and 8 weeks of a single birth dose of TOPV, using an umbilical cord blood draw at the time of birth to establish baseline antibody levels. The percentage of newborns who seroconverted at 8 weeks range 6-42% for poliovirus type 1, 2-63% for type 2, and 1-35% for type 3). For mOPV type 1, seroconversion ranged from 10-76%; mOPV type 3, the range was 12-58%; and for the one study reporting bOPV, it was 20% for type 1 and 7% for type 3. There were four studies of IPV in newborns with a seroconversion rate of 8-100% for serotype 1, 15-100% for serotype 2, and 15-94% for serotype 3, measured at 4-6 weeks of life. No serious adverse events related to newborn OPV or IPV dosing were reported, including no cases of acute flaccid paralysis. Conclusions There is great variability of the immunogenicity of a birth dose of OPV for reasons largely unknown. Our review confirms the utility of a birth dose of OPV, particularly in countries where early induction of polio immunity is imperative. IPV has higher seroconversion rates in newborns and may be a superior choice in countries which can afford IPV, but there have been studies of an IPV dose for newborns. PMID:22728224

Are Recommended Doses of Acetaminophen Effective for Children Aged 2 to 3 Years? A Pharmacokinetic Modeling Answer.

PubMed

Abourbih, Daniel Asher; Gosselin, Sophie; Villeneuve, Eric; Kazim, Sara

2016-01-01

Acetaminophen (APAP) elixir is a widely used pediatric antipyretic medication. It has been shown that up to 30% of febrile children presenting to a large urban pediatric emergency department received inadequate APAP dosages at home with errors primarily due to age-based dosing. Parental education material in the form of weight-based dosing guides has been proposed; however, validation of current recommended APAP dosages using pharmacokinetic models is needed. This study used a mathematical model of APAP absorption to predict plasma concentrations and to compare them with the range required to reach and achieve antipyresis (10-20 μg/mL). A common APAP preparation (Children's Tylenol Elixir) was tested (children aged 2-3 years, 10.9-15.9 kg). The manufacturer's suggested dose of 160 mg was compared with the standard 10 to 15 mg/kg dose range. The model predicts a peak plasma concentration between 6.38 and 8.55 μg/mL for 10 mg/kg dose and 9.57 and 12.8 μg/mL for 15 mg/kg dose. The manufacturer's suggested dose of 160 mg was tested across the limits of the weight range (10.9-15.9 kg). A peak plasma concentration between 9.36 and 12.6 μg/mL was found for the lower weight limit (10.9 kg child) and 6.42 to 8.61 μg/mL for the upper weight limit (15.9 kg child). With the use of this model, the 10 mg/kg dose does not reach the plasma concentration value for antipyresis (10-20 μg/mL), whereas 15 mg/kg is adequate only if assuming a greater absorption constant. The 160 mg dose is effective only for children weighing 10.9 kg. Individual differences in drug bioavailability, volume of distribution, and absorption/elimination constants undoubtedly exist, and future studies directly measuring plasma APAP concentration and pharmacokinetics are needed. However, these results indicate that dosages for APAP in children should be weight based and manufacturers should review their dosing recommendations.

A multicenter study of plasma use in the United States.

PubMed

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

2015-06-01

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

Accuracy and Radiation Dose Reduction of Limited-Range CT in the Evaluation of Acute Appendicitis in Pediatric Patients.

PubMed

Jin, Michael; Sanchez, Thomas R; Lamba, Ramit; Fananapazir, Ghaneh; Corwin, Michael T

2017-09-01

The purpose of this article is to determine the accuracy and radiation dose reduction of limited-range CT prescribed from the top of L2 to the top of the pubic symphysis in children with suspected acute appendicitis. We performed a retrospective study of 210 consecutive pediatric patients from December 11, 2012, through December 11, 2014, who underwent abdominopelvic CT for suspected acute appendicitis. Two radiologists independently reviewed the theoretic limited scans from the superior L2 vertebral body to the top of the pubic symphysis, to assess for visualization of the appendix, acute appendicitis, alternative diagnoses, and incidental findings. Separately, the same parameters were assessed on the full scan by the same two reviewers. Whole-body effective doses were determined for the full- and limited-range scans and were compared using the paired t test. The appendix or entire cecum was visualized on the limited scan in all cases, and no cases of acute appendicitis were missed on the simulated limited scan compared with the full scan. Two alternative diagnoses were missed with the limited scan: one case of hydronephrosis and one of acute acalculous cholecystitis. The mean effective dose for the original scan was 5.6 mSv and that for the simulated limited scan was 3.0 mSv, resulting in a dose reduction of 46.4% (p < 0.001). A limited-range CT examination performed from the top of L2 to the top of the pubic symphysis is as accurate as a full-range abdominopelvic CT in evaluating pediatric patients with suspected appendicitis and reduces the dose by approximately 46%.

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

PubMed

El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

Determination of output factors for small proton therapy fields.

PubMed

Fontenot, Jonas D; Newhauser, Wayne D; Bloch, Charles; White, R Allen; Titt, Uwe; Starkschall, George

2007-02-01

Current protocols for the measurement of proton dose focus on measurements under reference conditions; methods for measuring dose under patient-specific conditions have not been standardized. In particular, it is unclear whether dose in patient-specific fields can be determined more reliably with or without the presence of the patient-specific range compensator. The aim of this study was to quantitatively assess the reliability of two methods for measuring dose per monitor unit (DIMU) values for small-field treatment portals: one with the range compensator and one without the range compensator. A Monte Carlo model of the Proton Therapy Center-Houston double-scattering nozzle was created, and estimates of D/MU values were obtained from 14 simulated treatments of a simple geometric patient model. Field-specific D/MU calibration measurements were simulated with a dosimeter in a water phantom with and without the range compensator. D/MU values from the simulated calibration measurements were compared with D/MU values from the corresponding treatment simulation in the patient model. To evaluate the reliability of the calibration measurements, six metrics and four figures of merit were defined to characterize accuracy, uncertainty, the standard deviations of accuracy and uncertainty, worst agreement, and maximum uncertainty. Measuring D/MU without the range compensator provided superior results for five of the six metrics and for all four figures of merit. The two techniques yielded different results primarily because of high-dose gradient regions introduced into the water phantom when the range compensator was present. Estimated uncertainties (approximately 1 mm) in the position of the dosimeter in these regions resulted in large uncertainties and high variability in D/MU values. When the range compensator was absent, these gradients were minimized and D/MU values were less sensitive to dosimeter positioning errors. We conclude that measuring D/MU without the range compensator present provides more reliable results than measuring it with the range compensator in place.

Radiation exposure assessment for portsmouth naval shipyard health studies.

PubMed

Daniels, R D; Taulbee, T D; Chen, P

2004-01-01

Occupational radiation exposures of 13,475 civilian nuclear shipyard workers were investigated as part of a retrospective mortality study. Estimates of annual, cumulative and collective doses were tabulated for future dose-response analysis. Record sets were assembled and amended through range checks, examination of distributions and inspection. Methods were developed to adjust for administrative overestimates and dose from previous employment. Uncertainties from doses below the recording threshold were estimated. Low-dose protracted radiation exposures from submarine overhaul and repair predominated. Cumulative doses are best approximated by a hybrid log-normal distribution with arithmetic mean and median values of 20.59 and 3.24 mSv, respectively. The distribution is highly skewed with more than half the workers having cumulative doses <10 mSv and >95% having doses <100 mSv. The maximum cumulative dose is estimated at 649.39 mSv from 15 person-years of exposure. The collective dose was 277.42 person-Sv with 96.8% attributed to employment at Portsmouth Naval Shipyard.

MCNPX simulation of proton dose distribution in homogeneous and CT phantoms

NASA Astrophysics Data System (ADS)

Lee, C. C.; Lee, Y. J.; Tung, C. J.; Cheng, H. W.; Chao, T. C.

2014-02-01

A dose simulation system was constructed based on the MCNPX Monte Carlo package to simulate proton dose distribution in homogeneous and CT phantoms. Conversion from Hounsfield unit of a patient CT image set to material information necessary for Monte Carlo simulation is based on Schneider's approach. In order to validate this simulation system, inter-comparison of depth dose distributions among those obtained from the MCNPX, GEANT4 and FLUKA codes for a 160 MeV monoenergetic proton beam incident normally on the surface of a homogeneous water phantom was performed. For dose validation within the CT phantom, direct comparison with measurement is infeasible. Instead, this study took the approach to indirectly compare the 50% ranges (R50%) along the central axis by our system to the NIST CSDA ranges for beams with 160 and 115 MeV energies. Comparison result within the homogeneous phantom shows good agreement. Differences of simulated R50% among the three codes are less than 1 mm. For results within the CT phantom, the MCNPX simulated water equivalent Req,50% are compatible with the CSDA water equivalent ranges from the NIST database with differences of 0.7 and 4.1 mm for 160 and 115 MeV beams, respectively.

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose

PubMed Central

Andrews, Louise M.; de Winter, Brenda C.M.; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H.N.; Koch, Birgit C.P.; van Gelder, Teun; Hesselink, Dennis A.

2017-01-01

Background Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. Methods For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Results Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. Conclusions This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients. PMID:28361113

An algorithm for treatment of patients with hypersensitivity reactions after vaccines.

PubMed

Wood, Robert A; Berger, Melvin; Dreskin, Stephen C; Setse, Rosanna; Engler, Renata J M; Dekker, Cornelia L; Halsey, Neal A

2008-09-01

Concerns about possible allergic reactions to immunizations are raised frequently by both patients/parents and primary care providers. Estimates of true allergic, or immediate hypersensitivity, reactions to routine vaccines range from 1 per 50000 doses for diphtheria-tetanus-pertussis to approximately 1 per 500000 to 1000000 doses for most other vaccines. In a large study from New Zealand, data were collected during a 5-year period on 15 marketed vaccines and revealed an estimated rate of 1 immediate hypersensitivity reaction per 450000 doses of vaccine administered. Another large study, conducted within the Vaccine Safety Datalink, described a range of reaction rates to >7.5 million doses. Depending on the study design and the time after the immunization event, reaction rates varied from 0.65 cases per million doses to 1.53 cases per million doses when additional allergy codes were included. For some vaccines, particularly when allergens such as gelatin are part of the formulation (eg, Japanese encephalitis), higher rates of serious allergic reactions may occur. Although these per-dose estimates suggest that true hypersensitivity reactions are quite rare, the large number of doses that are administered, especially for the commonly used vaccines, makes this a relatively common clinical problem. In this review, we present background information on vaccine hypersensitivity, followed by a detailed algorithm that provides a rational and organized approach for the evaluation and treatment of patients with suspected hypersensitivity. We then include 3 cases of suspected allergic reactions to vaccines that have been referred to the Clinical Immunization Safety Assessment network to demonstrate the practical application of the algorithm.

Effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation: phantom study.

PubMed

Schindera, Sebastian T; Nelson, Rendon C; Toth, Thomas L; Nguyen, Giao T; Toncheva, Greta I; DeLong, David M; Yoshizumi, Terry T

2008-02-01

The purpose of this study was to evaluate in a phantom study the effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation. One or two 4-cm-thick circumferential layers of fat-equivalent material were added to the abdomen of an anthropomorphic phantom to simulate patients of three sizes: small (cross-sectional dimensions, 18 x 22 cm), average size (26 x 30 cm), and oversize (34 x 38 cm). Imaging was performed with a 64-MDCT scanner with combined z-axis and xy-axis tube current modulation according to two protocols: protocol A had a noise index of 12.5 H, and protocol B, 15.0 H. Radiation doses to three abdominal organs and the skin were assessed. Image noise also was measured. Despite increasing patient size, the image noise measured was similar for protocol A (range, 11.7-12.2 H) and protocol B (range, 13.9-14.8 H) (p > 0.05). With the two protocols, in comparison with the dose of the small patient, the abdominal organ doses of the average-sized patient and the oversized patient increased 161.5-190.6%and 426.9-528.1%, respectively (p < 0.001). The skin dose increased as much as 268.6% for the average-sized patient and 816.3% for the oversized patient compared with the small patient (p < 0.001). Oversized patients undergoing abdominal MDCT with tube current modulation receive significantly higher doses than do small patients. The noise index needs to be adjusted to the body habitus to ensure dose efficiency.

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

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

Clinical results of proton beam therapy for twenty older patients with esophageal cancer

PubMed Central

Ono, Takashi; Nakamura, Tatsuya; Azami, Yusuke; Yamaguchi, Hisashi; Hayashi, Yuichiro; Suzuki, Motohisa; Hatayama, Yoshiomi; Tsukiyama, Iwao; Hareyama, Masato; Kikuchi, Yasuhiro; Nemoto, Kenji

2015-01-01

Background In an aging society, increasing number of older patients are diagnosed with esophageal cancer. The purpose of this study was to assess the clinical efficacy and safety of proton beam therapy for older patients with esophageal cancer. Patients and methods. Older patients (age: ≥ 65 years) newly diagnosed with esophageal cancer between January 2009 and June 2013 were enrolled in this study. All patients underwent either proton beam therapy alone or proton beam therapy with initial X-ray irradiation. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results Twenty patients were eligible for this study and all completed the treatment. The median age was 78 years (range: 65–89 years) and the median follow-up time was 26.5 months (range: 6–62 months). Seven patients had lymph node metastases and 10 had stage II/III cancer. The median dose of proton beam therapy was 72.6 Gy relative biological dose effectiveness (RBE) (range: 66–74.8 Gy [RBE]) for proton beam therapy alone and 33 Gy (RBE) (range: 30.8–39.6 Gy [RBE]; total dose range: 66.8–75.6 Gy [RBE]) for proton beam therapy with initial X-ray irradiation. The 2-year overall survival rate was 81.8% (95% confidence interval [CI]: 62.4%–100%), and the 2-year local control rate was 89.4% (95% CI: 75.5%–100%). Grade 2 or 3 toxicities occurred in some cases; however, no grade 4 or 5 toxicity was observed. Conclusions High-dose (66–75.6 Gy [RBE]) proton beam therapy without chemotherapy was an efficacious and safe treatment for older patients with esophageal cancer. PMID:26834524

Safety of multiple stereotactic radiosurgery treatments for multiple brain lesions.

PubMed

Hillard, Virany H; Shih, Lynn L; Chin, Shing; Moorthy, Chitti R; Benzil, Deborah L

2003-07-01

Stereotactic radiosurgery (SRS) is a widely used therapy for multiple brain lesions, and studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined. We have retrospectively studied 10 patients who received multiple SRS treatments for multiple brain lesions to assess the cumulative toxicity of these treatments. In a retrospective review of all patients treated with SRS using the X-knife (Radionics, Burlington, MA) at Westchester Medical Center/New York Medical College between December 1995 and December 2000, 10 patients were identified who received at least two treatments to at least 3 isocenters and had a minimum follow-up period of 6 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain and critical brain structures. Toxicities and complications were identified by chart and radiological review. The average of the maximum doses (cGy) to a point within the whole brain was 2402 (range 1617-3953); to the brainstem, 1059 (range 48-4126); to the right optic nerve, 223 (range 14-1012); to the left optic nerve, 159 (range 17-475); and to the optic chiasm, 219 (range 15-909). There were no focal neurological toxicities, including visual disturbances, cranial nerve palsies, or ataxia in any of the 10 patients. There were also no global toxicities, including cognitive decline or secondary tumors. Only one patient developed seizures that were difficult to control in association with radiation necrosis. Multiple SRS treatments at the cumulative doses used in our study are a safe therapy for patients with multiple brain lesions.

Biases in Multicenter Longitudinal PET Standardized Uptake Value Measurements1

PubMed Central

Doot, Robert K; Pierce, Larry A; Byrd, Darrin; Elston, Brian; Allberg, Keith C; Kinahan, Paul E

2014-01-01

This study investigates measurement biases in longitudinal positron-emission tomography/computed tomography (PET/CT) studies that are due to instrumentation variability including human error. Improved estimation of variability between patient scans is of particular importance for assessing response to therapy and multicenter trials. We used National Institute of Standards and Technology-traceable calibration methodology for solid germanium-68/gallium-68 (68Ge/68Ga) sources used as surrogates for fluorine-18 (18F) in radionuclide activity calibrators. One cross-calibration kit was constructed for both dose calibrators and PET scanners using the same 9-month half-life batch of 68Ge/68Ga in epoxy. Repeat measurements occurred in a local network of PET imaging sites to assess standardized uptake value (SUV) errors over time for six dose calibrators from two major manufacturers and for six PET/CT scanners from three major manufacturers. Bias in activity measures by dose calibrators ranged from -50% to 9% and was relatively stable over time except at one site that modified settings between measurements. Bias in activity concentration measures by PET scanners ranged from -27% to 13% with a median of 174 days between the six repeat scans (range, 29 to 226 days). Corresponding errors in SUV measurements ranged from -20% to 47%. SUV biases were not stable over time with longitudinal differences for individual scanners ranging from -11% to 59%. Bias in SUV measurements varied over time and between scanner sites. These results suggest that attention should be paid to PET scanner calibration for longitudinal studies and use of dose calibrator and scanner cross-calibration kits could be helpful for quality assurance and control. PMID:24772207

An exponential model equation for thiamin loss in irradiated ground pork as a function of dose and temperature of irradiation

NASA Astrophysics Data System (ADS)

Fox, J. B.; Thayer, D. W.; Phillips, J. G.

The effect of low dose γ-irradiation on the thiamin content of ground pork was studied in the range of 0-14 kGy at 2°C and at radiation doses from 0.5 to 7 kGy at temperatures -20, 10, 0, 10 and 20°C. The detailed study at 2°C showed that loss of thiamin was exponential down to 0kGy. An exponential expression was derived for the effect of radiation dose and temperature of irradiation on thiamin loss, and compared with a previously derived general linear expression. Both models were accurate depictions of the data, but the exponential expression showed a significant decrease in the rate of loss between 0 and -10°C. This is the range over which water in meat freezes, the decrease being due to the immobolization of reactive radiolytic products of water in ice crystals.

Improvements in opti-chromic dosimeters for radiation processing

NASA Astrophysics Data System (ADS)

Humpherys, K. C.; Kantz, A. D.

"Opti-Chromic" dosimeters consisting of radiachromic dye in flourinated polymer tubing have been introduced as a dosimetry system in the range from 10 1 to 5 × 10 4 Gy. Batches of "Opti-Chromic" dosimeters have been produced to evaluate performance under large scale industrial conditions. A systematic study was undertaken to determine the effect of various dosimeter parameters on radiation sensitivity, shelf life, and response characteristics at the higher absorbed doses. These parameters were (A) Type of flourinated polymer tubing; (B) Organic solvent used to activate the radiachromic dye; (C) Concentration of radiachromic dye; (D) Additives to provide proper viscosity, color stability, and high-dose response. Prototype batches were produced and experimental dosimeters exposed to a range of absorbed doses and the response measured as a function of shelf life and dose. The results of the study are presented, and an improved formulation recommended for application to Food Processing. Other formulations may be of value in specific requirements of sensitivity or temperature.

The Shigella human challenge model.

PubMed

Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

2013-02-01

Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development.

PubMed

Kimmel, Gary L; Kimmel, Carole A; Williams, Amy L; DeSesso, John M

2013-02-01

The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission's 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations. In addition, the results of six unpublished developmental toxicity studies in rats were considered. Five of the seven rabbit studies (dose range: 10-500 mg/kg/day) were GLP- and testing guideline-compliant for the era in which the studies were performed; a sixth study predated testing and GLP guidelines, but generally adhered to these principles. The seventh study was judged inadequate. In each of the adequate studies, offspring effects occurred only at doses that also caused maternal toxicity. An integrated evaluation of the six adequate studies, using conservative assumptions, demonstrated that neither the overall malformation rate nor the incidence of cardiovascular malformations increased with dose up to the point where severe maternal toxicity was observed (generally ≥150 mg/kg/day). Random occurrences of cardiovascular malformations were observed across all dose groups (including controls) and did not exhibit a dose-response relationship. In the six rat studies (dose range: 30-3500 mg/kg/day), a low incidence of sporadic cardiovascular malformations was reported that was clearly not related to treatment. In summary, assessment of the entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy.

Treatment Plan Technique and Quality for Single-Isocenter Stereotactic Ablative Radiotherapy of Multiple Lung Lesions with Volumetric-Modulated Arc Therapy or Intensity-Modulated Radiosurgery

PubMed Central

Quan, Kimmen; Xu, Karen M.; Lalonde, Ron; Horne, Zachary D.; Bernard, Mark E.; McCoy, Chuck; Clump, David A.; Burton, Steven A.; Heron, Dwight E.

2015-01-01

The aim of this study is to provide a practical approach to the planning technique and evaluation of plan quality for the multi-lesion, single-isocenter stereotactic ablative radiotherapy (SABR) of the lung. Eleven patients with two or more lung lesions underwent single-isocenter volumetric-modulated arc therapy (VMAT) radiosurgery or IMRS. All plans were normalized to the target maximum dose. For each plan, all targets were treated to the same dose. Plan conformity and dose gradient were maximized with dose-control tuning structures surrounding targets. For comparison, multi-isocenter plans were retrospectively created for four patients. Conformity index (CI), homogeneity index (HI), gradient index (GI), and gradient distance (GD) were calculated for each plan. V5, V10, and V20 of the lung and organs at risk (OARs) were collected. Treatment time and total monitor units (MUs) were also recorded. One patient had four lesions and the remainder had two lesions. Six patients received VMAT and five patients received intensity-modulated radiosurgery (IMRS). For those treated with VMAT, two patients received 3-arc VMAT and four received 2-arc VMAT. For those treated with IMRS, two patients were treated with 10 and 11 beams, respectively, and the rest received 12 beams. Prescription doses ranged from 30 to 54 Gy in three to five fractions. The median prescribed isodose line was 84% (range: 80–86%). The median maximum dose was 57.1 Gy (range: 35.7–65.1 Gy). The mean combined PTV was 49.57 cm3 (range: 14.90–87.38 cm3). For single-isocenter plans, the median CI was 1.15 (range: 0.97–1.53). The median HI was 1.19 (range: 1.16–1.28). The median GI was 4.60 (range: 4.16–7.37). The median maximum radiation dose (Dmax) to total lung was 55.6 Gy (range: 35.7–62.0 Gy). The median mean radiation dose to the lung (Dmean) was 4.2 Gy (range: 1.1–9.3 Gy). The median lung V5 was 18.7% (range: 3.8–41.3%). There was no significant difference in CI, HI, GI, GD, V5, V10, and V20 (lung, heart, trachea, esophagus, and spinal cord) between single-isocenter and multi-isocenter plans. This multi-lesion, single-isocenter lung SABR planning technique demonstrated excellent plan quality and clinical efficiency and is recommended for radiosurgical treatment of two or more lung targets for well-suited patients. PMID:26500888

Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.

PubMed

Greenwald, M; Peloso, P M; Mandel, D; Soto, O; Mehta, A; Frontera, N; Boice, J A; Zhan, X J; Curtis, S P

2011-10-01

To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

Study of the absorption spectra of Fricke Xylenol Orange gel dosimeters

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

Gambarini, Grazia; Artuso, Emanuele; Liosi, Giulia Maria

2015-07-01

A systematic study of the absorption spectra of Fricke Xylenol Orange gel dosimeters has been performed, in the wavelength range from 300 nm to 700 nm. The spectrum of Xylenol Orange (without ferrous sulphate solution) has been achieved, in order to subtract its contribution from the absorption spectra of the irradiated Fricke Xylenol Orange gel dosimeters. The absorbance due to ferric ions chelated by Xylenol Orange has been studied for various irradiation doses. Two absorbance peaks are visible, mainly at low doses: the first peak increases with the dose more slowly than the second one. This effect can explain themore » apparent threshold dose that was frequently evidenced. (authors)« less

Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects

PubMed Central

Frost, Charles; Wang, Jessie; Nepal, Sunil; Schuster, Alan; Barrett, Yu Chen; Mosqueda-Garcia, Rogelio; Reeves, Richard A; LaCreta, Frank

2013-01-01

Aims To evaluate apixaban single dose safety, tolerability, pharmacokinetics and pharmacodynamics and assess the effect of food on apixaban pharmacokinetics. Methods A double-blind, placebo-controlled, single ascending-dose, first-in-human study assessed apixaban safety, pharmacokinetics and pharmacodynamics in healthy subjects randomized to oral apixaban (n = 43; 0.5–2.5 mg as solution or 5–50 mg as tablets) or placebo (n = 14) under fasted conditions. An open label, randomized, two treatment crossover study investigated apixaban pharmacokinetics/pharmacodynamics in healthy subjects (n = 21) administered apixaban 10 mg in fasted and fed states. Both studies measured apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT) or a modified PT (mPT). Results In the single ascending-dose study increases in apixaban exposure appeared dose-proportional. Median tmax occurred 1.5–3.3 h following oral administration. Mean terminal half-life ranged between 3.6 and 6.8 h following administration of solution doses ≤2.5 mg and between 11.1 and 26.8 h for tablet doses ≥5 mg. Concentration-related changes in pharmacodynamic assessments were observed. After a 50 mg dose, peak aPTT, INR and mPT increased by 1.2-, 1.6- and 2.9-fold, respectively, from baseline. In the food effect study: 90% confidence intervals of geometric mean ratios of apixaban Cmax and AUC in a fed vs. fasted state were within the predefined no effect (80–125%) range. Apixaban half-life was approximately 11.5 h. The effect of apixaban on INR, PT and aPTT was comparable following fed and fasted administration. Conclusions Single doses of apixaban were well tolerated with a predictable pharmacokinetic/pharmacodynamic profile and a half-life of approximately 12 h. Apixaban can be administered with or without food. PMID:22759198

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

SU-E-T-577: Obliquity Factor and Surface Dose in Proton Beam Therapy

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

Das, I; Andersen, A; Coutinho, L

2015-06-15

Purpose: The advantage of lower skin dose in proton beam may be diminished creating radiation related sequalae usually seen with photon and electron beams. This study evaluates the surface dose as a complex function of beam parameters but more importantly the effect of beam angle. Methods: Surface dose in proton beam depends on the beam energy, source to surface distance, the air gap between snout and surface, field size, material thickness in front of surface, atomic number of the medium, beam angle and type of nozzle (ie double scattering, (DS), uniform scanning (US) or pencil beam scanning (PBS). Obliquity factormore » (OF) is defined as ratio of surface dose in 0° to beam angle Θ. Measurements were made in water phantom at various beam angles using very small microdiamond that has shown favorable beam characteristics for high, medium and low proton energy. Depth dose measurements were performed in the central axis of the beam in each respective gantry angle. Results: It is observed that surface dose is energy dependent but more predominantly on the SOBP. It is found that as SSD increases, surface dose decreases. In general, SSD, and air gap has limited impact in clinical proton range. High energy has higher surface dose and so the beam angle. The OF rises with beam angle. Compared to OF of 1.0 at 0° beam angle, the value is 1.5, 1.6, 1,7 for small, medium and large range respectively for 60 degree angle. Conclusion: It is advised that just like range and SOBP, surface dose should be clearly understood and a method to reduce the surface dose should be employed. Obliquity factor is a critical parameter that should be accounted in proton beam therapy and a perpendicular beam should be used to reduce surface dose.« less

Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

PubMed

George, Rani; Haywood, Alison; Good, Phillip; Hennig, Stefanie; Khan, Sohil; Norris, Ross; Hardy, Janet

2017-09-01

Methadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. Patients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. Fifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6-113.0 ng/mL) and 62.0 ng/mL (28.7-116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0-203.2 ng/mL) and 44.2 (16.2-149.7 ng/mL). No relationship could be established between plasma and saliva concentrations for l- and d-methadone (r 2 = 0.35 and 0.25). The saliva-to-plasma concentration analyzed with the methadone dose showed higher saliva concentrations at lower doses. Dose-normalized saliva concentrations followed a similar pattern over time compared with plasma concentrations. No correlation was found between l-methadone plasma, d-methadone plasma, l-methadone saliva, d-methadone saliva concentrations, and pain score. Saliva concentration was not a better predictor of pain control than plasma concentration for dose optimization and monitoring studies of methadone in patients with cancer. Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Radiation dose enhancement of gold nanoparticle on different polymer gel dosimeters

NASA Astrophysics Data System (ADS)

Jabaseelan Samuel, E. James; Srinivasan, K.; Poopathi, V.

2017-05-01

In this work, we evaluated the dose enhancement produced by gold nanoparticle on ten different polymer gel dosimeters with a concentration of 7mgAu /g over a wide photon energy range of 15KeV to 20MeV and the results were compared with Soft tissue ICRU-44 produced. Our result showed that maximum DEF was observed at 40KeV, while it was almost negligible at higher energy range. Dose enhancement produced by AuNP on the gel dosimeter medium was varied compared to the reference ICRU-44 tissue, it was ± <1% for PAGAT, NIPAM, nPAG and ± <5% for PABIG, VIPAR, HEAG, BANG1, nMAG & ± <10% for MAGIC, ABAGIC gel dosimeters. Hence, we conclude that choosing the proper gel dosimeter is essential in dose enhancement study.

Direct cardiac effects of intracoronary bupivacaine, levobupivacaine and ropivacaine in the sheep

PubMed Central

Chang, Dennis H-T; Ladd, Leigh A; Copeland, Susan; Iglesias, Miguel A; Plummer, John L; Mather, Laurence E

2001-01-01

The racemic local anaesthetic agent bupivacaine is widely used clinically for its long duration of action. Levobupivacaine and ropivacaine are bupivacaine enantiopure congeners, developed to improve upon the clinical safety of bupivacaine, especially the risk of fatal arrhythmogenesis. In previous preclinical studies of the safety of these drugs with intravenous administration in conscious ewes over a wide dose range, we found that central nervous system (CNS) excito-toxicity reversed the cardiac depressant effects when doses approached the convulsant threshold and thus precluded accurate comparison of their cardiovascular system (CVS) effects. To study CVS effects over a wide range of doses with minimal CNS and other influences, brief (3 min) infusions of bupivacaine, levobupivacaine or ropivacaine were administered into the left main coronary arteries of previously instrumented conscious ewes (∼50 Kg body weight). After dose-ranging studies, the drugs were compared in a randomized, blinded, parallel group design. Equimolar doses were increased from 8 μmol (≈amp;2.5 mg) in 8 μmol increments, to either a fatal outcome or a 40 μmol (≈amp;12.5 mg) maximum. All three drugs produced tachycardia, decreased myocardial contractility and stroke volume and widening of electrocardiographic QRS complexes. Thirteen of 19 animals died of ventricular fibrillation: four of six with bupivacaine (mean±s.e.mean actual fatal dose: 21.8±6.4 μmol), five of seven with levobupivacaine (22.9±3.5 μmol), four of six with ropivacaine (22.9±5.9 μmol). No significant differences in survival or in fatal doses between these drugs were found. The findings suggest that ropivacaine, levobupivacaine and bupivacaine have similar intrinsic ability to cause direct fatal cardiac toxicity when administered by left intracoronary arterial infusion in conscious sheep and do not explain the differences between the drugs found with intravenous dosage. PMID:11159717

The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

NASA Technical Reports Server (NTRS)

Hada, M.; George, K.; Cucinotta, F. A.

2010-01-01

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to 28Si- ions with energies ranging from 90 to 600 MeV/u, or to 56Fe-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Fe beams in this study ranged from 145 to 440 keV/micron and the LET of the Si ions ranged from 48 to 158 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to -rays. The estimates of RBE(sub max) values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBE(sub max) value for Fe ions was obtained with the 600-Mev/u beam, and the highest RBE(sub max) value for Si ions was obtained with the 170 MeV/u beam. For both ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/ m for Si, and decreasing with further increase in LET. Additional studies for low doses 28Si-ions down to 0.02 Gy will be discussed.

Radon exposure assessment for underground workers: a case of Seoul Subway Police officers in Korea.

PubMed

Song, Myeong Han; Chang, Byung-Uck; Kim, Yongjae; Cho, Kun-Woo

2011-11-01

The objective of this study is the systematic and individual assessment of the annual effective dose due to inhaled radon for the Seoul Subway Police officers, Korea. The annual average radon concentrations were found to be in the range of 18.9-114 Bq·m(-3) in their workplaces. The total annual effective doses which may likely to be received on duty were assessed to be in the range of 0.41-1.64 mSv·y(-1). These were well below the recommended action level 10 mSv·y(-1) by ICRP. However, the effective doses were higher than subway station staff in Seoul, Korea.

Methamphetamine blood concentrations in human abusers: application to pharmacokinetic modeling.

PubMed

Melega, William P; Cho, Arthur K; Harvey, Dennis; Laćan, Goran

2007-04-01

Characterization of methamphetamine's (METH) dose-dependent effects on brain neurochemistry may represent a critical component for better understanding the range of resultant behavioral pathologies. Most human studies, however, have assessed only the effects of long term, high dose METH abuse (e.g., greater than 1000 mg/day) in individuals meeting DSM-IV criteria for METH dependence. Yet, for the majority of METH abusers, their patterns of METH exposure that consist of lower doses remain less well-characterized. In this study, blood samples were obtained from 105 individuals detained by police for possible criminal activity and testing positive for stimulants by EMIT assay. METH blood concentrations were subsequently quantified by GC-MS and were predominantly in the low micromolar range (0.1-11.1 microM), with median and mean values of 1.3 microM (0.19 mg/l) and 2 microM (0.3 mg/l), respectively. Pharmacokinetic calculations based on these measured values were used to estimate initial METH body burdens, the median value being 52 mg. Modeling a 52 mg dose for a 4 day-METH maintenance exposure pattern of 4 doses/day at 4 h intervals showed that blood concentrations remained between 1 and 4 microM during this period. Collectively, these data present evidence for a METH exposure pattern distinct from high dose-METH abuse and provide the rationale for assessing potential brain pathology associated with such lower dose-METH exposure.

NEUROBEHAVIORAL EVALUATIONS OF BINARY AND TERTIARY MIXTURES OF CHEMICALS: LESSIONS LEARNING.

EPA Science Inventory

The classical approach to the statistical analysis of binary chemical mixtures is to construct full dose-response curves for one compound in the presence of a range of doses of the second compound (isobolographic analyses). For interaction studies using more than two chemicals, ...

Integrated pharmacokinetics and pharmacodynamics of Ro 48-8684, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.

PubMed

van Gerven, J M; Roncari, G; Schoemaker, R C; Massarella, J; Keesmaat, P; Kooyman, H; Heizmann, P; Zell, M; Cohen, A F; Dingemanse, J

1997-11-01

This study aimed to investigate the pharmacodynamics and pharmacokinetics of ascending doses of Ro 48-8684, compared with midazolam, in healthy subjects during first administration to man. The study was double-blind and five-way crossover (three ascending doses, placebo, fixed midazolam dose), performed in two groups of five males. Ro 48-8684 was infused in doses of 0.1-0.3-1 mg in the first group, and 1-3-10 mg in the second, with different infusion rates (expressed as mg min(-1)) among doses. Midazolam was infused at 0.1 mg(-1) kg. Infusions were stopped after 20 min or if sedation became too strong for proper performance of saccadic eye movements. Pharmacokinetics and pharmacodynamics and their relationships were evaluated as described in the companion article. Ro 48-8684 caused dose-dependent sedation. No serious adverse events occurred. The volume of distribution and clearance of Ro 48-8684 were larger than of midazolam (337+/-114 vs 50+/-121 and 2.4+/-0.5 vs 0.47+/-0.11 l min(-1), resp). The recovery of saccadic eye movements from equal levels of sedation was on average almost half an hour faster for Ro 48-8684 than for midazolam, with considerable interindividual differences (range 2, 55 min). The doses of Ro 48-8684 leading to the same clinical endpoint as midazolam were comparable, but the corresponding predicted effect compartment concentrations of Ro 48-8684 were on average 2.6 times lower (range 1.5, 4.9 times). The slope of the linear concentration-effect-relationship for saccadic peak velocity was on average 2.2 times steeper for 10 mg Ro 48-8684 than for midazolam (range 1.3, 3.3). The slope decreased on average 4.4-fold (range 1.6, 7.3 times), with doses of Ro 48-8684 increasing from 1 to 10 mg. The metabolite Ro 61-2466 had a longer half-life than the parent compound Ro 48-8684. The influence of this metabolite during prolonged administration should be further investigated. These results show that Ro 48-8684 has a considerably shorter duration of action than midazolam. There may be a reduction of sensitivity to Ro 48-8684 with repeated administration of rising doses due to as yet undetermined factors.

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

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

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

Estimating peak skin and eye lens dose from neuroperfusion examinations: use of Monte Carlo based simulations and comparisons to CTDIvol, AAPM Report No. 111, and ImPACT dosimetry tool values.

PubMed

Zhang, Di; Cagnon, Chris H; Villablanca, J Pablo; McCollough, Cynthia H; Cody, Dianna D; Zankl, Maria; Demarco, John J; McNitt-Gray, Michael F

2013-09-01

CT neuroperfusion examinations are capable of delivering high radiation dose to the skin or lens of the eyes of a patient and can possibly cause deterministic radiation injury. The purpose of this study is to: (a) estimate peak skin dose and eye lens dose from CT neuroperfusion examinations based on several voxelized adult patient models of different head size and (b) investigate how well those doses can be approximated by some commonly used CT dose metrics or tools, such as CTDIvol, American Association of Physicists in Medicine (AAPM) Report No. 111 style peak dose measurements, and the ImPACT organ dose calculator spreadsheet. Monte Carlo simulation methods were used to estimate peak skin and eye lens dose on voxelized patient models, including GSF's Irene, Frank, Donna, and Golem, on four scanners from the major manufacturers at the widest collimation under all available tube potentials. Doses were reported on a per 100 mAs basis. CTDIvol measurements for a 16 cm CTDI phantom, AAPM Report No. 111 style peak dose measurements, and ImPACT calculations were performed for available scanners at all tube potentials. These were then compared with results from Monte Carlo simulations. The dose variations across the different voxelized patient models were small. Dependent on the tube potential and scanner and patient model, CTDIvol values overestimated peak skin dose by 26%-65%, and overestimated eye lens dose by 33%-106%, when compared to Monte Carlo simulations. AAPM Report No. 111 style measurements were much closer to peak skin estimates ranging from a 14% underestimate to a 33% overestimate, and with eye lens dose estimates ranging from a 9% underestimate to a 66% overestimate. The ImPACT spreadsheet overestimated eye lens dose by 2%-82% relative to voxelized model simulations. CTDIvol consistently overestimates dose to eye lens and skin. The ImPACT tool also overestimated dose to eye lenses. As such they are still useful as a conservative predictor of dose for CT neuroperfusion studies. AAPM Report No. 111 style measurements are a better predictor of both peak skin and eye lens dose than CTDIvol and ImPACT for the patient models used in this study. It should be remembered that both the AAPM Report No. 111 peak dose metric and CTDIvol dose metric are dose indices and were not intended to represent actual organ doses.

Estimating peak skin and eye lens dose from neuroperfusion examinations: Use of Monte Carlo based simulations and comparisons to CTDIvol, AAPM Report No. 111, and ImPACT dosimetry tool values

PubMed Central

Zhang, Di; Cagnon, Chris H.; Villablanca, J. Pablo; McCollough, Cynthia H.; Cody, Dianna D.; Zankl, Maria; Demarco, John J.; McNitt-Gray, Michael F.

2013-01-01

Purpose: CT neuroperfusion examinations are capable of delivering high radiation dose to the skin or lens of the eyes of a patient and can possibly cause deterministic radiation injury. The purpose of this study is to: (a) estimate peak skin dose and eye lens dose from CT neuroperfusion examinations based on several voxelized adult patient models of different head size and (b) investigate how well those doses can be approximated by some commonly used CT dose metrics or tools, such as CTDIvol, American Association of Physicists in Medicine (AAPM) Report No. 111 style peak dose measurements, and the ImPACT organ dose calculator spreadsheet. Methods: Monte Carlo simulation methods were used to estimate peak skin and eye lens dose on voxelized patient models, including GSF's Irene, Frank, Donna, and Golem, on four scanners from the major manufacturers at the widest collimation under all available tube potentials. Doses were reported on a per 100 mAs basis. CTDIvol measurements for a 16 cm CTDI phantom, AAPM Report No. 111 style peak dose measurements, and ImPACT calculations were performed for available scanners at all tube potentials. These were then compared with results from Monte Carlo simulations. Results: The dose variations across the different voxelized patient models were small. Dependent on the tube potential and scanner and patient model, CTDIvol values overestimated peak skin dose by 26%–65%, and overestimated eye lens dose by 33%–106%, when compared to Monte Carlo simulations. AAPM Report No. 111 style measurements were much closer to peak skin estimates ranging from a 14% underestimate to a 33% overestimate, and with eye lens dose estimates ranging from a 9% underestimate to a 66% overestimate. The ImPACT spreadsheet overestimated eye lens dose by 2%–82% relative to voxelized model simulations. Conclusions: CTDIvol consistently overestimates dose to eye lens and skin. The ImPACT tool also overestimated dose to eye lenses. As such they are still useful as a conservative predictor of dose for CT neuroperfusion studies. AAPM Report No. 111 style measurements are a better predictor of both peak skin and eye lens dose than CTDIvol and ImPACT for the patient models used in this study. It should be remembered that both the AAPM Report No. 111 peak dose metric and CTDIvol dose metric are dose indices and were not intended to represent actual organ doses. PMID:24007152

Pharmacokinetics and clinical application of intravenous valproate in Thai epileptic children.

PubMed

Visudtibhan, Anannit; Bhudhisawadi, Kasama; Vaewpanich, Jarin; Chulavatnatol, Suvatna; Kaojareon, Sming

2011-03-01

Roles of intravenous administration of valproate in status epilepticus and serial seizures are documented in adults and children. Pharmacokinetic parameters are necessary to predict the optimum therapeutic level after administration. A cross-sectional study to determine the pharmacokinetic parameters and safety of intravenous valproate for future application was conducted in Thai children from January to December 2008. There were eleven children, age-range 1-15 years (mean age 9.5 years) enrolled. Valproate of 15-20 mg/kg was administrated intravenously at the rate of 3 mg/kg/min, followed by 6 mg/kg every 6 h. Valproate level was determined prior to the initial dose and at ½, 1, 2, 4, 5, and 6 h postdose. Complete blood count, serum ammonia, and liver function tests were collected prior to the initial dose and at 6 h. Median loading dose was 19 mg/kg (range 15-20.5 mg/kg). Median maximum concentration at 30 min after infusion was 98.8 mcg/mL (range 67-161 mcg/mL). Median volume of distribution was 0.20 L/kg (range 0.15-0.53 L/kg). Median half-life was 9.5 h (range 4.4-24.2 h). Median clearance was 0.02 L/h/kg (range 0.01-0.05 L/h/kg). Six hours after initial dose, eight children did not have recurrent seizure. One child had brief seizure at 20 min after initial dose. Seizure recurred in two children at 4th and 5th hour. Asymptomatic transient elevation of serum ammonia was observed in two children. Volume of distribution of 0.20 L/kg could be applied for initial intravenous administration with a favorable efficacy. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico

PubMed Central

Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

2015-01-01

Determining ionizing radiation in a geographic area serves to assess its effects on a population’s health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h−1. At the same sites, 48 soil samples were taken to obtain the activity concentrations of 226Ra, 232Th and 40K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h−1. Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg−1, for 226Ra, 232Th and 40K, respectively. From the analysis, the spatial distribution of 232Th, 226Ra and 40K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize. PMID:26437425

Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

PubMed

Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Éric; Dublineau, Isabelle; Aigueperse, Jocelyne; Bohand, Sandra; Martin, Jean-Charles; Souidi, Maâmar

2016-01-01

Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L -1 ; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose-effect pattern and identify additional potential biomarkers in urine samples. Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L -1 ). LC-MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L -1 . Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L -1 .

Characterization of a MOSkin detector for in vivo skin dose measurements during interventional radiology procedures

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

Safari, M. J.; Wong, J. H. D.; Ng, K. H., E-mail: ngkh@um.edu.my

2015-05-15

Purpose: The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures. Methods: The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualitiesmore » were carried out using RQR standard radiation qualities in free-in-air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth-dose, and source-to-surface distance (SSD), were carried out using a solid water phantom under a clinical x-ray unit. Results: The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (±1%), field size (±1%), frame rate (±3%), or beam energy (±5%). The detector angular dependence was within ±5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ±3%. Conclusions: The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x-ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.« less

Characterization of a MOSkin detector for in vivo skin dose measurements during interventional radiology procedures.

PubMed

Safari, M J; Wong, J H D; Ng, K H; Jong, W L; Cutajar, D L; Rosenfeld, A B

2015-05-01

The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures. The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualities were carried out using RQR standard radiation qualities in free-in-air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth-dose, and source-to-surface distance (SSD), were carried out using a solid water phantom under a clinical x-ray unit. The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (± 1%), field size (± 1%), frame rate (± 3%), or beam energy (± 5%). The detector angular dependence was within ± 5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ± 3%. The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x-ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.

Dose Reduction Study in Vaginal Balloon Packing Filled With Contrast for HDR Brachytherapy Treatment;HDR; Uterine cervix cancer; Vaginal balloon packing; Contrast; Monte Carlo

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

Saini, Amarjit S.; Zhang, Geoffrey G., E-mail: geoffrey.zhang@moffitt.org; Finkelstein, Steven E.

2011-07-15

Purpose: Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. Methods and Materials: In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken withmore » each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. Results: Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 {+-} 0.002 for contrast/saline solution and 0.808 {+-} 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 {+-} 0.010 and 0.781 {+-} 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. Conclusions: The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.« less

Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico.

PubMed

Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

2015-09-30

Determining ionizing radiation in a geographic area serves to assess its effects on a population's health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h(-1). At the same sites, 48 soil samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and (40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h(-1). Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg(-1), for (226)Ra, (232)Th and (40)K, respectively. From the analysis, the spatial distribution of (232)Th, (226)Ra and (40)K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

PubMed

Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

2018-06-01

To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

The Role of Radiotherapy in Extramammary Paget Disease: A Systematic Review.

PubMed

Tagliaferri, L; Casà, C; Macchia, G; Pesce, A; Garganese, G; Gui, B; Perotti, G; Gentileschi, S; Inzani, F; Autorino, R; Cammelli, S; Morganti, A G; Valentini, V; Gambacorta, M A

2018-05-01

Extramammary Paget disease (EMPD) is a rare neoplasm of the skin generally affecting the anogenital area. Because of the low-frequency of the disease, no specific guidelines about the treatment strategy are available. Surgery is the recommended therapy for resectable and localized disease, but several other local treatments have been reported such as radiotherapy (RT). Most articles report small retrospective studies, referring to patients treated decades ago with large heterogeneity in terms of RT dose and technique. The aim of this study was to systematically review the main experiences in RT for the treatment of EMPD in the past 30 years. A systematic search of the bibliographic databases PubMed and Scopus from January 1986 to January 2017 was performed including studies published in English, Italian, Spanish, French, and German language. According to the search strategy, 19 full-text articles, published from 1991 to 2015, fulfilled inclusion criteria and were included in the final review. All articles were retrospective analyses with no randomized controlled trials. These studies evaluated 195 EMPD patients treated with RT, delivered in several settings. A large variability in terms of RT doses, fractionation, clinical setting, and techniques was found.Radiotherapy was administered as definitive treatment for primary or recurrent disease after surgery in 18 studies with doses ranging from 30 to 80.2 Gy delivered in 3 to 43 fractions. Radiotherapy was administered as postoperative adjuvant treatment in 9 articles with doses ranging between 32 and 64.8 Gy in 20 to 30 fractions. Two studies reported the RT use in preoperative neoadjuvant setting with doses ranging between 40 and 43.30 Gy, and 2 experiences reported the RT treatment for in situ EMPD, using 39.6 to 40 Gy. Adverse events were reported in almost all but 2 articles and were grade 2 or lower.The 18 studies evaluating RT as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively.In patients with EMPD and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death. To date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.

The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

NASA Technical Reports Server (NTRS)

Hada, M.; George, Kerry; Cucinotta, F. A.

2011-01-01

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, Ti-48-ions with energies ranging from 240 to 1000 MeV/u, or to Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Si beams in this study ranged from 48 to 158 keV/ m, the LET of the Ti ions ranged from 107 to 240 keV/micron, and the LET of the Fe-ions ranged from 145 to 440 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to gamma-rays. The estimates of RBEmax values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, 21.4+/-1.7 to 28.3+/-2.4 for Ti ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBEmax value for Fe ions was obtained with the 600 MeV/u beam, the highest RBEmax value for Ti ions was obtained 1000 MeV/u beam, and the highest RBEmax value for Si ions was obtained with the 170 MeV/u beam. For Si and Fe ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreasing with further increase in LET. Additional studies for low doses Si-28-ions down to 0.02 Gy will be discussed.

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

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

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

2010-03-01

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

Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design.

PubMed

Tevaarwerk, Amye; Wilding, George; Eickhoff, Jens; Chappell, Rick; Sidor, Carolyn; Arnott, Jamie; Bailey, Howard; Schelman, William; Liu, Glenn

2012-06-01

MKC-1 is an oral cell-cycle inhibitor with broad antitumor activity in preclinical models. Clinical studies demonstrated modest antitumor activity using intermittent dosing schedule, however additional preclinical data suggested continuous dosing could be efficacious with additional effects against the mTor/AKT pathway. The primary objectives were to determine the maximum tolerated dose (MTD) and response of continuous MKC-1. Secondary objectives included characterizing the dose limiting toxicities (DLTs) and pharmacokinetics (PK). Patients with solid malignancies were eligible, if they had measurable disease, ECOG PS ≤1, and adequate organ function. Exclusions included brain metastases and inability to receive oral drug. MKC-1 was dosed twice daily, continuously in 28-day cycles. Other medications were eliminated if there were possible drug interactions. Doses were assigned using a TITE-CRM algorithm following enrollment of the first 3 pts. Disease response was assessed every 8 weeks. Between 5/08-9/09, 24 patients enrolled (15 M/9 F, median 58 years, range 44-77). Patients 1-3 received 120 mg/d of MKC-1; patients 4-24 were dosed per the TITE-CRM algorithm: 150 mg [n = 1], 180 [2], 200 [1], 230 [1], 260 [5], 290 [6], 320 [5]. The median time on drug was 8 weeks (range 4-28). The only DLT occurred at 320 mg (grade 3 fatigue). Stable disease occurred at 150 mg/d (28 weeks; RCC) and 320 mg/d (16 weeks; breast, parotid). Escalation halted at 320 mg/d. Day 28 pharmacokinetics indicated absorption and active metabolites. Continuous MKC-1 was well-tolerated; there were no RECIST responses, although clinical benefit occurred in 3/24 pts. Dose escalation stopped at 320 mg/d, and this is the MTD as defined by the CRM dose escalation algorithm; this cumulative dose/cycle exceeds that determined from intermittent dosing studies. A TITE-CRM allowed for rapid dose escalation and was able to account for late toxicities with continuous dosing via a modified algorithm.

Breast surface radiation dose during coronary CT angiography: reduction by breast displacement and lead shielding.

PubMed

Foley, Shane J; McEntee, Mark F; Achenbach, Stephan; Brennan, Patrick C; Rainford, Louise S; Dodd, Jonathan D

2011-08-01

The purpose of this study was to prospectively evaluate the effect of cranial breast displacement and lead shielding on in vivo breast surface radiation dose in women undergoing coronary CT angiography. Fifty-four women (mean age, 59.2 ± 9.8 years) prospectively underwent coronary 64-MDCT angiography for evaluation of chest pain. The patients were randomly assigned to a control group (n = 16), breast displacement group (n = 22), or breast displacement plus lead shielding group (n = 16). Thermoluminescent dosimeters (TLDs) were placed superficially on each breast quadrant and the areolar region of both breasts. Breast surface radiation doses, the degree of breast displacement, and coronary image quality were compared between groups. A phantom dose study was conducted to compare breast doses with z-axis positioning on the chest wall. A total of 1620 TLD dose measurements were recorded. Compared with control values, the mean breast surface dose was reduced 23% in the breast displacement group (24.3 vs 18.6 mGy, p = 0.015) and 36% in the displacement plus lead shielding group (24.3 vs 15.6 mGy, p = 0.0001). Surface dose reductions were greatest in the upper outer (displacement alone, 66%; displacement plus shielding, 63%), upper inner (65%, 58%), and areolar quadrants (44%, 53%). The smallest surface dose reductions were recorded for A-cup breasts: 7% for the displacement group and 3% for the displacement plus lead group (p = 0.741). Larger reductions in surface dose were recorded for B-cup (25% and 56%, p = 0.273), C-cup (38% and 60%, p = 0.001), and D-cup (31% and 25%, p = 0.095) sizes. Most of the patients (79%) had either good (< 50% of breast above scan range) or excellent (< 75% of breast above the scan range) breast displacement. No significant difference in coronary image quality was detected between groups. The phantom dose study showed that surface TLD measurements were underestimates of absorbed tissue dose by a mean of 9% and that a strong negative correlation exists between the amount of cranial displacement and breast dose. Use of breast displacement during coronary CTA substantially reduces the radiation dose to the breast surface.

Gamma ray induced decomposition of double nitrates of lanthanum and cerium with some mono and bivalent cations in solid state

NASA Astrophysics Data System (ADS)

Kulkarni, S. P.; Garg, A. N.

Gamma ray induced decomposition of two series of double nitrates; 2M INO 3⋯Ln(NO 3) 3⋯ x H 2O (where MI = NH+4, Na+, K+, Rb+, Cs+; LnIII = La3+, Ce3+ and x = 2 or 4) and 3M II(NO 3) 2·2Ln III(NO 3) 3⋯24H 2O (where MII = Mg2+, Co2+, Zn2+; LnIII = La3+, Ce3+) has been studied in solid state over a wide absorbed dose range at room temperature. G(NO -2) values have been found to depend on the absorbed dose and the nature of cation in both the series of double salts. Radiation sensitivity of lanthanum double nitrates with monovalent cations at an absorbed dose of 158 kGy follows the order NH +4 < Rb + ≅ Cs + < Na + < K + and those of cerium NH +4 < Rb +

Spectral calibration of EBT3 and HD-V2 radiochromic film response at high dose using 20 MeV proton beams

NASA Astrophysics Data System (ADS)

Feng, Yiwei; Tiedje, Henry F.; Gagnon, Katherine; Fedosejevs, Robert

2018-04-01

Radiochromic film is used extensively in many medical, industrial, and scientific applications. In particular, the film is used in analysis of proton generation and in high intensity laser-plasma experiments where very high dose levels can be obtained. The present study reports calibration of the dose response of Gafchromic EBT3 and HD-V2 radiochromic films up to high exposure densities. A 2D scanning confocal densitometer system is employed to carry out accurate optical density measurements up to optical density 5 on the exposed films at the peak spectral absorption wavelengths. Various wavelengths from 400 to 740 nm are also scanned to extend the practical dose range of such films by measuring the response at wavelengths removed from the peak response wavelengths. Calibration curves for the optical density versus exposure dose are determined and can be used for quantitative evaluation of measured doses based on the measured optical densities. It was found that blue and UV wavelengths allowed the largest dynamic range though at some trade-off with overall accuracy.

Errors and Uncertainties in Dose Reconstruction for Radiation Effects Research

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

Strom, Daniel J.

Dose reconstruction for studies of the health effects of ionizing radiation have been carried out for many decades. Major studies have included Japanese bomb survivors, atomic veterans, downwinders of the Nevada Test Site and Hanford, underground uranium miners, and populations of nuclear workers. For such studies to be credible, significant effort must be put into applying the best science to reconstructing unbiased absorbed doses to tissues and organs as a function of time. In many cases, more and more sophisticated dose reconstruction methods have been developed as studies progressed. For the example of the Japanese bomb survivors, the dose surrogatemore » “distance from the hypocenter” was replaced by slant range, and then by TD65 doses, DS86 doses, and more recently DS02 doses. Over the years, it has become increasingly clear that an equal level of effort must be expended on the quantitative assessment of uncertainty in such doses, and to reducing and managing uncertainty. In this context, this paper reviews difficulties in terminology, explores the nature of Berkson and classical uncertainties in dose reconstruction through examples, and proposes a path forward for Joint Coordinating Committee for Radiation Effects Research (JCCRER) Project 2.4 that requires a reasonably small level of effort for DOSES-2008.« less

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Efficacy and Safety of the Glucagon Receptor Antagonist PF-06291874: A 12-Week, Randomized, Dose-Response Study in Patients With Type 2 Diabetes Mellitus on Background Metformin Therapy.

PubMed

Kazierad, David J; Chidsey, Kristin; Somayaji, Veena R; Bergman, Arthur J; Calle, Roberto A

2018-06-19

To conduct a dose-response assessment of the efficacy and safety of the glucagon receptor antagonist PF-06291874 in adults with type 2 diabetes (T2DM) receiving stable doses of metformin. This randomized, double-blind, statin-stratified, placebo-controlled, 4-arm, parallel-group study was conducted in patients with T2DM receiving background metformin. After an 8-week, non-metformin oral antidiabetic agent washout period, 206 patients were randomized to placebo or PF-06291874 (30, 60, or 100 mg once daily) for 12 weeks. Glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and safety endpoints were assessed at baseline and postbaseline. Dose-dependent mean reductions from baseline in HbA1c for PF-06291874 ranged from -0.67% (-7.29 mmol/mol) to -0.93% (-10.13 mmol/mol); and in FPG from -16.6 to -33.3 mg/dL after 12 weeks of dosing. The incidence of hypoglycemia was low and similar between groups receiving PF-06291874. Small, non-dose-dependent increases in LDL cholesterol (<10%) and blood pressure (BP; systolic BP>2 mmHg, diastolic BP>1 mmHg) were observed with PF-06291874. Modest non-dose-dependent median increases were observed across PF-06291874 groups at 12 weeks for alanine aminotransferase (range, 37.6-48.7 U/L versus placebo) and aspartate aminotransferase (range, 33.3-36.6 U/L versus placebo) that were not associated with bilirubin changes. Small increases were observed for body weight (<0.5 kg) in each PF-06291874 group versus placebo. In patients with T2DM, PF-06291874 significantly lowered HbA1c and glucose, was well tolerated, and had low risk of hypoglycemia. Small, non-dose-related increases in BP, lipids, and hepatic transaminases were observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

PubMed

White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

2016-09-22

KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .).

Radiation dosimetry properties of smartphone CMOS sensors.

PubMed

Van Hoey, Olivier; Salavrakos, Alexia; Marques, Antonio; Nagao, Alexandre; Willems, Ruben; Vanhavere, Filip; Cauwels, Vanessa; Nascimento, Luana F

2016-03-01

During the past years, several smartphone applications have been developed for radiation detection. These applications measure radiation using the smartphone camera complementary metal-oxide-semiconductor sensor. They are potentially useful for data collection and personal dose assessment in case of a radiological incident. However, it is important to assess these applications. Six applications were tested by means of irradiations with calibrated X-ray and gamma sources. It was shown that the measurement stabilises only after at least 10-25 min. All applications exhibited a flat dose rate response in the studied ambient dose equivalent range from 2 to 1000 μSv h(-1). Most applications significantly over- or underestimate the dose rate or are not calibrated in terms of dose rate. A considerable energy dependence was observed below 100 keV but not for the higher energy range more relevant for incident scenarios. Photon impact angle variation gave a measured signal variation of only about 10 %. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Independent dose verification system with Monte Carlo simulations using TOPAS for passive scattering proton therapy at the National Cancer Center in Korea

NASA Astrophysics Data System (ADS)

Shin, Wook-Geun; Testa, Mauro; Kim, Hak Soo; Jeong, Jong Hwi; Byeong Lee, Se; Kim, Yeon-Joo; Min, Chul Hee

2017-10-01

For the independent validation of treatment plans, we developed a fully automated Monte Carlo (MC)-based patient dose calculation system with the tool for particle simulation (TOPAS) and proton therapy machine installed at the National Cancer Center in Korea to enable routine and automatic dose recalculation for each patient. The proton beam nozzle was modeled with TOPAS to simulate the therapeutic beam, and MC commissioning was performed by comparing percent depth dose with the measurement. The beam set-up based on the prescribed beam range and modulation width was automated by modifying the vendor-specific method. The CT phantom was modeled based on the DICOM CT files with TOPAS-built-in function, and an in-house-developed C++ code directly imports the CT files for positioning the CT phantom, RT-plan file for simulating the treatment plan, and RT-structure file for applying the Hounsfield unit (HU) assignment, respectively. The developed system was validated by comparing the dose distributions with those calculated by the treatment planning system (TPS) for a lung phantom and two patient cases of abdomen and internal mammary node. The results of the beam commissioning were in good agreement of up to 0.8 mm2 g-1 for B8 option in both of the beam range and the modulation width of the spread-out Bragg peaks. The beam set-up technique can predict the range and modulation width with an accuracy of 0.06% and 0.51%, respectively, with respect to the prescribed range and modulation in arbitrary points of B5 option (128.3, 132.0, and 141.2 mm2 g-1 of range). The dose distributions showed higher than 99% passing rate for the 3D gamma index (3 mm distance to agreement and 3% dose difference) between the MC simulations and the clinical TPS in the target volume. However, in the normal tissues, less favorable agreements were obtained for the radiation treatment planning with the lung phantom and internal mammary node cases. The discrepancies might come from the limitations of the clinical TPS, which is the inaccurate dose calculation algorithm for the scattering effect, in the range compensator and inhomogeneous material. Moreover, the steep slope of the compensator, conversion of the HU values to the human phantom, and the dose calculation algorithm for the HU assignment also could be reasons of the discrepancies. The current study could be used for the independent dose validation of treatment plans including high inhomogeneities, the steep compensator, and riskiness such as lung, head & neck cases. According to the treatment policy, the dose discrepancies predicted with MC could be used for the acceptance decision of the original treatment plan.

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera)

PubMed Central

Maze, Ian S.; Wright, Geraldine A.; Mustard, Julie A.

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses lead to hemolymph ethanol levels of approximately 40 to 100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 hr post-ingestion for low doses and at 24 to 48 hours for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior. PMID:17070538

Evaluation of World Population-Weighted Effective Dose due to Cosmic Ray Exposure

PubMed Central

Sato, Tatsuhiko

2016-01-01

After the release of the Report of the United Nations Scientific Committee of the Effects of Atomic Radiation in 2000 (UNSCEAR2000), it became commonly accepted that the world population-weighted effective dose due to cosmic-ray exposure is 0.38 mSv, with a range from 0.3 to 2 mSv. However, these values were derived from approximate projections of altitude and geographic dependences of the cosmic-ray dose rates as well as the world population. This study hence re-evaluated the population-weighted annual effective doses and their probability densities for the entire world as well as for 230 individual nations, using a sophisticated cosmic-ray flux calculation model in tandem with detailed grid population and elevation databases. The resulting world population-weighted annual effective dose was determined to be 0.32 mSv, which is smaller than the UNSCEAR’s evaluation by 16%, with a range from 0.23 to 0.70 mSv covering 99% of the world population. These values were noted to vary with the solar modulation condition within a range of approximately 15%. All assessed population-weighted annual effective doses as well as their statistical information for each nation are provided in the supplementary files annexed to this report. These data improve our understanding of cosmic-ray radiation exposures to populations globally. PMID:27650664

Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit.

PubMed

Stamenić, Tamara Timić; Poe, Michael M; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M; Savić, Miroslav M

2016-11-15

We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABA A receptors containing the α5 subunit (α5GABA A Rs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABA A receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2'F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200mg/kg), but at the price of activating non-α5 GABA A Rs as well as the desired α5GABA A Rs at the highest dose. At the dose of 10mg/kg, which elicits a strong positive modulation of α5GABA A Rs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABA A Rs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. Copyright © 2016 Elsevier B.V. All rights reserved.

Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit

PubMed Central

Stamenić, Tamara Timić; Poe, Michael M.; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M.; Savić, Miroslav M.

2016-01-01

We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABAA receptors containing the α5 subunit (α5GABAARs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10 mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABAA receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2′F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200 mg/kg), but at the price of activating non-α5 GABAARs as well as the desired α5GABAARs at the highest dose. At the dose of 10 mg/kg, which elicits a strong positive modulation of α5GABAARs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10 mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABAARs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. PMID:27639297

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

Characteristics of an OSLD in the diagnostic energy range.

PubMed

Al-Senan, Rani M; Hatab, Mustapha R

2011-07-01

Optically stimulated luminescence (OSL) dosimetry has been recently introduced in radiation therapy as a potential alternative to the thermoluminescent dosimeter (TLD) system. The aim of this study was to investigate the feasibility of using OSL point dosimeters in the energy range used in diagnostic imaging. NanoDot OSL dosimeters (OSLDs) were used in this study, which started with testing the homogeneity of a new packet of nanoDots. Reproducibility and the effect of optical treatment (bleaching) were then examined, followed by an investigation of the effect of accumulated dose on the OSLD indicated doses. OSLD linearity, angular dependence, and energy dependence were also studied. Furthermore, comparison with LiF:Mg,Ti TLD chips using standard CT dose phantoms at 80 and 120 kVp settings was performed. Batch homogeneity showed a coefficient of variation of <5%. Single-irradiation measurements with bleaching after each OSL readout was found to be associated with a 3.3% reproducibility (one standard deviation measured with a 8 mGy test dose), and no systematic change in OSLDs sensitivity could be noted from measurement to measurement. In contrast, the multiple-irradiation readout without bleaching in between measurements was found to be associated with an uncertainty (using a 6 mGy test dose) that systematically increased with accumulated dose, reaching 42% at 82 mGy. Good linearity was shown by nanoDots under general x-ray, CT, and mammography units with an R2 > 0.99. The angular dependence test showed a drop of approximately 70% in the OSLD response at 90 degrees in mammography (25 kVp). With the general radiography unit, the maximum drop was 40% at 80 kVp and 20% at 120 kVp, and it was only 10% with CT at both 80 and 120 kVp. The energy dependence study showed a range of ion chamber-to-OSLDs ratios between 0.81 and 1.56, at the energies investigated (29-62 keV). A paired t-test for comparing the OSLDs and TLDs showed no significant variation (p > 0.1). OSLDs exhibited good batch homogeneity (<5%) and reproducibility (3.3%), as well as a linear response. In addition, they showed no statistically significant difference with TLDs in CT measurements (p > 0.1). However, high uncertainty (42%) in the dose estimate was found as a result of relatively high accumulated dose. Furthermore, nanoDots showed high angular dependence (up to 70%) in low kVp techniques. Energy dependence of about 60% was found, and correction factors were suggested for the range of energies investigated. Therefore, if angular and energy dependences are taken into consideration and the uncertainty associated with accumulated dose is avoided, OSLDs (nanoDots) can be suitable for use as point dosimeters in diagnostic settings.

SU-F-T-106: A Dosimetric Study of Intensity Modulated Radiation Therapy to Decrease Radiation Dose to the Thoracic Vertebral Bodies in Patients Receiving Concurrent Chemoradiation for Lung Cancer

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

DiCostanzo, Dominic; Barney, Christian L.; Bazan, Jose G.

Purpose: Recent clinical studies have shown a correlation between radiation dose to the thoracic vertebral bodies (TVB) and the development of hematologic toxicity (HT) in patients receiving chemoradiation (CRT) for lung cancer (LuCa). The feasibility of a bone-marrow sparing (BMS) approach in this group of patients is unknown. We hypothesized that radiation dose to the TVB can be reduced with an intensity modulated radiation therapy(IMRT)/volumetric modulated arc radiotherapy(VMAT) without affecting plan quality. Methods: We identified LuCa cases treated with curative intent CRT using IMRT/VMAT from 4/2009 to 2/2015. The TVBs from T1–T10 were retrospectively contoured. No constraints were placed onmore » the TVB structure initially. A subset were re-planned with BMS-IMRT/VMAT with an objective or reducing the mean TVB dose to <23 Gy. The following data were collected on the initial and BMS plans: mean dose to planning target volume (PTV), lungs-PTV, esophagus, heart; lung V20; cord max dose. Pairwise comparisons were performed using the signed rank test. Results: 94 cases received CRT with IMRT/VMAT. We selected 11 cases (7 IMRT, 4 VMAT) with a range of initial mean TVB doses (median 35.7 Gy, range 18.9–41.4 Gy). Median prescription dose was 60 Gy. BMS-IMRT/VMAT significantly reduced the mean TVB dose by a median of 10.2 Gy (range, 1.0–16.7 Gy, p=0.001) and reduced the cord max dose by 2.9 Gy (p=0.014). BMS-IMRT/VMAT had no impact on lung mean (median +17 cGy, p=0.700), lung V20 (median +0.5%, p=0.898), esophagus mean (median +13 cGy, p=1.000) or heart mean (median +16 cGy, p=0.365). PTV-mean dose was not affected by BMS-IMRT/VMAT (median +13 cGy, p=0.653). Conclusion: BMS-IMRT/VMAT was able to significantly reduce radiation dose to the TVB without compromising plan quality. Prospective evaluation of BMS-IMRT/VMAT in patients receiving CRT for LuCa is warranted to determine if this approach results in clinically significant reductions in HT.« less

In vivo verification of particle therapy: how Compton camera configurations affect 3D image quality

NASA Astrophysics Data System (ADS)

Mackin, D.; Draeger, E.; Peterson, S.; Polf, J.; Beddar, S.

2017-05-01

The steep dose gradients enabled by the Bragg peaks of particle therapy beams are a double edged sword. They enable highly conformal dose distributions, but even small deviations from the planned beam range can cause overdosing of healthy tissue or under-dosing of the tumour. To reduce this risk, particle therapy treatment plans include margins large enough to account for all the sources of range uncertainty, which include patient setup errors, patient anatomy changes, and CT number to stopping power ratios. Any system that could verify the beam range in vivo, would allow reduced margins and more conformal dose distributions. Toward our goal developing such a system based on Compton camera (CC) imaging, we studied how three configurations (single camera, parallel opposed, and orthogonal) affect the quality of the 3D images. We found that single CC and parallel opposed configurations produced superior images in 2D. The increase in parallax produced by an orthogonal CC configuration was shown to be beneficial in producing artefact free 3D images.

A MULTI-ELEMENT THICK GAS ELECTRON MULTIPLIER-BASED MICRODOSEMETER FOR MEASUREMENT OF NEUTRONS DOSE-EQUIVALENT: A MONTE CARLO STUDY.

PubMed

Moslehi, A; Raisali, G

2017-11-01

To determine the dose-equivalent of neutrons in an extended energy range, in the present work a multi-element thick gas electron multiplier-based microdosemeter made of PMMA (Perspex) walls of 10 mm in thickness is designed. Each cavity is filled with the propane-based tissue-equivalent (TE) gas simulating 1 µm of tissue. Also, a few weight fractions of 3He are assumed to be added to the TE gas. The dose-equivalents are determined for 11 neutron energies between thermal and 14 MeV using the lineal energy distributions calculated by Geant4 simulation toolkit and also the lineal energy-based quality factors. The results show that by adding 0.04% of 3He to the TE gas in each cavity, an energy-independent dose-equivalent response within 30% uncertainty around a median value of 0.91 in the above energy range is achieved. It is concluded that after its construction, the studied microdosemeter can be used to measure the dose-equivalent of neutrons, favorably. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Spectral correction factors for conventional neutron dosemeters used in high-energy neutron environments.

PubMed

Lee, K W; Sheu, R J

2015-04-01

High-energy neutrons (>10 MeV) contribute substantially to the dose fraction but result in only a small or negligible response in most conventional moderated-type neutron detectors. Neutron dosemeters used for radiation protection purpose are commonly calibrated with (252)Cf neutron sources and are used in various workplace. A workplace-specific correction factor is suggested. In this study, the effect of the neutron spectrum on the accuracy of dose measurements was investigated. A set of neutron spectra representing various neutron environments was selected to study the dose responses of a series of Bonner spheres, including standard and extended-range spheres. By comparing (252)Cf-calibrated dose responses with reference values based on fluence-to-dose conversion coefficients, this paper presents recommendations for neutron field characterisation and appropriate correction factors for responses of conventional neutron dosemeters used in environments with high-energy neutrons. The correction depends on the estimated percentage of high-energy neutrons in the spectrum or the ratio between the measured responses of two Bonner spheres (the 4P6_8 extended-range sphere versus the 6″ standard sphere). © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Meeting The Joint Commission's Dose Incident Identification and External Benchmarking Requirements Using the ACR's Dose Index Registry.

PubMed

Bohl, Michael A; Goswami, Roopa; Strassner, Brett; Stanger, Paula

2016-08-01

The purpose of this investigation was to evaluate the potential of using the ACR's Dose Index Registry(®) to meet The Joint Commission's requirements to identify incidents in which the radiation dose index from diagnostic CT examinations exceeded the protocol's expected dose index range. In total, 10,970 records in the Dose Index Registry were statistically analyzed to establish both an upper and lower expected dose index for each protocol. All 2015 studies to date were then retrospectively reviewed to identify examinations whose total examination dose index exceeded the protocol's defined upper threshold. Each dose incident was then logged and reviewed per the new Joint Commission requirements. Facilities may leverage their participation in the ACR's Dose Index Registry to fully meet The Joint Commission's dose incident identification review and external benchmarking requirements. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

DICOM organ dose does not accurately represent calculated dose in mammography

NASA Astrophysics Data System (ADS)

Suleiman, Moayyad E.; Brennan, Patrick C.; McEntee, Mark F.

2016-03-01

This study aims to analyze the agreement between the mean glandular dose estimated by the mammography unit (organ dose) and mean glandular dose calculated using Dance et al published method (calculated dose). Anonymised digital mammograms from 50 BreastScreen NSW centers were downloaded and exposure information required for the calculation of dose was extracted from the DICOM header along with the organ dose estimated by the system. Data from quality assurance annual tests for the included centers were collected and used to calculate the mean glandular dose for each mammogram. Bland-Altman analysis and a two-tailed paired t-test were used to study the agreement between calculated and organ dose and the significance of any differences. A total of 27,869 dose points from 40 centers were included in the study, mean calculated dose and mean organ dose (+/- standard deviation) were 1.47 (+/-0.66) and 1.38 (+/-0.56) mGy respectively. A statistically significant 0.09 mGy bias (t = 69.25; p<0.0001) with 95% limits of agreement between calculated and organ doses ranging from -0.34 and 0.52 were shown by Bland-Altman analysis, which indicates a small yet highly significant difference between the two means. The use of organ dose for dose audits is done at the risk of over or underestimating the calculated dose, hence, further work is needed to identify the causal agents for differences between organ and calculated doses and to generate a correction factor for organ dose.

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

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

Talarico, O; Krylova, T; Lebedenko, I

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

Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children.

PubMed

Englund, Janet A; Karron, Ruth A; Cunningham, Coleen K; Larussa, Philip; Melvin, Ann; Yogev, Ram; Handelsman, Ed; Siberry, George K; Thumar, Bhavanji; Schappell, Elizabeth; Bull, Catherine V; Chu, Helen Y; Schaap-Nutt, Anne; Buchholz, Ursula; Collins, Peter L; Schmidt, Alexander C

2013-11-19

Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children. Copyright © 2013 Elsevier Ltd. All rights reserved.

A dual two dimensional electronic portal imaging device transit dosimetry model based on an empirical quadratic formalism

PubMed Central

Metwaly, M; Glegg, M; Baggarley, S P; Elliott, A

2015-01-01

Objective: This study describes a two dimensional electronic portal imaging device (EPID) transit dosimetry model that can predict either: (1) in-phantom exit dose, or (2) EPID transit dose, for treatment verification. Methods: The model was based on a quadratic equation that relates the reduction in intensity to the equivalent path length (EPL) of the attenuator. In this study, two sets of quadratic equation coefficients were derived from calibration dose planes measured with EPID and ionization chamber in water under reference conditions. With two sets of coefficients, EPL can be calculated from either EPID or treatment planning system (TPS) dose planes. Consequently, either the in-phantom exit dose or the EPID transit dose can be predicted from the EPL. The model was tested with two open, five wedge and seven sliding window prostate and head and neck intensity-modulated radiation therapy (IMRT) fields on phantoms. Results were analysed using absolute gamma analysis (3%/3 mm). Results: The open fields gamma pass rates were >96.8% for all comparisons. For wedge and IMRT fields, comparisons between predicted and TPS-computed in-phantom exit dose resulted in mean gamma pass rate of 97.4% (range, 92.3–100%). As for the comparisons between predicted and measured EPID transit dose, the mean gamma pass rate was 97.5% (range, 92.6–100%). Conclusion: An EPID transit dosimetry model that can predict in-phantom exit dose and EPID transit dose was described and proven to be valid. Advances in knowledge: The described model is practical, generic and flexible to encourage widespread implementation of EPID dosimetry for the improvement of patients' safety in radiotherapy. PMID:25969867

Pharmacodynamics and pharmacokinetics of single doses of subcutaneous pegylated human G-CSF mutant (Ro 25-8315) in healthy volunteers: comparison with single and multiple daily doses of filgrastim.

PubMed

van Der Auwera, P; Platzer, E; Xu, Z X; Schulz, R; Feugeas, O; Capdeville, R; Edwards, D J

2001-04-01

Ro 25-8315 is produced by conjugation of rhG-CSF mutant with polyethylene glycol (PEG). The purpose of this study was to examine the pharmacodynamics and pharmacokinetics of Ro 25-8315 in comparison with Filgrastim (rhG-CSF). Subjects received single subcutaneous doses of Ro 25-8315 ranging from 10 to 150 microg/kg using a double-blind, randomized, placebo-controlled design. Filgrastim was administered as a single dose (5 or 10 microg/kg) and, following a 14-day washout period, daily for 7 days. Ro 25-8315 increased absolute neutrophil count (ANC) by 6- to 8-fold and CD34+ cell count more than 30-fold at the highest doses tested. Single doses (60-150 microg/kg) of Ro 25-8315 and multiple doses of Filgrastim had similar effects on ANC and CD34+, although Ro 25-8315 had a greater effect on CFU-GM. The pharmacokinetics of Ro 25-8315 were dose-dependent, with peak concentrations and area under the serum concentration-time curve (AUC) increasing 100-fold over the range of doses studied. Time to reach peak concentration (T(max)) and half-life of Ro 25-8315 averaged 20-30 hr at all doses, approximately three times longer than with Filgrastim. Adverse events were not serious and occurred with similar frequency with both products. Pegylation of rhG-CSF mutant results in more desirable pharmacokinetic properties and a longer duration of action with effective increases in ANC and measures of peripheral blood progenitor cell mobilization for at least 1 week. Copyright 2001 Wiley-Liss, Inc.

RADRUE METHOD FOR RECONSTRUCTION OF EXTERNAL PHOTON DOSES TO CHERNOBYL LIQUIDATORS IN EPIDEMIOLOGICAL STUDIES

PubMed Central

Kryuchkov, Victor; Chumak, Vadim; Maceika, Evaldas; Anspaugh, Lynn R.; Cardis, Elisabeth; Bakhanova, Elena; Golovanov, Ivan; Drozdovitch, Vladimir; Luckyanov, Nickolas; Kesminiene, Ausrele; Voillequé, Paul; Bouville, André

2010-01-01

Between 1986 and 1990, several hundred thousand workers, called “liquidators” or “clean-up workers”, took part in decontamination and recovery activities within the 30-km zone around the Chernobyl nuclear power plant in Ukraine, where a major accident occurred in April 1986. The Chernobyl liquidators were mainly exposed to external ionizing radiation levels that depended primarily on their work locations and the time after the accident when the work was performed. Because individual doses were often monitored inadequately or were not monitored at all for the majority of liquidators, a new method of photon (i.e. gamma and x-rays) dose assessment, called “RADRUE” (Realistic Analytical Dose Reconstruction with Uncertainty Estimation) was developed to obtain unbiased and reasonably accurate estimates for use in three epidemiologic studies of hematological malignancies and thyroid cancer among liquidators. The RADRUE program implements a time-and-motion dose reconstruction method that is flexible and conceptually easy to understand. It includes a large exposure rate database and interpolation and extrapolation techniques to calculate exposure rates at places where liquidators lived and worked within ~70 km of the destroyed reactor. The RADRUE technique relies on data collected from subjects’ interviews conducted by trained interviewers, and on expert dosimetrists to interpret the information and provide supplementary information, when necessary, based upon their own Chernobyl experience. The RADRUE technique was used to estimate doses from external irradiation, as well as uncertainties, to the bone-marrow for 929 subjects and to the thyroid gland for 530 subjects enrolled in epidemiologic studies. Individual bone-marrow dose estimates were found to range from less than one μGy to 3,300 mGy, with an arithmetic mean of 71 mGy. Individual thyroid dose estimates were lower and ranged from 20 μGy to 507 mGy, with an arithmetic mean of 29 mGy. The uncertainties, expressed in terms of geometric standard deviations, ranged from 1.1 to 5.8, with an arithmetic mean of 1.9. PMID:19741357

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances

PubMed Central

ORITO, Kensuke; KAWARAI-SHIMAMURA, Asako; OGAWA, Atsushi; NAKAMURA, Atsushi

2017-01-01

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20–50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25–50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26–370 sec), median duration of emesis was 151.5 sec (range, 30–780 sec), and median number of emesis episodes was 2 (range, 1–8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting. PMID:29093310

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

PubMed

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

2017-05-01

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

Proposed linear energy transfer areal detector for protons using radiochromic film

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

Mayer, Rulon; Lin, Liyong; Fager, Marcus

2015-04-15

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured atmore » a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%–10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%–15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.« less

Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients.

PubMed

Yeaman, Fiona; Meek, Robert; Egerton-Warburton, Diana; Rosengarten, Pamela; Graudins, Andis

2014-06-01

There are currently no studies assessing effectiveness of sub-dissociative intranasal (IN) ketamine as the initial analgesic for adult patients in the ED. The study aims to examine the effectiveness of sub-dissociative IN ketamine as a primary analgesic agent for adult patients in the ED. This is a prospective, observational study of adult ED patients presenting with severe pain (≥6 on 11-point scale at triage). IN ketamine dose was 0.7 mg/kg, with secondary dose of 0.5 mg/kg at 15 min if pain did not improve. After 6 months, initial dose was increased to 1.0 mg/kg with the same optional secondary dose. The primary outcomes are change in VAS rating at 30 min; percentage of patients reporting clinically significant reduction in VAS (≥20 mm) at 30 min; dose resulting in clinically significant pain reduction. Of the 72 patients available for analysis, median age was 34.5 years and 64% were men. Median initial VAS rating was 76 mm (interquartile range [IQR]: 65-82). Median total dose of IN ketamine for all patients was 0.98 mg/kg (IQR: 0.75-1.15, range: 0.59-1.57). Median reduction in VAS rating at 30 min was 24 mm (IQR: 2-45). Forty (56%, 95% CI: 44.0-66.7) reported VAS reduction ≥20 mm, these patients having had a total median ketamine dose of 0.94 mg/kg (IQR: 0.72-1.04). IN ketamine, at a dose of about 1 mg/kg, was an effective analgesic agent in 56% of study patients. The place of IN ketamine in analgesic guidelines for adults requires further investigation. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Validating the Effectiveness of Switching the Vancomycin TDM Analysis Software Based on the Predictive Accuracy.

PubMed

Imai, Shungo; Yamada, Takehiro; Ishiguro, Nobuhisa; Miyamoto, Takenori; Kagami, Keisuke; Tomiyama, Naoki; Niinuma, Yusuke; Nagasaki, Daisuke; Suzuki, Koji; Yamagami, Akira; Kasashi, Kumiko; Kobayashi, Masaki; Iseki, Ken

2017-01-01

Based on the predictive performance in our previous study, we switched the therapeutic drug monitoring (TDM) analysis software for dose setting of vancomycin (VCM) from "Vancomycin MEEK TDM analysis software Ver2.0" (MEEK) to "SHIONOGI-VCM-TDM ver.2009" (VCM-TDM) in January 2015. In the present study, our aim was to validate the effectiveness of the changing VCM TDM analysis software in initial dose setting of VCM. The enrolled patients were divided into two groups, each having 162 patients in total, who received VCM with the initial dose set using MEEK (MEEK group) or VCM-TDM (VCM-TDM group). We compared the rates of attaining the therapeutic range (trough value; 10-20 μg/mL) of serum VCM concentration between the groups. Multivariate logistic regression analysis was performed to confirm that changing the VCM TDM analysis software was an independent factor related to attaining the therapeutic range. Switching the VCM TDM analysis software from MEEK to VCM-TDM improved the rate of attaining the therapeutic range by 21.6% (MEEK group: 42.6% vs. VCM-TDM group: 64.2%, p<0.01). Patient age ≥65 years, concomitant medication (furosemide) and the TDM analysis software used VCM-TDM were considered to be independent factors for attaining the therapeutic range. These results demonstrated the effectiveness of switching the VCM TDM analysis software from MEEK to VCM-TDM for initial dose setting of VCM.

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.

Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity.

PubMed

Mennenga, Sarah E; Gerson, Julia E; Koebele, Stephanie V; Kingston, Melissa L; Tsang, Candy W S; Engler-Chiurazzi, Elizabeth B; Baxter, Leslie C; Bimonte-Nelson, Heather A

2015-04-01

Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ranging from puberty to reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection, modeling the daily rise and fall of serum EE levels with oral regimens. Study II also investigated the impact of low, medium and high doses of EE on the basal forebrain cholinergic system. The low and medium doses utilized here correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. We evaluate cognition using a battery of maze tasks tapping several domains of spatial learning and memory as well as basal forebrain cholinergic integrity using immunohistochemistry and unbiased stereology to estimate the number of choline acetyltransferase (ChAT)-producing cells in the medial septum and vertical/diagonal bands. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; tonic delivery of low EE, a dose that corresponds to the most popular doses used in the clinic today, did not impact cognition on any measure. Both medium and high injection doses of EE reduced the number of ChAt-immunoreactive cells in the basal forebrain, and cell population estimates in the vertical/diagonal bands negatively correlated with working memory errors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biphasic Elimination of Tenofovir Diphosphate and Nonlinear Pharmacokinetics of Zidovudine Triphosphate in a Microdosing Study

PubMed Central

Chen, Jianmeng; Flexner, Charles; Liberman, Rosa G.; Skipper, Paul L.; Louissaint, Nicolette; Tannenbaum, Steven R.; Hendrix, Craig; Fuchs, Edward

2012-01-01

Objective Phase 0 studies can provide initial pharmacokinetics (PK) data in humans and help to facilitate early drug development, but their predictive value for standard dosing is controversial. To evaluate the prediction of microdosing for active intracellular drug metabolites, we compared the PK profile of two antiretroviral drugs, zidovudine (ZDV) and tenofovir (TFV), in microdose and standard dosing regimens. Study Design We administered a microdose (100 μg) of 14C-labeled drug (ZDV or tenofovir disoproxil fumarate (TDF)) with or without a standard unlabelled dose (300 mg) to healthy volunteers. Both the parent drug in plasma and the active metabolite, ZDV-triphosphate (ZDV-TP) or TFV-diphosphate (TFV-DP) in PBMCs and CD4+ cells were measured by AMS. Results The intracellular ZDV-TP concentration increased less than proportionally over the dose range studied (100 μg to 300 mg), while the intracellular TFV-DP PK were linear over the same dose range. ZDV-TP concentrations were lower in CD4+ cells versus total peripheral blood mononuclear cells (PBMCs), while TFV-DP concentrations were not different in CD4+ cells and PBMCs. Conclusion Our data were consistent with a rate-limiting step in the intracellular phosphorylation of ZDV but not TFV. AMS shows promise for predicting the PK of active intracellular metabolites of nucleosides, but nonlinearity of PK may be seen with some drugs. PMID:23187888

Evaluation of adverse events noted in children receiving continuous infusions of dexmedetomidine in the intensive care unit.

PubMed

Honey, Brooke L; Harrison, Donald L; Gormley, Andrew K; Johnson, Peter N

2010-01-01

Dexmedetomidine is an α(2)-adrenergic receptor agonist with sedative and analgesic effects in mechanically ventilated adults and children. Safety and efficacy data are limited in children. The purpose of this study is to retrospectively identify the incidence and types of adverse events noted in children receiving continuous infusions of dexmedetomidine and evaluate potential risk factors for adverse events. Between July 1, 2006, and July 31, 2007, data were collected on all children (< 18 years) who received continuous infusions of dexmedetomidine. Data collection included demographics, dexmedetomidine regimen, and type/number of adverse events. The primary endpoint was the total number of adverse events noted, including: transient hypertension, hypotension, neurological manifestations, apnea, and bradycardia. Secondary endpoints included categorization of each type of adverse event and an assessment of risk factors. A logistic regression model was used to assess the relationship of adverse events with independent variables including length of ICU stay, cumulative dose, peak infusion rate, duration of therapy, PRISM III score, and bolus dose. Thirty-six patients received dexmedetomidine representing 41 infusions. The median age was 16 months (range, 0.1-204 months) and median PRISM III score was 2 (range, 0-18). Eighteen (43.9%) patients received a bolus dose of dexmedetomidine. The median cumulative dose (mcg/kg) and peak dose (mcg/kg/hr) were 8.5 (range, 2.2-193.7) and 0.5 (range, 0.2-0.7), respectively. Dexmedetomidine was continued for a median of 20 (range, 3-263) hours. Six (14.6%) patients were slowly tapered off the continuous infusions. Twenty-one adverse events were noted in 17 patients, including 4 neurologic manifestations. Fourteen patients required interventions for adverse events. ICU length of stay was the only independent risk factor (p=0.036) for development of adverse events. Several potential adverse events were noted with dexmedetomidine continuous infusions including possible neurological manifestations. Further studies are needed looking at adverse events associated with dexmedetomidine use in the pediatric population.

External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

NASA Astrophysics Data System (ADS)

Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

2009-01-01

Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

PubMed

MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed gamma: neutron-radiation, delivered at various dose rates from a total body, bilateral, rotational, or unilateral exposure aspect. The DRRs established by a probit analysis vs. linear dose relationship were characterized by two main parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values for studies that used 250 kVp x radiation (five primary studies combined, n = 338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498, 542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30 values and slopes were also determined for total body, non-uniform, unilateral, pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337, 432] and 412 rad [359, 460]. Secondary data sets of limited studies that did not describe a DRR were used to support the mid-to-high lethal dose range for the H-ARS and the threshold dose range for the concurrent acute GI ARS. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in young rhesus macaques exposed to 250 kVp uniform total body x radiation without the benefit of medical management. A less substantial but consistent database demonstrated the DRR for total body exposure of differing radiation quality, dose rate and non-uniform exposure. The DRR for the H-ARS is characterized by steep slopes and relative LD50/30 values that reflect the radiation quality, exposure aspect, and dose rate over a range in time from 1954-2012.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

PubMed

Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

Summary of retrospective asbestos and welding fume exposure estimates for a nuclear naval shipyard and their correlation with radiation exposure estimates.

PubMed

Zaebst, D D; Seel, E A; Yiin, J H; Nowlin, S J; Chen, P

2009-07-01

In support of a nested case-control study at a U.S. naval shipyard, the results of the reconstruction of historical exposures were summarized, and an analysis was undertaken to determine the impact of historical exposures to potential chemical confounders. The nested case-control study (N = 4388) primarily assessed the relationship between lung cancer and external ionizing radiation. Chemical confounders considered important were asbestos and welding fume (as iron oxide fume), and the chromium and nickel content of welding fume. Exposures to the potential confounders were estimated by an expert panel based on a set of quantitatively defined categories of exposure. Distributions of the estimated exposures and trends in exposures over time were examined for the study population. Scatter plots and Spearman rank correlation coefficients were used to assess the degree of association between the estimates of exposure to asbestos, welding fume, and ionizing radiation. Correlation coefficients were calculated separately for 0-, 15-, 20-, and 25-year time-lagged cumulative exposures, total radiation dose (which included medical X-ray dose) and occupational radiation dose. Exposed workers' estimated cumulative exposures to asbestos ranged from 0.01 fiber-days/cm(3) to just under 20,000 fiber-days/cm(3), with a median of 29.0 fiber-days/cm(3). Estimated cumulative exposures to welding fume ranged from 0.16 mg-days/m(3) to just over 30,000 mg-days/m(3), with a median of 603 mg-days/m(3). Spearman correlation coefficients between cumulative radiation dose and cumulative asbestos exposures ranged from 0.09 (occupational dose) to 0.47 (total radiation dose), and those between radiation and welding fume from 0.14 to 0.47. The estimates of relative risk for ionizing radiation and lung cancer were unchanged when lowest and highest estimates of asbestos and welding fume were considered. These results suggest a fairly large proportion of study population workers were exposed to asbestos and welding fume, that the absolute level of confounding exposure did not affect the risk estimates, and that weak relationships existed between monitored lifetime cumulative occupational radiation dose and asbestos or welding fume.

Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users.

PubMed

Morefield, Kate M; Keane, Michael; Felgate, Peter; White, Jason M; Irvine, Rodney J

2011-07-01

To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-ethylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Assessment of effective radiation dose of an extremity CBCT, MSCT and conventional X ray for knee area using MOSFET dosemeters.

PubMed

Koivisto, Juha; Kiljunen, Timo; Wolff, Jan; Kortesniemi, Mika

2013-12-01

The objective of this study was to assess and compare the organ and effective doses in the knee area resulting from different commercially available multislice computed tomography devices (MSCT), one cone beam computed tomography device (CBCT) and one conventional X-ray radiography device using MOSFET dosemeters and an anthropomorphic RANDO knee phantom. Measurements of the MSCT devices resulted in effective doses ranging between 27 and 48 µSv. The CBCT measurements resulted in an effective dose of 12.6 µSv. The effective doses attained using the conventional radiography device were 1.8 µSv for lateral and 1.2 µSv for anterior-posterior projections. The effective dose resulting from conventional radiography was considerably lower than those recorded for the CBCT and MSCT devices. The MSCT effective dose results were two to four times higher than those measured on the CBCT device. This study demonstrates that CBCT can be regarded as a potential low-dose 3D imaging technique for knee examinations.

Evaluation and comparison of absorbed dose for electron beams by LiF and diamond dosimeters

NASA Astrophysics Data System (ADS)

Mosia, G. J.; Chamberlain, A. C.

2007-09-01

The absorbed dose response of LiF and diamond thermoluminescent dosimeters (TLDs), calibrated in 60Co γ-rays, has been determined using the MCNP4B Monte Carlo code system in mono-energetic megavoltage electron beams from 5 to 20 MeV. Evaluation of the dose responses was done against the dose responses of published works by other investigators. Dose responses of both dosimeters were compared to establish if any relation exists between them. The dosimeters were irradiated in a water phantom with the centre of their top surfaces (0.32×0.32 cm 2), placed at dmax perpendicular to the radiation beam on the central axis. For LiF TLD, dose responses ranged from 0.945±0.017 to 0.997±0.011. For the diamond TLD, the dose response ranged from 0.940±0.017 to 1.018±0.011. To correct for dose responses by both dosimeters, energy correction factors were generated from dose response results of both TLDs. For LiF TLD, these correction factors ranged from 1.003 up to 1.058 and for diamond TLD the factors ranged from 0.982 up to 1.064. The results show that diamond TLDs can be used in the place of the well-established LiF TLDs and that Monte Carlo code systems can be used in dose determinations for radiotherapy treatment planning.

Dysthymic disorder: treatment with citalopram.

PubMed

Dunner, David L; Hendricksen, Helen E; Bea, Carolyn; Budech, Chris B; Friedman, S D

2002-01-01

We studied 15 patients with dysthymic disorder with open-label citalopram. The purpose of this study was to determine the dose range and safety of citalopram necessary for treatment of patients with dysthymic disorder and to attempt to increase doses in order to enhance remission of patients with dysthymic disorder when treated. Citalopram was well tolerated. The mean dose used in this 10-week study was 37.3 mg and the majority of patients responded to treatment. Various criteria for response and remission were employed. These findings are intended to give guidelines for a subsequent treatment study of dysthymic patients with citalopram using a double-blind placebo-controlled strategy. Copyright 2002 Wiley-Liss, Inc.

Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.

PubMed

Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi W; Chappell, Phillip; Wajsbrot, Dalia B; Nagraj, Praneeta; Abbas, Richat; Palumbo, Donna

2018-06-01

To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day; participants were titrated in 10-20 mg/day increments weekly based on efficacy and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. Mean MPH ERCT daily dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1 (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1 [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

Population dose commitments due to radioactive releases from nuclear-power-plant sites in 1978

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

Peloquin, R.A.; Schwab, J.D.; Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1978. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each site. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each site is a histogram showing the fraction of the total population within 2 to 80 km around each site receiving variousmore » average dose commitments from the airborne pathways. The total dose commitment from both liquid and airborne pathways ranged from a high of 200 person-rem to a low of 0.0004 person-rem with an arithmetic mean of 14 person-rem. The total population dose for allsites was estimated at 660 person-rem for the 93 million people considered at risk. The average individual dose commitment from all pathways on a site basis ranged from a low of 3 x 10/sup -6/ mrem to a high of 0.08 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population dose commitments due to radioactive releases from Nuclear-Power-Plant Sites in 1979

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

Baker, D.A.; Peloquin, R.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1979. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each site. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each site is a histogram showing the fraction of the total population within 2 to 80 km around each site receiving variousmore » average dose commitments from the airborne pathways. The total dose commitment from both liquid and airborne pathways ranged from a high of 1300 person-rem to a low of 0.0002 person-rem with an arithmetic mean of 38 person-rem. The total population dose for all sites was estimated at 1800 person-rem for the 94 million people considered at risk. The average individual dose commitment from all pathways on a site basis ranged from a low of 2 x 10/sup -6/ mrem to a high of 0.7 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population Dose Commitments Due to Radioactive Releases from Nuclear Power Plant Sites in 1977

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

Baker, D. A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1977. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each site. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ, Also included for each site is a histogram showing the fraction of the total population within 2 to 80 km around each site receiving variousmore » average dose commitments from the airborne pathways. The total dose commitment from both liquid and airborne pathways ranged from a high of 220 person-rem to a low of 0.003 person-rem with an arithmetic mean of 16 person-rem. The total population dose for all sites was estimated at 700 person-rem for the 92 million people considered at risk. The average individual dose commitment from all pathways on a site basis ranged from a low of 2 x 10{sup -5} mrem to a high of 0.1 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Dose density in adjuvant chemotherapy for breast cancer.

PubMed

Citron, Marc L

2004-01-01

Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.

Pharmacokinetics of fixed-dose combinations of empagliflozin/metformin compared with individual tablets in healthy subjects.

PubMed

Rojas, Christina; Link, Jasmin; Meinicke, Thomas; Macha, Sreeraj

2016-04-01

To compare the pharmacokinetics of fixed-dose combination (FDC) tablets of empagliflozin/metformin with individual tablets taken together. In 3 randomized, open-label studies, healthy subjects received a single FDC tablet of empagliflozin/metformin in 1 of 6 dose combinations (empagliflozin 12.5 mg or 5 mg; metformin 500 mg, 850 mg, or 1,000 mg) in 1 period and the individual tablets taken together under fed conditions in another period. Empagliflozin 12.5 mg/metformin 1,000 mg FDC and individual tablets were also given under fasted conditions. Adjusted geometric mean ratios (GMRs) of empagliflozin area under the plasma concentration-time curve (AUC(0-∞)) for the FDCs vs. individual tablets ranged from 97.92 to 106.00%, and 90% CIs ranged from 93.53 to 109.39%. Adjusted GMRs of empagliflozin maximum plasma concentrations (C(max)) for the FDCs vs. individual tablets ranged from 100.97 to 106.52%, and 90% CIs ranged from 95.86 to 118.35%. Adjusted GMRs of metformin AUC(0-∞) for the FDCs vs. individual tablets ranged from 96.25 to 101.61%, and 90% CIs ranged from 88.54 to 106.62%. Adjusted GMRs of metformin C(max) for the FDCs vs. individual tablets ranged from 93.83 to 102.95%, and 90% CIs ranged from 88.01 to 109.08%. Bioequivalence was also established under fasted conditions for empagliflozin 12.5 mg/metformin 1,000 mg FDC vs. individual tablets taken together. All treatments were well tolerated. Empagliflozin/metformin FDC tablets were found to be bioequivalent to individual tablets taken together at all tested dose strengths.

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

Ryan, E. Ronan, E-mail: ronan@ronanryan.com; Thornton, Raymond; Sofocleous, Constantinos T.

PurposeTo quantify radiation exposure to the primary operator and staff during PET/CT-guided interventional procedures.MethodsIn this prospective study, 12 patients underwent PET/CT-guided interventions over a 6 month period. Radiation exposure was measured for the primary operator, the radiology technologist, and the nurse anesthetist by means of optically stimulated luminescence dosimeters. Radiation exposure was correlated with the procedure time and the use of in-room image guidance (CT fluoroscopy or ultrasound).ResultsThe median effective dose was 0.02 (range 0-0.13) mSv for the primary operator, 0.01 (range 0-0.05) mSv for the nurse anesthetist, and 0.02 (range 0-0.05) mSv for the radiology technologist. The median extremitymore » dose equivalent for the operator was 0.05 (range 0-0.62) mSv. Radiation exposure correlated with procedure duration and with the use of in-room image guidance. The median operator effective dose for the procedure was 0.015 mSv when conventional biopsy mode CT was used, compared to 0.06 mSv for in-room image guidance, although this did not achieve statistical significance as a result of the small sample size (p = 0.06).ConclusionThe operator dose from PET/CT-guided procedures is not significantly different than typical doses from fluoroscopically guided procedures. The major determinant of radiation exposure to the operator from PET/CT-guided interventional procedures is time spent in close proximity to the patient.« less

The Creating an Optimal Warfarin Nomogram (CROWN) Study

PubMed Central

Perlstein, Todd S.; Goldhaber, Samuel Z.; Nelson, Kerrie; Joshi, Victoria; Morgan, T. Vance; Lesko, Lawrence J.; Lee, Joo-Yeon; Gobburu, Jogarao; Schoenfeld, David; Kucherlapati, Raju; Freeman, Mason W.; Creager, Mark A.

2014-01-01

A significant proportion of warfarin dose variability is explained by variation in the genotypes of the cytochrome P450 CYP2C9 and the vitamin K epoxide reductase complex, VKORC1, enzymes that influence warfarin metabolism and sensitivity, respectively. We sought to develop an optimal pharmacogenetic warfarin dosing algorithm that incorporated clinical and genetic information. We enroled patients initiating warfarin therapy. Genotyping was performed of the VKORC1, –1639G>A, the CYP2C9*2, 430C>T, and the CYP2C9*3, 1075C>A genotypes. The initial warfarin dosing algorithm (Algorithm A) was based upon established clinical practice and published warfarin pharmacogenetic information. Subsequent dosing algorithms (Algorithms B and Algorithm C) were derived from pharmacokinetic / pharmacodynamic (PK/PD) modelling of warfarin dose, international normalised ratio (INR), clinical and genetic factors from patients treated by the preceding algorithm(s). The primary outcome was the time in the therapeutic range, considered an INR of 1.8 to 3.2. A total of 344 subjects are included in the study analyses. The mean percentage time within the therapeutic range for each subject increased progressively from Algorithm A to Algorithm C from 58.9 (22.0), to 59.7 (23.0), to 65.8 (16.9) percent (p = 0.04). Improvement also occurred in most secondary endpoints, which included the per-patient percentage of INRs outside of the therapeutic range (p = 0.004), the time to the first therapeutic INR (p = 0.07), and the time to achieve stable therapeutic anticoagulation (p < 0.001). In conclusion, warfarin pharmacogenetic dosing can be optimised in real time utilising observed PK/PD information in an adaptive fashion. Clinical Trial Registration ClinicalTrials.gov (NCT00401414) PMID:22116191

A Phase I Study of Zoledronic Acid and Low Dose Cyclophosphamide in Recurrent/Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) Study

PubMed Central

Russell, Heidi V.; Groshen, Susan G.; Ara, Tasnim; DeClerck, Yves A.; Hawkins, Randy; Jackson, Hollie A.; Daldrup-Link, Heike E.; Marachelian, Araz; Skerjanec, Andrej; Park, Julie R.; Katzenstein, Howard; Matthay, Katherine K.; Blaney, Susan M.; Villablanca, Judith G.

2010-01-01

Background Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials. Procedure Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m2/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL-6, and sIL-6R were evaluated. Results Twenty-one patients, median age 7.5 (range 0.8 - 25.6) years were treated with 2 mg/m2 (n=4), 3 mg/m2 (n=3), or 4 mg/m2 (n=14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1-18) courses was given. Two dose limiting toxicities (Grade 3 hypophosphatemia) occurred at 4 mg/m2 zoledronic acid. Other Grade 3-4 toxicities included hypocalcemia (n=2), elevated transaminases (n=1), neutropenia (n=2), anemia (n=1), lymphopenia (n=1), and hypokalemia (n=1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3-18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL-6 levels decreased with therapy. Conclusions Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m2 every 28 days. PMID:21671363

Characterization of MOSFET dosimeters for low‐dose measurements in maxillofacial anthropomorphic phantoms

PubMed Central

Wolff, Jan E.; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-01-01

The aims of this study were to characterize reinforced metal‐oxide‐semiconductor field‐effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low‐dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50–90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point‐dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k=2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low‐dose limit. The sensitivity was 3.09±0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was −8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD‐comparable low‐dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low. PACS number: 87.50.wj PMID:26219008

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.

Improvement of attention with amphetamine in low- and high-performing rats.

PubMed

Turner, Karly M; Burne, Thomas H J

2016-09-01

Attentional deficits occur in a range of neuropsychiatric disorders, such as schizophrenia and attention deficit hyperactivity disorder. Psychostimulants are one of the main treatments for attentional deficits, yet there are limited reports of procognitive effects of amphetamine in preclinical studies. Therefore, task development may be needed to improve predictive validity when measuring attention in rodents. This study aimed to use a modified signal detection task (SDT) to determine if and at what doses amphetamine could improve attention in rats. Sprague-Dawley rats were trained on the SDT prior to amphetamine challenge (0.1, 0.25, 0.75 and 1.25 mg/kg). This dose range was predicted to enhance and disrupt cognition with the effect differing between individuals depending on baseline performance. Acute low dose amphetamine (0.1 and 0.25 mg/kg) improved accuracy, while the highest dose (1.25 mg/kg) significantly disrupted performance. The effects differed for low- and high-performing groups across these doses. The effect of amphetamine on accuracy was found to significantly correlate with baseline performance in rats. This study demonstrates that improvement in attentional performance with systemic amphetamine is dependent on baseline accuracy in rats. Indicative of the inverted U-shaped relationship between dopamine and cognition, there was a baseline-dependent shift in performance with increasing doses of amphetamine. The SDT may be a useful tool for investigating individual differences in attention and response to psychostimulants in rodents.

Effect of multiple short highly energetic X-ray pulses on the synthesis of endoglucanase by a mutant strain of Trichoderma reesei-M7.

PubMed

Gemishev, Orlin; Zapryanov, Stanislav; Blagoev, Alexander; Markova, Maya; Savov, Valentin

2014-09-03

Bioconversion of cellulose-containing substrate to glucose represents an important area of modern biotechnology. Enzymes for the degradation of the polysaccharide part of biomass have been produced, mostly by fungi belonging to genus Trichoderma . Studies were carried out with the mutant strain Trichoderma reesei- M7, a cellulase producer. Spores of the enzyme producer were irradiated with different doses of characteristic X-ray radiation from metallic tungsten (mainly the W Kα1 and Kα2 lines) with a high dose rate. The latter is a specific property of the dense plasma focus (DPF) device, which has pulsed operation and thus gives short and highly energetic pulses of multiple types of rays and particles. In this case, we focused our study on the influence of hard X-rays. The doses of X-rays absorbed by the spores varied in the range of approximately 5-11,000 mSv measured with thermoluminescent dosimeters (TLD). The influence of the applied doses in combination with exceptionally high dose rates (in the order of tens of millisieverts per microsecond) on the activity of the produced endoglucanase, amount of biomass and extra-cellular protein, was studied in batch cultivation conditions. In the dose range of 200-1200 mSv, some enhancement of endoglucanase activity was obtained: around 18%-32%, despite the drop of the biomass amount, compared with the untreated material.

Effect of multiple short highly energetic X-ray pulses on the synthesis of endoglucanase by a mutant strain of Trichoderma reesei-M7

PubMed Central

Gemishev, Orlin; Zapryanov, Stanislav; Blagoev, Alexander; Markova, Maya; Savov, Valentin

2014-01-01

Bioconversion of cellulose-containing substrate to glucose represents an important area of modern biotechnology. Enzymes for the degradation of the polysaccharide part of biomass have been produced, mostly by fungi belonging to genus Trichoderma. Studies were carried out with the mutant strain Trichoderma reesei-M7, a cellulase producer. Spores of the enzyme producer were irradiated with different doses of characteristic X-ray radiation from metallic tungsten (mainly the W Kα1 and Kα2 lines) with a high dose rate. The latter is a specific property of the dense plasma focus (DPF) device, which has pulsed operation and thus gives short and highly energetic pulses of multiple types of rays and particles. In this case, we focused our study on the influence of hard X-rays. The doses of X-rays absorbed by the spores varied in the range of approximately 5–11,000 mSv measured with thermoluminescent dosimeters (TLD). The influence of the applied doses in combination with exceptionally high dose rates (in the order of tens of millisieverts per microsecond) on the activity of the produced endoglucanase, amount of biomass and extra-cellular protein, was studied in batch cultivation conditions. In the dose range of 200–1200 mSv, some enhancement of endoglucanase activity was obtained: around 18%–32%, despite the drop of the biomass amount, compared with the untreated material. PMID:26019569

Dosimetric characteristics of a PIN diode for radiotherapy application.

PubMed

Kumar, R; Sharma, S D; Philomina, A; Topkar, A

2014-08-01

The PIN diode developed by Bhabha Atomic Research Centre (BARC) was modified for its use as a dosimeter in radiation therapy. For this purpose the diode was mounted on a printed circuit board (PCB) and provided with necessary connections so that its response against irradiation can be recorded by a standard radiotherapy electrometer. The dosimetric characteristics of the diode were studied in Co-60 gamma rays as well as high energy X-rays. The measured sensitivity of this PIN diode is 4 nC/cGy which is about ten times higher than some commercial diode dosimeters. The leakage current from the diode is 0.04 nA. The response of the PIN diode is linear in the range of 20-1000 cGy which covers the full range of radiation dose encountered in radiotherapy treatments. The non-linearity of the diode response is 3.5% at 20 cGy and it is less than 1.5% at higher dose values. Its repeatability is within 0.5%. The angular response variation is about 5.6% within 6608 with respect to normal beam incidence. The response of the PIN diode at 6 and 18 MV X-rays varies within 2% with respect to its response at Co-60 gamma rays. The source to surface distance (SSD) dependence of the PIN diode was studied for Co-60 beam. It was found that the response of the diode decreases almost linearly relative to given dose for beams with constant collimator setting but increasing SSD (decreasing dose-rate). Within this study the diode response varied by about 2.5% between the maximum and minimum SSD. The dose-rate dependence of the PIN diode for 6 and 15 MV-rays was studied. The variation in response of diode for both energies in the studied dose range is less than 1%. The field size dependence of the PIN diode response is within 1% with respect to the response of ionisation chamber. These studies indicate that the characteristics of the PIN diode are suitable for use in radiotherapy dosimetry.

Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sites

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

Zorlu, Faruk; Dugel, Gozde; Ozyigit, Gokhan

Purpose: The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations. Methods: The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotalmore » skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). Results: The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035-2.71 Gy) and 0.34 Gy (range, 0.066-3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03-0.159 Gy) and 0.05 Gy (range, 0.015-0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056-1.97 Gy) and 0.306 Gy (range, 0.065-2.25 Gy). Conclusions: Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.« less

Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

PubMed

Yorbik, Ozgur; Mutlu, Caner; Ozilhan, Selma; Eryilmaz, Gul; Isiten, Nuket; Alparslan, Serdar; Saglam, Esra

2015-06-01

There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.

LiF TLD-100 as a dosimeter in high energy proton beam therapy--can it yield accurate results?

PubMed

Zullo, John R; Kudchadker, Rajat J; Zhu, X Ronald; Sahoo, Narayan; Gillin, Michael T

2010-01-01

In the region of high-dose gradients at the end of the proton range, the stopping power ratio of the protons undergoes significant changes, allowing for a broad spectrum of proton energies to be deposited within a relatively small volume. Because of the potential linear energy transfer dependence of LiF TLD-100 (thermolumescent dosimeter), dose measurements made in the distal fall-off region of a proton beam may be less accurate than those made in regions of low-dose gradients. The purpose of this study is to determine the accuracy and precision of dose measured using TLD-100 for a pristine Bragg peak, particularly in the distal fall-off region. All measurements were made along the central axis of an unmodulated 200-MeV proton beam from a Probeat passive beam-scattering proton accelerator (Hitachi, Ltd., Tokyo, Japan) at varying depths along the Bragg peak. Measurements were made using TLD-100 powder flat packs, placed in a virtual water slab phantom. The measurements were repeated using a parallel plate ionization chamber. The dose measurements using TLD-100 in a proton beam were accurate to within +/-5.0% of the expected dose, previously seen in our past photon and electron measurements. The ionization chamber and the TLD relative dose measurements agreed well with each other. Absolute dose measurements using TLD agreed with ionization chamber measurements to within +/- 3.0 cGy, for an exposure of 100 cGy. In our study, the differences in the dose measured by the ionization chamber and those measured by TLD-100 were minimal, indicating that the accuracy and precision of measurements made in the distal fall-off region of a pristine Bragg peak is within the expected range. Thus, the rapid change in stopping power ratios at the end of the range should not affect such measurements, and TLD-100 may be used with confidence as an in vivo dosimeter for proton beam therapy. Copyright 2010 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

A Long-Acting Human Growth Hormone With Delayed Clearance (VRS-317): Results of a Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Growth Hormone–Deficient Adults

PubMed Central

Yuen, Kevin C. J.; Conway, Gerard S.; Popovic, Vera; Merriam, George R.; Bailey, Timothy; Hamrahian, Amir H.; Biller, Beverly M. K.; Kipnes, Mark; Moore, Jerome A.; Humphriss, Eric; Cleland, Jeffrey L.

2013-01-01

Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3–5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between −1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing. PMID:23585663

Preoperative single fraction partial breast radiotherapy for early-stage breast cancer.

PubMed

Palta, Manisha; Yoo, Sua; Adamson, Justus D; Prosnitz, Leonard R; Horton, Janet K

2012-01-01

Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. The median breast volume was 1,713 cm(3) (range: 1,014-2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute effects of a wild green-oat (Avena sativa) extract on cognitive function in middle-aged adults: A double-blind, placebo-controlled, within-subjects trial.

PubMed

Kennedy, David O; Jackson, Philippa A; Forster, Joanne; Khan, Julie; Grothe, Torsten; Perrinjaquet-Moccetti, Tania; Haskell-Ramsay, Crystal F

2017-02-01

A wild green-oats extract (Neuravena ® ) containing a range of potentially bioactive components, including flavonoids and triterpene saponins, has previously been shown to enhance animal stress responses and memory, and improve cognitive performance in humans at a dose of 1600 mg. Methods This double-blind, placebo-controlled, counterbalanced cross-over study assessed the effects of single doses of the green-oat extract (GOE) across a broad range of cognitive domains in healthy adults aged 40-65 years who self-reported that they felt that their memory had declined with age. Participants attended on six occasions, receiving a single dose of either placebo, 800, or 1600 mg GOE on each occasion, with the counterbalanced order of treatments repeated twice for each participant. Cognitive function was assessed with a range of computerized tasks measuring attention, spatial/working/episodic memory, and executive function pre-dose and at 1, 2.5, 4, and 6 hours post-dose. Results The results showed that 800mg GOE increased the speed of performance across post-dose assessments on a global measure including data from all of the timed tasks. It also improved performance of a delayed word recall task in terms of errors and an executive function task (Peg and Ball) in terms of decreased thinking time and overall completion time. Working memory span (Corsi blocks) was also increased, but only on the second occasion that this dose was taken. Discussion These results confirm the acute cognitive effects of GOE seen in previous research, and suggest that the optimal dose lies at or below 800 mg.

Effect of gamma irradiation on the color, structure and morphology of nickel-doped polyvinyl alcohol films: Alternative use as dosimeter or irradiation indicator

NASA Astrophysics Data System (ADS)

Raouafi, A.; Daoudi, M.; Jouini, K.; Charradi, K.; Hamzaoui, A. H.; Blaise, P.; Farah, K.; Hosni, F.

2018-06-01

Nickel-doped poly vinyl alcohol (PVA) films were developed for potential application in industrial sectors like radiation processing. We report in this paper the results of an experimental investigation of 60Co source γ-radiation effect on colorimetric, structural and morphological properties of PVA films doped with 0.5% Ni2+ ions (PVA/Ni2+). The PVA/Ni2+ films were irradiated by different gamma-radiation doses varying from 5 to 100 kGy. Color modification of films were studied using L∗, a∗ and b∗ color space measurements as function of the γ-dose and post-irradiation time. The visual change in all samples was verified by microstructure analysis, Fourier transforms infrared (FTIR) spectroscopy, X-Rays diffraction (XRD) and scanning electron microscopy (SEM). The color space exhibited a linear dose response at a dose ranging from 5 to 50 kGy, and then it reached saturation for higher γ-doses. The calculated color changes (ΔE) show a linear dose response relationship from 9.90 to 115.02 in the dose range from 0 to 50 kGy. It showed also the activation of stable color centers. The variability of the color change did not exceed 3% during 80 h (h) post-irradiation. Furthermore, the microstructure analysis evidenced that the color modification due to the optical activation of nickel-oxide (NiO) color center were obtained by complexing Ni2+ ions in irradiated PVA films. The obtained results inspire the possibility to use PVA films for the control process in industrial radiation facilities in dose range 5-50 kGy.

Peripheral organ doses from radiotherapy for heterotopic ossification of non-hip joints: is there a risk for radiation-induced malignancies?

PubMed

Berris, Theocharis; Mazonakis, Michalis; Kachris, Stefanos; Damilakis, John

2014-05-01

Radiotherapy, used for heterotopic ossification (HO) management, may increase radiation risk to patients. This study aimed to determine the peripheral dose to radiosensitive organs and the associated cancer risks due to radiotherapy of HO in common non-hip joints. A Monte Carlo model of a medical linear accelerator combined with a mathematical phantom representing an average adult patient were employed to simulate radiotherapy for HO with standard AP and PA fields in the regions of shoulder, elbow and knee. Radiation dose to all out-of-field radiosensitive organs defined by the International Commission on Radiological Protection was calculated. Cancer induction risk was estimated using organ-specific risk coefficients. Organ dose change with increased field dimensions was also evaluated. Radiation therapy for HO with a 7 Gy target dose in the sites of shoulder, elbow and knee, resulted in the following equivalent organ dose ranges of 0.85-62 mSv, 0.28-1.6 mSv and 0.04-1.6 mSv, respectively. Respective ranges for cancer risk were 0-5.1, 0-0.6 and 0-1.3 cases per 10(4) persons. Increasing the field size caused an average increase of peripheral doses by 15-20%. Individual organ dose increase depends upon the primary treatment site and the distance between organ of interest and treatment volume. Relatively increased risks of more than 1 case per 10,000 patients were found for skin, breast and thyroid malignancies after treatment in the region of shoulder and for skin cancer following elbow irradiation. The estimated risk for inducing any other malignant disease ranges from negligible to low. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Poster - Thur Eve - 03: LDR to HDR: RADPOS applications in brachytherapy.

PubMed

Cherpak, A J; Cygler, J E; Kertzscher, G; E, C; Perry, G

2012-07-01

The RADPOS in vivo dosimetry system combines an electromagnetic positioning sensor and either one or five MOSFET dosimeters. The feasibility of using the system for quality control has been explored for a range of radiotherapy treatment techniques including most recently transperineal interstitial permanent prostate brachytherapy and high dose rate (HDR) treatments. Dose and position information was collected by a RADPOS array detector inside a Foley catheter within patients' urethra during permanent seed implantation. Ten patients were studied, and average displacement during implantation was Δr = (1.4-5.1) mm, with movements up to 9.7 mm due to the removal of the transrectal ultrasound probe. Maximum integral dose in the prostatic urethra ranged from 110-195 Gy, and it was found that the dose can change up to 63 cGy (62.0%) depending on whether the rectal probe is in place. For HDR, a RADPOS detector was first calibrated with an Ir-192 source. A treatment was then simulated using a total of 50 dwell positions in 5 catheters in an acrylic phantom. Dwell positions ranged from 1 to 10 cm away from the RADPOS detector and dose was measured for each source position. An average calibration coefficient of 0.74±0.11 cGy/mV was calculated for the detector and the average absolute difference between measured values and expected dose was 0.7±5.4 cGy (5±20%). The demonstrated accuracy of RADPOS dose measurements along with its ability to simultaneously measure displacement makes it a powerful tool for brachytherapy treatments, where high dose gradients can present unique in vivo dosimetry challenges. © 2012 American Association of Physicists in Medicine.

Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy Quality Assurance

PubMed Central

Liuzzi, Raffaele; Savino, Federica; D’Avino, Vittoria; Pugliese, Mariagabriella; Cella, Laura

2015-01-01

Background Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT) beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2–12 cGy/pulse) during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters. Methods LiF:Mg,Ti dosimeters (TLD-100) were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0–10 Gy in step of 2Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy. Results The TLD-100 dose-response curves were obtained. In the dose range of 0–10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05). Conclusions This study demonstrates that the TLD dose response, for doses ≤10Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided. PMID:26427065

Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy Quality Assurance.

PubMed

Liuzzi, Raffaele; Savino, Federica; D'Avino, Vittoria; Pugliese, Mariagabriella; Cella, Laura

2015-01-01

Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT) beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2-12 cGy/pulse) during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters. LiF:Mg,Ti dosimeters (TLD-100) were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0-10 Gy in step of 2 Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy. The TLD-100 dose-response curves were obtained. In the dose range of 0-10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05). This study demonstrates that the TLD dose response, for doses ≤10 Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided.

Measurement of eye lens dose for Varian On-Board Imaging with different cone-beam computed tomography acquisition techniques

PubMed Central

Deshpande, Sudesh; Dhote, Deepak; Thakur, Kalpna; Pawar, Amol; Kumar, Rajesh; Kumar, Munish; Kulkarni, M. S.; Sharma, S. D.; Kannan, V.

2016-01-01

The objective of this work was to measure patient eye lens dose for different cone-beam computed tomography (CBCT) acquisition protocols of Varian's On-Board Imaging (OBI) system using optically stimulated luminescence dosimeter (OSLD) and to study the variation in eye lens dose with patient geometry and distance of isocenter to the eye lens. During the experimental measurements, OSLD was placed on the patient between the eyebrows of both eyes in line of nose during CBCT image acquisition to measure eye lens doses. The eye lens dose measurements were carried out for three different cone-beam acquisition protocols (standard dose head, low-dose head [LDH], and high-quality head [HQH]) of Varian OBI. Measured doses were correlated with patient geometry and distance between isocenter and eye lens. Measured eye lens doses for standard head and HQH protocols were in the range of 1.8–3.2 mGy and 4.5–9.9 mGy, respectively. However, the measured eye lens dose for the LDH protocol was in the range of 0.3–0.7 mGy. The measured data indicate that eye lens dose to patient depends on the selected imaging protocol. It was also observed that eye lens dose does not depend on patient geometry but strongly depends on distance between eye lens and treatment field isocenter. However, undoubted advantages of imaging system should not be counterbalanced by inappropriate selection of imaging protocol, especially for very intense imaging protocol. PMID:27651564

Kilovoltage Imaging Doses in the Radiotherapy of Pediatric Cancer Patients

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

Deng Jun, E-mail: jun.deng@yale.edu; Chen Zhe; Roberts, Kenneth B.

Purpose: To investigate doses induced by kilovoltage cone-beam computed tomography (kVCBCT) to pediatric cancer patients undergoing radiotherapy, as well as strategies for dose reduction. Methods and Materials: An EGS4 Monte Carlo code was used to calculate three-dimensional dose deposition due to kVCBCT on 4 pediatric cancer patients. Absorbed doses to various organs were analyzed for both half-fan and full-fan modes. Clinical conditions, such as distance from organ at risk (OAR) to CBCT field border, kV peak energy, and testicular shielding, were studied. Results: The mean doses induced by one CBCT scan operated at 125 kV in half-fan mode to testes,more » liver, kidneys, femoral heads, spinal cord, brain, eyes, lens, and optical nerves were 2.9, 4.7, 7.7, 10.5, 8.8, 7.6, 7.7, 7.8, and 7.2 cGy, respectively. Increasing the distances from OARs to CBCT field border greatly reduced the doses to OARs, ranging from 33% reduction for spinal cord to 2300% reduction for testes. As photon beam energy increased from 60 to 125 kV, the dose increase due to kVCBCT ranged from 170% for lens to 460% for brain and spinal cord. A testicular shielding made of 1-cm cerrobend could reduce CBCT doses down to 31%, 51%, 68%, and 82%, respectively, for 60, 80, 100, and 125 kV when the testes lay within the CBCT field. Conclusions: Generally speaking, kVCBCT deposits much larger doses to critical structures in children than in adults, usually by a factor of 2 to 3. Increasing the distances from OARs to CBCT field border greatly reduces doses to OARs. Depending on OARs, kVCBCT-induced doses increase linearly or exponentially with photon beam energy. Testicular shielding works more efficiently at lower kV energies. On the basis of our study, it is essential to choose an appropriate scanning protocol when kVCBCT is applied to pediatric cancer patients routinely.« less

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

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

Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from themore » histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.« less

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

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

Chung, Eugene; Corbett, James R.; Moran, Jean M.

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses tomore » the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.« less

SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

PubMed

Troeller, A; Soehn, M; Yan, D

2012-06-01

Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way it is commonly done for the gEUD. © 2012 American Association of Physicists in Medicine.

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.

Dual Inhibition of the Epidermal Growth Factor Receptor Pathway with Cetuximab and Erlotinib: A Phase I Study in Patients with Advanced Solid Malignancies

PubMed Central

Guarino, Michael J.; Schneider, Charles J.; Hosford, Martha A.; Brahmer, Julie R.; Rudin, Charles M.; Finckenstein, Friedrich Graf; Philip-Norton, Robyn E.; Lu, Haolan; Weber, Martin R.; Ettinger, David S.

2017-01-01

Purpose To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies. Patients and Methods Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m2 i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity. Results Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1–31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1–25.1 weeks). Conclusion Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m2 i.v. weekly for cetuximab and 150 mg daily orally for erlotinib. PMID:19182243

The cytokinesis-blocked micronucleus assay: dose-response calibration curve, background frequency in the population and dose estimation.

PubMed

Rastkhah, E; Zakeri, F; Ghoranneviss, M; Rajabpour, M R; Farshidpour, M R; Mianji, F; Bayat, M

2016-03-01

An in vitro study of the dose responses of human peripheral blood lymphocytes was conducted with the aim of creating calibrated dose-response curves for biodosimetry measuring up to 4 Gy (0.25-4 Gy) of gamma radiation. The cytokinesis-blocked micronucleus (CBMN) assay was employed to obtain the frequencies of micronuclei (MN) per binucleated cell in blood samples from 16 healthy donors (eight males and eight females) in two age ranges of 20-34 and 35-50 years. The data were used to construct the calibration curves for men and women in two age groups, separately. An increase in micronuclei yield with the dose in a linear-quadratic way was observed in all groups. To verify the applicability of the constructed calibration curve, MN yields were measured in peripheral blood lymphocytes of two real overexposed subjects and three irradiated samples with unknown dose, and the results were compared with dose values obtained from measuring dicentric chromosomes. The comparison of the results obtained by the two techniques indicated a good agreement between dose estimates. The average baseline frequency of MN for the 130 healthy non-exposed donors (77 men and 55 women, 20-60 years old divided into four age groups) ranged from 6 to 21 micronuclei per 1000 binucleated cells. Baseline MN frequencies were higher for women and for the older age group. The results presented in this study point out that the CBMN assay is a reliable, easier and valuable alternative method for biological dosimetry.

Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.

PubMed

Dolton, Michael J; Perera, Vidya; Pont, Lisa G; McLachlan, Andrew J

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

Estimation of annual effective dose due to ingestion of natural radionuclides in foodstuffs and water at a proposed uranium mining site in India.

PubMed

Giri, Soma; Jha, V N; Singh, Gurdeep; Tripathi, R M

2013-12-01

To study the distribution of (210)Po, (226)Ra, (230)Th and U(nat) (naturally occurring radioisotopes of uranium [(234)U, (235)U and (238)U]) in food and water around the Bagjata uranium mining area in India. Radionuclides were analyzed in food samples of plant and animal origin after acid digestion. Intake and ingestion dose of the radionuclides were estimated. (210)Po, (226)Ra, (230)Th and U(nat) in all the dietary components ranged widely from < 0.2-36, < 0.02-1.58, < 0.01-2.8 and < 0.017-0.39 Bqkg(-1), respectively. The range of (226)Ra and U(nat) in water was < 3.5-206 and < 12.6-693 mBql(-1), respectively. The intake of radionuclides considering food and water was calculated to be 760 BqY(-1) while the ingestion dose was 601 μSvY(-1). The estimated doses reflect the natural background dose via route of ingestion, which is below the 1 mSvY(-1) limit set by the International Commission on Radiological Protection (ICRP). However, the doses are more than the dose constraint of 300 μSvY(-1) as suggested by the ICRP for members of the public for planned disposal of long-lived radioactive waste. The study confirms that current levels of radionuclides do not pose significant radiological risk to the local inhabitants, but they need close investigation in the near future.

Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-PHNO.

PubMed

Tateno, Amane; Sakayori, Takeshi; Kim, Woo-Chan; Honjo, Kazuyoshi; Nakayama, Haruo; Arakawa, Ryosuke; Okubo, Yoshiro

2018-06-01

Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%-84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%-88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%-87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%-88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.

Dosimetric characteristics of PASSAG as a new polymer gel dosimeter with negligible toxicity

NASA Astrophysics Data System (ADS)

Farhood, Bagher; Abtahi, Seyed Mohammad Mahdi; Geraily, Ghazale; Ghorbani, Mehdi; Mahdavi, Seied Rabi; Zahmatkesh, Mohammad Hasan

2018-06-01

Despite many advantages of polymer gel dosimeters, their clinical use is only not realized now. Toxicity of polymer gel dosimeters can be considered as one of their main limitations for use in routine clinical applications. In the current study, a new polymer gel dosimeter is introduced with negligible toxicity. For this purpose, 2-Acrylamido-2-Methy-1-PropaneSulfonic acid (AMPS) sodium salt monomer was replaced instead of acrylamide monomer used in PAGAT gel dosimeter by using %6 T and %50 C to the gel formula and the new formulation is called PASSAG (Poly AMPS Sodium Salt and Gelatin) polymer gel dosimeter. The irradiation of gel dosimeters was carried out using a Co-60 therapy machine. MRI technique was used to quantify the dose responses of the PASSAG gel dosimeter. Then, the MRI responses (R2) of the gel dosimeter was analyzed at different dose values, post-irradiation times, and scanning temperatures. The results showed that the new gel formulation has a negligible toxicity and it is also eco-friendly. In addition, carcinogenicity and genetic toxicity tests are negative for the monomer used in PASSAG. The radiological properties of PASSAG gel dosimeter showed that this substance can be considered as a soft tissue/water equivalent material. Furthermore, dosimetric evaluation of the new polymer gel dosimeter revealed an excellent linear R2-dose response in the evaluated dose range (0-15 Gy). The R2-dose sensitivity and dose resolution of PASSAG gel dosimeter were 0.081 s-1Gy-1 (in 0-15 Gy dose range) and 1 Gy (in 0-10 Gy dose range), respectively. Moreover, it was shown that the R2-dose sensitivity and dose resolution of the new gel dosimeter improves over time after irradiation. It was also found that the R2 response of the PASSAG gel dosimeter has less dependency to the 18, 20, and 24 °C scanning temperature in comparison to that of room temperature (22 °C).

Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B: applying mechanistic modeling to enable preclinical to clinical translation and guide clinical trial design.

PubMed

Vugmeyster, Yulia; Rohde, Cynthia; Perreault, Mylene; Gimeno, Ruth E; Singh, Pratap

2013-01-01

TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD) data (e.g., body weight gain) obtained in lean cynomolgus and obese rhesus monkeys following single doses ranging from 0.3 to 60 mg/kg. A target-mediated drug disposition (TMDD) model was used to describe the observed nonlinear PK and Emax approach was used to describe the observed dose-dependent PD effect. The TMDD model development was supported by the experimental determination of the binding affinity constant (9.4 nM) and internalization rate of the drug-target complex (2.08 h(-1)). These mechanistic analyses enabled linking of exposure, target (TrkB) coverage, and pharmacological activity (e.g., PD) in monkeys, and indicated that ≥ 38% target coverage (time-average) was required to achieve significant body weight gain in monkeys. Based on the scaling of the TMDD model from monkeys to humans and assuming similar relationship between the target coverage and pharmacological activity between monkey and humans, subcutaneous (SC) doses of 1 and 15 mg/kg in humans were projected to be the minimally and the fully pharmacologically active doses, respectively. Based on the minimal anticipated biological effect level (MABEL) approach for starting dose selection, the dose of 0.05 mg/kg (3 mg for a 60 kg human) SC was recommended as the starting dose for FIH trials, because at this dose level<10% target coverage was projected at Cmax (and all other time points). This study illustrates a rational mechanistic approach for the selection of FIH dose range for a therapeutic protein with a complex model of action.

Extrapolation of plasma clearance to understand species differences in toxicokinetics of bisphenol A.

PubMed

Poet, Torka; Hays, Sean

2017-10-13

1. Understanding species differences in the toxicokinetics of bisphenol A (BPA) is central to setting acceptable exposure limits for human exposures to BPA. BPA toxicokinetics have been well studied, with controlled oral dosing studies in several species and across a wide dose range. 2. We analyzed the available toxicokinetic data for BPA following oral dosing to assess potential species differences and dose dependencies. BPA is rapidly conjugated and detoxified in all species. The toxicokinetics of BPA can be well described using non-compartmental analyses. 3. Several studies measured free (unconjugated) BPA in blood and reported area under the curve (AUC) of free BPA in blood of mice, rats, monkeys, chimpanzees and humans following controlled oral doses. Extrinsic clearance was calculated and analyzed across species and dose using allometric scaling. 4. The results indicate free BPA clearance is well described using allometric scaling with high correlation coefficients across all species and doses up to 10 mg/kg. The results indicate a human equivalent dose factor (HEDf) of 0.9 is appropriate for extrapolating a point of departure from mice and rats to a human equivalent dose (HED), thereby replacing default uncertainty factors for animal to human toxicokinetics.

Accuracy of Monte Carlo simulations compared to in-vivo MDCT dosimetry.

PubMed

Bostani, Maryam; Mueller, Jonathon W; McMillan, Kyle; Cody, Dianna D; Cagnon, Chris H; DeMarco, John J; McNitt-Gray, Michael F

2015-02-01

The purpose of this study was to assess the accuracy of a Monte Carlo simulation-based method for estimating radiation dose from multidetector computed tomography (MDCT) by comparing simulated doses in ten patients to in-vivo dose measurements. MD Anderson Cancer Center Institutional Review Board approved the acquisition of in-vivo rectal dose measurements in a pilot study of ten patients undergoing virtual colonoscopy. The dose measurements were obtained by affixing TLD capsules to the inner lumen of rectal catheters. Voxelized patient models were generated from the MDCT images of the ten patients, and the dose to the TLD for all exposures was estimated using Monte Carlo based simulations. The Monte Carlo simulation results were compared to the in-vivo dose measurements to determine accuracy. The calculated mean percent difference between TLD measurements and Monte Carlo simulations was -4.9% with standard deviation of 8.7% and a range of -22.7% to 5.7%. The results of this study demonstrate very good agreement between simulated and measured doses in-vivo. Taken together with previous validation efforts, this work demonstrates that the Monte Carlo simulation methods can provide accurate estimates of radiation dose in patients undergoing CT examinations.

A study of the parameters affecting the effectiveness of Moringa oleifera in drinking water purification

NASA Astrophysics Data System (ADS)

Pritchard, M.; Craven, T.; Mkandawire, T.; Edmondson, A. S.; O'Neill, J. G.

The powder obtained from the seeds of the Moringa oleifera tree has been shown to be an effective primary coagulant for water treatment. When the seeds are dried, dehusked, crushed and added to water, the powder acts as a coagulant binding colloidal particles and bacteria to form agglomerated particles (flocs), which settle allowing the clarified supernatant to be poured off. Very little research has been undertaken on the parameters affecting the effectiveness of M. oleifera, especially in Malawi, for purification of drinking water and there is a great need for further testing in this area. Conclusive data needs to be compiled to demonstrate the effects of various water parameters have on the efficiency of the seeds. A parametric study was undertaken at Leeds Metropolitan University, UK, with the aim to establish the most appropriate dosing method; the optimum dosage for removal of turbidity; the influence of pH and temperature; together with the shelf life of the M. oleifera seeds. The study revealed that the most suitable dosing method was to mix the powder into a concentrated paste, hence forming a stock suspension. The optimum M. oleifera dose, for turbidity values between 40 and 200 NTU, ranged between 30 and 55 mg/l. With turbidity set at 130 NTU and a M. oleifera dose within the optimum range at 50 mg/l, pH levels were varied between 4 and 9. It was discovered that the coagulant performance was not too sensitive to pH fluctuations when conditions were within the optimum range. The most efficient coagulation, determined by the greatest reduction in turbidity, occurred at pH 6.5. Alkaline conditions were overall more favourable than acidic conditions; pH 9 had an efficiency of 65% of optimum, whilst at pH 5 the efficiency dropped to around 55%. The efficiency further dropped at pH 4, where the powder only produced results of around 10% of optimum conditions. A temperature range of 4-60 °C was studied in this research. Colder waters (<15 °C) were found to hinder the effectiveness of the coagulation process. The higher the temperature the more effective was the coagulation. It was also found that the age of the seeds, up to 18 months, did not have any noticeable effect on dose level and percentage reduction in turbidity, although at 18 months the seeds had a narrower dosing range to produce near-optimum reduction. Seeds aged 24 months showed a significant decline in coagulant efficiency.

A study of atmospheric dispersion of radionuclides at a coastal site using a modified Gaussian model and a mesoscale sea breeze model

NASA Astrophysics Data System (ADS)

Venkatesan, R.; Mathiyarasu, R.; Somayaji, K. M.

Ground level concentration and sky-shine dose due to radioactive emissions from a nuclear power plant at a coastal site have been estimated using the standard Gaussian Plume Model (GPM) and the modified GPM suggested by Misra (Atmospheric Environment 14 (1980) 397), which incorporates fumigation effect under sea breeze condition. The difference in results between these two models is analysed in order to understand their significance and errors that would occur if proper choice were not made. Radioactive sky-shine dose from 41Ar, emitted from a 100 m stack of the nuclear plant is continuously recorded by environmental gamma dose monitors and the data is used to validate the modified GPM. It is observed that the dose values increase by a factor of about 2 times than those of the standard GPM estimates, up to a downwind distance of 6 km during sea breeze hours. In order to examine the dispersion of radioactive effluents in the mesoscale range, a sea breeze model coupled with a particle dispersion model is used. The deposited activity, thyroid dose and sky-shine radioactive dose are simulated for a range of 30 km. In this range, the plume is found to deviate from its straight-line trajectory, as otherwise assumed in GPM. A secondary maximum in the concentration and the sky-shine dose is also observed in the model results. These results are quite significant in realistically estimating the area affected under any unlikely event of an accidental release of radioactivity.

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

Liang, Xiaodong, E-mail: lxdctopone@sina.com; Ni, Lingqin; Hu, Wei

The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 tomore » 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.« less

Margin estimation and disturbances of irradiation field in layer-stacking carbon-ion beams for respiratory moving targets.

PubMed

Tajiri, Shinya; Tashiro, Mutsumi; Mizukami, Tomohiro; Tsukishima, Chihiro; Torikoshi, Masami; Kanai, Tatsuaki

2017-11-01

Carbon-ion therapy by layer-stacking irradiation for static targets has been practised in clinical treatments. In order to apply this technique to a moving target, disturbances of carbon-ion dose distributions due to respiratory motion have been studied based on the measurement using a respiratory motion phantom, and the margin estimation given by the square root of the summation Internal margin2+Setup margin2 has been assessed. We assessed the volume in which the variation in the ratio of the dose for a target moving due to respiration relative to the dose for a static target was within 5%. The margins were insufficient for use with layer-stacking irradiation of a moving target, and an additional margin was required. The lateral movement of a target converts to the range variation, as the thickness of the range compensator changes with the movement of the target. Although the additional margin changes according to the shape of the ridge filter, dose uniformity of 5% can be achieved for a spherical target 93 mm in diameter when the upward range variation is limited to 5 mm and the additional margin of 2.5 mm is applied in case of our ridge filter. Dose uniformity in a clinical target largely depends on the shape of the mini-peak as well as on the bolus shape. We have shown the relationship between range variation and dose uniformity. In actual therapy, the upper limit of target movement should be considered by assessing the bolus shape. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

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

PubMed

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

2011-05-01

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

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

PubMed Central

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

2011-01-01

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

Effect of supplementation with flaxseed oil and different doses of fish oil for 2 weeks on plasma phosphatidylcholine fatty acids in young women.

PubMed

Hodson, Leanne; Crowe, Francesca L; McLachlan, Kirsten J; Skeaff, C Murray

2018-06-01

Although assumed, it remains unclear that fatty acid (FA) biomarkers of n-3 long-chain PUFA reflect wide ranges of intake. However, to be utilised as biomarkers, to predict dietary intake, dose-response curves that cover a spectrum of intakes are required. The aim of the study was to investigate whether the FA composition of plasma phosphatidylcholine (PC) is a sensitive biomarker of n-3 FAs from fish oil, across a range of supplementation doses, and alpha-linolenic acid (ALA) supplementation, in young, healthy women. A total of 303 young women were randomised to intakes ranging between 0.33 and 4.50 g EPA+DHA/day from fish oil (not all doses used in each year) or flaxseed oil (5.90-6.60 g/d) daily for 14 days in a series of trials, over 5 years. Fasting blood was collected at baseline (day 0) and day 14 and plasma PC FA composition, total and HDL-cholesterol and triglyceride concentrations measured. Fourteen days supplementation with fish oil significantly (P < 0.01) increased, in a dose-dependent fashion, plasma PC EPA, DPA and DHA at all doses except 1 and 3 mL/day. For the combined group of women who consumed any fish oil there was a 16% (P < 0.01) decrease in plasma triacylglycerol concentrations after 14 days supplementation. Flaxseed oil supplementation for 14 day resulted in significant (P < 0.01) increases in ALA, EPA and DPA, whilst DHA remained unchanged. Our data demonstrate plasma PC is a sensitive biomarker of n-3 FA intake and reflects changes within 14 days across a range of intakes.

A dose-volume analysis of magnetic resonance imaging-aided high-dose-rate image-based interstitial brachytherapy for uterine cervical cancer.

PubMed

Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

2010-07-01

To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results. (c) 2010 Elsevier Inc. All rights reserved.

Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

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

Liu, B.; Huang, R.; Kuang, A.

2011-10-15

Purpose: The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ({sup 131}I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of {sup 131}I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Methods: Seventy-eight consecutive DTC patients (mean age 45 {+-} 17 years, 60%, female) undergoing {sup 131}I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of {sup 131}I to assess kinetics in themore » salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. Results: The maximum uptakes in percentage of administered {sup 131}I activity per kilogram of gland tissue (%/kg) were 12.9% {+-} 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% {+-} 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of {sup 131}I in the parotid and submandibular glands were 9.3 {+-} 3.5 h (range, 1.5-19.8 h) and 8.6 {+-} 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 {+-} 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 {+-} 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose contribution. Photon-absorbed dose fractions of total absorbed dose were 4.9% {+-} 1.3% (range, 1.1%-8.7%) and 3.7% {+-} 2.5% (range, 0.8%-7.9%) for the parotid and submandibular glands, respectively. Conclusions: The iodine uptake of salivary glands is continuously reduced during the courses of therapy. The phenomenon of hyper-radiosensitivity may to some extent account for the occurrence of salivary gland hypofunction at very low radiation doses with low dose rates in {sup 131}I therapy. On the other hand, failure to incorporate a nonuniform and preferential uptake by salivary gland ductal cells may result in underestimating the actual dose for the critical tissue. Other methods, including {sup 124}I voxel-based dosimetry, are warranted to further investigate the {sup 131}I-induced salivary gland toxicity.« less

Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.

PubMed

Elmore, E; Lao, X-Y; Kapadia, R; Redpath, J L

2009-06-01

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

Phase I safety, pharmacokinetic, and pharmacodynamic study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced cancer.

PubMed

Hoekstra, Ronald; de Vos, Filip Y F L; Eskens, Ferry A L M; Gietema, Jourik A; van der Gaast, Ate; Groen, Harry J M; Knight, Raymond A; Carr, Robert A; Humerickhouse, Rod A; Verweij, Jaap; de Vries, Elisabeth G E

2005-08-01

ABT-510 is an angiogenesis inhibitor derived from thrombospondin-1, a naturally occurring inhibitor of angiogenesis. We investigated ABT-510, which was administered subcutaneously in patients with advanced solid malignancies, to assess safety, pharmacokinetics, and serum markers of angiogenesis. ABT-510 was administered subcutaneously as a continuous infusion (100 mg/24 h) and bolus injections (100, 200, and 260 mg once daily; 50 and 100 mg twice daily) in 28-day cycles. Thirty-nine patients received a total of 144 treatment cycles. Administration by continuous infusion was hampered by the onset of painful skin infiltrates at the injection site. In the bolus injection regimens, the most common toxicities observed were mild injection-site reactions and fatigue. Maximum-tolerated dose was not defined, but 260 mg was defined as the maximum clinically practical dose. ABT-510 pharmacokinetics were linear across the dosage ranges tested, and the potential therapeutic threshold (plasma concentrations > 100 ng/mL > 3 h/d) was achieved with all dose regimens. Median serum basic fibroblast growth factor (bFGF) levels decreased from 14.1 pg/mL (range, 0.5 to 77.7 pg/mL) at baseline to 3.2 pg/mL (range, 0.2 to 29.4 pg/mL) after 56 days of treatment (P = .003). No correlations with time on study or ABT-510 dose or exposure were observed for individual changes in bFGF. Stable disease lasting for six cycles or more was seen in six patients. ABT-510 demonstrated a favorable toxicity profile and linear and time-independent pharmacokinetics with biologically relevant plasma concentrations. The significant number of patients with prolonged stable disease and the convenient method of dosing merit further studies with this angiogenesis inhibitor.

Current worldwide nuclear cardiology practices and radiation exposure: results from the 65 country IAEA Nuclear Cardiology Protocols Cross-Sectional Study (INCAPS).

PubMed

Einstein, Andrew J; Pascual, Thomas N B; Mercuri, Mathew; Karthikeyan, Ganesan; Vitola, João V; Mahmarian, John J; Better, Nathan; Bouyoucef, Salah E; Hee-Seung Bom, Henry; Lele, Vikram; Magboo, V Peter C; Alexánderson, Erick; Allam, Adel H; Al-Mallah, Mouaz H; Flotats, Albert; Jerome, Scott; Kaufmann, Philipp A; Luxenburg, Osnat; Shaw, Leslee J; Underwood, S Richard; Rehani, Madan M; Kashyap, Ravi; Paez, Diana; Dondi, Maurizio

2015-07-07

To characterize patient radiation doses from nuclear myocardial perfusion imaging (MPI) and the use of radiation-optimizing 'best practices' worldwide, and to evaluate the relationship between laboratory use of best practices and patient radiation dose. We conducted an observational cross-sectional study of protocols used for all 7911 MPI studies performed in 308 nuclear cardiology laboratories in 65 countries for a single week in March-April 2013. Eight 'best practices' relating to radiation exposure were identified a priori by an expert committee, and a radiation-related quality index (QI) devised indicating the number of best practices used by a laboratory. Patient radiation effective dose (ED) ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratory ED ranged from 2.2 to 24.4 mSv (median 10.4 mSv); only 91 (30%) laboratories achieved the median ED ≤ 9 mSv recommended by guidelines. Laboratory QIs ranged from 2 to 8 (median 5). Both ED and QI differed significantly between laboratories, countries, and world regions. The lowest median ED (8.0 mSv), in Europe, coincided with high best-practice adherence (mean laboratory QI 6.2). The highest doses (median 12.1 mSv) and low QI (4.9) occurred in Latin America. In hierarchical regression modelling, patients undergoing MPI at laboratories following more 'best practices' had lower EDs. Marked worldwide variation exists in radiation safety practices pertaining to MPI, with targeted EDs currently achieved in a minority of laboratories. The significant relationship between best-practice implementation and lower doses indicates numerous opportunities to reduce radiation exposure from MPI globally. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Current worldwide nuclear cardiology practices and radiation exposure: results from the 65 country IAEA Nuclear Cardiology Protocols Cross-Sectional Study (INCAPS)

PubMed Central

Einstein, Andrew J.; Pascual, Thomas N. B.; Mercuri, Mathew; Karthikeyan, Ganesan; Vitola, João V.; Mahmarian, John J.; Better, Nathan; Bouyoucef, Salah E.; Hee-Seung Bom, Henry; Lele, Vikram; Magboo, V. Peter C.; Alexánderson, Erick; Allam, Adel H.; Al-Mallah, Mouaz H.; Flotats, Albert; Jerome, Scott; Kaufmann, Philipp A.; Luxenburg, Osnat; Shaw, Leslee J.; Underwood, S. Richard; Rehani, Madan M.; Kashyap, Ravi; Paez, Diana; Dondi, Maurizio

2015-01-01

Aims To characterize patient radiation doses from nuclear myocardial perfusion imaging (MPI) and the use of radiation-optimizing ‘best practices’ worldwide, and to evaluate the relationship between laboratory use of best practices and patient radiation dose. Methods and results We conducted an observational cross-sectional study of protocols used for all 7911 MPI studies performed in 308 nuclear cardiology laboratories in 65 countries for a single week in March–April 2013. Eight ‘best practices’ relating to radiation exposure were identified a priori by an expert committee, and a radiation-related quality index (QI) devised indicating the number of best practices used by a laboratory. Patient radiation effective dose (ED) ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratory ED ranged from 2.2 to 24.4 mSv (median 10.4 mSv); only 91 (30%) laboratories achieved the median ED ≤ 9 mSv recommended by guidelines. Laboratory QIs ranged from 2 to 8 (median 5). Both ED and QI differed significantly between laboratories, countries, and world regions. The lowest median ED (8.0 mSv), in Europe, coincided with high best-practice adherence (mean laboratory QI 6.2). The highest doses (median 12.1 mSv) and low QI (4.9) occurred in Latin America. In hierarchical regression modelling, patients undergoing MPI at laboratories following more ‘best practices’ had lower EDs. Conclusion Marked worldwide variation exists in radiation safety practices pertaining to MPI, with targeted EDs currently achieved in a minority of laboratories. The significant relationship between best-practice implementation and lower doses indicates numerous opportunities to reduce radiation exposure from MPI globally. PMID:25898845

A retrospective study on annual evaluation of radiation processing for frozen bone allografts complying to quality system requirements.

PubMed

Ramalingam, Saravana; Mohd, Suhaili; Samsuddin, Sharifah Mazni; Min, N G Wuey; Yusof, Norimah; Mansor, Azura

2015-12-01

Bone allografts have been used widely to fill up essential void in orthopaedic surgeries. The benefit of using allografts to replace and reconstruct musculoskeletal injuries, fractures or disease has obtained overwhelming acceptance from orthopaedic surgeons worldwide. However, bacterial infection and disease transmission through bone allograft transplantation have always been a significant issue. Sterilization by radiation is an effective method to eliminate unwanted microorganisms thus assist in preventing life threatening allograft associated infections. Femoral heads procured from living donors and long bones (femur and tibia) procured from cadaveric donors were sterilized at 25 kGy in compliance with international standard ISO 11137. According to quality requirements, all records of bone banking were evaluated annually. This retrospective study was carried out on annual evaluation of radiation records from 1998 until 2012. The minimum doses absorbed by the bones were ranging from 25.3 to 38.2 kGy while the absorbed maximum doses were from 25.4 to 42.3 kGy. All the bones supplied by our UMMC Bone Bank were sterile at the required minimum dose of 25 kGy. Our analysis on dose variation showed that the dose uniformity ratios in 37 irradiated boxes of 31 radiation batches were in the range of 1.003-1.251, which indicated the doses were well distributed.

Chromosome aberrations in workers occupationally exposed to tritium.

PubMed

Tawn, E Janet; Curwen, Gillian B; Riddell, Anthony E

2018-06-01

This paper reports the findings of an historical chromosome analysis for unstable aberrations, undertaken on 34 nuclear workers with monitored exposure to tritium. The mean recorded β-particle dose from tritium was 9.33 mGy (range 0.25-79.71 mGy) and the mean occupational dose from external, mainly γ-ray, irradiation was 1.94 mGy (range 0.00-7.71 mGy). The dicentric frequency of 1.91 ± 0.53 × 10 -3 per cell was significantly raised, in comparison with that of 0.61 ± 0.30 × 10 -3 per cell for a group of 66 comparable worker controls unexposed to occupational radiation. The frequency of total aberrations was also significantly higher in the tritium workers. Comparisons with in vitro studies indicate that at these dose levels an increase in aberration frequency is not expected. However, the available historical tritium dose records were produced for the purposes of radiological protection and based on a methodology that has since been updated, so tritium doses are subject to considerable uncertainty. It is therefore recommended that, if possible, tritium doses are reassessed using information on historical recording practices in combination with current dosimetry methodology, and that further chromosome studies are undertaken using modern FISH techniques to establish stable aberration frequencies, as these will provide information on a cumulative biological effect.

Study of Dose Perturbation at Bone-Tissue Interfaces in Megavoltage Photon Beam Therapy.

NASA Astrophysics Data System (ADS)

Das, Indra Jeet

Dose perturbations during photon beam irradiation occur at interfaces between two dissimilar media due to the loss of electronic equilibrium. The human body contains many different types of interfaces between soft tissue and other media such as, air cavities, lungs, bones, and high atomic number (Z) materials. The dose to critical organs in the vicinity of high Z interfaces, is what leads to this project. This work describes the dose perturbation at high Z (from bone to lead) interfaces with soft tissue for clinically used megavoltage photon beams in the range of CO-60 gamma rays to 24 MV X-rays. It is divided into three main sections: (1) the dose outside the inhomogeneity in the direction of backscatter, (2) the dose inside the inhomogeneity, and (3) the dose on the photon transmission side of the inhomogeneity. Using different types of parallel plate ion chambers, TLD (powder and chip), and film as dosimeters, the dose perturbation is studied as a function of photon energy, thickness, width, and depth of inhomogeneity, distance from the interface and radiation field size. The concept of Bragg-Gray cavity theory is applied and verified for dose determination inside the inhomogeneity. A significant dose enhancement has been observed on the backscatter side for all photon energies. It is strongly dependent on the atomic number of the inhomogeneity and less dependent on the photon energy, thickness, depth, width, and field size. In the forward direction, a dose reduction occurs at the interface at beam energies lower than 10 MV, whereas a dose enhancement occurs for higher photon energies. The interface effect persists up to a few millimeters on the backscatter side but a distance equivalent to the secondary electron range for the particular photon beams in the forward direction. The dose perturbation is explained on the basis of production and transport of secondary electrons. Empirical functions are derived from the experimental data to predict the dose distribution in the vicinity of an inhomogeneity. These equations could form the basis of a treatment planning system that would accurately represent the dose both at the interface and surrounding tissue.

Comparison of doses to the rectum derived from treatment planning system with in-vivo dose values in vaginal vault brachytherapy using cylinder applicators

PubMed Central

Obed, Rachel Ibhade; Akinlade, Bidemi Idayat; Ntekim, Atara

2015-01-01

Purpose In-vivo measurements to determine doses to organs-at-risk can be an essential part of brachytherapy quality assurance (QA). This study compares calculated doses to the rectum with measured dose values as a means of QA in vaginal vault brachytherapy using cylinder applicators. Material and methods At the Department of Radiotherapy, University College Hospital (UCH), Ibadan, Nigeria, intracavitary brachytherapy (ICBT) was delivered by a GyneSource high-dose-rate (HDR) unit with 60Co. Standard 2D treatment plans were created with HDR basic 2.6 software for prescription doses 5-7 Gy at points 5 mm away from the posterior surface of vaginal cylinder applicators (20, 25, and 30 mm diameters). The LiF:Mg, Ti thermoluminescent dosimeter rods (1 x 6 mm) were irradiated to a dose of 7 Gy on Theratron 60Co machine for calibration purpose prior to clinical use. Measurements in each of 34 insertions involving fourteen patients were performed with 5 TLD-100 rods placed along a re-usable rectal marker positioned in the rectum. The dosimeters were read in Harshaw 3500 TLD reader and compared with doses derived from the treatment planning system (TPS) at 1 cm away from the dose prescription points. Results The mean calculated and measured doses ranged from 2.1-3.8 Gy and 1.2-5.6 Gy with averages of 3.0 ± 0.5 Gy and 3.1 ± 1.1 Gy, respectively, for treatment lengths 2-8 cm along the cylinder-applicators. The mean values correspond to 48.9% and 50.8% of the prescribed doses, respectively. The deviations of the mean in-vivo doses from the TPS values ranged from –1.9 to 2.1 Gy with a p-value of 0.427. Conclusions This study was part of efforts to verify rectal dose obtained from the TPS during vaginal vault brachytherapy. There was no significant difference in the dose to the rectum from the two methods of measurements. PMID:26816506

Hematopoietic stimulation by porphyrin photosensitizers (Invited Paper)

NASA Astrophysics Data System (ADS)

Levy, Julia G.; Hunt, David W. C.; Mitchell, David W.; Jamieson, Catriona H. M.

1992-06-01

The effects of the photosensitizers, PhotofrinTM and benozoporphyrin derivative monoacid ring A (BPD) on a variety of hematopoietic cell functions have been studied, both in the presence and absence of light activation. A marked increase in hematopoiesis was observed in the bone marrow and spleens of DBA/2 mice administered high dose Photofrin but not BPD. This was manifested in an increased relative spleen weight, nucleated spleen cell number and circulating white blood cell concentration 7 days following Photofrin injection. We have shown that BPD and light doses just below phototoxic ranges stimulate the growth of human colony forming committed myeloid progenitors as well as pluripotent stem cells grown in long term marrow culture. Studies on the effect of BPD on the function of T lymphocytes in the absence of light has also demonstrated a stimulatory effect. The dose range in which this is observed is considerably broader than that observed with light activation. The mechanisms involved in this stimulatory effect have been studied and are discussed.

Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI).

PubMed

Dunbar, Geoffrey C; Inglis, Fraser; Kuchibhatla, Ramana; Sharma, Tonmoy; Tomlinson, Mark; Wamsley, James

2007-03-01

Cognitive decline seen in the normal elderly is associated with selective loss of neuronal nicotinic acetylcholine receptors (nAChRs). Nicotine given either by inhalation or transdermally helps cognition, but unacceptable side effects limit its utility. The present study assessed the safety, tolerability and effect on cognition of ispronicline, a highly selective partial agonist at the 4beta2 nAChR, in elderly subjects (n =76) with age associated memory impairment (AAMI). This double-blind, placebo-controlled cross-over study explored ascending oral doses of ispronicline in the range 50-150 mg given as a single morning dose for a period of 3 weeks. Pharmacokinetics (PK) were assessed, as well as cognitive function measured by means of the Cognitive Drug Research (CDR) computerized test battery. Ispronicline had a favourable safety profile and was well tolerated at doses below 150 mg. No effect of clinical importance was seen on biochemistry, haematology, urine analysis, vital signs, electrocardiogram (ECG) or Holter monitoring. The most frequent drug induced adverse event was light-headedness (dizziness). A beneficial effect was seen on cognition across the dose range. This was most marked at 50 mg on factors measuring attention and episodic memory. PK analysis indicated a plasma Cmax range of 5-25/35 ng/ml ispronicline was associated with the most beneficial effect. These early results demonstrate ispronicline was well tolerated and did not display the side effects typical of nicotine. Ispronicline also had a beneficial effect on cognition in subjects with AAMI. This was seen most strongly in a Cmax range that had been predicted from pre-clinical animal studies.

The thermoluminescence response of doped SiO2 optical fibres subjected to photon and electron irradiations.

PubMed

Hashim, S; Al-Ahbabi, S; Bradley, D A; Webb, M; Jeynes, C; Ramli, A T; Wagiran, H

2009-03-01

Modern linear accelerators, the predominant teletherapy machine in major radiotherapy centres worldwide, provide multiple electron and photon beam energies. To obtain reasonable treatment times, intense electron beam currents are achievable. In association with this capability, there is considerable demand to validate patient dose using systems of dosimetry offering characteristics that include good spatial resolution, high precision and accuracy. Present interest is in the thermoluminescence response and dosimetric utility of commercially available doped optical fibres. The important parameter for obtaining the highest TL yield during this study is to know the dopant concentration of the SiO2 fibre because during the production of the optical fibres, the dopants tend to diffuse. To achieve this aim, proton-induced X-ray emission (PIXE), which has no depth resolution but can unambiguously identify elements and analyse for trace elements with detection limits approaching microg/g, was used. For Al-doped fibres, the dopant concentration in the range 0.98-2.93 mol% have been estimated, with equivalent range for Ge-doped fibres being 0.53-0.71 mol%. In making central-axis irradiation measurements a solid water phantom was used. For 6-MV photons and electron energies in the range 6, 9 and 12 MeV, a source to surface distance of 100 cm was used, with a dose rate of 400 cGy/min for photons and electrons. The TL measurements show a linear dose-response over the delivered range of absorbed dose from 1 to 4 Gy. Fading was found to be minimal, less than 10% over five days subsequent to irradiation. The minimum detectable dose for 6-MV photons was found to be 4, 30 and 900 microGy for TLD-100 chips, Ge- and Al-doped fibres, respectively. For 6-, 9- and 12-MeV electron energies, the minimum detectable dose were in the range 3-5, 30-50 and 800-1400 microGy for TLD-100 chip, Ge-doped and Al-doped fibres, respectively.

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

NASA Astrophysics Data System (ADS)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-02-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

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

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

Zheng Yuanshui; Liu Yaxi; Zeidan, Omar

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

Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

PubMed

He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

2015-04-22

Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pharmacokinetics of temozolomide given three times a day in pediatric and adult patients.

PubMed

Riccardi, Anna; Mazzarella, Giorgio; Cefalo, Graziella; Garrè, Maria Luisa; Massimino, Maura; Barone, Carlo; Sandri, Alessandro; Ridola, Vita; Ruggiero, Antonio; Mastrangelo, Stefano; Lazzareschi, Ilaria; Caldarelli, Massimo; Maira, Giulio; Madon, Enrico; Riccardi, Riccardo

2003-12-01

To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. TMZ pharmacokinetic parameters were characterized in pediatric and adult patients with primary central nervous system tumors treated with doses ranging from 120 to 200 mg/m2 per day, divided into three doses daily for 5 days. Plasma levels were measured over 8 h following oral administration in a fasting state. A total of 40 courses were studied in 22 children (mean age 10 years, range 3-16 years) and in 8 adults (mean age 30 years, range 19-54 years). In all patients, a linear relationship was found between systemic exposure (AUC) and increasing doses of TMZ. Time to peak concentration, elimination half-life, apparent clearance and volume of distribution were not related to TMZ dose. No differences were seen among TMZ C(max), t(1/2), V(d) or CL/F in children compared with adults. Intra- and interpatient variability of systemic exposure were limited in both children and adults. No statistically significant differences were found between the AUCs of children who experienced grade 4 hematologic toxicity and children who did not. No difference appears to exist between pharmacokinetic parameters in adults and children when TMZ is administered in three doses daily. Hematologic toxicity was not related to TMZ AUC. AUC measurement does not appear to be of any use in optimizing TMZ treatment.

Genetic effects on heavy ions in drosophila

NASA Technical Reports Server (NTRS)

Kale, P. G.

1986-01-01

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

The Northern Marshall Islands Radiological Survey: data and dose assessments.

PubMed

Robison, W L; Noshkin, V E; Conrado, C L; Eagle, R J; Brunk, J L; Jokela, T A; Mount, M E; Phillips, W A; Stoker, A C; Stuart, M L; Wong, K M

1997-07-01

Fallout from atmospheric nuclear tests, especially from those conducted at the Pacific Proving Grounds between 1946 and 1958, contaminated areas of the Northern Marshall Islands. A radiological survey at some Northern Marshall Islands was conducted from September through November 1978 to evaluate the extent of residual radioactive contamination. The atolls included in the Northern Marshall Islands Radiological Survey (NMIRS) were Likiep, Ailuk, Utirik, Wotho, Ujelang, Taka, Rongelap, Rongerik, Bikar, Ailinginae, and Mejit and Jemo Islands. The original test sites, Bikini and Enewetak Atolls, were also visited on the survey. An aerial survey was conducted to determine the external gamma exposure rate. Terrestrial (soil, food crops, animals, and native vegetation), cistern and well water samples, and marine (sediment, seawater, fish and clams) samples were collected to evaluate radionuclide concentrations in the atoll environment. Samples were processed and analyzed for 137Cs, 90Sr, 239+240Pu and 241Am. The dose from the ingestion pathway was calculated using the radionuclide concentration data and a diet model for local food, marine, and water consumption. The ingestion pathway contributes 70% to 90% of the estimated dose. Approximately 95% of the dose is from 137Cs. 90Sr is the second most significant radionuclide via ingestion. External gamma exposure from 137Cs accounts for about 10% to 30% of the dose. 239+240Pu and 241Am are the major contributors to dose via the inhalation pathway; however, inhalation accounts for only about 1% of the total estimated dose, based on surface soil levels and resuspension studies. All doses are computed for concentrations decay corrected to 1996. The maximum annual effective dose from manmade radionuclides at these atolls ranges from .02 mSv y(-1) to 2.1 mSv y(-1). The background dose in the Marshall Islands is estimated to be 2.4 mSv y(-1). The combined dose from both background and bomb related radionuclides ranges from slightly over 2.4 mSv y(-1) to 4.5 mSv y(-1). The 50-y integral dose ranges from 0.5 to 65 mSv.

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

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

Carver, D; Kost, S; Fraser, N

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

Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low–dose rate delivery techniques

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

Li, Jie; Lang, Jinyi; Wang, Pei

2014-01-01

Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low–dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatmentmore » planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7 cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4 cGy. The maximum doses ranged between 22.9 and 34.8 cGy. The minimum doses ranged from 8.2 to 17.5 cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6 cGy. The maximum doses per gantry angle were between 24.0 and 34.7 cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4 cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. The volume receiving an 18-Gy (V{sub 18}) dose for the left and right kidneys was reduced by 10.6% and 12.5%, respectively, for the pancreatic plans. The volume receiving a 45-Gy (V{sub 45}) dose for the small bowel decreased from 65.3% to 45.5%. For the cases with prostate cancer, the volume receiving a 40-Gy (V{sub 40}) dose for the bladder and the rectum was reduced significantly by 25.1% and 51.2%, respectively. When compared with the RapidArc technique, the volume receiving a 30-Gy (V{sub 30}) dose for the left and the right kidneys was lower in the IMRT plans. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. These results clearly demonstrated that the PLDR-IMRT plan was suitable for PLDR pancreatic and prostate cancer treatments in terms of the overall plan quality. A significant reduction in the OAR dose was achieved with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. When compared with the PLDR-3DCRT plan, the PLDR-IMRT plan could provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent pancreatic and prostate cancers. The PLDR-IMRT plan is an effective treatment choice for recurrent cancers in most cancer centers.« less

PBDE exposure from food in Ireland: optimising data exploitation in probabilistic exposure modelling.

PubMed

Trudel, David; Tlustos, Christina; Von Goetz, Natalie; Scheringer, Martin; Hungerbühler, Konrad

2011-01-01

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants added to plastics, polyurethane foam, electronics, textiles, and other products. These products release PBDEs into the indoor and outdoor environment, thus causing human exposure through food and dust. This study models PBDE dose distributions from ingestion of food for Irish adults on congener basis by using two probabilistic and one semi-deterministic method. One of the probabilistic methods was newly developed and is based on summary statistics of food consumption combined with a model generating realistic daily energy supply from food. Median (intermediate) doses of total PBDEs are in the range of 0.4-0.6 ng/kg(bw)/day for Irish adults. The 97.5th percentiles of total PBDE doses lie in a range of 1.7-2.2 ng/kg(bw)/day, which is comparable to doses derived for Belgian and Dutch adults. BDE-47 and BDE-99 were identified as the congeners contributing most to estimated intakes, accounting for more than half of the total doses. The most influential food groups contributing to this intake are lean fish and salmon which together account for about 22-25% of the total doses.

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

PubMed Central

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-01-01

Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Dose estimates for the local inhabitants from 210Po ingestion via dietary sources at a proposed uranium mining site in India.

PubMed

Giri, Soma; Jha, V N; Singh, Gurdeep; Tripathi, R M

2012-07-01

To study the distribution of (210)Po activity in food in Bagjata in East Singhbhum, India. (210)Po were analyzed in the food samples of plant origin such as cereals, pulses, fruits, vegetables and food of animal origin such fish, chicken, egg, etc., in and around Bagjata uranium mining area as a part of baseline study after acid digestion. The intake and ingestion dose of the radionuclide was estimated. The general range of (210)Po activity in all the dietary components ranged widely from <0.2-36 Bqkg(-1)(fresh). In the food of plant origin, the minimum activity of (210)Po was estimated in vegetables while maximum in pulses. In food of animal origin, the observed minimum activity of (210)Po was in eggs and the maximum observed was in chicken samples. The intake of (210)Po considering all dietary components was found to be 464 Bq.Y(-1) while the ingestion dose was calculated to be 557 μSv.Y(-1), respectively. The estimated doses are reflecting the natural background dose via the route of ingestion, which is much below the 1 mSv limit set in the International Commission on Radiological Protection (ICRP) recommendations. The study confirms that current levels of (210)Po do not pose a significant radiological risk to the local inhabitants.

Evaluation Of Microdosing Strategies For Studies In Preclinical Drug Development: Demonstration Of Linear Pharmacokinetics In Dogs Of A Nucleoside Analogue Over A 50-Fold Dose Range

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

Sandhu, P; Vogel, J S; Rose, M J

The technique of accelerator mass spectrometry (AMS) was validated successfully and utilized to study the pharmacokinetics and disposition in dogs of a preclinical drug candidate (Compound A), after oral and intravenous administration. The primary objective of this study was to examine whether Compound A displayed linear kinetics across sub-pharmacological (microdose) and pharmacological dose ranges in an animal model, prior to initiation of a human microdose study. The AMS-derived disposition properties of Compound A were comparable to data obtained via conventional techniques such as LC-MS/MS and liquid scintillation counting analyses. Thus, Compound A displayed multiphasic kinetics and possessed low plasma clearancemore » (4.4 mL/min/kg), a long terminal elimination half-life (19.4 hr) and high oral bioavailability (82%). Currently there are no published comparisons of the kinetics of a pharmaceutical compound at pharmacological versus sub-pharmacological doses employing microdosing strategies. The present study thus provides the first description of the pharmacokinetics of a drug candidate assessed under these two dosing regimens. The data demonstrated that the pharmacokinetic properties of Compound A were similar following dosing at 0.02 mg/kg as at 1 mg/kg, indicating that in the case of Compound A, the kinetics of absorption, distribution and elimination in the dog appear to be linear across this 50-fold dose range. Moreover, the exceptional sensitivity of AMS provided a pharmacokinetic profile of Compound A, even following a microdose, which revealed aspects of the disposition of this agent that were inaccessible by conventional techniques. The applications of accelerator mass spectrometry (AMS) are broad ranging and vary from studying environmental and ecological issues such as the isotopic composition of the atmosphere, soil and water (Hughen et al., 2000; Beck et al., 2001; Keith-Roach et al., 2001; Mironov et al., 2002), to archaeology and volcanology (Stafford et al., 1984; Vogel et al., 1990; Smith et al., 1999) to its use as a bioanalytical tool for nutritional research (Buchholz et al., 1999; Deuker et al., 2000; Weaver and Liebman, 2002). Biomedical applications of AMS and its use in the arena of pharmaceutical research also have been detailed in review articles (Barker and Garner, 1999; Garner, 2000; Turteltaub and Vogel, 2000). To date, most studies on the metabolism and disposition of xenobiotics by AMS have focused on how carcinogens bind to DNA and proteins to form adducts (Turteltaub et al., 1990, 1997; Frantz et al., 1995; Dingley et al., 1999; Li et al., 2003). Its application to the field of pharmaceutical sciences has been limited to a few studies (Kaye et al., 1997; Young et al., 2001; Garner et al., 2002). However, the pharmaceutical industry is becoming increasingly aware of the potential benefits that may accrue from the ultra high sensitivity afforded by AMS in terms of evaluating the pharmacokinetics of lead drug candidates in early development. Specifically, AMS allows administration of sub-pharmacological doses (microdoses) of carbon-14 or tritium-labeled investigational drugs to animals or humans at radiologically insignificant levels with the goal of obtaining preliminary information regarding the absorption, distribution, metabolism, and excretion of test compounds (Turteltaub and Vogel, 2000). An unresolved issue, however, is whether the pharmacokinetics determined following a microdose are representative of those following a conventional (pharmacological) dose (Lappin and Garner, 2003). This paper examines the linearity of kinetics of an antiviral nucleoside analogue, Compound A, across sub-pharmacological and pharmacological dose ranges in the dog prior to initiation of a human microdose study. The specific objectives of this study, therefore, were (1) to assess the pharmacokinetics of Compound A in dogs by a conventional dosing approach utilizing LC-MS/MS for sample analysis, (2) to assess the pharmacokinetics of Compound A in dogs by the microdose approach utilizing AMS for sample analysis, (3) to compare the pharmacokinetics of Compound A at a microdose versus a pharmacological dose, and (4) to validate AMS for this application and to compare the sensitivity of AMS to that of LC-MS/MS.« less

Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development

PubMed Central

Kimmel, Gary L.; Kimmel, Carole A.; Williams, Amy L.

2013-01-01

The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission’s 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations. In addition, the results of six unpublished developmental toxicity studies in rats were considered. Five of the seven rabbit studies (dose range: 10–500 mg/kg/day) were GLP- and testing guideline-compliant for the era in which the studies were performed; a sixth study predated testing and GLP guidelines, but generally adhered to these principles. The seventh study was judged inadequate. In each of the adequate studies, offspring effects occurred only at doses that also caused maternal toxicity. An integrated evaluation of the six adequate studies, using conservative assumptions, demonstrated that neither the overall malformation rate nor the incidence of cardiovascular malformations increased with dose up to the point where severe maternal toxicity was observed (generally ≥150 mg/kg/day). Random occurrences of cardiovascular malformations were observed across all dose groups (including controls) and did not exhibit a dose–response relationship. In the six rat studies (dose range: 30–3500 mg/kg/day), a low incidence of sporadic cardiovascular malformations was reported that was clearly not related to treatment. In summary, assessment of the entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy. PMID:23286529

Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle - an update.

PubMed

Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve A C; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald A H

2012-12-05

To provide information on dose-response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of the bovine prion protein gene on disease incidence and revises estimates of effective oral exposure. Following interim published results, two further cattle, one dosed with 100 mg and culled at 127 months post exposure and the other dosed with 10 mg and culled at 110 months post exposure, developed BSE. Both had a similar pathological phenotype to previous cases. Based on attack rate and incubation period distribution according to dose, the dose estimate at which 50% of confirmed cases would be clinically affected was revised to 0.15 g of the brain homogenate used in the experiment, with a 95% confidence interval of 0.03-0.79 g. Neither the full open reading frame nor the promoter region of the prion protein gene of dosed cattle appeared to influence susceptibility to BSE, but this may be due to the sample size. Oral exposure of cattle to a large range of doses of a BSE brainstem homogenate produced disease in all dose groups. The pathological presentation resembled natural disease. The attack rate and incubation period were dependent on the dose.

Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy.

PubMed

May, Theodor W; Brandt, Christian; Helmer, Renate; Bien, Christian G; Cawello, Willi

2015-07-01

This study was carried out to estimate the exposure of the central nervous system (CNS) to the antiepileptic drug (AED) lacosamide, under steady state conditions, in patients with epilepsy who take oral lacosamide alongside up to three other AEDs. Twenty-seven serum and cerebral spinal fluid (CSF) samples were collected from 21 patients receiving lacosamide for the treatment of epilepsy (50-600 mg/day over two or three doses). This included 23 time-matched pairs of serum and CSF samples from 19 patients. The concentration of lacosamide in each sample was determined using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Linear regression was used to characterize the relationship between the CSF-to-serum ratio of lacosamide concentration and the time since dosing, the daily lacosamide dose, or the daily dose normalized by volume of distribution (Vd , approximated to total body water), and between the drug concentrations in each compartment (CSF vs. serum). Concentrations of lacosamide in CSF (mean ± standard deviation [SD] 7.37 ± 3.73 μg/ml, range 1.24-14.95, n = 27) and serum (mean ± SD 8.16 ± 3.82 μg/ml, range 2.29-15.45, n = 27) samples showed a good correlation over the dose range investigated. The mean CSF-to-serum ratio of lacosamide concentrations was 0.897 ± 0.193 (range 0.492-1.254, n = 23 time-matched pairs) and was independent of lacosamide dose. Drug concentrations in the CSF are often used to indicate those in the brain interstitial fluid. In patients with epilepsy who follow a stable oral AED dosing regimen, lacosamide concentration in CSF is approximately 85% of that found in serum, suggesting that serum may be a valuable indicator of lacosamide concentration in the CNS. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Investigation of Kodak extended dose range (EDR) film for megavoltage photon beam dosimetry.

PubMed

Chetty, Indrin J; Charland, Paule M

2002-10-21

We have investigated the dependence of the measured optical density on the incident beam energy, field size and depth for a new type of film, Kodak extended dose range (Kodak EDR). Film measurements have been conducted over a range of field sizes (3 x 3 cm2 to 25 x 25 cm2) and depths (d(max) to 15 cm), for 6 MV and 15 MV photons within a solid water phantom, and the variation in sensitometric response (net optical density versus dose) has been reported. Kodak EDR film is found to have a linear response with dose, from 0 to 350 cGy, which is much higher than that typically seen for Kodak XV film (0-50 cGy). The variation in sensitometric response for Kodak EDR film as a function of field size and depth is observed to be similar to that of Kodak XV film; the optical density varied in the order of 2-3% for field sizes of 3 x 3 cm2 and 10 x 10 cm2 at depths of d(max), 5 cm and 15 cm in the phantom. Measurements for a 25 x 25 cm2 field size showed consistently higher optical densities at depths of d(max), 5 cm and 15 cm, relative to a 10 x 10 cm2 field size at 5 cm depth, with 4-5% differences noted at a depth of 15 cm. Fractional depth dose and profiles conducted with Kodak EDR film showed good agreement (2%/2 mm) with ion chamber measurements for all field sizes except for the 25 x 25 cm2 at depths greater than 15 cm, where differences in the order of 3-5% were observed. In addition, Kodak EDR film measurements were found to be consistent with those of Kodak XV film for all fractional depth doses and profiles. The results of this study indicate that Kodak EDR film may be a useful tool for relative dosimetry at higher dose ranges.

Sizes of particles formed during municipal wastewater treatment.

PubMed

Lech, Smoczynski; Marta, Kosobucka; Michal, Smoczynski; Harsha, Ratnaweera; Krystyna, Pieczulis-Smoczynska

2017-02-01

Volumetric diameters Dv and specific surface area SpS of sludge particles formed during chemical coagulation and electrocoagulation of sewage were determined. The obtained aggregate-flocs differed substantially in both Dv and SpS values. The differences in Dv and SpS values of the analyzed particles were interpreted based on theoretical models for expanding aggregates. The most uniform particles were formed under exposure to: (a) optimal and maximal doses of PIX, (b) optimal doses of PAX, (c) maximal doses of the Al electro-coagulant. The lowest PIX dose produced the least uniform particles. Sludge aggregates-particles produced under exposure to minimal doses of PIX and the Al electro-coagulant were characterized by the lowest SpS values. Sludge particles coagulated by PAX and the particles formed at higher doses of PIX and the Al electro-coagulant had higher SpS values. The particles formed at all doses of the applied coagulants and electro-coagulants were generally classified into two size ranges: the main range and the secondary range. Most particles belonged to the main size range. An increase in the percentage of colloidal hydroxide particles in sewage sludge increased SpS.

Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.

PubMed

Kampouraki, Emmanouela; Avery, Peter J; Wynne, Hilary; Biss, Tina; Hanley, John; Talks, Kate; Kamali, Farhad

2017-09-01

Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients. © 2017 John Wiley & Sons Ltd.

SU-E-T-238: Monte Carlo Estimation of Cerenkov Dose for Photo-Dynamic Radiotherapy

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

Chibani, O; Price, R; Ma, C

Purpose: Estimation of Cerenkov dose from high-energy megavoltage photon and electron beams in tissue and its impact on the radiosensitization using Protoporphyrine IX (PpIX) for tumor targeting enhancement in radiotherapy. Methods: The GEPTS Monte Carlo code is used to generate dose distributions from 18MV Varian photon beam and generic high-energy (45-MV) photon and (45-MeV) electron beams in a voxel-based tissueequivalent phantom. In addition to calculating the ionization dose, the code scores Cerenkov energy released in the wavelength range 375–425 nm corresponding to the pick of the PpIX absorption spectrum (Fig. 1) using the Frank-Tamm formula. Results: The simulations shows thatmore » the produced Cerenkov dose suitable for activating PpIX is 4000 to 5500 times lower than the overall radiation dose for all considered beams (18MV, 45 MV and 45 MeV). These results were contradictory to the recent experimental studies by Axelsson et al. (Med. Phys. 38 (2011) p 4127), where Cerenkov dose was reported to be only two orders of magnitude lower than the radiation dose. Note that our simulation results can be corroborated by a simple model where the Frank and Tamm formula is applied for electrons with 2 MeV/cm stopping power generating Cerenkov photons in the 375–425 nm range and assuming these photons have less than 1mm penetration in tissue. Conclusion: The Cerenkov dose generated by high-energy photon and electron beams may produce minimal clinical effect in comparison with the photon fluence (or dose) commonly used for photo-dynamic therapy. At the present time, it is unclear whether Cerenkov radiation is a significant contributor to the recently observed tumor regression for patients receiving radiotherapy and PpIX versus patients receiving radiotherapy only. The ongoing study will include animal experimentation and investigation of dose rate effects on PpIX response.« less

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

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

Pharmacokinetics of theophylline: a dose-range study.

PubMed Central

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

1982-01-01

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

SU-F-T-170: Patient Surface Dose Measurements Using Optically Stimulated Luminescence Dosimeters in Scanning Proton Beam Therapy for Breast Cancer

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

Yu, J; Strauss, D; Langner, U

Purpose: To establish patient surface dose dosimetry for scanning proton beam therapy (SPBT) for breast cancer using optically stimulated luminescence dosimeters (OSLD). Methods: OSLDs were calibrated with SPB under the similar conditions as the treatments for breast cancer. A range shifter (RS) of 5 cm water equivalent thickness (WET) was used. The air gap from the surface of the range shifter to the surface of the phantom was 15 cm. A uniform planar dose generated by nominal energy of 118 MeV was delivered. The range of 118 MeV proton beam after the 5cm RS is approximately 5 cm in water,more » which is the common range for breast treatments. The OSLDs were placed on the surface of high density polyethylene slabs, and a bolus of 1.06 cm WET was used for buildup. A variety of dose levels in the range of 0.5 to 8 Gy were delivered. Under the same condition, an ADCL calibrated parallel plate (PP) chamber was used to measure the reference dose. The correlation between the output signals of OSLDs and the reference doses was established. The calibration of OSLD was verified against the PP chamber measurements for two SPBT breast plans calculated for two patients. Results: the least squares fitting for the OSLD calibration curve was a polynomial function to the order of 2 in the range of 0.5 to 8 Gy (RBE). The differences between the dose measured with OSLDs and PP chamber were within 3% for the two breast proton plans. Conclusion: the calibrated OSLDs under the similar conditions as the treatments can be used for patient surface dose measurements.« less

Nanogram quantities of a DNA vaccine protect rainbow trout fry against heterologous strains of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Corbeil, S.; LaPatra, S.E.; Anderson, E.D.; Kurath, G.

2000-01-01

The efficacy of a DNA vaccine containing the glycoprotein gene of infectious hematopoietic necrosis virus (IHNV), a rhabdovirus affecting trout and salmon, was investigated. The minimal dose of vaccine required, the protection against heterologous strains, and the titers of neutralizing antibodies produced were used to evaluate the potential of the vaccine as a control pharmaceutical. Results indicated that a single dose of as little as 1–10 ng of vaccine protected rainbow trout fry against waterborne challenge by IHNV. An optimal dose of 100 ng per fish was selected to assure strong protection under various conditions. Neutralizing antibody titers were detected in fish vaccinated with concentrations of DNA ranging from 5 to 0.01 μg. Furthermore, the DNA vaccine protected fish against a broad range of viral strains from different geographic locations, including isolates from France and Japan, suggesting that the vaccine could be used worldwide. A single dose of this DNA vaccine induced protection in fish at a lower dose than is usually reported in mammalian DNA vaccine studies.

Noise exposure levels for musicians during rehearsal and performance times.

PubMed

McIlvaine, Devon; Stewart, Michael; Anderson, Robert

2012-03-01

The purpose of this study was to determine daily noise doses and 8-hour time weighted averages for rock band musicians, crew members, and spectators during a typical rehearsal and performance using both Occupational Safety and Health Administration (OSHA) and National Institute of Occupational Safety and Health (NIOSH) measurement criteria. Personal noise dosimetry was completed on five members of a rock band during one 2-hr rehearsal and one 4-hr performance. Time-weighted averages (TWA) and daily dose values were calculated using both OSHA and NIOSH criteria and compared to industry guidelines for enrollment in hearing conservation programs and the use of hearing protection devices. TWA values ranged from 84.3 to 90.4 dBA (OSHA) and from 90.0 to 96.4 dBA (NIOSH) during the rehearsal. The same values ranged from 91.0 to 99.7 dBA (OSHA) and 94.0 to 102.8 dBA (NIOSH) for the performance. During the rehearsal, daily noise doses ranged from 45.54% to 106.7% (OSHA) and from 317.74% to 1396.07% (NIOSH). During the performance, doses ranged from 114.66% to 382.49% (OSHA) and from 793.31% to 5970.15% (NIOSH). The musicians in this study were exposed to dangerously high levels of noise and should be enrolled in a hearing conservation programs. Hearing protection devices should be worn, especially during performances. The OSHA measurement criteria yielded values significantly more conservative than those produced by NIOSH criteria. Audiologists should counsel musician-patients about the hazards of excessive noise (music) exposure and how to protect their hearing.

Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease.

PubMed

Nguyen, Natalie L; Kome, Anne M; Lowe, Denise K; Coyne, Patrick; Hawks, Kelly G

2015-01-01

The objectives of this study were to evaluate the efficacy and safety of adjuvant intravenous (IV) lidocaine in adults with sickle cell disease (SCD). This was a retrospective review. Adults with SCD receiving at least one IV lidocaine infusion from 2004 to 2014 were included. Patient demographics, lidocaine treatment parameters, pain scores, pain medications, and adverse effects were recorded. Eleven patients were identified, yielding 15 IV lidocaine trials. Clinical improvement in pain scores from pre-lidocaine challenge to 24 hours post-lidocaine challenge, defined by ≥ 20% reduction in pain scores, was achieved in 53.3% (8 of 15) of IV lidocaine challenges. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre-lidocaine challenge to 24 hours post-lidocaine challenge was 32.2%. Additionally, clinically successful trials had a mean initial and a maximum dose of 1 mg/kg/h (range: 0.5-2.7 mg/kg/h) and 1.3 mg/kg/h (range: 0.5-1.9 mg/kg/h), respectively. On average, these patients underwent 3 dose titrations (range: 1-8) and received lidocaine infusions for 4.4 days (range: 2-8 days). Two patients experienced disorientation and dizziness. The authors conclude that adjuvant IV lidocaine provided pain relief and a mean reduction in MDE during sickle cell pain crisis. These results provide preliminary insight into the use of IV lidocaine for treating pain in patients with SCD, although prospective studies are needed to determine efficacy, dosing, and tolerability of IV lidocaine in this patient population.

Design and implementation of a head-and-neck phantom for system audit and verification of intensity-modulated radiation therapy.

PubMed

Webster, Gareth J; Hardy, Mark J; Rowbottom, Carl G; Mackay, Ranald I

2008-04-16

The head and neck is a challenging anatomic site for intensity-modulated radiation therapy (IMRT), requiring thorough testing of planning and treatment delivery systems. Ideally, the phantoms used should be anatomically realistic, have radiologic properties identical to those of the tissues concerned, and allow for the use of a variety of devices to verify dose and dose distribution in any target or normaltissue structure. A phantom that approaches the foregoing characteristics has been designed and built; its specific purpose is verification for IMRT treatments in the head-andneck region. This semi-anatomic phantom, HANK, is constructed of Perspex (Imperial Chemical Industries, London, U.K.) and provides for the insertion of heterogeneities simulating air cavities in a range of fixed positions. Chamber inserts are manufactured to incorporate either a standard thimble ionization chamber (0.125 cm3: PTW, Freiburg, Germany) or a smaller PinPoint chamber (0.015 cm3: PTW), and measurements can be made with either chamber in a range of positions throughout the phantom. Coronal films can also be acquired within the phantom, and additional solid blocks of Perspex allow for transverse films to be acquired within the head region. Initial studies using simple conventional head-and-neck plans established the reproducibility of the phantom and the measurement devices to within the setup uncertainty of +/- 0.5 mm. Subsequent verification of 9 clinical head-and-neck IMRT plans demonstrated the efficacy of the phantom in making a range of patient-specific dose measurements in regions of dosimetric and clinical interest. Agreement between measured values and those predicted by the Pinnacle3 treatment planning system (Philips Medical Systems, Andover, MA) was found to be generally good, with a mean error on the calculated dose to each point of +0.2% (range: -4.3% to +2.2%; n = 9) for the primary planning target volume (PTV), -0.1% (range: -1.5% to +2.0%; n = 8) for the nodal PTV, and +0.0% (range: -1.8% to +4.3%, n = 9) for the spinal cord. The suitability of the phantom for measuring combined dose distributions using radiographic film was also evaluated. The phantom has proved to be a valuable tool in the development and implementation of clinical head-and-neck IMRT, allowing for accurate verification of absolute dose and dose distributions in regions of clinical and dosimetric interest.

Radiation absorbed dose estimates for 18F-BPA PET.

PubMed

Kono, Yuzuru; Kurihara, Hiroaki; Kawamoto, Hiroshi; Yasui, Naoko; Honda, Naoki; Igaki, Hiroshi; Itami, Jun

2017-09-01

Background Boron neutron capture therapy (BNCT) is a molecular radiation therapy approach based on the 10 B (n, α) 7 Li nuclear reaction in cancer cells. In BNCT, delivery of 10 B in the form of 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is important. The PET tracer 4-borono-2-18F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. Purpose To determine the biodistribution and dosimetric parameters in 18F-BPA PET/CT studies. Material and Methods Human biokinetic data were obtained during clinical 18F-BPA PET studies between February and June 2015 at one institution. Nine consecutive patients were studied prospectively. The internal radiation dose was calculated on the basis of radioactivity data from blood, urine, and normal tissue of the heart, liver, spleen, kidney, and other parts of the body at each time point using OLINDA/EXM1.1 program. We compared our calculations with published 18F-FDG data. Results Adult patients (3 men, 3 women; age range, 28-68 years) had significantly smaller absorbed doses than pediatric patients (3 patients; age range, 5-12 years) ( P = 0.003). The mean effective dose was 57% lower in adult patients compared with pediatric patients. Mean effective doses for 18F-BPA were 25% lower than those for 18F-FDG presented in International Commission of Radiation Protection (ICRP) publication 106. Conclusion We found significant differences in organ absorbed doses for 18F-BPA against those for 18F-FDG presented in ICRP publication 106. Mean effective doses for 18F-BPA were smaller than those for 18F-FDG in the publication by 0.5-38% (mean difference, 25%).

Deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation: multicenter phase I study (KSGCT1302).

PubMed

Tachibana, Takayoshi; Kanda, Junya; Machida, Shinichiro; Saito, Takeshi; Tanaka, Masatsugu; Najima, Yuho; Koyama, Satoshi; Miyazaki, Takuya; Yamamoto, Eri; Takeuchi, Masahiro; Morita, Satoshi; Kanda, Yoshinobu; Kanamori, Heiwa; Okamoto, Shinichiro

2018-05-01

The aim of this study was to assess the safety and optimal dose of deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation (HCT). The primary endpoint was the maximum tolerated dose of deferasirox that was determined by the intrapatient dose escalation methods. A total of 16 patients with post-HCT iron overload were enrolled in the study. After excluding one case of early relapse, 15 remained evaluable. Their median age was 42 years (range 22-68). Median time from HCT to deferasirox administration was 9 months (range 6-84). Deferasirox was started at a dose of 5 mg/kg, and the dose was increased to 7.5 and 10 mg/kg every 4 weeks unless there were no grade ≥ 2 of adverse events. Achievement rates of planned medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in 10 mg/kg (9 of 15), respectively. The reasons for discontinuation of the drug were grade 2 of adverse events (n = 4), late relapse (n = 1), and self-cessation (n = 1). None of the patients developed grade ≥ 3 of adverse events or exacerbation of GVHD. Among 11 evaluable cases, mean value of ferritin decreased from 1560 ng/ml pre-treatment to 1285 ng/ml post-treatment. These data suggested that 10 mg/kg of deferasirox may be maximum tolerated dose when given after HCT. Our dose escalating method of deferasirox is useful to identify the optimal dosage of the drug in each patient. UMIN000011251.

Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic Consortium Cohort Database

PubMed Central

Liu, Rong; Li, Xi; Zhang, Wei; Zhou, Hong-Hao

2015-01-01

Objective Multiple linear regression (MLR) and machine learning techniques in pharmacogenetic algorithm-based warfarin dosing have been reported. However, performances of these algorithms in racially diverse group have never been objectively evaluated and compared. In this literature-based study, we compared the performances of eight machine learning techniques with those of MLR in a large, racially-diverse cohort. Methods MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied in warfarin dose algorithms in a cohort from the International Warfarin Pharmacogenetics Consortium database. Covariates obtained by stepwise regression from 80% of randomly selected patients were used to develop algorithms. To compare the performances of these algorithms, the mean percentage of patients whose predicted dose fell within 20% of the actual dose (mean percentage within 20%) and the mean absolute error (MAE) were calculated in the remaining 20% of patients. The performances of these techniques in different races, as well as the dose ranges of therapeutic warfarin were compared. Robust results were obtained after 100 rounds of resampling. Results BART, MARS and SVR were statistically indistinguishable and significantly out performed all the other approaches in the whole cohort (MAE: 8.84–8.96 mg/week, mean percentage within 20%: 45.88%–46.35%). In the White population, MARS and BART showed higher mean percentage within 20% and lower mean MAE than those of MLR (all p values < 0.05). In the Asian population, SVR, BART, MARS and LAR performed the same as MLR. MLR and LAR optimally performed among the Black population. When patients were grouped in terms of warfarin dose range, all machine learning techniques except ANN and LAR showed significantly higher mean percentage within 20%, and lower MAE (all p values < 0.05) than MLR in the low- and high- dose ranges. Conclusion Overall, machine learning-based techniques, BART, MARS and SVR performed superior than MLR in warfarin pharmacogenetic dosing. Differences of algorithms’ performances exist among the races. Moreover, machine learning-based algorithms tended to perform better in the low- and high- dose ranges than MLR. PMID:26305568

Characteristics of an OSLD in the diagnostic energy range

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

Al-Senan, Rani M.; Hatab, Mustapha R.

2011-07-15

Purpose: Optically stimulated luminescence (OSL) dosimetry has been recently introduced in radiation therapy as a potential alternative to the thermoluminescent dosimeter (TLD) system. The aim of this study was to investigate the feasibility of using OSL point dosimeters in the energy range used in diagnostic imaging. Methods: NanoDot OSL dosimeters (OSLDs) were used in this study, which started with testing the homogeneity of a new packet of nanoDots. Reproducibility and the effect of optical treatment (bleaching) were then examined, followed by an investigation of the effect of accumulated dose on the OSLD indicated doses. OSLD linearity, angular dependence, and energymore » dependence were also studied. Furthermore, comparison with LiF:Mg,Ti TLD chips using standard CT dose phantoms at 80 and 120 kVp settings was performed. Results: Batch homogeneity showed a coefficient of variation of <5%. Single-irradiation measurements with bleaching after each OSL readout was found to be associated with a 3.3% reproducibility (one standard deviation measured with a 8 mGy test dose), and no systematic change in OSLDs sensitivity could be noted from measurement to measurement. In contrast, the multiple-irradiation readout without bleaching in between measurements was found to be associated with an uncertainty (using a 6 mGy test dose) that systematically increased with accumulated dose, reaching 42% at 82 mGy. Good linearity was shown by nanoDots under general x-ray, CT, and mammography units with an R{sup 2} > 0.99. The angular dependence test showed a drop of approximately 70% in the OSLD response at 90 deg. in mammography (25 kVp). With the general radiography unit, the maximum drop was 40% at 80 kVp and 20% at 120 kVp, and it was only 10% with CT at both 80 and 120 kVp. The energy dependence study showed a range of ion chamber-to-OSLDs ratios between 0.81 and 1.56, at the energies investigated (29-62 keV). A paired t-test for comparing the OSLDs and TLDs showed no significant variation (p > 0.1). Conclusions: OSLDs exhibited good batch homogeneity (<5%) and reproducibility (3.3%), as well as a linear response. In addition, they showed no statistically significant difference with TLDs in CT measurements (p > 0.1). However, high uncertainty (42%) in the dose estimate was found as a result of relatively high accumulated dose. Furthermore, nanoDots showed high angular dependence (up to 70%) in low kVp techniques. Energy dependence of about 60% was found, and correction factors were suggested for the range of energies investigated. Therefore, if angular and energy dependences are taken into consideration and the uncertainty associated with accumulated dose is avoided, OSLDs (nanoDots) can be suitable for use as point dosimeters in diagnostic settings.« less

[Carcinogenic efficacy of the transuranium elements americium-241 and curium-244].

PubMed

Rudnitskaia, E I

1984-01-01

Albino female rats were used in the experiments. After a single intraperitoneal administration of 241Am and 244Cm chloride is doses ranging from 0.37 to 185 kBq/kg (14 doses were used) it was established that the doses applied had different effect on the average life of animals. The largest doses shortened and the lowest increased the life span of experimental animals as compared to the controls. The carcinogenic effect of the studied radionuclides and the development of malignant tumors were detected at sufficiently low doses absorbed. Malignant tumors developed in the experimental and control animals were different not only in their incidence but also their localization and spectrum.

DOSE-RESPONSE FOR UV-INDUCED IMMUNE SUPPRESSION IN PEOPLE OF COLOR: DIFFERENCES BASED ON ERYTHEMAL REACTIVITY RATHER THAN SKIN PIGMENTATION

EPA Science Inventory

Ultraviolet radiation (UVR) is known to suppress immune responses in human subjects. The purpose of this study was to develop dose responses across a broad range of skin pigmentation in order to facilitate risk assessment. UVR was administered using FS 20 bulbs. Skin pigmentation...

Shared Dosimetry Error in Epidemiological Dose-Response Analyses

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

Stram, Daniel O.; Preston, Dale L.; Sokolnikov, Mikhail

2015-03-23

Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takesmore » up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. Use of these methods for several studies, including the Mayak Worker Cohort and the U.S. Atomic Veterans Study, is discussed.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1985

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commericial power reactors operating during 1985. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 61 sites. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each of the sites is a histogram showing the fraction of the total population within 2 to 80 km aroundmore » each site receiving various average dose commitments from the airborne pathways. The total dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 73 person-rem to a low of 0.011 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 3 person-rem. The total population dose for all sites was estimated at 200 person-rem for the 110 million people considered at risk. The site average individual dose commitment from all pathways ranged from a low of 5 /times/ 10/sup /minus/6/ mrem to a high of 0.02 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1984

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1984. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 56 sites. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each of the sites is a histogram showing the fraction of the total population within 2 to 80 km aroundmore » each site receiving various average dose commitments from the airborne pathways. The total dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 110 person-rem to a low of 0.002 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 5 person-rem. The total population dose for all sites was estimated at 280 person-rem for the 100 million people considered at risk. The site average individual dose commitment from all pathways ranged from a low of 6 x 10/sup -6/ mrem to a high of 0.04 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1986

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

Baker, D.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1986. Fifty-year dose commitments for a one-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 66 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for each of the sites is a histogram showing the fraction of the total population within 2 to 80 kmmore » around each site receiving various average dose commitments from the airborne pathways. The total dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 31 person-rem to a low of 0.0007 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 1.7 person-rem. The total population dose for all sites was estimated at 110 person-rem for the 140 million people considered at risk. The site average individual dose commitment from all pathways ranged from a low of 2 {times} 10{sup -6} mrem to a high of 0.02 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites. 12 refs.« less

Population dose commitments due to radioactive releases from nuclear power plant sites in 1982. Volume 4

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

Baker, D.A.; Peloquin, R.A.

Population radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1982. Fifty-year dose commitments from a one-year exposure were calculated from both liquid and atmospheric releases for four population groups (infant, child, teen-ager and adult) residing between 2 and 80 km from each of 51 sites. This report tabulates the results of these calculations, showing the dose commitments for both liquid and airborne pathways for each age group and organ. Also included for each site is a histogram showing the fraction of the total population within 2 to 80 km around each sitemore » receiving various average dose commitments from the airborne pathways. The total dose commitments from both liquid and airborne pathways ranged from a high of 30 person-rem to a low of 0.007 person-rem for the sites with plants operating throughout the year with an arithmetic mean of 3 person-rem. The total population dose for all sites was estimated at 130 person-rem for the 100 million people considered at risk. The average individual dose commitment from all pathways on a site basis ranged from a low of 6 x 10/sup -7/ mrem to a high of 0.06 mrem. No attempt was made in this study to determine the maximum dose commitment received by any one individual from the radionuclides released at any of the sites.« less

A U.S. Multicenter Study of Recorded Occupational Radiation Badge Doses in Nuclear Medicine.

PubMed

Villoing, Daphnée; Yoder, R Craig; Passmore, Christopher; Bernier, Marie-Odile; Kitahara, Cari M

2018-05-01

Purpose To summarize occupational badge doses recorded for a sample of U.S. nuclear medicine technologists. Materials and Methods Nine large U.S. medical institutions identified 208 former and current nuclear medicine technologists certified after 1979 and linked these individuals to historic badge dose records maintained by a commercial dosimetry company (Landauer), yielding a total of 2618 annual dose records. The distributions of annual and cumulative occupational doses were described by using summary statistics. Results Between 1992 and 2015, the median annual personal dose equivalent per nuclear medicine technologist was 2.18 mSv (interquartile range [IQR], 1.25-3.47 mSv; mean, 2.69 mSv). Median annual personal dose equivalents remained relatively constant over this period (range, 1.40-3.30 mSv), while maximum values generally increased over time (from 8.00 mSv in 1992 to 13.9 mSv in 2015). The median cumulative personal dose equivalent was 32.9 mSv (IQR, 18.1-65.5 mSv; mean, 51.4 mSv) for 45 technologists who had complete information and remained employed through 2015. Conclusion Occupational radiation doses were well below the established occupational limits and were consistent with those observed for nuclear medicine technologists worldwide and were greater than those observed for nuclear and general medical workers in the United States These results should be informative for radiation monitoring and safety efforts in nuclear medicine departments. © RSNA, 2018 Online supplemental material is available for this article.

Dose response and repair kinetics of gamma-H2AX foci induced by in vitro irradiation of whole blood and T-lymphocytes with X- and gamma-radiation.

PubMed

Beels, Laurence; Werbrouck, Joke; Thierens, Hubert

2010-09-01

Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

Unified approach for extrapolation and bridging of adult information in early-phase dose-finding paediatric studies.

PubMed

Petit, Caroline; Samson, Adeline; Morita, Satoshi; Ursino, Moreno; Guedj, Jérémie; Jullien, Vincent; Comets, Emmanuelle; Zohar, Sarah

2018-06-01

The number of trials conducted and the number of patients per trial are typically small in paediatric clinical studies. This is due to ethical constraints and the complexity of the medical process for treating children. While incorporating prior knowledge from adults may be extremely valuable, this must be done carefully. In this paper, we propose a unified method for designing and analysing dose-finding trials in paediatrics, while bridging information from adults. The dose-range is calculated under three extrapolation options, linear, allometry and maturation adjustment, using adult pharmacokinetic data. To do this, it is assumed that target exposures are the same in both populations. The working model and prior distribution parameters of the dose-toxicity and dose-efficacy relationships are obtained using early-phase adult toxicity and efficacy data at several dose levels. Priors are integrated into the dose-finding process through Bayesian model selection or adaptive priors. This calibrates the model to adjust for misspecification, if the adult and pediatric data are very different. We performed a simulation study which indicates that incorporating prior adult information in this way may improve dose selection in children.

Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Volunteers Treated With GDC-0853, a Selective Reversible Bruton's Tyrosine Kinase Inhibitor.

PubMed

Herman, Ann E; Chinn, Leslie W; Kotwal, Shweta G; Murray, Elaine R; Zhao, Rui; Florero, Marilyn; Lin, Alyse; Moein, Anita; Wang, Rena; Bremer, Meire; Kokubu, Serika; Serone, Adrian P; Hanze, Eva L; Viberg, Anders; Morimoto, Alyssa M; Winter, Helen R; Katsumoto, Tamiko R

2018-06-01

GDC-0853 is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) that is highly selective and noncovalent, leading to reversible binding. In double-blind, randomized, and placebo-controlled phase I healthy volunteer studies, GDC-0853 was well tolerated, with no dose-limiting adverse events (AEs) or serious AEs. The maximum tolerated dose was not reached during dose escalation (≤600 mg, single ascending dose (SAD) study; ≤250 mg twice daily (b.i.d.) and ≤500 mg once daily, 14-day multiple ascending dose (MAD) study). Plasma concentrations peaked 1-3 hours after oral administration and declined thereafter, with a steady-state half-life ranging from 4.2-9.9 hours. Independent assays demonstrated dose-dependent BTK target engagement. Based on pharmacokinetic/pharmacodynamic (PK/PD) simulations, a once-daily dosing regimen (e.g., 100 mg, q.d.) is expected to maintain a high level of BTK inhibition over the dosing interval. Taken together, the safety and PK/PD data support GDC-0853 evaluation in rheumatoid arthritis, lupus, and other autoimmune or inflammatory indications. © 2018 American Society for Clinical Pharmacology and Therapeutics.

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

PubMed Central

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

2017-01-01

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

Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Philippe, Michael; Ranchon, Florence; Gilis, Lila; Schwiertz, Vérane; Vantard, Nicolas; Ader, Florence; Labussiere-Wallet, Hélène; Thomas, Xavier; Nicolini, Franck-Emmanuel; Wattel, Eric; Ducastelle-Leprêtre, Sophie; Barraco, Fiorenza; Lebras, Laure; Salles, Gilles; Michallet, Mauricette; Rioufol, Catherine

2016-04-01

After allogeneic hematopoietic stem cell transplantation (HSCT), BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance < 60 mL/min) and 2 severe (creatinine clearance < 30 mLmin). Mean decrease in creatinine clearance after cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs were observed independently of cidofovir dose or administration route. Cidofovir is an effective therapy for BKV-HC but requires very precise renal function management to avoid toxicity. Cidofovir treatment modalities (high dose, intravesical instillation, or low dose [≤1 mg/kg]) needs to be investigated in randomized controlled trials. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Optimization of the temporal pattern of radiation: An IMRT based study

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

Altman, Michael B.; Chmura, Steven J.; Deasy, Joseph O.

Purpose: To investigate how the temporal pattern of dose applied during a single-intensity modulated radiation therapy (IMRT) fraction can be arranged to maximize or minimize cell kill. Methods and Materials: Using the linear-quadratic repair-time model and a simplified IMRT delivery pattern model, the surviving fraction of cells for a single fraction was calculated for all permutations of the dose delivery pattern for an array of clinically based IMRT cases. Maximization of cell kill was achieved by concentrating the highest doses in the middle of a fraction, while minimization was achieved by spreading the highest doses between the beginning and end.more » The percent difference between maximum and minimum cell kill (%Diff{sub min/max}) and the difference between maximum and minimum total doses normalized to 2 Gy/fx ({delta}NTD{sub 2Gy}) was calculated for varying fraction durations (T), {alpha}/{beta} ratios, and doses/fx. Results: %Diff{sub min/max} and {delta}NTD{sub 2Gy} both increased with increasing T and with decreasing {alpha}/{beta}. The largest increases occurred with dose/fx. With {alpha}/{beta} = 3 Gy and 30 min/fx, %Diff{sub min/max} ranged from 2.7-5.3% for 2 Gy/fx to 48.6-74.1% for 10 Gy/fx, whereas {delta}NTD{sub 2Gy} ranged from 1.2 Gy-2.4 Gy for 30 fractions of 2 Gy/fx to 2.3-4.8 Gy for 2 fractions of 10.84 Gy/fx. Using {alpha}/{beta} = 1.5 Gy, an analysis of prostate hypofractionation schemes yielded differences in clinical outcome based on the pattern of applied dose ranging from 3.2%-6.1% of the treated population. Conclusions: Rearrangement of the temporal pattern of dose for a single IMRT fraction could be used to optimize cell kill and to directly, though modestly, affect treatment outcome.« less

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

Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin

Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of themore » tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.« less

Can the Equivalent Sphere Model Approximate Organ Doses in Space Radiation Environments?

NASA Technical Reports Server (NTRS)

Zi-Wei, Lin

2007-01-01

In space radiation calculations it is often useful to calculate the dose or dose equivalent in blood-forming organs (BFO). the skin or the eye. It has been customary to use a 5cm equivalent sphere to approximate the BFO dose. However previous studies have shown that a 5cm sphere gives conservative dose values for BFO. In this study we use a deterministic radiation transport with the Computerized Anatomical Man model to investigate whether the equivalent sphere model can approximate organ doses in space radiation environments. We find that for galactic cosmic rays environments the equivalent sphere model with an organ-specific constant radius parameter works well for the BFO dose equivalent and marginally well for the BFO dose and the dose equivalent of the eye or the skin. For solar particle events the radius parameters for the organ dose equivalent increase with the shielding thickness, and the model works marginally for BFO but is unacceptable for the eye or the skin The ranges of the radius parameters are also shown and the BFO radius parameters are found to be significantly larger than 5 cm in all eases.

Estimation of patient radiation dose from whole body 18F- FDG PET/CT examination in cancer imaging: a preliminary study

NASA Astrophysics Data System (ADS)

Mahmud, M. H.; Nordin, A. J.; Saad, F. F. Ahmad; Fattah Azman, A. Z.

2014-11-01

This study aims to estimate the radiation effective dose resulting from whole body fluorine-18 flourodeoxyglucose Positron Emission Tomography (18F-FDG PET) scanning as compared to conservative Computed Tomography (CT) techniques in evaluating oncology patients. We reviewed 19 oncology patients who underwent 18F-FDG PET/CT at our centre for cancer staging. Internal and external doses were estimated using radioactivity of injected FDG and volume CT Dose Index (CTDIvol), respectively with employment of the published and modified dose coefficients. The median differences of dose among the conservative CT and PET protocols were determined using Kruskal Wallis test with p < 0.05 considered as significant. The median (interquartile range, IQR) effective doses of non-contrasted CT, contrasted CT and PET scanning protocols were 7.50 (9.35) mSv, 9.76 (3.67) mSv and 6.30 (1.20) mSv, respectively, resulting in the total dose of 21.46 (8.58) mSv. Statistically significant difference was observed in the median effective dose between the three protocols (p < 0.01). The effective doses of whole body 18F-FDG PET technique may be effective the lowest amongst the conventional CT imaging techniques.

On the need for quality assurance in superficial kilovoltage radiotherapy.

PubMed

Austerlitz, C; Mota, H; Gay, H; Campos, D; Allison, R; Sibata, C

2008-01-01

External auditing of beam output and energy qualities of four therapeutic X-ray machines were performed in three radiation oncology centres in northeastern Brazil. The output and half-value layers (HVLs) were determined using a parallel-plate ionisation chamber and high-purity aluminium foils, respectively. The obtained values of absorbed dose to water and energy qualities were compared with those obtained by the respective institutions. The impact on the prescribed dose was analysed by determining the half-value depth (D(1/2)). The beam outputs presented percent differences ranging from -13 to +25%. The ratio between the HVL in use by the institution and the measurements obtained in this study ranged from 0.75 to 2.33. Such deviations in HVL result in percent differences in dose at D(1/2) ranging from -52 to +8%. It was concluded that dosimetric quality audit programmes in radiation therapy should be expanded to include dermatological radiation therapy and such audits should include HVL verification.

Initial Dosing and Taper Complexity of Methadone and Morphine for Treatment of Neonatal Abstinence Syndrome

PubMed Central

Ibach, Bethany W.; Johnson, Peter N.; Ernst, Kimberly D.; Harrison, Donald; Miller, Jamie L.

2016-01-01

Background: Methadone and morphine are commonly used to treat neonatal abstinence syndrome (NAS). Limited data exist to describe the most appropriate initial doses and taper regimens of these agents. Objectives: Describe the median initial dose and frequency of methadone and morphine for NAS. Compare dose adjustments, time to symptom relief, and taper complexity between groups. Methods: Retrospective study of neonates receiving enteral methadone or morphine for NAS over a 4-year period. Data collection included medication regimen, abstinence scores based on the Modified Finnegan Neonatal Abstinence Scoring Tool, and adverse events. Planned home taper complexity was assessed using the Medication Taper Complexity Score–Revised (MTCS-R). The primary outcome was initial opioid dose. Secondary outcomes included number of dose adjustments, time to symptom relief, and MTCS-R score. Results: Fifty neonates were initially treated for NAS with methadone (n = 36) or morphine (n = 14). The median initial dose was 0.09 mg/kg (range = 0.03-0.2) for methadone and 0.04 mg/kg (range = 0.03-0.4) for morphine. The most common initial dosing interval was q8h for methadone versus q3h for morphine. Number of dose adjustments and time to symptom relief were similar between groups. Median MTCS-R scores were similar between groups. There was no difference in adverse events between groups. Limitations included small sample size, preference toward methadone use, and variability of initial opioid dosing and titration. Conclusions: There was significant variability in initial doses of both agents. Neonates receiving methadone required less frequent dosing than morphine, which may result in easier administration and may allow for safer outpatient administration.

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

PubMed

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

2014-02-01

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

Reduction of cardiac and pulmonary complication probabilities after breathing adapted radiotherapy for breast cancer

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

Korreman, Stine S.; Pedersen, Anders N.; Aarup, Lasse Rye

Purpose: Substantial reductions of cardio-pulmonary radiation doses can be achieved using voluntary deep inspiration breath-hold (DIBH) or free breathing inspiration gating (IG) in radiotherapy after conserving surgery for breast cancer. The purpose of this study is to evaluate the radiobiological implications of such dosimetric benefits. Methods and Materials: Patients from previously reported studies were pooled for a total of 33 patients. All patients underwent DIBH and free breathing (FB) scans, and 17 patients underwent an additional IG scan. Tangential conformal treatment plans covering the remaining breast, internal mammary, and periclavicular nodes were optimized for each scan, prescription dose 48 Gy.more » Normal tissue complication probabilities were calculated using the relative seriality model for the heart, and the model proposed by Burman et al. for the lung. Results: Previous computed tomography studies showed that both voluntary DIBH and IG provided reduction of the lung V{sub 5} (relative volume receiving more than 50% of prescription dose) on the order of 30-40%, and a 80-90% reduction of the heart V{sub 5} for left-sided cancers. Corresponding pneumonitis probability of 28.1% (range, 0.7-95.6%) for FB could be reduced to 2.6% (range, 0.1-40.1%) for IG, and 4.3% (range, 0.1-59%) for DIBH. The cardiac mortality probability could be reduced from 4.8% (range, 0.1-23.4%) in FB to 0.5% (range, 0.1-2.6%) for IG and 0.1% (range, 0-3.0%) for DIBH. Conclusions: Remarkable potential is shown for simple voluntary DIBH and free breathing IG to reduce the risk of both cardiac mortality and pneumonitis for the common technique of adjuvant tangential breast irradiation.« less

Practical strategies when using a stable isotope labeled microtracer for absolute bioavailability assessment: A case study of a high oral dose clinical candidate GDC-0810.

PubMed

Chen, Buyun; Lu, Pingping; Freeman, Dugan; Gao, Yang; Choo, Edna; DeMent, Kevin; Savage, Scott; Zhang, Kelly; Milanwoski, Dennis; Liu, Lichuan; Dean, Brian; Deng, Yuzhong

2018-05-30

The pH labile metabolite, hydrophobicity, high oral dose and systematic exposure of GDC-0810 posed tremendous challenges to develop a LC-MS method for a stable isotope labeled aBA study. In this study, we explored practical solutions to balance stability and sensitivity and to cope with the impact of high C p.o. to C i.v. ratio on the labeling selection and assay dynamic range. A [ 13 C 9 ] GDC-0810 was synthesized to minimize the isotopic interference between PO dose, internal standard and I.V. microtracer. A highly sensitive LC-MS assay was validated for quantitation of [ 13 C 9 ] GDC-0810 from 5 to 1250 pg/mL. The optimized method was applied to a proof of concept cynomolgus monkey aBA study and the bioavailability calculated using microtracer dosing and regular dosing were similar to each other. Copyright © 2018 Elsevier B.V. All rights reserved.

Bismuth-Silicon and Bismuth-Polyurethane Composite Shields for Breast Protection in Chest Computed Tomography Examinations

PubMed Central

Mehnati, Parinaz; Arash, Mehran; Akhlaghi, Parisa

2018-01-01

The article aims at constructing protective composite shields for breasts in chest computed tomography and investigating the effects of applying these new bismuth composites on dose and image quality. Polyurethane and silicon with 5% of bismuth were fabricated as a protective shield. At first, their efficiency in attenuating the X-ray beam was investigated by calculating the total attenuation coefficients at diagnostic energy range. Then, a physical chest phantom was scanned without and with these shields at tube voltage of 120 kVp, and image parameters together with dose values were studied. The results showed that these two shields have great effects on attenuating the X-ray beam, especially for lower energies (<40 kV), and in average, the attenuation coefficients of bismuth-polyurethane composite are higher in this energy range. The maximum relative differences between the average Hounsfield units (HUs) and noises of images without and with shield for both composites in 13 regions of interest were 4.5% and 15.7%, respectively. Moreover, primary investigation confirmed the ability of both shields (especially polyurethane-bismuth composite) in dose reduction. Comparing these two composites regarding the amount of dose reduction, the changes in HU and noise, and attenuation coefficients in diagnostic energy range, it seems that polyurethane composite is more useful for dose reduction, especially for higher tube voltages. PMID:29628636

Optimizing Radiation Doses for Computed Tomography Across Institutions: Dose Auditing and Best Practices.

PubMed

Demb, Joshua; Chu, Philip; Nelson, Thomas; Hall, David; Seibert, Anthony; Lamba, Ramit; Boone, John; Krishnam, Mayil; Cagnon, Christopher; Bostani, Maryam; Gould, Robert; Miglioretti, Diana; Smith-Bindman, Rebecca

2017-06-01

Radiation doses for computed tomography (CT) vary substantially across institutions. To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After the audit and meeting, head CT doses varied less, although some institutions increased and some decreased mean head CT doses and the proportion above benchmarks. Reviewing institutional doses and sharing dose-optimization best practices resulted in lower radiation doses for chest and abdominal CT and more consistent doses for head CT.

Pharmacokinetics and Pharmacodynamics of Twice Daily and Once Daily Regimens of Empagliflozin in Healthy Subjects.

PubMed

Macha, Sreeraj; Brand, Tobias; Meinicke, Thomas; Link, Jasmin; Broedl, Uli C

2015-08-01

This study was undertaken to compare the steady-state pharmacokinetic and pharmacodynamic properties of empagliflozin 5 mg twice daily (BID) and 10 mg once daily (QD) in healthy subjects. In an open-label, 2-way crossover study, subjects (n = 16) received empagliflozin 5 mg BID for 5 days and empagliflozin 10 mg QD for 5 days in a randomized order, with a washout period of ≥6 days between each treatment. The primary objective was the comparison of the overall exposure during a 24-hour period at steady state (AUC0-24,ss) for empagliflozin, based on standard bioequivalence criteria, with BID and QD dose regimens. The study population comprised 7 (43.8%) men and 9 (56.3%) women with a baseline median age of 38.0 years (range, 23-47 years) and a median body mass index of 23.3 kg/m(2) (range, 19.8-27.8 kg/m(2)). Based on standard bioequivalence criteria, there was no difference in the overall exposure of empagliflozin between BID and QD dose regimens (geometric mean ratio of AUC0-24,ss for empagliflozin 5 mg BID compared with empagliflozin 10 mg QD = 99.36%; 90% CI, 94.29-104.71). For empagliflozin 10 mg QD, mean (%CV) AUC during the dosing interval was 1900 nmol · h/L (20.6%), mean (%CV) Cmax,ss was 330 nmol/L (25.3%), and median (range) Tmax,ss was 1.0 hour (0.7-2.0 hours). For empagliflozin 5 mg BID, mean (%CV) AUC during the dosing interval was 1010 nmol · h/L (15.1%) and 867 nmol · h/L (18.6%) after the morning and evening dose, respectively, mean (%CV) Cmax,ss was 193 nmol/L (16.5%) and 120 nmol/L (21.0%), respectively, and median Tmax,ss was 1.0 hour (range, 0.7-2.0 hours) and 2.0 hours (range, 1.0-4.0 hours), respectively. The mean (%CV) cumulative amount of glucose excreted in urine during 24 hours was 52.1 g (32.1%) with empagliflozin 5 mg BID and 43.9 g (30.3%) with empagliflozin 10 mg QD. Adverse events were reported in six subjects (37.5%) receiving empagliflozin 5 mg BID and four (25.0%) receiving empagliflozin 10 mg QD. Headache was the most frequent AE. No severe, serious, or drug-related AEs were reported. There were no clinically relevant differences in pharmacokinetic or pharmacodynamic properties between BID and QD dose regimens of empagliflozin in healthy subjects. Both dose regimens were well tolerated. EU Clinical Trials Register (EudraCT) number: 2009-012524-90. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

SU-E-T-486: Effect of the Normalized Prescription Isodose Line On Target Dose Deficiency in Lung SBRT Based On Monte Carlo Calculation

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

Zheng, D; Zhang, Q; Zhou, S

Purpose: To investigate the impact of normalized prescription isodose line on target dose deficiency calculated with Monte Carlo (MC) vs. pencil Beam (PB) in lung SBRT. RTOG guidelines recommend prescription lines between 60% and 90% for lung SBRT. How this affects the magnitude of MC-calculated target dose deficiency has never been studied. Methods: Under an IRB-approved protocol, four lung SBRT patients were replanned following RTOG0813 by a single physicist. For each patient, four alternative plans were generated based on PB calculation prescribing to 60–90% isodose lines, respectively. Each plan consisted of 360o coplanar dynamic conformal arcs with beam apertures manuallymore » optimized to achieve similar dose coverage and conformity for all plans of the same patient. Dose distribution was calculated with MC and compared to that with PB. PTV dose-volume endpoints were compared, including Dmin, D5, Dmean, D95, and Dmax. PTV V100 coverage, conformity index (CI), and heterogeneity index (HI) were also evaluated. Results: For all 16 plans, median (range) PTV V100 and CI were 99.7% (97.5–100%) and 1.27 (1.20–1.41), respectively. As expected, lower prescription line resulted in higher target dose heterogeneity, yielding median (range) HI of 1.26 (1.05–1.51) for all plans. Comparing MC to PB, median (range) D95, Dmean, D5 PTV dose deficiency were 18.9% (11.2–23.2%), 15.6% (10.0–22.7%), and 9.4%(5.5–13.6%) of the prescription dose, respectively. The Dmean, D5, and Dmax deficiency was found to monotonically increase with decreasing prescription line from 90% to 60%, while the Dmin deficiency monotonically decreased. D95 deficiency exhibited more complex trend, reaching the largest deficiency at 80% for all patients. Conclusion: Dependence on prescription isodose line was found for MC-calculated PTV dose deficiency of lung SBRT. When comparing reported MC dose deficiency values from different institutions, their individual selections of prescription line should be considered in addition to other factors affecting the deficiency magnitude.« less

Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-11-08

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

Pergolide: multiple-dose pharmacokinetics in patients with mild to moderate Parkinson disease.

PubMed

Thalamas, Claire; Rajman, Iris; Kulisevsky, Jaime; Lledó, Alberto; Mackie, Alison E; Blin, Olivier; Gillespie, Todd A; Seger, Mary; Rascol, Olivier

2005-01-01

The primary objective of this study was to describe the pharmacokinetics of oral pergolide in patients with mild to moderate Parkinson disease using a new high-performance liquid chromatography-tandem mass spectrometry assay. A secondary objective was to investigate the relationship between plasma concentrations and efficacy. Fourteen patients with a diagnosis of Parkinson disease completed this multicenter, open-label, dose-escalating study. Pergolide was administered for 58 days, using increasing daily doses from 0.05 mg daily up to 1 mg three times daily and then tapering the dose. The steady-state pharmacokinetic profile and motor score were determined at dose levels of 0.25, 0.5, and 1 mg three times a day and during elimination after the last dose. Pergolide was absorbed with a median time to maximum concentration of 2 to 3 hours across the dose range. Systemic exposure appeared to increase proportionally with dose over the range of 0.25 to 1 mg three times daily within a patient, but there was a large variability in exposures between patients (interpatient coefficients of variation were 56.4% for the area under the curve). Pergolide was widely distributed (volume of distribution, approximately 14,000 L) and was eliminated with a mean half-life of 21 hours. Motor scores improved as both peak plasma pergolide concentrations and exposure increased. No unexpected safety concerns were identified. Pergolide is absorbed relatively quickly into the systemic circulation, has a large apparent volume of distribution, and has a relatively long half-life (mean, 21 hours). This prolonged half-life is of particular interest, given the current hypothesis that more continuous dopaminergic receptor stimulation may reduce motor complications in patients with Parkinson disease.

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

In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model.

PubMed

Lepak, Alexander J; Andes, David R

2016-08-01

Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0-∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship observed with escalating doses of delafloxacin. Maximal organism reductions ranged from 2 log10 to more than 4 log10 The median free-drug AUC/MIC magnitude associated with net stasis for each species group was 1.45, 0.56, and 40.3 for S. aureus, S. pneumoniae, and K. pneumoniae, respectively. AUC/MIC targets for the 1-log kill endpoint were 2- to 5-fold higher. Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes. These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints for delafloxacin for the treatment of lower respiratory tract infections involving these pathogens. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model

PubMed Central

Lepak, Alexander J.

2016-01-01

Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae. Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0–∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship observed with escalating doses of delafloxacin. Maximal organism reductions ranged from 2 log10 to more than 4 log10. The median free-drug AUC/MIC magnitude associated with net stasis for each species group was 1.45, 0.56, and 40.3 for S. aureus, S. pneumoniae, and K. pneumoniae, respectively. AUC/MIC targets for the 1-log kill endpoint were 2- to 5-fold higher. Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes. These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints for delafloxacin for the treatment of lower respiratory tract infections involving these pathogens. PMID:27216072

An atlas-based organ dose estimator for tomosynthesis and radiography

NASA Astrophysics Data System (ADS)

Hoye, Jocelyn; Zhang, Yakun; Agasthya, Greeshma; Sturgeon, Greg; Kapadia, Anuj; Segars, W. Paul; Samei, Ehsan

2017-03-01

The purpose of this study was to provide patient-specific organ dose estimation based on an atlas of human models for twenty tomosynthesis and radiography protocols. The study utilized a library of 54 adult computational phantoms (age: 18-78 years, weight 52-117 kg) and a validated Monte-Carlo simulation (PENELOPE) of a tomosynthesis and radiography system to estimate organ dose. Positioning of patient anatomy was based on radiographic positioning handbooks. The field of view for each exam was calculated to include relevant organs per protocol. Through simulations, the energy deposited in each organ was binned to estimate normalized organ doses into a reference database. The database can be used as the basis to devise a dose calculator to predict patient-specific organ dose values based on kVp, mAs, exposure in air, and patient habitus for a given protocol. As an example of the utility of this tool, dose to an organ was studied as a function of average patient thickness in the field of view for a given exam and as a function of Body Mass Index (BMI). For tomosynthesis, organ doses can also be studied as a function of x-ray tube position. This work developed comprehensive information for organ dose dependencies across tomosynthesis and radiography. There was a general exponential decrease dependency with increasing patient size that is highly protocol dependent. There was a wide range of variability in organ dose across the patient population, which needs to be incorporated in the metrology of organ dose.

Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window

PubMed Central

2016-01-01

Background: Abundant evidence at the anatomical, electrophysiological, and molecular levels implicates metabotropic glutamate receptor subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studies were subjected to a systematic review to find out if mGluR5 NAMs have a therapeutic potential that can be translated to the clinic. Methods: Literature on consumption/self-administration and reinstatement of drug seeking as outcomes of interest published up to April 2015 was retrieved via PubMed. The review focused on the effects of systemic (i.p., i.v., s.c.) administration of the mGluR5 NAMs 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP) on paradigms with cocaine, ethanol, nicotine, and food in rats. Results: MTEP and MPEP were found to reduce self-administration of cocaine, ethanol, and nicotine at doses ≥1mg/kg and 2.5mg/kg, respectively. Dose-response relationship resembled a sigmoidal curve, with low doses not reaching statistical significance and high doses reliably inhibiting self-administration of drugs of abuse. Importantly, self-administration of cocaine, ethanol, and nicotine, but not food, was reduced by MTEP and MPEP in the dose range of 1 to 2mg/kg and 2.5 to 3.2mg/kg, respectively. This dose range corresponds to approximately 50% to 80% mGluR5 occupancy. Interestingly, the limited data found in mice and monkeys showed a similar therapeutic window. Conclusion: Altogether, this review suggests a therapeutic window for mGluR5 NAMs that can be translated to the treatment of substance-related and addictive disorders. PMID:26802568

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

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children

PubMed Central

Balaguru, Duraisamy; Rodriguez, Matthew; Leon, Stephanie; Wagner, Louis K; Beasley, Charles W; Sultzer, Andrew; Numan, Mohammed T

2018-01-01

Objectives: Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot® (Landauer, Glenwood, IL, USA). Background: Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. Materials and Methods: The nanoDot® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. Results: A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3–86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values (R2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. Conclusions: Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients. PMID:29440825

Comparison of skin dose measurement using nanoDot® dosimeter and machine readings of radiation dose during cardiac catheterization in children.

PubMed

Balaguru, Duraisamy; Rodriguez, Matthew; Leon, Stephanie; Wagner, Louis K; Beasley, Charles W; Sultzer, Andrew; Numan, Mohammed T

2018-01-01

Direct measurement of skin dose of radiation for children using optically stimulated luminescence (OSL) technology using nanoDot ® (Landauer, Glenwood, IL, USA). Radiation dose is estimated as cumulative air kerma (AK) and dosearea product based on standards established for adult size patients. Body size of pediatric patients who undergo cardiac catheterization for congenital heart disease vary widely from newborn to adolescence. Direct, skindose measurement applying OSL technology may eliminate errors in the estimate. The nanoDot ® (1 cm × 1 cm × flat plastic cassette) is applied to patient's skin using adhesive tape during cardiac catheterization and radiation skin doses were read within 24 hrs. nanoDot ® values were compared to the currently available cumulative AK values estimated and displayed on fluoroscopy monitor. A total of 12 children were studied, aged 4 months to 18 years (median 1.1 years) and weight range 5.3-86 kg (median 8.4 kg). nanoDot® readings ranged from 2.58 mGy to 424.8 mGy (median 84.1 mGy). Cumulative AK ranged from 16.2 mGy to 571.2 mGy (median 171.1 mGy). Linear correlation was noted between nanoDot® values and AK values ( R 2 = 0.88, R = 0.94). nanoDot® readings were approximately 65% of the estimated cumulative AK estimated using the International Electrotechnical Commission standards. Application of OSL technology using nanoDot® provides an alternative to directly measure fluoroscopic skin dose in children during cardiac catheterization. Our data show that the actual skin dose for children is approximately one-third lower than the AK estimated using international standards for adult size patients.

Evaluating health risks from occupational exposure to pesticides and the regulatory response.

PubMed Central

Woodruff, T J; Kyle, A D; Bois, F Y

1994-01-01

In this study, we used measurements of occupational exposures to pesticides in agriculture to evaluate health risks and analyzed how the federal regulatory program is addressing these risks. Dose estimates developed by the State of California from measured occupational exposures to 41 pesticides were compared to standard indices of acute toxicity (LD50) and chronic effects (reference dose). Lifetime cancer risks were estimated using cancer potencies. Estimated absorbed daily doses for mixers, loaders, and applicators of pesticides ranged from less than 0.0001% to 48% of the estimated human LD50 values, and doses for 10 of 40 pesticides exceeded 1% of the estimated human LD50 values. Estimated lifetime absorbed daily doses ranged from 0.1% to 114,000% of the reference doses developed by the U.S. Environmental Protection Agency, and doses for 13 of 25 pesticides were above them. Lifetime cancer risks ranged from 1 per million to 1700 per million, and estimates for 12 of 13 pesticides were above 1 per million. Similar results were obtained for field workers and flaggers. For the pesticides examined, exposures pose greater risks of chronic effects than acute effects. Exposure reduction measures, including use of closed mixing systems and personal protective equipment, significantly reduced exposures. Proposed regulations rely primarily on requirements for personal protective equipment and use restrictions to protect workers. Chronic health risks are not considered in setting these requirements. Reviews of pesticides by the federal pesticide regulatory program have had little effect on occupational risks. Policy strategies that offer immediate protection for workers and that are not dependent on extensive review of individual pesticides should be pursued. Images Figure 1. PMID:7713022

WE-D-BRE-06: Quantification of Dose-Response for High Grade Esophagtis Patients Using a Novel Voxel-To-Voxel Method

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

Niedzielski, J; Martel, M; Tucker, S

2014-06-15

Purpose: Radiation induces an inflammatory response in the esophagus, discernible on CT studies. This work objectively quantifies the voxel esophageal radiation-response for patients with acute esophagitis. This knowledge is an important first-step towards predicting the effect of complex dose distributions on patient esophagitis symptoms. Methods: A previously validated voxel-based methodology of quantifying radiation esophagitis severity was used to identify the voxel dose-response for 18 NSCLC patients with severe esophagitis (CTCAE grading criteria, grade2 or higher). The response is quantified as percent voxel volume change for a given dose. During treatment (6–8 weeks), patients had weekly 4DCT studies and esophagitis scoring.more » Planning CT esophageal contours were deformed to each weekly CT using a demons DIR algorithm. An algorithm using the Jacobian Map from the DIR of the planning CT to all weekly CTs was used to quantify voxel-volume change, along with corresponding delivered voxel dose, to the planning voxel. Dose for each voxel for each time-point was calculated on each previous weekly CT image, and accumulated using DIR. Thus, for each voxel, the volume-change and delivered dose was calculated for each time-point. The data was binned according to when the volume-change first increased by a threshold volume (10%–100%, in 10% increments), and the average delivered dose calculated for each bin. Results: The average dose resulting in a voxel volume increase of 10–100% was 21.6 to 45.9Gy, respectively. The mean population dose to give a 50% volume increase was 36.3±4.4Gy, (range:29.8 to 43.5Gy). The average week of 50% response was 4.1 (range:4.9 to 2.8 weeks). All 18 patients showed similar dose to first response curves, showing a common trend in the initial inflammatoryresponse. Conclusion: We extracted the dose-response curve of the esophagus on a voxel-to-voxel level. This may be useful for estimating the esophagus response (and patient symptoms) to complicated dose distributions.« less

Radiation dose delivered to the proximal penis as a predictor of the risk of erectile dysfunction after three-dimensional conformal radiotherapy for localized prostate cancer

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

Wernicke, A. Gabriella; Valicenti, Richard; DiEva, Kelly

2004-12-01

Purpose/objective: In this study, we evaluated in a serial manner whether radiation dose to the bulb of the penis is predictive of erectile dysfunction, ejaculatory difficulty (EJ), and overall satisfaction with sex life (quality of life) by using serial validated self-administered questionnaires. Methods and materials: Twenty-nine potent men with AJCC Stage II prostate cancer treated with three-dimensional conformal radiation therapy alone to a median dose 72.0 Gy (range: 66.6-79.2 Gy) were evaluated by determining the doses received by the penile bulb. The penile bulb was delineated volumetrically, and the dose-volume histogram was obtained on each patient. Results: The median follow-upmore » time was 35 months (range, 16-43 months). We found that for D{sub 30}, D{sub 45}, D{sub 60}, and D{sub 75} (doses to a percent volume of PB: 30%, 45%, 60%, and 75%), higher than the corresponding median dose (defined as high-dose group) correlated with an increased risk of impotence (erectile dysfunction firmness score = 0) (odds ratio [OR] = 7.5, p = 0.02; OR = 7.5, p = 0.02; OR = 8.6, p = 0.008; and OR = 6.9, p = 0.015, respectively). Similarly, for EJD D{sub 30}, D{sub 45}, D{sub 60}, and D{sub 75}, doses higher than the corresponding median ones correlated with worsening ejaculatory function score (EJ = 0 or 1) (OR = 8, p = 0.013; OR = 8, p 0.013; OR = 9.2, p = 0.015; and OR = 8, p = 0.026, respectively). For quality of life, low ({<=}median dose) dose groups of patients improve over time, whereas high-dose groups of patients worsen. Conclusions: This study supports the existence of a penile bulb dose-volume relationship underlying the development of radiation-induced erectile dysfunction. Our data may guide the use of inverse treatment planning to maximize the probability of maintaining sexual potency after radiation therapy.« less

SU-E-J-06: Additional Imaging Guidance Dose to Patient Organs Resulting From X-Ray Tubes Used in CyberKnife Image Guidance System

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

Sullivan, A; Ding, G

Purpose: The use of image-guided radiation therapy (IGRT) has become increasingly common, but the additional radiation exposure resulting from repeated image guidance procedures raises concerns. Although there are many studies reporting imaging dose from different image guidance devices, imaging dose for the CyberKnife Robotic Radiosurgery System is not available. This study provides estimated organ doses resulting from image guidance procedures on the CyberKnife system. Methods: Commercially available Monte Carlo software, PCXMC, was used to calculate average organ doses resulting from x-ray tubes used in the CyberKnife system. There are seven imaging protocols with kVp ranging from 60 – 120 kVmore » and 15 mAs for treatment sites in the Cranium, Head and Neck, Thorax, and Abdomen. The output of each image protocol was measured at treatment isocenter. For each site and protocol, Adult body sizes ranging from anorexic to extremely obese were simulated since organ dose depends on patient size. Doses for all organs within the imaging field-of-view of each site were calculated for a single image acquisition from both of the orthogonal x-ray tubes. Results: Average organ doses were <1.0 mGy for every treatment site and imaging protocol. For a given organ, dose increases as kV increases or body size decreases. Higher doses are typically reported for skeletal components, such as the skull, ribs, or clavicles, than for softtissue organs. Typical organ doses due to a single exposure are estimated as 0.23 mGy to the brain, 0.29 mGy to the heart, 0.08 mGy to the kidneys, etc., depending on the imaging protocol and site. Conclusion: The organ doses vary with treatment site, imaging protocol and patient size. Although the organ dose from a single image acquisition resulting from two orthogonal beams is generally insignificant, the sum of repeated image acquisitions (>100) could reach 10–20 cGy for a typical treatment fraction.« less

Comparison of Kodak EDR2 and Gafchromic EBT film for intensity-modulated radiation therapy dose distribution verification.

PubMed

Sankar, A; Ayyangar, Komanduri M; Nehru, R Mothilal; Kurup, P G Gopalakrishna; Murali, V; Enke, Charles A; Velmurugan, J

2006-01-01

The quantitative dose validation of intensity-modulated radiation therapy (IMRT) plans require 2-dimensional (2D) high-resolution dosimetry systems with uniform response over its sensitive region. The present work deals with clinical use of commercially available self-developing Radio Chromic Film, Gafchromic EBT film, for IMRT dose verification. Dose response curves were generated for the films using a VXR-16 film scanner. The results obtained with EBT films were compared with the results of Kodak extended dose range 2 (EDR2) films. The EBT film had a linear response between the dose range of 0 to 600 cGy. The dose-related characteristics of the EBT film, such as post irradiation color growth with time, film uniformity, and effect of scanning orientation, were studied. There was up to 8.6% increase in the color density between 2 to 40 hours after irradiation. There was a considerable variation, up to 8.5%, in the film uniformity over its sensitive region. The quantitative differences between calculated and measured dose distributions were analyzed using DTA and Gamma index with the tolerance of 3% dose difference and 3-mm distance agreement. The EDR2 films showed consistent results with the calculated dose distributions, whereas the results obtained using EBT were inconsistent. The variation in the film uniformity limits the use of EBT film for conventional large-field IMRT verification. For IMRT of smaller field sizes (4.5 x 4.5 cm), the results obtained with EBT were comparable with results of EDR2 films.

Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers.

PubMed

Smit, H J; Rogers, P J

2000-10-01

Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola). This study measured the effects of 0, 12.5, 25, 50 and 100 mg caffeine on cognitive performance, mood and thirst in adults with low and moderate to high habitual caffeine intakes. This was a double-blind, within-subjects study. Following overnight caffeine abstinence, participants (n=23) completed a test battery once before and three times after placebo or caffeine administration. The test battery consisted of two performance tests, a long duration simple reaction time task and a rapid visual information processing task, and a mood questionnaire (including also an item on thirst). Effects on performance and mood confirmed a psychostimulant action of caffeine. All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.

Analysis of patient CT dose data using virtualdose

NASA Astrophysics Data System (ADS)

Bennett, Richard

X-ray computer tomography has many benefits to medical and research applications. Recently, over the last decade CT has had a large increase in usage in hospitals and medical diagnosis. In pediatric care, from 2000 to 2006, abdominal CT scans increased by 49 % and chest CT by 425 % in the emergency room (Broder 2007). Enormous amounts of effort have been performed across multiple academic and government groups to determine an accurate measure of organ dose to patients who undergo a CT scan due to the inherent risks with ionizing radiation. Considering these intrinsic risks, CT dose estimating software becomes a necessary tool that health care providers and radiologist must use to determine many metrics to base the risks versus rewards of having an x-ray CT scan. This thesis models the resultant organ dose as body mass increases for patients with all other related scan parameters fixed. In addition to this,this thesis compares a modern dose estimating software, VirtualDose CT to two other programs, CT-Expo and ImPACT CT. The comparison shows how the software's theoretical basis and the phantom they use to represent the human body affect the range of results in organ dose. CT-Expo and ImPACT CT dose estimating software uses a different model for anatomical representation of the organs in the human body and the results show how that approach dramatically changes the outcome. The results categorizes four datasets as compared to the three software types where the appropriate phantom was available. Modeling was done to simulate chest abdominal pelvis scans and whole body scans. Organ dose difference versus body mass index shows as body mass index (BMI) ranges from 23.5 kg/m 2 to 45 kg/m2 the amount of organ dose also trends a percent change from -4.58 to -176.19 %. Comparing organ dose difference with increasing x-ray tube potential from 120 kVp to 140 kVp the percent change in organ dose increases from 55 % to 65 % across all phantoms. In comparing VirtualDose to CT-Expo for organ dose difference versus age, male phantoms show percent difference of -19 % to 25 % for various organs minus bone surface and breast tissues results. Finally, for organ dose difference across all software for average adult phantom the results range from -45 % to 6 % in the comparison of ImPACT CT to VirtualDose and -27 % to 66 % for the comparison of CT-Expo to VirtualDose. In the comparison for increased BMI (done only in VirtualDose), results show that with all other parameters fixed, the organ dose goes down as BMI increases, which is due to the increase in adipose tissue and bulk of the patient model. The range of results when comparing all the three softwares have a wide range, in some cases greater than 150 %, it is evident that using a different anatomical basis for the human phantom and the theoretical basis for the dose estimation will cause fluctuation in the results. Therefore, choosing the software with the most accurate human phantom will provide a closer range to the true dose to the organ.

Terbinafine in Combination with Other Antifungal Agents for Treatment of Resistant or Refractory Mycoses: Investigating Optimal Dosing Regimens Using a Physiologically Based Pharmacokinetic Model

PubMed Central

Dolton, Michael J.; Perera, Vidya; Pont, Lisa G.

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens. PMID:24126579

Efficacy of Formoterol Fumarate Delivered by Metered Dose Inhaler Using Co-Suspension™ Delivery Technology Versus Foradil® Aerolizer® in Moderate-To-Severe COPD: A Randomized, Dose-Ranging Study.

PubMed

Sethi, Sanjay; Fogarty, Charles; Hanania, Nicola A; Martinez, Fernando J; Rennard, Stephen; Fries, Michael; Orevillo, Chad; Darken, Patrick; St Rose, Earl; Strom, Shannon; Fischer, Tracy; Golden, Michael; Dwivedi, Sarvajna; Reisner, Colin

2016-11-17

Background: Co-Suspension™ Delivery Technology offers a novel pharmaceutical platform for inhaled drug therapy. This randomized, double-blind, placebo-controlled, single-dose study (NCT01349868) evaluated the efficacy of a range of doses for formoterol fumarate (FF) delivered using Co-Suspension delivery technology via a pressurized metered dose inhaler (MDI) versus placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Secondary objectives included determination of non-inferior efficacy and systemic exposure compared with open-label Foradil ® 12 μg (Foradil ® Aerolizer ® ; formoterol fumarate dry powder inhaler). Methods: Patients received each of the 6 study treatments (FF MDI [7.2, 9.6 and 19.2μg], placebo MDI and open-label Foradil ® [12 and 24µg]), separated by 3-10 days. Spirometry was performed 60 and 30 minutes prior to and at regular intervals up to 12 hours post-administration of study drug. The primary outcome measure was the change in forced expiratory volume in 1 second (FEV 1 ) area under the curve between 0 and 12 hours (AUC 0-12 ) relative to test day baseline. Results: A total of 50 patients were randomized to study treatment sequences. All doses of FF MDI demonstrated superiority to placebo ( p <0.0001) and non-inferiority to Foradil ® 12μg, on bronchodilator outcome measures. No serious adverse events were reported during the study. Conclusions: This study demonstrates non-inferiority of bronchodilator response and bioequivalent exposure of FF MDI 9.6μg to Foradil ® 12μg, with both agents exhibiting a similar safety profile in patients with moderate-to-severe COPD. This study supports the selection of FF MDI 9.6µg for further evaluation in Phase III trials.