SU-E-T-329: Dosimetric Impact of Implementing Metal Artifact Reduction Methods and Metal Energy Deposition Kernels for Photon Dose Calculations

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

Huang, J; Followill, D; Howell, R

2015-06-15

Purpose: To investigate two strategies for reducing dose calculation errors near metal implants: use of CT metal artifact reduction methods and implementation of metal-based energy deposition kernels in the convolution/superposition (C/S) method. Methods: Radiochromic film was used to measure the dose upstream and downstream of titanium and Cerrobend implants. To assess the dosimetric impact of metal artifact reduction methods, dose calculations were performed using baseline, uncorrected images and metal artifact reduction Methods: Philips O-MAR, GE’s monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI imaging with metal artifact reduction software applied (MARs).To assess the impact of metal kernels, titaniummore » and silver kernels were implemented into a commercial collapsed cone C/S algorithm. Results: The CT artifact reduction methods were more successful for titanium than Cerrobend. Interestingly, for beams traversing the metal implant, we found that errors in the dimensions of the metal in the CT images were more important for dose calculation accuracy than reduction of imaging artifacts. The MARs algorithm caused a distortion in the shape of the titanium implant that substantially worsened the calculation accuracy. In comparison to water kernel dose calculations, metal kernels resulted in better modeling of the increased backscatter dose at the upstream interface but decreased accuracy directly downstream of the metal. We also found that the success of metal kernels was dependent on dose grid size, with smaller calculation voxels giving better accuracy. Conclusion: Our study yielded mixed results, with neither the metal artifact reduction methods nor the metal kernels being globally effective at improving dose calculation accuracy. However, some successes were observed. The MARs algorithm decreased errors downstream of Cerrobend by a factor of two, and metal kernels resulted in more accurate backscatter dose upstream of metals. Thus, these two strategies do have the potential to improve accuracy for patients with metal implants in certain scenarios. This work was supported by Public Health Service grants CA 180803 and CA 10953 awarded by the National Cancer Institute, United States of Health and Human Services, and in part by Mobius Medical Systems.« less

Assessment of the dose reduction potential of a model-based iterative reconstruction algorithm using a task-based performance metrology

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

Samei, Ehsan, E-mail: samei@duke.edu; Richard, Samuel

2015-01-15

Purpose: Different computed tomography (CT) reconstruction techniques offer different image quality attributes of resolution and noise, challenging the ability to compare their dose reduction potential against each other. The purpose of this study was to evaluate and compare the task-based imaging performance of CT systems to enable the assessment of the dose performance of a model-based iterative reconstruction (MBIR) to that of an adaptive statistical iterative reconstruction (ASIR) and a filtered back projection (FBP) technique. Methods: The ACR CT phantom (model 464) was imaged across a wide range of mA setting on a 64-slice CT scanner (GE Discovery CT750 HD,more » Waukesha, WI). Based on previous work, the resolution was evaluated in terms of a task-based modulation transfer function (MTF) using a circular-edge technique and images from the contrast inserts located in the ACR phantom. Noise performance was assessed in terms of the noise-power spectrum (NPS) measured from the uniform section of the phantom. The task-based MTF and NPS were combined with a task function to yield a task-based estimate of imaging performance, the detectability index (d′). The detectability index was computed as a function of dose for two imaging tasks corresponding to the detection of a relatively small and a relatively large feature (1.5 and 25 mm, respectively). The performance of MBIR in terms of the d′ was compared with that of ASIR and FBP to assess its dose reduction potential. Results: Results indicated that MBIR exhibits a variability spatial resolution with respect to object contrast and noise while significantly reducing image noise. The NPS measurements for MBIR indicated a noise texture with a low-pass quality compared to the typical midpass noise found in FBP-based CT images. At comparable dose, the d′ for MBIR was higher than those of FBP and ASIR by at least 61% and 19% for the small feature and the large feature tasks, respectively. Compared to FBP and ASIR, MBIR indicated a 46%–84% dose reduction potential, depending on task, without compromising the modeled detection performance. Conclusions: The presented methodology based on ACR phantom measurements extends current possibilities for the assessment of CT image quality under the complex resolution and noise characteristics exhibited with statistical and iterative reconstruction algorithms. The findings further suggest that MBIR can potentially make better use of the projections data to reduce CT dose by approximately a factor of 2. Alternatively, if the dose held unchanged, it can improve image quality by different levels for different tasks.« less

Low tube voltage dual source computed tomography to reduce contrast media doses in adult abdomen examinations: A phantom study

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

Thor, Daniel; Brismar, Torkel B., E-mail: torkel.brismar@gmail.com; Fischer, Michael A.

Purpose: To evaluate the potential of low tube voltage dual source (DS) single energy (SE) and dual energy (DE) computed tomography (CT) to reduce contrast media (CM) dose in adult abdominal examinations of various sizes while maintaining soft tissue and iodine contrast-to-noise ratio (CNR). Methods: Four abdominal phantoms simulating a body mass index of 16 to 35 kg/m{sup 2} with four inserted syringes of 0, 2, 4, and 8 mgI/ml CM were scanned using a 64-slice DS-CT scanner. Six imaging protocols were used; one single source (SS) reference protocol (120 kV, 180 reference mAs), four low kV SE protocols (70more » and 80 kV using both SS and DS), and one DE protocol at 80/140 kV. Potential CM reduction with unchanged CNRs relative to the 120 kV protocol was calculated along with the corresponding increase in radiation dose. Results: The potential contrast media reductions were determined to be approximately 53% for DS 70 kV, 51% for SS 70 kV, 44% for DS 80 kV, 40% for SS 80 kV, and 20% for DE (all differences were significant, P < 0.05). Constant CNR could be achieved by using DS 70 kV for small to medium phantom sizes (16–26 kg/m{sup 2}) and for all sizes (16–35 kg/m{sup 2}) when using DS 80 kV and DE. Corresponding radiation doses increased by 60%–107%, 23%–83%, and 6%–12%, respectively. Conclusions: DS single energy CT can be used to reduce CM dose by 44%–53% with maintained CNR in adult abdominal examinations at the cost of an increased radiation dose. DS dual-energy CT allows reduction of CM dose by 20% at similar radiation dose as compared to a standard 120 kV single source.« less

Testosterone Dose Dependently Prevents Bone and Muscle Loss in Rodents after Spinal Cord Injury

PubMed Central

Conover, Christine F.; Beggs, Luke A.; Beck, Darren T.; Otzel, Dana M.; Balaez, Alexander; Combs, Sarah M.; Miller, Julie R.; Ye, Fan; Aguirre, J. Ignacio; Neuville, Kathleen G.; Williams, Alyssa A.; Conrad, Bryan P.; Gregory, Chris M.; Wronski, Thomas J.; Bose, Prodip K.; Borst, Stephen E.

2014-01-01

Abstract Androgen administration protects against musculoskeletal deficits in models of sex-steroid deficiency and injury/disuse. It remains unknown, however, whether testosterone prevents bone loss accompanying spinal cord injury (SCI), a condition that results in a near universal occurrence of osteoporosis. Our primary purpose was to determine whether testosterone-enanthate (TE) attenuates hindlimb bone loss in a rodent moderate/severe contusion SCI model. Forty (n=10/group), 14 week old male Sprague-Dawley rats were randomized to receive: (1) Sham surgery (T9 laminectomy), (2) moderate/severe (250 kdyne) SCI, (3) SCI+Low-dose TE (2.0 mg/week), or (4) SCI+High-dose TE (7.0 mg/week). Twenty-one days post-injury, SCI animals exhibited a 77–85% reduction in hindlimb cancellous bone volume at the distal femur (measured via μCT) and proximal tibia (measured via histomorphometry), characterized by a >70% reduction in trabecular number, 13–27% reduction in trabecular thickness, and increased trabecular separation. A 57% reduction in cancellous volumetric bone mineral density (vBMD) at the distal femur and a 20% reduction in vBMD at the femoral neck were also observed. TE dose dependently prevented hindlimb bone loss after SCI, with high-dose TE fully preserving cancellous bone structural characteristics and vBMD at all skeletal sites examined. Animals receiving SCI also exhibited a 35% reduction in hindlimb weight bearing (triceps surae) muscle mass and a 22% reduction in sublesional non-weight bearing (levator ani/bulbocavernosus [LABC]) muscle mass, and reduced prostate mass. Both TE doses fully preserved LABC mass, while only high-dose TE ameliorated hindlimb muscle losses. TE also dose dependently increased prostate mass. Our findings provide the first evidence indicating that high-dose TE fully prevents hindlimb cancellous bone loss and concomitantly ameliorates muscle loss after SCI, while low-dose TE produces much less profound musculoskeletal benefit. Testosterone-induced prostate enlargement, however, represents a potential barrier to the clinical implementation of high-dose TE as a means of preserving musculoskeletal tissue after SCI. PMID:24378197

Dose comparison between conventional and quasi-monochromatic systems for diagnostic radiology

NASA Astrophysics Data System (ADS)

Baldelli, P.; Taibi, A.; Tuffanelli, A.; Gambaccini, M.

2004-09-01

Several techniques have been introduced in the last year to reduce the dose to the patient by minimizing the risk of tumour induced by radiation. In this work the radiological potential of dose reduction in quasi-monochromatic spectra produced via mosaic crystal Bragg diffraction has been evaluated, and a comparison with conventional spectra has been performed for four standard examinations: head, chest, abdomen and lumbar sacral spine. We have simulated quasi-monochromatic x-rays with the Shadow code, and conventional spectra with the Spectrum Processor. By means of the PCXMC software, we have simulated four examinations according to parameters established by the European Guidelines, and calculated absorbed dose for principal organs and the effective dose. Simulations of quasi-monochromatic laminar beams have been performed without anti-scatter grid, because of their inherent scatter geometry, and compared with simulations with conventional beams with anti-scatter grids. Results have shown that the dose reduction due to the introduction of quasi-monochromatic x-rays depends on different parameters related to the quality of the beam, the organ composition and the anti-scatter grid. With parameters chosen in this study a significant dose reduction can be achieved for two out of four kinds of examination.

Task-based image quality evaluation of iterative reconstruction methods for low dose CT using computer simulations

NASA Astrophysics Data System (ADS)

Xu, Jingyan; Fuld, Matthew K.; Fung, George S. K.; Tsui, Benjamin M. W.

2015-04-01

Iterative reconstruction (IR) methods for x-ray CT is a promising approach to improve image quality or reduce radiation dose to patients. The goal of this work was to use task based image quality measures and the channelized Hotelling observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT applications. We performed realistic computer simulations at five radiation dose levels, from a clinical reference low dose D0 to 25% D0. A fixed size and contrast lesion was inserted at different locations into the liver of the XCAT phantom to simulate a weak signal. The simulated data were reconstructed on a commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany) using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The reconstructed images were analyzed by CHOs with both rotationally symmetric (RS) and rotationally oriented (RO) channels, and with different numbers of lesion locations (5, 10, and 20) in a signal known exactly (SKE), background known exactly but variable (BKEV) detection task. The area under the receiver operating characteristic curve (AUC) was used as a summary measure to compare the IR and analytic methods; the AUC was also used as the equal performance criterion to derive the potential dose reduction factor of IR. In general, there was a good agreement in the relative AUC values of different reconstruction methods using CHOs with RS and RO channels, although the CHO with RO channels achieved higher AUCs than RS channels. The improvement of IR over analytic methods depends on the dose level. The reference dose level D0 was based on a clinical low dose protocol, lower than the standard dose due to the use of IR methods. At 75% D0, the performance improvement was statistically significant (p < 0.05). The potential dose reduction factor also depended on the detection task. For the SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25% from D0 was achieved.

A study on the indirect urea dosing method in the Selective Catalytic Reduction system

NASA Astrophysics Data System (ADS)

Brzeżański, M.; Sala, R.

2016-09-01

This article presents the results of studies on concept solution of dosing urea in a gas phase in a selective catalytic reduction system. The idea of the concept was to heat-up and evaporate the water urea solution before introducing it into the exhaust gas stream. The aim was to enhance the processes of urea converting into ammonia, what is the target reductant for nitrogen oxides treatment. The study was conducted on a medium-duty Euro 5 diesel engine with exhaust line consisting of DOC catalyst, DPF filter and an SCR system with a changeable setup allowing to dose the urea in liquid phase (regular solution) and to dose it in a gas phase (concept solution). The main criteria was to assess the effect of physical state of urea dosed on the NOx conversion ratio in the SCR catalyst. In order to compare both urea dosing methods a special test procedure was developed which consisted of six test steps covering a wide temperature range of exhaust gas generated at steady state engine operation condition. Tests were conducted for different urea dosing quantities defined by the a equivalence ratio. Based on the obtained results, a remarkable improvement in NOx reduction was found for gas urea application in comparison to the standard liquid urea dosing. Measured results indicate a high potential to increase an efficiency of the SCR catalyst by using a gas phase urea and provide the basis for further scientific research on this type of concept.

Low radiation dose in computed tomography: the role of iodine

PubMed Central

Aschoff, Andrik J; Catalano, Carlo; Krix, Martin; Albrecht, Thomas

2017-01-01

Recent approaches to reducing radiation exposure during CT examinations typically utilize automated dose modulation strategies on the basis of lower tube voltage combined with iterative reconstruction and other dose-saving techniques. Less clearly appreciated is the potentially substantial role that iodinated contrast media (CM) can play in low-radiation-dose CT examinations. Herein we discuss the role of iodinated CM in low-radiation-dose examinations and describe approaches for the optimization of CM administration protocols to further reduce radiation dose and/or CM dose while maintaining image quality for accurate diagnosis. Similar to the higher iodine attenuation obtained at low-tube-voltage settings, high-iodine-signal protocols may permit radiation dose reduction by permitting a lowering of mAs while maintaining the signal-to-noise ratio. This is particularly feasible in first pass examinations where high iodine signal can be achieved by injecting iodine more rapidly. The combination of low kV and IR can also be used to reduce the iodine dose. Here, in optimum contrast injection protocols, the volume of CM administered rather than the iodine concentration should be reduced, since with high-iodine-concentration CM further reductions of iodine dose are achievable for modern first pass examinations. Moreover, higher concentrations of CM more readily allow reductions of both flow rate and volume, thereby improving the tolerability of contrast administration. PMID:28471242

Clinical experience in treating hypertension with fixed-dose combination therapy: angiotensin II receptor blocker losartan plus hydrochlorothiazide.

PubMed

Abe, Masanori; Okada, Kazuyoshi; Matsumoto, Koichi

2009-10-01

The goal of antihypertensive treatment is to reduce cardiovascular and cerebrovascular events associated with high blood pressure. A combination therapy with different antihypertensive agents is more successful than monotherapy in most hypertensive patients, with the added advantage of a better safety profile. Therefore, treatment of hypertensive patients with fixed-dose combination therapy consisting of the angiotensin II receptor blocker losartan along with hydrochlorothiazide (HCTZ) has several potential benefits over monotherapy with each individual component. It provides more effective blood pressure control, a reduction in the likelihood of adverse effects and facilitation of patient compliance due to a simple once-daily regimen. One of the advantages of the combination of losartan with HCTZ is the potential reduction in HCTZ-induced metabolic disorders; in particular, this combination can have attractive benefits for patients of hyperuricemia. Losartan plus HCTZ fixed-dose combination therapy is frequently recommended for the treatment of hypertension and lowers blood pressure in mild-to-moderate and even severe hypertensive patients to a level comparable with other classes of antihypertensive agents in combination with HCTZ. Fixed-dose combination therapy with losartan plus HCTZ is a logical choice as antihypertensive therapy for patients in whom combination therapy is necessary to achieve additional blood pressure reduction.

The effect of dose reduction on the detection of anatomical structures on panoramic radiographs.

PubMed

Kaeppler, G; Dietz, K; Reinert, S

2006-07-01

The aim was to evaluate the effect of dose reduction on diagnostic accuracy using different screen-film combinations and digital techniques for panoramic radiography. Five observers assessed 201 pairs of panoramic radiographs (a total of 402 panoramic radiographs) taken with the Orthophos Plus (Sirona, Bensheim, Germany), for visualization of 11 anatomical structures on each side, using a 3-point scale -1, 0 and 1. Two radiographs of each patient were taken at two different times (conventional setting and setting with decreased dose, done by increasing tube potential settings or halving tube current). To compare the dose at different tube potential settings dose-length product was measured at the secondary collimator. Films with medium and regular intensifying screens (high and low tube potential settings) and storage phosphor plates (low tube potential setting, tube current setting equivalent to regular intensifying screen and halved) were compared. The five observers made 27 610 assessments. Intrarater agreement was expressed by Cohen's kappa coefficient. The results demonstrated an equivalence of regular screens (low tube potential setting) and medium screens (high and low tube potential settings). A significant difference existed between medium screens (low tube potential setting, mean score 0.92) and the group of regular film-screen combinations at high tube potential settings (mean score 0.89) and between all film-screen combinations and the digital system irrespective of exposure (mean score below 0.82). There were no significant differences between medium and regular screens (mean score 0.88 to 0.92) for assessment of the periodontal ligament space, but there was a significant difference compared with the digital system (mean score below 0.76). The kappa coefficient for intrarater agreement was moderate (0.55). New regular intensifying screens can replace medium screens at low tube potential settings. Digital panoramic radiographs should be taken at low tube potential levels with an exposure equivalent at least to a regular intensifying screen.

CT breast dose reduction with the use of breast positioning and organ-based tube current modulation.

PubMed

Fu, Wanyi; Tian, Xiaoyu; Sturgeon, Gregory M; Agasthya, Greeshma; Segars, William Paul; Goodsitt, Mitchell M; Kazerooni, Ella A; Samei, Ehsan

2017-02-01

This study aimed to investigate the breast dose reduction potential of a breast-positioning (BP) technique for thoracic CT examinations with organ-based tube current modulation (OTCM). This study included 13 female anthropomorphic computational phantoms (XCAT, age range: 27-65 y.o., weight range: 52-105.8 kg). Each phantom was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were then morphed to emulate BP that constrained the majority of the breast tissue inside the 120° anterior tube current (mA) reduction zone. The OTCM mA value was modeled using a ray-tracing program, which reduced the mA to 20% in the anterior region with a corresponding increase to the posterior region. The organ doses were estimated by a validated Monte Carlo program for a typical clinical CT system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDI vol were used to compare three CT protocols: attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCM BP ). On average, compared to ATCM, OTCM reduced breast dose by 19.3 ± 4.5%, whereas OTCM BP reduced breast dose by 38.6 ± 8.1% (an additional 23.8 ± 9.4%). The dose saving of OTCM BP was more significant for larger breasts (on average 33, 38, and 44% reduction for 0.5, 1, and 2 kg breasts, respectively). Compared to ATCM, OTCM BP also reduced thymus and heart dose by 15.1 ± 7.4% and 15.9 ± 6.2% respectively. In thoracic CT examinations, OTCM with a breast-positioning technique can markedly reduce unnecessary exposure to radiosensitive organs in anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts. © 2016 American Association of Physicists in Medicine.

Soft-tissue imaging with C-arm cone-beam CT using statistical reconstruction

NASA Astrophysics Data System (ADS)

Wang, Adam S.; Webster Stayman, J.; Otake, Yoshito; Kleinszig, Gerhard; Vogt, Sebastian; Gallia, Gary L.; Khanna, A. Jay; Siewerdsen, Jeffrey H.

2014-02-01

The potential for statistical image reconstruction methods such as penalized-likelihood (PL) to improve C-arm cone-beam CT (CBCT) soft-tissue visualization for intraoperative imaging over conventional filtered backprojection (FBP) is assessed in this work by making a fair comparison in relation to soft-tissue performance. A prototype mobile C-arm was used to scan anthropomorphic head and abdomen phantoms as well as a cadaveric torso at doses substantially lower than typical values in diagnostic CT, and the effects of dose reduction via tube current reduction and sparse sampling were also compared. Matched spatial resolution between PL and FBP was determined by the edge spread function of low-contrast (˜40-80 HU) spheres in the phantoms, which were representative of soft-tissue imaging tasks. PL using the non-quadratic Huber penalty was found to substantially reduce noise relative to FBP, especially at lower spatial resolution where PL provides a contrast-to-noise ratio increase up to 1.4-2.2× over FBP at 50% dose reduction across all objects. Comparison of sampling strategies indicates that soft-tissue imaging benefits from fully sampled acquisitions at dose above ˜1.7 mGy and benefits from 50% sparsity at dose below ˜1.0 mGy. Therefore, an appropriate sampling strategy along with the improved low-contrast visualization offered by statistical reconstruction demonstrates the potential for extending intraoperative C-arm CBCT to applications in soft-tissue interventions in neurosurgery as well as thoracic and abdominal surgeries by overcoming conventional tradeoffs in noise, spatial resolution, and dose.

Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

PubMed Central

Gilbert, Mary E.; Sui, Li

2008-01-01

Background Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. Objectives The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. Methods Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. Results At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Conclusions Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate. PMID:18560531

Effect of comfort pads and incubator design on neonatal radiography.

PubMed

Jiang, Xia; Baad, Michael; Reiser, Ingrid; Feinstein, Kate A; Lu, Zhengfeng

2016-01-01

There has been increasing interest in patient dose reduction in neonatal intensive care units. Removing comfort pads for radiography has been identified as a potential means to decrease patient dose. To assess the effect of comfort pads and support trays on detector entrance exposure (DEE) and image quality for neonatal radiography, and its implication for patient dose. Comfort pads and support trays from three incubator and warmer systems were examined. The attenuation of the primary beam by these structures was measured using a narrow beam geometry. Their effect on DEE and image quality was then assessed using typical neonatal chest radiography techniques with three configurations: 1) both the comfort pad and support included in the beam, 2) only the support tray included and 3) both the comfort pad and support tray removed. Comfort pads and support trays were found to attenuate the primary beam by 6-15%. Eliminating these structures from the X-ray beam's path was found to increase the detector entrance exposure by 28-36% and increase contrast-to-noise ratio by more than 21%, suggesting room for patient dose reduction when the same image quality is maintained. Comfort pads and tray support devices can have a considerable effect on DEE and image quality, with large variations among different incubator designs. Positioning the image detector directly underneath neonatal patients for radiography is a potential means for patient dose reduction. However, such benefit should be weighed against the risks of moving the patient.

A combination of spatial and recursive temporal filtering for noise reduction when using region of interest (ROI) fluoroscopy for patient dose reduction in image guided vascular interventions with significant anatomical motion

NASA Astrophysics Data System (ADS)

Setlur Nagesh, S. V.; Khobragade, P.; Ionita, C.; Bednarek, D. R.; Rudin, S.

2015-03-01

Because x-ray based image-guided vascular interventions are minimally invasive they are currently the most preferred method of treating disorders such as stroke, arterial stenosis, and aneurysms; however, the x-ray exposure to the patient during long image-guided interventional procedures could cause harmful effects such as cancer in the long run and even tissue damage in the short term. ROI fluoroscopy reduces patient dose by differentially attenuating the incident x-rays outside the region-of-interest. To reduce the noise in the dose-reduced regions previously recursive temporal filtering was successfully demonstrated for neurovascular interventions. However, in cardiac interventions, anatomical motion is significant and excessive recursive filtering could cause blur. In this work the effects of three noise-reduction schemes, including recursive temporal filtering, spatial mean filtering, and a combination of spatial and recursive temporal filtering, were investigated in a simulated ROI dose-reduced cardiac intervention. First a model to simulate the aortic arch and its movement was built. A coronary stent was used to simulate a bioprosthetic valve used in TAVR procedures and was deployed under dose-reduced ROI fluoroscopy during the simulated heart motion. The images were then retrospectively processed for noise reduction in the periphery, using recursive temporal filtering, spatial filtering and a combination of both. Quantitative metrics for all three noise reduction schemes are calculated and are presented as results. From these it can be concluded that with significant anatomical motion, a combination of spatial and recursive temporal filtering scheme is best suited for reducing the excess quantum noise in the periphery. This new noise-reduction technique in combination with ROI fluoroscopy has the potential for substantial patient-dose savings in cardiac interventions.

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

NASA Astrophysics Data System (ADS)

Gaddy, Melissa R.; Yıldız, Sercan; Unkelbach, Jan; Papp, Dávid

2018-01-01

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79-97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest achievable mean liver BED. The results indicate that spatiotemporal treatments can achieve substantial reductions in normal tissue dose and BED, and that local optimization techniques provide high-quality plans that are close to realizing the maximum potential normal tissue dose reduction.

A novel curvilinear approach for prostate seed implantation

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

Podder, Tarun K.; Dicker, Adam P.; Hutapea, Parsaoran

Purpose: A new technique called ''curvilinear approach'' for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy. Methods: Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I-125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved-needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V{sub 100}). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D{sub 90},more » V{sub 150}, V{sub 200}), urethra (D{sub 30}, D{sub 10}) and rectum (D{sub 5}, V{sub 100}) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two-tailed student's t-test. Results: Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D{sub 30} reduced by 10.1% (p < 0.01) and D{sub 10} reduced by 9.9% (p < 0.02). Reduction in rectum dose D{sub 5} was 18.5% (p < 0.03) and V{sub 100} was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V{sub 150} and V{sub 200} coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively. Conclusions: Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V{sub 150}, V{sub 200}) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear implantation approach is dosimetrically superior to conventional rectilinear implantation technique.« less

Effect of variations in the redox potential of Gleysol on barium mobility and absorption in rice plants.

PubMed

Magalhães, Marcio Osvaldo Lima; Sobrinho, Nelson Moura Brasil do Amaral; Zonta, Everaldo; de Carvalho, Michel Miranda; Tolón-Becerra, Alfredo

2012-09-01

Two assays were designed to obtain information about the influence of redox potential variations on barium mobility and bioavailability in soil. One assay was undertaken in leaching columns, and the other was conducted in pots cultivated with rice (Oryza sativa) using soil samples collected from the surface of Gleysol in both assays. Three doses of barium (100,300 mg kg(-1) and 3000 mg kg(-1)-soil dry weight) and two redox potential values (oxidizing and reducing) were evaluated. During the incubation period, the redox potential (Eh) was monitored in columns and pots until values of -250 mV were reached. After the incubation period, geochemical partitioning was conducted on the barium using the European Communities Bureau of Reference (BCR) method. Rainfall of 200 mm d(-1) was simulated in the columns and in the planting of rice seedlings in the pots. The results of the geochemical partitioning demonstrated that the condition of reduction favors increased barium concentrations in the more labile chemical forms and decreased levels in the chemical forms related to oxides. The highest barium concentrations in leached extracts (3.36 mg L(-1)) were observed at the highest dose and condition of reduction at approximately five times above the drinking water standard. The high concentrations of barium in the soil did not affect plant dry matter production. The highest levels and accumulation of barium in roots, leaves, and grains of rice were found at the highest dose and condition of reduction. These results demonstrate that reduction leads to solubilization of barium sulfate, thereby favoring greater mobility and bioavailability of this element. Copyright © 2012 Elsevier Ltd. All rights reserved.

SU-C-206-07: A Practical Sparse View Ultra-Low Dose CT Acquisition Scheme for PET Attenuation Correction in the Extended Scan Field-Of-View

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

Miao, J; Fan, J; Gopinatha Pillai, A

Purpose: To further reduce CT dose, a practical sparse-view acquisition scheme is proposed to provide the same attenuation estimation as higher dose for PET imaging in the extended scan field-of-view. Methods: CT scans are often used for PET attenuation correction and can be acquired at very low CT radiation dose. Low dose techniques often employ low tube voltage/current accompanied with a smooth filter before backprojection to reduce CT image noise. These techniques can introduce bias in the conversion from HU to attenuation values, especially in the extended CT scan field-of-view (FOV). In this work, we propose an ultra-low dose CTmore » technique for PET attenuation correction based on sparse-view acquisition. That is, instead of an acquisition of full amount of views, only a fraction of views are acquired. We tested this technique on a 64-slice GE CT scanner using multiple phantoms. CT scan FOV truncation completion was performed based on the published water-cylinder extrapolation algorithm. A number of continuous views per rotation: 984 (full), 246, 123, 82 and 62 have been tested, corresponding to a CT dose reduction of none, 4x, 8x, 12x and 16x. We also simulated sparse-view acquisition by skipping views from the fully-acquired view data. Results: FBP reconstruction with Q. AC filter on reduced views in the full extended scan field-of-view possesses similar image quality to the reconstruction on acquired full view data. The results showed a further potential for dose reduction compared to the full acquisition, without sacrificing any significant attenuation support to the PET. Conclusion: With the proposed sparse-view method, one can potential achieve at least 2x more CT dose reduction compared to the current Ultra-Low Dose (ULD) PET/CT protocol. A pre-scan based dose modulation scheme can be combined with the above sparse-view approaches, which can even further reduce the CT scan dose during a PET/CT exam.« less

Can reduction of uncertainties in cervix cancer brachytherapy potentially improve clinical outcome?

PubMed

Nesvacil, Nicole; Tanderup, Kari; Lindegaard, Jacob C; Pötter, Richard; Kirisits, Christian

2016-09-01

The aim of this study was to quantify the impact of different types and magnitudes of dosimetric uncertainties in cervix cancer brachytherapy (BT) on tumour control probability (TCP) and normal tissue complication probability (NTCP) curves. A dose-response simulation study was based on systematic and random dose uncertainties and TCP/NTCP models for CTV and rectum. Large patient cohorts were simulated assuming different levels of dosimetric uncertainties. TCP and NTCP were computed, based on the planned doses, the simulated dose uncertainty, and an underlying TCP/NTCP model. Systematic uncertainties of 3-20% and random uncertainties with a 5-30% standard deviation per BT fraction were analysed. Systematic dose uncertainties of 5% lead to a 1% decrease/increase of TCP/NTCP, while random uncertainties of 10% had negligible impact on the dose-response curve at clinically relevant dose levels for target and OAR. Random OAR dose uncertainties of 30% resulted in an NTCP increase of 3-4% for planned doses of 70-80Gy EQD2. TCP is robust to dosimetric uncertainties when dose prescription is in the more flat region of the dose-response curve at doses >75Gy. For OARs, improved clinical outcome is expected by reduction of uncertainties via sophisticated dose delivery and treatment verification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dose reduction and image quality optimizations in CT of pediatric and adult patients: phantom studies

NASA Astrophysics Data System (ADS)

Jeon, P.-H.; Lee, C.-L.; Kim, D.-H.; Lee, Y.-J.; Jeon, S.-S.; Kim, H.-J.

2014-03-01

Multi-detector computed tomography (MDCT) can be used to easily and rapidly perform numerous acquisitions, possibly leading to a marked increase in the radiation dose to individual patients. Technical options dedicated to automatically adjusting the acquisition parameters according to the patient's size are of specific interest in pediatric radiology. A constant tube potential reduction can be achieved for adults and children, while maintaining a constant detector energy fluence. To evaluate radiation dose, the weighted CT dose index (CTDIw) was calculated based on the CT dose index (CTDI) measured using an ion chamber, and image noise and image contrast were measured from a scanned image to evaluate image quality. The dose-weighted contrast-to-noise ratio (CNRD) was calculated from the radiation dose, image noise, and image contrast measured from a scanned image. The noise derivative (ND) is a quality index for dose efficiency. X-ray spectra with tube voltages ranging from 80 to 140 kVp were used to compute the average photon energy. Image contrast and the corresponding contrast-to-noise ratio (CNR) were determined for lesions of soft tissue, muscle, bone, and iodine relative to a uniform water background, as the iodine contrast increases at lower energy (i.e., k-edge of iodine is 33 keV closer to the beam energy) using mixed water-iodine contrast normalization (water 0, iodine 25, 100, 200, and 1000 HU, respectively). The proposed values correspond to high quality images and can be reduced if only high-contrast organs are assessed. The potential benefit of lowering the tube voltage is an improved CNRD, resulting in a lower radiation dose and optimization of image quality. Adjusting the tube potential in abdominal CT would be useful in current pediatric radiography, where the choice of X-ray techniques generally takes into account the size of the patient as well as the need to balance the conflicting requirements of diagnostic image quality and radiation dose optimization.

Urethra sparing - potential of combined Nickel-Titanium stent and intensity modulated radiation therapy in prostate cancer.

PubMed

Thomsen, Jakob Borup; Arp, Dennis Tideman; Carl, Jesper

2012-05-01

To investigate a novel method for sparing urethra in external beam radiotherapy of prostate cancer and to evaluate the efficacy of such a treatment in terms of tumour control using a mathematical model. This theoretical study includes 20 patients previously treated for prostate cancer using external beam radiotherapy. All patients had a Nickel-Titanium (Ni-Ti) stent inserted into the prostate part of urethra. The stent has been used during the treatment course as an internal marker for patient positioning prior to treatment. In this study the stent is used for delineating urethra while intensity modulated radiotherapy was used for lowering dose to urethra. Evaluation of the dose plans were performed using a tumour control probability model based on the concept of uniform equivalent dose. The feasibility of the urethra dose reduction method is validated and a reduction of about 17% is shown to be possible. Calculations suggest a nearly preserved tumour control probability. A new concept for urethra dose reduction is presented. The method relies on the use of a Ni-Ti stent as a fiducial marker combined with intensity modulated radiotherapy. Theoretical calculations suggest preserved tumour control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Use of automatic exposure control in multislice computed tomography of the coronaries: comparison of 16‐slice and 64‐slice scanner data with conventional coronary angiography

PubMed Central

Deetjen, Anja; Möllmann, Susanne; Conradi, Guido; Rolf, Andreas; Schmermund, Axel; Hamm, Christian W; Dill, Thorsten

2007-01-01

Objective To evaluate the radiation‐dose‐reduction potential of automatic exposure control (AEC) in 16‐slice and 64‐slice multislice computed tomography (MSCT) of the coronary arteries (computed tomography angiography, CTA) in patients. The rapid growth in MSCT CTA emphasises the necessity of adjusting technique factors to reduce radiation dose exposure. Design A retrospective data analysis was performed for 154 patients who had undergone MSCT CTA. Group 1 (n = 56) had undergone 16‐slice MSCT without AEC, and group 2 (n = 51), with AEC. In group 1, invasive coronary angiography (ICA) had been performed in addition. Group 3 (n = 47) had been examined using a 64‐slice scanner (with AEC, without ECG‐triggered tube current modulation). Results In group 1, the mean (SD) effective dose (ED) for MSCT CTA was 9.76 (1.84) mSv and for ICA it was 2.6 (1.27) mSv. In group 2, the mean ED for MSCT CTA was 5.83 (1.73) mSv, which signifies a 42.8% dose reduction for CTA by the use of AEC. In comparison to ICA, MSCT CTA without AEC shows a 3.8‐fold increase in radiation dose, and the radiation dose of CTA with AEC was increased by a factor of 1.9. In group 3, the mean ED for MSCT CTA was 13.58 (2.80) mSV. Conclusions This is the first study to show the significant dose‐reduction potential (42.8%) of AEC in MSCT CTA in patients. This relatively new technique can be used to optimise the radiation dose levels in MSCT CTA. PMID:17395667

Full dose reduction potential of statistical iterative reconstruction for head CT protocols in a predominantly pediatric population

PubMed Central

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

2016-01-01

Purpose To implement the maximum level of statistical iterative reconstruction that can be used to establish dose-reduced head CT protocols in a primarily pediatric population. Methods Select head examinations (brain, orbits, sinus, maxilla and temporal bones) were investigated. Dose-reduced head protocols using an adaptive statistical iterative reconstruction (ASiR) were compared for image quality with the original filtered back projection (FBP) reconstructed protocols in phantom using the following metrics: image noise frequency (change in perceived appearance of noise texture), image noise magnitude, contrast-to-noise ratio (CNR), and spatial resolution. Dose reduction estimates were based on computed tomography dose index (CTDIvol) values. Patient CTDIvol and image noise magnitude were assessed in 737 pre and post dose reduced examinations. Results Image noise texture was acceptable up to 60% ASiR for Soft reconstruction kernel (at both 100 and 120 kVp), and up to 40% ASiR for Standard reconstruction kernel. Implementation of 40% and 60% ASiR led to an average reduction in CTDIvol of 43% for brain, 41% for orbits, 30% maxilla, 43% for sinus, and 42% for temporal bone protocols for patients between 1 month and 26 years, while maintaining an average noise magnitude difference of 0.1% (range: −3% to 5%), improving CNR of low contrast soft tissue targets, and improving spatial resolution of high contrast bony anatomy, as compared to FBP. Conclusion The methodology in this study demonstrates a methodology for maximizing patient dose reduction and maintaining image quality using statistical iterative reconstruction for a primarily pediatric population undergoing head CT examination. PMID:27056425

Angular on-line tube current modulation in multidetector CT examinations of children and adults: The influence of different scanning parameters on dose reduction

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

Papadakis, Antonios E.; Perisinakis, Kostas; Damilakis, John

2007-07-15

The purpose of this study was to assess the potential of angular on-line tube current modulation on dose reduction in pediatric and adult patients undergoing multidetector computed tomography (MDCT) examinations. Five physical anthropomorphic phantoms that simulate the average individual as neonate, 1-year-old, 5-year-old, 10-year-old, and adult were employed in the current study. Phantoms were scanned with the use of on-line tube current modulation (TCM). Percent dose reduction (%DR) factors achieved by applying TCM, were determined for standard protocols used for head and neck, shoulder, thorax, thorax and abdomen, abdomen, abdomen and pelvis, pelvis, and whole body examinations. A preliminary studymore » on the application of TCM in MDCT examinations of adult patients was performed to validate the results obtained in anthropomorphic phantoms. Dose reduction was estimated as the percentage difference of the modulated milliamperes for each scan and the preset milliamperes prescribed by the scan protocol. The dose reduction in children was found to be much lower than the corresponding reduction achieved for adults. For helical scans the %DR factors, ranged between 1.6% and 7.4% for the neonate, 2.9% and 8.7% for the 1-year old, 2% and 6% for the 5-year-old, 5% and 10.9% for the 10-year-old, and 10.4% and 20.7% for the adult individual. For sequential scans the corresponding %DR factors ranged between 1.3% and 6.7%, 4.5% and 11%, 4.2% and 6.6%, 6.4% and 12.3%, and 8.9% and 23.3%, respectively. Broader beam collimations are associated with decreased %DR factors, when other scanning parameters are held constant. TCM did not impair image noise. In adult patients, the %DR values were found to be in good agreement with the corresponding results obtained in the anthropomorphic adult phantom. In conclusion, on-line TCM may be considered as a valuable tool for reducing dose in routine CT examinations of pediatric and adult patients. However, the dose reduction achieved with TCM in neonates and young children was found to be lower than that obtained for adults. Therefore, on-line TCM should work as an additional means to reduce dose and should not replace other conventional means of reducing dose, especially in neonates and young children.« less

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach

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

Sasso, A.F., E-mail: sasso.alan@epa.gov; Schlosser, P.M., E-mail: schlosser.paul@epa.gov

Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastricmore » juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses. - Highlights: • We outline a new in vivo model for hexavalent chromium reduction in the stomach. • We examine in vivo reduction for mice, rats, and humans under varying conditions. • Species differences in toxicokinetics may explain susceptibility. • We show that a simplified stomach reduction model is adequate for extrapolation. • Internal dose uncertainties still exist.« less

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach.

PubMed

Sasso, A F; Schlosser, P M

2015-09-15

Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastric juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses. Published by Elsevier Inc.

Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

PubMed

Rao, Bola Sadashiva Satish; Upadhya, Dinesh; Adiga, Satish Kumar

2008-01-01

The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (p<0.001) reduction in micronucleated binucleate cells (MNBNC%) after various doses of CDE treatment in V79 cells and HPBLs. The optimum dose of CDE (40 and 50 microg/ml in HPBLs and V79 cells, respectively) with the greatest reduction in micronuclei was further used in combination with various doses of gamma radiation (0.5, 1, 2, 3, and 4 Gy) exposed 1 h after CDE treatment. A linear dose-dependent MNBNC% increase in radiation alone group was observed, while 40/50 microg/ml CDE significantly resulted in the reduction of MNBNC%, compared to the respective radiation alone groups. CDE resulted in a dose-dependent increase in free radical scavenging ability against various free radicals, viz., 2, 2-diphenyl-2-picryl-hydrazyl (DPPH); 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE.

Six steps to a successful dose-reduction strategy

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

Bennett, M.

1995-03-01

The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3)more » prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management.« less

Radiation Dose Reduction by Indication-Directed Focused z-Direction Coverage for Neck CT.

PubMed

Parikh, A K; Shah, C C

2016-06-01

The American College of Radiology-American Society of Neuroradiology-Society for Pediatric Radiology Practice Parameter for a neck CT suggests that coverage should be from the sella to the aortic arch. It also recommends using CT scans judiciously to achieve the clinical objective. Our purpose was to analyze the potential dose reduction by decreasing the scan length of a neck CT and to assess for any clinically relevant information that might be missed from this modified approach. This retrospective study included 126 children who underwent a neck CT between August 1, 2013, and September 30, 2014. Alteration of the scan length for the modified CT was suggested on the topographic image on the basis of the indication of the study, with the reader blinded to the images and the report. The CT dose index volume of the original scan was multiplied by the new scan length to calculate the dose-length product of the modified study. The effective dose was calculated for the original and modified studies by using age-based conversion factors from the American Association of Physicists in Medicine Report No. 96. Decreasing the scan length resulted in an average estimated dose reduction of 47%. The average reduction in scan length was 10.4 cm, decreasing the overall coverage by 48%. The change in scan length did not result in any missed findings that altered management. Of the 27 abscesses in this study, none extended to the mediastinum. All of the lesions in question were completely covered. Decreasing the scan length of a neck CT according to the indication provides a significant savings in radiation dose, while not altering diagnostic ability or management. © 2016 by American Journal of Neuroradiology.

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

PubMed

Jensterle, Mojca; Goricar, Katja; Janez, Andrej

2016-04-01

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

Implementation of dual-energy technique for virtual monochromatic and linearly mixed CBCTs

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

Li Hao; Giles, William; Ren Lei

Purpose: To implement dual-energy imaging technique for virtual monochromatic (VM) and linearly mixed (LM) cone beam CTs (CBCTs) and to demonstrate their potential applications in metal artifact reduction and contrast enhancement in image-guided radiation therapy (IGRT). Methods: A bench-top CBCT system was used to acquire 80 kVp and 150 kVp projections, with an additional 0.8 mm tin filtration. To implement the VM technique, these projections were first decomposed into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of VM CBCT on the metal artifact reduction was evaluated withmore » an in-house titanium-BB phantom. The optimal VM energy to maximize contrast-to-noise ratio (CNR) for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The LM technique was implemented by linearly combining the low-energy (80 kVp) and high-energy (150 kVp) CBCTs. The dose partitioning between low-energy and high-energy CBCTs was varied (20%, 40%, 60%, and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125, and 150 kVp. Results: The VM technique showed substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared to a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference of average noise levels measured in the phantom background was 1.2% between dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning are better than those of 150 kVp single-energy CBCTs. The average CNR for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low-contrast objects improved as dose partitioning was more heavily weighted toward low-energy (80 kVp) for LM CBCTs. Conclusions: Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared to single-energy CBCT acquired with equivalent dose.« less

Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.

PubMed

Duong, Phuong-Anh; Little, Brent P

2014-08-01

Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial.

PubMed

San-Miguel, Jesús F; Hungria, Vania T M; Yoon, Sung-Soo; Beksac, Meral; Dimopoulos, Meletios A; Elghandour, Ashraf; Jedrzejczak, Wieslaw W; Guenther, Andreas; Na Nakorn, Thanyaphong; Siritanaratkul, Noppadol; Schlossman, Robert L; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae-Hoon; Einsele, Hermann; Salwender, Hans; Sopala, Monika; Redhu, Suman; Paul, Sofia; Corrado, Claudia; Richardson, Paul G

2017-10-01

Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes. © 2017 John Wiley & Sons Ltd.

Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light.

PubMed

Fryk, Jesse J; Marks, Denese C; Hobson-Peters, Jody; Watterson, Daniel; Hall, Roy A; Young, Paul R; Reichenberg, Stefan; Tolksdorf, Frank; Sumian, Chryslain; Gravemann, Ute; Seltsam, Axel; Faddy, Helen M

2017-11-01

Zika virus (ZIKV) has emerged as a potential threat to transfusion safety worldwide. Pathogen inactivation is one approach to manage this risk. In this study, the efficacy of the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system to inactivate ZIKV in platelet concentrates (PCs) and plasma was investigated. PCs spiked with ZIKV were treated with the THERAFLEX UV-Platelets system at 0.05, 0.10, 0.15, and 0.20 J/cm 2 UVC. Plasma spiked with ZIKV was treated with the THERAFLEX MB-Plasma system at 20, 40, 60, and 120 J/cm 2 light at 630 nm with at least 0.8 µmol/L methylene blue (MB). Samples were taken before the first and after each illumination dose and tested for residual virus. For each system the level of viral reduction was determined. Treatment of PCs with THERAFLEX UV-Platelets system resulted in a mean of 5 log reduction in ZIKV infectivity at the standard UVC dose (0.20 J/cm 2 ), with dose dependency observed with increasing UVC dose. For plasma treated with MB and visible light, ZIKV infectivity was reduced by a mean of at least 5.68 log, with residual viral infectivity reaching the detection limit of the assay at 40 J/cm 2 (one-third the standard dose). Our study demonstrates that the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system can reduce ZIKV infectivity in PCs and pooled plasma to the detection limit of the assays used. These findings suggest both systems have the capacity to be an effective option to manage potential ZIKV transfusion transmission risk. © 2017 AABB.

Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats.

PubMed

Singh, Santosh Kumar; Kesari, Achyut Narayan; Gupta, Rajesh Kumar; Jaiswal, Dolly; Watal, Geeta

2007-11-01

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.

Sci-Thur PM – Brachytherapy 05: Surface Collimation Applied to Superficial Flap High Dose-Rate Brachytherapy

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

Liu, Derek; Sabondjian, Eric; Lawrence, Kailin

Purpose: To apply surface collimation for superficial flap HDR skin brachytherapy utilizing common clinical resources and to demonstrate the potential for OAR dose reduction within a clinically relevant setting. Methods: Two phantom setups were used. 3 mm lead collimation was applied to a solid slab phantom to determine appropriate geometries relating to collimation and dwell activation. The same collimation was applied to the temple of an anthropomorphic head phantom to demonstrate lens dose reduction. Each setup was simulated and planned to deliver 400 cGy to a 3 cm circular target to 3 mm depth. The control and collimated irradiations weremore » sequentially measured using calibrated radiochromic films. Results: Collimation for the slab phantom attenuated the dose beyond the collimator opening, decreasing the fall-off distances by half and reducing the area of healthy skin irradiated. Target coverage can be negatively impacted by a tight collimation margin, with the required margin approximated by the primary beam geometric penumbra. Surface collimation applied to the head phantom similarly attenuated the surrounding normal tissue dose while reducing the lens dose from 84 to 68 cGy. To ensure consistent setup between simulation and treatment, additional QA was performed including collimator markup, accounting for collimator placement uncertainties, standoff distance verification, and in vivo dosimetry. Conclusions: Surface collimation was shown to reduce normal tissue dose without compromising target coverage. Lens dose reduction was demonstrated on an anthropomorphic phantom within a clinical setting. Additional QA is proposed to ensure treatment fidelity.« less

Performance evaluation of iterative reconstruction algorithms for achieving CT radiation dose reduction — a phantom study

PubMed Central

Dodge, Cristina T.; Tamm, Eric P.; Cody, Dianna D.; Liu, Xinming; Jensen, Corey T.; Wei, Wei; Kundra, Vikas

2016-01-01

The purpose of this study was to characterize image quality and dose performance with GE CT iterative reconstruction techniques, adaptive statistical iterative reconstruction (ASiR), and model‐based iterative reconstruction (MBIR), over a range of typical to low‐dose intervals using the Catphan 600 and the anthropomorphic Kyoto Kagaku abdomen phantoms. The scope of the project was to quantitatively describe the advantages and limitations of these approaches. The Catphan 600 phantom, supplemented with a fat‐equivalent oval ring, was scanned using a GE Discovery HD750 scanner at 120 kVp, 0.8 s rotation time, and pitch factors of 0.516, 0.984, and 1.375. The mA was selected for each pitch factor to achieve CTDIvol values of 24, 18, 12, 6, 3, 2, and 1 mGy. Images were reconstructed at 2.5 mm thickness with filtered back‐projection (FBP); 20%, 40%, and 70% ASiR; and MBIR. The potential for dose reduction and low‐contrast detectability were evaluated from noise and contrast‐to‐noise ratio (CNR) measurements in the CTP 404 module of the Catphan. Hounsfield units (HUs) of several materials were evaluated from the cylinder inserts in the CTP 404 module, and the modulation transfer function (MTF) was calculated from the air insert. The results were confirmed in the anthropomorphic Kyoto Kagaku abdomen phantom at 6, 3, 2, and 1 mGy. MBIR reduced noise levels five‐fold and increased CNR by a factor of five compared to FBP below 6 mGy CTDIvol, resulting in a substantial improvement in image quality. Compared to ASiR and FBP, HU in images reconstructed with MBIR were consistently lower, and this discrepancy was reversed by higher pitch factors in some materials. MBIR improved the conspicuity of the high‐contrast spatial resolution bar pattern, and MTF quantification confirmed the superior spatial resolution performance of MBIR versus FBP and ASiR at higher dose levels. While ASiR and FBP were relatively insensitive to changes in dose and pitch, the spatial resolution for MBIR improved with increasing dose and pitch. Unlike FBP, MBIR and ASiR may have the potential for patient imaging at around 1 mGy CTDIvol. The improved low‐contrast detectability observed with MBIR, especially at low‐dose levels, indicate the potential for considerable dose reduction. PACS number(s): 87.57.Q‐, 87.57,nf, 87.57.C‐, 87.57.cj, 87.57.cf, 87.57.cm, 87.57.uq PMID:27074454

Does Iterative Reconstruction Lower CT Radiation Dose: Evaluation of 15,000 Examinations

PubMed Central

Noël, Peter B.; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A.; Rummeny, Ernst J.; Dobritz, Martin

2013-01-01

Purpose Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Method and Materials Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. Results IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). Conclusion The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving. PMID:24303035

Does iterative reconstruction lower CT radiation dose: evaluation of 15,000 examinations.

PubMed

Noël, Peter B; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A; Rummeny, Ernst J; Dobritz, Martin

2013-01-01

Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving.

Achieving routine submillisievert CT scanning: report from the summit on management of radiation dose in CT.

PubMed

McCollough, Cynthia H; Chen, Guang Hong; Kalender, Willi; Leng, Shuai; Samei, Ehsan; Taguchi, Katsuyuki; Wang, Ge; Yu, Lifeng; Pettigrew, Roderic I

2012-08-01

This Special Report presents the consensus of the Summit on Management of Radiation Dose in Computed Tomography (CT) (held in February 2011), which brought together participants from academia, clinical practice, industry, and regulatory and funding agencies to identify the steps required to reduce the effective dose from routine CT examinations to less than 1 mSv. The most promising technologies and methods discussed at the summit include innovations and developments in x-ray sources; detectors; and image reconstruction, noise reduction, and postprocessing algorithms. Access to raw projection data and standard data sets for algorithm validation and optimization is a clear need, as is the need for new, clinically relevant metrics of image quality and diagnostic performance. Current commercially available techniques such as automatic exposure control, optimization of tube potential, beam-shaping filters, and dynamic z-axis collimators are important, and education to successfully implement these methods routinely is critically needed. Other methods that are just becoming widely available, such as iterative reconstruction, noise reduction, and postprocessing algorithms, will also have an important role. Together, these existing techniques can reduce dose by a factor of two to four. Technical advances that show considerable promise for additional dose reduction but are several years or more from commercial availability include compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors. This report offers a strategic roadmap for the CT user and research and manufacturer communities toward routinely achieving effective doses of less than 1 mSv, which is well below the average annual dose from naturally occurring sources of radiation.

Effectiveness of pelvic lead blanket to reduce the doses to eye lens and hands of interventional cardiologists and assistant nurses.

PubMed

Grabowicz, W; Domienik-Andrzejewska, J; Masiarek, K; Górnik, T; Grycewicz, T; Brodecki, M; Lubiński, A

2017-09-01

The aim of the present study is to analyse quantitatively the potential reduction of doses to the eye lens and the hands of an operator and a nurse by the use of a pelvic lead blanket during coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA) procedures. Thermoluminescent dosimeters were used to assess dose levels to the left eye lens and fingers on both hands of both physician and nurses during single procedures performed with or without the lead blanket. The measurements were carried out at one medical centre and include dosimetric data from 100 procedures. Additional measurements including physician's and patient's doses were made on phantoms in the laboratory. In order to determine the reduction potential of the lead blanket, the doses normalized to DAP (Dose-Area Product) corresponding to the same position of dosimeter were compared against each other for both procedure categories (with and without protection). There was no statistically significant decrease observed in physicians' and nurses' eye lens doses, nor in doses normalized to DAP due to the use of the lead pelvic shield in clinic. However, some trend in reducing the eye lens doses by this shield can be observed. Regarding finger doses, the differences are statistically significant but only for physicians. The mean DAP-normalised doses to the eye lens and left and right finger of physicians, in the presence of a ceiling-suspended transparent lead shield, were 2.24e-5 ± 1.41e-5 mSv/μGym 2 , 2.31e-4 ± 1.21e-4 mSv/μGym 2 , and 2.60e-5 ± 1.57e-5 mSv/μGym 2 for standard procedures performed without the lead blanket, and 1.77e-5 ± 1.17e-5 mSv/μGym 2 , 1.70e-4 ± 1.01e-4 mSv/μGym 2 , and 1.86e-5 ± 1.13e-5 mSv/μGym 2 for procedures performed with it. A comparison of the results from the laboratory and the clinic shows that they are consistent regarding the eye lens, while for fingers it suggests that the dose reduction properties of the lead shield are related to the physician's work technique and both patient and lead blanket sizes or its positioning. The highest degree of reduction is observed for cranial and caudal projections together with the use of a patient-adjustable lead blanket; about a 2-fold decrease in finger doses is expected for optimum conditions. However, the laboratory measurements suggest that the use of lead blanket might slightly increase the patient dose, but only when specific projections are constantly used. This limitation should be considered by cardiologists during clinical work if this protection is used. In the light of the presented results, the ceiling-suspended transparent lead shield and the lead glasses seem to be the preferred way to reduce the doses to the eye lens, compared to the lead blanket.

Experimental benchmarking of a Monte Carlo dose simulation code for pediatric CT

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Yoshizumi, Terry; Colsher, James G.; Jones, Robert P.; Frush, Donald P.

2007-03-01

In recent years, there has been a desire to reduce CT radiation dose to children because of their susceptibility and prolonged risk for cancer induction. Concerns arise, however, as to the impact of dose reduction on image quality and thus potentially on diagnostic accuracy. To study the dose and image quality relationship, we are developing a simulation code to calculate organ dose in pediatric CT patients. To benchmark this code, a cylindrical phantom was built to represent a pediatric torso, which allows measurements of dose distributions from its center to its periphery. Dose distributions for axial CT scans were measured on a 64-slice multidetector CT (MDCT) scanner (GE Healthcare, Chalfont St. Giles, UK). The same measurements were simulated using a Monte Carlo code (PENELOPE, Universitat de Barcelona) with the applicable CT geometry including bowtie filter. The deviations between simulated and measured dose values were generally within 5%. To our knowledge, this work is one of the first attempts to compare measured radial dose distributions on a cylindrical phantom with Monte Carlo simulated results. It provides a simple and effective method for benchmarking organ dose simulation codes and demonstrates the potential of Monte Carlo simulation for investigating the relationship between dose and image quality for pediatric CT patients.

The impact of various protective tools on the dose reduction in the eye lens in an interventional cardiology-clinical study.

PubMed

Domienik, J; Bissinger, A; Grabowicz, W; Jankowski, Ł; Kręcki, R; Makowski, M; Masiarek, K; Plewka, M; Lubiński, A; Peruga, J Z

2016-06-01

The aim of the study was to check, in clinical practice, the potential for the dose reduction of lead eyewear and a ceiling-suspended shield used to protect the eye lens of physicians working in interventional cardiology. To this end, for the lead eyewear, the dose reduction factors were derived to correct the readings from a dosimeter used routinely outside the glasses. Four types of lead eyewear with attached loose thermoluminescent dosimeters and EYE-D dosimeters were worn by physicians in two clinical centres, for two-month periods, during coronary angiography (CA), percutaneous coronary intervention (PCI), and pacemaker procedures. In order to analyse, separately, how a ceiling-suspended lead screen absorbs the scattered radiation, a series of measurements was carried out during single CA/PCI procedures performed with and without the protection. The lead eyewear may reduce the doses to the eye closest to the x-ray tube by a factor between 1.1 and 3.4, depending on its model and the physician's position. The effectiveness of the eyewear may, however, vary-even for the same model and physician-almost twofold between different working periods. The ceiling-suspended shield decreases the doses in clinical practice by a factor of 2.3. The annual eye lens doses without the eyewear estimated from routine measurements are high-above or close to the new eye lens dose limit established by the recent EU Basic Safety Standards, even though the ceiling-suspended shield was used. Therefore, to comply with the new dose limit that is set in the Directive, protection of the eyes of physicians with high workloads might require the use of both the eyewear and the ceiling-suspended shield.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

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

Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

PubMed

Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

2016-05-01

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

A pragmatic approach to determine the optimal kVp in cone beam CT: balancing contrast-to-noise ratio and radiation dose

PubMed Central

Silkosessak, O; Jacobs, R; Bogaerts, R; Bosmans, H; Panmekiate, S

2014-01-01

Objectives: To determine the optimal kVp setting for a particular cone beam CT (CBCT) device by maximizing technical image quality at a fixed radiation dose. Methods: The 3D Accuitomo 170 (J. Morita Mfg. Corp., Kyoto, Japan) CBCT was used. The radiation dose as a function of kVp was measured in a cylindrical polymethyl methacrylate (PMMA) phantom using a small-volume ion chamber. Contrast-to-noise ratio (CNR) was measured using a PMMA phantom containing four materials (air, aluminium, polytetrafluoroethylene and low-density polyethylene), which was scanned using 180 combinations of kVp/mA, ranging from 60/1 to 90/8. The CNR was measured for each material using PMMA as background material. The pure effect of kVp and mAs on the CNR values was analysed. Using a polynomial fit for CNR as a function of mA for each kVp value, the optimal kVp was determined at five dose levels. Results: Absorbed doses ranged between 0.034 mGy mAs−1 (14 × 10 cm, 60 kVp) and 0.108 mGy mAs−1 (14 × 10 cm, 90 kVp). The relation between kVp and dose was quasilinear (R2 > 0.99). The effect of mA and kVp on CNR could be modelled using a second-degree polynomial. At a fixed dose, there was a tendency for higher CNR values at increasing kVp values, especially at low dose levels. A dose reduction through mA was more efficient than an equivalent reduction through kVp in terms of image quality deterioration. Conclusions: For the investigated CBCT model, the most optimal contrast at a fixed dose was found at the highest available kVp setting. There is great potential for dose reduction through mA with a minimal loss in image quality. PMID:24708447

CT-guided brachytherapy of prostate cancer: reduction of effective dose from X-ray examination

NASA Astrophysics Data System (ADS)

Sanin, Dmitriy B.; Biryukov, Vitaliy A.; Rusetskiy, Sergey S.; Sviridov, Pavel V.; Volodina, Tatiana V.

2014-03-01

Computed tomography (CT) is one of the most effective and informative diagnostic method. Though the number of CT scans among all radiographic procedures in the USA and European countries is 11% and 4% respectively, CT makes the highest contribution to the collective effective dose from all radiographic procedures, it is 67% in the USA and 40% in European countries [1-5]. Therefore it is necessary to understand the significance of dose value from CT imaging to a patient . Though CT dose from multiple scans and potential risk is of great concern in pediatric patients, this applies to adults as well. In this connection it is very important to develop optimal approaches to dose reduction and optimization of CT examination. International Commission on Radiological Protection (ICRP) in its publications recommends radiologists to be aware that often CT image quality is higher than it is necessary for diagnostic confidence[6], and there is a potential to reduce the dose which patient gets from CT examination [7]. In recent years many procedures, such as minimally invasive surgery, biopsy, brachytherapy and different types of ablation are carried out under guidance of computed tomography [6;7], and during a procedures multiple CT scans focusing on a specific anatomic region are performed. At the Clinics of MRRC different types of treatment for patients with prostate cancer are used, incuding conformal CT-guided brachytherapy, implantation of microsources of I into the gland under guidance of spiral CT [8]. So, the purpose of the study is to choose optimal method to reduce radiation dose from CT during CT-guided prostate brachytherapy and to obtain the image of desired quality.

Ocular bioavailability and systemic loss of topically applied ophthalmic drugs.

PubMed

Patton, T F; Francoeur, M

1978-02-01

We used 20-day-old rabbits as a model to show that the ocular bioavailability of topically applied pilocarpine nitrate increased as the instilled volume of the drug was decreased. Decreasing the instilled volume from 25 to 5 microliter permitted a dosage reduction of greater than 2.5 times without sacrificing overall drug concentrations in the eye. Since only a small fraction of topically applied doses to the eye actually reached the interior of the eye, the remainder of the dose was lost and available for systemic absorption. The reduction in dosage permitted by this approach resulted in less drug appearing in the general circulation, as shown by comparative plasma level-time profiles. The advantages of reducing drop size are improved ocular bioavailability permitting the use of smaller doses; and less systemic drug loss, thus reducing the potential for systemic side effects. These advantages could be especially significant in the pediatric and geriatric age groups.

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency

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

Dial, Christian; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu

Purpose: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. Methods: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a “no-adapt” scenario that simulatesmore » delivery of an initial plan throughout treatment, (2) a “midadapt” scenario that implements a single replan for fraction 18, (3) a “weekly adapt” scenario that simulates weekly adaptations, and (4) a “full-adapt” scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Results: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20{sub lung}) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66{sub heart}), and dose received by 33% of the heart (D33{sub heart}), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). Conclusions: Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.« less

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

PubMed

Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

2016-10-01

In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Radiation-Induced Noncancer Risks in Interventional Cardiology: Optimisation of Procedures and Staff and Patient Dose Reduction

PubMed Central

Khairuddin Md Yusof, Ahmad

2013-01-01

Concerns about ionizing radiation during interventional cardiology have been increased in recent years as a result of rapid growth in interventional procedure volumes and the high radiation doses associated with some procedures. Noncancer radiation risks to cardiologists and medical staff in terms of radiation-induced cataracts and skin injuries for patients appear clear potential consequences of interventional cardiology procedures, while radiation-induced potential risk of developing cardiovascular effects remains less clear. This paper provides an overview of the evidence-based reviews of concerns about noncancer risks of radiation exposure in interventional cardiology. Strategies commonly undertaken to reduce radiation doses to both medical staff and patients during interventional cardiology procedures are discussed; optimisation of interventional cardiology procedures is highlighted. PMID:24027768

SU-F-J-145: MRI-Guided Interventional Boost Radiotherapy for Rectal Cancer: Investigating the Feasibility of Adapting the Anatomy

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

Kleijnen, J J E; Couwenberg, A M; Asselen, B van

Purpose: The recent development of an MRI-linac allows adaptation of treatments to the anatomy of the moment. This anatomy, in turn, could be altered into a more favorable situation for radiotherapy purposes. The purpose of this study is to investigate the potential dosimetric benefits of manipulating rectal anatomy in MRI-guided interventional external-beam radiotherapy for rectal cancer. Methods: For this retrospective analysis, four patients (1M/3F) diagnosed with rectal cancer were included. These underwent MR-imaging using sonography transmission gel as endorectal contrast at time of diagnosis and standard, non-contrast, MR-imaging prior to radiotherapy planning. In the contrast scan, the rectum is inflatedmore » by the inserted contrast gel, thereby potentially increasing the distance between tumor and the organs-at-risk (OAR). Both anatomies were delineated and 7- beam IMRT-plans were calculated for both situations (RT-standard and RT-inflated), using in-house developed treatment planning software. Each plan was aimed to deliver 15Gy to the planning target volume (PTV; tumor+3mm margin) with a D99>95% and Dmax<120% of the planned dose. The D2cc dose to the OAR were then compared for both situations. Results: At equal (or better) target coverage, we found a mean reduction in D2cc of 4.1Gy/237% [range 2.6Gy–6.3Gy/70%–621%] for the bladder and of 2.0Gy/145% [range −0.7Gy–7.9Gy/−73%–442%] for the small-bowel, for the RT-inflated compared to the RT-standard plans. For the three female patients, a reduction in D2cc of 5.2Gy/191% [range 3.2Gy–9.2Gy/44%–475%] for the gynecological organs was found. We found all D2cc doses to be better for the RT-inflated plans, except for one patient for whom the bladder D2cc dose was slightly increased. Conclusion: Reduction of OAR dose by manipulation of anatomy is feasible. Inflation of the rectum results in more distance between OAR and PTV. This leads to a substantial reduction in dose to OAR at equal or better target coverage.« less

SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT

PubMed Central

Halliburton, Sandra S.; Abbara, Suhny; Chen, Marcus Y.; Gentry, Ralph; Mahesh, Mahadevappa; Raff, Gilbert L.; Shaw, Leslee J.; Hausleiter, Jörg

2012-01-01

Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. PMID:21723512

Radiation dose in 320-slice multidetector cardiac CT: a single center experience of evolving dose minimization.

PubMed

Tung, Matthew K; Cameron, James D; Casan, Joshua M; Crossett, Marcus; Troupis, John M; Meredith, Ian T; Seneviratne, Sujith K

2013-01-01

Minimization of radiation exposure remains an important subject that occurs in parallel with advances in scanner technology. We report our experience of evolving radiation dose and its determinants after the introduction of 320-multidetector row cardiac CT within a single tertiary cardiology referral service. Four cohorts of consecutive patients (total 525 scans), who underwent cardiac CT at defined time points as early as 2008, are described. These include a cohort just after scanner installation, after 2 upgrades of the operating system, and after introduction of an adaptive iterative image reconstruction algorithm. The proportions of nondiagnostic coronary artery segments and studies with nondiagnostic segments were compared between cohorts. Significant reductions were observed in median radiation doses in all cohorts compared with the initial cohort (P < .001). Median dose-length product fell from 944 mGy · cm (interquartile range [IQR], 567.3-1426.5 mGy · cm) to 156 mGy · cm (IQR, 99.2-265.0 mGy · cm). Although the proportion of prospectively triggered scans has increased, reductions in radiation dose have occurred independently of distribution of scan formats. In multiple regression that combined all groups, determinants of dose-length product were tube output, the number of cardiac cycles scanned, tube voltage, scan length, scan format, body mass index, phase width, and heart rate (adjusted R(2) = 0.85, P < .001). The proportion of nondiagnostic coronary artery segments was slightly increased in group 4 (2.9%; P < .01). While maintaining diagnostic quality in 320-multidetector row cardiac CT, the radiation dose has decreased substantially because of a combination of dose-reduction protocols and technical improvements. Continued minimization of radiation dose will increase the potential for cardiac CT to expand as a cardiac imaging modality. Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System.

PubMed

Fan, Qiyong; Yeung, Anamaria R; Amdur, Robert; Helmig, Richard; Park, Justin; Li, Jonathan; Kahler, Darren; Liu, Chihray; Lu, Bo

2017-06-01

The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively. The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm 3 is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system. In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% ± 4.2% (from 276 ± 57 to 182 ± 38 cGy), corresponding to an extra sparing distance of 7.9 ± 1.1 mm. The maximum sparing distance variation per patient is 1.4 ± 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5°, respectively, in all directions. The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer.

Assessment of female breast dose for thoracic cone-beam CT using MOSFET dosimeters.

PubMed

Sun, Wenzhao; Wang, Bin; Qiu, Bo; Liang, Jian; Xie, Weihao; Deng, Xiaowu; Qi, Zhenyu

2017-03-21

To assess the breast dose during a routine thoracic cone-beam CT (CBCT) check with the efforts to explore the possible dose reduction strategy. Metal oxide semiconductor field-effect transistor (MOSFET) dosimeters were used to measure breast surface doses during a thorax kV CBCT scan in an anthropomorphic phantom. Breast doses for different scanning protocols and breast sizes were compared. Dose reduction was attempted by using partial arc CBCT scan with bowtie filter. The impact of this dose reduction strategy on image registration accuracy was investigated. The average breast surface doses were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with filtration, respectively. This indicates a dose reduction of 41.8% by use of bowtie filter. It was found 220° partial arc scanning significantly reduced the dose to contralateral breast (44.4% lower than ipsilateral breast), while the image registration accuracy was not compromised. Breast dose reduction can be achieved by using ipsilateral 220° partial arc scan with bowtie filter. This strategy also provides sufficient image quality for thorax image registration in daily patient positioning verification.

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

PubMed Central

Dickson, Patricia; Peinovich, Maryn; McEntee, Michael; Lester, Thomas; Le, Steven; Krieger, Aimee; Manuel, Hayden; Jabagat, Catherine; Passage, Merry; Kakkis, Emil D.

2008-01-01

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human α-l-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of α-l-iduronidase–specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9–44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases. PMID:18654665

Achieving Routine Submillisievert CT Scanning: Report from the Summit on Management of Radiation Dose in CT

PubMed Central

Chen, Guang Hong; Kalender, Willi; Leng, Shuai; Samei, Ehsan; Taguchi, Katsuyuki; Wang, Ge; Yu, Lifeng; Pettigrew, Roderic I.

2012-01-01

This Special Report presents the consensus of the Summit on Management of Radiation Dose in Computed Tomography (CT) (held in February 2011), which brought together participants from academia, clinical practice, industry, and regulatory and funding agencies to identify the steps required to reduce the effective dose from routine CT examinations to less than 1 mSv. The most promising technologies and methods discussed at the summit include innovations and developments in x-ray sources; detectors; and image reconstruction, noise reduction, and postprocessing algorithms. Access to raw projection data and standard data sets for algorithm validation and optimization is a clear need, as is the need for new, clinically relevant metrics of image quality and diagnostic performance. Current commercially available techniques such as automatic exposure control, optimization of tube potential, beam-shaping filters, and dynamic z-axis collimators are important, and education to successfully implement these methods routinely is critically needed. Other methods that are just becoming widely available, such as iterative reconstruction, noise reduction, and postprocessing algorithms, will also have an important role. Together, these existing techniques can reduce dose by a factor of two to four. Technical advances that show considerable promise for additional dose reduction but are several years or more from commercial availability include compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors. This report offers a strategic roadmap for the CT user and research and manufacturer communities toward routinely achieving effective doses of less than 1 mSv, which is well below the average annual dose from naturally occurring sources of radiation. © RSNA, 2012 PMID:22692035

Dose reduction with adaptive statistical iterative reconstruction for paediatric CT: phantom study and clinical experience on chest and abdomen CT.

PubMed

Gay, F; Pavia, Y; Pierrat, N; Lasalle, S; Neuenschwander, S; Brisse, H J

2014-01-01

To assess the benefit and limits of iterative reconstruction of paediatric chest and abdominal computed tomography (CT). The study compared adaptive statistical iterative reconstruction (ASIR) with filtered back projection (FBP) on 64-channel MDCT. A phantom study was first performed using variable tube potential, tube current and ASIR settings. The assessed image quality indices were the signal-to-noise ratio (SNR), the noise power spectrum, low contrast detectability (LCD) and spatial resolution. A clinical retrospective study of 26 children (M:F = 14/12, mean age: 4 years, range: 1-9 years) was secondarily performed allowing comparison of 18 chest and 14 abdominal CT pairs, one with a routine CT dose and FBP reconstruction, and the other with 30 % lower dose and 40 % ASIR reconstruction. Two radiologists independently compared the images for overall image quality, noise, sharpness and artefacts, and measured image noise. The phantom study demonstrated a significant increase in SNR without impairment of the LCD or spatial resolution, except for tube current values below 30-50 mA. On clinical images, no significant difference was observed between FBP and reduced dose ASIR images. Iterative reconstruction allows at least 30 % dose reduction in paediatric chest and abdominal CT, without impairment of image quality. • Iterative reconstruction helps lower radiation exposure levels in children undergoing CT. • Adaptive statistical iterative reconstruction (ASIR) significantly increases SNR without impairing spatial resolution. • For abdomen and chest CT, ASIR allows at least a 30 % dose reduction.

Potential of dosage reduction in cone-beam-computed tomography (CBCT) for radiological diagnostics of the paranasal sinuses.

PubMed

Güldner, C; Ningo, A; Voigt, J; Diogo, I; Heinrichs, J; Weber, R; Wilhelm, T; Fiebich, M

2013-03-01

More than 10 years ago, cone-beam-computed tomography (CBCT) was introduced in ENT radiology. Until now, the focus of research was to evaluate clinical limits of this technique. The aim of this work is the evaluation of specific dosages and the identification of potential optimization in the performance of CBCT of the paranasal sinuses. Based on different tube parameters (tube current, tube voltage, and rotation angles), images of the nose and the paranasal sinuses were taken on a phantom head with the Accu-I-tomo F17 (Morita, Kyoto, Japan). The dosages applied to the lens and parotid gland were measured with OSL dosimetry. The imaging quality was evaluated by independent observers. All datasets were reviewed according to a checklist of surgically important anatomic structures. Even for lowest radiation exposure (4 mA, 76 kV, 180°, computed tomography dosage index (CTDI) = 1.8 mGy), the imaging quality was sufficient. Of course a significant reduction of the imaging quality could be seen, so a reliable mean was set for 4 mA, 84 kV, and 180° rotation angle (CTDI = 2.4 mGy). In this combination, a reduction of 92 % in lens-dose and of 77 % of dosage at the parotid gland was observed in comparison to the maximal possible adjustments (8 mA, 90 kV, 360°, CTDI = 10.9 mGy). There is potential for optimization in CBCT. Changing the rotation angle (180° instead of 360°) leads to a dose reduction of 50 %. Furthermore from clinical point of view in case of chronic rhinosinusitis a relevant reduction of dosage is possible. Therefore, it is necessary to intensify the interdisciplinary discussion about the disease specifics required quality of imaging.

SU-C-207-05: A Comparative Study of Noise-Reduction Algorithms for Low-Dose Cone-Beam Computed Tomography

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

Mukherjee, S; Yao, W

2015-06-15

Purpose: To study different noise-reduction algorithms and to improve the image quality of low dose cone beam CT for patient positioning in radiation therapy. Methods: In low-dose cone-beam CT, the reconstructed image is contaminated with excessive quantum noise. In this study, three well-developed noise reduction algorithms namely, a) penalized weighted least square (PWLS) method, b) split-Bregman total variation (TV) method, and c) compressed sensing (CS) method were studied and applied to the images of a computer–simulated “Shepp-Logan” phantom and a physical CATPHAN phantom. Up to 20% additive Gaussian noise was added to the Shepp-Logan phantom. The CATPHAN phantom was scannedmore » by a Varian OBI system with 100 kVp, 4 ms and 20 mA. For comparing the performance of these algorithms, peak signal-to-noise ratio (PSNR) of the denoised images was computed. Results: The algorithms were shown to have the potential in reducing the noise level for low-dose CBCT images. For Shepp-Logan phantom, an improvement of PSNR of 2 dB, 3.1 dB and 4 dB was observed using PWLS, TV and CS respectively, while for CATPHAN, the improvement was 1.2 dB, 1.8 dB and 2.1 dB, respectively. Conclusion: Penalized weighted least square, total variation and compressed sensing methods were studied and compared for reducing the noise on a simulated phantom and a physical phantom scanned by low-dose CBCT. The techniques have shown promising results for noise reduction in terms of PSNR improvement. However, reducing the noise without compromising the smoothness and resolution of the image needs more extensive research.« less

Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

NASA Astrophysics Data System (ADS)

Lee, Boram; Lee, Sunyoung; Yang, Injeong; Yoon, Myeonggeun

2014-05-01

The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.

Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

PubMed

St Louis, Erik K; Louis, Erik K

2009-06-01

The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

Cholesterol-lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-induced Hypercholesterolemic Mice.

PubMed

Yamamoto, Tsuyoshi; Harada-Shiba, Mariko; Nakatani, Moeka; Wada, Shunsuke; Yasuhara, Hidenori; Narukawa, Keisuke; Sasaki, Kiyomi; Shibata, Masa-Aki; Torigoe, Hidetaka; Yamaoka, Tetsuji; Imanishi, Takeshi; Obika, Satoshi

2012-05-15

Recent findings in molecular biology implicate the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in low-density lipoprotein receptor (LDLR) protein regulation. The cholesterol-lowering potential of anti-PCSK9 antisense oligonucleotides (AONs) modified with bridged nucleic acids (BNA-AONs) including 2',4'-BNA (also called as locked nucleic acid (LNA)) and 2',4'-BNA(NC) chemistries were demonstrated both in vitro and in vivo. An in vitro transfection study revealed that all of the BNA-AONs induce dose-dependent reductions in PCSK9 messenger RNA (mRNA) levels concomitantly with increases in LDLR protein levels. BNA-AONs were administered to atherogenic diet-fed C57BL/6J mice twice weekly for 6 weeks; 2',4'-BNA-AON that targeted murine PCSK9 induced a dose-dependent reduction in hepatic PCSK9 mRNA and LDL cholesterol (LDL-C); the 43% reduction of serum LDL-C was achieved at a dose of 20 mg/kg/injection with only moderate increases in toxicological indicators. In addition, the serum high-density lipoprotein cholesterol (HDL-C) levels increased. These results support antisense inhibition of PCSK9 as a potential therapeutic approach. When compared with 2',4'-BNA-AON, 2',4'-BNA(NC)-AON showed an earlier LDL-C-lowering effect and was more tolerable in mice. Our results validate the optimization of 2',4'-BNA(NC)-based anti-PCSK9 antisense molecules to produce a promising therapeutic agent for the treatment of hypercholesterolemia.

Potential benefit of the CT adaptive statistical iterative reconstruction method for pediatric cardiac diagnosis

NASA Astrophysics Data System (ADS)

Miéville, Frédéric A.; Ayestaran, Paul; Argaud, Christophe; Rizzo, Elena; Ou, Phalla; Brunelle, Francis; Gudinchet, François; Bochud, François; Verdun, Francis R.

2010-04-01

Adaptive Statistical Iterative Reconstruction (ASIR) is a new imaging reconstruction technique recently introduced by General Electric (GE). This technique, when combined with a conventional filtered back-projection (FBP) approach, is able to improve the image noise reduction. To quantify the benefits provided on the image quality and the dose reduction by the ASIR method with respect to the pure FBP one, the standard deviation (SD), the modulation transfer function (MTF), the noise power spectrum (NPS), the image uniformity and the noise homogeneity were examined. Measurements were performed on a control quality phantom when varying the CT dose index (CTDIvol) and the reconstruction kernels. A 64-MDCT was employed and raw data were reconstructed with different percentages of ASIR on a CT console dedicated for ASIR reconstruction. Three radiologists also assessed a cardiac pediatric exam reconstructed with different ASIR percentages using the visual grading analysis (VGA) method. For the standard, soft and bone reconstruction kernels, the SD is reduced when the ASIR percentage increases up to 100% with a higher benefit for low CTDIvol. MTF medium frequencies were slightly enhanced and modifications of the NPS shape curve were observed. However for the pediatric cardiac CT exam, VGA scores indicate an upper limit of the ASIR benefit. 40% of ASIR was observed as the best trade-off between noise reduction and clinical realism of organ images. Using phantom results, 40% of ASIR corresponded to an estimated dose reduction of 30% under pediatric cardiac protocol conditions. In spite of this discrepancy between phantom and clinical results, the ASIR method is as an important option when considering the reduction of radiation dose, especially for pediatric patients.

Toward assessing the diagnostic influence of dose reduction in pediatric CT: a study based on simulated lung nodules

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; DeLong, David M.; Jones, Robert P.; Colsher, James G.; Frush, Donald P.

2008-03-01

The purpose of this study is to evaluate the effect of reduced tube current, as a surrogate for radiation dose, on lung nodule detection in pediatric chest multi-detector CT (MDCT). Normal chest MDCT images of 13 patients aged 1 to 7 years old were used as templates for this study. The original tube currents were between 70 mA and 180 mA. Using proprietary noise addition software, noise was added to the images to create 13 cases at the lowest common mA (i.e. 70 mA), 13 cases at 35 mA (50% reduction), and 13 cases at 17.5 mA (75% reduction). Three copies of each case were made for a total of 117 series for simulated nodule insertion. A technique for three-dimensional simulation of small lung nodules was developed, validated through an observer study, and used to add nodules to the series. Care was taken to ensure that each of three lung zones (upper, middle, lower) contained 0 or 1 nodule. The series were randomized and the presence of a nodule in each lung zone was rated independently and blindly by three pediatric radiologists on a continuous scale between 0 (definitely absent) and 100 (definitely present). Receiver operating characteristic analysis of the data showed no general significant difference in diagnostic accuracy between the reduced mA values and 70 mA, suggesting a potential for dose reduction with preserved diagnostic quality. To our knowledge, this study is the first controlled, systematic, and task-specific assessment of the influence of dose reduction in pediatric chest CT.

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

Caillet, V; Colvill, E; Royal North Shore Hospital, Sydney, NSW

Purpose: The objective of this study was to investigate the dosimetric benefits of multi-leaf collimator (MLC) tracking for lung SABR treatments in end-to-end clinically realistic planning and delivery scenarios. Methods: The clinical benefits of MLC tracking were assessed using previously delivered treatment plans and physical experiments. The 10 most recent single lesion lung SABR patients were re-planned following a 4D-GTV-based real-time adaptive protocol (PTV defined as the end-of-exhalation GTV plus 5.0 mm margins). The plans were delivered on a Trilogy Varian linac. Electromagnetic transponders (Calypso, Varian Medical Systems, USA) were embedded into a programmable moving phantom (HexaMotion platform) tracked withmore » the Varian Calypso system. For each physical experiment, the MLC positions were collected and used as input for dose reconstruction. For both planned and physical experiments, the OAR dose metrics from the conventional and real-time adaptive SABR plans (Mean Lung Dose (MLD), V20 for lung, and near-maximum dose (D2%) for spine and heart) were statistically compared. The Wilcoxon test was used to compare plan and physical experiment dose metrics. Results: While maintaining target coverage, percentage reductions in dose metrics to the OARs were observed for both planned and physical experiments. Comparing the two plans showed MLD percentage reduction (MLDr) of 25.4% (absolute differences of 1.41 Gy) and 28.9% (1.29%) for the V20r. D2% percentage reduction for spine and heart were respectively 27.9% (0.3 Gy) and 20.2% (0.3 Gy). For the physical experiments, MLDr was 23.9% (1.3 Gy), and V20r 37.4% (1.6%). D2% reduction for spine and heart were respectively 27.3% (0.3 Gy) and 19.6% (0.3 Gy). For both plans and physical experiments, significant OAR dose differences (p<0.05) were found between the conventional SABR and real-time adaptive plans. Conclusion: Application of MLC tracking for lung SABR patients has the potential to reduce the dose to OARs during radiation therapy.« less

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

PubMed

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

2015-05-15

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

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

PubMed Central

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

2013-01-01

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

Metsulfuron spray drift reduces fruit yield of hawthorn (Crataegus monogyna L.).

PubMed

Kjaer, Christian; Strandberg, Morten; Erlandsen, Mogens

2006-03-01

This study was carried out to investigate whether spray drift of metsulfuron has a potential to negatively affect hawthorn (Crataegus monogyna) hedgerows near agricultural fields. For this purpose four doses of metsulfuron ranging from 5% to 40% of the field dose (4 g metsulfuron per hectare) were sprayed on trees in seven different hawthorn hedgerows. The actual deposition on the leaves was measured by means of a tracer (glycine). Spraying was conducted both at the bud stage and at early flowering. Leaves, flowers, green berries and mature berries were harvested and the number and weight of each were measured. The spraying at the bud stage caused a highly significant reduction in number and dry weight of berries, whereas it had no effects on leaf and flower production. The berry reduction was close to 100% at actual depositions relevant for spray drift under normal conditions. Spraying at early flowering also significantly reduced berries although the effect was smaller than for the spraying at bud stage. The early flower stage spraying caused no reduction in number and size of leaves. The possible ecological consequence is that metsulfuron spray drift from agricultural fields has a potential to reduce the amount of berries available for frugivorous birds in nearby hedgerows. A potential need for regulatory measures to reduce herbicide spray drift to hedgerows situated near agricultural fields with herbicide use is also indicated.

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

PubMed

Eekers, Daniëlle B P; Roelofs, Erik; Jelen, Urszula; Kirk, Maura; Granzier, Marlies; Ammazzalorso, Filippo; Ahn, Peter H; Janssens, Geert O R J; Hoebers, Frank J P; Friedmann, Tobias; Solberg, Timothy; Walsh, Sean; Troost, Esther G C; Kaanders, Johannes H A M; Lambin, Philippe

2016-12-01

In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D 2 ) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Effect of reduced agalsidase Beta dosage in fabry patients: the Australian experience.

PubMed

Ghali, Joanna; Nicholls, Kathy; Denaro, Charles; Sillence, David; Chapman, Ian; Goldblatt, Jack; Thomas, Mark; Fletcher, Janice

2012-01-01

In Australia, enzyme replacement therapy (ERT) for Fabry Disease (FD), both Agalsidase alfa (Replagal, Shire HGT) and beta (Fabrazyme, Genzyme), is funded and monitored through a specific government program. Agalsidase beta supply has been rationed by Genzyme since 2009 due to manufacturing issues. Consequently, the Australian Fabry Disease Advisory Committee has treated patients on Agalsidase beta at 50% of their usual dose from mid-2009, with a further reduction to 30% for some patients from late 2009. To determine the clinical effect of Agalsidase beta dose reduction in the Australian FD patient cohort. A questionnaire assessing FD symptoms was administered to 40 patients on long-term ERT. Clinical data from The Fabry Registry for patients receiving Agalsidase alfa or beta, for at least 2 years prior to the time of enforced Agalsidase beta dose reduction, were reviewed. Disease burden and quality of life (QOL) were graded using the Disease Severity Scoring System, Mainz Severity Score Index, Brief Pain Inventory and Short Form 36 Health Survey at 2 years before dose reduction, at the time of dose reduction and at the most recent clinical review following dose reduction. Disease severity and QOL scores did not change between the ERT groups. Males on Agalsidase beta reported lower energy levels after dose reduction, while no change was reported by females on either product or by males on a stable dose of Agalsidase alfa. This study suggests that energy levels in male patients worsen after dose reduction of Agalsidase beta.

Efficacy of radiation safety glasses in interventional radiology.

PubMed

van Rooijen, Bart D; de Haan, Michiel W; Das, Marco; Arnoldussen, Carsten W K P; de Graaf, R; van Zwam, Wim H; Backes, Walter H; Jeukens, Cécile R L P N

2014-10-01

This study was designed to evaluate the reduction of the eye lens dose when wearing protective eyewear in interventional radiology and to identify conditions that optimize the efficacy of radiation safety glasses. The dose reduction provided by different models of radiation safety glasses was measured on an anthropomorphic phantom head. The influence of the orientation of the phantom head on the dose reduction was studied in detail. The dose reduction in interventional radiological practice was assessed by dose measurements on radiologists wearing either leaded or no glasses or using a ceiling suspended screen. The different models of radiation safety glasses provided a dose reduction in the range of a factor of 7.9-10.0 for frontal exposure of the phantom. The dose reduction was strongly reduced when the head is turned to the side relative to the irradiated volume. The eye closest to the tube was better protected due to side shielding and eyewear curvature. In clinical practice, the mean dose reduction was a factor of 2.1. Using a ceiling suspended lead glass shield resulted in a mean dose reduction of a factor of 5.7. The efficacy of radiation protection glasses depends on the orientation of the operator's head relative to the irradiated volume. Glasses can offer good protection to the eye under clinically relevant conditions. However, the performance in clinical practice in our study was lower than expected. This is likely related to nonoptimized room geometry and training of the staff as well as measurement methodology.

Assessment of female breast dose for thoracic cone-beam CT using MOSFET dosimeters

PubMed Central

Qiu, Bo; Liang, Jian; Xie, Weihao; Deng, Xiaowu; Qi, Zhenyu

2017-01-01

Objective: To assess the breast dose during a routine thoracic cone-beam CT (CBCT) check with the efforts to explore the possible dose reduction strategy. Materials and Methods: Metal oxide semiconductor field-effect transistor (MOSFET) dosimeters were used to measure breast surface doses during a thorax kV CBCT scan in an anthropomorphic phantom. Breast doses for different scanning protocols and breast sizes were compared. Dose reduction was attempted by using partial arc CBCT scan with bowtie filter. The impact of this dose reduction strategy on image registration accuracy was investigated. Results: The average breast surface doses were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with filtration, respectively. This indicates a dose reduction of 41.8% by use of bowtie filter. It was found 220° partial arc scanning significantly reduced the dose to contralateral breast (44.4% lower than ipsilateral breast), while the image registration accuracy was not compromised. Conclusions: Breast dose reduction can be achieved by using ipsilateral 220° partial arc scan with bowtie filter. This strategy also provides sufficient image quality for thorax image registration in daily patient positioning verification. PMID:28423624

Assessment of Risk Reduction for Lymphedema Following Sentinel Lymph Noded Guided Surgery for Primary Breast Cancer

DTIC Science & Technology

2006-10-01

patients with breast cancer underwent scanning with a hybrid camera which combined a dual-head SPECT camera and a low-dose, single slice CT scanner , (GE...investigated a novel approach which combines the output of a dual-head SPECT camera and a low-dose, single slice CT scanner , (GE Hawkeye®). This... scanner , (Hawkeye®, GE Medical system) is attempted in this study. This device is widely available in cardiology community and has the potential to

Hexavalent chrome: threshold concept for carcinogenicity.

PubMed

Jones, R E

1990-03-01

Certain hexavalent chromium (Cr6+) compounds when administered via inhalation at high doses have the potential to induce lung tumors in humans and experimental animals. Trivalent chromium (Cr3+) is an essential human and animal nutrient at levels of 50 to 200 micrograms/day. Recent data have shown that the human body is able to reduce Cr6+ to Cr3+. This reduction occurs in bodily fluids such as gastric juice, epithelial lining fluid of the respiratory tract, blood, and other fluids. Secondary reduction occurs at the cellular level by the cytosol, mitochondria, and microsomes. Thus, at low levels of exposure hexavalent chromium ions are reduced before the 6+ ions can interact with DNA unless the dose is sufficient to overwhelm the body's reduction capacity. This paper summarizes the available data concerning the reducing ability of the body and formulates the steps in the mechanism of cancer induction. These steps include: (1) only certain Cr6+ compounds have the capacity to interact with cellular components; (2) Cr6+ is reduced by body fluids and excess Cr6+ enters the cell (Cr3+ is poorly absorbed across membranes); (3) cellular organelles and the cytoplasm reduce Cr6+ to Cr3+; (4) excess Cr6+ can enter the nucleus; (5) Cr6+ reduction through 5+ and 4+ to 3+ has a potential to interact with the DNA molecule; and (6) if unrepaired, this DNA damage can lead to cancer induction. On the basis of current evidence Cr6+ has a threshold for carcinogenic potential in humans that is greater than the current TLV.

Adaptive Statistical Iterative Reconstruction-V Versus Adaptive Statistical Iterative Reconstruction: Impact on Dose Reduction and Image Quality in Body Computed Tomography.

PubMed

Gatti, Marco; Marchisio, Filippo; Fronda, Marco; Rampado, Osvaldo; Faletti, Riccardo; Bergamasco, Laura; Ropolo, Roberto; Fonio, Paolo

The aim of this study was to evaluate the impact on dose reduction and image quality of the new iterative reconstruction technique: adaptive statistical iterative reconstruction (ASIR-V). Fifty consecutive oncologic patients acted as case controls undergoing during their follow-up a computed tomography scan both with ASIR and ASIR-V. Each study was analyzed in a double-blinded fashion by 2 radiologists. Both quantitative and qualitative analyses of image quality were conducted. Computed tomography scanner radiation output was 38% (29%-45%) lower (P < 0.0001) for the ASIR-V examinations than for the ASIR ones. The quantitative image noise was significantly lower (P < 0.0001) for ASIR-V. Adaptive statistical iterative reconstruction-V had a higher performance for the subjective image noise (P = 0.01 for 5 mm and P = 0.009 for 1.25 mm), the other parameters (image sharpness, diagnostic acceptability, and overall image quality) being similar (P > 0.05). Adaptive statistical iterative reconstruction-V is a new iterative reconstruction technique that has the potential to provide image quality equal to or greater than ASIR, with a dose reduction around 40%.

Radiation dose reduction efficiency of buildings after the accident at the Fukushima Daiichi Nuclear Power Station.

PubMed

Monzen, Satoru; Hosoda, Masahiro; Osanai, Minoru; Tokonami, Shinji

2014-01-01

Numerous radionuclides were released from the Fukushima Daiichi Nuclear Power Station (F1-NPS) in Japan following the magnitude 9.0 earthquake and tsunami on March 11, 2011. Local residents have been eager to calculate their individual radiation exposure. Thus, absorbed dose rates in the indoor and outdoor air at evacuation sites in the Fukushima Prefecture were measured using a gamma-ray measuring devices, and individual radiation exposure was calculated by assessing the radiation dose reduction efficiency (defined as the ratio of absorbed dose rate in the indoor air to the absorbed dose rate in the outdoor air) of wood, aluminum, and reinforced concrete buildings. Between March 2011 and July 2011, dose reduction efficiencies of wood, aluminum, and reinforced concrete buildings were 0.55 ± 0.04, 0.15 ± 0.02, and 0.19 ± 0.04, respectively. The reduction efficiency of wood structures was 1.4 times higher than that reported by the International Atomic Energy Agency. The efficiency of reinforced concrete was similar to previously reported values, whereas that of aluminum structures has not been previously reported. Dose reduction efficiency increased in proportion to the distance from F1-NPS at 8 of the 18 evacuation sites. Time variations did not reflect dose reduction efficiencies at evacuation sites although absorbed dose rates in the outdoor air decreased. These data suggest that dose reduction efficiency depends on structure types, levels of contamination, and evacuee behaviors at evacuation sites.

Reducing radiation dose to the female breast during conventional and dedicated breast computed tomography

NASA Astrophysics Data System (ADS)

Rupcich, Franco John

The purpose of this study was to quantify the effectiveness of techniques intended to reduce dose to the breast during CT coronary angiography (CTCA) scans with respect to task-based image quality, and to evaluate the effectiveness of optimal energy weighting in improving contrast-to-noise ratio (CNR), and thus the potential for reducing breast dose, during energy-resolved dedicated breast CT. A database quantifying organ dose for several radiosensitive organs irradiated during CTCA, including the breast, was generated using Monte Carlo simulations. This database facilitates estimation of organ-specific dose deposited during CTCA protocols using arbitrary x-ray spectra or tube-current modulation schemes without the need to run Monte Carlo simulations. The database was used to estimate breast dose for simulated CT images acquired for a reference protocol and five protocols intended to reduce breast dose. For each protocol, the performance of two tasks (detection of signals with unknown locations) was compared over a range of breast dose levels using a task-based, signal-detectability metric: the estimator of the area under the exponential free-response relative operating characteristic curve, AFE. For large-diameter/medium-contrast signals, when maintaining equivalent AFE, the 80 kV partial, 80 kV, 120 kV partial, and 120 kV tube-current modulated protocols reduced breast dose by 85%, 81%, 18%, and 6%, respectively, while the shielded protocol increased breast dose by 68%. Results for the small-diameter/high-contrast signal followed similar trends, but with smaller magnitude of the percent changes in dose. The 80 kV protocols demonstrated the greatest reduction to breast dose, however, the subsequent increase in noise may be clinically unacceptable. Tube output for these protocols can be adjusted to achieve more desirable noise levels with lesser dose reduction. The improvement in CNR of optimally projection-based and image-based weighted images relative to photon-counting was investigated for six different energy bin combinations using a bench-top energy-resolving CT system with a cadmium zinc telluride (CZT) detector. The non-ideal spectral response reduced the CNR for the projection-based weighted images, while image-based weighting improved CNR for five out of the six investigated bin combinations, despite this non-ideal response, indicating potential for image-based weighting to reduce breast dose during dedicated breast CT.

Estimated ultraviolet radiation doses in wetlands in six national parks

USGS Publications Warehouse

Diamond, S.A.; Trenham, P.C.; Adams, Michael J.; Hossack, B.R.; Knapp, R.A.; Stark, L.; Bradford, D.; Corn, P.S.; Czarnowski, K.; Brooks, P.D.; Fagre, D.B.; Breen, B.; Dentenbeck, N.E.; Tonnessen, K.

2005-01-01

Ultraviolet-B radiation (UV-B, 280–320-nm wavelengths) doses were estimated for 1024 wetlands in six national parks: Acadia (Acadia), Glacier (Glacier), Great Smoky Mountains (Smoky), Olympic (Olympic), Rocky Mountain (Rocky), and Sequoia/Kings Canyon (Sequoia). Estimates were made using ground-based UV-B data (Brewer spectrophotometers), solar radiation models, GIS tools, field characterization of vegetative features, and quantification of DOC concentration and spectral absorbance. UV-B dose estimates were made for the summer solstice, at a depth of 1 cm in each wetland. The mean dose across all wetlands and parks was 19.3 W-h m−2 (range of 3.4–32.1 W-h m−2). The mean dose was lowest in Acadia (13.7 W-h m−2) and highest in Rocky (24.4 W-h m−2). Doses were significantly different among all parks. These wetland doses correspond to UV-B flux of 125.0 μW cm−2 (range 21.4–194.7 μW cm−2) based on a day length, averaged among all parks, of 15.5 h. Dissolved organic carbon (DOC), a key determinant of water-column UV-B flux, ranged from 0.6 (analytical detection limit) to 36.7 mg C L−1 over all wetlands and parks, and reduced potential maximal UV-B doses at 1-cm depth by 1%–87 %. DOC concentration, as well as its effect on dose, was lowest in Sequoia and highest in Acadia (DOC was equivalent in Acadia, Glacier, and Rocky). Landscape reduction of potential maximal UV-B doses ranged from zero to 77% and was lowest in Sequoia. These regional differences in UV-B wetland dose illustrate the importance of considering all aspects of exposure in evaluating the potential impact of UV-B on aquatic organisms.

Effect of leaded glasses and thyroid shielding on cone beam CT radiation dose in an adult female phantom

PubMed Central

Goren, AD; Prins, RD; Dauer, LT; Quinn, B; Al-Najjar, A; Faber, RD; Patchell, G; Branets, I; Colosi, DC

2013-01-01

Objectives: This study aims to demonstrate the effectiveness of leaded glasses in reducing the lens of eye dose and of lead thyroid collars in reducing the dose to the thyroid gland of an adult female from dental cone beam CT (CBCT). The effect of collimation on the radiation dose in head organs is also examined. Methods: Dose measurements were conducted by placing optically stimulated luminescent dosemeters in an anthropomorphic female phantom. Eye lens dose was measured by placing a dosemeter on the anterior surface of the phantom eye location. All exposures were performed on one commercially available dental CBCT machine, using selected collimation and exposure techniques. Each scan technique was performed without any lead shielding and then repeated with lead shielding in place. To calculate the percent reduction from lead shielding, the dose measured with lead shielding was divided by the dose measured without lead shielding. The percent reduction from collimation was calculated by comparing the dose measured with collimation to the dose measured without collimation. Results: The dose to the internal eye for one of the scans without leaded glasses or thyroid shield was 0.450 cGy and with glasses and thyroid shield was 0.116 cGy (a 74% reduction). The reduction to the lens of the eye was from 0.396 cGy to 0.153 cGy (a 61% reduction). Without glasses or thyroid shield, the thyroid dose was 0.158 cGy; and when both glasses and shield were used, the thyroid dose was reduced to 0.091 cGy (a 42% reduction). Conclusions: Collimation alone reduced the dose to the brain by up to 91%, with a similar reduction in other organs. Based on these data, leaded glasses, thyroid collars and collimation minimize the dose to organs outside the field of view. PMID:23412460

Attenuation-based automatic kilovolt (kV)-selection in computed tomography of the chest: effects on radiation exposure and image quality.

PubMed

Eller, Achim; Wuest, Wolfgang; Scharf, Michael; Brand, Michael; Achenbach, Stephan; Uder, Michael; Lell, Michael M

2013-12-01

To evaluate an automated attenuation-based kV-selection in computed tomography of the chest in respect to radiation dose and image quality, compared to a standard 120 kV protocol. 104 patients were examined using a 128-slice scanner. Fifty examinations (58 ± 15 years, study group) were performed using the automated adaption of tube potential (100-140 kV), based on the attenuation profile of the scout scan, 54 examinations (62 ± 14 years, control group) with fixed 120 kV. Estimated CT dose index (CTDI) of the software-proposed setting was compared with a 120 kV protocol. After the scan CTDI volume (CTDIvol) and dose length product (DLP) were recorded. Image quality was assessed by region of interest (ROI) measurements, subjective image quality by two observers with a 4-point scale (3--excellent, 0--not diagnostic). The algorithm selected 100 kV in 78% and 120 kV in 22%. Overall CTDIvol reduction was 26.6% (34% in 100 kV) overall DLP reduction was 22.8% (32.1% in 100 kV) (all p<0.001). Subjective image quality was excellent in both groups. The attenuation based kV-selection algorithm enables relevant dose reduction (~27%) in chest-CT while keeping image quality parameters at high levels. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses.

PubMed

Harborne, Lyndal R; Sattar, Naveed; Norman, Jane E; Fleming, Richard

2005-08-01

Metformin treatment of women with polycystic ovary syndrome (PCOS) is widespread, as determined by studies with diverse patient populations. No comparative examination of weight changes or metabolite responses to different doses has been reported. The aim of this study was to determine whether different doses of metformin (1500 or 2550 mg/d) would have different effects on body weight, circulating hormones, markers of inflammation, and lipid profiles. The study included prospective cohorts randomized to two doses of metformin. The study was performed at a university teaching hospital with patients from gynecology/endocrinology clinics. The patients studied were obese (body mass index, 30 to <37 kg/m2; n = 42) and morbidly obese (body mass index, > or =37 kg/m2; n = 41) women with PCOS. Patients were randomized to two doses of metformin, and parameters were assessed after 4 and 8 months. The main outcome measures were changes in body mass, circulating hormones, markers of inflammation, and lipid profiles. Intention to treat analyses showed significant weight loss in both dose groups. Only the obese subgroup showed a dose relationship (1.5 and 3.6 kg in 1500- and 2550-mg groups, respectively; P = 0.04). The morbidly obese group showed similar reductions (3.9 and 3.8 kg) in both groups. Suppression of androstenedione was significant with both metformin doses, but there was no clear dose relationship. Generally, beneficial changes in lipid profiles were not related to dose. Weight loss is a feature of protracted metformin therapy in obese women with PCOS, with greater weight reduction potentially achievable with higher doses. Additional studies are required to determine whether other aspects of the disorder may benefit from the higher dose of metformin.

Evidence-based Critical Evaluation of Glycemic Potential of Cynodon dactylon

PubMed Central

Singh, Santosh Kumar; Rai, Prashant Kumar; Jaiswal, Dolly

2008-01-01

The present study is an extension of our previous work carried out on Cynodon dactylon. This study deals with the critical evaluation of glycemic potential of ethanolic extract of defatted C. dactylon. The doses of 250, 500 and 750 mg kg−1 bw of the extract were administered orally to normal as well as Streptozotocin-induced diabetic rats to study its glycemic potential. The effect of repeated oral administration of the same doses of ethanolic extract was also studied on serum lipid profile of severely diabetic (SD) rats. The dose of 500 mg kg−1 bw was identified as the most effective dose as it lowered the blood glucose levels of normal by 42.12% and of diabetic by 43.42% during fasting blood glucose (FBG) and glucose tolerance test respectively. The SD rats were also treated daily with this identified dose of 500 mg kg−1 bw for 2 weeks and a significant reduction of 56.34% was observed in FBG level. Total cholesterol, low density lipoprotein and triglyceride levels were also decreased by 32.94, 64.06 and 48.46% respectively in SD rats whereas, cardioprotective high density lipoprotein increased by 16.45%. The reduced urine sugar level and increased body weight are additional advantages. These evidences clearly indicate that the ethanolic extract of defatted C. dactylon has high antidiabetic potential along with good hypolipidemic profile. PMID:18955211

Fetal shielding combined with state of the art CT dose reduction strategies during maternal chest CT.

PubMed

Chatterson, Leslie C; Leswick, David A; Fladeland, Derek A; Hunt, Megan M; Webster, Stephen; Lim, Hyun

2014-07-01

Custom bismuth-antimony shields were previously shown to reduce fetal dose by 53% on an 8DR (detector row) CT scanner without dynamic adaptive section collimation (DASC), automatic tube current modulation (ATCM) or adaptive statistical iterative reconstruction (ASiR). The purpose of this study is to compare the effective maternal and average fetal organ dose reduction both with and without bismuth-antimony shields on a 64DR CT scanner using DASC, ATCM and ASiR during maternal CTPA. A phantom with gravid prosthesis and a bismuth-antimony shield were used. Thermoluminescent dosimeters (TLDs) measured fetal radiation dose. The average fetal organ dose and effective maternal dose were determined using 100 kVp, scanning from the lung apices to the diaphragm utilizing DASC, ATCM and ASiR on a 64DR CT scanner with and without shielding in the first and third trimester. Isolated assessment of DASC was done via comparing a new 8DR scan without DASC to a similar scan on the 64DR with DASC. Average third trimester unshielded fetal dose was reduced from 0.22 mGy ± 0.02 on the 8DR to 0.13 mGy ± 0.03 with the conservative 64DR protocol that included 30% ASiR, DASC and ATCM (42% reduction, P<0.01). Use of a shield further reduced average third trimester fetal dose to 0.04 mGy ± 0.01 (69% reduction, P<0.01). The average fetal organ dose reduction attributable to DASC alone was modest (6% reduction from 0.17 mGy ± 0.02 to 0.16 mGy ± 0.02, P=0.014). First trimester fetal organ dose on the 8DR protocol was 0.07 mGy ± 0.03. This was reduced to 0.05 mGy ± 0.03 on the 64DR protocol without shielding (30% reduction, P=0.009). Shields further reduced this dose to below accurately detectable levels. Effective maternal dose was reduced from 4.0 mSv on the 8DR to 2.5 mSv on the 64DR scanner using the conservative protocol (38% dose reduction). ASiR, ATCM and DASC combined significantly reduce effective maternal and fetal organ dose during CTPA. Shields continue to be an effective means of fetal dose reduction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Estimation of the collective ionizing dose in the Portuguese population for the years 2011 and 2012, due to nuclear medicine exams.

PubMed

Costa, F; Teles, P; Nogueira, A; Barreto, A; Santos, A I; Carvalho, A; Martins, B; Oliveira, C; Gaspar, C; Barros, C; Neves, D; Costa, D; Rodrigues, E; Godinho, F; Alves, F; Cardoso, G; Cantinho, G; Conde, I; Vale, J; Santos, J; Isidoro, J; Pereira, J; Salgado, L; Rézio, M; Vieira, M; Simãozinho, P; Almeida, P; Castro, R; Parafita, R; Pintão, S; Lúcio, T; Reis, T; Vaz, P

2015-01-01

In 2009-2010 a Portuguese consortium was created to implement the methodologies proposed by the Dose Datamed II (DDM2) project, aiming to collect data from diagnostic X-ray and nuclear medicine (NM) procedures, in order to determine the most frequently prescribed exams and the associated ionizing radiation doses for the Portuguese population. The current study is the continuation of this work, although it focuses only on NM exams for the years 2011 and 2012. The annual frequency of each of the 28 selected NM exams and the average administered activity per procedure was obtained by means of a nationwide survey sent to the 35 NM centres in Portugal. The results show a reduction of the number of cardiac exams performed in the last two years compared with 2010, leading to a reduction of the annual average effective dose of Portuguese population due to NM exams from 0.08 mSv ± 0.017 mSv/caput to 0.059 ± 0.011 mSv/caput in 2011 and 0.054 ± 0.011 mSv/caput in 2012. Portuguese total annual average collective effective dose due to medical procedures was estimated to be 625.6 ± 110.9 manSv in 2011 and 565.1 ± 117.3 manSv in 2012, a reduction in comparison with 2010 (840.3 ± 183.8 manSv). The most frequent exams and the ones that contributed the most for total population dose were the cardiac and bone exams, although a decrease observed in 2011 and in 2012 was verified. The authors intend to perform this study periodically to identify trends in the annual Portuguese average effective dose and to help to raise awareness about the potential dose optimization. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Combination of atorvastatin with sulindac or naproxen profoundly inhibits colonic adenocarcinomas by suppressing the p65/β-catenin/cyclin D1 signaling pathway in rats

PubMed Central

Suh, Nanjoo; Reddy, Bandaru S.; DeCastro, Andrew; Paul, Shiby; Lee, Hong Jin; Smolarek, Amanda K.; So, Jae Young; Simi, Barbara; Wang, Chung Xiou; Janakiram, Naveena B.; Steele, Vernon; Rao, Chinthalapally V.

2011-01-01

Evidence supports the protective role of non-steroidal anti-inflammatory drugs (NSAIDs) and statins against colon cancer. Experiments were designed to evaluate the efficacies atorvastatin and NSAIDs administered individually and in combination against colon tumor formation. F344 rats were fed AIN-76A diet and colon tumors were induced with azoxymethane (AOM). One week after the second AOM-treatment groups of rats were fed diets containing atorvastatin (200 ppm), sulindac (100 ppm) or naproxen (150 ppm), or their combinations with low-dose atorvastatin (100 ppm) for 45 weeks. Administration of atorvastatin at 200 ppm significantly suppressed both adenocarcinoma incidence (52% reduction, p=0.005) and multiplicity (58% reduction, p=0.008). Most importantly, colon tumor multiplicities were profoundly decreased (80–85% reduction, p<0.0001) when given low-dose atorvastatin with either sulindac or naproxen. Also, a significant inhibition of colon tumor incidence was observed when given a low-dose atorvastatin with either sulindac (p=0.001) or naproxen (p =0.0005). Proliferation markers, proliferating cell nuclear antigen, cyclin D1 and β-catenin in tumors of rats exposed to sulindac, naproxen, atorvastatin, and/or combinations showed a significant suppression. Importantly, colon adenocarcinomas from atorvastatin and NSAIDs fed animals showed reduced key inflammatory markers, inducible nitric oxide synthase and cyclooxygenase-2, phospho-p65, as well as inflammatory cytokines, TNF-α, IL-1β, and IL-4. Overall, this is the first report on the combination treatment using low-dose atorvastatin with either low dose sulindac or naproxen, which greatly suppress the colon adenocarcinoma incidence and multiplicity. Our results suggest that low-dose atorvastatin with sulindac or naproxen might potentially be useful combinations for colon cancer prevention in humans. PMID:21764859

Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors, decreases ethanol consumption in alcohol-preferring UChB rats.

PubMed

Quiroz, Gabriel; Guerra-Díaz, Nicolás; Iturriaga-Vásquez, Patricio; Rivera-Meza, Mario; Quintanilla, María Elena; Sotomayor-Zárate, Ramón

2018-09-03

Alcohol abuse is a worldwide health problem with high economic costs to health systems. Emerging evidence suggests that modulation of brain nicotinic acetylcholine receptors (nAChRs) may be a therapeutic target for alcohol dependence. In this work, we assess the effectiveness of four doses of erysodine (1.5, 2.0, 4.0 or 8.0 mg/kg/day, i.p.), a competitive antagonist of nAChRs, on voluntary ethanol consumption behavior in alcohol-preferring UChB rats, administered during three consecutive days. Results show that erysodine administration produces a dose-dependent reduction in ethanol consumption respect to saline injection (control group). The highest doses of erysodine (4 and 8 mg/kg) reduce (45 and 66%, respectively) the ethanol intake during treatment period and first day of post-treatment compared to control group. While, the lowest doses of erysodine (1.5 and 2 mg/kg) only reduce ethanol intake during one day of treatment period. These effective reductions in ethanol intake were 23 and 29% for 1.5 and 2 mg/kg erysodine, respectively. Locomotor activity induced by a high dose of erysodine (10 mg/kg) was similar to those observed with saline injection in control rats, showing that the reduction in ethanol intake was not produced by hypolocomotor effect induced by erysodine. This is the first report showing that erysodine reduces ethanol intake in UChB rats in a dose-dependent manner. Our results highlight the role of nAChRs in the reward effects of ethanol and its modulation as a potentially effective pharmacological alternative for alcohol dependence treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans.

PubMed

Chaikh, Abdulhamid; Calugaru, Valentin; Bondiau, Pierre-Yves; Thariat, Juliette; Balosso, Jacques

2018-06-07

The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. 14 pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < 0.05, using the three NTCP concepts. However, applying the same TD 50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Since estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD 50/5 , a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient's plan.

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

PubMed

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

2017-07-01

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

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction

PubMed Central

Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-01-01

Introduction Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. Materials and Methods A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Results Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13–53.8% reduction in low dose protocol. Conclusion The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose. PMID:27437322

Low Dose MDCT with Tube Current Modulation: Role in Detection of Urolithiasis and Patient Effective Dose Reduction.

PubMed

Koteshwar, Prakashini; Kakkar, Chandan; Sripathi, Smiti; Parakh, Anushri; Shrivastav, Rajendra

2016-05-01

Urolithiasis is one of the major, recurring problem in young individuals and CT being the commonest diagnostic modality used. In order to reduce the radiation dose to the patient who are young and as stone formation is a recurring process; one of the simplest way would be, low dose CT along with tube current modulation. Aim of this study was to compare the sensitivity and specificity of low dose (70mAs) with standard dose (250mAs) protocol in detecting urolithiasis and to define the tube current and mean effective patient dose by these protocols. A prospective study was conducted in 200 patients over a period of 2 years with acute flank pain presentation. CT was performed in 100 cases with standard dose and another 100 with low dose protocol using tube current modulation. Sensitivity and specificity for calculus detection, percentage reduction of dose and tube current with low dose protocol was calculated. Urolithiasis was detected in 138 patients, 67 were examined by high dose and 71 were by low dose protocol. Sensitivity and Specificity of low dose protocol was 97.1% and 96.4% with similar results found in high BMI patients. Tube current modulation resulted in reduction of effective tube current by 12.17%. The mean effective patient dose for standard dose was 10.33 mSv whereas 2.92 mSv for low dose with 51.13-53.8% reduction in low dose protocol. The study has reinforced that low-dose CT with tube current modulation is appropriate for diagnosis of urolithiasis with significant reduction in tube current and patient effective dose.

Bupropion-varenicline interactions and nicotine self-administration behavior in rats.

PubMed

Hall, Brandon J; Slade, Susan; Wells, Corinne; Rose, Jed E; Levin, Edward D

2015-03-01

Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone. Copyright © 2015 Elsevier Inc. All rights reserved.

Can image enhancement allow radiation dose to be reduced whilst maintaining the perceived diagnostic image quality required for coronary angiography?

PubMed Central

Joshi, Anuja; Gislason-Lee, Amber J; Keeble, Claire; Sivananthan, Uduvil M

2017-01-01

Objective: The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to confidently make a diagnosis. Methods: Incremental amounts of image noise were added to five PCI angiograms, simulating the angiogram as having been acquired at corresponding lower dose levels (10–89% dose reduction). 16 observers with relevant experience scored the image quality of these angiograms in 3 states—with no image processing and with 2 different modern image processing algorithms applied. These algorithms are used on state-of-the-art and previous generation cardiac interventional X-ray systems. Ordinal regression allowing for random effects and the delta method were used to quantify the dose reduction possible by the processing algorithms, for equivalent image quality scores. Results: Observers rated the quality of the images processed with the state-of-the-art and previous generation image processing with a 24.9% and 15.6% dose reduction, respectively, as equivalent in quality to the unenhanced images. The dose reduction facilitated by the state-of-the-art image processing relative to previous generation processing was 10.3%. Conclusion: Results demonstrate that statistically significant dose reduction can be facilitated with no loss in perceived image quality using modern image enhancement; the most recent processing algorithm was more effective in preserving image quality at lower doses. Advances in knowledge: Image enhancement was shown to maintain perceived image quality in coronary angiography at a reduced level of radiation dose using computer software to produce synthetic images from real angiograms simulating a reduction in dose. PMID:28124572

DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker.

PubMed

Daudee, Rotem; Gonen, Rafi; German, Uzi; Orion, Itzhak; Alfassi, Zeev B; Priel, Esther

2018-06-01

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60 Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.

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

Brady, S; Shulkin, B

Purpose: To develop ultra-low dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultra-low doses (10–35 mAs). CT quantitation: noise, low-contrast resolution, and CT numbers for eleven tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% CTDIvol (0.39/3.64; mGy) radiation dose from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET images were reconstructed withmore » the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUVbw) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation organ dose, as derived from patient exam size specific dose estimate (SSDE), was converted to effective dose using the standard ICRP report 103 method. Effective dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative patient population dose reduction and noise control. Results: CT numbers were constant to within 10% from the non-dose reduced CTAC image down to 90% dose reduction. No change in SUVbw, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols reconstructed with ASiR and down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62%–86% (3.2/8.3−0.9/6.2; mSv). Noise magnitude in dose-reduced patient images increased but was not statistically different from pre dose-reduced patient images. Conclusion: Using ASiR allowed for aggressive reduction in CTAC dose with no change in PET reconstructed images while maintaining sufficient image quality for co-localization of hybrid CT anatomy and PET radioisotope uptake.« less

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia.

PubMed

Ferreira, António Miguel; Marques da Silva, Pedro

2017-06-01

Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and high-density lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatin-ezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia.

Dose and risk in diagnostic radiology: How big How little Lecture Number 16

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

Webster, E.W.

1992-01-01

This lecture is divided into two parts: dose and risk. The dose segment is technical and noncontroversial since it deals with straightforward measurements or calculations which do not depend on unproven hypotheses. Some conflicting contributions of low dose epidemiological studies to the appraisal of risk are briefly presented. Attention is focused on the following: dose reduction in radiography; dose reduction in fluoroscopy; limitations of dose reduction; estimated radiation risks for diagnostic radiology examinations; excess breast cancer following X-ray examinations for scoliosis; dose-response relation for human mammary cancer; lung cancer from protracted X-irradiation; leukemia and diagnostic X-ray exposure; and thyroid cancermore » after diagnostic dose of I-131.« less

Low-voltage chest CT: another way to reduce the radiation dose in asbestos-exposed patients.

PubMed

Macía-Suárez, D; Sánchez-Rodríguez, E; Lopez-Calviño, B; Diego, C; Pombar, M

2017-09-01

To assess whether low voltage chest computed tomography (CT) can be used to successfully diagnose disease in patients with asbestos exposure. Fifty-six former employees of the shipbuilding industry, who were candidates to receive a standard-dose chest CT due to their occupational exposure to asbestos, underwent a routine CT. Immediately after this initial CT, they underwent a second acquisition using low-dose chest CT parameters, based on a low potential (80 kV) and limited tube current. The findings of the two CT protocols were compared based on typical diseases associated with asbestos exposure. The kappa coefficient for each parameter and for an overall rating (grouping them based on mediastinal, pleural, and pulmonary findings) were calculated in order to test for correlations between the two protocols. A good correlation between routine and low-dose CT was demonstrated for most parameters with a mean radiation dose reduction of up to 83% of the effective dose based on the dose-length product between protocols. Low-dose chest CT, based on a limited tube potential, is useful for patients with an asbestos exposure background. Low-dose chest CT can be successfully used to minimise the radiation dose received by patients, as this protocol produced an estimated mean effective dose similar to that of an abdominal or pelvis plain film. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

PubMed Central

Gomes, Melba; Ribeiro, Isabela; Warsame, Marian; Karunajeewa, Harin; Petzold, Max

2008-01-01

Background Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria. Methods Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success. Results Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether. Conclusion Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy. PMID:18373841

A simple method for low-contrast detectability, image quality and dose optimisation with CT iterative reconstruction algorithms and model observers.

PubMed

Bellesi, Luca; Wyttenbach, Rolf; Gaudino, Diego; Colleoni, Paolo; Pupillo, Francesco; Carrara, Mauro; Braghetti, Antonio; Puligheddu, Carla; Presilla, Stefano

2017-01-01

The aim of this work was to evaluate detection of low-contrast objects and image quality in computed tomography (CT) phantom images acquired at different tube loadings (i.e. mAs) and reconstructed with different algorithms, in order to find appropriate settings to reduce the dose to the patient without any image detriment. Images of supraslice low-contrast objects of a CT phantom were acquired using different mAs values. Images were reconstructed using filtered back projection (FBP), hybrid and iterative model-based methods. Image quality parameters were evaluated in terms of modulation transfer function; noise, and uniformity using two software resources. For the definition of low-contrast detectability, studies based on both human (i.e. four-alternative forced-choice test) and model observers were performed across the various images. Compared to FBP, image quality parameters were improved by using iterative reconstruction (IR) algorithms. In particular, IR model-based methods provided a 60% noise reduction and a 70% dose reduction, preserving image quality and low-contrast detectability for human radiological evaluation. According to the model observer, the diameters of the minimum detectable detail were around 2 mm (up to 100 mAs). Below 100 mAs, the model observer was unable to provide a result. IR methods improve CT protocol quality, providing a potential dose reduction while maintaining a good image detectability. Model observer can in principle be useful to assist human performance in CT low-contrast detection tasks and in dose optimisation.

Dosimetric effects of polyethylene glycol surface coatings on gold nanoparticle radiosensitization

NASA Astrophysics Data System (ADS)

Koger, B.; Kirkby, C.

2017-11-01

One of the main appeals of using gold nanoparticles (GNPs) as radiosensitizers is that their surface coatings can be altered to manipulate their pharmacokinetic properties. However, Monte Carlo studies of GNP dosimetry tend to neglect these coatings, potentially changing the dosimetric results. This study quantifies the dosimetric effects of including a polyethylene glycol (PEG) surface coating on GNPs over both nanoscopic and microscopic ranges. Two dosimetric scales were explored using PENELOPE Monte Carlo simulations. In microscopic simulations, 500-1000 GNPs, with and without coatings, were placed in cavities of side lengths 0.8-4 µm, and the reduction of dose deposited to surrounding medium within these volumes due to the coating was quantified. Including PEG surface coatings of up to 20 nm thickness resulted in reductions of up to 7.5%, 4.0%, and 2.0% for GNP diameters of 10, 20, and 50 nm, respectively. Nanoscopic simulations observed the dose falloff in the first 500 nm surrounding a single GNP both with and without surface coatings of various thicknesses. Over the first 500 nm surrounding a single GNP, the presence of a PEG surface coating reduced dose by 5-26%, 8-28%, 8-30%, and 8-34% for 2, 10, 20, and 50 nm diameter GNPs, respectively, for various energies and coating thicknesses. Reductions in dose enhancement due to the inclusion of a GNP surface coating are non-negligible and should be taken into consideration when investigating GNP dose enhancement. Further studies should be carried out to investigate the biological effects of these coatings.

Anticancer activity of bacteriophage T4 and its mutant HAP1 in mouse experimental tumour models.

PubMed

Dabrowska, Krystyna; Opolski, Adam; Wietrzyk, Joanna; Switala-Jelen, Kinga; Godlewska, Joanna; Boratynski, Janusz; Syper, Danuta; Weber-Dabrowska, Beata; Gorski, Andrzej

2004-01-01

Previously, we have shown the ability of the bacteriophage T4 and its substrain HAP1 (selected for a higher affinity to melanoma cells) to reveal antimetastatic activity in a mouse melanoma model. Here, we investigated the potential phage anticancer activity in primary tumour models. Mice were inoculated subcutaneously with B16 or LLC cells (collected from in vitro culture). Bacteriophages T4 and HAP1 were injected intraperitoneally daily (8 x 10(8)pfu/mouse, except the experiment concerning the dose-dependence). Treatment with purified preparations of bacteriophage T4 resulted in significant reduction of tumour size, the effect being dose-dependent. HAP1 was more effective than T4 and its activity was also dose-dependent. Parallel experiments with non-purified bacteriophage lysates resulted in significant stimulation of tumour growth. These data suggest that purified bacteriophages may inhibit tumour growth, a phenomenon with potentially important clinical implications in oncology.

Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial.

PubMed

van Herwaarden, Noortje; van der Maas, Aatke; Minten, Michiel J M; van den Hoogen, Frank H J; Kievit, Wietske; van Vollenhoven, Ronald F; Bijlsma, Johannes W J; van den Bemt, Bart J F; den Broeder, Alfons A

2015-04-09

To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or etanercept, is non-inferior in maintaining disease control in patients with rheumatoid arthritis compared with usual care. Randomised controlled, open label, non-inferiority strategy trial. Two rheumatology outpatient clinics in the Netherlands, from December 2011 to May 2014. 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care. Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was restarted or escalated. Difference in proportions of patients with major flare (DAS28-CRP based flare longer than three months) between the two groups at 18 months, compared against a non-inferiority margin of 20%. Secondary outcomes included TNF inhibitor use at study end, functioning, quality of life, radiographic progression, and adverse events. Dose reduction of adalimumab or etanercept was non-inferior to usual care (proportion of patients with major flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval -12% to 12%). In the dose reduction group, TNF inhibitor use could successfully be stopped in 20% (95% confidence interval 13% to 28%), the injection interval successfully increased in 43% (34% to 53%), but no dose reduction was possible in 37% (28% to 46%). Functional status, quality of life, relevant radiographic progression, and adverse events did not differ between the groups, although short lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were more frequent in dose reduction than usual care. A disease activity guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid arthritis is non-inferior to usual care with regard to major flaring, while resulting in the successful dose reduction or stopping in two thirds of patients.Trial registration Dutch trial register (www.trialregister.nl), NTR 3216. © van Herwaarden et al 2015.

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

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

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

Lee, J; Chung, J

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designedmore » for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.« less

CPP-115, a Potent γ-Aminobutyric Acid Aminotransferase Inactivator for the Treatment of Cocaine Addiction

PubMed Central

Pan, Yue; Gerasimov, Madina R.; Kvist, Trine; Wellendorph, Petrine; Madsen, Karsten K.; Pera, Elena; Lee, Hyunbeom; Schousboe, Arne; Chebib, Mary; Bräuner-Osborne, Hans; Craft, Cheryl M.; Brodie, Jonathan D.; Schiffer, Wynne K.; Dewey, Stephen L.; Miller, Steven R.; Silverman, Richard B.

2011-01-01

Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target activities and is rapidly and completely orally absorbed and eliminated. Using in vivo microdialysis techniques in freely moving rats and micro-PET imaging techniques, CPP-115 produced similar inhibition of cocaine-induced increases in extracellular dopamine and in synaptic dopamine in the nucleus accumbens at 1/300–1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20–40 times higher than those needed to treat addiction in rats, exhibited reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction with a significantly reduced risk of visual field defects. PMID:22128851

Neonatal outcomes following exposure in utero to fallout from Chernobyl.

PubMed

Hatch, Maureen; Little, Mark P; Brenner, Alina V; Cahoon, Elizabeth K; Tereshchenko, Valery; Chaikovska, Ludmyla; Pasteur, Igor; Likhtarov, Ilya; Bouville, Andre; Shpak, Victor; Bolshova, Olena; Zamotayeva, Galyna; Grantz, Katherine; Sun, Liping; Mabuchi, Kiyohiko; Albert, Paul; Tronko, Mykola

2017-12-01

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members' prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (-1.0 cm/Gy, P = 0.005) and chest circumference (-0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (-0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

PubMed

Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F

2016-02-25

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

Ultralow dose computed tomography attenuation correction for pediatric PET CT using adaptive statistical iterative reconstruction

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

Brady, Samuel L., E-mail: samuel.brady@stjude.org; Shulkin, Barry L.

2015-02-15

Purpose: To develop ultralow dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultralow doses (10–35 mA s). CT quantitation: noise, low-contrast resolution, and CT numbers for 11 tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% volume computed tomography dose index (0.39/3.64; mGy) from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET imagesmore » were reconstructed with the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUV{sub bw}) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative dose reduction and noise control. Results: CT numbers were constant to within 10% from the nondose reduced CTAC image for 90% dose reduction. No change in SUV{sub bw}, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols was found down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62% and 86% (3.2/8.3–0.9/6.2). Noise magnitude in dose-reduced patient images increased but was not statistically different from predose-reduced patient images. Conclusions: Using ASiR allowed for aggressive reduction in CT dose with no change in PET reconstructed images while maintaining sufficient image quality for colocalization of hybrid CT anatomy and PET radioisotope uptake.« less

SU-F-P-45: Clinical Experience with Radiation Dose Reduction of CT Examinations Using Iterative Reconstruction Algorithms

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

Weir, V; Zhang, J

2016-06-15

Purpose: Iterative reconstruction (IR) algorithms have been adopted by medical centers in the past several years. IR has a potential to substantially reduce patient dose while maintaining or improving image quality. This study characterizes dose reductions in clinical settings for CT examinations using IR. Methods: We retrospectively analyzed dose information from patients who underwent abdomen/pelvis CT examinations with and without contrast media in multiple locations of our Healthcare system. A total of 743 patients scanned with ASIR on 64 slice GE lightspeed VCTs at three sites, and 30 patients scanned with SAFIRE on a Siemens 128 slice Definition Flash inmore » one site was retrieved. For comparison, patient data (n=291) from a GE scanner and patient data (n=61) from two Siemens scanners where filtered back-projection (FBP) was used was collected retrospectively. 30% and 10% ASIR, and SAFIRE Level 2 was used. CTDIvol, Dose-length-product (DLP), weight and height from all patients was recorded. Body mass index (BMI) was calculated accordingly. To convert CTDIvol to SSDE, AP and lateral dimensions at the mid-liver level was measured for each patient. Results: Compared with FBP, 30% ASIR reduces dose by 44.1% (SSDE: 12.19mGy vs. 21.83mGy), while 10% ASIR reduced dose by 20.6% (SSDE 17.32mGy vs. 21.83). Use of SAFIRE reduced dose by 61.4% (SSDE: 8.77mGy vs. 22.7mGy). The geometric mean for patients scanned with ASIR was larger than for patients scanned with FBP (geometric mean is 297.48 mmm vs. 284.76 mm). The same trend was observed for the Siemens scanner where SAFIRE was used (geometric mean: 316 mm with SAFIRE vs. 239 mm with FBP). Patient size differences suggest that further dose reduction is possible. Conclusion: Our data confirmed that in clinical practice IR can significantly reduce dose to patients who undergo CT examinations, while meeting diagnostic requirements for image quality.« less

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

PubMed

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

2017-01-01

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

Radiation dose management in thoracic CT: an international survey.

PubMed

Molinari, Francesco; Tack, Denis M; Boiselle, Philip; Ngo, Long; Mueller-Mang, Christina; Litmanovich, Diana; Bankier, Alexander A

2013-01-01

We aimed to examine current practice patterns of international thoracic radiologists regarding radiation dose management in adult thoracic computed tomography (CT) examinations. An electronic questionnaire was sent to 800 members of five thoracic radiology societies in North America, Europe, Asia, and Latin America addressing radiation dose training and education, standard kVp and mAs settings for thoracic CT, dose reduction practices, clinical scenarios, and demographics. Of the 800 radiologists, 146 responded to our survey. Nearly half (66/146, 45% [95% confidence interval, 37%-53%]) had no formal training in dose reduction, with "self-study of the literature" being the most common form of training (54/146, 37% [29%-45%]). One hundred and seventeen (80% [74%-87%]) had automatic exposure control, and 76 (65% [56%-74%]) used it in all patients. Notably, most respondents (89% [84%-94%]) used a 120 to 125 kVp standard setting, whereas none used 140 kVp. The most common average dose-length-product (DLP) value was 150 to 249 mGy.cm (75/146, 51% [43%-59%]), and 59% (51%-67%) delivered less than 250 mGy.cm in a 70 kg patient. There was a tendency towards higher DLP values with multidetector-row CT. Age, gender, and pregnancy were associated more with dose reduction than weight and clinical indication. Efforts for reducing patient radiation dose are highly prevalent among thoracic radiologists. Areas for improvement include reduction of default tube current settings, reduction of anatomical scan coverage, greater use of automatic exposure control, and eventually, reduction of current reference dose values. Our study emphasizes the need for international guidelines to foster greater conformity in dose reduction by thoracic radiologists.

Paediatric cardiac CT examinations: impact of the iterative reconstruction method ASIR on image quality--preliminary findings.

PubMed

Miéville, Frédéric A; Gudinchet, François; Rizzo, Elena; Ou, Phalla; Brunelle, Francis; Bochud, François O; Verdun, Francis R

2011-09-01

Radiation dose exposure is of particular concern in children due to the possible harmful effects of ionizing radiation. The adaptive statistical iterative reconstruction (ASIR) method is a promising new technique that reduces image noise and produces better overall image quality compared with routine-dose contrast-enhanced methods. To assess the benefits of ASIR on the diagnostic image quality in paediatric cardiac CT examinations. Four paediatric radiologists based at two major hospitals evaluated ten low-dose paediatric cardiac examinations (80 kVp, CTDI(vol) 4.8-7.9 mGy, DLP 37.1-178.9 mGy·cm). The average age of the cohort studied was 2.6 years (range 1 day to 7 years). Acquisitions were performed on a 64-MDCT scanner. All images were reconstructed at various ASIR percentages (0-100%). For each examination, radiologists scored 19 anatomical structures using the relative visual grading analysis method. To estimate the potential for dose reduction, acquisitions were also performed on a Catphan phantom and a paediatric phantom. The best image quality for all clinical images was obtained with 20% and 40% ASIR (p < 0.001) whereas with ASIR above 50%, image quality significantly decreased (p < 0.001). With 100% ASIR, a strong noise-free appearance of the structures reduced image conspicuity. A potential for dose reduction of about 36% is predicted for a 2- to 3-year-old child when using 40% ASIR rather than the standard filtered back-projection method. Reconstruction including 20% to 40% ASIR slightly improved the conspicuity of various paediatric cardiac structures in newborns and children with respect to conventional reconstruction (filtered back-projection) alone.

Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats.

PubMed

Iannone, Michelangelo; Bulotta, Stefania; Paolino, Donatella; Zito, Maria Cristina; Gratteri, Santo; Costanzo, Francesco S; Rotiroti, Domenicantonio

2006-02-16

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db) demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power) of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation. Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties.

DOSE-DEPENDENT REDUCTIONS IN SPATIAL LEARING AND SYNAPTIC FUNCTION IN THE DENTATE GYRUS OF ADULT RATS FOLLOWING DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY.

EPA Science Inventory

The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

Prospective Measurement of Patient Exposure to Radiation During Pediatric Ureteroscopy

PubMed Central

Kokorowski, Paul J.; Chow, Jeanne S.; Strauss, Keith; Pennison, Melanie; Routh, Jonathan C.; Nelson, Caleb P.

2013-01-01

Objective Little data have been reported regarding radiation exposure during pediatric endourologic procedures, including ureteroscopy (URS). We sought to measure radiation exposure during pediatric URS and identify opportunities for exposure reduction. Methods We prospectively observed URS procedures as part of a quality improvement initiative. Pre-operative patient characteristics, operative factors, fluoroscopy settings and radiation exposure were recorded. Our outcomes were entrance skin dose (ESD, in mGy) and midline dose (MLD, in mGy). Specific modifiable factors were identified as targets for potential quality improvement. Results Direct observation was performed on 56 consecutive URS procedures. Mean patient age was 14.8 ± 3.8 years (range 7.4 to 19.2); 9 children were under age 12 years. Mean ESD was 46.4 ± 48 mGy. Mean MLD was 6.2 ± 5.0 mGy. The most important major determinant of radiation dose was total fluoroscopy time (mean 2.68 ± 1.8 min) followed by dose rate setting, child anterior-posterior (AP) diameter, and source to skin distance (all p<0.01). The analysis of factors affecting exposure levels found that the use of ureteral access sheaths (p=0.01) and retrograde pyelography (p=0.04) were significantly associated with fluoroscopy time. We also found that dose rate settings were higher than recommended in up to 43% of cases and ideal C-arm positioning could have reduced exposure 14% (up to 49% in some cases). Conclusions Children receive biologically significant radiation doses during URS procedures. Several modifiable factors contribute to dose and could be targeted in efforts to implement dose reduction strategies. PMID:22341275

Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

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

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bussière, Marc R.; Chapman, Paul H.

2016-07-01

Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dosemore » delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in all fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.« less

[Examination of patient dose reduction in cardiovasucular X-ray systems with a metal filter].

PubMed

Yasuda, Mitsuyoshi; Kato, Kyouichi; Tanabe, Nobuaki; Sakiyama, Koushi; Uchiyama, Yushi; Suzuki, Yoshiaki; Suzuki, Hiroshi; Nakazawa, Yasuo

2012-01-01

In interventional X-ray for cardiology of flat panel digital detector (FPD), the phenomenon that exposure dose was suddenly increased when a subject thickness was thickened was recognized. At that time, variable metal built-in filters in FPD were all off. Therefore, we examined whether dose reduction was possible without affecting a clinical image using metal filter (filter) which we have been conventionally using for dose reduction. About 45% dose reduction was achieved when we measured an exposure dose at 30 cm of acrylic thickness in the presence of a filter. In addition, we measured signal to noise ratio/contrast to noise ratio/a resolution limit by the visual evaluation, and there was no influence by filter usage. In the clinical examination, visual evaluation of image quality of coronary angiography (40 cases) using a 5-point evaluation scale by a physician was performed. As a result, filter usage did not influence the image quality (p=NS). Therefore, reduction of sudden increase of exposure dose was achieved without influencing an image quality by adding filter to FPD.

Evaluation of energy in heated water vapor for the application of lung volume reduction in patients with severe emphysema.

PubMed

Henne, Erik; Kesten, Steven; Herth, Felix J F

2013-01-01

A method of achieving endoscopic lung volume reduction for emphysema has been developed that utilizes precise amounts of thermal energy in the form of water vapor to ablate lung tissue. This study evaluates the energy output and implications of the commercial InterVapor system and compares it to the clinical trial system. Two methods of evaluating the energy output of the vapor systems were used, a direct energy measurement and a quantification of resultant thermal profile in a lung model. Direct measurement of total energy and the component attributable to gas (vapor energy) was performed by condensing vapor in a water bath and measuring the temperature and mass changes. Infrared images of a lung model were taken after vapor delivery. The images were quantified to characterize the thermal profile. The total energy and vapor energy of the InterVapor system was measured at various dose levels and compared to the clinical trial system at a dose of 10.0 cal/g. An InterVapor dose of 8.5 cal/g was found to have the most similar vapor energy output with the smallest associated reduction in total energy. This was supported by characterization of the thermal profile in the lung model that demonstrated the profile of InterVapor at 8.5 cal/g to not exceed the profile of the clinical trial system. Considering both total energy and vapor energy is important during the development of clinical vapor applications. For InterVapor, a closer study of both energy types justified a reduced target vapor-dosing range for lung volume reduction. The clinical implication is a potential improvement for benefiting the risk profile. Copyright © 2013 S. Karger AG, Basel.

Potential antimalarial activity of Methyl Jasmonate and its effect on lipid profiles in Plasmodium Berghei infected mice.

PubMed

Oyinloye, Oladapo E; Kosoko, Ayokulehin M; Emikpe, Benjamin; Falade, Catherine O; Ademowo, Olusegun G

2015-09-01

The antimalarial activity and lipid profiles of Methyl Jasmonate (MJ) were investigated against established malaria infection in vivo using BALB/c mice. Arteether (AE) and chloroquine (CQ) were used as reference drugs while ethanol was used as the vehicle for drug delivery for MJ. Mice treated with 10 and 25 mg/kg MJ showed a remarkable reduction in percentage parasitemia by 68.3% and 78.2% on day 10(post treatment) respectively while 45.4% and 87.2% reduction in percentage parasitemia were observed in the group treated with 50 mg/kg on day 3 and 10 (post treatment) respectively. The highest mean survival time was observed in CQ followed by AE and MJ in dose-dependent manner. A progressive decrease in packed cell volume (PCV) was observed in infected untreated mice which led to the death of all the mice by day 9 (post treatment). Infected mice treated with MJ showed reduced level of HDL and LDL compared with infected untreated group. As the dose of MJ increased in infected mice cholesterol levels increased while there was reduction in triglyceride. Overall there was marked decrease in parasitemia in Plasmodium berghei infected mice treated with graded doses of MJ but appears to have reduced antimalarial activity compared with CQ and AE.

Visual grading characteristics and ordinal regression analysis during optimisation of CT head examinations.

PubMed

Zarb, Francis; McEntee, Mark F; Rainford, Louise

2015-06-01

To evaluate visual grading characteristics (VGC) and ordinal regression analysis during head CT optimisation as a potential alternative to visual grading assessment (VGA), traditionally employed to score anatomical visualisation. Patient images (n = 66) were obtained using current and optimised imaging protocols from two CT suites: a 16-slice scanner at the national Maltese centre for trauma and a 64-slice scanner in a private centre. Local resident radiologists (n = 6) performed VGA followed by VGC and ordinal regression analysis. VGC alone indicated that optimised protocols had similar image quality as current protocols. Ordinal logistic regression analysis provided an in-depth evaluation, criterion by criterion allowing the selective implementation of the protocols. The local radiology review panel supported the implementation of optimised protocols for brain CT examinations (including trauma) in one centre, achieving radiation dose reductions ranging from 24 % to 36 %. In the second centre a 29 % reduction in radiation dose was achieved for follow-up cases. The combined use of VGC and ordinal logistic regression analysis led to clinical decisions being taken on the implementation of the optimised protocols. This improved method of image quality analysis provided the evidence to support imaging protocol optimisation, resulting in significant radiation dose savings. • There is need for scientifically based image quality evaluation during CT optimisation. • VGC and ordinal regression analysis in combination led to better informed clinical decisions. • VGC and ordinal regression analysis led to dose reductions without compromising diagnostic efficacy.

Dose reduction of scattered photons from concrete walls lined with lead: Implications for improvement in design of megavoltage radiation therapy facility mazes.

PubMed

Al-Affan, I A M; Hugtenburg, R P; Bari, D S; Al-Saleh, W M; Piliero, M; Evans, S; Al-Hasan, M; Al-Zughul, B; Al-Kharouf, S; Ghaith, A

2015-02-01

This study explores the possibility of using lead to cover part of the radiation therapy facility maze walls in order to absorb low energy photons and reduce the total dose at the maze entrance of radiation therapy rooms. Experiments and Monte Carlo simulations were utilized to establish the possibility of using high-Z materials to cover the concrete walls of the maze in order to reduce the dose of the scattered photons at the maze entrance. The dose of the backscattered photons from a concrete wall was measured for various scattering angles. The dose was also calculated by the FLUKA and EGSnrc Monte Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy room to study the effect of multiple scattering when adding lead to cover the concrete walls of the maze. Monoenergetic photons were used to represent the main components of the x ray spectrum up to 10 MV. It was observed that when the concrete wall was covered with just 2 mm of lead, the measured dose rate at all backscattering angles was reduced by 20% for photons of energy comparable to Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS showed that the reduction in the dose was potentially even higher when lead was added. One explanation for the reduction is the increased absorption of backscattered photons due to the photoelectric interaction in lead. The results also showed that adding 2 mm lead to the concrete walls and floor of the maze reduced the dose at the maze entrance by up to 90%. This novel proposal of covering part or the entire maze walls with a few millimeters of lead would have a direct implication for the design of radiation therapy facilities and would assist in upgrading the design of some mazes, especially those in facilities with limited space where the maze length cannot be extended to sufficiently reduce the dose. © 2015 American Association of Physicists in Medicine.

Dose reduction of scattered photons from concrete walls lined with lead: Implications for improvement in design of megavoltage radiation therapy facility mazes

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

Al-Affan, I. A. M., E-mail: info@medphys-environment.co.uk; Hugtenburg, R. P.; Piliero, M.

Purpose: This study explores the possibility of using lead to cover part of the radiation therapy facility maze walls in order to absorb low energy photons and reduce the total dose at the maze entrance of radiation therapy rooms. Methods: Experiments and Monte Carlo simulations were utilized to establish the possibility of using high-Z materials to cover the concrete walls of the maze in order to reduce the dose of the scattered photons at the maze entrance. The dose of the backscattered photons from a concrete wall was measured for various scattering angles. The dose was also calculated by themore » FLUKA and EGSnrc Monte Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy room to study the effect of multiple scattering when adding lead to cover the concrete walls of the maze. Monoenergetic photons were used to represent the main components of the x ray spectrum up to 10 MV. Results: It was observed that when the concrete wall was covered with just 2 mm of lead, the measured dose rate at all backscattering angles was reduced by 20% for photons of energy comparable to Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS showed that the reduction in the dose was potentially even higher when lead was added. One explanation for the reduction is the increased absorption of backscattered photons due to the photoelectric interaction in lead. The results also showed that adding 2 mm lead to the concrete walls and floor of the maze reduced the dose at the maze entrance by up to 90%. Conclusions: This novel proposal of covering part or the entire maze walls with a few millimeters of lead would have a direct implication for the design of radiation therapy facilities and would assist in upgrading the design of some mazes, especially those in facilities with limited space where the maze length cannot be extended to sufficiently reduce the dose.« less

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

PubMed Central

Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca-Ann B.

2015-01-01

Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. Methods We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the “funny” current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1–30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). Results In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. Conclusions We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. PMID:26025323

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

PubMed

Capel, Rebecca A; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J; Terrar, Derek A; Burton, Rebecca-Ann B

2015-10-01

Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Single-source chest-abdomen-pelvis cancer staging on a third generation dual-source CT system: comparison of automated tube potential selection to second generation dual-source CT.

PubMed

Park, Clara; Gruber-Rouh, Tatjana; Leithner, Doris; Zierden, Amelie; Albrecht, Mortiz H; Wichmann, Julian L; Bodelle, Boris; Elsabaie, Mohamed; Scholtz, Jan-Erik; Kaup, Moritz; Vogl, Thomas J; Beeres, Martin

2016-10-10

Evaluation of latest generation automated attenuation-based tube potential selection (ATPS) impact on image quality and radiation dose in contrast-enhanced chest-abdomen-pelvis computed tomography examinations for gynaecologic cancer staging. This IRB approved single-centre, observer-blinded retrospective study with a waiver for informed consent included a total of 100 patients with contrast-enhanced chest-abdomen-pelvis CT for gynaecologic cancer staging. All patients were examined with activated ATPS for adaption of tube voltage to body habitus. 50 patients were scanned on a third-generation dual-source CT (DSCT), and another 50 patients on a second-generation DSCT. Predefined image quality setting remained stable between both groups at 120 kV and a current of 210 Reference mAs. Subjective image quality assessment was performed by two blinded readers independently. Attenuation and image noise were measured in several anatomic structures. Signal-to-noise ratio (SNR) was calculated. For the evaluation of radiation exposure, CT dose index (CTDI vol ) values were compared. Diagnostic image quality was obtained in all patients. The median CTDI vol (6.1 mGy, range 3.9-22 mGy) was 40 % lower when using the algorithm compared with the previous ATCM protocol (median 10.2 mGy · cm, range 5.8-22.8 mGy). A reduction in potential to 90 kV occurred in 19 cases, a reduction to 100 kV in 23 patients and a reduction to 110 kV in 3 patients of our experimental cohort. These patients received significantly lower radiation exposure compared to the former used protocol. Latest generation automated ATPS on third-generation DSCT provides good diagnostic image quality in chest-abdomen-pelvis CT while average radiation dose is reduced by 40 % compared to former ATPS protocol on second-generation DSCT.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction Versus Treatment Switch

PubMed Central

Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; González, Hans Guerrero; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-01-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3–0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m2 (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0–606) mg/g to 216 (0–2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate. PMID:24556354

Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.

PubMed

Weidemann, Frank; Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; Guerrero González, Hans; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-04-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.

Relationship between radiation dose reduction and image quality change in photostimulable phosphor luminescence X-ray imaging systems.

PubMed

Sakurai, T; Kawamata, R; Kozai, Y; Kaku, Y; Nakamura, K; Saito, M; Wakao, H; Kashima, I

2010-05-01

The aim of the study was to clarify the change in image quality upon X-ray dose reduction and to re-analyse the possibility of X-ray dose reduction in photostimulable phosphor luminescence (PSPL) X-ray imaging systems. In addition, the study attempted to verify the usefulness of multiobjective frequency processing (MFP) and flexible noise control (FNC) for X-ray dose reduction. Three PSPL X-ray imaging systems were used in this study. Modulation transfer function (MTF), noise equivalent number of quanta (NEQ) and detective quantum efficiency (DQE) were evaluated to compare the basic physical performance of each system. Subjective visual evaluation of diagnostic ability for normal anatomical structures was performed. The NEQ, DQE and diagnostic ability were evaluated at base X-ray dose, and 1/3, 1/10 and 1/20 of the base X-ray dose. The MTF of the systems did not differ significantly. The NEQ and DQE did not necessarily depend on the pixel size of the system. The images from all three systems had a higher diagnostic utility compared with conventional film images at the base and 1/3 X-ray doses. The subjective image quality was better at the base X-ray dose than at 1/3 of the base dose in all systems. The MFP and FNC-processed images had a higher diagnostic utility than the images without MFP and FNC. The use of PSPL imaging systems may allow a reduction in the X-ray dose to one-third of that required for conventional film. It is suggested that MFP and FNC are useful for radiation dose reduction.

Low Dose of Doxorubicin Potentiates the Effect of Temozolomide in Glioblastoma Cells.

PubMed

Villodre, Emilly Schlee; Kipper, Franciele Cristina; Silva, Andrew Oliveira; Lenz, Guido; Lopez, Patrícia Luciana da Costa

2018-05-01

Glioblastoma (GBM) is an aggressive brain tumor with temozolomide (TMZ)-based chemotherapy as the main therapeutic strategy. Doxorubicin (DOX) is not used in gliomas due to its low bioavailability in the brain; however, new delivery strategies and low doses may be effective in the long term, especially as part of a drug cocktail. Our aim was to evaluate the chronic effects of low doses of DOX and TMZ in GBM. Human U87-ATCC cells and a primary GBM culture were chronically treated with TMZ (5 μM) and DOX (1 and 10 nM) alone or combined. DOX resulted in a reduction in the number of cells over a period of 35 days and delayed the cell regrowth. In addition, DOX induced cell senescence and reduced tumor sphere formation and the proportion of NANOG- and OCT4-positive cells after 7 days. Low doses of TMZ potentiated the effects of DOX on senescence and sphere formation. This combined response using low doses of DOX may pave the way for its use in glioma therapy, with new technologies to overcome its low blood-brain barrier permeability.

Potential dosimetric benefits of adaptive tumor tracking over the internal target volume concept for stereotactic body radiation therapy of pancreatic cancer.

PubMed

Karava, Konstantina; Ehrbar, Stefanie; Riesterer, Oliver; Roesch, Johannes; Glatz, Stefan; Klöck, Stephan; Guckenberger, Matthias; Tanadini-Lang, Stephanie

2017-11-09

Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk. Two volumetric-modulated arc therapy (VMAT) treatment plans (5 × 5 Gy) were created for each of the 12 previously treated pancreatic cancer patients, one using the ITV concept and one the tumor tracking approach. To better evaluate the overall dose delivered to the moving tumor volume, 4D dose calculations were performed on four-dimensional computed tomography (4DCT) scans. The resulting planning target volume (PTV) size for each technique was analyzed. Target and OAR dose parameters were reported and analyzed for both 3D and 4D dose calculation. Tumor motion ranged from 1.3 to 11.2 mm. Tracking led to a reduction of PTV size (max. 39.2%) accompanied with significant better tumor coverage (p<0.05, paired Wilcoxon signed rank test) both in 3D and 4D dose calculations and improved organ at risk sparing. Especially for duodenum, stomach and liver, the mean dose was significantly reduced (p<0.05) with tracking for 3D and 4D dose calculations. By using an adaptive tumor tracking approach for respiratory-induced pancreatic motion management, a significant reduction in PTV size can be achieved, which subsequently facilitates treatment planning, and improves organ dose sparing. The dosimetric benefit of tumor tracking is organ and patient-specific.

Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis.

PubMed

To, Minh-Son; Prakash, Shivesh; Poonnoose, Santosh I; Bihari, Shailesh

2018-05-01

The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage. Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse. The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352). The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessing cost and effectiveness of radiation decontamination in Fukushima Prefecture, Japan.

PubMed

Yasutaka, Tetsuo; Naito, Wataru

2016-01-01

Despite the enormous cost of radiation decontamination in Fukushima Prefecture, it is not clear what levels of reduction in external radiation exposure are possible in the Special Decontamination Area, the Intensive Contamination Survey Areas and the whole of Fukushima. The objective of this study was to evaluate the cost and effectiveness of radiation decontamination in Fukushima Prefecture in its entirety. Using a geographic information system, we calculated the costs of removal, storage containers, transport, and temporary and interim storage facilities as well as the reduction in air dose rate for a cumulative external exposure for 9000 1 km × 1 km mesh units incorporating 51 municipalities. The decontamination cost for the basic scenario, for which forested areas within 20 m of habitation areas were decontaminated, was JPY2.53-5.12 trillion; the resulting reduction in annual external dose was about 2500 person-Sv. The transport, storage, and administrative costs of decontamination waste and removed soil reached JPY1.55-2.12 trillion under this scenario. Although implementing decontamination of all forested areas provides some major reductions in the external radiation dose for the average inhabitant, decontamination costs could potentially exceed JPY16 trillion. These results indicate that technologies for reducing the volume of decontamination waste and removed soil should be considered to reduce storage costs and that further discussions about forest decontamination policies are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

The current status of artisanal cannabis for the treatment of epilepsy in the United States.

PubMed

Sulak, Dustin; Saneto, Russell; Goldstein, Bonni

2017-05-01

The widespread patient use of artisanal cannabis preparations has preceded quality validation of cannabis use for epilepsy. Neurologists and cannabinoid specialists are increasingly in a position to monitor and guide the use of herbal cannabis in epilepsy patients. We report the retrospective data on efficacy and adverse effects of artisanal cannabis in Patients with medically refractory epilepsy with mixed etiologies in Washington State, California, and Maine. Clinical considerations, including potential risks and benefits, challenges related to artisanal preparations, and cannabinoid dosing, are discussed. Of 272 combined patients from Washington State and California, 37 (14%) found cannabis ineffective at reducing seizures, 29 (15%) experienced a 1-25% reduction in seizures, 60 (18%) experienced a 26-50% reduction in seizures, 45 (17%) experienced a 51-75% reduction in seizures, 75 (28%) experienced a 76-99% reduction in seizures, and 26 (10%) experienced a complete clinical response. Overall, adverse effects were mild and infrequent, and beneficial side effects such as increased alertness were reported. The majority of patients used cannabidiol (CBD)-enriched artisanal formulas, some with the addition of delta-9-tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA). Four case reports are included that illustrate clinical responses at doses <0.1mg/kg/day, biphasic dose-response effects, the use of THCA for seizure prevention, the use of THC for seizure rescue, and the synergy of cannabinoids and terpenoids in artisanal preparations. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-10-10

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

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.

PubMed

Kourlaba, Georgia; Dimopoulos, Meletios A; Pectasides, Dimitrios; Skarlos, Dimosthenis V; Gogas, Helen; Pentheroudakis, George; Koutras, Angelos; Fountzilas, George; Maniadakis, Nikos

2015-07-01

The aim of this study was to compare the effectiveness of prophylactic single fixed dose of pegfilgrastim and daily administration of filgrastim on febrile neutropenia (FN), severe neutropenia, treatment delay, and dose reduction in patients with breast cancer receiving dose-dense adjuvant chemotherapy. A retrospective cohort study with 1058 breast cancer patients matched by age and chemotherapy was conducted. The primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>10 % reduction of the dose planned), and treatment delay (dose given more than 2 days later). Eighteen episodes of FN (3.4%) in the filgrastim group and 23 (4.3%) in the pegfilgrastim group (p = 0.500) were recorded. More than half of the total episodes (27/41) occurred during the first 4 cycles of treatment. Patients who received filgrastim were almost three times more likely to experience a severe neutropenia episode and were significantly more likely to experience a dose reduction (18.5%) compared to those who received pegfilgrastim (10.8%) (p < 0.001). The percentage of patients, who received their planned dose on time, was significantly lower in patients receiving filgrastim (58%) compared to those receiving pegfilgrastim (72.4%, p < 0.001). No significant difference was detected on FN rate between daily administration of filgrastim and single administration of pegfilgrastim. However, patients receiving pegfilgrastim had a significantly lower rate of severe neutropenia, as well as dose reduction and treatment delay, thus, achieving a higher dose density.

Dose reduction and cost-benefit analysis at Japan`s Tokai No. 2 Plant

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

Humamoto, Hisao; Suzuki, Seishiro; Taniguchi, Kazufumi

1995-03-01

In the Tokai No. 2 power plant of the Japan Atomic Power Company, about 80% of the annual dose equivalent is received during periodic maintenance outages. A project group for dose reduction was organized at the company`s headquarters in 1986; in 1988, they proposed a five-year program to reduce by half the collective dose of 4 person-Sv per normal outage work. To achieve the target dose value, some dose-reduction measures were undertaken, namely, permanent radiation shielding, decontamination, automatic, operating machines, and ALARA organization. As the result, the collective dose from normal outage work was 1.6 person-Sv in 1992, which wasmore » less than the initial target value.« less

High-pitch computed tomography coronary angiography-a new dose-saving algorithm: estimation of radiation exposure.

PubMed

Ketelsen, Dominik; Buchgeister, Markus; Korn, Andreas; Fenchel, Michael; Schmidt, Bernhard; Flohr, Thomas G; Thomas, Christoph; Schabel, Christoph; Tsiflikas, Ilias; Syha, Roland; Claussen, Claus D; Heuschmid, Martin

2012-01-01

Purpose. To estimate effective dose and organ equivalent doses of prospective ECG-triggered high-pitch CTCA. Materials and Methods. For dose measurements, an Alderson-Rando phantom equipped with thermoluminescent dosimeters was used. The effective dose was calculated according to ICRP 103. Exposure was performed on a second-generation dual-source scanner (SOMATOM Definition Flash, Siemens Medical Solutions, Germany). The following scan parameters were used: 320 mAs per rotation, 100 and 120 kV, pitch 3.4 for prospectively ECG-triggered high-pitch CTCA, scan range of 13.5 cm, collimation 64 × 2 × 0.6 mm with z-flying focal spot, gantry rotation time 280 ms, and simulated heart rate of 60 beats per minute. Results. Depending on the applied tube potential, the effective whole-body dose of the cardiac scan ranged from 1.1 mSv to 1.6 mSv and from 1.2 to 1.8 mSv for males and females, respectively. The radiosensitive breast tissue in the range of the primary beam caused an increased female-specific effective dose of 8.6%±0.3% compared to males. Decreasing the tube potential, a significant reduction of the effective dose of 35.8% and 36.0% can be achieved for males and females, respectively (P < 0.001). Conclusion. The radiologist and the CT technician should be aware of this new dose-saving strategy to keep the radiation exposure as low as reasonablly achievable.

A quantitative comparison of noise reduction across five commercial (hybrid and model-based) iterative reconstruction techniques: an anthropomorphic phantom study.

PubMed

Patino, Manuel; Fuentes, Jorge M; Hayano, Koichi; Kambadakone, Avinash R; Uyeda, Jennifer W; Sahani, Dushyant V

2015-02-01

OBJECTIVE. The objective of our study was to compare the performance of three hybrid iterative reconstruction techniques (IRTs) (ASiR, iDose4, SAFIRE) and their respective strengths for image noise reduction on low-dose CT examinations using filtered back projection (FBP) as the standard reference. Also, we compared the performance of these three hybrid IRTs with two model-based IRTs (Veo and IMR) for image noise reduction on low-dose examinations. MATERIALS AND METHODS. An anthropomorphic abdomen phantom was scanned at 100 and 120 kVp and different tube current-exposure time products (25-100 mAs) on three CT systems (for ASiR and Veo, Discovery CT750 HD; for iDose4 and IMR, Brilliance iCT; and for SAFIRE, Somatom Definition Flash). Images were reconstructed using FBP and using IRTs at various strengths. Nine noise measurements (mean ROI size, 423 mm(2)) on extracolonic fat for the different strengths of IRTs were recorded and compared with FBP using ANOVA. Radiation dose, which was measured as the volume CT dose index and dose-length product, was also compared. RESULTS. There were no significant differences in radiation dose and image noise among the scanners when FBP was used (p > 0.05). Gradual image noise reduction was observed with each increasing increment of hybrid IRT strength, with a maximum noise suppression of approximately 50% (48.2-53.9%). Similar noise reduction was achieved on the scanners by applying specific hybrid IRT strengths. Maximum noise reduction was higher on model-based IRTs (68.3-81.1%) than hybrid IRTs (48.2-53.9%) (p < 0.05). CONCLUSION. When constant scanning parameters are used, radiation dose and image noise on FBP are similar for CT scanners made by different manufacturers. Significant image noise reduction is achieved on low-dose CT examinations rendered with IRTs. The image noise on various scanners can be matched by applying specific hybrid IRT strengths. Model-based IRTs attain substantially higher noise reduction than hybrid IRTs irrespective of the radiation dose.

Ultrasound-assisted activation of zero-valent magnesium for nitrate denitrification: identification of reaction by-products and pathways.

PubMed

Ileri, Burcu; Ayyildiz, Onder; Apaydin, Omer

2015-07-15

Zero-valent magnesium (Mg(0)) was activated by ultrasound (US) in an aim to promote its potential use in water treatment without pH control. In this context, nitrate reduction was studied at batch conditions using various doses of magnesium powder and ultrasound power. While neither ultrasound nor zero-valent magnesium alone was effective for reducing nitrate in water, their combination removed up to 90% of 50 mg/L NO3-N within 60 min. The rate of nitrate reduction by US/Mg(0) enhanced with increasing ultrasonic power and magnesium dose. Nitrogen gas (N2) and nitrite (NO2(-)) were detected as the major reduction by-products, while magnesium hydroxide Mg(OH)2 and hydroxide ions (OH(-)) were identified as the main oxidation products. The results from SEM-EDS measurements revealed that the surface oxide level decreased significantly when the samples of Mg(0) particles were exposed to ultrasonic treatment. The surface passivation of magnesium particles was successfully minimized by mechanical forces of ultrasound, which in turn paved the way to sustain the catalyst activity toward nitrate reduction. Copyright © 2015 Elsevier B.V. All rights reserved.

PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

PubMed

Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik F; Persson, Robert; Møller, Marianne R; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen M; Koch, Troels

2012-02-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two locked nucleic acid (LNA) antisense oligonucleotides targeting PCSK9 produce sustained reduction of LDL-C in nonhuman primates after a loading dose (20 mg/kg) and four weekly maintenance doses (5 mg/kg). PCSK9 messenger RNA (mRNA) and serum PCSK9 protein were reduced by 85% which resulted in a 50% reduction in circulating LDL-C. Serum total cholesterol (TC) levels were reduced to the same extent as LDL-C with no reduction in high-density lipoprotein levels, demonstrating a specific pharmacological effect on LDL-C. The reduction in hepatic PCSK9 mRNA correlated with liver LNA oligonucleotide content. This verified that anti-PCSK9 LNA oligonucleotides regulated LDL-C through an antisense mechanism. The compounds were well tolerated with no observed effects on toxicological parameters (liver and kidney histology, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine). The pharmacologic evidence and initial safety profile of the compounds used in this study indicate that LNA antisense oligonucleotides targeting PCSK9 provide a viable therapeutic strategy and are potential complements to statins in managing high LDL-C.

Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats

PubMed Central

Rock, EM; Parker, LA

2013-01-01

Background and Purpose To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5–0.1 μg·kg−1) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, ondansetron (OND). Experimental Approach We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined. Key Results CBDA (at doses as low as 0.5 μg·kg−1) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg−1) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg−1) there was an enhancement in the suppression of LiCl-induced conditioned gaping. Conclusions and Implications CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients. PMID:23488964

Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats.

PubMed

Rock, E M; Parker, L A

2013-06-01

To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5-0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND). We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined. CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping. CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

Initial apixaban dosing in patients with atrial fibrillation.

PubMed

Buchholz, Alexander; Ueberham, Laura; Gorczynska, Kaja; Dinov, Borislav; Hilbert, Sebastian; Dagres, Nikolaos; Husser, Daniela; Hindricks, Gerhard; Bollmann, Andreas

2018-05-01

Apixaban is a non-vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function. The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction. Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing-relevant secondary diagnoses and co-medication. We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664-0.816, P < 0.0001), patient weight (OR: 1.120, 95% CI: 1.076-1.166, P < 0.0001), and serum creatinine level (OR: 0.910, 95% CI: 0.881-0.940, P < 0.0001) were independent predictors for apixaban underdosage. In clinical practice, apixaban dosing is frequently inconsistent with labeling. Factors associated with inappropriate dose reduction are age, patient weight, and serum creatinine level, the same factors used as criteria for dose adjustment. However, in underdosed patients, the 3 factors did not meet the criteria for dose reduction. © 2018 Wiley Periodicals, Inc.

Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

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

Binkley, Michael S.; Shrager, Joseph B.; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California

2014-09-01

Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABRmore » and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.« less

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

PubMed Central

Lücke, Caroline; Heidegger, Tonio; Röhner, Mirjam; Toennes, Stefan W; Krivanekova, Lucia; Müller-Dahlhaus, Florian; Ziemann, Ulf

2014-01-01

Ingesting ethanol (EtOH) at low doses during social drinking is a common human behavior for its facilitating effects on social interactions. However, low-dose EtOH may have also detrimental effects that so far are underexplored. Here we sought to test the effects of low-dose EtOH on long-term potentiation (LTP)-like plasticity in human motor cortex. Previous cellular experiments showed that low-dose EtOH potentiates extrasynaptic GABAAR and reduces NMDAR-mediated currents, processes that would limit the expression of LTP. Paired associative transcranial magnetic stimulation (PASLTP) was employed in nine healthy subjects for induction of LTP-like plasticity, indexed by a long-term increase in motor-evoked potential input–output curves. Synaptic α1-GABAAR function was measured by saccadic peak velocity (SPV). Very low doses of EtOH (resulting in blood concentrations of <5 mM) suppressed LTP-like plasticity but did not affect SPV when compared with a placebo condition. In contrast, 1 mg of alprazolam, a classical benzodiazepine, or 10 mg of zolpidem, a non-benzodiazepine hypnotic, decreased SPV but did not significantly affect LTP-like plasticity when compared with placebo. This double dissociation of low-dose EtOH vs alprazolam/zolpidem effects is best explained by the putatively high affinity of EtOH but not alprazolam/zolpidem to extrasynaptic GABAARs and to NMDARs. Findings suggest that enhancement of extrasynaptic GABAAR-mediated tonic inhibition and/or reduction of NMDAR-mediated neurotransmission by EtOH blocks LTP-like plasticity in human cortex at very low doses that are easily reached during social drinking. Therefore, low-dose EtOH may jeopardize LTP-dependent processes, such as learning and memory formation. PMID:24385131

Lethal effects of Clostridium perfringens epsilon toxin are potentiated by alpha and perfringolysin-O toxins in a mouse model.

PubMed

Fernandez-Miyakawa, Mariano E; Jost, B Helen; Billington, Stephen J; Uzal, Francisco A

2008-03-18

Epsilon toxin (ETX) is the most important virulence factor of Clostridium perfringens type D. Two other important toxins, alpha toxin (CPA) and perfringolysin-O (PFO), are encoded and potentially produced by most C. perfringens type D isolates. The biological effects of these toxins are dissimilar although they are all lethal. Since the possible interaction of these toxins during infection is unknown, the effects of CPA and PFO on the lethal activity of ETX were studied in a mouse model. Mice were injected intravenously or intragastrically with CPA or PFO with or without ETX. Sublethal doses of CPA or PFO did not affect the lethality of ETX when either was injected together with the latter intravenously. However, sublethal or lethal doses of CPA or PFO resulted in reduction of the survival time of mice injected simultaneously with ETX when compared with the intravenous effect of ETX injected alone. When PFO was inoculated intragastrically with ETX, a reduction of the survival time was observed. CPA did not alter the survival time when inoculated intragastrically with ETX. The results of the present study suggest that both CPA and PFO have the potential to enhance the ETX lethal effects during enterotoxemia in natural hosts such as sheep and goats.

The role of gut microbiota in the regulation of standard metabolic rate in female Periplaneta americana.

PubMed

Ayayee, Paul A; Ondrejech, Andrew; Keeney, George; Muñoz-Garcia, Agustí

2018-01-01

Insect gut microbiota contribute significantly to host nutritional ecology. Disrupting insect gut microbial assemblages impacts nutrient provisioning functions, and can potentially affect host standard metabolic rate (SMR), a measure of host energy balance. In this study, we evaluated the effect of disrupting gut microbial assemblages on the SMR of female Periplaneta americana cockroaches fed dog food (DF, high protein/carbohydrate (p/c) ratio), and cellulose-amended dog food (CADF, 30% dog food, 70% cellulose, low p/c ratio) diets, supplemented with none, low, or high antibiotic doses. Bacterial loads decreased significantly between diet types ( P = 0.04) and across antibiotic doses ( P = 0.04). There was a significant diet type x antibiotic dose interaction on SMR of females on both diets ( P = 0.05) by the end of the seven-day experimental period. In CADF-fed females, SMR decreased linearly with decreasing bacterial load. However, SMR of DF-fed females on the low dose was significantly higher than those in the control and high dose groups. This is interpreted as a diet-dependent response by low dose DF-fed females to the loss of nutritional services provided by gut bacteria. Severe reductions in bacterial load at high doses reduced SMR of females on both diet types. This study provides insights into the potential role of gut bacteria as modulators of host energy expenditure under varying dietary conditions.

Opioid systems in the response to inflammatory pain: sustained blockade suggests role of kappa- but not mu-opioid receptors in the modulation of nociception, behaviour and pathology.

PubMed

Millan, M J; Colpaert, F C

1991-01-01

One day after intraplantar inoculation of Mycobacterium butyricum into the right hind-paw, unilaterally inflamed and control rats were implanted subcutaneously with osmotic mini-pumps delivering naloxone at 0.16 or 3.0 mg/kg/h or vehicle. As determined three days after implantation, 0.16 mg/kg/h of naloxone completely antagonized the antinociceptive action of the mu-agonist, morphine, but did not affect antinociception evoked by the kappa-agonist, U69,593. In contrast, at 3.0 mg/kg/h, naloxone blocked both morphine- and U69,593-induced antinociception. Thus, 0.16 mg/kg ("low dose") and 3.0 mg/kg ("high dose") of naloxone block mu, or mu- plus kappa-opioid receptors, respectively. Pumps were removed one week following their implantation. Inoculation was associated with a sustained hyperalgesia of the inflamed paw to noxious pressure, and elevation in resting core temperature, a loss of body weight, hypophagia, hypodipsia and a reduction in mobility. These parameters were differentially modified by the high as compared to the low dose of naloxone. Two days following implantation of pumps delivering the high dose of naloxone, the hyperalgesia of the inflamed paw was potentiated: by six days, this effect was lost. Further, one day after removal of pumps yielding the high dose, the inflamed paw showed a normalization of thresholds, that is a "rebound antinociception". One day later, this effect had subsided. In distinction, at no time did the low dose of naloxone modify nociceptive thresholds. The high dose of naloxone enhanced the reduction in body weight and food intake shown by unilaterally inflamed rats whereas the low dose was ineffective. Neither dose affected the reduction in water intake or hypothermia of unilaterally inflamed animals. The high dose of naloxone reduced the mobility of unilaterally inflamed rats whereas the low dose was ineffective. Finally, by 10 days following pump removal, pathology had transferred to the contralateral paw. In rats which had received the high but not the low dose, this transfer was blocked. It is concluded that blockade of kappa-opioid receptors with a high dose of naloxone experts pronounced functional effects in unilaterally inflamed rats. In distinction, selective blockade of mu-receptors with a low dose is ineffective. The changes seen include not only an enhancement of the hyperalgesia of the inflamed tissue, but also an exacerbation of variables (body weight, food intake and motility) which reflect pain states.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation dose-reduction strategies in thoracic CT.

PubMed

Moser, J B; Sheard, S L; Edyvean, S; Vlahos, I

2017-05-01

Modern computed tomography (CT) machines have the capability to perform thoracic CT for a range of clinical indications at increasingly low radiation doses. This article reviews several factors, both technical and patient-related, that can affect radiation dose and discusses current dose-reduction methods relevant to thoracic imaging through a review of current techniques in CT acquisition and image reconstruction. The fine balance between low radiation dose and high image quality is considered throughout, with an emphasis on obtaining diagnostic quality imaging at the lowest achievable radiation dose. The risks of excessive radiation dose reduction are also considered. Inappropriately low dose may result in suboptimal or non-diagnostic imaging that may reduce diagnostic confidence, impair diagnosis, or result in repeat examinations incurring incremental ionising radiation exposure. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

PubMed Central

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai

2017-01-01

Abstract Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3‐by‐1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration–recommended 3‐by‐1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3‐by‐1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90‐μg test dose and a 720‐μg reference dose (42% cost reduction). Combining a 180‐μg test dose and a 720‐μg reference dose produced an estimated 36% cost reduction. PMID:29281130

Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers.

PubMed

Skerjanec, Andrej; Wang, Jixian; Maren, Kelly; Rojkjaer, Lisa

2010-02-01

Deferasirox, a newly developed iron chelator, was coadministered orally with either a known inducer of drug metabolism or with cosubstrates for cytochrome P450 (CYP) to characterize the potential for drug-drug interactions. In the induction assessment, single-dose deferasirox pharmacokinetics were obtained in the presence and absence of a repeated-dose regimen of rifampin. In the CYP3A interaction evaluation, midazolam and its active hydroxylated metabolite were assessed after single doses of midazolam in the presence and absence of steady-state concentrations of deferasirox. To test for interaction at the level of CPY2C8, single-dose repaglinide pharmacokinetics/pharmacodynamics were determined with and without repeated-dose administration of deferasirox. After rifampin, a significant reduction (44%) in plasma exposure (AUC) to deferasirox was observed. Upon coadministration of midazolam, there was a modest reduction of up to 22% in midazolam exposure (AUC, C(max)), suggesting a modest induction of CYP3A4/5 by deferasirox. Def erasirox caused increases in repaglinide plasma C(max) and AUC of 1.5-fold to over 2-fold, respectively, with little change in blood glucose measures. Specific patient prescribing recommendations were established when coadministering deferasirox with midazolam, repaglinide, and rifampin. These recommendations may also apply to other substrates of CYP3A4/5 and CYP2C8 or potent inducers of glucuronidation.

(1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent γ-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction.

PubMed

Pan, Yue; Gerasimov, Madina R; Kvist, Trine; Wellendorph, Petrine; Madsen, Karsten K; Pera, Elena; Lee, Hyunbeom; Schousboe, Arne; Chebib, Mary; Bräuner-Osborne, Hans; Craft, Cheryl M; Brodie, Jonathan D; Schiffer, Wynne K; Dewey, Stephen L; Miller, Steven R; Silverman, Richard B

2012-01-12

Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115, compound 1) and observed that it does not exhibit other GABAergic or off-target activities and is rapidly and completely orally absorbed and eliminated. By use of in vivo microdialysis techniques in freely moving rats and microPET imaging techniques, 1 produced similar inhibition of cocaine-induced increases in extracellular dopamine and in synaptic dopamine in the nucleus accumbens at (1)/(300) to (1)/(600) the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose (1)/(300) that of vigabatrin. Electroretinographic (ERG) responses in rats treated with 1, at doses 20-40 times higher than those needed to treat addiction in rats, exhibited reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, 1 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction with a significantly reduced risk of visual field defects.

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

PubMed Central

Muller, David A.; Pearson, Frances E.; Fernando, Germain J.P.; Agyei-Yeboah, Christiana; Owens, Nick S.; Corrie, Simon R.; Crichton, Michael L.; Wei, Jonathan C.J.; Weldon, William C.; Oberste, M. Steven; Young, Paul R.; Kendall, Mark A. F.

2016-01-01

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats

PubMed Central

Iannone, Michelangelo; Bulotta, Stefania; Paolino, Donatella; Zito, Maria Cristina; Gratteri, Santo; Costanzo, Francesco S; Rotiroti, Domenicantonio

2006-01-01

Background 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. Results We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db) demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power) of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation. Conclusion Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties. PMID:16480519

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

PubMed

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

2011-11-03

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

Measuring radiation dose in computed tomography using elliptic phantom and free-in-air, and evaluating iterative metal artifact reduction algorithm

NASA Astrophysics Data System (ADS)

Morgan, Ashraf

The need for an accurate and reliable way for measuring patient dose in multi-row detector computed tomography (MDCT) has increased significantly. This research was focusing on the possibility of measuring CT dose in air to estimate Computed Tomography Dose Index (CTDI) for routine quality control purposes. New elliptic CTDI phantom that better represent human geometry was manufactured for investigating the effect of the subject shape on measured CTDI. Monte Carlo simulation was utilized in order to determine the dose distribution in comparison to the traditional cylindrical CTDI phantom. This research also investigated the effect of Siemens health care newly developed iMAR (iterative metal artifact reduction) algorithm, arthroplasty phantom was designed and manufactured that purpose. The design of new phantoms was part of the research as they mimic the human geometry more than the existing CTDI phantom. The standard CTDI phantom is a right cylinder that does not adequately represent the geometry of the majority of the patient population. Any dose reduction algorithm that is used during patient scan will not be utilized when scanning the CTDI phantom, so a better-designed phantom will allow the use of dose reduction algorithms when measuring dose, which leads to better dose estimation and/or better understanding of dose delivery. Doses from a standard CTDI phantom and the newly-designed phantoms were compared to doses measured in air. Iterative reconstruction is a promising technique in MDCT dose reduction and artifacts correction. Iterative reconstruction algorithms have been developed to address specific imaging tasks as is the case with Iterative Metal Artifact Reduction or iMAR which was developed by Siemens and is to be in use with the companys future computed tomography platform. The goal of iMAR is to reduce metal artifact when imaging patients with metal implants and recover CT number of tissues adjacent to the implant. This research evaluated iMAR capability of recovering CT numbers and reducing noise. Also, the use of iMAR should allow using lower tube voltage instead of 140 KVp which is used frequently to image patients with shoulder implants. The evaluations of image quality and dose reduction were carried out using an arthroplasty phantom.

Practical Advice on Calculating Confidence Intervals for Radioprotection Effects and Reducing Animal Numbers in Radiation Countermeasure Experiments

PubMed Central

Landes, Reid D.; Lensing, Shelly Y.; Kodell, Ralph L.; Hauer-Jensen, Martin

2014-01-01

The dose of a substance that causes death in P% of a population is called an LDP, where LD stands for lethal dose. In radiation research, a common LDP of interest is the radiation dose that kills 50% of the population by a specified time, i.e., lethal dose 50 or LD50. When comparing LD50 between two populations, relative potency is the parameter of interest. In radiation research, this is commonly known as the dose reduction factor (DRF). Unfortunately, statistical inference on dose reduction factor is seldom reported. We illustrate how to calculate confidence intervals for dose reduction factor, which may then be used for statistical inference. Further, most dose reduction factor experiments use hundreds, rather than tens of animals. Through better dosing strategies and the use of a recently available sample size formula, we also show how animal numbers may be reduced while maintaining high statistical power. The illustrations center on realistic examples comparing LD50 values between a radiation countermeasure group and a radiation-only control. We also provide easy-to-use spreadsheets for sample size calculations and confidence interval calculations, as well as SAS® and R code for the latter. PMID:24164553

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

PubMed

Dedes, G; De Angelis, L; Rit, S; Hansen, D; Belka, C; Bashkirov, V; Johnson, R P; Coutrakon, G; Schubert, K E; Schulte, R W; Parodi, K; Landry, G

2017-07-12

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than  -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

Trends in anemia management among US hemodialysis patients.

PubMed

Coladonato, Joseph A; Frankenfield, Diane L; Reddan, Donal N; Klassen, Preston S; Szczech, Lynda A; Johnson, Curtis A; Owen, William F

2002-05-01

This study was undertaken to describe the relationship between hematocrit (Hct) and changes in the prescribed dose of erythropoietin (EPO) as well as selected patient and process care measures across annual national samples of hemodialysis patients from 1994 to 1998. This study uses the cohorts identified in the ESRD Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660 patients, stratified by ESRD Networks drawn for each year from 1994 to 1998. Patient demographic and clinical information was collected from October to December for each year. Surrogates of iron stores and patterns of iron and EPO administration were profiled from 1996 to 1998. Multivariable stepwise linear regression analyses were performed to adjust for potential confounding variables and to identify independent variables associated with Hct and EPO dose. Mean Hct and EPO dose increased each year from 31.1 +/- 5.2% to 34.1 +/- 3.7% and from 58.2 +/- 41.8 U/kg to 68.2 +/- 55.0 U/kg, respectively (P = 0.0001). Increasing Hct was positively associated with male gender, more years on dialysis, older age, higher urea reduction ratio and transferrin saturation, prescription of intravenous iron, and lower ferritin and EPO dose in multivariable models (all P = 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight, urea reduction ration, and transferrin saturation were associated with lower EPO doses (all P < 0.01). Conversely, intravenous EPO and iron were associated with higher prescribed EPO doses (all P = 0.0001). Although increasing Hct is associated with decreasing EPO dose at the patient level, the increase in Hct seen across years among the cohorts of hemodialysis patients in the United States has been associated with increasing doses of EPO at the population level.

Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl.

PubMed

Shoushtarian, Mehrnaz; McGlade, Desmond P; Delacretaz, Louis J; Liley, David T J

2016-12-01

The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 μg/kg (fentanyl low dose, FLD) or 24 μg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.

ORANGE: a Monte Carlo dose engine for radiotherapy.

PubMed

van der Zee, W; Hogenbirk, A; van der Marck, S C

2005-02-21

This study presents data for the verification of ORANGE, a fast MCNP-based dose engine for radiotherapy treatment planning. In order to verify the new algorithm, it has been benchmarked against DOSXYZ and against measurements. For the benchmarking, first calculations have been done using the ICCR-XIII benchmark. Next, calculations have been done with DOSXYZ and ORANGE in five different phantoms (one homogeneous, two with bone equivalent inserts and two with lung equivalent inserts). The calculations have been done with two mono-energetic photon beams (2 MeV and 6 MeV) and two mono-energetic electron beams (10 MeV and 20 MeV). Comparison of the calculated data (from DOSXYZ and ORANGE) against measurements was possible for a realistic 10 MV photon beam and a realistic 15 MeV electron beam in a homogeneous phantom only. For the comparison of the calculated dose distributions and dose distributions against measurements, the concept of the confidence limit (CL) has been used. This concept reduces the difference between two data sets to a single number, which gives the deviation for 90% of the dose distributions. Using this concept, it was found that ORANGE was always within the statistical bandwidth with DOSXYZ and the measurements. The ICCR-XIII benchmark showed that ORANGE is seven times faster than DOSXYZ, a result comparable with other accelerated Monte Carlo dose systems when no variance reduction is used. As shown for XVMC, using variance reduction techniques has the potential for further acceleration. Using modern computer hardware, this brings the total calculation time for a dose distribution with 1.5% (statistical) accuracy within the clinical range (less then 10 min). This means that ORANGE can be a candidate for a dose engine in radiotherapy treatment planning.

No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight

PubMed Central

Smith, Daniel L.; Robertson, Henry; Desmond, Renee; Nagy, Tim R.; Allison, David B.

2010-01-01

Objective The health and longevity effects of body weight reduction resulting from exercise and caloric restriction in rodents are well known, but less is known about whether similar effects occur with weight reduction from the use of a pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake inhibitor. Results & Conclusion Using data from a two-year toxicology study of sibutramine in CD rats and CD-1 mice, despite a dose-dependent reduction in food intake and body weight in rats compared to controls, and a body weight reduction in mice at the highest dose, there was no compelling evidence for reductions in mortality rate. PMID:21079617

Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes

DOE PAGES

Griffith, David A.; Kung, Daniel W.; Esler, William P.; ...

2014-11-25

Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. We disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate formore » the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. In conclusion, this demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.« less

TU-AB-201-08: Rotating Shield High Dose Rate Brachytherapy with 153Gd and 75Se Isotopes

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

Renaud, M; Seuntjens, J; Enger, S

Purpose: To introduce rotating shield brachytherapy (RSBT) for different cancer sites with {sup 153}Gd and {sup 75}Se isotopes. RSBT is a form of intensity modulated brachytherapy, using shielded rotating catheters to provide a better dose distribution in the tumour while protecting healthy tissue. Methods: BrachySource, a Geant4-based Monte Carlo dose planning system was developed for investigation of RSBT with {sup 153}Gd and {sup 75}Se for different cancer sites. Dose distributions from {sup 153}Gd, {sup 75}Se and {sup 192}Ir isotopes were calculated in a 40 cm radius water phantom by using the microSelectron-v2 source model. The source was placed inside amore » cylindrical platinum shield with 1.3 mm diameter. An emission window coinciding with the active core of the source was created by removing half (180°) of the wall of the shield. Relative dose rate distributions of the three isotopes were simulated. As a proof of concept, a breast cancer patient originally treated with Mammosite was re-simulated with unshielded {sup 192}Ir and shielded {sup 153}Gd. Results: The source with the lowest energy, {sup 153}Gd, decreased the dose on the shielded side by 91%, followed by {sup 75}Se and {sup 192}Ir with 36% and 16% reduction at 1 cm from the source. The breast cancer patient simulation showed the ability of shielded {sup 153}Gd to spare the chest wall by a 90% dose reduction when only one emission window angle is considered. In this case, fully covering the PTV would require more delivery angles and the chest wall dose reduction would be less, however, the simulation demonstrates the potential of shielded {sup 153}Gd to selectively isolate organs at risk. Conclusion: Introducing {sup 153}Gd and {sup 75}Se sources combined with RSBT will allow escalation of dose in the target volume while maintaining low doses in radiation sensitive healthy tissue. Tailoring treatments to each individual patient by treating all parts of the tumour without over-irradiation of normal tissues will be possible. The author acknowledges partial support by the CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant number: 432290), and the Quebec Fonds de recherche Nature et Technologies.« less

Caffeine intake increases plasma ketones: an acute metabolic study in humans.

PubMed

Vandenberghe, Camille; St-Pierre, Valérie; Courchesne-Loyer, Alexandre; Hennebelle, Marie; Castellano, Christian-Alexandre; Cunnane, Stephen C

2017-04-01

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer's disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

The clinical case for proton beam therapy

PubMed Central

2012-01-01

Abstract Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence Proton beam therapy is a technically advanced and promising form of radiation therapy. PMID:23083010

Using a Reduced Spot Size for Intensity-Modulated Proton Therapy Potentially Improves Salivary Gland-Sparing in Oropharyngeal Cancer

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

Water, Tara A. van de, E-mail: t.a.van.de.water@rt.umcg.nl; Lomax, Antony J.; Bijl, Hendrik P.

2012-02-01

Purpose: To investigate whether intensity-modulated proton therapy with a reduced spot size (rsIMPT) could further reduce the parotid and submandibular gland dose compared with previously calculated IMPT plans with a larger spot size. In addition, it was investigated whether the obtained dose reductions would theoretically translate into a reduction of normal tissue complication probabilities (NTCPs). Methods: Ten patients with N0 oropharyngeal cancer were included in a comparative treatment planning study. Both IMPT plans delivered simultaneously 70 Gy to the boost planning target volume (PTV) and 54 Gy to the elective nodal PTV. IMPT and rsIMPT used identical three-field beam arrangements.more » In the IMPT plans, the parotid and submandibular salivary glands were spared as much as possible. rsIMPT plans used identical dose-volume objectives for the parotid glands as those used by the IMPT plans, whereas the objectives for the submandibular glands were tightened further. NTCPs were calculated for salivary dysfunction and xerostomia. Results: Target coverage was similar for both IMPT techniques, whereas rsIMPT clearly improved target conformity. The mean doses in the parotid glands and submandibular glands were significantly lower for three-field rsIMPT (14.7 Gy and 46.9 Gy, respectively) than for three-field IMPT (16.8 Gy and 54.6 Gy, respectively). Hence, rsIMPT significantly reduced the NTCP of patient-rated xerostomia and parotid and contralateral submandibular salivary flow dysfunction (27%, 17%, and 43% respectively) compared with IMPT (39%, 20%, and 79%, respectively). In addition, mean dose values in the sublingual glands, the soft palate and oral cavity were also decreased. Obtained dose and NTCP reductions varied per patient. Conclusions: rsIMPT improved sparing of the salivary glands and reduced NTCP for xerostomia and parotid and submandibular salivary dysfunction, while maintaining similar target coverage results. It is expected that rsIMPT improves quality of life during and after radiotherapy treatment.« less

High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

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

Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay

Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis ofmore » tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.« less

The Acute and Chronic Effects of the Novel Anticonvulsant Lacosamide in an Experimental Model of Status Epilepticus

PubMed Central

Wasterlain, Claude G.; Stöhr, Thomas; Matagne, Alain

2011-01-01

The effective management of status epilepticus (SE) continues to be a therapeutic challenge. The aim of this study was to investigate the efficacy of lacosamide treatment in an experimental model of self-sustaining SE. Rats were treated with lacosamide (3, 10, 30 or 50 mg/kg) either 10 minutes (early treatment) or 40 minutes (late treatment) after the initiation of perforant path stimulation. Early lacosamide treatment significantly and dose-dependently reduced acute SE seizure activity; late treatment showed only a non-significant trend towards reduced seizure activity. Early lacosamide treatment also dose-dependently reduced the number of spontaneous recurrent seizures following a 6-week waiting period, with 70% reduction at the highest dose tested (50 mg/kg); there was also a significant reduction in the number of spikes and the cumulative time spent in seizures. Late treatment with high-dose lacosamide (30–50 mg/kg) reduced the number of animals that developed spontaneous recurrent seizures (33% vs 100% in controls, P <0.05), but did not significantly reduce seizure severity or frequency in rats that developed spontaneous recurrent seizures.. The results presented here suggest that lacosamide deserves investigation for the clinical treatment of SE. Potential for disease modification in this rat model of self-sustaining SE will require further studies. PMID:21277168

Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior. Study 1--Role of NMDA receptors in efferent transmission from the cat amygdala.

PubMed

Adamec, R E

1998-01-01

The anxiogenic beta-carboline, FG-7142, produces intense anxiety in humans and anxiety-like behavior in animals. FG-7142 also mimics the effects of exogenous stressors. In cats, FG-7142 lastingly changes defensive and aggressive behavior. Long-term potentiation (LTP) of neural transmission between limbic structures known to modulate feline defensive response to threat accompany behavioral changes. A series of three reports describes experiments designed to test the hypothesis that behavioral changes depend upon an N-methyl-D-aspartate (NMDA) receptor-based LTP of efferent transmission from the amygdala. This first study characterizes the dose and time effects of injection of the NMDA receptor blocker 7-amino-phosphono-heptanoic acid (AP7) on efferent transmission from the cat amygdala to the ventromedial hypothalamus (VMH). Effects of doses of 0.5-10mg/kg (i.v.) of AP7 on potentials evoked in the VMH by single pulse stimulation of the basal amygdala were examined. In order to localize the action of the drug, concurrent measurements were taken of potentials evoked in the VMH by stimulation of the efferent fibers from the amygdala to the VMH (ventral amygdalofugal pathway, VAF). There was a dose-dependent reduction in the amygdalo-VMH evoked potential. The greatest reduction occurred at 5 mg/kg. Effects peaked at 10 min, and persisted for at least 1 h after injection. In contrast, AP7 increased the VAF-VMH-evoked potential at 10 min after injection, with a maximal increase at 5mg/kg. The data suggest that NMDA receptors intrinsic to the amygdala modulate excitatory efferent transmission from amygdala to VMH in the cat. It is speculated that a glutamatergic projection to gamma-aminobutyric acid tonic inhibitory systems in the VMH accounts for the VAF-VMH results.

Radiation dose reduction in digital breast tomosynthesis (DBT) by means of deep-learning-based supervised image processing

NASA Astrophysics Data System (ADS)

Liu, Junchi; Zarshenas, Amin; Qadir, Ammar; Wei, Zheng; Yang, Limin; Fajardo, Laurie; Suzuki, Kenji

2018-03-01

To reduce cumulative radiation exposure and lifetime risks for radiation-induced cancer from breast cancer screening, we developed a deep-learning-based supervised image-processing technique called neural network convolution (NNC) for radiation dose reduction in DBT. NNC employed patched-based neural network regression in a convolutional manner to convert lower-dose (LD) to higher-dose (HD) tomosynthesis images. We trained our NNC with quarter-dose (25% of the standard dose: 12 mAs at 32 kVp) raw projection images and corresponding "teaching" higher-dose (HD) images (200% of the standard dose: 99 mAs at 32 kVp) of a breast cadaver phantom acquired with a DBT system (Selenia Dimensions, Hologic, CA). Once trained, NNC no longer requires HD images. It converts new LD images to images that look like HD images; thus the term "virtual" HD (VHD) images. We reconstructed tomosynthesis slices on a research DBT system. To determine a dose reduction rate, we acquired 4 studies of another test phantom at 4 different radiation doses (1.35, 2.7, 4.04, and 5.39 mGy entrance dose). Structural SIMilarity (SSIM) index was used to evaluate the image quality. For testing, we collected half-dose (50% of the standard dose: 32+/-14 mAs at 33+/-5 kVp) and full-dose (standard dose: 68+/-23 mAs at 33+/-5 kvp) images of 10 clinical cases with the DBT system at University of Iowa Hospitals and Clinics. NNC converted half-dose DBT images of 10 clinical cases to VHD DBT images that were equivalent to full dose DBT images. Our cadaver phantom experiment demonstrated 79% dose reduction.

Food avoidance behavior to dietary octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) exposure in the northern bobwhite (Colinusvirginianus).

PubMed

Johnson, Mark S; Gogal, Robert M; Larsen, Calvert T

2005-08-13

High-melting explosive (HMX; octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) is a widely utilized explosive component of munitions used by the military. Consequently, production and use through testing and training at military installations has resulted in deposition of HMX in soil. Since these areas are often used by birds, the oral toxicity of HMX exposure to northern bobwhite (Colinus virginianus) was evaluated. Attempts to determine the acute lethal dose were unsuccessful. Initially, 8 birds (1 male/1 female per dose group) were orally dosed at levels ranging from 125 to 2125 mg HMX/kg body weight. A single death at the midrange resulted in subsequent trials of oral doses up to 10,760 mg/kg body weight. Only a single death occurred at 7173 mg/kg. A subsequent 28-d feeding study was then conducted to evaluate the potential for toxicity resulting from repetitive oral exposures. Northern bobwhite were exposed to concentrations of HMX in feed of either 10000, 1000, 100, or 0 mg/kg. These exposures resulted in a clear concentration-related reduction in feed consumption and body mass. Reductions in egg production in females were correlated with changes in body mass and feed consumption. Other physiological indicators were consistent with a considerable reduction in feed intake. These results suggest that HMX concentration is responsible for intense feed aversion behavior and thus not likely a factor that would appreciably contribute to risk for wild birds at military ranges.

SU-E-T-625: Potential for Reduced Radiation Induced Toxicity for the Treatment of Inoperable Non-Small-Cell Lung Cancer Using RapidArc Planning

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

Pokhrel, D; Sood, S; Badkul, R

2015-06-15

Purpose: To investigate the feasibility of using RapidArc (RA) treatment planning to reduce irradiation volume of normal lung and other organs at risk (OARs) in the treatment of inoperable non-small-cell lung cancer (NSCLC) patients. Methods: A retrospective treatment planning and delivery study was performed to compare target coverage and the volumes of the normal lung, spinal cord, heart and esophagus on 4D-CT scan above their dose tolerances delivered by RA vs. IMRT for ten inoperable NSCLC patients (Stage I-IIIB). RA plans consisted of either one-full or two-partial co-planar arcs used to treat 95% of the planning target volume (PTV) withmore » 6MV beam to a prescription of 66Gy in 33 fractions. IMRT plans were generated using 5–7 co-planar fields with 6MV beam. PTV coverage, dose-volume histograms, homogeneity/conformity indices (CI), total number of monitor units(MUs), beam-on time and delivery accuracy were compared between the two treatment plans. Results: Similar target coverage was obtained between the two techniques. RA (CI=1.02) provided more conformal plans without loss of homogeneity compared to IMRT plans (CI=1.12). Compared to IMRT, RA achieved a significant median dose reduction in V10 (3%), V20 (8%), and mean lung dose (3%) on average, respectively. On average, V5 was comparable between the two treatment plans. RA reduced mean esophagus (6%), mean heart (18%), and maximum spinal cord dose (7%), on average, respectively. Total number of MUs and beam-on time were each reduced almost by a factor of 2 when compared to IMRT-patient comfort, reduced intra-fraction-motion and leakage dose. The average IMRT and RA QA pass rate was about 98% for both types of plans for 3%/3mm criterion. Conclusion: Compared to IMRT plans, RA provided not only comparable target coverage, but also improved conformity, treatment time, and significant reduction in irradiation of OARs. This may potentially allow for target dose escalation without increase in normal tissue toxicity.« less

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

PubMed

Chan, Maria F; Song, Yulin; Burman, Chandra; Chui, Chen S; Schupak, Karen

2006-01-01

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Opioid interruptions, pain, and withdrawal symptoms in nursing home residents.

PubMed

Redding, Sarah E; Liu, Sophia; Hung, William W; Boockvar, Kenneth S

2014-11-01

Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for ≥1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre- and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P < 0.015). In patients with interruptions, there were statistically insignificant changes in mean (SD) pain score (difference -0.50 [2.66]; 95% CI, -3.16 to 2.16) and withdrawal score (difference -0.91 [3.12]; 95% CI, -4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with patients without interruptions, patients with interruptions experienced larger increases in pain scores during the follow-up periods (difference 0.09 points per day; 95% CI, -0.01 to 0.019; P = 0.08). In particular, patients who received the highest quartile of opioid dose before interruption experienced increases in pain scores over time that were 0.22 points per day larger (95% CI, 0.02 to 0.41; P = 0.03) than those without interruption. Withdrawal scores were not associated with opioid interruption regardless of dose before interruption. Nursing home patients often experience interruptions in opioid dosing, which can be associated with worse pain, but not withdrawal symptoms, during acute illnesses. Clinicians should be aware of the potential risks and effects of opioid interruptions during acute illnesses in this patient group. Published by Elsevier Inc.

Evaluation of an iterative model-based CT reconstruction algorithm by intra-patient comparison of standard and ultra-low-dose examinations.

PubMed

Noël, Peter B; Engels, Stephan; Köhler, Thomas; Muenzel, Daniela; Franz, Daniela; Rasper, Michael; Rummeny, Ernst J; Dobritz, Martin; Fingerle, Alexander A

2018-01-01

Background The explosive growth of computer tomography (CT) has led to a growing public health concern about patient and population radiation dose. A recently introduced technique for dose reduction, which can be combined with tube-current modulation, over-beam reduction, and organ-specific dose reduction, is iterative reconstruction (IR). Purpose To evaluate the quality, at different radiation dose levels, of three reconstruction algorithms for diagnostics of patients with proven liver metastases under tumor follow-up. Material and Methods A total of 40 thorax-abdomen-pelvis CT examinations acquired from 20 patients in a tumor follow-up were included. All patients were imaged using the standard-dose and a specific low-dose CT protocol. Reconstructed slices were generated by using three different reconstruction algorithms: a classical filtered back projection (FBP); a first-generation iterative noise-reduction algorithm (iDose4); and a next generation model-based IR algorithm (IMR). Results The overall detection of liver lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The IMR dataset at standard dose yielded the highest overall detectability, while the low-dose FBP dataset showed the lowest detectability. For the low-dose protocols, a significantly improved detectability of the liver lesion can be reported compared to FBP or iDose 4 ( P = 0.01). The radiation dose decreased by an approximate factor of 5 between the standard-dose and the low-dose protocol. Conclusion The latest generation of IR algorithms significantly improved the diagnostic image quality and provided virtually noise-free images for ultra-low-dose CT imaging.

What timing of vaccination is potentially dangerous for children younger than 2 years?

PubMed

Gras, Pauline; Bailly, Anne-Charlotte; Lagrée, Marion; Dervaux, Benoit; Martinot, Alain; Dubos, François

2016-08-02

Vaccine-preventable diseases still occur although measured coverage rates at 2 y of age are high. The occurrence of these diseases may be explained in part by untimely, that is, late vaccination. Our objective was to identify potentially dangerous vaccination delays for each dose of each vaccine in children younger than 2 y. A 3-round Delphi process was conducted by e-mail. We recruited 37 French experts in vaccines for children: 16 from the Infovac-France group and 21 from the French study group for pediatric infectious diseases. Items were generated by a literature review for the 10 vaccine doses recommended before 2 y of age. Item reduction in round 1 and 2 and any consensus in round 3 used a 70% consensus cutoff. The mean participation rate was 79%. Delays that should not be exceeded were identified for all vaccine doses. The 70% consensus was reached for 6 of the 10 vaccine doses: 15 d after the recommended date for the first 2 doses of the diphtheria-tetanus-acellular pertussis-inactivated polio vaccine/Haemophilus influenzae b vaccine and for the second dose of the pneumococcal conjugate vaccine, 1 month for the meningococcal C vaccine and for the first dose of the measles-mumps-rubella vaccine, and 11 y of age for completion of the hepatitis B vaccination. This Delphi process identified potentially dangerous vaccination delays for children to the age of 2 y. These can be used as new indicators in further studies of vaccine effectiveness and can help to improve the quality of vaccine protection in children.

Analysis of esophageal-sparing treatment plans for patients with high-grade esophagitis.

PubMed

Niedzielski, Joshua; Bluett, Jaques B; Williamson, Ryan T; Liao, Zhongxing; Gomez, Daniel R; Court, Laurence E

2013-07-08

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11-beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three-dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm(3), respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans' mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm(3), respectively, compared with the clinical plans. The normalized plans' mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints.

Analysis of esophageal‐sparing treatment plans for patients with high‐grade esophagitis

PubMed Central

Bluett, Jaques B.; Williamson, Ryan T.; Liao, Zhongxing; Gomez, Daniel R.; Court, Laurence E.

2013-01-01

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11‐beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three‐dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm3, respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans’ mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm3, respectively, compared with the clinical plans. The normalized plans’ mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints. PACS number: 87.53 Tf PMID:23835390

Method for simulating dose reduction in digital mammography using the Anscombe transformation.

PubMed

Borges, Lucas R; Oliveira, Helder C R de; Nunes, Polyana F; Bakic, Predrag R; Maidment, Andrew D A; Vieira, Marcelo A C

2016-06-01

This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study

USDA-ARS?s Scientific Manuscript database

Background: The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not l...

Neuroprotective Effects of Filgrastim in Rotenone-Induced Parkinson's Disease in Rats: Insights into its Anti-Inflammatory, Neurotrophic, and Antiapoptotic Effects.

PubMed

Azmy, Mariama S; Menze, Esther T; El-Naga, Reem N; Tadros, Mariane G

2018-01-11

All current treatments of Parkinson's disease (PD) focus on enhancing the dopaminergic effects and providing symptomatic relief; however, they cannot delay the disease progression. Filgrastim, a recombinant methionyl granulocyte colony-stimulating factor, demonstrated neuroprotection in many neurodegenerative and neurological diseases. This study aimed to assess the neuroprotective effects of filgrastim in rotenone-induced rat model of PD and investigate the potential underlying mechanisms of filgrastim actions. The effects of two doses of filgrastim (20 and 40 μg/kg) on spontaneous locomotion, catalepsy, body weight, histology, and striatal dopamine (DA) content, as well as tyrosine hydroxylase (TH) and α-synuclein expression, were evaluated. Then, the effective dose was further tested for its potential anti-inflammatory, neurotrophic, and antiapoptotic effects. Filgrastim (40 μg/kg) prevented rotenone-induced motor deficits, weight reduction, striatal DA depletion, and histological damage. Besides, it significantly inhibited rotenone-induced decrease in TH expression and increase in α-synuclein immunoreactivity in the midbrains and striata of the rats. These effects were associated with reduction of rotenone-induced neuroinflammation, apoptosis, and brain-derived neurotrophic factor depletion. Collectively, these results suggest that filgrastim might be a good candidate for management of PD.

The Impact of Gamma Radiation on Sediment Microbial Processes

PubMed Central

Brown, Ashley R.; Boothman, Christopher; Pimblott, Simon M.

2015-01-01

Microbial communities have the potential to control the biogeochemical fate of some radionuclides in contaminated land scenarios or in the vicinity of a geological repository for radioactive waste. However, there have been few studies of ionizing radiation effects on microbial communities in sediment systems. Here, acetate and lactate amended sediment microcosms irradiated with gamma radiation at 0.5 or 30 Gy h−1 for 8 weeks all displayed NO3− and Fe(III) reduction, although the rate of Fe(III) reduction was decreased in 30-Gy h−1 treatments. These systems were dominated by fermentation processes. Pyrosequencing indicated that the 30-Gy h−1 treatment resulted in a community dominated by two Clostridial species. In systems containing no added electron donor, irradiation at either dose rate did not restrict NO3−, Fe(III), or SO42− reduction. Rather, Fe(III) reduction was stimulated in the 0.5-Gy h−1-treated systems. In irradiated systems, there was a relative increase in the proportion of bacteria capable of Fe(III) reduction, with Geothrix fermentans and Geobacter sp. identified in the 0.5-Gy h−1 and 30-Gy h−1 treatments, respectively. These results indicate that biogeochemical processes will likely not be restricted by dose rates in such environments, and electron accepting processes may even be stimulated by radiation. PMID:25841009

Method for inserting noise in digital mammography to simulate reduction in radiation dose

NASA Astrophysics Data System (ADS)

Borges, Lucas R.; de Oliveira, Helder C. R.; Nunes, Polyana F.; Vieira, Marcelo A. C.

2015-03-01

The quality of clinical x-ray images is closely related to the radiation dose used in the imaging study. The general principle for selecting the radiation is ALARA ("as low as reasonably achievable"). The practical optimization, however, remains challenging. It is well known that reducing the radiation dose increases the quantum noise, which could compromise the image quality. In order to conduct studies about dose reduction in mammography, it would be necessary to acquire repeated clinical images, from the same patient, with different dose levels. However, such practice would be unethical due to radiation related risks. One solution is to simulate the effects of dose reduction in clinical images. This work proposes a new method, based on the Anscombe transformation, which simulates dose reduction in digital mammography by inserting quantum noise into clinical mammograms acquired with the standard radiation dose. Thus, it is possible to simulate different levels of radiation doses without exposing the patient to new levels of radiation. Results showed that the achieved quality of simulated images generated with our method is the same as when using other methods found in the literature, with the novelty of using the Anscombe transformation for converting signal-independent Gaussian noise into signal-dependent quantum noise.

The potential of intensity-modulated proton radiotherapy to reduce swallowing dysfunction in the treatment of head and neck cancer: A planning comparative study.

PubMed

van der Laan, Hans Paul; van de Water, Tara A; van Herpt, Heleen E; Christianen, Miranda E M C; Bijl, Hendrik P; Korevaar, Erik W; Rasch, Coen R; van 't Veld, Aart A; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A

2013-04-01

Predictive models for swallowing dysfunction were developed previously and showed the potential of improved intensity-modulated radiotherapy to reduce the risk of swallowing dysfunction. Still the risk is high. The aim of this study was to determine the potential of swallowing-sparing (SW) intensity-modulated proton therapy (IMPT) in head and neck cancer (HNC) for reducing the risk of swallowing dysfunction relative to currently used photon therapy. Twenty-five patients with oropharyngeal (n = 21) and hypopharyngeal (n = 4) cancer received primary radiotherapy, including bilateral neck irradiation, using standard (ST) intensity-modulated photon therapy (IMRT). Prophylactic (54 Gy) and therapeutic (70 Gy) target volumes were defined. The dose to the parotid and submandibular glands was reduced as much as possible. Four additional radiotherapy plans were created for each patient: SW-IMRT, ST-IMPT, 3-beam SW-IMPT (3B-SW-IMPT) and 7-beam SW-IMPT (7B-SW-IMPT). All plans were optimized similarly, with additional attempts to spare the swallowing organs at risk (SWOARs) in the SW plans. Probabilities of swallowing dysfunction were calculated with recently developed predictive models. All plans complied with standard HNC radiotherapy objectives. The mean parotid gland doses were similar for the ST and SW photon plans, but clearly lower in all IMPT plans (ipsilateral parotid gland ST-IMRT: 46 Gy, 7B-SW-IMPT: 29 Gy). The mean dose in the SWOARs was lowest with SW-IMPT, in particular with 7B-SW-IMPT (supraglottic larynx ST-IMRT: 60 Gy, 7B-SW-IMPT: 40 Gy). The observed dose reductions to the SWOARs translated into substantial overall reductions in normal tissue complication risks for different swallowing dysfunction endpoints. Compared with ST-IMRT, the risk of physician-rated grade 2-4 swallowing dysfunction was reduced on average by 8.8% (95% CI 6.5-11.1%) with SW-IMRT, and by 17.2% (95% CI: 12.7-21.7%) with 7B-SW-IMPT. SWOAR-sparing with proton therapy has the potential to substantially reduce the risk of swallowing dysfunction compared to similar treatment with photons.

Dose assessment according to changes in algorithm in cardiac CT

NASA Astrophysics Data System (ADS)

Jang, H. C.; Cho, J. H.; Lee, H. K.; Hong, I. S.; Cho, M. S.; Park, C. S.; Lee, S. Y.; Dong, K. R.; Goo, E. H.; Chung, W. K.; Ryu, Y. H.; Lim, C. S.

2012-06-01

The principal objective of this study was to determine the effects of the application of the adaptive statistical iterative reconstruction (ASIR) technique in combination with another two factors (body mass index (BMI) and tube potential) on radiation dose in cardiac computed tomography (CT). For quantitative analysis, regions of interest were positioned on the central region of the great coronary artery, the right coronary artery, and the left anterior descending artery, after which the means and standard deviations of measured CT numbers were obtained. For qualitative analysis, images taken from the major coronary arteries (right coronary, left anterior descending, and left circumflex) were graded on a scale of 1-5, with 5 indicating the best image quality. Effective dose, which was calculated by multiplying the value of the dose length product by a standard conversion factor of 0.017 for the chest, was employed as a measure of radiation exposure dose. In cardiac CT in patients with BMI of less than 25 kg/m2, the use of 40% ASIR in combination with a low tube potential of 100 kVp resulted in a significant reduction in the radiation dose without compromising diagnostic quality. Additionally, the combination of the 120 kVp protocol and the application of 40% ASIR application for patients with BMI higher than 25 kg/m2 yielded similar results.

Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer

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

Ding, Chuxiong; Chun, Stephen G.; Sumer, Baran D.

The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid D{sub max} (mean 20.6 Gy reduction, p <0.001), contralateral carotidmore » D{sub max} (mean 28.1 Gy reduction, p <0.001), and thyroid D{sub mean} (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord D{sub max} (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This “phantom-to-clinic” feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.« less

Pediatric CT: implementation of ASIR for substantial radiation dose reduction while maintaining pre-ASIR image noise.

PubMed

Brady, Samuel L; Moore, Bria M; Yee, Brian S; Kaufman, Robert A

2014-01-01

To determine a comprehensive method for the implementation of adaptive statistical iterative reconstruction (ASIR) for maximal radiation dose reduction in pediatric computed tomography (CT) without changing the magnitude of noise in the reconstructed image or the contrast-to-noise ratio (CNR) in the patient. The institutional review board waived the need to obtain informed consent for this HIPAA-compliant quality analysis. Chest and abdominopelvic CT images obtained before ASIR implementation (183 patient examinations; mean patient age, 8.8 years ± 6.2 [standard deviation]; range, 1 month to 27 years) were analyzed for image noise and CNR. These measurements were used in conjunction with noise models derived from anthropomorphic phantoms to establish new beam current-modulated CT parameters to implement 40% ASIR at 120 and 100 kVp without changing noise texture or magnitude. Image noise was assessed in images obtained after ASIR implementation (492 patient examinations; mean patient age, 7.6 years ± 5.4; range, 2 months to 28 years) the same way it was assessed in the pre-ASIR analysis. Dose reduction was determined by comparing size-specific dose estimates in the pre- and post-ASIR patient cohorts. Data were analyzed with paired t tests. With 40% ASIR implementation, the average relative dose reduction for chest CT was 39% (2.7/4.4 mGy), with a maximum reduction of 72% (5.3/18.8 mGy). The average relative dose reduction for abdominopelvic CT was 29% (4.8/6.8 mGy), with a maximum reduction of 64% (7.6/20.9 mGy). Beam current modulation was unnecessary for patients weighing 40 kg or less. The difference between 0% and 40% ASIR noise magnitude was less than 1 HU, with statistically nonsignificant increases in patient CNR at 100 kVp of 8% (15.3/14.2; P = .41) for chest CT and 13% (7.8/6.8; P = .40) for abdominopelvic CT. Radiation dose reduction at pediatric CT was achieved when 40% ASIR was implemented as a dose reduction tool only; no net change to the magnitude of noise in the reconstructed image or the patient CNR occurred. © RSNA, 2013.

Pros and Cons of 3D Image Fusion in Endovascular Aortic Repair: A Systematic Review and Meta-analysis.

PubMed

Goudeketting, Seline R; Heinen, Stefan G H; Ünlü, Çağdaş; van den Heuvel, Daniel A F; de Vries, Jean-Paul P M; van Strijen, Marco J; Sailer, Anna M

2017-08-01

To systematically review and meta-analyze the added value of 3-dimensional (3D) image fusion technology in endovascular aortic repair for its potential to reduce contrast media volume, radiation dose, procedure time, and fluoroscopy time. Electronic databases were systematically searched for studies published between January 2010 and March 2016 that included a control group describing 3D fusion imaging in endovascular aortic procedures. Two independent reviewers assessed the methodological quality of the included studies and extracted data on iodinated contrast volume, radiation dose, procedure time, and fluoroscopy time. The contrast use for standard and complex endovascular aortic repairs (fenestrated, branched, and chimney) were pooled using a random-effects model; outcomes are reported as the mean difference with 95% confidence intervals (CIs). Seven studies, 5 retrospective and 2 prospective, involving 921 patients were selected for analysis. The methodological quality of the studies was moderate (median 17, range 15-18). The use of fusion imaging led to an estimated mean reduction in iodinated contrast of 40.1 mL (95% CI 16.4 to 63.7, p=0.002) for standard procedures and a mean 70.7 mL (95% CI 44.8 to 96.6, p<0.001) for complex repairs. Secondary outcome measures were not pooled because of potential bias in nonrandomized data, but radiation doses, procedure times, and fluoroscopy times were lower, although not always significantly, in the fusion group in 6 of the 7 studies. Compared with the control group, 3D fusion imaging is associated with a significant reduction in the volume of contrast employed for standard and complex endovascular aortic procedures, which can be particularly important in patients with renal failure. Radiation doses, procedure times, and fluoroscopy times were reduced when 3D fusion was used.

Brachytherapy devices and methods employing americium-241

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

Gray, L. A.

1985-04-16

Sources and methods for radiation therapy, particularly brachytherapy, employing americium-241 (60 keV gamma emission and 433 year half-life) provide major advantages for radiotherapy, including simplified radiation protection, dose reduction to healthy tissue, increased dose to tumor, and improved dose distributions. A number of apparent drawbacks and unfavorable considerations including low gamma factor, high self-absorption, increased activity required and alpha-particle generation leading to helium gas pressure buildup and potential neutron contamination in the generated radiation are all effectively dealt with and overcome through recognition of subtle favorable factors unique to americium-241 among brachytherapy sources and through suitable constructional techniques. Due tomore » an additional amount of radiation, in the order of 50%, provided primarily to nearby regions as a result of Compton scatter in tissue and water, higher dose rates occur than would be predicted by conventional calculations.« less

SparseCT: interrupted-beam acquisition and sparse reconstruction for radiation dose reduction

NASA Astrophysics Data System (ADS)

Koesters, Thomas; Knoll, Florian; Sodickson, Aaron; Sodickson, Daniel K.; Otazo, Ricardo

2017-03-01

State-of-the-art low-dose CT methods reduce the x-ray tube current and use iterative reconstruction methods to denoise the resulting images. However, due to compromises between denoising and image quality, only moderate dose reductions up to 30-40% are accepted in clinical practice. An alternative approach is to reduce the number of x-ray projections and use compressed sensing to reconstruct the full-tube-current undersampled data. This idea was recognized in the early days of compressed sensing and proposals for CT dose reduction appeared soon afterwards. However, no practical means of undersampling has yet been demonstrated in the challenging environment of a rapidly rotating CT gantry. In this work, we propose a moving multislit collimator as a practical incoherent undersampling scheme for compressed sensing CT and evaluate its application for radiation dose reduction. The proposed collimator is composed of narrow slits and moves linearly along the slice dimension (z), to interrupt the incident beam in different slices for each x-ray tube angle (θ). The reduced projection dataset is then reconstructed using a sparse approach, where 3D image gradients are employed to enforce sparsity. The effects of the collimator slits on the beam profile were measured and represented as a continuous slice profile. SparseCT was tested using retrospective undersampling and compared against commercial current-reduction techniques on phantoms and in vivo studies. Initial results suggest that SparseCT may enable higher performance than current-reduction, particularly for high dose reduction factors.

Directional interstitial brachytherapy from simulation to application

NASA Astrophysics Data System (ADS)

Lin, Liyong

Organs at risk (OAR) are sometimes adjacent to or embedded in or overlap with the clinical target volume (CTV) to be treated. The purpose of this PhD study is to develop directionally low energy gamma-emitting interstitial brachytherapy sources. These sources can be applied between OAR to selectively reduce hot spots in the OARs and normal tissues. The reduction of dose over undesired regions can expand patient eligibility or reduce toxicities for the treatment by conventional interstitial brachytherapy. This study covers the development of a directional source from design optimization to construction of the first prototype source. The Monte Carlo code MCNP was used to simulate the radiation transport for the designs of directional sources. We have made a special construction kit to assemble radioactive and gold-shield components precisely into D-shaped titanium containers of the first directional source. Directional sources have a similar dose distribution as conventional sources on the treated side but greatly reduced dose on the shielded side, with a sharp dose gradient between them. A three-dimensional dose deposition kernel for the 125I directional source has been calculated. Treatment plans can use both directional and conventional 125I sources at the same source strength for low-dose-rate (LDR) implants to optimize the dose distributions. For prostate tumors, directional 125I LDR brachytherapy can potentially reduce genitourinary and gastrointestinal toxicities and improve potency preservation for low risk patients. The combination of better dose distribution of directional implants and better therapeutic ratio between tumor response and late reactions enables a novel temporary LDR treatment, as opposed to permanent or high-dose-rate (HDR) brachytherapy for the intermediate risk T2b and high risk T2c tumors. Supplemental external-beam treatments can be shortened with a better brachytherapy boost for T3 tumors. In conclusion, we have successfully finished the design optimization and construction of the first prototype directional source. Potential clinical applications and potential benefits of directional sources have been shown for prostate and breast tumors.

ANI/MAELU engineering inspection criteria 8.3 ALARA

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

Schneider, L.

1995-03-01

The purpose of this criteria section is to provide guidelines for programs whose intent is to achieve occupational doses and doses to members of the public that are as low as is reasonably achievable (ALARA). The success that has been achieved by applying ALARA concepts at nuclear power plants is clearly illustrated by the major reductions in the annual cumulative dose to workers at many sites over the last few years. This success is the combined result of the general maturity of the nuclear industry, the intensive study of dose reduction practices by industry groups, and the successful sharing ofmore » experience and practices among plants. Source term reduction should be used as a primary ALARA mechanism. Methods which should be considered include: satellite and cobalt reduction, chemistry control, decontamination, submicron filters, zinc addition, hot spot reduction and permanent or temporary shielding.« less

A dual tracer ratio method for comparative emission measurements in an experimental dairy housing

NASA Astrophysics Data System (ADS)

Mohn, Joachim; Zeyer, Kerstin; Keck, Margret; Keller, Markus; Zähner, Michael; Poteko, Jernej; Emmenegger, Lukas; Schrade, Sabine

2018-04-01

Agriculture, and in particular dairy farming, is an important source of ammonia (NH3) and non-carbon dioxide greenhouse gas (GHG) emissions. This calls for the development and quantification of effective mitigation strategies. Our study presents the implementation of a dual tracer ratio method in a novel experimental dairy housing with two identical, but spatially separated housing areas. Modular design and flexible floor elements allow the assessment of structural, process engineering and organisational abatement measures at practical scale. Thereby, the emission reduction potential of specific abatement measures can be quantified in relation to a reference system. Emissions in the naturally ventilated housing are determined by continuous dosing of two artificial tracers (sulphur hexafluoride SF6, trifluoromethylsulphur pentafluoride SF5CF3) and their real-time detection in the ppt range with an optimized GC-ECD method. The two tracers are dosed into different experimental sections, which enables the independent assessment of both housing areas. Mass flow emissions of NH3 and GHGs are quantified by areal dosing of tracer gases and multipoint sampling as well as real-time analysis of both tracer and target gases. Validation experiments demonstrate that the technique is suitable for both areal and point emission sources and achieves an uncertainty of less than 10% for the mass emissions of NH3, methane (CH4) and carbon dioxide (CO2), which is superior to other currently available methods. Comparative emission measurements in this experimental dairy housing will provide reliable, currently unavailable information on emissions for Swiss dairy farming and demonstrate the reduction potential of mitigation measures for NH3, GHGs and potentially other pollutants.

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short-Acting β-Agonist Formulations.

PubMed

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai; Ahrens, Richard C

2018-04-01

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Disinfection and reduction of organic load of sewage water by electron beam radiation

NASA Astrophysics Data System (ADS)

Maruthi, Y. Avasn; Das, N. Lakshmana; Hossain, Kaizar; Sarma, K. S. S.; Rawat, K. P.; Sabharwal, S.

2011-09-01

The efficacy of electron beam radiation for the disinfection and reduction of organic load of sewage water was assessed with ILU-6 Accelerator at Radiation Technology Development Division of the Bhabha Atomic Research Centre, Mumbai India. The current problem on environmental health in relation to water pollution insists for the safe disposal of sewage water. In general, sewage water comprises heterogeneous organic based chemicals as well as pathogens. EB treatment of the wastewater has found to be very effective in reducing the pathogens as well as organic load. EB dose of 1.5 kGy was sufficient for complete elimination of total coli forms. The experimental results elucidated the reduction of biological oxygen demand—BOD (35 and 51.7%) in both inlet and outlet sewage samples. Similarly reduction of chemical oxygen demand—COD was observed (37.54 and 52.32%) in both sewage samples with respect to increase in irradiation doses (0.45-6 kGy). The present study demonstrated the potential of ionizing radiation for disinfection of sewage and to increase the water quality of the wastewater by decreasing BOD and COD. So, the irradiation sewage water can find its application either in agriculture for irrigation, in industry for cooling purpose and some selected domestic purposes.

Head CT: Image quality improvement of posterior fossa and radiation dose reduction with ASiR - comparative studies of CT head examinations.

PubMed

Guziński, Maciej; Waszczuk, Łukasz; Sąsiadek, Marek J

2016-10-01

To evaluate head CT protocol developed to improve visibility of the brainstem and cerebellum, lower bone-related artefacts in the posterior fossa and maintain patient radioprotection. A paired comparison of head CT performed without Adaptive Statistical Iterative Reconstruction (ASiR) and a clinically indicated follow-up with 40 % ASiR was acquired in one group of 55 patients. Patients were scanned in the axial mode with different scanner settings for the brain and the posterior fossa. Objective image quality analysis was performed with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality analysis was based on brain structure visibility and evaluation of the artefacts. We achieved 19 % reduction of total DLP and significantly better image quality of posterior fossa structures. SNR for white and grey matter in the cerebellum were 34 % to 36 % higher, respectively, CNR was improved by 142 % and subjective analyses were better for images with ASiR. When imaging parameters are set independently for the brain and the posterior fossa imaging, ASiR has a great potential to improve CT performance: image quality of the brainstem and cerebellum is improved, and radiation dose for the brain as well as total radiation dose are reduced. •With ASiR it is possible to lower radiation dose or improve image quality •Sequentional imaging allows setting scan parameters for brain and posterior-fossa independently •We improved visibility of brainstem structures and decreased radiation dose •Total radiation dose (DLP) was decreased by 19.

Treating locally advanced lung cancer with a 1.5T MR-Linac - Effects of the magnetic field and irradiation geometry on conventionally fractionated and isotoxic dose-escalated radiotherapy.

PubMed

Bainbridge, Hannah E; Menten, Martin J; Fast, Martin F; Nill, Simeon; Oelfke, Uwe; McDonald, Fiona

2017-11-01

This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients. Ten patients with LA NSCLC were retrospectively re-planned six times: three treatment plans were created according to a protocol for conventionally fractionated radiotherapy and three treatment plans following guidelines for isotoxic target dose escalation. In each case, two plans were designed for the MR-Linac, either with standard (∼7mm) or reduced (∼3mm) planning target volume (PTV) margins, while one conventional linac plan was created with standard margins. Treatment plan quality was evaluated using dose-volume metrics or by quantifying dose escalation potential. All generated treatment plans fulfilled their respective planning constraints. For conventionally fractionated treatments, MR-Linac plans with standard margins had slightly increased skin dose when compared to conventional linac plans. Using reduced margins alleviated this issue and decreased exposure of several other organs-at-risk (OAR). Reduced margins also enabled increased isotoxic target dose escalation. It is feasible to generate treatment plans for LA NSCLC patients on a 1.5T MR-Linac. Margin reduction, facilitated by an envisioned MRI-guided workflow, enables increased OAR sparing and isotoxic target dose escalation for the respective treatment approaches. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Metabolites and JAK/STAT pathway were involved in the liver and spleen damage in male Wistar rats fed with mequindox.

PubMed

Wang, Xu; Huang, Xian-Ju; Ihsan, Awais; Liu, Zhao-Ying; Huang, Ling-Li; Zhang, Hua-Hai; Zhang, Hong-Fei; Zhou, Wen; Liu, Qin; Xue, Xi-Juan; Yuan, Zong-Hui

2011-02-27

Mequindox (MEQ) is a novel synthetic quinoxaline 1,4-dioxides antibacterial agent and growth promoter in animal husbandry. This study was to investigate whether reactive oxygen species (ROS), the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway, suppressors of cytokine signaling (SOCS) and inflammatory cytokines were involved in toxicities of MEQ. Our data demonstrated that high dose of MEQ (275 mg/kg) apparently led to tissue impairment combined with imbalance of redox in liver. In liver and spleen samples, hydroxylation metabolites and desoxymequindox were detected, directly confirming the potential link of N→O group reduction metabolism with its organ toxicity. Moreover, up-regulation of JAK/STAT, SOCS family, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were also observed in the high-dose group. Meanwhile, significant changes of oxidative stress indices in liver were observed in the high-dose group. As for NADPH subunit, the mRNA levels of many subunits were significantly up-regulated at low doses but down-regulated in a dose-dependent manner in liver and spleen, suggesting an involvement of NADPH in MEQ metabolism and ROS generation. In conclusion, we reported the dose-dependent long-term toxicity as well as the discussion of the potential mechanism and pathways of MEQ, which raised further awareness of its toxicity following with the dose change. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

SU-C-BRF-01: Correlation of DIBH Breath Hold Amplitude with Dosimetric Sparing of Heart and Left Anterior Descending Artery in Left Breast Radiotherapy

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

Kim, Taeho; Reardon, Kelli; Sukovich, Kaitlyn

Purpose: A 7.4% increase in major coronary events per 1 Gy increase in mean heart dose has been reported from the population-based analysis of radiation-induced cardiac toxicity following treatment of left sided breast cancer. Deep inhalation breath-hold (DIBH) is clinically utilized to reduce radiation dose to heart and left anterior descending artery (LAD). We investigated the correlation of dose sparing in heart and LAD with internal DIBH amplitude to develop a quantitative predictive model for expected dose to heart and LAD based on internal breath hold amplitude. Methods: A treatment planning study (Prescription Dose = 50 Gy) was performed onmore » 50 left breast cancer patients underwent DIBH whole breast radiotherapy. Two CT datasets, free breathing (FB) and DIBH, were utilized for treatment planning and for determination of the internal anatomy DIBH amplitude (difference between sternum position at FB and DIBH). The heart and LAD dose between FB and DIBH plans was compared and dose to the heart and LAD as a function of breath hold amplitude was determined. Results: Average DIBH amplitude using internal anatomy was 13.9±4.2 mm. The DIBH amplitude-mean dose reduction correlation is 20%/5mm (0.3 Gy/5mm) for the heart and 18%/5mm (1.1 Gy/5mm) for LAD. The correlation with max dose reduction is 12%/5mm (3.8 Gy/5mm) for the heart and 16%/5mm (3.2 Gy/5mm) for LAD. We found that average dose reductions to LAD from 6.0±6.5 Gy to 2.0±1.6 Gy with DIBH (4.0 Gy reduction: -67%, p < 0.001) and average dose reduction to the heart from 1.3±0.7 Gy to 0.7±0.2 Gy with DIBH (0.6 Gy reduction: -46%, p < 0.001). That suggests using DIBH may reduce the risk of the major coronary event for left sided breast cancer patients. Conclusion: The correlation between breath hold amplitude and dosimetric sparing suggests that dose sparing linearly increases with internal DIBH amplitude.« less

Virtual Colonoscopy Screening With Ultra Low-Dose CT and Less-Stressful Bowel Preparation: A Computer Simulation Study

NASA Astrophysics Data System (ADS)

Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong

2008-10-01

Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.

4D planning over the full course of fractionation: assessment of the benefit of tumor trailing

NASA Astrophysics Data System (ADS)

McQuaid, D.; Bortfeld, T.

2011-11-01

Tumor trailing techniques have been proposed as a method of reducing the problem of intrafraction motion in radiotherapy. However the dosimetric assessment of trailing strategies is complicated by the requirement to study dose deposition over a full fraction delivery. Common 4D planning strategies allowing assessment of dosimetric motion effects study a single cycle acquired with 4DCT. In this paper, a methodology to assess dose deposited over an entire treatment course is advanced and used to assess the potential benefit of tumor trailing strategies for lung cancer patients. Two digital phantoms mimicking patient anatomy were each programmed to follow the tumor respiratory trajectory observed from 33 lung cancer patients. The two phantoms were designed to represent the cases of a small (volume = 13.6 cm3) and large (volume = 181.7 cm3) lung lesion. Motion margins required to obtain CTV coverage by 95% of the prescription dose to 90% of the available cases were computed for a standard treatment strategy and a trailing treatment strategy. The trailing strategy facilitated a margin reduction of over 30% relative to the conventional delivery. When the dose was computed across the entire delivery for the 33 cases, the trailing strategy was found to significantly reduce the underdosage to the outlier cases and the reduced trailing margin facilitated a 15% (small lesion) and 4% (large lesion) reduction for the mean lung dose and 7% (small lesion) and 10% (large lesion) for the mean esophagus dose. Finally, for comparison an ideal continuous tracking strategy was assessed and found to further reduce the mean lung and esophagus dose. However, this improvement comes at the price of increased delivery complexity and increased reliance on tumor localization accuracy.

Head CT: Image quality improvement with ASIR-V using a reduced radiation dose protocol for children.

PubMed

Kim, Hyun Gi; Lee, Ho-Joon; Lee, Seung-Koo; Kim, Hyun Ji; Kim, Myung-Joon

2017-09-01

To investigate the quality of images reconstructed with adaptive statistical iterative reconstruction V (ASIR-V), using pediatric head CT protocols. A phantom was scanned at decreasing 20% mA intervals using our standard pediatric head CT protocols. Each study was then reconstructed at 10% ASIR-V intervals. After the phantom study, we reduced mA by 10% in the protocol for <3-year-old patients and applied 30% ASIR-V and by 30% in the protocol for 3- to 15-year-old patients and applied 40% ASIR-V. Increasing the percentage of ASIR-V resulted in lower noise and higher contrast-to-noise ratio (CNR) and preserved spatial resolution in the phantom study. Compared to a conventional-protocol, reduced-dose protocol with ASIR-V achieved 12.8% to 34.0% of dose reduction and showed images of lower noise (9.22 vs. 10.73, P = 0.043) and higher CNR in different levels (centrum semiovale, 2.14 vs. 1.52, P = 0.003; basal ganglia, 1.46 vs. 1.07, P = 0.001; and cerebellum, 2.18 vs. 1.33, P < 0.001). Qualitative analysis showed higher gray-white matter differentiation and sharpness and preserved overall diagnostic quality in the images with ASIR-V. Use of ASIR-V allowed a 12.8% to 34.0% dose reduction in each age group with potential to improve image quality. • It is possible to reduce radiation dose and improve image quality with ASIR-V. • We improved noise and CNR and decreased radiation dose. • Sharpness improved with ASIR-V. • Total radiation dose was decreased by 12.8% to 34.0%.

The causes and prevention of cancer: gaining perspective.

PubMed Central

Ames, B N; Gold, L S

1997-01-01

Epidemiological studies have identified several factors that are likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors include avoidance of intense sun exposure, increased physical activity, and reduced consumption of alcohol and possibly red meat. Risks of many types of cancer can already be reduced, and the potential for further reductions is great. In the United States, cancer death rates for all cancers combined are decreasing, if lung cancer (90% of which is due to smoking), is excluded from the analysis. We review the research on causes of cancer and show why much cancer is preventable. The idea that traces of synthetic chemicals, such as DDT, are major contributors to human cancer is not supported by the evidence, yet public concern and resource allocation for reduction of chemical pollution are very high, in part because standard risk assessment uses linear extrapolation from limited data in high-dose animal cancer tests. These tests are done at the maximum tolerated dose (MTD) and are typically misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at such high doses. Almost all chemicals in the human diet are natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of the natural pesticides that have been tested at the MTD are rodent carcinogens. Cooking food produces large numbers of natural dietary chemicals. Roasted coffee, for example, contains more than 1000 chemicals: of 27 tested, 19 are rodent carcinogens. Increasing evidence supports the idea that the high frequency of positive results in rodent bioassays is due to testing at the MTD, which frequently can cause chronic cell killing and consequent cell replacement-a risk factor for cancer that can be limited to high doses. Because default risk assessments use linear extrapolation, which ignores effects of the high dose itself, low-dose risks are often exaggerated. PMID:9255573

The causes and prevention of cancer: gaining perspective.

PubMed

Ames, B N; Gold, L S

1997-06-01

Epidemiological studies have identified several factors that are likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors include avoidance of intense sun exposure, increased physical activity, and reduced consumption of alcohol and possibly red meat. Risks of many types of cancer can already be reduced, and the potential for further reductions is great. In the United States, cancer death rates for all cancers combined are decreasing, if lung cancer (90% of which is due to smoking), is excluded from the analysis. We review the research on causes of cancer and show why much cancer is preventable. The idea that traces of synthetic chemicals, such as DDT, are major contributors to human cancer is not supported by the evidence, yet public concern and resource allocation for reduction of chemical pollution are very high, in part because standard risk assessment uses linear extrapolation from limited data in high-dose animal cancer tests. These tests are done at the maximum tolerated dose (MTD) and are typically misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at such high doses. Almost all chemicals in the human diet are natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of the natural pesticides that have been tested at the MTD are rodent carcinogens. Cooking food produces large numbers of natural dietary chemicals. Roasted coffee, for example, contains more than 1000 chemicals: of 27 tested, 19 are rodent carcinogens. Increasing evidence supports the idea that the high frequency of positive results in rodent bioassays is due to testing at the MTD, which frequently can cause chronic cell killing and consequent cell replacement-a risk factor for cancer that can be limited to high doses. Because default risk assessments use linear extrapolation, which ignores effects of the high dose itself, low-dose risks are often exaggerated.

Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

PubMed

Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

2017-03-27

Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall wastage to maximize the potential number of doses that can be withdrawn and delivered. Copyright © 2017 PATH. Published by Elsevier Ltd.. All rights reserved.

Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data.

PubMed

Gatidis, Sergios; Würslin, Christian; Seith, Ferdinand; Schäfer, Jürgen F; la Fougère, Christian; Nikolaou, Konstantin; Schwenzer, Nina F; Schmidt, Holger

2016-01-01

Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors. (18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach. (18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose-reduced datasets based on clinical (18)F-FDG PET data demonstrated the clinical applicability of the proposed data. Simulation of PET tracer dose reduction is possible with retrospective undersampling of list-mode data. Resulting simulated low-dose images have equivalent characteristics with PET images actually measured at lower doses and can be used to derive optimal tracer dose regimes.

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

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

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

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

Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial

PubMed Central

2012-01-01

Background Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (Cmax). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use. Methods This trial evaluated the effect of exenatide co-administration on single- and multiple-dose pharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 μg, levonorgestrel [LV] 150 μg [Microgynon 30®]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects received a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28. During treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and evening meals at 5 μg BID from Days 1 through 4 and at 10 μg BID from Days 5 through 22. Single- (Day 8) and multiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period. Results Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) Cmax reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in Cmax reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial. Conclusions The observed reduction in Cmax is likely of limited importance given the unaltered oral contraceptive bioavailability and trough concentrations; however, for oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before exenatide injection. Trial registration ClinicalTrials.gov: NCT00254800. PMID:22429273

Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

PubMed

Segovia, Javier; Gerosa, Gino; Almenar, Luis; Livi, Ugolino; Viganò, Mario; Arizón, Jose Maria; Yonan, Nizar; Di Salvo, Thomas G; Renlund, Dale G; Kobashigawa, Jon A

2008-01-01

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

SU-F-J-48: Effect of Scan Length On Magnitude of Imaging Dose in KV CBCT

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

Deshpande, S; Naidu, S; Sutar, A

Purpose: To study effect of scan length on magnitude of imaging dose deposition in Varian kV CBCT for head & neck and pelvis CBCT. Methods: To study effect of scan length we measured imaging dose at depth of 8 cm for head and neck Cone Beam Computed Tomography (CBCT) acquisition ( X ray beam energy is used 100kV and 200 degree of gantry rotation) and at 16 cm depth for pelvis CBCT acquisition ( X ray beam energy used is 125 kV and 360 degree of gantry rotation) in specially designed phantom. We used farmer chamber which was calibrated inmore » kV X ray range for measurements .Dose was measured with default field size, and reducing field size along y direction to 10 cm and 5 cm. Results: As the energy of the beam decreases the scattered radiation increases and this contributes significantly to the dose deposited in the patient. By reducing the scan length to 10 Cm from default 20.6 cm we found a dose reduction of 14% for head and neck CBCT protocol and a reduction of 26% for pelvis CBCT protocol. Similarly for a scan length of 5cm compared to default the dose reduction in head and neck CBCT protocol is 36% while in the pelvis CBCT protocol the dose reduction is 50%. Conclusion: By limiting the scan length we can control the scatter radiation generated and hence the dose to the patient. However the variation in dose reduction for same length used in two protocols is because of the scan geometry. The pelvis CBCT protocol uses a full rotation and head and neck CBCT protocol uses partial rotation.« less

Evaluating the effect of increased pitch, iterative reconstruction and dual source CT on dose reduction and image quality.

PubMed

Gariani, Joanna; Martin, Steve P; Botsikas, Diomidis; Becker, Christoph D; Montet, Xavier

2018-06-14

To compare radiation dose and image quality of thoracoabdominal scans obtained with a high-pitch protocol (pitch 3.2) and iterative reconstruction (Sinogram Affirmed Iterative Reconstruction) in comparison to standard pitch reconstructed with filtered back projection (FBP) using dual source CT. 114 CT scans (Somatom Definition Flash, Siemens Healthineers, Erlangen, Germany), 39 thoracic scans, 54 thoracoabdominal scans and 21 abdominal scans were performed. Analysis of three protocols was undertaken; pitch of 1 reconstructed with FBP, pitch of 3.2 reconstructed with SAFIRE, pitch of 3.2 with stellar detectors reconstructed with SAFIRE. Objective and subjective image analysis were performed. Dose differences of the protocols used were compared. Dose was reduced when comparing scans with a pitch of 1 reconstructed with FBP to high-pitch scans with a pitch of 3.2 reconstructed with SAFIRE with a reduction of volume CT dose index of 75% for thoracic scans, 64% for thoracoabdominal scans and 67% for abdominal scans. There was a further reduction after the implementation of stellar detectors reflected in a reduction of 36% of the dose-length product for thoracic scans. This was not at the detriment of image quality, contrast-to-noise ratio, signal-to-noise ratio and the qualitative image analysis revealed a superior image quality in the high-pitch protocols. The combination of a high pitch protocol with iterative reconstruction allows significant dose reduction in routine chest and abdominal scans whilst maintaining or improving diagnostic image quality, with a further reduction in thoracic scans with stellar detectors. Advances in knowledge: High pitch imaging with iterative reconstruction is a tool that can be used to reduce dose without sacrificing image quality.

Impact of electronic health record-based, pharmacist-driven valganciclovir dose optimization in solid organ transplant recipients.

PubMed

Hensler, David; Richardson, Chad L; Brown, Joslyn; Tseng, Christine; DeCamp, Phyllis J; Yang, Amy; Pawlowski, Anna; Ho, Bing; Ison, Michael G

2018-04-01

Prophylaxis with valganciclovir reduces the incidence of cytomegalovirus (CMV) infection following solid organ transplant (SOT). Under-dosing of valganciclovir is associated with an increased risk of CMV infection and development of ganciclovir-resistant CMV. An automated electronic health record (EHR)-based, pharmacist-driven program was developed to optimize dosing of valganciclovir in solid organ transplant recipients at a large transplant center. Two cohorts of kidney, pancreas-kidney, and liver transplant recipients from our center pre-implementation (April 2011-March 2012, n = 303) and post-implementation of the optimization program (September 2012-August 2013, n=263) had demographic and key outcomes data collected for 1 year post-transplant. The 1-year incidence of CMV infection dropped from 56 (18.5%) to 32 (12.2%, P = .05) and the incidence of breakthrough infections on prophylaxis was cut in half (61% vs 34%, P = .03) after implementation of the dose optimization program. The hazard ratio of developing CMV was 1.64 (95% CI 1.06-2.60, P = .027) for the pre-implementation group after adjusting for potential confounders. The program also resulted in a numerical reduction in the number of ganciclovir-resistant CMV cases (2 [0.7%] pre-implementation vs 0 post-implementation). An EHR-based, pharmacist-driven valganciclovir dose optimization program was associated with reduction in CMV infections. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing.

PubMed

Karaboyas, Angelo; Zee, Jarcy; Morgenstern, Hal; Nolen, Jacqueline G; Hakim, Raymond; Kalantar-Zadeh, Kamyar; Zager, Philip; Pisoni, Ronald L; Port, Friedrich K; Robinson, Bruce M

2015-10-07

Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time. Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation. Copyright © 2015 by the American Society of Nephrology.

Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing

PubMed Central

Zee, Jarcy; Morgenstern, Hal; Nolen, Jacqueline G.; Hakim, Raymond; Kalantar-Zadeh, Kamyar; Zager, Philip; Pisoni, Ronald L.; Port, Friedrich K.; Robinson, Bruce M.

2015-01-01

Background and objectives Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels. Design, setting, participants, & measurements Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients’ changes in ferritin over time. Results Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009–2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period. Conclusions In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation. PMID:26286925

Failure mode and effect analysis oriented to risk-reduction interventions in intraoperative electron radiation therapy: the specific impact of patient transportation, automation, and treatment planning availability.

PubMed

López-Tarjuelo, Juan; Bouché-Babiloni, Ana; Santos-Serra, Agustín; Morillo-Macías, Virginia; Calvo, Felipe A; Kubyshin, Yuri; Ferrer-Albiach, Carlos

2014-11-01

Industrial companies use failure mode and effect analysis (FMEA) to improve quality. Our objective was to describe an FMEA and subsequent interventions for an automated intraoperative electron radiotherapy (IOERT) procedure with computed tomography simulation, pre-planning, and a fixed conventional linear accelerator. A process map, an FMEA, and a fault tree analysis are reported. The equipment considered was the radiance treatment planning system (TPS), the Elekta Precise linac, and TN-502RDM-H metal-oxide-semiconductor-field-effect transistor in vivo dosimeters. Computerized order-entry and treatment-automation were also analyzed. Fifty-seven potential modes and effects were identified and classified into 'treatment cancellation' and 'delivering an unintended dose'. They were graded from 'inconvenience' or 'suboptimal treatment' to 'total cancellation' or 'potentially wrong' or 'very wrong administered dose', although these latter effects were never experienced. Risk priority numbers (RPNs) ranged from 3 to 324 and totaled 4804. After interventions such as double checking, interlocking, automation, and structural changes the final total RPN was reduced to 1320. FMEA is crucial for prioritizing risk-reduction interventions. In a semi-surgical procedure like IOERT double checking has the potential to reduce risk and improve quality. Interlocks and automation should also be implemented to increase the safety of the procedure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation of CNS activities of aerial parts of Cynodon dactylon Pers. in mice.

PubMed

Pal, Dilipkumar

2008-01-01

The dried extracts of aerial parts of Cynodon dactylon Pers. (Graminae) were evaluated for CNS activities in mice. The ethanol extract of aerial parts of C. dactylon (EECD) was found to cause significant depression in general behavioral profiles in mice. EECD significantly potentiated the sleeping time in mice induced by standard hypnotics viz. pentobarbitone sodium, diazepam, and meprobamate in a dose dependant manner. EECD showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. EECD inhibited the onset and the incidence of convulsion in a dose dependent manner against pentylenetetrazole (PTZ)-induced convulsion. The present study indicates that EECD has significant CNS depressant activities.

Hepatoprotective potential of Fumaria indica Pugsley whole plant extracts, fractions and an isolated alkaloid protopine.

PubMed

Rathi, Anshu; Srivastava, Arvind Kumar; Shirwaikar, Annie; Singh Rawat, Ajay Kumar; Mehrotra, Shanta

2008-06-01

The present investigation demonstrates the hepatoprotective potential of 50% ethanolic water extract of whole plant of Fumaria indica and its three fractions viz., hexane, chloroform and butanol against d-galactosamine induced hepatotoxicity in rats. The hepatoprotection was assessed in terms reduction in histological damage, changes in serum enzymes (SGOT, SGPT, ALP) and metabolites bilirubin, reduced glutathione (GSH) and lipid peroxidation (MDA content). Among fractions more than 90% protection was found with butanol fraction in which alkaloid protopine was quantified as highest i.e. about 0.2mg/g by HPTLC. The isolated protopine in doses of 10-20mg p.o. also proved equally effective hepatoprotectants as standard drug silymarine (single dose 25mg p.o.). In general all treatments excluding hexane fraction proved hepatoprotective at par with silymarine (p

TH-AB-BRA-08: Simulated Tumor Tracking in An MRI Linac for Lung Tumor Lesions Using the Monaco Treatment Planning System

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

Al-Ward, S; Kim, A; McCann, C

2016-06-15

Purpose: To simulate tumor tracking in an Elekta MRI-linac (MRL) and to compare this tracking method with our current ITV approach in terms of OAR sparing for lung cancer patients. Methods: Five SABR-NSCLC patients with central lung tumors were selected for reasons of potential enhancement of tumor-tissue delineation using MRI. The Monaco TPS was used to compare the current clinical ITV approach to a simulated, novel tracking method which used a 7MV MRL beam in the presence of an orthogonal 1.5 T magnetic field (4D-MRL method). In the simulated tracking scenario, achieved using the virtual couch shift (VCS), the PTVmore » was defined using an isotropic 5mm margin applied to the GTV of each phase, as acquired from an 8-phase amplitude-binned 4DCT. These VCS plans were optimized and weighted on each phase. The dose weighting was performed using the patient-specific breathing traces. The doses were accumulated on the inhale phase. The two methods were compared by assessing the OAR DVHs. Results: The 4D-MRL method resulted in a reduced target volume (by an average of 29% over all patients). The benefits of using an MRL tracking system depended on the tumor motion amplitude and the relative OAR motion (ROM) to the target. The reduction in mean doses to parallel organs was up to 3 Gy for the heart and 2.1 Gy for the lung. The reductions in maximum doses to serial organs were up to 9.4 Gy, 5.6 Gy, and 8.7 Gy for the esophagus, spinal cord, and the trachea, respectively. Serial organs benefited from MRL tracking when the ROM was ≥ 0.3 cm despite small tumor motion amplitude in some cases. Conclusions: This work demonstrated the potential benefit for an MRL tracking system to spare OARs in SABR-NSCLC patients with central tumors. The benefits are embodied in the target volume reduction. This project was made possible with the financial support of Elekta.« less

Undulator Radiation Damage Experience at LCLS

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

Nuhn, H. D.; Field, C.; Mao, S.

2015-01-06

The SLAC National Accelerator Laboratory has been running the Linac Coherent Light Source (LCLS), the first x-ray Free Electron Laser since 2009. Undulator magnet damage from radiation, produced by the electron beam traveling through the 133-m long straight vacuum tube, has been and is a concern. A damage measurement experiment has been performed in 2007 in order to obtain dose versus damage calibrations. Radiation reduction and detection devices have been integrated into the LCLS undulator system. The accumulated radiation dose rate was continuously monitored and recorded. In addition, undulator segments have been routinely removed from the beamline to be checkedmore » for magnetic (50 ppm, rms) and mechanic (about 0.25 µm, rms) changes. A reduction in strength of the undulator segments is being observed, at a level, which is now clearly above the noise. Recently, potential sources for the observed integrated radiation levels have been investigated. The paper discusses the results of these investigation as well as comparison between observed damage and measured dose accumulations and discusses, briefly, strategies for the new LCLS-II upgrade, which will be operating at more than 300 times larger beam rate.« less

REDUCTION OF DOSES IN DIAGNOSTIC USES OF RADIOISOTOPES

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

Hosain, F.

1960-03-01

> A moderately low-level counting technique with anticoincidence gas- flow counter was developed for use in metabolic and diagnostic tracer studies with radioisotopes. Several important experiments and results were reported which have been carried out with reduced doses of tracer isotopes. A reduction of the tracer dose of ahout 1/30th of the present conventional doses was achieved which helps to minimize the chances of radiation hazards. (auth)

Dose reduction of risperidone and olanzapine and estimated dopamine D₂ receptor occupancy in stable patients with schizophrenia: findings from an open-label, randomized, controlled study.

PubMed

Takeuchi, Hiroyoshi; Suzuki, Takefumi; Bies, Robert R; Remington, Gary; Watanabe, Koichiro; Mimura, Masaru; Uchida, Hiroyuki

2014-11-01

While acute-phase antipsychotic response has been attributed to 65%-80% dopamine D₂ receptor blockade, the degree of occupancy for relapse prevention in the maintenance treatment of schizophrenia remains unknown. In this secondary study of an open-label, 28-week, randomized, controlled trial conducted between April 2009 and August 2011, clinically stable patients with schizophrenia (DSM-IV) treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50%) or maintenance group (dose kept constant). Plasma antipsychotic concentrations at peak and trough before and after dose reduction were estimated with population pharmacokinetic techniques, using 2 collected plasma samples. Corresponding dopamine D₂ occupancy levels were then estimated using the model we developed. Relapse was defined as worsening in 4 Positive and Negative Syndrome Scale-Positive subscale items: delusion, conceptual disorganization, hallucinatory behavior, and suspiciousness. Plasma antipsychotic concentrations were available for 16 and 15 patients in the reduction and maintenance groups, respectively. Estimated dopamine D₂ occupancy (mean ± SD) decreased following dose reduction from 75.6% ± 4.9% to 66.8% ± 6.4% at peak and 72.3% ± 5.7% to 62.0% ± 6.8% at trough. In the reduction group, 10 patients (62.5%) did not demonstrate continuous D₂ receptor blockade above 65% (ie, < 65% at trough) after dose reduction; furthermore, 7 patients (43.8%) did not achieve a threshold of 65% occupancy even at peak. Nonetheless, only 1 patient met our relapse criteria after dose reduction during the 6 months of the study. The results suggest that the therapeutic threshold regarding dopamine D₂ occupancy may be lower for those who are stable in antipsychotic maintenance versus acute-phase treatment. Positron emission tomography studies are warranted to further test our preliminary findings. UMIN Clinical Trials Registry identifier: UMIN000001834. © Copyright 2014 Physicians Postgraduate Press, Inc.

Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations

PubMed Central

Matthews, Holly; Deakin, Jon; Rajab, May; Idris-Usman, Maryam

2017-01-01

The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26–32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product. PMID:28257497

NOTE: Investigating the potential of polymer gel dosimetry for interventional radiology: first results

NASA Astrophysics Data System (ADS)

Antoniou, P. E.; Bousbouras, P.; Sandaltzopoulos, R.; Kaldoudi, E.

2008-04-01

Complex interventional radiology (IR) procedures contribute an increasing percentage of the overall medical radiation exposure of the population making accurate dosimetry a challenge. Magnetic resonance (MR) based polymer gel dosimetry has been widely employed in complex dosimetric problems in radiotherapy. The aim of this note is to investigate the feasibility of normoxic gel dosimetry in IR. Dose response, energy dependence and dose rate dependence were investigated in irradiation set-ups relevant to IR for a particular normoxic gel, based on methacrylic acid (MAA) as the monomer and including tetrakis-hydroxy-methyl-phosphonium chloride (THPC) as antioxidant. The gel presents a linear dose response beyond a 25 cGy threshold. No significant energy dependence was observed in the useful range of interventional radiology (80-110 kVp). A linear correlation between the gel response and dose rate was observed in the range of dose rates relevant to IR (5-8 cGy min-1). These results demonstrate a reduction of gel sensitivity at very low dose rate levels. A possible explanation of this effect is suggested.

Potential Offsite Radiological Doses Estimated for the Proposed Divine Strake Experiment, Nevada Test Site

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

Ron Warren

2006-12-01

An assessment of the potential radiation dose that residents offsite of the Nevada Test Site (NTS) might receive from the proposed Divine Strake experiment was made to determine compliance with Subpart H of Part 61 of Title 40 of the Code of Federal Regulations, National Emission Standards for Emissions of Radionuclides Other than Radon from Department of Energy Facilities. The Divine Strake experiment, proposed by the Defense Threat Reduction Agency, consists of a detonation of 700 tons of heavy ammonium nitrate fuel oil-emulsion above the U16b Tunnel complex in Area 16 of the NTS. Both natural radionuclides suspended, and historicmore » fallout radionuclides resuspended from the detonation, have potential to be transported outside the NTS boundary by wind. They may, therefore, contribute radiological dose to the public. Subpart H states ''Emissions of radionuclides to the ambient air from Department of Energy facilities shall not exceed those amounts that would cause any member of the public to receive in any year an effective dose equivalent of 10 mrem/yr'' (Title 40 of the Code of Federal Regulations [CFR] 61.92) where mrem/yr is millirem per year. Furthermore, application for U.S. Environmental Protection Agency (EPA) approval of construction of a new source or modification of an existing source is required if the effective dose equivalent, caused by all emissions from the new construction or modification, is greater than or equal to 0.1 mrem/yr (40 CFR 61.96). In accordance with Section 61.93, a dose assessment was conducted with the computer model CAP88-PC, Version 3.0. In addition to this model, a dose assessment was also conducted by the National Atmospheric Release Advisory Center (NARAC) at the Lawrence Livermore National Laboratory. This modeling was conducted to obtain dose estimates from a model designed for acute releases and which addresses terrain effects and uses meteorology from multiple locations. Potential radiation dose to a hypothetical maximally exposed individual at the closest NTS boundary to the proposed Divine Strake experiment, as estimated by the CAP88-PC model, was 0.005 mrem with wind blowing directly towards that location. Boundary dose, as modeled by NARAC, ranged from about 0.006 to 0.007 mrem. Potential doses to actual offsite populated locations were generally two to five times lower still, or about 40 to 100 times lower then the 0.1 mrem level at which EPA approval is required pursuant to Section 61.96.« less

Novel treatment options for transfusional iron overload in patients with myelodysplastic syndromes.

PubMed

Goldberg, Stuart L

2007-12-01

Red blood cell transfusion dependency is common in myelodysplastic syndromes and is associated with inferior survival. The use of parenteral deferoxamine therapy for transfusional iron overload has been sparse, in part due to cumbersome administration schedules. Deferasirox is an oral iron-chelating agent with favorable pharmacokinetics, including a long half-life allowing continuous 24-hour chelation with once-daily dosing. Deferasirox produces dose-dependent reductions in liver iron content and reduces cardiac iron levels. In-vitro studies with deferasirox suggest improved cardiomyocyte contractility potentially important in reducing excess cardiac mortality noted in transfusion-dependent MDS. Deferasirox has a manageable safety profile with favorable patient satisfaction reports.

Delayed luminescence in a multiparameter approach to evaluation and reduction of radiobiological risks

NASA Astrophysics Data System (ADS)

Grasso, Rosaria; Cammarata, Francesco Paolo; Minafra, Luigi; Marchese, Valentina; Russo, Giorgio; Manti, Lorenzo; Musumeci, Francesco; Scordino, Agata

2017-07-01

In the framework of the research project ETHICS "Pre-clinical experimental and theoretical studies to improve treatment and protection by charged particles" funded by the National Nuclear Physics Institute, Italy, we studied the phenomenon called delayed luminescence emitted by non-tumorigenic breast epithelial MCF10A cell line after proton irradiation at different doses (0.5, 2, 6, 9 Gy). The aim is to found possible correlations between delayed luminescence and in vitro damaging induced by ion irradiation. The first results of this research show that the delayed luminescence kinetics is proton dose dependent. An interesting correlation between delayed luminescence and clonogenic potential was observed.

A potential drug interaction between phenobarbital and dolutegravir: A case report.

PubMed

Hikasa, Shinichi; Sawada, Akihiro; Seino, Hitomi; Shimabukuro, Shota; Hideta, Kyoko; Uwa, Noriko; Higasa, Satoshi; Tokugawa, Tazuko; Kimura, Takeshi

2018-06-01

In this report, we describe a human immunodeficiency virus (HIV)-infected patient in whom changes in phenobarbital (PB) dosage resulted in associated changes in plasma concentrations of dolutegravir (DTG). His plasma concentrations of DTG were 0.934, 0.584, 1.003 and 3.25 μg/mL, respectively, with concomitant daily PB doses of 40, 70, 30 and 0 mg, respectively. This case suggests that PB can lead to a remarkable reduction in the plasma concentration of DTG in a dose-dependent manner. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Effect of Fibre Supplementation on Body Weight and Composition, Frequency of Eating and Dietary Choice in Overweight Individuals

PubMed Central

Solah, Vicky A.; Kerr, Deborah A.; Hunt, Wendy J.; Johnson, Stuart K.; Boushey, Carol J.; Delp, Edward J.; Meng, Xingqiong; Gahler, Roland J.; James, Anthony P.; Mukhtar, Aqif S.; Fenton, Haelee K.; Wood, Simon

2017-01-01

Fibre supplementation can potentially reduce energy intake and contribute to weight loss. The mechanism may be reduced frequency of eating, resulting in reduced food consumption. The objective of this research was to determine the effectiveness of fibre supplementation with PolyGlycopleX® (PGX®), on body weight and composition, frequency of eating and dietary intake in 118 overweight adults. In a three-arm, parallel, blind, randomised controlled trial participants were randomised to one of three groups; 4.5 g PGX as softgels (PGXS), 5 g PGX granules (PGXG) or 5 g rice flour (RF) control. Prior to supplementation and at 12 weeks, participants captured before and after images of all food and beverages consumed within 4 days using a mobile food record app (mFR). The mFR images were analysed for food group serving sizes and number of eating occasions. In the PGXG group, intention-to-treat analysis showed there was a significant reduction in waist circumference (2.5 cm; p = 0.003). Subgroup analysis showed that PGXG supplementation at the recommended dose resulted in a reduction in body weight (−1.4 ± 0.10 kg, p < 0.01), body mass index (BMI) reduction (−0.5 ± 0.10, p < 0.01), reduced number of eating occasions (−1.4 ± 1.2, p < 0.01) and a reduced intake of grain food (−1.52 ± 1.84 serves, p = 0.019). PGXG at the recommended dose resulted in a reduction in weight and BMI which was significantly greater than that for RF (p = 0.001). These results demonstrate the potential benefits of PGX fibre in controlling frequency of eating and in weight loss. PMID:28212353

Effect of Fibre Supplementation on Body Weight and  Composition, Frequency of Eating and Dietary  Choice in Overweight Individuals.

PubMed

Solah, Vicky A; Kerr, Deborah A; Hunt, Wendy J; Johnson, Stuart K; Boushey, Carol J; Delp, Edward J; Meng, Xingqiong; Gahler, Roland J; James, Anthony P; Mukhtar, Aqif S; Fenton, Haelee K; Wood, Simon

2017-02-16

Fibre supplementation can potentially reduce energy intake and contribute to weight loss. The mechanism may be reduced frequency of eating, resulting in reduced food consumption. The objective of this research was to determine the effectiveness of fibre supplementation with PolyGlycopleX® (PGX®), on body weight and composition, frequency of eating and dietary intake in 118 overweight adults. In a three-arm, parallel, blind, randomised controlled trial participants were randomised to one of three groups; 4.5 g PGX as softgels (PGXS), 5 g PGX granules (PGXG) or 5 g rice flour (RF) control. Prior to supplementation and at 12 weeks, participants captured before and after images of all food and beverages consumed within 4 days using a mobile food record app (mFR). The mFR images were analysed for food group serving sizes and number of eating occasions. In the PGXG group, intention-to-treat analysis showed there was a significant reduction in waist circumference (2.5 cm; p = 0.003). Subgroup analysis showed that PGXG supplementation at the recommended dose resulted in a reduction in body weight (-1.4 ± 0.10 kg, p < 0.01), body mass index (BMI) reduction (-0.5 ± 0.10, p < 0.01), reduced number of eating occasions (-1.4 ± 1.2, p < 0.01) and a reduced intake of grain food (-1.52 ± 1.84 serves, p = 0.019). PGXG at the recommended dose resulted in a reduction in weight and BMI which was significantly greater than that for RF (p = 0.001). These results demonstrate the potential benefits of PGX fibre in controlling frequency of eating and in weight loss.

Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

PubMed Central

Sharma, Meenakshi; Sehgal, Rakesh; Kaur, Sukhbir

2012-01-01

Background Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. An antineoplastic drug, cisplatin (cis-diamminedichloroplatinum II; CDDP), is recognized as a DNA-damaging drug which also induces alteration of cell-cycle in both promastigotes and amastigotes leading to cell death. First in vivo reports from our laboratory revealed the leishmanicidal potential of cisplatin. However, high doses of cisplatin produce impairment of kidney, which can be reduced by the administration of antioxidants. Methodology/Principal Findings The present study was designed to evaluate the antileishmanial effect of cisplatin at higher doses (5 mg and 2.5 mg/kg body weight) and its combination with different antioxidants (vitamin C, vitamin E and silibinin) so as to eliminate the parasite completely and reduce the toxicity. In addition, various immunological, hematological and biochemical changes induced by it in uninfected and Leishmania donovani infected BALB/c mice were investigated. Conclusion/Significance A significant reduction in parasite load, higher IgG2a and lower IgG1 levels, enhanced DTH responses, and greater concentration of Th1 cytokines (IFN-γ, IL-2) with a concomitant down regulation of IL-10 and IL-4 pointed towards the generation of the protective Th1 type of immune response. A combination of cisplatin with antioxidants resulted in successful reduction of nephrotoxicity by normalizing the enzymatic levels of various liver and kidney function tests. Reduction in parasite load, increase in Th1 type of immune responses, and normalization of various biochemical parameters occurred in animals treated with cisplatin in combination with various antioxidants as compared to those treated with the drug only. The above results are promising as antioxidants reduced the potential toxicity of high doses of cisplatin, making the combination a potential anti-leishmanial therapy, especially in resistant cases. PMID:22563510

Magnitudes of biomarker reductions in response to controlled reductions in cigarettes smoked per day: a one-week clinical confinement study.

PubMed

Theophilus, Eugenia H; Coggins, Christopher R E; Chen, Peter; Schmidt, Eckhardt; Borgerding, Michael F

2015-03-01

Tobacco toxicant-related exposure reduction is an important tool in harm reduction. Cigarette per day reduction (CPDR) occurs as smokers migrate from smoking cigarettes to using alternative tobacco/nicotine products, or quit smoking. Few reports characterize the dose-response relationships between CPDR and effects on exposure biomarkers, especially at the low end of CPD exposure (e.g., 5 CPD). We present data on CPDR by characterizing magnitudes of biomarker reductions. We present data from a well-controlled, one-week clinical confinement study in healthy smokers who were switched from smoking 19-25 CPD to smoking 20, 10, 5 or 0 CPD. Biomarkers were measured in blood, plasma, urine, and breath, and included smoke-related toxicants, urine mutagenicity, smoked cigarette filter analyses (mouth level exposure), and vital signs. Many of the biomarkers (e.g., plasma nicotine) showed strong CPDR dose-response reductions, while others (e.g., plasma thiocyanate) showed weaker dose-response reductions. Factors that lead to lower biomarker reductions include non-CPD related contributors to the measured response (e.g., other exposure sources from environment, life style, occupation; inter-individual variability). This study confirms CPDR dose-responsive biomarkers and suggests that a one-week design is appropriate for characterizing exposure reductions when smokers switch from cigarettes to new tobacco products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Radiation dose reduction in chest radiography using a flat-panel amorphous silicon detector.

PubMed

Hosch, W P; Fink, C; Radeleff, B; kampschulte a, A; Kauffmann, G W; Hansmann, J

2002-10-01

The aim of this study was to evaluate the image quality and the potential for radiation dose reduction with a digital flat-panel amorphous silicon detector radiography system. Using flat-panel technology, radiographs of an anthropomorphic thorax phantom were taken with a range of technical parameters (125kV, 200mA and 5, 4, 3.2, 2, 1, 0.5, and 0.25mAs) which were equivalent to a radiation dose of 332, 263, 209, 127, 58.7, 29, and 14 microGy, respectively. These images were compared to radiographs obtained by a conventional film-screen radiography system at 125kV, 200mA and 5mAs (equivalent to 252 microGy) which served as reference. Three observers evaluated independently the visibility of simulated rounded lesions and anatomical structures, comparing printed films from the flat-panel amorphous silicon detector and conventional x-ray system films. With flat-panel technology, the visibility of rounded lesions and normal anatomical structures at 5, 4, and 3.2mAs was superior compared to the conventional film-screen radiography system. (P< or =0.0001). At 2mAs, improvement was only marginal (P=0.19). At 1.0, 0.5 and 0.25mAs, the visibility of simulated rounded lesions was worse (P< or =0.004). Comparing fine lung parenchymal structures, the flat-panel amorphous silicon detector showed improvement for all exposure levels down to 2mAs and equality at 1mAs. Compared to a conventional x-ray film system, the flat-panel amorphous silicon detector demonstrated improved image quality and the possibility for a reduction of the radiation dose by 50% without loss in image quality.

Liraglutide, leptin, and their combined effects on feeding: additive intake reduction through common intracellular signaling mechanisms

PubMed Central

Kanoski, Scott E.; Ong, Zhi Yi; Fortin, Samantha M.; Schlessinger, Elizabeth S.; Grill, Harvey J.

2014-01-01

Aims Glucagon like peptide-1 receptor (GLP-1R) agonists and leptin each exert anorexigenic effects. In combination, the intake inhibitory and weight loss effects are greater than either treatment alone, however the mechanisms unclear. Materials and methods Effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (SC) or to the 3rd ventricle respectively, on cumulative intake, meal patterns, and hypothalamic expression of intracellular signaling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] were examined in lean rats. Results A low-dose combination of liraglutide (25μg/kg) and leptin (0.75μg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75μg/kg) and leptin (4μg) examined separately each reduced meal frequency, cumulative food intake, and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot showed elevated pSTAT3 in hypothalamic tissue following liraglutide-leptin co-treatment, an effect greater than leptin treatment alone. In addition, SC liraglutide reduced expression of PTP1B (a negative regulator of leptin receptor signaling), revealing a potential mechanism for the enhanced pSTAT3 response following liraglutide-leptin co-administration. Conclusions Collectively, these results provide novel behavioral and molecular mechanisms underlying the additive reduction in food intake and body weight following liraglutide-leptin combination treatment. PMID:25475828

Efficacy of a radiation absorbing shield in reducing dose to the interventionalist during peripheral endovascular procedures: a single centre pilot study.

PubMed

Power, S; Mirza, M; Thakorlal, A; Ganai, B; Gavagan, L D; Given, M F; Lee, M J

2015-06-01

This prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures. A commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used to measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated. TLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142). Initial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator's body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Method for simulating dose reduction in digital mammography using the Anscombe transformation

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

Borges, Lucas R., E-mail: lucas.rodrigues.borges@usp.br; Oliveira, Helder C. R. de; Nunes, Polyana F.

2016-06-15

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtainedmore » by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.« less

Method for simulating dose reduction in digital mammography using the Anscombe transformation

PubMed Central

Borges, Lucas R.; de Oliveira, Helder C. R.; Nunes, Polyana F.; Bakic, Predrag R.; Maidment, Andrew D. A.; Vieira, Marcelo A. C.

2016-01-01

Purpose: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. Methods: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. Results: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. Conclusions: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions. PMID:27277017

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.

SU-E-I-89: Assessment of CT Radiation Dose and Image Quality for An Automated Tube Potential Selection Algorithm Using Pediatric Anthropomorphic and ACR Phantoms

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

Mahmood, U; Erdi, Y; Wang, W

Purpose: To assess the impact of General Electrics automated tube potential algorithm, kV assist (kVa) on radiation dose and image quality, with an emphasis on optimizing protocols based on noise texture. Methods: Radiation dose was assessed by inserting optically stimulated luminescence dosimeters (OSLs) throughout the body of a pediatric anthropomorphic phantom (CIRS). The baseline protocol was: 120 kVp, 80 mA, 0.7s rotation time. Image quality was assessed by calculating the contrast to noise ratio (CNR) and noise power spectrum (NPS) from the ACR CT accreditation phantom. CNRs were calculated according to the steps described in ACR CT phantom testing document.more » NPS was determined by taking the 3D FFT of the uniformity section of the ACR phantom. NPS and CNR were evaluated with and without kVa and for all available adaptive iterative statistical reconstruction (ASiR) settings, ranging from 0 to 100%. Each NPS was also evaluated for its peak frequency difference (PFD) with respect to the baseline protocol. Results: For the baseline protocol, CNR was found to decrease from 0.460 ± 0.182 to 0.420 ± 0.057 when kVa was activated. When compared against the baseline protocol, the PFD at ASiR of 40% yielded a decrease in noise magnitude as realized by the increase in CNR = 0.620 ± 0.040. The liver dose decreased by 30% with kVa activation. Conclusion: Application of kVa reduces the liver dose up to 30%. However, reduction in image quality for abdominal scans occurs when using the automated tube voltage selection feature at the baseline protocol. As demonstrated by the CNR and NPS analysis, the texture and magnitude of the noise in reconstructed images at ASiR 40% was found to be the same as our baseline images. We have demonstrated that 30% dose reduction is possible when using 40% ASiR with kVa in pediatric patients.« less

Oxytocin Reduces Ethanol Self-Administration in Mice.

PubMed

King, Courtney E; Griffin, William C; Luderman, Lauryn N; Kates, Malcolm M; McGinty, Jacqueline F; Becker, Howard C

2017-05-01

Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption. Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge-like drinking ("drinking in the dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive-ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose. These results indicate that oxytocin reduces EtOH consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

Concentration transport calculations by an original C++ program with interediate fidelity physics through user-defined buildings with an emphasis on release scenarios in radiological facilities

NASA Astrophysics Data System (ADS)

Sayre, George Anthony

The purpose of this dissertation was to develop the C ++ program Emergency Dose to calculate transport of radionuclides through indoor spaces using intermediate fidelity physics that provides improved spatial heterogeneity over well-mixed models such as MELCORRTM and much lower computation times than CFD codes such as FLUENTRTM . Modified potential flow theory, which is an original formulation of potential flow theory with additions of turbulent jet and natural convection approximations, calculates spatially heterogeneous velocity fields that well-mixed models cannot predict. Other original contributions of MPFT are: (1) generation of high fidelity boundary conditions relative to well-mixed-CFD coupling methods (conflation), (2) broadening of potential flow applications to arbitrary indoor spaces previously restricted to specific applications such as exhaust hood studies, and (3) great reduction of computation time relative to CFD codes without total loss of heterogeneity. Additionally, the Lagrangian transport module, which is discussed in Sections 1.3 and 2.4, showcases an ensemble-based formulation thought to be original to interior studies. Velocity and concentration transport benchmarks against analogous formulations in COMSOLRTM produced favorable results with discrepancies resulting from the tetrahedral meshing used in COMSOLRTM outperforming the Cartesian method used by Emergency Dose. A performance comparison of the concentration transport modules against MELCORRTM showed that Emergency Dose held advantages over the well-mixed model especially in scenarios with many interior partitions and varied source positions. A performance comparison of velocity module against FLUENTRTM showed that viscous drag provided the largest error between Emergency Dose and CFD velocity calculations, but that Emergency Dose's turbulent jets well approximated the corresponding CFD jets. Overall, Emergency Dose was found to provide a viable intermediate solution method for concentration transport with relatively low computation times.

[Inhaled corticosteroids and growth: should we be worried?].

PubMed

Pouessel, G; Gueorguieva, I; Bernaczyk, Y; Flammarion, S; Thumerelle, C; Deschildre, A

2015-08-01

Inhaled corticosteroids (ICSs) are the cornerstone and the first stage of asthma treatment. The objective of this study was to synthesize data on the potential effects of ICSs on growth in children. Studies on the short-term impact of ICSs on growth evaluated by knemometry cannot be extrapolated to the medium or long term and therefore have no utility in real life for a given person. In the medium term, the various ICSs given at the usual doses cause a small reduction in growth after 6 months of treatment. This slowdown occurs at the beginning of treatment, especially in younger children, and the growth velocity corrects itself later but without catching up. In the long term, the prolonged use of ICSs seems to induce a small reduction in the final size in adulthood (close to 1cm) occurring in the first 2 years of treatment without worsening over time. The impact of gender, age at onset of treatment, different ICSs, modes of inhalation, and severity of asthma should also be studied further. The benefit of ICSs in asthma treatment is greater than the risk of side effects, including on growth. The majority of the therapeutic effect is obtained for small to moderate doses of ICSs. Regular adjustment of ICS dose for optimal asthma control should also reduce ICS dose and the impact on growth. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2010-06-01

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

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.

Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle?

PubMed

Tschakovsky, Michael E; Sujirattanawimol, Kittiphong; Ruble, Stephen B; Valic, Zoran; Joyner, Michael J

2002-06-01

Sympathetic vasoconstriction of muscle vascular beds is important in the regulation of systemic blood pressure. However, vasoconstriction during exercise can also compromise blood flow support of muscle metabolism. This study tested the hypothesis that local factors in exercising muscle blunt vessel responsiveness to sympathetic vasoconstriction. We performed selective infusions of three doses of tyramine into the brachial artery (n = 8) to evoke endogenous release of noradrenaline (norepinephrine) at rest and during moderate and heavy rhythmic handgrip exercise. In separate experiments, tyramine was administered during two doses of adenosine infusion (n = 7) and two doses of sodium nitroprusside (SNP) infusion (n = 8). Vasoconstrictor effectiveness across conditions was assessed as the percentage reduction in forearm vascular conductance (FVC), calculated from invasive blood pressure and non-invasive Doppler ultrasound blood flow measurements at the brachial artery. Tyramine evoked a similar dose-dependent vasoconstriction at rest in all three groups, with the highest dose resulting in a 42-46 % reduction in FVC. This vasoconstriction was blunted with increasing exercise intensity (e.g. tyramine high dose percentage reduction in FVC; rest -43.4 +/- 3.7 %, moderate exercise -27.5 +/- 2.3 %, heavy exercise -16.7 +/- 3.6 %; P < 0.05). In contrast, tyramine infusion resulted in a greater percentage reduction in FVC during both doses of adenosine vs. rest (P < 0.05). Finally, percentage change in FVC was greater during low dose SNP infusion vs. rest (P < 0.05), but not different from rest at the high dose of SNP infusion (P = 0.507). A blunted percentage reduction in FVC during endogenous noradrenaline release in exercise but not vasodilator infusion indicates that sympathetic vasoconstriction is blunted in exercising muscle. This blunting appears to be exercise intensity-dependent.

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

PubMed Central

Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

2008-01-01

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

Reducing radiation dose to selected organs by selecting the tube start angle in MDCT helical scans: A Monte Carlo based study

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

Zhang Di; Zankl, Maria; DeMarco, John J.

Purpose: Previous work has demonstrated that there are significant dose variations with a sinusoidal pattern on the peripheral of a CTDI 32 cm phantom or on the surface of an anthropomorphic phantom when helical CT scanning is performed, resulting in the creation of ''hot'' spots or ''cold'' spots. The purpose of this work was to perform preliminary investigations into the feasibility of exploiting these variations to reduce dose to selected radiosensitive organs solely by varying the tube start angle in CT scans. Methods: Radiation dose to several radiosensitive organs (including breasts, thyroid, uterus, gonads, and eye lenses) resulting from MDCTmore » scans were estimated using Monte Carlo simulation methods on voxelized patient models, including GSF's Baby, Child, and Irene. Dose to fetus was also estimated using four pregnant female models based on CT images of the pregnant patients. Whole-body scans were simulated using 120 kVp, 300 mAs, both 28.8 and 40 mm nominal collimations, and pitch values of 1.5, 1.0, and 0.75 under a wide range of start angles (0 deg. - 340 deg. in 20 deg. increments). The relationship between tube start angle and organ dose was examined for each organ, and the potential dose reduction was calculated. Results: Some organs exhibit a strong dose variation, depending on the tube start angle. For small peripheral organs (e.g., the eye lenses of the Baby phantom at pitch 1.5 with 40 mm collimation), the minimum dose can be 41% lower than the maximum dose, depending on the tube start angle. In general, larger dose reductions occur for smaller peripheral organs in smaller patients when wider collimation is used. Pitch 1.5 and pitch 0.75 have different mechanisms of dose reduction. For pitch 1.5 scans, the dose is usually lowest when the tube start angle is such that the x-ray tube is posterior to the patient when it passes the longitudinal location of the organ. For pitch 0.75 scans, the dose is lowest when the tube start angle is such that the x-ray tube is anterior to the patient when it passes the longitudinal location of the organ. Conclusions: Helical MDCT scanning at pitch 1.5 and pitch 0.75 results in ''cold spots'' and ''hot spots'' that are created both at surface and in-depth locations within patients. For organs that have a relatively small longitudinal extent, dose can vary considerably with different start angles. While current MDCT systems do not provide the user with the ability to control the tube start angle, these results indicate that in these specific situations (pitch 1.5 or pitch 0.75, small organs and especially small patients), there could be significant dose savings to organs if that functionality would be provided.« less

Evaluation of a High Concentrated Contrast Media Injection Protocol in Combination with Low Tube Current for Dose Reduction in Coronary Computed Tomography Angiography: A Randomized, Two-center Prospective Study.

PubMed

Sun, Yibo; Hua, Yanqing; Wang, Mingpeng; Mao, Dingbiao; Jin, Xiu; Li, Cheng; Shi, Kailei; Xu, Jianrong

2017-12-01

The study aimed to prospectively evaluate the radiation dose reduction potential and image quality (IQ) of a high-concentration contrast media (HCCM) injection protocol in combination with a low tube current (mAs) in coronary computed tomography angiography. Eighty-one consecutive patients (mean age: 62 years; 34 females; body mass index: 18-31) were included and randomized-assigned into two groups. All computed tomography (CT) examinations were performed in two groups with the same tube voltage (100 kV), flow rate of contrast medium (5.0 mL/s), and iodine dose (22.8 g). An automatic mAs and low concentration contrast medium (300 mgI/mL) were used in group A, whereas effective mAs was reduced by a factor 0.6 along with HCCM (400 mgI/mL) in group B. Radiation dose was assessed (CT dose index [CTDI vol ] and dose length product), and vessel-based objective IQ for various regions of interest (enhancement, noise, signal-to-noise ratio, and contrast-to-noise ratio), subjective IQ, noise, and motion artifacts were analyzed overall and vessel-based with a 5-point Likert scale. The CT attenuation of coronary arteries and image noise in group B were significantly higher than those in group A (ranges: 507.5-548.1 Hounsfield units vs 407.5-444.5 Hounsfield units; and 20.3 ± 8.6 vs 17.7 ± 8.0) (P ≤ 0.0166). There was no significant difference between the two groups in signal-to-noise ratio, contrast-to-noise ratio, and subjective IQ of coronary arteries (29.4-31.7, 30.0-37.0, and medium score of 5 in group A vs 29.4-32.4, 27.7-36.3, and medium score of 5 in group B, respectively, P ≥ 0.1859). Both mean CTDI vol and dose length product in group B were 58% of those of group A. HCCM combined with low tube current allows dose reduction in coronary computed tomography angiography and does not compromise IQ. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

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

A Complier Average Causal Effect Analysis of the Stimulant Reduction Intervention using Dosed Exercise Study.

PubMed

Carmody, Thomas; Greer, Tracy L; Walker, Robrina; Rethorst, Chad D; Trivedi, Madhukar H

2018-06-01

Exercise is a promising treatment for substance use disorders, yet an intention-to-treat analysis of a large, multi-site study found no reduction in stimulant use for exercise versus health education. Exercise adherence was sub-optimal; therefore, secondary post-hoc complier average causal effects (CACE) analysis was conducted to determine the potential effectiveness of adequately dosed exercise. The STimulant use Reduction Intervention using Dosed Exercise study was a randomized controlled trial comparing a 12 kcal/kg/week (KKW) exercise dose versus a health education control conducted at nine residential substance use treatment settings across the U.S. that are affiliated with the National Drug Abuse Treatment Clinical Trials Network. Participants were sedentary but medically approved for exercise, used stimulants within 30 days prior to study entry, and received a DSM-IV stimulant abuse or dependence diagnosis within the past year. A CACE analysis adjusted to include only participants with a minimum threshold of adherence (at least 8.3 KKW) and using a negative-binomial hurdle model focused on 218 participants who were 36.2% female, mean age 39.4 years ( SD =11.1), and averaged 13.0 ( SD =9.2) stimulant use days in the 30 days before residential treatment. The outcome was days of stimulant use as assessed by the self-reported TimeLine Follow Back and urine drug screen results. The CACE-adjusted analysis found a significantly lower probability of relapse to stimulant use in the exercise group versus the health education group (41.0% vs. 55.7%, p <.01) and significantly lower days of stimulant use among those who relapsed (5.0 days vs. 9.9 days, p <.01). The CACE adjustment revealed significant, positive effects for exercise. Further research is warranted to develop strategies for exercise adherence that can ensure achievement of an exercise dose sufficient to produce a significant treatment effect.

Pediatric cT: Implementation of ASIR for Substantial Radiation Dose Reduction While Maintaining Pre-ASIR Image Noise1

PubMed Central

Brady, Samuel L.; Moore, Bria M.; Yee, Brian S.; Kaufman, Robert A.

2015-01-01

Purpose To determine a comprehensive method for the implementation of adaptive statistical iterative reconstruction (ASIR) for maximal radiation dose reduction in pediatric computed tomography (CT) without changing the magnitude of noise in the reconstructed image or the contrast-to-noise ratio (CNR) in the patient. Materials and Methods The institutional review board waived the need to obtain informed consent for this HIPAA-compliant quality analysis. Chest and abdominopelvic CT images obtained before ASIR implementation (183 patient examinations; mean patient age, 8.8 years ± 6.2 [standard deviation]; range, 1 month to 27 years) were analyzed for image noise and CNR. These measurements were used in conjunction with noise models derived from anthropomorphic phantoms to establish new beam current–modulated CT parameters to implement 40% ASIR at 120 and 100 kVp without changing noise texture or magnitude. Image noise was assessed in images obtained after ASIR implementation (492 patient examinations; mean patient age, 7.6 years ± 5.4; range, 2 months to 28 years) the same way it was assessed in the pre-ASIR analysis. Dose reduction was determined by comparing size-specific dose estimates in the pre- and post-ASIR patient cohorts. Data were analyzed with paired t tests. Results With 40% ASIR implementation, the average relative dose reduction for chest CT was 39% (2.7/4.4 mGy), with a maximum reduction of 72% (5.3/18.8 mGy). The average relative dose reduction for abdominopelvic CT was 29% (4.8/6.8 mGy), with a maximum reduction of 64% (7.6/20.9 mGy). Beam current modulation was unnecessary for patients weighing 40 kg or less. The difference between 0% and 40% ASIR noise magnitude was less than 1 HU, with statistically nonsignificant increases in patient CNR at 100 kVp of 8% (15.3/14.2; P = .41) for chest CT and 13% (7.8/6.8; P = .40) for abdominopelvic CT. Conclusion Radiation dose reduction at pediatric CT was achieved when 40% ASIR was implemented as a dose reduction tool only; no net change to the magnitude of noise in the reconstructed image or the patient CNR occurred. PMID:23901128

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

Numerical study and ex vivo assessment of HIFU treatment time reduction through optimization of focal point trajectory

NASA Astrophysics Data System (ADS)

Grisey, A.; Yon, S.; Pechoux, T.; Letort, V.; Lafitte, P.

2017-03-01

Treatment time reduction is a key issue to expand the use of high intensity focused ultrasound (HIFU) surgery, especially for benign pathologies. This study aims at quantitatively assessing the potential reduction of the treatment time arising from moving the focal point during long pulses. In this context, the optimization of the focal point trajectory is crucial to achieve a uniform thermal dose repartition and avoid boiling. At first, a numerical optimization algorithm was used to generate efficient trajectories. Thermal conduction was simulated in 3D with a finite difference code and damages to the tissue were modeled using the thermal dose formula. Given an initial trajectory, the thermal dose field was first computed, then, making use of Pontryagin's maximum principle, the trajectory was iteratively refined. Several initial trajectories were tested. Then, an ex vivo study was conducted in order to validate the efficicency of the resulting optimized strategies. Single pulses were performed at 3MHz on fresh veal liver samples with an Echopulse and the size of each unitary lesion was assessed by cutting each sample along three orthogonal planes and measuring the dimension of the whitened area based on photographs. We propose a promising approach to significantly shorten HIFU treatment time: the numerical optimization algorithm was shown to provide a reliable insight on trajectories that can improve treatment strategies. The model must now be improved in order to take in vivo conditions into account and extensively validated.

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

Metronidazole stewardship initiative at Christchurch hospitals-achievable with immediate benefits.

PubMed

Gardiner, Sharon J; Metcalf, Sarah Cl; Chin, Paul Kl; Doogue, Matthew P; Dalton, Simon C; Chambers, Stephen T

2018-04-13

To evaluate an antimicrobial stewardship (AMS) initiative to change hospital prescribing practice for metronidazole. In October 2015, the Canterbury District Health Board (CDHB) AMS committee changed advice for metronidazole to promote two times daily dosing for most indications, prioritisation of the oral route and avoidance of double anaerobic cover. Adoption of the initiative was facilitated via change in prescribing guidelines, education and ongoing pharmacy support. Usage and expenditure on metronidazole for adult inpatients were compared for the five years pre- and two years post-change. Other district health boards (DHBs) were surveyed to determine their dosing recommendation for metronidazole IV. Mean annual metronidazole IV use, as defined daily doses per 1,000 occupied bed days, decreased by 43% post-initiative. Use of non-IV (oral or rectal) formulations increased by 104%. Total savings associated with the initiative were approximately $33,400 in drug costs plus $78,200 per annum in IV giving sets and post-dose flushes. Twelve of 20 (60%) DHBs (including CDHB) endorse twice daily IV dosing. In addition to financial savings, reduction in IV doses has potential benefits, including avoidance of IV catheter-associated complications such as bloodstream infections. Approaches to metronidazole dosing vary across DHBs and could benefit from national coordination.

Modulatory effects of naringin on hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetes in rats.

PubMed

Pari, Leelavinothan; Chandramohan, Ramasamy

2017-07-01

We evaluated the modulatory effects of naringin on altered hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetic rats. Oral treatment of naringin at a doses of 20, 40 and 80 mg/kg body weight to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, blood glycosylated hemoglobin and increase in the levels of plasma insulin and blood hemoglobin. The altered activities of the hepatic key enzymes of carbohydrate metabolism such as hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase, glycogen phosphorylase and glycogen content of diabetic rats were significantly reverted to near normal levels by the treatment of naringin in a dose-dependent manner. Naringin at a dose of 80 mg/kg body weight showed the highest significant effect than the other two doses (20 and 40 mg/kg). Further, immunohistochemical observation of pancreas revealed that naringin-treated diabetic rats showed the increased number of insulin immunoreactive β-cells, which confirmed the biochemical findings. These findings revealed that naringin has potential antihyperglycemic activity in high-fat diet/low-dose streptozotocin-induced diabetic rats.

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

Griffith, David A.; Kung, Daniel W.; Esler, William P.

We found that Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. Here, we disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 asmore » a clinical candidate for the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. This demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.« less

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

Griffith, David A.; Kung, Daniel W.; Esler, William P.

Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. We disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate formore » the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. In conclusion, this demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.« less

The effects of administration of monoamine oxidase-B inhibitors on rat striatal neurone responses to dopamine.

PubMed Central

Berry, M D; Scarr, E; Zhu, M Y; Paterson, I A; Juorio, A V

1994-01-01

1. (-)-Deprenyl has been shown to potentiate rat striatal neurone responses to dopamine agonists at doses not altering dopamine metabolism. Since there are a number of effects of (-)-deprenyl which could result in this phenomenon, we have investigated the effects of MDL 72,145 and Ro 19-6327, whose only common effect with (-)-deprenyl is an inhibition of monoamine oxidase-B (MAO-B), on rat striatal neurone responses to dopamine and on striatal dopamine metabolism. 2. Using in vivo electrophysiology, i.p. injection of either MDL 72,145 or Ro 19-6327 was found to produce a dose-dependent potentiation of striatal neurone responses to dopamine but not gamma-aminobutyric acid. 3. Neurochemical investigations revealed that this occurred at doses (0.25-1 mg kg-1) which, while not affecting levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid or homovanillic acid, did cause a significant, dose-dependent, elevation in striatal levels of the putative neuromodulator, 2-phenylethylamine (PE). 4. Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327. 5. Neurochemical analysis revealed this to occur at a dose of NSD 1015 (10 mg kg-1) selective for reduction of elevated PE levels. 6. These results suggest that PE can act as a neuromodulator of dopaminergic responses and that MAO-B inhibitors may potentiate neuronal responses to dopamine via the indirect mechanism of elevation of PE following MAO-B inhibition. PMID:7889269

SU-G-IeP3-05: Effects of Image Receptor Technology and Dose Reduction Software On Radiation Dose Estimates for Fluoroscopically-Guided Interventional (FGI) Procedures

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

Merritt, Z; Dave, J; Eschelman, D

Purpose: To investigate the effects of image receptor technology and dose reduction software on radiation dose estimates for most frequently performed fluoroscopically-guided interventional (FGI) procedures at a tertiary health care center. Methods: IRB approval was obtained for retrospective analysis of FGI procedures performed in the interventional radiology suites between January-2011 and December-2015. This included procedures performed using image-intensifier (II) based systems which were subsequently replaced, flat-panel-detector (FPD) based systems which were later upgraded with ClarityIQ dose reduction software (Philips Healthcare) and relatively new FPD system already equipped with ClarityIQ. Post procedure, technologists entered system-reported cumulative air kerma (CAK) and kerma-areamore » product (KAP; only KAP for II based systems) in RIS; these values were analyzed. Data pre-processing included correcting typographical errors and cross-verifying CAK and KAP. The most frequent high and low dose FGI procedures were identified and corresponding CAK and KAP values were compared. Results: Out of 27,251 procedures within this time period, most frequent high and low dose procedures were chemo/immuno-embolization (n=1967) and abscess drainage (n=1821). Mean KAP for embolization and abscess drainage procedures were 260,657, 310,304 and 94,908 mGycm{sup 2}, and 14,497, 15,040 and 6307 mGycm{sup 2} using II-, FPD- and FPD with ClarityIQ- based systems, respectively. Statistically significant differences were observed in KAP values for embolization procedures with respect to different systems but for abscess drainage procedures significant differences were only noted between systems with FPD and FPD with ClarityIQ (p<0.05). Mean CAK reduced significantly from 823 to 308 mGy and from 43 to 21 mGy for embolization and abscess drainage procedures, respectively, in transitioning to FPD systems with ClarityIQ (p<0.05). Conclusion: While transitioning from II- to FPD- based systems was not associated with dose reduction for the most frequently performed FGI procedures, substantial dose reduction was noted with relatively newer systems and dose reduction software.« less

Monte Carlo simulations to assess the effects of tube current modulation on breast dose for multidetector CT

NASA Astrophysics Data System (ADS)

Angel, Erin; Yaghmai, Nazanin; Matilda Jude, Cecilia; DeMarco, John J.; Cagnon, Christopher H.; Goldin, Jonathan G.; Primak, Andrew N.; Stevens, Donna M.; Cody, Dianna D.; McCollough, Cynthia H.; McNitt-Gray, Michael F.

2009-02-01

Tube current modulation was designed to reduce radiation dose in CT imaging while maintaining overall image quality. This study aims to develop a method for evaluating the effects of tube current modulation (TCM) on organ dose in CT exams of actual patient anatomy. This method was validated by simulating a TCM and a fixed tube current chest CT exam on 30 voxelized patient models and estimating the radiation dose to each patient's glandular breast tissue. This new method for estimating organ dose was compared with other conventional estimates of dose reduction. Thirty detailed voxelized models of patient anatomy were created based on image data from female patients who had previously undergone clinically indicated CT scans including the chest area. As an indicator of patient size, the perimeter of the patient was measured on the image containing at least one nipple using a semi-automated technique. The breasts were contoured on each image set by a radiologist and glandular tissue was semi-automatically segmented from this region. Previously validated Monte Carlo models of two multidetector CT scanners were used, taking into account details about the source spectra, filtration, collimation and geometry of the scanner. TCM data were obtained from each patient's clinical scan and factored into the model to simulate the effects of TCM. For each patient model, two exams were simulated: a fixed tube current chest CT and a tube current modulated chest CT. X-ray photons were transported through the anatomy of the voxelized patient models, and radiation dose was tallied in the glandular breast tissue. The resulting doses from the tube current modulated simulations were compared to the results obtained from simulations performed using a fixed mA value. The average radiation dose to the glandular breast tissue from a fixed tube current scan across all patient models was 19 mGy. The average reduction in breast dose using the tube current modulated scan was 17%. Results were size dependent with smaller patients getting better dose reduction (up to 64% reduction) and larger patients getting a smaller reduction, and in some cases the dose actually increased when using tube current modulation (up to 41% increase). The results indicate that radiation dose to glandular breast tissue generally decreases with the use of tube current modulated CT acquisition, but that patient size (and in some cases patient positioning) may affect dose reduction.

Effect of caffeine coadministration and of nitric oxide synthesis inhibition on the antinociceptive action of ketorolac.

PubMed

López-Muñoz, F J; Castañeda-Hernández, G; Flores-Murrieta, F J; Granados-Soto, V

1996-07-25

The effects of caffeine and nitric oxide synthesis inhibition on the antinociceptive action of ketorolac were assessed using the pain-induced functional impairment model in the rat. Nociception was induced by the intra-articular injection of uric acid. Ketorolac, but not caffeine, produced an antinociceptive effect which was reduced by NG nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration potentiated the ketorolac effect. L-NAME induced a dose-dependent reduction of this potentiation. The results suggest the participation of the L-arginine-nitric oxide-cyclic GMP pathway in the caffeine potentiation of ketorolac-induced antinociception.

Pyrrolidine-Acridine hybrid in Artemisinin-based combination: a pharmacodynamic study.

PubMed

Pandey, Swaroop Kumar; Biswas, Subhasish; Gunjan, Sarika; Chauhan, Bhavana Singh; Singh, Sunil Kumar; Srivastava, Kumkum; Singh, Sarika; Batra, Sanjay; Tripathi, Renu

2016-09-01

Aiming to develop new artemisinin-based combination therapy (ACT) for malaria, antimalarial effect of a new series of pyrrolidine-acridine hybrid in combination with artemisinin derivatives was investigated. Synthesis, antimalarial and cytotoxic evaluation of a series of hybrid of 2-(3-(substitutedbenzyl)pyrrolidin-1-yl)alkanamines and acridine were performed and mode of action of the lead compound was investigated. In vivo pharmacodynamic properties (parasite clearance time, parasite reduction ratio, dose and regimen determination) against multidrug resistant (MDR) rodent malaria parasite and toxicological parameters (median lethal dose, liver function test, kidney function test) were also investigated. 6-Chloro-N-(4-(3-(3,4-dimethoxybenzyl)pyrrolidin-1-yl)butyl)-2-methoxyacridin-9-amine (15c) has shown a dose dependent haem bio-mineralization inhibition and was found to be the most effective and safe compound against MDR malaria parasite in Swiss mice model. It displayed best antimalarial potential with artemether (AM) in vitro as well as in vivo. The combination also showed favourable pharmacodynamic properties and therapeutic response in mice with established MDR malaria infection and all mice were cured at the determined doses. The combination did not show toxicity at the doses administered to the Swiss mice. Taken together, our findings suggest that compound 15c is a potential partner with AM for the ACT and could be explored for further development.

Automated tube voltage adaptation in head and neck computed tomography between 120 and 100 kV: effects on image quality and radiation dose.

PubMed

May, Matthias S; Kramer, Manuel R; Eller, Achim; Wuest, Wolfgang; Scharf, Michael; Brand, Michael; Saake, Marc; Schmidt, Bernhard; Uder, Michael; Lell, Michael M

2014-09-01

Low tube voltage allows for computed tomography (CT) imaging with increased iodine contrast at reduced radiation dose. We sought to evaluate the image quality and potential dose reduction using a combination of attenuation based tube current modulation (TCM) and automated tube voltage adaptation (TVA) between 100 and 120 kV in CT of the head and neck. One hundred thirty consecutive patients with indication for head and neck CT were examined with a 128-slice system capable of TCM and TVA. Reference protocol was set at 120 kV. Tube voltage was reduced to 100 kV whenever proposed by automated analysis of the localizer. An additional small scan aligned to the jaw was performed at a fixed 120 kV setting. Image quality was assessed by two radiologists on a standardized Likert-scale and measurements of signal- (SNR) and contrast-to-noise ratio (CNR). Radiation dose was assessed as CTDIvol. Diagnostic image quality was excellent in both groups and did not differ significantly (p = 0.34). Image noise in the 100 kV data was increased and SNR decreased (17.8/9.6) in the jugular veins and the sternocleidomastoid muscle when compared to 120 kV (SNR 24.4/10.3), but not in fatty tissue and air. However, CNR did not differ statistically significant between 100 (23.5/14.4/9.4) and 120 kV data (24.2/15.3/8.6) while radiation dose was decreased by 7-8%. TVA between 100 and 120 kV in combination with TCM led to a radiation dose reduction compared to TCM alone, while keeping CNR constant though maintaining diagnostic image quality.

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

PubMed Central

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

Aim: To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Methods: Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Results: Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple Emax model with a fixed E0, which provided a common Emax and an approximate twofold difference in ED50 for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. Conclusion: The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries. PMID:21151159

Simvastatin in the treatment of asthma: lack of steroid-sparing effect.

PubMed

Cowan, Douglas C; Cowan, Jan O; Palmay, Rochelle; Williamson, Avis; Taylor, D Robin

2010-10-01

Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma. Small trials have failed to show a significant benefit, but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out. A randomised, placebo-controlled, crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred, followed by an increase until regain of control ('minimum' dose required) in 51 patients with asthma and sputum eosinophils (steroid-free) ≥ 2%. 43 patients completed the study. There was no significant difference in 'minimum' inhaled corticosteroid (ICS) dose requirement between simvastatin and placebo: (median (IQR) 50 μg daily (0-250) vs 100 μg daily (0-250), p=0.931). 'Minimum' dose distribution was similar (p=0.269). The fluticasone dose at which loss of control occurred did not differ significantly between simvastatin and placebo (p=0.404). In patients with loss of control in both treatment arms, fluticasone dose at loss of control was similar with simvastatin and placebo (median (IQR) 50 μg daily (0-100) for both, p=0.620). In those patients who reached 0 μg/day (n=18), Astma Control Questionnaire (ACQ) was lower (p=0.037), forced expiratory volume in 1 s (FEV(1)) higher (p<0.01) and sputum eosinophils lower with simvastatin compared with placebo (9.5% compared with 25.4%, p=0.033). Simvastatin does not have clinically important steroid-sparing effects in patients with eosinophilic asthma. In the absence of steroid, simvastatin is associated with minor improvements in symptoms and lung function, and a reduction in sputum eosinophils. Clinical trial number ACTRN12606000531516.

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients.

PubMed

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple E(max) model with a fixed E(0), which provided a common E(max) and an approximate twofold difference in ED(50) for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries.

Evaluation of optimum room entry times for radiation therapists after high energy whole pelvic photon treatments.

PubMed

Ho, Lavine; White, Peter; Chan, Edward; Chan, Kim; Ng, Janet; Tam, Timothy

2012-01-01

Linear accelerators operating at or above 10 MV produce neutrons by photonuclear reactions and induce activation in machine components, which are a source of potential exposure for radiation therapists. This study estimated gamma dose contributions to radiation therapists during high energy, whole pelvic, photon beam treatments and determined the optimum room entry times, in terms of safety of radiation therapists. Two types of technique (anterior-posterior opposing and 3-field technique) were studied. An Elekta Precise treatment system, operating up to 18 MV, was investigated. Measurements with an area monitoring device (a Mini 900R radiation monitor) were performed, to calculate gamma dose rates around the radiotherapy facility. Measurements inside the treatment room were performed when the linear accelerator was in use. The doses received by radiation therapists were estimated, and optimum room entry times were determined. The highest gamma dose rates were approximately 7 μSv/h inside the treatment room, while the doses in the control room were close to background (~0 μSv/h) for all techniques. The highest personal dose received by radiation therapists was estimated at 5 mSv/yr. To optimize protection, radiation therapists should wait for up to11 min after beam-off prior to room entry. The potential risks to radiation therapists with standard safety procedures were well below internationally recommended values, but risks could be further decreased by delaying room entry times. Dependent on the technique used, optimum entry times ranged between 7 to 11 min. A balance between moderate treatment times versus reduction in measured equivalent doses should be considered.

Is there a role for pharmacokinetic/pharmacodynamic-guided dosing for novel oral anticoagulants?

PubMed

Chan, Noel; Sager, Philip T; Lawrence, Jack; Ortel, Thomas's; Reilly, Paul; Berkowitz, Scott; Kubitza, Dagmar; Eikelboom, John; Florian, Jeffry; Stockbridge, Norman; Rose, Martin; Temple, Robert; Seltzer, Jonathan H

2018-05-01

The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety. Based on these analyses, pharmaceutical manufacturers and regulatory authorities have provided contraindications and dosing recommendations based on clinical characteristics that are associated with drug levels and/or pharmacodynamic responses, stroke reduction, and bleeding risk to optimize the risk-benefit profile of the NOACs in the real world. The current fixed-dosing strategy of NOACs has triggered discussions about the potential value of laboratory monitoring and dose adjustment in customizing drug exposure to further improve the safety and efficacy of the NOACs in patients with atrial fibrillation. As there is neither high-quality evidence nor consensus about the potential role of laboratory monitoring and dose adjustment for the NOACs, a Cardiac Research Safety Consortium "Think Tank" meeting was held at the American College of Cardiology Heart House in December 2015 to discussions these issues. This manuscript reports on the deliberations and the conclusions reached at that meeting. Copyright © 2017. Published by Elsevier Inc.

Can body composition be used to optimize the dose of platinum chemotherapy in lung cancer? A feasibility study.

PubMed

Crosby, Vincent; D'Souza, Catherine; Bristow, Carina; Proffitt, Amy; Hussain, Asmah; Potter, Vanessa; Hennig, Ivo; O'Connor, Richard; Baracos, Vickie; Wilcock, Andrew

2017-04-01

Current methods of dosing platinum-based chemotherapy are suboptimal. Potentially, taking lean body mass into account may help. To inform the design of a future study, we first examined the feasibility and acceptability of such an approach using dual-energy X-ray absorptiometry (DEXA) and explored aspects suggestive of over- and under-dosing. Patients with lung cancer offered platinum-based chemotherapy over 1 year were identified and, if eligible, invited to take part in a prospective feasibility study. Questionnaires examined acceptability of the DEXA scan and of a future study that randomized between traditional dosing and one adjusted according to body composition. Dose-limiting toxicity (DLT) and a lack of neutropenia explored potential over- and under-dosing, respectively. Of the 173 patients offered chemotherapy, 123 (71%) were ineligible, mostly because of failing entry criteria (84, 49%). Of the 50 approached, 18 (36%) participated, most receiving carboplatin, with 17 providing data. All found a DEXA scan acceptable; other assessments were fully completed, except nadir and pre-chemotherapy blood counts. Most (94%) were prepared to take part in a future study, although the additional hospital visits for a nadir blood count were unpopular with some. Five (29%) patients experienced six episodes of DLT which resulted in discontinuation (3), dose reduction (2) or change to a less toxic regimen (1). Nine (60%) patients experienced either no (2) or inconsistent (7) neutropenia. A randomized trial appears acceptable and feasible in patients receiving carboplatin. Adjustment of our entry criteria and avoiding a hospital visit for a nadir blood count should aid recruitment.

Quantitative Analysis of the Effect of Iterative Reconstruction Using a Phantom: Determining the Appropriate Blending Percentage

PubMed Central

Kim, Hyun Gi; Lee, Young Han; Choi, Jin-Young; Park, Mi-Suk; Kim, Myeong-Jin; Kim, Ki Whang

2015-01-01

Purpose To investigate the optimal blending percentage of adaptive statistical iterative reconstruction (ASIR) in a reduced radiation dose while preserving a degree of image quality and texture that is similar to that of standard-dose computed tomography (CT). Materials and Methods The CT performance phantom was scanned with standard and dose reduction protocols including reduced mAs or kVp. Image quality parameters including noise, spatial, and low-contrast resolution, as well as image texture, were quantitatively evaluated after applying various blending percentages of ASIR. The optimal blending percentage of ASIR that preserved image quality and texture compared to standard dose CT was investigated in each radiation dose reduction protocol. Results As the percentage of ASIR increased, noise and spatial-resolution decreased, whereas low-contrast resolution increased. In the texture analysis, an increasing percentage of ASIR resulted in an increase of angular second moment, inverse difference moment, and correlation and in a decrease of contrast and entropy. The 20% and 40% dose reduction protocols with 20% and 40% ASIR blending, respectively, resulted in an optimal quality of images with preservation of the image texture. Conclusion Blending the 40% ASIR to the 40% reduced tube-current product can maximize radiation dose reduction and preserve adequate image quality and texture. PMID:25510772

Novel low-kVp beamlet system for choroidal melanoma

PubMed Central

Esquivel, Carlos; Fuller, Clifton D; Waggener, Robert G; Wong, Adrian; Meltz, Martin; Blough, Melissa; Eng, Tony Y; Thomas, Charles R

2006-01-01

Background Treatment of choroidal melanoma with radiation often involves placement of customized brachytherapy eye-plaques. However, the dosimetric properties inherent in source-based radiotherapy preclude facile dose optimization to critical ocular structures. Consequently, we have constructed a novel system for utilizing small beam low-energy radiation delivery, the Beamlet Low-kVp X-ray, or "BLOKX" system. This technique relies on an isocentric rotational approach to deliver dose to target volumes within the eye, while potentially sparing normal structures. Methods Monte Carlo N-Particle (MCNP) transport code version 5.0(14) was used to simulate photon interaction with normal and tumor tissues within modeled right eye phantoms. Five modeled dome-shaped tumors with a diameter and apical height of 8 mm and 6 mm, respectively, were simulated distinct positions with respect to the macula iteratively. A single fixed 9 × 9 mm2 beamlet, and a comparison COMS protocol plaque containing eight I-125 seeds (apparent activity of 8 mCi) placed on the scleral surface of the eye adjacent to the tumor, were utilized to determine dosimetric parameters at tumor and adjacent tissues. After MCNP simulation, comparison of dose distribution at each of the 5 tumor positions for each modality (BLOKX vs. eye-plaque) was performed. Results Tumor-base doses ranged from 87.1–102.8 Gy for the BLOKX procedure, and from 335.3–338.6 Gy for the eye-plaque procedure. A reduction of dose of at least 69% to tumor base was noted when using the BLOKX. The BLOKX technique showed a significant reduction of dose, 89.8%, to the macula compared to the episcleral plaque. A minimum 71.0 % decrease in dose to the optic nerve occurred when the BLOKX was used. Conclusion The BLOKX technique allows more favorable dose distribution in comparison to standard COMS brachytherapy, as simulated using a Monte Carlo iterative mathematical modeling. Future series to determine clinical utility of such an approach are warranted. PMID:16965624

Breastfeeding linked to the reduction of both rotavirus shedding and IgA levels after Rotarix® immunization in Mexican infants.

PubMed

Bautista-Marquez, Aurora; Velasquez, Daniel E; Esparza-Aguilar, Marcelino; Luna-Cruz, Maria; Ruiz-Moran, Tatiana; Sugata, Ken; Jiang, Baoming; Parashar, Umesh; Patel, Manish; Richardson, Vesta

2016-10-17

We examined potential risk factors on vaccine virus shedding and antibody seroresponse to human rotavirus vaccine (Rotarix) in Mexican infants. Two doses of Rotarix were administered to infants during the first two visits for their routine childhood immunization (∼8 and 15weeks of age) in Mexico City. Infant's characteristics and socioeconomic indicators were obtained, including history of long-term feeding practices (exclusively/predominantly breastfed and exclusively/predominantly non-breastfed). Two serum specimens were collected, one during the second rotavirus vaccine visit and one 7weeks later. Stool specimens were collected between days 4-7 after each of the two rotavirus vaccine doses. Rotavirus IgA and IgG titers in serum were determined by enzyme immunoassays (EIA) and rotavirus shedding in stool was assessed by EIA and confirmed by RT-PCR. The overall rotavirus IgA geometric mean titers (GMT) increased significantly post dose 2 from post dose 1 [176 (95%CI: 113-273) to 335 (238-471); p=0.020). Infants who were exclusively/predominantly breastfed were less likely to shed vaccine virus in stool than those who were formula-fed (22% vs. 43%, p=0.016). Infants who were breastfed had lower rotavirus IgA titers than those who were formula-fed after dose 1 [GMT: 145 (84-250) vs. 267 (126-566) p=0.188] and dose 2 [236 (147-378) vs.578 (367-910), p=0.007]. Infants who shed vaccine virus post dose 1 had significantly higher serum IgA GMT than those who did not shed [425 (188-965) vs. 150 (84-266), p=0.038]. Breastfeeding was linked with the reduction of both stool vaccine shedding, and IgA seroresponse. The reduced rotavirus replication in the gut and shedding after dose 1 may explain in part the lower IgA response in serum. Published by Elsevier Ltd.

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.

PubMed

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G

2013-12-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06mg/kg) under an FR 3 schedule during daily 23h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose-response relationships were very well described by the exponential demand function (r(2) values>0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. Copyright © 2013 Elsevier Inc. All rights reserved.

4D cone-beam computed tomography (CBCT) using a moving blocker for simultaneous radiation dose reduction and scatter correction

NASA Astrophysics Data System (ADS)

Zhao, Cong; Zhong, Yuncheng; Duan, Xinhui; Zhang, You; Huang, Xiaokun; Wang, Jing; Jin, Mingwu

2018-06-01

Four-dimensional (4D) x-ray cone-beam computed tomography (CBCT) is important for a precise radiation therapy for lung cancer. Due to the repeated use and 4D acquisition over a course of radiotherapy, the radiation dose becomes a concern. Meanwhile, the scatter contamination in CBCT deteriorates image quality for treatment tasks. In this work, we propose the use of a moving blocker (MB) during the 4D CBCT acquisition (‘4D MB’) and to combine motion-compensated reconstruction to address these two issues simultaneously. In 4D MB CBCT, the moving blocker reduces the x-ray flux passing through the patient and collects the scatter information in the blocked region at the same time. The scatter signal is estimated from the blocked region for correction. Even though the number of projection views and projection data in each view are not complete for conventional reconstruction, 4D reconstruction with a total-variation (TV) constraint and a motion-compensated temporal constraint can utilize both spatial gradient sparsity and temporal correlations among different phases to overcome the missing data problem. The feasibility simulation studies using the 4D NCAT phantom showed that 4D MB with motion-compensated reconstruction with 1/3 imaging dose reduction could produce satisfactory images and achieve 37% improvement on structural similarity (SSIM) index and 55% improvement on root mean square error (RMSE), compared to 4D reconstruction at the regular imaging dose without scatter correction. For the same 4D MB data, 4D reconstruction outperformed 3D TV reconstruction by 28% on SSIM and 34% on RMSE. A study of synthetic patient data also demonstrated the potential of 4D MB to reduce the radiation dose by 1/3 without compromising the image quality. This work paves the way for more comprehensive studies to investigate the dose reduction limit offered by this novel 4D MB method using physical phantom experiments and real patient data based on clinical relevant metrics.

4D cone-beam computed tomography (CBCT) using a moving blocker for simultaneous radiation dose reduction and scatter correction.

PubMed

Zhao, Cong; Zhong, Yuncheng; Duan, Xinhui; Zhang, You; Huang, Xiaokun; Wang, Jing; Jin, Mingwu

2018-05-03

Four-dimensional (4D) X-ray cone-beam computed tomography (CBCT) is important for a precise radiation therapy for lung cancer. Due to the repeated use and 4D acquisition over a course of radiotherapy, the radiation dose becomes a concern. Meanwhile, the scatter contamination in CBCT deteriorates image quality for treatment tasks. In this work, we propose to use a moving blocker (MB) during the 4D CBCT acquisition ("4D MB") and to combine motion-compensated reconstruction to address these two issues simultaneously. In 4D MB CBCT, the moving blocker reduces the X-ray flux passing through the patient and collects the scatter information in the blocked region at the same time. The scatter signal is estimated from the blocked region for correction. Even though the number of projection views and projection data in each view are not complete for conventional reconstruction, 4D reconstruction with a total-variation (TV) constraint and a motion-compensated temporal constraint can utilize both spatial gradient sparsity and temporal correlations among different phases to overcome the missing data problem. The feasibility simulation studies using the 4D NCAT phantom showed that 4D MB with motion-compensated reconstruction with 1/3 imaging dose reduction could produce satisfactory images and achieve 37% improvement on structural similarity (SSIM) index and 55% improvement on root mean square error (RMSE), compared to 4D reconstruction at the regular imaging dose without scatter correction. For the same 4D MB data, 4D reconstruction outperformed 3D TV reconstruction by 28% on SSIM and 34% on RMSE. A study of synthetic patient data also demonstrated the potential of 4D MB to reduce the radiation dose by 1/3 without compromising the image quality. This work paves the way for more comprehensive studies to investigate the dose reduction limit offered by this novel 4D MB method using physical phantom experiments and real patient data based on clinical relevant metrics. © 2018 Institute of Physics and Engineering in Medicine.

Safety assessment of Hibiscus sabdariffa after maternal exposure on male reproductive parameters in rats.

PubMed

de Arruda, Aline; Cardoso, Claudia Andrea L; Vieira, Maria do Carmo; Arena, Arielle Cristina

2016-01-01

Hibiscus sabdariffa L. (Malvaceae) is a species widely used in folk medicine for the treatment of some disorders. This study evaluated the effects of H. sabdariffa (HS) on the development of the male reproductive tract in rats following in utero exposure. Pregnant rats received 250 or 500 mg/kg of HS extract or vehicle from gestational day 12 until day 21 of lactation. Both doses of HS increased the body weight of male offspring at weaning, without compromising the puberty onset parameters. At puberty, there was a significant increase in the vas deferens absolute weight and a significant reduction in the relative weight of kidney at higher dose. These animals also presented a significant reduction in the sperm number in the caput/corpus of epididymis after exposure to both doses and a reduction in the sperm number in the cauda epididymis for the lower dose. At adulthood, the highest dose significantly reduced the sperm production in relation to controls and both doses provoked a reduction in the relative sperm number in the epididymis without affecting the sperm morphology. These findings demonstrated that maternal exposure to H. sabdariffa can adversely influence the male reproductive system in rats.

Mutagenic potential of Cordia ecalyculata alone and in association with Spirulina maxima for their evaluation as candidate anti-obesity drugs.

PubMed

Araldi, R P; Rechiutti, B M; Mendes, T B; Ito, E T; Souza, E B

2014-07-07

Obesity is one of the most important nutritional disorders, and can be currently considered as an epidemic. Although there are few weight reduction drugs available on the market, some new drug candidates have been proposed, including Cordia ecalyculata, a Brazilian plant with anorectic properties, and Spirulina maxima, a cyanobacterium with antioxidant and anti-genotoxic activity. In this study, we evaluated the mutagenic potential of C. ecalyculata at doses of 150, 300, and 500 mg/kg alone and in association with S. maxima at doses of 75, 150, and 250 mg/kg, respectively, through an in vivo micronucleus test, using mice of both sexes, and an in vitro micronucleus test and comet assay, using human peripheral blood. For all tests, cyclophosphamide was used as a positive control. The results showed that treatment of 300 mg/kg C. ecalyculata and the combination treatment of 500 mg/kg C. ecalyculata with 250 mg/kg S. maxima resulted in anorectic effects. The mutagenic tests did not reveal any clastogenic or genotoxic activity for any treatment, indicating that these candidates could be marketed as weight-reduction drugs. Moreover, the drugs contain chemo-preventive substances that can protect against tumorigenesis, which has been associated with obesity.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). In nonhuman primates, PGJ₂ administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ₂ is neuroprotective when administered up to 5 hours after induction of pNAION. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Surface dose measurements from air gaps under a bolus by using a MOSFET dosimeter in clinical oblique photon beams

NASA Astrophysics Data System (ADS)

Chung, Jin-Beom; Kim, Jae-Sung; Kim, In-Ah; Lee, Jeong-Woo

2012-10-01

This study is intended to investigate the effects of surface dose from air gaps under the bolus in clinically used oblique photon beams by using a Markus parallel-plate chamber and a metal-oxide semiconductor field-effect transistor (MOSFET) dosimeter. To evaluate the performances of the two detectors, the percentage surface doses of the MOSFET dosimeters in without an air gap under the bolus material were measured and compared with those of the Markus parallel-plate chamber. MOSFET dosimeters at the surface provided results mostly in good agreement with the parallelplate chamber. The MOSFET dosimeters seemed suitable for surface dose measurements having excellent accuracy for clinical used photon beams. The relative surface doses were measured with air gaps (2, 5, 10 mm) and without an air gap under 3 different bolus setups: (1) unbolused (no bolus), (2) 5-mm bolus, and (3) 10-mm bolus. The reductions in the surface dose substantially increased with small field size, thick bolus, and large air gap. The absolute difference in the reductions of the surface dose between the MOSFET dosimeter and the Markus parallel-plate chamber was less than 1.1%. Results at oblique angles of incidence showed larger reductions in surface dose with increasing angle of incidence. The largest reduction in surface dose was recorded for a 6 × 6 cm2 field at a 60° angle of incidence with an 10-mm air gap under a 10-mm bolus. When a 10-mm bolus was used, a reduction in the surface dose with an air gap of up to 10.5% could be achieved by varying the field size and the incident angle. Therefore, air gaps under the bolus should be avoided in radiotherapy treatment, especially for photon beam with highly oblique angles of incidence.

SU-E-I-49: The Evaluation of Usability of Multileaf Collimator for Diagnostic Radiation in Cephalometric Exposure

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

Han, S; Kim, K; Jung, H

Purpose: This study evaluated usability of Multileaf collimator (MLC) for diagnostic radiation in cephalometric exposure using optical stimulated luminance dosimeters (OSLDs) Methods: The MLC material was made alloy tool steel (SKD-11) and the density of it is 7.89g/m3 that is similar to it of steel (Fe, 7.85 g/m3) and the MLC was attached to general radiography unit (Rex-650R, Listem Inc, Korea) for cephalometric exposure. The OSLDs that used were nanoDotTM Dosimeter (Landauer Inc, Glenwood, USA) and we read out OSLDs with micro star system (Landauer Inc, Glenwood, USA). The Optical annealing system contained fluorescent lamps (Osram lumilux, 24 W, 280more » ∼780 nm). To measure absorbed dose using OSLDs, was carried out dosimetric characteristics of OSLDs. Based on these, we evaluated dose reduction of critical organ (Eyes, Thyroids) with MLC in cephalometric exposure Results: The dosimetric characteristics were following that batch homogeneity was 1.21% and reproducibility was 0.96% of the coefficient of variation The linearity was that the correlation of between dose and count was fitted by linear function (dose,mGy = 0.00029 × Count, R2 =0.997). The range of angular dependence was from −3.6% to 3.7% variation when each degree was normalized by zero degree. The organ dose of Rt. eye, Lt eye, thyroids were 77.8 μGy, 337.0 μGy, 323.1μGy, respectively in open field and the dose reduction of organ dose was 10.6%(8.3μGy), 12.4 %(42 μGy), 87.1%(281.4μGy) with MLC Conclusion: We certified dose reduction of organ dose in cephalometric exposure. The dose reduction of Eye was 11% because of reduction of field size and it of thyroids was 87% by primary beam shielding.« less

Prospective Evaluation of Prior Image Constrained Compressed Sensing (PICCS) Algorithm in Abdominal CT: A comparison of reduced dose with standard dose imaging

PubMed Central

Lubner, Meghan G.; Pickhardt, Perry J.; Kim, David H.; Tang, Jie; Munoz del Rio, Alejandro; Chen, Guang-Hong

2014-01-01

Purpose To prospectively study CT dose reduction using the “prior image constrained compressed sensing” (PICCS) reconstruction technique. Methods Immediately following routine standard dose (SD) abdominal MDCT, 50 patients (mean age, 57.7 years; mean BMI, 28.8) underwent a second reduced-dose (RD) scan (targeted dose reduction, 70-90%). DLP, CTDIvol and SSDE were compared. Several reconstruction algorithms (FBP, ASIR, and PICCS) were applied to the RD series. SD images with FBP served as reference standard. Two blinded readers evaluated each series for subjective image quality and focal lesion detection. Results Mean DLP, CTDIvol, and SSDE for RD series was 140.3 mGy*cm (median 79.4), 3.7 mGy (median 1.8), and 4.2 mGy (median 2.3) compared with 493.7 mGy*cm (median 345.8), 12.9 mGy (median 7.9 mGy) and 14.6 mGy (median 10.1) for SD series, respectively. Mean effective patient diameter was 30.1 cm (median 30), which translates to a mean SSDE reduction of 72% (p<0.001). RD-PICCS image quality score was 2.8±0.5, improved over the RD-FBP (1.7±0.7) and RD-ASIR(1.9±0.8)(p<0.001), but lower than SD (3.5±0.5)(p<0.001). Readers detected 81% (184/228) of focal lesions on RD-PICCS series, versus 67% (153/228) and 65% (149/228) for RD-FBP and RD-ASIR, respectively. Mean image noise was significantly reduced on RD-PICCS series (13.9 HU) compared with RD-FBP (57.2) and RD-ASIR (44.1) (p<0.001). Conclusion PICCS allows for marked dose reduction at abdominal CT with improved image quality and diagnostic performance over reduced-dose FBP and ASIR. Further study is needed to determine indication-specific dose reduction levels that preserve acceptable diagnostic accuracy relative to higher-dose protocols. PMID:24943136

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

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

Zhou, Rachel; Ng, Angela; Constine, Louis S.

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohortmore » and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.« less

Impact of hydroquinone used as a redox effector model on potential denitrification, microbial activity and redox condition of a cultivable soil.

PubMed

Perotti, Elda B R

2015-01-01

In this microcosm study, we analyzed the effect produced by hydroquinone on the expression of soil biological denitrification, in relation to the redox state of the soil, both in terms of intensity factor (Eh') and capacity factor (amount of oxidized or reduced compounds). The supplementation of an Argiudoll soil with hydroquinone decreased the soil apparent reduction potential (Eh') and soil dehydrogenase activity (formazan production from tetrazolium chloride reduction; redox capacity factor), the relationship between both factors being highly significative, r=0.99 (p<0.001). The bacterial population (measured by colony forming units) increased, and the production of N2O was greater (p<0.001) at 200 and 400μg/g dry soil doses. Furthermore, there was an inverse relationship between soil dehydrogenase activity and the number of bacteria (r=-0.82; p<0.05), increased denitrification activity and changes in the CO2/N2O ratio value. These results suggest that hydroquinone at supplemented doses modified the soil redox state and the functional structure of the microbial population. Acetate supplementation on soil with hydroquinone, to ensure the availability of an energy source for microbial development, confirmed the tendency of the results obtained with the supplementation of hydroquinone alone. The differences observed at increased doses of hydroquinone might be explained by differences on the hydroquinone redox species between treatments. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Improving the biocontrol potential of Steinernema feltiae against Delia radicum through dosage, application technique and timing.

PubMed

Beck, Bert; Spanoghe, Pieter; Moens, Maurice; Brusselman, Eva; Temmerman, Femke; Pollet, Sabien; Nuyttens, David

2014-05-01

The potential of the entomopathogenic nematode (EPN) Steinernema feltiae Filipjev as a biocontrol agent against the cabbage maggot Delia radicum (L.), was assessed in three field tests, focusing on EPN dosage, application technique and timing. Spraying cabbage plant trays with different doses of infective juveniles (IJs) (50,000, 100,000 and 200,000 per plant) generated a similar reduction of plant mortality. Spraying plant trays with 200,000 IJs of Steinernema feltiae per plant temporarily reduced the number of maggots around the plants' roots, while neither spraying a lower dose (50,000 IJs/plant) nor soil drenching with 200,000 or 50,000 IJs/plant) reduced maggot numbers. When applied as a plant tray spray, IJs of S. feltiae took 1-2 weeks to spread through the soil surrounding the roots. The pathogenicity of the EPNs, as evaluated by a Galleria mellonella bait test, was highest (up to 100% mortality) until up to five weeks after application, and declined to control levels after 4-7 weeks. Follow-up drench applications with EPNs, applied one and/or two weeks after the first EPN application, did not influence control of Delia radicum. Plant tray spraying provides better placement of Steinernema feltiae than soil drench treatments for control of Delia radicum. Plant mortality was not dose-dependent in the presented trials, unlike the reduction of maggot numbers. Further research into timing and application technique of follow-up treatments with S. feltiae is required to increase efficacy to commercial standards. © 2013 Society of Chemical Industry.

Statistical model based iterative reconstruction in clinical CT systems. Part III. Task-based kV/mAs optimization for radiation dose reduction

PubMed Central

Li, Ke; Gomez-Cardona, Daniel; Hsieh, Jiang; Lubner, Meghan G.; Pickhardt, Perry J.; Chen, Guang-Hong

2015-01-01

Purpose: For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems. Methods: The optimal selection of kV and mAs was formulated as a constrained optimization problem to minimize the objective function, Dose(kV,mAs), under the constraint that the achievable detectability index d′(kV,mAs) is not lower than the prescribed value of d℞′ for a given imaging task. Since it is difficult to analytically model the dependence of d′ on kV and mAs for the highly nonlinear MBIR method, this constrained optimization problem is solved with comprehensive measurements of Dose(kV,mAs) and d′(kV,mAs) at a variety of kV–mAs combinations, after which the overlay of the dose contours and d′ contours is used to graphically determine the optimal kV–mAs combination to achieve the lowest dose while maintaining the needed detectability for the given imaging task. As an example, d′ for a 17 mm hypoattenuating liver lesion detection task was experimentally measured with an anthropomorphic abdominal phantom at four tube potentials (80, 100, 120, and 140 kV) and fifteen mA levels (25 and 50–700) with a sampling interval of 50 mA at a fixed rotation time of 0.5 s, which corresponded to a dose (CTDIvol) range of [0.6, 70] mGy. Using the proposed method, the optimal kV and mA that minimized dose for the prescribed detectability level of d℞′=16 were determined. As another example, the optimal kV and mA for an 8 mm hyperattenuating liver lesion detection task were also measured using the developed framework. Both an in vivo animal and human subject study were used as demonstrations of how the developed framework can be applied to the clinical work flow. Results: For the first task, the optimal kV and mAs were measured to be 100 and 500, respectively, for FBP, which corresponded to a dose level of 24 mGy. In comparison, the optimal kV and mAs for MBIR were 80 and 150, respectively, which corresponded to a dose level of 4 mGy. The topographies of the iso-d′ map and the iso-CNR map were the same for FBP; thus, the use of d′- and CNR-based optimization methods generated the same results for FBP. However, the topographies of the iso-d′ and iso-CNR map were significantly different in MBIR; the CNR-based method overestimated the performance of MBIR, predicting an overly aggressive dose reduction factor. For the second task, the developed framework generated the following optimization results: for FBP, kV = 140, mA = 350, dose = 37.5 mGy; for MBIR, kV = 120, mA = 250, dose = 18.8 mGy. Again, the CNR-based method overestimated the performance of MBIR. Results of the preliminary in vivo studies were consistent with those of the phantom experiments. Conclusions: A unified and task-driven kV/mAs optimization framework has been developed in this work. The framework is applicable to both linear and nonlinear CT systems such as those using the MBIR method. As expected, the developed framework can be reduced to the conventional CNR-based kV/mAs optimization frameworks if the system is linear. For MBIR-based nonlinear CT systems, however, the developed task-based kV/mAs optimization framework is needed to achieve the maximal dose reduction while maintaining the desired diagnostic performance. PMID:26328971

Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: A single-blinded, 52-week, randomized controlled study.

PubMed

Zhou, Yanling; Li, Guannan; Li, Dan; Cui, Hongmei; Ning, Yuping

2018-05-01

The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all p<0.05). Post hoc analyses showed significant improvement in Positive and Negative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all p<0.05). This study indicated that a risperidone or olanzapine dose reduction of 50% may not lead to more severe symptomatology but can improve speed of processing, working memory and negative symptoms in patients with stabilized schizophrenia.

Comparative reduction of Norwalk virus, poliovirus type 1, F+ RNA coliphage MS2 and Escherichia coli in miniature soil columns.

PubMed

Meschke, J S; Sobsey, M D

2003-01-01

Norwalk-like viruses (NLVs) are important agents of waterborne illness and have been linked to several groundwater-related outbreaks. The presence of human enteric viruses, in particular the presence of NLVs, is difficult to detect in the environment. Consequently, surrogate organisms are typically used as indicators of viruses from faecal contamination. Whether traditional bacterial indicators are reliable indicators for viral pathogens remains uncertain. Few studies have directly compared mobility and reduction of bacterial indicators (e.g. coliforms, Escherichia coli) and other surrogate indicators (coliphages) with pathogenic human viruses in soil systems. In this study the mobility and comparative reduction of the prototype NLV, Norwalk Virus (NV), was compared to poliovirus 1 (PV1), a bacterial indicator (E coli, EC) and a viral indicator (coliphage MS2) through miniature soil columns. Replicate, 10 cm deep, miniature columns were prepared using three soils representing a range of soil textures (sand, organic muck, and clay). Columns were initially conditioned, then incubated at 10-14 degrees C, dosed twice weekly for 8 weeks with one column pore volume of virus-seeded groundwater per dose, followed by 8 weeks of dosing with one column pore volume per dose of unseeded, simulated rainwater. Columns were allowed to drain after each dosing until an effluent volume equivalent to an applied dose was collected. Column effluents and doses were assayed for all viruses and EC. Rapid mobility with minimal reduction was observed for all organisms in the sand. Similar reductions were observed in organic muck for most organisms but NV showed a greater reduction. No organisms were shown to pass through the clay columns. Elution of viruses, in particular PV1, from the columns was gradual. After cessation of microbe dosing, E. coli was less detectable than viruses in column effluents and, therefore, unreliable as a virus indicator.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

PubMed Central

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-01-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. PMID:25755255

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

NASA Astrophysics Data System (ADS)

Brivio, D.; Zygmanski, P.; Arnoldussen, M.; Hanlon, J.; Chell, E.; Sajo, E.; Makrigiorgos, G. M.; Ngwa, W.

2015-12-01

This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g-1, which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 μm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.

A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

PubMed Central

2012-01-01

Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats.

PubMed

Afolabi, Saheed O; Akindele, Abidemi J; Awodele, Olufunsho; Anunobi, Chidozie C; Adeyemi, Olufunmilayo O

2012-06-28

The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250-3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males.

Evaluation of patritumab with or without erlotinib in combination with standard cytotoxic agents against pediatric sarcoma xenograft models.

PubMed

Bandyopadhyay, Abhik; Favours, Edward; Phelps, Doris A; Pozo, Vanessa Del; Ghilu, Samson; Kurmashev, Dias; Michalek, Joel; Trevino, Aron; Guttridge, Denis; London, Cheryl; Hirotani, Kenji; Zhang, Ling; Kurmasheva, Raushan T; Houghton, Peter J

2018-02-01

Integrating molecularly targeted agents with cytotoxic drugs used in curative treatment of pediatric cancers is complex. An evaluation was undertaken with the ERBB3/Her3-specific antibody patritumab (P) either alone or with the ERBB1/epidermal growth factor receptor inhibitor erlotinib (E) in combination with standard cytotoxic agents, cisplatin, vincristine, and cyclophosphamide, in pediatric sarcoma xenograft models that express receptors and ligands targeted by these agents. Tumor models were selected based upon ERBB3 expression and phosphorylation, and ligand (heregulin) expression. Patritumab, E, or these agents combined was evaluated without or with concomitant cytotoxic agents using procedures developed by the Pediatric Preclinical Testing Program. Full doses of cytotoxic agents were tolerated when combined with P, whereas dose reductions of 25% (vincristine, cisplatin) or 50% (cyclophosphamide) were required when combined with P + E. Patritumab, E alone, or in combination did not significantly inhibit growth of any tumor model, except for Rh18 xenografts (E alone). Patritumab had no single-agent activity and marginally enhanced the activity of vincristine and cisplatin only in Ewing sarcoma ES-4. P + E did not increase the antitumor activity of vincristine or cisplatin, whereas dose-reduced cyclophosphamide was significantly less active than cyclophosphamide administered at its maximum tolerated dose when combined with P + E. P had no single-agent activity, although it marginally potentiated the activity of vincristine and cisplatin in one of three models studied. However, the addition of E necessitated dose reduction of each cytotoxic agent, abrogating the enhancement observed with P alone. © 2017 Wiley Periodicals, Inc.

[Effects of sevoflurane and propofol on evoked potentials during neurosurgical anesthesia].

PubMed

Nakagawa, Itsuo; Hidaka, Syozo; Okada, Hironori; Kubo, Takashi; Okamura, Kenta; Kato, Takahiro

2006-06-01

The effect of anesthetics on somatosensory evoked potential (SEP) and auditory brain stem response (ABR) has been a subject of intense reseach over the last two decades. In fact, volatile anesthetics have been repeatedly shown to decrease cortical amplitude in a dose-dependent fashion but the information regarding the effect of propofol is incomplete. The purpose of this study was to compare the effects of sevoflurane and propofol on evoked potentials during comparable depth of anesthesia guided by bispectral index (BIS). Forty four patients scheduled for neurosurgery were studied. Anesthesia was maintained with intravenous propofol using target controlled infusion (TCI). We measured the change of amplitude and latency of SEP(N20-P25), ABR (V wave) and visual evoked potential (VEP: P100) at three sets of sevoflurane (0%, 1%, 2%) or propofol concentrations (effect site concentration of 1.5, 2.0, 3.0 microug x ml(-1)). BIS monitor was used to measure relative depth of hypnosis. With increasing concentrations of sevoflurane (0, 1% and 2%), SEP showed dose-related reduction in its amplitude, ABR produced less marked changes and VEP showed a significant reduction at 1%. VEP at the propofol concentration of 3.0 microg x ml(-1) was decreased significantly compared with the amplitude at 1.5 microg x ml(-1) concentration. No significant change was observed with SEP and ABR during the change of propofol dosages. BIS values were almost the same with each anesthetics. VEP was most strongly affected with anesthetics, and ABR showed less marked influence of sevoflurane and propofol. Propofol based TIVA technique would induce less change in evoked potentials than sevoflurane.

Intussusception reduction: Effect of air vs. liquid enema on radiation dose.

PubMed

Kaplan, Summer L; Magill, Dennise; Felice, Marc A; Edgar, J Christopher; Anupindi, Sudha A; Zhu, Xiaowei

2017-10-01

Both air and radiopaque liquid contrast are used to reduce ileocolic intussusception under fluoroscopy. Some suggest air lowers radiation dose due to shorter procedure times. However, air enema likely lowers radiation dose regardless of fluoroscopy time due to less density over the automatic exposure control cells. We test the hypothesis that air enema reduction of ileocolic intussusception results in lower radiation dose than liquid contrast enema independent of fluoroscopy time. We describe a role for automatic exposure control in this dose difference. We retrospectively evaluated air and liquid intussusception reductions performed on a single digital fluoroscopic unit during a 26-month period. We compared patient age, weight, gender, exam time of day and year, performing radiologist(s), radiographic image acquisitions, grid and magnification use, fluoroscopy time and dose area product. We compared categorical and continuous variables statistically using chi-square and Mann-Whitney U tests, respectively. The mean dose area product was 2.7-fold lower for air enema, 1.3 ± 0.9 dGy·cm 2 , than for liquid, 3.5 ± 2.5 dGy·cm 2 (P<0.005). The mean fluoroscopy time was similar between techniques. The mean dose area product/min was 2.3-fold lower for air, 0.6 ± 0.2 dGy·cm 2 /min, than for liquid, 1.4 ± 0.5 dGy·cm 2 /min (P<0.001). No group differences were identified in other measured dose parameters. Fluoroscopic intussusception reduction using air enema uses less than half the radiation dose of liquid contrast enema. Dose savings are independent of fluoroscopy time and are likely due to automatic exposure control interaction.

Characterization of adaptive statistical iterative reconstruction algorithm for dose reduction in CT: A pediatric oncology perspective

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

Brady, S. L.; Yee, B. S.; Kaufman, R. A.

Purpose: This study demonstrates a means of implementing an adaptive statistical iterative reconstruction (ASiR Trade-Mark-Sign ) technique for dose reduction in computed tomography (CT) while maintaining similar noise levels in the reconstructed image. The effects of image quality and noise texture were assessed at all implementation levels of ASiR Trade-Mark-Sign . Empirically derived dose reduction limits were established for ASiR Trade-Mark-Sign for imaging of the trunk for a pediatric oncology population ranging from 1 yr old through adolescence/adulthood. Methods: Image quality was assessed using metrics established by the American College of Radiology (ACR) CT accreditation program. Each image quality metricmore » was tested using the ACR CT phantom with 0%-100% ASiR Trade-Mark-Sign blended with filtered back projection (FBP) reconstructed images. Additionally, the noise power spectrum (NPS) was calculated for three common reconstruction filters of the trunk. The empirically derived limitations on ASiR Trade-Mark-Sign implementation for dose reduction were assessed using (1, 5, 10) yr old and adolescent/adult anthropomorphic phantoms. To assess dose reduction limits, the phantoms were scanned in increments of increased noise index (decrementing mA using automatic tube current modulation) balanced with ASiR Trade-Mark-Sign reconstruction to maintain noise equivalence of the 0% ASiR Trade-Mark-Sign image. Results: The ASiR Trade-Mark-Sign algorithm did not produce any unfavorable effects on image quality as assessed by ACR criteria. Conversely, low-contrast resolution was found to improve due to the reduction of noise in the reconstructed images. NPS calculations demonstrated that images with lower frequency noise had lower noise variance and coarser graininess at progressively higher percentages of ASiR Trade-Mark-Sign reconstruction; and in spite of the similar magnitudes of noise, the image reconstructed with 50% or more ASiR Trade-Mark-Sign presented a more smoothed appearance than the pre-ASiR Trade-Mark-Sign 100% FBP image. Finally, relative to non-ASiR Trade-Mark-Sign images with 100% of standard dose across the pediatric phantom age spectrum, similar noise levels were obtained in the images at a dose reduction of 48% with 40% ASIR Trade-Mark-Sign and a dose reduction of 82% with 100% ASIR Trade-Mark-Sign . Conclusions: The authors' work was conducted to identify the dose reduction limits of ASiR Trade-Mark-Sign for a pediatric oncology population using automatic tube current modulation. Improvements in noise levels from ASiR Trade-Mark-Sign reconstruction were adapted to provide lower radiation exposure (i.e., lower mA) instead of improved image quality. We have demonstrated for the image quality standards required at our institution, a maximum dose reduction of 82% can be achieved using 100% ASiR Trade-Mark-Sign ; however, to negate changes in the appearance of reconstructed images using ASiR Trade-Mark-Sign with a medium to low frequency noise preserving reconstruction filter (i.e., standard), 40% ASiR Trade-Mark-Sign was implemented in our clinic for 42%-48% dose reduction at all pediatric ages without a visually perceptible change in image quality or image noise.« less

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

PubMed

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

2016-03-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. Copyright © 2016 by the American Society of Nephrology.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-Up

PubMed Central

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank

2016-01-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. PMID:26185201

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

SU-F-I-09: Improvement of Image Registration Using Total-Variation Based Noise Reduction Algorithms for Low-Dose CBCT

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

Mukherjee, S; Farr, J; Merchant, T

Purpose: To study the effect of total-variation based noise reduction algorithms to improve the image registration of low-dose CBCT for patient positioning in radiation therapy. Methods: In low-dose CBCT, the reconstructed image is degraded by excessive quantum noise. In this study, we developed a total-variation based noise reduction algorithm and studied the effect of the algorithm on noise reduction and image registration accuracy. To study the effect of noise reduction, we have calculated the peak signal-to-noise ratio (PSNR). To study the improvement of image registration, we performed image registration between volumetric CT and MV- CBCT images of different head-and-neck patientsmore » and calculated the mutual information (MI) and Pearson correlation coefficient (PCC) as a similarity metric. The PSNR, MI and PCC were calculated for both the noisy and noise-reduced CBCT images. Results: The algorithms were shown to be effective in reducing the noise level and improving the MI and PCC for the low-dose CBCT images tested. For the different head-and-neck patients, a maximum improvement of PSNR of 10 dB with respect to the noisy image was calculated. The improvement of MI and PCC was 9% and 2% respectively. Conclusion: Total-variation based noise reduction algorithm was studied to improve the image registration between CT and low-dose CBCT. The algorithm had shown promising results in reducing the noise from low-dose CBCT images and improving the similarity metric in terms of MI and PCC.« less

Antimalarial Activity of Cocos nucifera Husk Fibre: Further Studies

PubMed Central

Adebayo, J. O.; Balogun, E. A.; Malomo, S. O.; Soladoye, A. O.; Olatunji, L. A.; Kolawole, O. M.; Oguntoye, O. S.; Babatunde, A. S.; Akinola, O. B.; Aguiar, A. C. C.; Andrade, I. M.; Souza, N. B.; Krettli, A. U.

2013-01-01

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25–500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles. PMID:23983800

Antimalarial Activity of Cocos nucifera Husk Fibre: Further Studies.

PubMed

Adebayo, J O; Balogun, E A; Malomo, S O; Soladoye, A O; Olatunji, L A; Kolawole, O M; Oguntoye, O S; Babatunde, A S; Akinola, O B; Aguiar, A C C; Andrade, I M; Souza, N B; Krettli, A U

2013-01-01

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25-500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.

Satratoxin-G from the black mold Stachybotrys chartarum induces rhinitis and apoptosis of olfactory sensory neurons in the nasal airways of rhesus monkeys.

PubMed

Carey, Stephan A; Plopper, Charles G; Hyde, Dallas M; Islam, Zahidul; Pestka, James J; Harkema, Jack R

2012-08-01

Satratoxin-G (SG) is a trichothecene mycotoxin of Stachybotrys chartarum, the black mold suggested to contribute etiologically to illnesses associated with water-damaged buildings. We have reported that intranasal exposure to SG evokes apoptosis of olfactory sensory neurons (OSNs) and acute inflammation in the nose and brain of laboratory mice. To further assess the potential human risk of nasal airway injury and neurotoxicity, we developed a model of SG exposure in monkeys, whose nasal airways more closely resemble those of humans. Adult, male rhesus macaques received a single intranasal instillation of 20 µg SG (high dose, n = 3), or 5 µg SG daily for four days (repeated low dose, n = 3) in one nasal passage, and saline vehicle in the contralateral nasal passage. Nasal tissues were examined using light and electron microscopy and morphometric analysis. SG induced acute rhinitis, atrophy of the olfactory epithelium (OE), and apoptosis of OSNs in both groups. High-dose and repeated low-dose SG elicited a 13% and 66% reduction in OSN volume density, and a 14-fold and 24-fold increase in apoptotic cells of the OE, respectively. This model provides new insight into the potential risk of nasal airway injury and neurotoxicity caused by exposure to water-damaged buildings.

Sublethal doses of imidacloprid disrupt sexual communication and host finding in a parasitoid wasp

NASA Astrophysics Data System (ADS)

Tappert, Lars; Pokorny, Tamara; Hofferberth, John; Ruther, Joachim

2017-02-01

Neonicotinoids are widely used insecticides, but their use is subject of debate because of their detrimental effects on pollinators. Little is known about the effect of neonicotinoids on other beneficial insects such as parasitoid wasps, which serve as natural enemies and are crucial for ecosystem functioning. Here we show that sublethal doses of the neonicotinoid imidacloprid impair sexual communication and host finding in the parasitoid wasp Nasonia vitripennis. Depending on the dose, treated females were less responsive to the male sex pheromone or unable to use it as a cue at all. Courtship behaviour of treated couples was also impeded resulting in a reduction of mating rates by up to 80%. Moreover, treated females were no longer able to locate hosts by using olfactory cues. Olfaction is crucial for the reproductive success of parasitoid wasps. Hence, sublethal doses of neonicotinoids might compromise the function of parasitoid wasps as natural enemies with potentially dire consequences for ecosystem services.

Silibinin as a potential therapeutic for sulfur mustard injuries.

PubMed

Balszuweit, Frank; John, Harald; Schmidt, Annette; Kehe, Kai; Thiermann, Horst; Steinritz, Dirk

2013-12-05

Sulfur mustard (SM) is a vesicating chemical warfare agent causing skin blistering, ulceration, impaired wound healing, prolonged hospitalization and permanent lesions. Silibinin, the lead compound from Silybum marianum, has also been discussed as a potential antidote to SM poisoning. However, its efficacy has been demonstrated only with regard to nitrogen mustards. Moreover, there are no data on the efficacy of the water-soluble prodrug silibinin-bis-succinat (silibinin-BS). We investigated the effect of SIL-BS treatment against SM toxicity in HaCaT cells with regard to potential reduction of necrosis, apoptosis and inflammation including dose-dependency of any protective effects. We also demonstrated the biotransformation of the prodrug into free silibinin. HaCaT cells were exposed to SM (30, 100, and 300μM) for 30min and treated thereafter with SIL-BS (10, 50, and 100μM) for 24h. Necrosis and apoptosis were quantified using the ToxiLight BioAssay and the nucleosome ELISA (CDDE). Pro-inflammatory interleukins-6 and -8 were determined by ELISA. HaCaT cells, incubated with silibinin-BS were lysed and investigated by LC-ESI MS/MS. LC-ESI MS/MS results suggest that SIL-BS is absorbed by HaCaT cells and biotransformed into free silibinin. SIL-BS dose-dependently reduced SM cytotoxicity, even after 300μM exposure. Doses of 50-100μM silibinin-BS were required for significant protection. Apoptosis and interleukin production remained largely unchanged by 10-50μM silibinin-BS but increased after 100μM treatment. Observed reductions of SM cytotoxicity by post-exposure treatment with SIL-BS suggest this as a promising approach for treatment of SM injuries. While 100μM SIL-BS is most effective to reduce necrosis, 50μM may be safer to avoid pro-inflammatory effects. Pro-apoptotic effects after high doses of SIL-BS are in agreement with findings in literature and might even be useful to eliminate cells irreversibly damaged by SM. Further investigations will focus on the protective mechanism of silibinin and its prodrug and should establish an optimum concentration for treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dose reduction in 64-row whole-body CT in multiple trauma: an optimized CT protocol with iterative image reconstruction on a gemstone-based scintillator.

PubMed

Geyer, Lucas L; Körner, Markus; Harrieder, Andreas; Mueck, Fabian G; Deak, Zsuzsanna; Wirth, Stefan; Linsenmaier, Ulrich

2016-01-01

Evaluation of potential dose savings by implementing adaptive statistical iterative reconstruction (ASiR) on a gemstone-based scintillator in a clinical 64-row whole-body CT (WBCT) protocol after multiple trauma. Dose reports of 152 WBCT scans were analysed for two 64-row multidetector CT scanners (Scanners A and B); the main scanning parameters were kept constant. ASiR and a gemstone-based scintillator were used in Scanner B, and the noise index was adjusted (head: 5.2 vs 6.0; thorax/abdomen: 29.0 vs 46.0). The scan length, CT dose index (CTDI) and dose-length product (DLP) were analysed. The estimated mean effective dose was calculated using normalized conversion factors. Student's t-test was used for statistics. Both the mean CTDI (mGy) (Scanner A: 53.8 ± 2.0, 10.3 ± 2.5, 14.4 ± 3.7; Scanner B: 48.7 ± 2.2, 7.1 ± 2.3, 9.1 ± 3.6; p < 0.001, respectively) and the mean DLP (mGy cm) (Scanner A: 1318.9 ± 167.8, 509.3 ± 134.7, 848.8 ± 254.0; Scanner B: 1190.6 ± 172.6, 354.6 ± 128.3, 561.0 ± 246.7; p < 0.001, respectively) for the head, thorax and abdomen were significantly reduced with Scanner B. There was no relevant difference in scan length. The total mean effective dose (mSv) was significantly decreased with Scanner B (24.4 ± 6.0, 17.2 ± 5.8; p < 0.001). The implementation of ASiR and a gemstone-based scintillator allows for significant dose savings in a clinical WBCT protocol. Recent technical developments can significantly reduce radiation dose of WBCT in multiple trauma. Dose reductions of 10-34% can be achieved.

Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus.

PubMed

Han, Jeonghoon; Won, Eun-Ji; Lee, Bo-Young; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Leung, Kenneth Mei Yee; Lee, Yong Sung; Lee, Jae-Seong

2014-07-01

Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96h, even in response to exposure to a high dose (800Gy) of radiation, but mortality rate was significantly increased 120h (5 days) after exposure to 600 or 800Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50-200Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus. Copyright © 2014 Elsevier B.V. All rights reserved.

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Radiation dose reduction to the breast in thoracic CT: Comparison of bismuth shielding, organ-based tube current modulation, and use of a globally decreased tube current

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

Wang Jia; Duan Xinhui; Christner, Jodie A.

2011-11-15

Purpose: The purpose of this work was to evaluate dose performance and image quality in thoracic CT using three techniques to reduce dose to the breast: bismuth shielding, organ-based tube current modulation (TCM) and global tube current reduction. Methods: Semi-anthropomorphic thorax phantoms of four different sizes (15, 30, 35, and 40 cm lateral width) were used for dose measurement and image quality assessment. Four scans were performed on each phantom using 100 or 120 kV with a clinical CT scanner: (1) reference scan; (2) scan with bismuth breast shield of an appropriate thickness; (3) scan with organ-based TCM; and (4)more » scan with a global reduction in tube current chosen to match the dose reduction from bismuth shielding. Dose to the breast was measured with an ion chamber on the surface of the phantom. Image quality was evaluated by measuring the mean and standard deviation of CT numbers within the lung and heart regions. Results: Compared to the reference scan, dose to the breast region was decreased by about 21% for the 15-cm phantom with a pediatric (2-ply) shield and by about 37% for the 30, 35, and 40-cm phantoms with adult (4-ply) shields. Organ-based TCM decreased the dose by 12% for the 15-cm phantom, and 34-39% for the 30, 35, and 40-cm phantoms. Global lowering of the tube current reduced breast dose by 23% for the 15-cm phantom and 39% for the 30, 35, and 40-cm phantoms. In phantoms of all four sizes, image noise was increased in both the lung and heart regions with bismuth shielding. No significant increase in noise was observed with organ-based TCM. Decreasing tube current globally led to similar noise increases as bismuth shielding. Streak and beam hardening artifacts, and a resulting artifactual increase in CT numbers, were observed for scans with bismuth shields, but not for organ-based TCM or global tube current reduction. Conclusions: Organ-based TCM produces dose reduction to the breast similar to that achieved with bismuth shielding for both pediatric and adult phantoms. However, organ-based TCM does not affect image noise or CT number accuracy, both of which are adversely affected by bismuth shielding. Alternatively, globally decreasing the tube current can produce the same dose reduction to the breast as bismuth shielding, with a similar noise increase, yet without the streak artifacts and CT number errors caused by the bismuth shields. Moreover, globally decreasing the tube current reduces the dose to all tissues scanned, not simply to the breast.« less

Longitudinal study of radiation exposure in computed tomography with an in-house developed dose monitoring system

NASA Astrophysics Data System (ADS)

Renger, Bernhard; Rummeny, Ernst J.; Noël, Peter B.

2013-03-01

During the last decades, the reduction of radiation exposure especially in diagnostic computed tomography is one of the most explored topics. In the same time, it seems challenging to quantify the long-term clinical dose reduction with regard to new hardware as well as software solutions. To overcome this challenge, we developed a Dose Monitoring System (DMS), which collects information from PACS, RIS, MPPS and structured reports. The integration of all sources overcomes the weaknesses of single systems. To gather all possible information, we integrated an optical character recognition system to extract, for example, information from the CT-dose-report. All collected data are transferred to a database for further evaluation, e.g., for calculations of effective as well as organ doses. The DMS provides a single database for tracking all essential study and patient specific information across different modality as well as different vendors. As an initial study, we longitudinally investigated the dose reduction in CT examination when employing a noise-suppressing reconstruction algorithm. For this examination type a significant long-term reduction in radiation exposure is reported, when comparing to a CT-system with standard reconstruction. In summary our DMS tool not only enables us to track radiation exposure on daily bases but further enables to analyses the long term effect of new dose saving strategies. In the future the statistical analyses of all retrospective data, which are available in a modern imaging department, will provide a unique overview of advances in reduction of radiation exposure.

Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia.

PubMed

Akdim, Fatima; Tribble, Diane L; Flaim, JoAnn D; Yu, Rosie; Su, John; Geary, Richard S; Baker, Brenda F; Fuhr, Rainard; Wedel, Mark K; Kastelein, John J P

2011-11-01

Mipomersen, an apolipoprotein (apo) B synthesis inhibitor, has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers. A randomized, double-blind, placebo-controlled, dose-escalation study was designed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia. Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 randomization ratio of active to placebo. Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week. Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins. In the 200 and 300 mg/week dose cohorts, mean reductions from baseline in LDL cholesterol were -45 ± 10% (P= 0.000) and -61 ± 8% (P= 0.000), corresponding to a -46 ± 11% (P= 0.000) and -61 ± 7% (P= 0.000) decrease in apoB levels. Triglyceride levels were also lowered with median reductions up to 53% (P= 0.021). The most common adverse events were injection site reactions. Seven of 40 subjects (18%) showed consecutive transaminase elevations >3× upper limit of normal. Five of these subjects received 400 mg/week, four of whom had apoB levels below the limit of detection. As a consequence, the 400 mg/week cohort was discontinued. Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins. Higher doses were associated with hepatic transaminase increases.

Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid

PubMed Central

Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

2016-01-01

Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. PMID:25142864

Reduction of myeloid-derived suppressor cells and lymphoma growth by a natural triterpenoid.

PubMed

Radwan, Faisal F Y; Hossain, Azim; God, Jason M; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

2015-01-01

Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. © 2014 Wiley Periodicals, Inc.

CT of the chest with model-based, fully iterative reconstruction: comparison with adaptive statistical iterative reconstruction.

PubMed

Ichikawa, Yasutaka; Kitagawa, Kakuya; Nagasawa, Naoki; Murashima, Shuichi; Sakuma, Hajime

2013-08-09

The recently developed model-based iterative reconstruction (MBIR) enables significant reduction of image noise and artifacts, compared with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP). The purpose of this study was to evaluate lesion detectability of low-dose chest computed tomography (CT) with MBIR in comparison with ASIR and FBP. Chest CT was acquired with 64-slice CT (Discovery CT750HD) with standard-dose (5.7 ± 2.3 mSv) and low-dose (1.6 ± 0.8 mSv) conditions in 55 patients (aged 72 ± 7 years) who were suspected of lung disease on chest radiograms. Low-dose CT images were reconstructed with MBIR, ASIR 50% and FBP, and standard-dose CT images were reconstructed with FBP, using a reconstructed slice thickness of 0.625 mm. Two observers evaluated the image quality of abnormal lung and mediastinal structures on a 5-point scale (Score 5 = excellent and score 1 = non-diagnostic). The objective image noise was also measured as the standard deviation of CT intensity in the descending aorta. The image quality score of enlarged mediastinal lymph nodes on low-dose MBIR CT (4.7 ± 0.5) was significantly improved in comparison with low-dose FBP and ASIR CT (3.0 ± 0.5, p = 0.004; 4.0 ± 0.5, p = 0.02, respectively), and was nearly identical to the score of standard-dose FBP image (4.8 ± 0.4, p = 0.66). Concerning decreased lung attenuation (bulla, emphysema, or cyst), the image quality score on low-dose MBIR CT (4.9 ± 0.2) was slightly better compared to low-dose FBP and ASIR CT (4.5 ± 0.6, p = 0.01; 4.6 ± 0.5, p = 0.01, respectively). There were no significant differences in image quality scores of visualization of consolidation or mass, ground-glass attenuation, or reticular opacity among low- and standard-dose CT series. Image noise with low-dose MBIR CT (11.6 ± 1.0 Hounsfield units (HU)) were significantly lower than with low-dose ASIR (21.1 ± 2.6 HU, p < 0.0005), low-dose FBP CT (30.9 ± 3.9 HU, p < 0.0005), and standard-dose FBP CT (16.6 ± 2.3 HU, p < 0.0005). MBIR shows greater potential than ASIR for providing diagnostically acceptable low-dose CT without compromising image quality. With radiation dose reduction of >70%, MBIR can provide equivalent lesion detectability of standard-dose FBP CT.

Evaluation of zinc oxide nanoparticles toxicity on marine algae chlorella vulgaris through flow cytometric, cytotoxicity and oxidative stress analysis.

PubMed

Suman, T Y; Radhika Rajasree, S R; Kirubagaran, R

2015-03-01

The increasing industrial use of nanomaterials during the last decades poses a potential threat to the environment and in particular to organisms living in the aquatic environment. In the present study, the toxicity of zinc oxide nanoparticles (ZnO NPs) was investigated in Marine algae Chlorella vulgaris (C. vulgaris). High zinc dissociation from ZnONPs, releasing ionic zinc in seawater, is a potential route for zinc assimilation and ZnONPs toxicity. To examine the mechanism of toxicity, C. vulgaris were treated with 50mg/L, 100mg/L, 200mg/L and 300 mg/L ZnO NPs for 24h and 72h. The detailed cytotoxicity assay showed a substantial reduction in the viability dependent on dose and exposure. Further, flow cytometry revealed the significant reduction in C. vulgaris viable cells to higher ZnO NPs. Significant reductions in LDH level were noted for ZnO NPs at 300 mg/L concentration. The activity of antioxidant enzyme superoxide dismutase (SOD) significantly increased in the C. vulgaris exposed to 200mg/L and 300 mg/L ZnO NPs. The content of non-enzymatic antioxidant glutathione (GSH) significantly decreased in the groups with a ZnO NPs concentration of higher than 100mg/L. The level of lipid peroxidation (LPO) was found to increase as the ZnO NPs dose increased. The FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells. The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (FESEM and CM). Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy of a Radiation Absorbing Shield in Reducing Dose to the Interventionalist During Peripheral Endovascular Procedures: A Single Centre Pilot Study

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

Power, S.; Mirza, M.; Thakorlal, A.

PurposeThis prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures.Materials and MethodsA commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used tomore » measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated.ResultsTLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142).ConclusionInitial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator’s body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.« less

Differences in rates of decrease of environmental radiation dose rates by ground surface property in Fukushima City after the Fukushima Daiichi nuclear power plant accident.

PubMed

Kakamu, Takeyasu; Kanda, Hideyuki; Tsuji, Masayoshi; Kobayashi, Daisuke; Miyake, Masao; Hayakawa, Takehito; Katsuda, Shin-ichiro; Mori, Yayoi; Okouchi, Toshiyasu; Hazama, Akihiro; Fukushima, Tetsuhito

2013-01-01

After the Great East Japan Earthquake on 11 March 2011, the environmental radiation dose in Fukushima City increased. On 11 April, 1 mo after the earthquake, the environmental radiation dose rate at various surfaces in the same area differed greatly by surface property. Environmental radiation measurements continue in order to determine the estimated time to 50% reduction in environmental radiation dose rates by surface property in order to make suggestions for decontamination in Fukushima. The measurements were carried out from 11 April to 11 November 2011. Forty-eight (48) measurement points were selected, including four kinds of ground surface properties: grass (13), soil (5), artificial turf (7), and asphalt (23). Environmental radiation dose rate was measured at heights of 100 cm above the ground surface. Time to 50% reduction of environmental radiation dose rates was estimated for each ground surface property. Radiation dose rates on 11 November had decreased significantly compared with those on 11 April for all surface properties. Artificial turf showed the longest time to 50% reduction (544.32 d, standard error: 96.86), and soil showed the shortest (213.20 d, standard error: 35.88). The authors found the environmental radiation dose rate on artificial materials to have a longer 50% reduction time than that on natural materials. These results contribute to determining an order of priority for decontamination after nuclear disasters.

Evaluation of entrance surface air kerma in pediatric chest radiography

NASA Astrophysics Data System (ADS)

Porto, L.; Lunelli, N.; Paschuk, S.; Oliveira, A.; Ferreira, J. L.; Schelin, H.; Miguel, C.; Denyak, V.; Kmiecik, C.; Tilly, J.; Khoury, H.

2014-11-01

The objective of this study was to evaluate the entrance surface air kerma in pediatric chest radiography. An evaluation of 301 radiographical examinations in anterior-posterior (AP) and posterior-anterior (PA) (166 examinations) and lateral (LAT) (135 examinations) projections was performed. The analyses were performed on patients grouped by age; the groups included ages 0-1 y, 1-5 y, 5-10 y, and 10-15 y. The entrance surface air kerma was determined with DoseCal software (Radiological Protection Center of Saint George's Hospital, London) and thermoluminescent dosimeters. Two different exposure techniques were compared. The doses received by patients who had undergone LAT examinations were 40% higher, on average, those in AP/PA examinations because of the difference in tube voltage. A large high-dose “tail” was observed for children up to 5 y old. An increase in tube potential and corresponding decrease in current lead to a significant dose reduction. The difference between the average dose values for different age ranges was not practically observed, implying that the exposure techniques are still not optimal. Exposure doses received using the higher tube voltage and lower current-time product correspond to the international diagnostic reference levels.

Model-based iterative reconstruction for reduction of radiation dose in abdominopelvic CT: comparison to adaptive statistical iterative reconstruction.

PubMed

Yasaka, Koichiro; Katsura, Masaki; Akahane, Masaaki; Sato, Jiro; Matsuda, Izuru; Ohtomo, Kuni

2013-12-01

To evaluate dose reduction and image quality of abdominopelvic computed tomography (CT) reconstructed with model-based iterative reconstruction (MBIR) compared to adaptive statistical iterative reconstruction (ASIR). In this prospective study, 85 patients underwent referential-, low-, and ultralow-dose unenhanced abdominopelvic CT. Images were reconstructed with ASIR for low-dose (L-ASIR) and ultralow-dose CT (UL-ASIR), and with MBIR for ultralow-dose CT (UL-MBIR). Image noise was measured in the abdominal aorta and iliopsoas muscle. Subjective image analyses and a lesion detection study (adrenal nodules) were conducted by two blinded radiologists. A reference standard was established by a consensus panel of two different radiologists using referential-dose CT reconstructed with filtered back projection. Compared to low-dose CT, there was a 63% decrease in dose-length product with ultralow-dose CT. UL-MBIR had significantly lower image noise than L-ASIR and UL-ASIR (all p<0.01). UL-MBIR was significantly better for subjective image noise and streak artifacts than L-ASIR and UL-ASIR (all p<0.01). There were no significant differences between UL-MBIR and L-ASIR in diagnostic acceptability (p>0.65), or diagnostic performance for adrenal nodules (p>0.87). MBIR significantly improves image noise and streak artifacts compared to ASIR, and can achieve radiation dose reduction without severely compromising image quality.

Genetic damage induced by a food coloring dye (sunset yellow) on meristematic cells of Brassica campestris L.

PubMed

Dwivedi, Kshama; Kumar, Girjesh

2015-01-01

We have performed the present piece of work to evaluate the effect of synthetic food coloring azo dye (sunset yellow) on actively dividing root tip cells of Brassica campestris L. Three doses of azo dye were administered for the treatment of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration along with control. Mitotic analysis clearly revealed the azo dye induced endpoint deviation like reduction in the frequency of normal divisions in a dose dependent manner. Mitotic divisions in the control sets were found to be perfectly normal while dose based reduction in MI was registered in the treated sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at various stages of cell cycle such as stickiness of chromosomes, micronuclei formation, precocious migration of chromosome, unorientation, forward movement of chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes was present in the highest frequency followed by partial genome elimination as micronuclei. The present study suggests that extensive use of synthetic dye should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus, there is an urgent need to assess potential hazardous effects of these dyes on other test systems like human and nonhuman biota for better scrutiny.

Genetic Damage Induced by a Food Coloring Dye (Sunset Yellow) on Meristematic Cells of Brassica campestris L.

PubMed Central

Dwivedi, Kshama; Kumar, Girjesh

2015-01-01

We have performed the present piece of work to evaluate the effect of synthetic food coloring azo dye (sunset yellow) on actively dividing root tip cells of Brassica campestris L. Three doses of azo dye were administered for the treatment of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration along with control. Mitotic analysis clearly revealed the azo dye induced endpoint deviation like reduction in the frequency of normal divisions in a dose dependent manner. Mitotic divisions in the control sets were found to be perfectly normal while dose based reduction in MI was registered in the treated sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at various stages of cell cycle such as stickiness of chromosomes, micronuclei formation, precocious migration of chromosome, unorientation, forward movement of chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes was present in the highest frequency followed by partial genome elimination as micronuclei. The present study suggests that extensive use of synthetic dye should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus, there is an urgent need to assess potential hazardous effects of these dyes on other test systems like human and nonhuman biota for better scrutiny. PMID:25954313

WE-AB-202-01: Evaluating the Toxicity Reduction with CT-Ventilation Functional Avoidance Radiation Therapy

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

Vinogradskiy, Y; Miyasaka, Y; Kadoya, N

Purpose: CT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Studies have proposed to use 4DCT-ventilation imaging for functional avoidance radiotherapy which implies designing treatment plans to spare functional portions of the lung. Although retrospective studies have been performed to evaluate the dosimetric gains to functional lung; no work has been done to translate the dosimetric gains to an improvement in pulmonary toxicity. The purpose of our work was to evaluate the potential reduction in toxicity for 4DCT-ventilation based functional avoidance. Methods: 70 lung cancer patients with 4DCT imaging were used for the study. CT-ventilationmore » maps were calculated using the patient’s 4DCT, deformable image registrations, and a density-change-based algorithm. Radiation pneumonitis was graded using imaging and clinical information. Log-likelihood methods were used to fit a normal-tissue-complication-probability (NTCP) model predicting grade 2+ radiation pneumonitis as a function of doses (mean and V20) to functional lung (>15% ventilation). For 20 patients a functional plan was generated that reduced dose to functional lung while meeting RTOG 0617-based constraints. The NTCP model was applied to the functional plan to determine the reduction in toxicity with functional planning Results: The mean dose to functional lung was 16.8 and 17.7 Gy with the functional and clinical plans respectively. The corresponding grade 2+ pneumonitis probability was 26.9% with the clinically-used plan and 24.6% with the functional plan (8.5% reduction). The V20-based grade 2+ pneumonitis probability was 23.7% with the clinically-used plan and reduced to 19.6% with the functional plan (20.9% reduction). Conclusion: Our results revealed a reduction of 9–20% in complication probability with functional planning. To our knowledge this is the first study to apply complication probability to convert dosimetric results to toxicity improvement. The results presented in the current work provide seminal data for prospective clinical trials in functional avoidance. YV discloses funding from State of Colorado. TY discloses National Lung Cancer Partnership; Young Investigator Research grant.« less

CT Fluoroscopy Shielding: Decreases in Scattered Radiation for the Patient and Operator

PubMed Central

Neeman, Ziv; Dromi, Sergio A.; Sarin, Shawn; Wood, Bradford J.

2008-01-01

PURPOSE High-radiation exposure occurs during computed tomographic (CT) fluoroscopy. Patient and operator doses during thoracic and abdominal interventional procedures were studied in the present experiment, and a novel shielding device to reduce exposure to the patient and operator was evaluated. MATERIALS AND METHODS With a 16-slice CT scanner in CT fluoroscopy mode (120 kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The shielding was composed of tungsten antimony in the form of a lightweight polymer sheet. Doses to the patient were measured with and without shielding for thoracic and abdominal procedures. Doses to the operator were recorded with and without phantom, gantry, and table shielding in place. Double-layer lead-free gloves were used by the operator during the procedures. RESULTS Tungsten antimony shielding adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the operator’s torso, gonads, and hands, respectively. The use of double-layer lead-free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS Methods to reduce exposure during CT fluoroscopy are effective and should be searched for. Significant reduction in radiation doses to the patient and operator can be accomplished with tungsten antimony shielding. PMID:17185699

Effects of dose reduction on bone strength prediction using finite element analysis

NASA Astrophysics Data System (ADS)

Anitha, D.; Subburaj, Karupppasamy; Mei, Kai; Kopp, Felix K.; Foehr, Peter; Noel, Peter B.; Kirschke, Jan S.; Baum, Thomas

2016-12-01

This study aimed to evaluate the effect of dose reduction, by means of tube exposure reduction, on bone strength prediction from finite-element (FE) analysis. Fresh thoracic mid-vertebrae specimens (n = 11) were imaged, using multi-detector computed tomography (MDCT), at different intensities of X-ray tube exposures (80, 150, 220 and 500 mAs). Bone mineral density (BMD) was estimated from the mid-slice of each specimen from MDCT images. Differences in image quality and geometry of each specimen were measured. FE analysis was performed on all specimens to predict fracture load. Paired t-tests were used to compare the results obtained, using the highest CT dose (500 mAs) as reference. Dose reduction had no significant impact on FE-predicted fracture loads, with significant correlations obtained with reference to 500 mAs, for 80 mAs (R2  = 0.997, p < 0.001), 150 mAs (R2 = 0.998, p < 0.001) and 220 mAs (R2 = 0.987, p < 0.001). There were no significant differences in volume quantification between the different doses examined. CT imaging radiation dose could be reduced substantially to 64% with no impact on strength estimates obtained from FE analysis. Reduced CT dose will enable early diagnosis and advanced monitoring of osteoporosis and associated fracture risk.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis.

PubMed

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-05-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Effects of the mosquito larvicide GB-1111 on red-winged blackbird embryos

USGS Publications Warehouse

Albers, P.H.; Hoffman, D.J.; Buscemi, D.M.; Melancon, M.J.

2003-01-01

Golden Bear Oil (GB-111 I; legal trade name for GB-1313) is a petroleum distillate that is used in the United States and other countries as a larvicide for mosquito suppression. As part of a multi-species evaluation of the potential effects of GB-1111 on birds, red-winged blackbird eggs were collected, artificially incubated, and treated with one of five amounts of GB-1111 varying from 0 to 10 times the expected exposure from a spray application of the maximum recommended amount (X=47 l/ha, 5 gal/ac). The application of 10 X caused a significant reduction in hatching success. A dose-related reduction of hepatic microsomal mono-oxygenase activity (EROD) was detected. Among body weights, skeletal measurements, and age at death, only crownrump length was different among experimental groups. Overall, the potential hazard to embryos of a representative wetland passerine appears minimal until the application rate exceeds 3 X.

Sugar substitutes: their energy values, bulk characteristics, and potential health benefits.

PubMed

Levin, G V; Zehner, L R; Saunders, J P; Beadle, J R

1995-11-01

Restriction of dietary energy extends life and reduces incidences of disease in animals. These benefits would likely extend to humans. However, diet restriction in animals imposes reductions of 30-50% in food intake, which is probably unacceptable to humans. Low-energy sweeteners used in beverages offer minor reductions in energy intake. However, they lack the bulk required for baked goods and other sugar-rich foods. Full-bulk sweeteners providing about one-half the energy of sugar are under development for such uses. Laxation limits their acceptable dose. Even within such limitations, they can help achieve the health benefits for humans indicated by diet restriction. D-Tagatose, a new candidate sweetener, is nearly as sweet as sucrose and has the bulk of sucrose, yet provides zero available energy. We discuss its potential contribution to human diet restriction along with its specific effect in delaying the aging effects of glycosylation.

Lowering the glycemic index of white bread using a white bean extract

PubMed Central

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Preuss, Harry G

2009-01-01

Background Phase 2® is a dietary supplement derived from the common white kidney bean (Phaseolus vulgaris). Phase 2 has been shown to inhibit alpha-amylase, the complex carbohydrate digesting enzyme, in vitro. The inhibition of alpha-amylase may result in the lowering of the effective Glycemic Index (GI) of certain foods. The objective of this study was to determine whether the addition of Phase 2 would lower the GI of a commercially available high glycemic food (white bread). Methods An open-label 6-arm crossover study was conducted with 13 randomized subjects. Standardized GI testing was performed on white bread with and without the addition of Phase 2 in capsule and powder form, each in dosages of 1500 mg, 2000 mg, and 3000 mg. Statistical analysis was performed by one-way ANOVA of all seven treatment groups using unadjusted multiple comparisons (t tests) to the white bread control. Results For the capsule formulation, the 1500 mg dose had no effect on the GI and the 2000 mg and 3000 mg capsule doses caused insignificant reductions in GI. For the powder, the 1500 mg and 2000 mg doses caused insignificant reductions in the GI, and the 3000 mg dose had a significant effect (-20.23 or 34.11%, p = 0.023) Conclusion Phase 2 white bean extract appears to be a novel and potentially effective method for reducing the GI of existing foods without modifying their ingredient profile. Trial Registration Trial Registration: ISRCTN50347345 PMID:19860922

Lowering the glycemic index of white bread using a white bean extract.

PubMed

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Preuss, Harry G

2009-10-28

Phase 2((R)) is a dietary supplement derived from the common white kidney bean (Phaseolus vulgaris). Phase 2 has been shown to inhibit alpha-amylase, the complex carbohydrate digesting enzyme, in vitro. The inhibition of alpha-amylase may result in the lowering of the effective Glycemic Index (GI) of certain foods. The objective of this study was to determine whether the addition of Phase 2 would lower the GI of a commercially available high glycemic food (white bread). An open-label 6-arm crossover study was conducted with 13 randomized subjects. Standardized GI testing was performed on white bread with and without the addition of Phase 2 in capsule and powder form, each in dosages of 1500 mg, 2000 mg, and 3000 mg. Statistical analysis was performed by one-way ANOVA of all seven treatment groups using unadjusted multiple comparisons (t tests) to the white bread control. For the capsule formulation, the 1500 mg dose had no effect on the GI and the 2000 mg and 3000 mg capsule doses caused insignificant reductions in GI. For the powder, the 1500 mg and 2000 mg doses caused insignificant reductions in the GI, and the 3000 mg dose had a significant effect (-20.23 or 34.11%, p = 0.023) Phase 2 white bean extract appears to be a novel and potentially effective method for reducing the GI of existing foods without modifying their ingredient profile. Trial Registration: ISRCTN50347345.

Method to monitor HC-SCR catalyst NOx reduction performance for lean exhaust applications

DOEpatents

Viola, Michael B [Macomb Township, MI; Schmieg, Steven J [Troy, MI; Sloane, Thompson M [Oxford, MI; Hilden, David L [Shelby Township, MI; Mulawa, Patricia A [Clinton Township, MI; Lee, Jong H [Rochester Hills, MI; Cheng, Shi-Wai S [Troy, MI

2012-05-29

A method for initiating a regeneration mode in selective catalytic reduction device utilizing hydrocarbons as a reductant includes monitoring a temperature within the aftertreatment system, monitoring a fuel dosing rate to the selective catalytic reduction device, monitoring an initial conversion efficiency, selecting a determined equation to estimate changes in a conversion efficiency of the selective catalytic reduction device based upon the monitored temperature and the monitored fuel dosing rate, estimating changes in the conversion efficiency based upon the determined equation and the initial conversion efficiency, and initiating a regeneration mode for the selective catalytic reduction device based upon the estimated changes in conversion efficiency.

[Therapy of arrhythmia induced by myocardial ischemia. Association of L-carnitine, propafenone and mexiletine].

PubMed

Mondillo, S; Faglia, S; D'Aprile, N; Mangiacotti, L; Campolo, M A; Agricola, E; Palazzuoli, V

1995-12-01

To assess the anti-arrythmic effect of L-carnitina, propafenone and mexiletine, we tested the drugs in 50 patients with effort angina and ventricular ectopic beats (VEB). The patients were randomized in 5 groups: Group A: was treated with oral L-carnitine at the dose of 2 g x 3 for two weeks. Group B: oral propafenone at the dose of 300 mg x 3 for two weeks. Group C: as group B+L-carnitine+g x 3 at the second weeks. Group D: oral mexiletine at the dose of 200 mg x 3 for two weeks. Group E: as group D+L-carnitine 2 gr x 3 at the second week. After 7 and 14 days of treatment, in all patients an Holter examination was performed. Our results show that L-carnitine exerts a significant reduction of the VEB and its administration potentiates the anti-arrythmic effect of propafenone and mexiletine.

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

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

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

PubMed

Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-06

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

Dose reduction of up to 89% while maintaining image quality in cardiovascular CT achieved with prospective ECG gating

NASA Astrophysics Data System (ADS)

Londt, John H.; Shreter, Uri; Vass, Melissa; Hsieh, Jiang; Ge, Zhanyu; Adda, Olivier; Dowe, David A.; Sabllayrolles, Jean-Louis

2007-03-01

We present the results of dose and image quality performance evaluation of a novel, prospective ECG-gated Coronary CT Angiography acquisition mode (SnapShot Pulse, LightSpeed VCT-XT scanner, GE Healthcare, Waukesha, WI), and compare it to conventional retrospective ECG gated helical acquisition in clinical and phantom studies. Image quality phantoms were used to measure noise, slice sensitivity profile, in-plane resolution, low contrast detectability and dose, using the two acquisition modes. Clinical image quality and diagnostic confidence were evaluated in a study of 31 patients scanned with the two acquisition modes. Radiation dose reduction in clinical practice was evaluated by tracking 120 consecutive patients scanned with the prospectively gated scan mode. In the phantom measurements, the prospectively gated mode resulted in equivalent or better image quality measures at dose reductions of up to 89% compared to non-ECG modulated conventional helical scans. In the clinical study, image quality was rated excellent by expert radiologist reviewing the cases, with pathology being identical using the two acquisition modes. The average dose to patients in the clinical practice study was 5.6 mSv, representing 50% reduction compared to a similar patient population scanned with the conventional helical mode.

Reduced Sodium Transport With Nasal Administration of the Prostasin Inhibitor Camostat in Subjects With Cystic Fibrosis

PubMed Central

Reeves, Ginger; Hathorne, Heather; Solomon, G. Martin; Abbi, Smita; Renard, Didier; Lock, Ruth; Zhou, Ping; Danahay, Henry; Clancy, John P.; Waltz, David A.

2013-01-01

Background: Prostasin, a trypsin-like serine protease, is a channel-activating protease and major regulator of epithelial sodium channel-mediated sodium absorption. Its direct inhibition by camostat represents a potential approach to inhibiting sodium transport in cystic fibrosis (CF). Methods: To determine whether a topical formulation of camostat represents an efficacious and tolerable approach to reducing Na+ transport in the CF airway, we conducted a two-part randomized, double-blind, placebo-controlled, crossover, ascending single-dose study to evaluate the pharmacodynamics, safety, and pharmacokinetics of camostat administered through a nasal spray pump in subjects with CF. Nasal potential difference (PD) was measured before and after treatment, and safety and pharmacokinetics were assessed by a standardized approach. Results: In part 1, nine subjects were enrolled, and six completed crossover dosing at the maximally tolerated dose. The change in maximal (most polarizing) basal PD 2 h following administration of camostat was +13.1 mV (1.6-mg dose group) compared with −8.6 mV following placebo (P < .005). Intrasubject change in Ringer and amiloride-sensitive PDs exhibited similar and consistent responses. Bayesian analysis in an additional six subjects in part 2 estimated a dose of 18 μg/mL to provide 50% of the maximum effect. There was no significant change in chloride transport or total nasal symptom score, nasal examination rating, and laboratory parameters. Conclusions: This study establishes the proof of concept that a reduction in sodium transport in the human CF airway can be achieved through inhibition of prostasin activity, identifying a potential therapeutic target in the disease. Trial registration: ClinicalTrials.gov; No.: NCT00506792; URL: www.clinicaltrials.gov PMID:23412700

Evaluation of the Effects of Sativex (THC BDS: CBD BDS) on Inhibition of Spasticity in a Chronic Relapsing Experimental Allergic Autoimmune Encephalomyelitis: A Model of Multiple Sclerosis

PubMed Central

Hilliard, A.; Stott, C.; Wright, S.; Guy, G.; Pryce, G.; Al-Izki, S.; Bolton, C.; Giovannoni, G.

2012-01-01

This study investigated the antispasticity potential of Sativex in mice. Chronic relapsing experimental allergic encephalomyelitis was induced in adult ABH mice resulting in hind limb spasticity development. Vehicle, Sativex, and baclofen (as a positive control) were injected intravenously and the “stiffness” of limbs assessed by the resistance force against hind limb flexion. Vehicle alone caused no significant change in spasticity. Baclofen (5 mg/kg) induced approximately a 40% peak reduction in spasticity. Sativex dose dependently reduced spasticity; 5 mg/kg THC + 5 mg/kg CBD induced approximately a 20% peak reduction; 10 mg/kg THC + 10 mg/kg CBD produced approximately a 40% peak reduction in spasticity. Sativex has the potential to reduce spasticity in an experimental mouse model of multiple sclerosis (MS). Baclofen reduced spasticity and served as a positive control. Sativex (10 mg/kg) was just as effective as baclofen, providing supportive evidence for Sativex use in the treatment of spasticity in MS. PMID:22928118

Detection and characterization of lesions on low-radiation-dose abdominal CT images postprocessed with noise reduction filters.

PubMed

Kalra, Mannudeep K; Maher, Michael M; Blake, Michael A; Lucey, Brian C; Karau, Kelly; Toth, Thomas L; Avinash, Gopal; Halpern, Elkan F; Saini, Sanjay

2004-09-01

To assess the effect of noise reduction filters on detection and characterization of lesions on low-radiation-dose abdominal computed tomographic (CT) images. Low-dose CT images of abdominal lesions in 19 consecutive patients (11 women, eight men; age range, 32-78 years) were obtained at reduced tube currents (120-144 mAs). These baseline low-dose CT images were postprocessed with six noise reduction filters; the resulting postprocessed images were then randomly assorted with baseline images. Three radiologists performed independent evaluation of randomized images for presence, number, margins, attenuation, conspicuity, calcification, and enhancement of lesions, as well as image noise. Side-by-side comparison of baseline images with postprocessed images was performed by using a five-point scale for assessing lesion conspicuity and margins, image noise, beam hardening, and diagnostic acceptability. Quantitative noise and contrast-to-noise ratio were obtained for all liver lesions. Statistical analysis was performed by using the Wilcoxon signed rank test, Student t test, and kappa test of agreement. Significant reduction of noise was observed in images postprocessed with filter F compared with the noise in baseline nonfiltered images (P =.004). Although the number of lesions seen on baseline images and that seen on postprocessed images were identical, lesions were less conspicuous on postprocessed images than on baseline images. A decrease in quantitative image noise and contrast-to-noise ratio for liver lesions was noted with all noise reduction filters. There was good interobserver agreement (kappa = 0.7). Although the use of currently available noise reduction filters improves image noise and ameliorates beam-hardening artifacts at low-dose CT, such filters are limited by a compromise in lesion conspicuity and appearance in comparison with lesion conspicuity and appearance on baseline low-dose CT images. Copyright RSNA, 2004

Tumor control probability reduction in gated radiotherapy of non-small cell lung cancers: a feasibility study.

PubMed

Siochi, R Alfredo; Kim, Yusung; Bhatia, Sudershan

2014-10-16

We studied the feasibility of evaluating tumor control probability (TCP) reductions for tumor motion beyond planned gated radiotherapy margins. Tumor motion was determined from cone-beam CT projections acquired for patient setup, intrafraction respiratory traces, and 4D CTs for five non-small cell lung cancer (NSCLC) patients treated with gated radiotherapy. Tumors were subdivided into 1 mm sections whose positions and doses were determined for each beam-on time point. (The dose calculation model was verified with motion phantom measurements.) The calculated dose distributions were used to generate the treatment TCPs for each patient. The plan TCPs were calculated from the treatment planning dose distributions. The treatment TCPs were compared to the plan TCPs for various models and parameters. Calculated doses matched phantom measurements within 0.3% for up to 3 cm of motion. TCP reductions for excess motion greater than 5mm ranged from 1.7% to 11.9%, depending on model parameters, and were as high as 48.6% for model parameters that simulated an individual patient. Repeating the worst case motion for all fractions increased TCP reductions by a factor of 2 to 3, while hypofractionation decreased these reductions by as much as a factor of 3. Treatment motion exceeding gating margins by more than 5 mm can lead to considerable TCP reductions. Appropriate margins for excess motion are recommended, unless applying daily tumor motion verification and adjusting thegating window.

Efficacy and toxicological studies of cremophor EL free alternative paclitaxel formulation.

PubMed

Utreja, Puneet; Jain, Subheet; Yadav, Subodh; Khandhuja, K L; Tiwary, A K

2011-11-01

In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated. Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect™ 96-well cell transformation assay. In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation. The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.

Impact of changes in blood pressure during the treatment of acute decompensated heart failure on renal and clinical outcomes†

PubMed Central

Testani, Jeffrey M.; Coca, Steven G.; McCauley, Brian D.; Shannon, Richard P.; Kimmel, Stephen E.

2011-01-01

Aims One of the primary determinants of blood flow in regional vascular beds is perfusion pressure. Our aim was to investigate if reduction in blood pressure during the treatment of decompensated heart failure would be associated with worsening renal function (WRF). Our secondary aim was to evaluate the prognostic significance of this potentially treatment-induced form of WRF. Methods and results Subjects included in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial limited data were studied (386 patients). Reduction in systolic blood pressure (SBP) was greater in patients experiencing WRF (−10.3 ± 18.5 vs. −2.8 ± 16.0 mmHg, P < 0.001) with larger reductions associated with greater odds for WRF (odds ratio = 1.3 per 10 mmHg reduction, P < 0.001). Systolic blood pressure reduction (relative change > median) was associated with greater doses of in-hospital oral vasodilators (P ≤ 0.017), thiazide diuretic use (P = 0.035), and greater weight reduction (P = 0.023). In patients with SBP-reduction, WRF was not associated with worsened survival [adjusted hazard ratio (HR) = 0.76, P = 0.58]. However, in patients without SBP-reduction, WRF was strongly associated with increased mortality (adjusted HR = 5.3, P < 0.001, P interaction = 0.001). Conclusion During the treatment of decompensated heart failure, significant blood pressure reduction is strongly associated with WRF. However, WRF that occurs in the setting of SBP-reduction is not associated with an adverse prognosis, whereas WRF in the absence of this provocation is strongly associated with increased mortality. These data suggest that WRF may represent the final common pathway of several mechanistically distinct processes, each with potentially different prognostic implications. PMID:21693504

Impact of changes in blood pressure during the treatment of acute decompensated heart failure on renal and clinical outcomes.

PubMed

Testani, Jeffrey M; Coca, Steven G; McCauley, Brian D; Shannon, Richard P; Kimmel, Stephen E

2011-08-01

One of the primary determinants of blood flow in regional vascular beds is perfusion pressure. Our aim was to investigate if reduction in blood pressure during the treatment of decompensated heart failure would be associated with worsening renal function (WRF). Our secondary aim was to evaluate the prognostic significance of this potentially treatment-induced form of WRF. Subjects included in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial limited data were studied (386 patients). Reduction in systolic blood pressure (SBP) was greater in patients experiencing WRF (-10.3 ± 18.5 vs. -2.8 ± 16.0 mmHg, P < 0.001) with larger reductions associated with greater odds for WRF (odds ratio = 1.3 per 10 mmHg reduction, P < 0.001). Systolic blood pressure reduction (relative change > median) was associated with greater doses of in-hospital oral vasodilators (P ≤ 0.017), thiazide diuretic use (P = 0.035), and greater weight reduction (P = 0.023). In patients with SBP-reduction, WRF was not associated with worsened survival [adjusted hazard ratio (HR) = 0.76, P = 0.58]. However, in patients without SBP-reduction, WRF was strongly associated with increased mortality (adjusted HR = 5.3, P < 0.001, P interaction = 0.001). During the treatment of decompensated heart failure, significant blood pressure reduction is strongly associated with WRF. However, WRF that occurs in the setting of SBP-reduction is not associated with an adverse prognosis, whereas WRF in the absence of this provocation is strongly associated with increased mortality. These data suggest that WRF may represent the final common pathway of several mechanistically distinct processes, each with potentially different prognostic implications.

Image guidance doses delivered during radiotherapy: Quantification, management, and reduction: Report of the AAPM Therapy Physics Committee Task Group 180.

PubMed

Ding, George X; Alaei, Parham; Curran, Bruce; Flynn, Ryan; Gossman, Michael; Mackie, T Rock; Miften, Moyed; Morin, Richard; Xu, X George; Zhu, Timothy C

2018-05-01

With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient. © 2018 American Association of Physicists in Medicine.

Using the benchmark dose (BMD) methodology to determine an appropriate reduction of certain ingredients in food products.

PubMed

Bi, Jian

2010-01-01

As the desire to promote health increases, reductions of certain ingredients, for example, sodium, sugar, and fat in food products, are widely requested. However, the reduction is not risk free in sensory and marketing aspects. Over reduction may change the taste and influence the flavor of a product and lead to a decrease in consumer's overall liking or purchase intent for the product. This article uses the benchmark dose (BMD) methodology to determine an appropriate reduction. Calculations of BMD and one-sided lower confidence limit of BMD are illustrated. The article also discusses how to calculate BMD and BMDL for over dispersed binary data in replicated testing based on a corrected beta-binomial model. USEPA Benchmark Dose Software (BMDS) were used and S-Plus programs were developed. The method discussed in the article is originally used to determine an appropriate reduction of certain ingredients, for example, sodium, sugar, and fat in food products, considering both health reason and sensory or marketing risk.

Occupational radiation dose to eyes from interventional radiology procedures in light of the new eye lens dose limit from the International Commission on Radiological Protection

PubMed Central

Walsh, C; Gallagher, A; Dowling, A; Guiney, M; Ryan, J M; McEniff, N; O'Reilly, G

2015-01-01

Objective: In 2011, the International Commission on Radiological Protection (ICRP) recommended a substantial reduction in the equivalent dose limit for the lens of the eye, in line with a reduced threshold of absorbed dose for radiation-induced cataracts. This is of particular relevance in interventional radiology (IR) where it is well established that staff doses can be significant, however, there is a lack of data on IR eye doses in terms of Hp(3). Hp(3) is the personal dose equivalent at a depth of 3 mm in soft tissue and is used for measuring lens dose. We aimed to obtain a reliable estimate of eye dose to IR operators. Methods: Lens doses were measured for four interventional radiologists over a 3-month period using dosemeters specifically designed to measure Hp(3). Results: Based on their typical workloads, two of the four interventional radiologists would exceed the new ICRP dose limit with annual estimated doses of 31 and 45 mSv to their left eye. These results are for an “unprotected” eye, and for IR staff who routinely wear lead glasses, the dose beneath the glasses is likely to be significantly lower. Staff eye dose normalized to patient kerma–area product and eye dose per procedure have been included in the analysis. Conclusion: Eye doses to IR operators have been established using a dedicated Hp(3) dosemeter. Estimated annual doses have the potential to exceed the new ICRP limit. Advances in knowledge: We have estimated lens dose to interventional radiologists in terms of Hp(3) for the first time in an Irish hospital setting. PMID:25761211

In vivo antimalarial activity of crude extracts and solvent fractions of leaves of Strychnos mitis in Plasmodium berghei infected mice.

PubMed

Fentahun, Selamawit; Makonnen, Eyasu; Awas, Tesfaye; Giday, Mirutse

2017-01-05

Malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-Saharan Africa. Today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. Medicinal plants are the unquestionable source of effective antimalarials. The present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant Strychnos mitis in Plasmodium berghei infected mice. Standard procedures were employed to investigate acute toxicity and 4-day suppressive effect of crude aqueous and hydro-methanolic extracts of the leaves of Strychnos mitis against P. berghei in Swiss albino mice. Water, n-hexane and chloroform fractions, obtained from crude hydro-methanolic extract, were also tested for their suppressive effect against P. berghei. All crude extracts revealed no obvious acute toxicity in mice up to the highest dose administered (2000 mg/kg). All crude and solvent fractions of the leaves of Strychnos mitis inhibited parasitaemia significantly (p < 0.01). At the highest dose of 600 mg/kg, both aqueous and hydro-methanolic extracts demonstrated higher performance with 95.5 and 93.97% parasitaemia suppression, respectively. All doses of crude extracts and fractions of leaves of Strychnos mitis prolonged survival time of infected mice dose dependently. The highest two doses of the crude aqueous and hydro-methanolic extracts, and chloroform and aqueous fractions prevented weight loss in a dose dependent manner. Whereas, all doses of n-hexane fraction prevented loss of body weight but not in a dose dependent manner. The crude aqueous extract at the doses of 400 mg/kg and 600 mg/kg and hydro-methanolic extract at all dose levels significantly (p < 0.01) prevented packed cell volume reduction. Crude aqueous extract at a dose of 600 mg/kg and hydro-methanolic extract at all dose levels significantly prevented temperature reduction. Phytochemical screening of the crude aqueous and hydro-methanolic extracts revealed the presence of alkaloids, anthraquinones, glycosides, terpenoids, saponins, tannins and phenols. The results of this study provide support the traditional therapeutic use of Strychnos mitis for treatment of malaria. However, further in-depth study is needed to evaluate the potential of the plant towards the development of new antimalarial agent.

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988-1993: II. In vivo planning and dosimetry.

PubMed

Planskoy, B; Tapper, P D; Bedford, A M; Davis, F M

1996-11-01

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were with in +/- 5% of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of 19 +/- 6.0% (1 s.d.) and in the lungs (40 patients, five slices) of 9.2 +/- 2.85% (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior-posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an increase in treatment set-up times.

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study.

PubMed

Mc Menamin, Úna C; Cardwell, Chris R; Hughes, Carmel M; Murray, Liam J

2017-04-01

Preclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality. We identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality. Post-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use. In this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

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

Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.

2014-02-01

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analysesmore » were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.« less

Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia.

PubMed

Parkitny, Luke; Younger, Jarred

2017-04-18

Fibromyalgia (FM) is a complex, multi-symptom condition that predominantly affects women. The majority of those affected are unlikely to gain significant symptomatic control from the few treatments that are approved for FM. In this 10-week, single-blind, crossover trial we tested the immune effects of eight weeks of oral administration of low-dose naltrexone (LDN). We enrolled eight women with an average age of 46 years, symptom severity of 62 out of 100, and symptom duration of 14 years. We found that LDN was associated with reduced plasma concentrations of interleukin (IL)-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN)-α, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF). We also found a 15% reduction of FM-associated pain and an 18% reduction in overall symptoms. The findings of this pilot trial suggest that LDN treatment in fibromyalgia is associated with a reduction of several key pro-inflammatory cytokines and symptoms. The potential role of LDN as an atypical anti-inflammatory medication should be explored further.

Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides.

PubMed

Chen, Feng; Eckman, Elizabeth A; Eckman, Christopher B

2006-06-01

For millennia, ginseng and some of its components have been used to treat a wide variety of medical conditions, including age-related memory impairment. Because of its purported effects and apparently low rate of side effects, ginseng remains one of the top selling natural product remedies in the United States. Given its potential role for improving age-related memory impairments and its common use in China for the treatment of Alzheimer's disease-like symptoms, we analyzed the effects of commercially available preparations of ginseng on the accumulation of the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In this model system, ginseng treatment resulted in a significant reduction in the levels of Abeta in the conditioned medium. We next examined the effects of several compounds isolated from ginseng and found that certain ginsenosides lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3 having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we found that three of these isolated components, ginsenoside Rg1, Rg3, and RE, resulted in significant reductions in the amount of Abeta detected in the brains of animals after single oral doses of these agents. The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease.

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.

PubMed

Younger, Jarred; Noor, Noorulain; McCue, Rebecca; Mackey, Sean

2013-02-01

To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue. Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain. When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported. The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication. Copyright © 2013 by the American College of Rheumatology.

Elicitation of dopaminergic features of Parkinson's disease in C. elegans by monocrotophos, an organophosphorous insecticide.

PubMed

Ali, Shaheen Jafri; Rajini, Padmanabhan Sharda

2012-12-01

Positive correlations have been suggested between usage of pesticides and the incidence of Parkinson's disease (PD) through epidemiological as well as few experimental evidences. Organophosphorus insecticides (OPI), which are extensively used in agricultural and household insect control, have been the subject of increasing concern in the past decades due to their neurotoxic potential. However, very few studies have demonstrated the potentials of OPI to induce features of PD in model organisms. In the present study, Caenorhabditis elegans was selected as the model organism to evaluate the potential of monocrotophos (MCP), an OPI, to elicit dopaminergic features of Parkinson's disease in terms of dopamine content, basic movement and integrity of dopaminergic neurons along with its effect on acetylcholinesterase (AChE) activity and life span. All the responses elicited by MCP were compared with that elicited by 1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyridine (MPTP) in both N2 and BZ555 worms. N2 worms were exposed to varying concentrations of MCP (50, 100 and 200 μM) or MPTP (200, 300 and 400 μM) for 48 hours and locomotory rate, as measured by the number of body bends made in 20 seconds, was enumerated. Worms subjected to the same dose paradigms were also analyzed for the dopamine content by HPLC. The results indicated a significant reduction in the dopamine levels in the worms that were treated with MCP/MPTP and this correlated with the changes in locomotion compared to untreated worms. Worms treated with MCP also exhibited significant reduction in AChE activity. Both MPTP and MCP caused a marked reduction in life span in the worms. Transgenic worms (BZ555, which has GFP tagged to its 8 dopaminergic neurons) exposed to MCP and MPTP at the above concentrations showed a dose-dependent reduction in the number of green pixels in CEP and ADE neurons which also correlated with the neurodegeneration as visualized by decreased fluorescence in photomicrographs. Taken together, our data demonstrate that low levels of MCP elicits dopaminergic features of PD in C. elegans.

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: Implications for nicotine regulation policy

PubMed Central

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G.

2013-01-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. PMID:24201048

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.

Significant Radiation Dose Reduction in the Hybrid Operating Room Using a Novel X-ray Imaging Technology.

PubMed

van den Haak, R F F; Hamans, B C; Zuurmond, K; Verhoeven, B A N; Koning, O H J

2015-10-01

To prospectively quantify radiation dose change in aortoiliac endovascular procedures in the hybrid operating room (OR) for patients and medical staff with a novel X-ray imaging technology (ClarityIQ technology), and to assess whether procedure or fluoroscopy time or dose of iodinated contrast was affected. A prospective study including 138 patients was performed to compare radiation dose before and after installation of a novel X-ray imaging technology. Endovascular aneurysm repair (EVAR) was performed in 37 patients and an endovascular procedure for aortoiliac occlusive disease (AIOD) in 101. Patient radiation dose in air kerma (AK) and dose area product (DAP), patient demographics, and procedural data were recorded. Staff radiation dose was measured with real time personal dosimetry measurements. In both the EVAR and AIOD groups the reference system, ALX (AlluraXper FD20; Philips Healthcare, Best, the Netherlands), was compared with the upgraded X-ray system, CIQ (AlluraClarity FD20; Philips Healthcare). Procedure time, fluoroscopy time, and iodinated contrast dose were recorded. Patient radiation dose reduction in the EVAR group, in median AK, was 56% (ALX = 1,262.5 mGy; CIQ = 556.0 mGy [p < .01]); and in median DAP it was 57% (ALX = 224.4 Gycm(2) and CIQ = 95.8 Gycm(2) [p < .01]). Patient radiation dose reduction in the AIOD group, in median AK, was 76% (ALX = 1,011.0 mGy; CIQ = 248.0 mGy [p < .01]); and in median DAP it was 73% (ALX = 138.1 Gycm(2); CIQ = 38.0 Gycm(2) [p < .01]). Staff dose reduction in the EVAR group was 16% (ALX = 70.1 μSv; CIQ = 59.2 μSv [p = .43]) and in the AIOD group it was 69% (ALX = 96.2 μSv; CIQ = 30.1 μSv [p < .01]). There was no statistically significant difference between patient demographics, procedure time, fluoroscopy time, and iodinated contrast medium use in the two treatment groups before and after installation. A novel X-ray imaging technology in the hybrid OR suite resulted in a significant reduction of patient and staff radiation dose without affecting procedure length, fluoroscopy time, or use of contrast. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

CT dose reduction using Automatic Exposure Control and iterative reconstruction: A chest paediatric phantoms study.

PubMed

Greffier, Joël; Pereira, Fabricio; Macri, Francesco; Beregi, Jean-Paul; Larbi, Ahmed

2016-04-01

To evaluate the impact of Automatic Exposure Control (AEC) on radiation dose and image quality in paediatric chest scans (MDCT), with or without iterative reconstruction (IR). Three anthropomorphic phantoms representing children aged one, five and 10-year-old were explored using AEC system (CARE Dose 4D) with five modulation strength options. For each phantom, six acquisitions were carried out: one with fixed mAs (without AEC) and five each with different modulation strength. Raw data were reconstructed with Filtered Back Projection (FBP) and with two distinct levels of IR using soft and strong kernels. Dose reduction and image quality indices (Noise, SNR, CNR) were measured in lung and soft tissues. Noise Power Spectrum (NPS) was evaluated with a Catphan 600 phantom. The use of AEC produced a significant dose reduction (p<0.01) for all anthropomorphic sizes employed. According to the modulation strength applied, dose delivered was reduced from 43% to 91%. This pattern led to significantly increased noise (p<0.01) and reduced SNR and CNR (p<0.01). However, IR was able to improve these indices. The use of AEC/IR preserved image quality indices with a lower dose delivered. Doses were reduced from 39% to 58% for the one-year-old phantom, from 46% to 63% for the five-year-old phantom, and from 58% to 74% for the 10-year-old phantom. In addition, AEC/IR changed the patterns of NPS curves in amplitude and in spatial frequency. In chest paediatric MDCT, the use of AEC with IR allows one to obtain a significant dose reduction while maintaining constant image quality indices. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Can use of adaptive statistical iterative reconstruction reduce radiation dose in unenhanced head CT? An analysis of qualitative and quantitative image quality

PubMed Central

Heggen, Kristin Livelten; Pedersen, Hans Kristian; Andersen, Hilde Kjernlie; Martinsen, Anne Catrine T

2016-01-01

Background Iterative reconstruction can reduce image noise and thereby facilitate dose reduction. Purpose To evaluate qualitative and quantitative image quality for full dose and dose reduced head computed tomography (CT) protocols reconstructed using filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR). Material and Methods Fourteen patients undergoing follow-up head CT were included. All patients underwent full dose (FD) exam and subsequent 15% dose reduced (DR) exam, reconstructed using FBP and 30% ASIR. Qualitative image quality was assessed using visual grading characteristics. Quantitative image quality was assessed using ROI measurements in cerebrospinal fluid (CSF), white matter, peripheral and central gray matter. Additionally, quantitative image quality was measured in Catphan and vendor’s water phantom. Results There was no significant difference in qualitative image quality between FD FBP and DR ASIR. Comparing same scan FBP versus ASIR, a noise reduction of 28.6% in CSF and between −3.7 and 3.5% in brain parenchyma was observed. Comparing FD FBP versus DR ASIR, a noise reduction of 25.7% in CSF, and −7.5 and 6.3% in brain parenchyma was observed. Image contrast increased in ASIR reconstructions. Contrast-to-noise ratio was improved in DR ASIR compared to FD FBP. In phantoms, noise reduction was in the range of 3 to 28% with image content. Conclusion There was no significant difference in qualitative image quality between full dose FBP and dose reduced ASIR. CNR improved in DR ASIR compared to FD FBP mostly due to increased contrast, not reduced noise. Therefore, we recommend using caution if reducing dose and applying ASIR to maintain image quality. PMID:27583169

Can use of adaptive statistical iterative reconstruction reduce radiation dose in unenhanced head CT? An analysis of qualitative and quantitative image quality.

PubMed

Østerås, Bjørn Helge; Heggen, Kristin Livelten; Pedersen, Hans Kristian; Andersen, Hilde Kjernlie; Martinsen, Anne Catrine T

2016-08-01

Iterative reconstruction can reduce image noise and thereby facilitate dose reduction. To evaluate qualitative and quantitative image quality for full dose and dose reduced head computed tomography (CT) protocols reconstructed using filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR). Fourteen patients undergoing follow-up head CT were included. All patients underwent full dose (FD) exam and subsequent 15% dose reduced (DR) exam, reconstructed using FBP and 30% ASIR. Qualitative image quality was assessed using visual grading characteristics. Quantitative image quality was assessed using ROI measurements in cerebrospinal fluid (CSF), white matter, peripheral and central gray matter. Additionally, quantitative image quality was measured in Catphan and vendor's water phantom. There was no significant difference in qualitative image quality between FD FBP and DR ASIR. Comparing same scan FBP versus ASIR, a noise reduction of 28.6% in CSF and between -3.7 and 3.5% in brain parenchyma was observed. Comparing FD FBP versus DR ASIR, a noise reduction of 25.7% in CSF, and -7.5 and 6.3% in brain parenchyma was observed. Image contrast increased in ASIR reconstructions. Contrast-to-noise ratio was improved in DR ASIR compared to FD FBP. In phantoms, noise reduction was in the range of 3 to 28% with image content. There was no significant difference in qualitative image quality between full dose FBP and dose reduced ASIR. CNR improved in DR ASIR compared to FD FBP mostly due to increased contrast, not reduced noise. Therefore, we recommend using caution if reducing dose and applying ASIR to maintain image quality.

Influence of different treatment techniques on radiation dose to the LAD coronary artery

PubMed Central

Nieder, Carsten; Schill, Sabine; Kneschaurek, Peter; Molls, Michael

2007-01-01

Background The purpose of this proof-of-principle study was to test the ability of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation dose to the heart plus the left ventricle and a coronary artery. Radiation-induced heart disease might be a serious complication in long-term cancer survivors. Methods Planning CT scans from 6 female patients were available. They were part of a previous study of mediastinal IMRT for target volumes used in lymphoma treatment that included 8 patients and represent all cases where the left anterior descending coronary artery (LAD) could be contoured. We compared 6 MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7-field step-and-shoot IMRT technique and evaluated DVH's for several structures. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). Results IMRT maintained target volume coverage but resulted in better dose reduction to the heart, left ventricle and LAD than the other techniques. Selective dose reduction could be accomplished, although not to the degree initially attempted. The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6 patients, IMRT was the best technique with regard to heart sparing. Conclusion IMRT techniques are able to reduce the radiation dose to the heart. In addition to dose reduction to whole heart, individualised dose distributions can be created, which spare, e.g., one ventricle plus one of the coronary arteries. Certain patients with well-defined vessel pathology might profit from an approach of general heart sparing with further selective dose reduction, accounting for the individual aspects of pre-existing damage. PMID:17547777

Generative Adversarial Networks for Noise Reduction in Low-Dose CT.

PubMed

Wolterink, Jelmer M; Leiner, Tim; Viergever, Max A; Isgum, Ivana

2017-12-01

Noise is inherent to low-dose CT acquisition. We propose to train a convolutional neural network (CNN) jointly with an adversarial CNN to estimate routine-dose CT images from low-dose CT images and hence reduce noise. A generator CNN was trained to transform low-dose CT images into routine-dose CT images using voxelwise loss minimization. An adversarial discriminator CNN was simultaneously trained to distinguish the output of the generator from routine-dose CT images. The performance of this discriminator was used as an adversarial loss for the generator. Experiments were performed using CT images of an anthropomorphic phantom containing calcium inserts, as well as patient non-contrast-enhanced cardiac CT images. The phantom and patients were scanned at 20% and 100% routine clinical dose. Three training strategies were compared: the first used only voxelwise loss, the second combined voxelwise loss and adversarial loss, and the third used only adversarial loss. The results showed that training with only voxelwise loss resulted in the highest peak signal-to-noise ratio with respect to reference routine-dose images. However, CNNs trained with adversarial loss captured image statistics of routine-dose images better. Noise reduction improved quantification of low-density calcified inserts in phantom CT images and allowed coronary calcium scoring in low-dose patient CT images with high noise levels. Testing took less than 10 s per CT volume. CNN-based low-dose CT noise reduction in the image domain is feasible. Training with an adversarial network improves the CNNs ability to generate images with an appearance similar to that of reference routine-dose CT images.

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.

Irreversible Inhibition of EGFR: Modeling the Combined Pharmacokinetic-Pharmacodynamic Relationship of Osimertinib and Its Active Metabolite AZ5104.

PubMed

Yates, James W T; Ashton, Susan; Cross, Darren; Mellor, Martine J; Powell, Steve J; Ballard, Peter

2016-10-01

Osimertinib (AZD9291) is a potent, selective, irreversible inhibitor of EGFR-sensitizing (exon 19 and L858R) and T790M-resistant mutation. In vivo, in the mouse, it is metabolized to an active des-methyl metabolite, AZ5104. To understand the therapeutic potential in patients, this study aimed to assess the relationship between osimertinib pharmacokinetics, the pharmacokinetics of the active metabolite, the pharmacodynamics of phosphorylated EGFR reduction, and efficacy in mouse xenograft models of EGFR-driven cancers, including two NSCLC lines. Osimertinib was dosed in xenografted models of EGFR-driven cancers. In one set of experiments, changes in phosphorylated EGFR were measured to confirm target engagement. In a second set of efficacy studies, the resulting changes in tumor volume over time after repeat dosing of osimertinib were observed. To account for the contributions of both molecules, a mathematical modeling approach was taken to integrate the resulting datasets. The model was able to describe the pharmacokinetics, pharmacodynamics, and efficacy in A431, PC9, and NCI-H1975 xenografts, with the differences in sensitivity described by the varying potency against wild-type, sensitizing, and T790M-mutant EGFR and the phosphorylated EGFR reduction required to reduce tumor volume. It was inferred that recovery of pEGFR is slower after chronic dosing due to reduced resynthesis. It was predicted and further demonstrated that although inhibition is irreversible, the resynthesis of EGFR is such that infrequent intermittent dosing is not as efficacious as once daily dosing. Mol Cancer Ther; 15(10); 2378-87. ©2016 AACR. ©2016 American Association for Cancer Research.

Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells.

PubMed

Pal, Rajarshi; Mamidi, Murali Krishna; Das, Anjan Kumar; Bhonde, Ramesh

2012-04-01

In vitro disease modeling using pluripotent stem cells can be a fast track screening tool for toxicological testing of candidate drug molecules. Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents in drug screening. In the present investigation, we exposed 14- to 21-day-old embryoid bodies (EBs) to three different concentrations of DMSO [0.01% (low dose), 0.1% (medium dose) and 1.0% (high dose)] to identify the safest dose that could effectively be used as solvent. We found that DMSO treatment substantially altered the morphology and attachment of cells in concurrence with a significant reduction in cell viability in a dose-dependent manner. Gene expression studies revealed a selective downregulation of key markers associated with stemness (Oct-4, Sox-2, Nanog and Rex-1); ectoderm (Nestin, TuJ1, NEFH and Keratin-15); mesoderm (HAND-1, MEF-2C, GATA-4 and cardiac-actin); and endoderm (SOX-17, HNF-3β, GATA-6 and albumin), indicating an aberrant and untimely differentiation trajectory. Furthermore, immunocytochemistry, flow cytometry and histological analyses demonstrated substantial decrease in the levels of albumin and CK-18 proteins coupled with a massive reduction in the number of cells positive for PAS staining, implicating reduced deposits of glycogen. Our study advocates for the first time that DMSO exposure not only affects the phenotypic characteristics but also induces significant alteration in gene expression, protein content and functionality of the differentiated hepatic cells. Overall, our experiments warrant that hESC-based assays can provide timely alerts about the outcome of widespread applications of DMSO as drug solvent, cryoprotectant and differentiating agent.

MO-C-18A-01: Advances in Model-Based 3D Image Reconstruction

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

Chen, G; Pan, X; Stayman, J

2014-06-15

Recent years have seen the emergence of CT image reconstruction techniques that exploit physical models of the imaging system, photon statistics, and even the patient to achieve improved 3D image quality and/or reduction of radiation dose. With numerous advantages in comparison to conventional 3D filtered backprojection, such techniques bring a variety of challenges as well, including: a demanding computational load associated with sophisticated forward models and iterative optimization methods; nonlinearity and nonstationarity in image quality characteristics; a complex dependency on multiple free parameters; and the need to understand how best to incorporate prior information (including patient-specific prior images) within themore » reconstruction process. The advantages, however, are even greater – for example: improved image quality; reduced dose; robustness to noise and artifacts; task-specific reconstruction protocols; suitability to novel CT imaging platforms and noncircular orbits; and incorporation of known characteristics of the imager and patient that are conventionally discarded. This symposium features experts in 3D image reconstruction, image quality assessment, and the translation of such methods to emerging clinical applications. Dr. Chen will address novel methods for the incorporation of prior information in 3D and 4D CT reconstruction techniques. Dr. Pan will show recent advances in optimization-based reconstruction that enable potential reduction of dose and sampling requirements. Dr. Stayman will describe a “task-based imaging” approach that leverages models of the imaging system and patient in combination with a specification of the imaging task to optimize both the acquisition and reconstruction process. Dr. Samei will describe the development of methods for image quality assessment in such nonlinear reconstruction techniques and the use of these methods to characterize and optimize image quality and dose in a spectrum of clinical applications. Learning Objectives: Learn the general methodologies associated with model-based 3D image reconstruction. Learn the potential advantages in image quality and dose associated with model-based image reconstruction. Learn the challenges associated with computational load and image quality assessment for such reconstruction methods. Learn how imaging task can be incorporated as a means to drive optimal image acquisition and reconstruction techniques. Learn how model-based reconstruction methods can incorporate prior information to improve image quality, ease sampling requirements, and reduce dose.« less

ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish.

PubMed

Monstad-Rios, Adrian T; Watson, Claire J; Kwon, Ronald Y

2018-02-01

Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adult tail fin regeneration, cyclopamine and dorsomorphin. By developing methods for rapid and cost-effective chemical administration in adult zebrafish, this study expands the potential for small molecule discovery in postembryonic models of development, disease, and regeneration.

Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia and other hematologic malignancies.

PubMed

Olin, Jacqueline L; Griffiths, Carrie L; Smith, Morgan B

2017-01-01

Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.

Methyl-{beta}-cyclodextrin enhances the susceptibility of human breast cancer cells to carboplatin and 5-fluorouracil: Involvement of Akt, NF-{kappa}B and Bcl-2

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

Upadhyay, Ankur Kumar; Singh, Sandeep; Chhipa, Rishi Raj

2006-10-15

The response rates of extensively used chemotherapeutic drugs, carboplatin (Carb) or 5-fluorouracil (5-FU) are relatively disappointing because of considerable side effects associated with their high-dose regimen. In the present study, we determined whether treatment with a cholesterol depleting agent, methyl-{beta}-cyclodextrin (MCD), enhances the weak efficacy of low doses of Carb or 5-FU in human breast cancer cells. Data demonstrate that pretreatment with MCD significantly potentiates the cytotoxic activity of Carb and 5-FU in both MCF-7 and MDA-MB-231. Furthermore, we explored the molecular basis of enhanced cytotoxicity, and our data revealed that low-dose treatment with these drugs in MCD pretreated cellsmore » exhibited significantly decreased Akt phosphorylation, NF-{kappa}B activity and down-regulation in expression of anti-apoptotic protein Bcl-2. In addition, MCD pretreated cells demonstrated an increased intracellular drug accumulation as compared to cells treated with drugs alone. Taken together, our data provide the basis for potential therapeutic application of MCD in combination with other conventional cytotoxic drugs to facilitate reduction of drug dosage that offers a better chemotherapeutic approach with low toxicity.« less

Evaluation of the toxic potential of calcium carbide in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9).

PubMed

Danish, Mohd; Fatima, Ambreen; Khanam, Saba; Jyoti, Smita; Rahul; Ali, Fahad; Naz, Falaq; Siddique, Yasir Hasan

2015-11-01

In the present study the toxic potential of calcium carbide (CaC2) was studied on the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9). The third instar larvae were exposed to 2, 4, 8, 16 and 32×10(-3)g/ml of CaC2 in diet for 24h. The results reveal that the dose 2×10(-3)g/ml was not toxic but the remaining doses showed a dose dependent significant increase in the hsp70 expression, β-galactosidase activity, tissue damage, oxidative stress markers (lipid peroxidation and protein carbonyl content), glutathione-S-transferase activity, expression of Caspase 3 and 9, apoptotic index and DNA damage (midgut cells). A significant reduction as compared to control group in total protein, glutathione content and acetylcholinesterase activity was also observed. The Inductively Coupled Plasma Atomic Emission Spectroscopy analysis (ICPAES) reveals the presence of copper, iron, sodium, aluminium, manganese, calcium, nickel and mercury. The toxic effects of CaC2 in the present study may be attributed to the impurities present in it. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evidence of dose saving in routine CT practice using iterative reconstruction derived from a national diagnostic reference level survey.

PubMed

Thomas, P; Hayton, A; Beveridge, T; Marks, P; Wallace, A

2015-09-01

To assess the influence and significance of the use of iterative reconstruction (IR) algorithms on patient dose in CT in Australia. We examined survey data submitted to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) National Diagnostic Reference Level Service (NDRLS) during 2013 and 2014. We compared median survey dose metrics with categorization by scan region and use of IR. The use of IR results in a reduction in volume CT dose index of between 17% and 44% and a reduction in dose-length product of between 14% and 34% depending on the specific scan region. The reduction was highly significant (p < 0.001, Wilcoxon rank-sum test) for all six scan regions included in the NDRLS. Overall, 69% (806/1167) of surveys included in the analysis used IR. The use of IR in CT is achieving dose savings of 20-30% in routine practice in Australia. IR appears to be widely used by participants in the ARPANSA NDRLS with approximately 70% of surveys submitted employing this technique. This study examines the impact of the use of IR on patient dose in CT on a national scale.

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.

Digital radiography: optimization of image quality and dose using multi-frequency software.

PubMed

Precht, H; Gerke, O; Rosendahl, K; Tingberg, A; Waaler, D

2012-09-01

New developments in processing of digital radiographs (DR), including multi-frequency processing (MFP), allow optimization of image quality and radiation dose. This is particularly promising in children as they are believed to be more sensitive to ionizing radiation than adults. To examine whether the use of MFP software reduces the radiation dose without compromising quality at DR of the femur in 5-year-old-equivalent anthropomorphic and technical phantoms. A total of 110 images of an anthropomorphic phantom were imaged on a DR system (Canon DR with CXDI-50 C detector and MLT[S] software) and analyzed by three pediatric radiologists using Visual Grading Analysis. In addition, 3,500 images taken of a technical contrast-detail phantom (CDRAD 2.0) provide an objective image-quality assessment. Optimal image-quality was maintained at a dose reduction of 61% with MLT(S) optimized images. Even for images of diagnostic quality, MLT(S) provided a dose reduction of 88% as compared to the reference image. Software impact on image quality was found significant for dose (mAs), dynamic range dark region and frequency band. By optimizing image processing parameters, a significant dose reduction is possible without significant loss of image quality.

A Matter of Timing: Identifying Significant Multi-Dose Radiotherapy Improvements by Numerical Simulation and Genetic Algorithm Search

PubMed Central

Angus, Simon D.; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17–18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy. PMID:25460164

A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

PubMed

Angus, Simon D; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy.

Multi-Case Knowledge-Based IMRT Treatment Planning in Head and Neck Cancer

NASA Astrophysics Data System (ADS)

Grzetic, Shelby Mariah

Head and neck cancer (HNC) IMRT treatment planning is a challenging process that relies heavily on the planner's experience. Previously, we used the single, best match from a library of manually planned cases to semi-automatically generate IMRT plans for a new patient. The current multi-case Knowledge Based Radiation Therapy (MC-KBRT) study utilized different matching cases for each of six individual organs-at-risk (OARs), then combined those six cases to create the new treatment plan. From a database of 103 patient plans created by experienced planners, MC-KBRT plans were created for 40 (17 unilateral and 23 bilateral) HNC "query" patients. For each case, 2D beam's-eye-view images were used to find similar geometric "match" patients separately for each of 6 OARs. Dose distributions for each OAR from the 6 matching cases were combined and then warped to suit the query case's geometry. The dose-volume constraints were used to create the new query treatment plan without the need for human decision-making throughout the IMRT optimization. The optimized MC-KBRT plans were compared against the clinically approved plans and Version 1 (previous KBRT using only one matching case with dose warping) using the dose metrics: mean, median, and maximum (brainstem and cord+5mm) doses. Compared to Version 1, MC-KBRT had no significant reduction of the dose to any of the OARs in either unilateral or bilateral cases. Compared to the manually planned unilateral cases, there was significant reduction of the oral cavity mean/median dose (>2Gy) at the expense of the contralateral parotid. Compared to the manually planned bilateral cases, reduction of dose was significant in the ipsilateral parotid, larynx, and oral cavity (>3Gy mean/median) while maintaining PTV coverage. MC-KBRT planning in head and neck cancer generates IMRT plans with better dose sparing than manually created plans. MC-KBRT using multiple case matches does not show significant dose reduction compared to using a single match case with dose warping.

SU-C-12A-07: Effect of Vertical Position On Dose Reduction Using X-Care

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

Silosky, M; Marsh, R

Purpose: Reduction of absorbed dose to radiosensitive tissues is an important goal in diagnostic radiology. Siemens Medical has introduced a technique (X-CARE) to lower CT dose to anterior anatomy by reducing the tube current during 80° of rotation over radiosensitive tissues. Phantom studies have shown 30-40% dose reduction when phantoms are positioned at isocenter. However, for CT face and sinus exams, the center of the head is commonly positioned below isocenter. This work investigated the effects of vertical patient positioning on dose reduction using X-CARE. Methods: A 16cm Computed Tomography Dose Index phantom was scanned on a Siemens Definition Flashmore » CT scanner using a routine head protocol, with the phantom positioned at scanner isocenter. Optically stimulated luminescent dosimeters were placed on the anterior and posterior sides of the phantom. The phantom was lowered in increments of 2cm and rescanned, up to 8cm below isocenter. The experiment was then repeated using the same scan parameters but adding the X-CARE technique. The mean dosimeter counts were determined for each phantom position, and the difference between XCARE and routine scans was plotted as a function of distance from isocenter. Results: With the phantom positioned at isocenter, using XCARE reduced dose to the anterior side of the phantom by 40%, compared to dose when X-CARE was not used. Positioned below isocenter, anterior dose was reduced by only 20-27%. Additionally, using X-CARE at isocenter reduced dose to the anterior portion of the phantom by 45.6% compared to scans performed without X-CARE 8cm below isocenter. Conclusion: While using X-CARE substantially reduced dose to the anterior side of the phantom, this effect was diminished when the phantom was positioned below isocenter, simulating common practice for face and sinus scans. This indicates that centering the head in the gantry will maximize the effect of X-CARE.« less

Proton therapy to the subdiaphragmatic region in the management of patients with Hodgkin lymphoma.

PubMed

Sachsman, Suzanne; Hoppe, Bradford S; Mendenhall, Nancy P; Holtzman, Adam; Li, Zuofeng; Slayton, William; Joyce, Mike; Sandler, Eric; Flampouri, Stella

2015-07-01

Twelve consecutive patients with classical Hodgkin lymphoma (HL) involving diaphragmatic or subdiaphragmatic regions were treated on an institutional review board-approved outcomes tracking protocol. All patients underwent treatment with proton therapy following chemotherapy and had comparative three-dimensional conformal photon radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans to evaluate differences in dose to organs at risk (OARs). Among the cohort, stomach doses with 3DCRT, IMRT and proton therapy were 21 Gy (median), 14 Gy and 6 Gy, respectively. Median dose reductions with proton therapy compared with 3DCRT and IMRT were 13 Gy (p = 0.0022) and 8 Gy (p = 0.0022) for the stomach. Additionally, there was significant dose reduction using proton therapy for the liver, pancreas, bowel, left kidney and right kidney. Proton therapy reduces the dose to the stomach, liver, pancreas, small bowel and kidneys compared with 3DCRT or IMRT in patients with HL requiring abdominal radiotherapy. These dose reductions are expected to translate into lower risks of secondary cancers and other late toxicities in survivors of HL.

Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.

PubMed

Walker, L A; Watson, E S; elSohly, M A

1995-08-01

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.

Behavioral and Psychological Predictors of Chemotherapy Adherence in Patients with Advanced Non-Small-Cell Lung Cancer

PubMed Central

Greer, Joseph A.; Pirl, William F.; Park, Elyse R.; Lynch, Thomas J.; Temel, Jennifer S.

2013-01-01

Objective Dose delays and reductions in chemotherapy due to hematologic toxicities are common among patients with advanced non-small-cell lung cancer (NSCLC). However, limited data exist on behavioral or psychological predictors of chemotherapy adherence. The goal of this study was to explore the frequency and clinical predictors of infusion dose delays and reductions in this patient population. Methods Fifty patients newly diagnosed with advanced NSCLC of high performance status (ECOG PS=0-1) completed baseline assessments on quality of life (FACT-L) and mood (HADS) within eight weeks of diagnosis. Participants were followed prospectively for six months. Chemotherapy dosing data came from medical chart review. Results All patients received chemotherapy during the course of the study, beginning with either a platinum-based doublet (74%), an oral epidermal growth factor receptor-tyrosine kinase inhibitor (14%), or a parenteral single agent (12%). Forty percent (N=20) of patients had either a dose delay (38%) and/or reduction (16%) in their scheduled infusions. Fisher’s exact tests showed that patients who experienced neutropenia, smoked at the time of diagnosis, or reported heightened baseline anxiety were significantly more likely to experience dose delays or reductions. There were no associations between chemotherapy adherence and patient demographics, performance status, or quality of life. Conclusion In this sample, over one-third of patients with advanced NSCLC experienced either a dose delay or reduction in prescribed chemotherapy regimens. Behavioral and psychological factors, such as tobacco use and anxiety symptoms, appear to play an important role in chemotherapy adherence, though further study is required to confirm these findings. PMID:19027443

Approaches to reducing photon dose calculation errors near metal implants

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

Huang, Jessie Y.; Followill, David S.; Howell, Reb

Purpose: Dose calculation errors near metal implants are caused by limitations of the dose calculation algorithm in modeling tissue/metal interface effects as well as density assignment errors caused by imaging artifacts. The purpose of this study was to investigate two strategies for reducing dose calculation errors near metal implants: implementation of metal-based energy deposition kernels in the convolution/superposition (C/S) dose calculation method and use of metal artifact reduction methods for computed tomography (CT) imaging. Methods: Both error reduction strategies were investigated using a simple geometric slab phantom with a rectangular metal insert (composed of titanium or Cerrobend), as well asmore » two anthropomorphic phantoms (one with spinal hardware and one with dental fillings), designed to mimic relevant clinical scenarios. To assess the dosimetric impact of metal kernels, the authors implemented titanium and silver kernels in a commercial collapsed cone C/S algorithm. To assess the impact of CT metal artifact reduction methods, the authors performed dose calculations using baseline imaging techniques (uncorrected 120 kVp imaging) and three commercial metal artifact reduction methods: Philips Healthcare’s O-MAR, GE Healthcare’s monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI with metal artifact reduction software (MARS) applied. For the simple geometric phantom, radiochromic film was used to measure dose upstream and downstream of metal inserts. For the anthropomorphic phantoms, ion chambers and radiochromic film were used to quantify the benefit of the error reduction strategies. Results: Metal kernels did not universally improve accuracy but rather resulted in better accuracy upstream of metal implants and decreased accuracy directly downstream. For the clinical cases (spinal hardware and dental fillings), metal kernels had very little impact on the dose calculation accuracy (<1.0%). Of the commercial CT artifact reduction methods investigated, the authors found that O-MAR was the most consistent method, resulting in either improved dose calculation accuracy (dental case) or little impact on calculation accuracy (spine case). GSI was unsuccessful at reducing the severe artifacts caused by dental fillings and had very little impact on calculation accuracy. GSI with MARS on the other hand gave mixed results, sometimes introducing metal distortion and increasing calculation errors (titanium rectangular implant and titanium spinal hardware) but other times very successfully reducing artifacts (Cerrobend rectangular implant and dental fillings). Conclusions: Though successful at improving dose calculation accuracy upstream of metal implants, metal kernels were not found to substantially improve accuracy for clinical cases. Of the commercial artifact reduction methods investigated, O-MAR was found to be the most consistent candidate for all-purpose CT simulation imaging. The MARS algorithm for GSI should be used with caution for titanium implants, larger implants, and implants located near heterogeneities as it can distort the size and shape of implants and increase calculation errors.« less

Influence of piperine and quercetin on antidiabetic potential of curcumin.

PubMed

Kaur, Ginpreet; Invally, Mihir; Chintamaneni, Meena

2016-09-01

Curcumin is a nutraceutical obtained from the rhizomes of Curcuma longa with a significant medicinal value against numerous disorders. However, the potential cannot be completely exploited due to low in vivo bioavailability. Hence, in order to enhance the bioavailability of curcumin, we combined it with the bioavailability enhancers like piperine and quercetin. The present study was targeted to explore the antidiabetic potential of combinatorial extract of curcumin with piperine and quercetin (CPQ) in streptozotocin- and nicotinamide-induced diabetic rats. Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin (55 mg/kg) and nicotinamide (120 mg/kg-1). CPQ was orally administered at 100 mg kg-1 dose/day for a period of 28 days. At the end of 28 days, blood was analyzed for glucose, high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol level. Oral glucose tolerance test (OGTT) was also conducted at the end of 28 days. Oral administration of CPQ at the dose of 100 mg kg-1 significantly (p<0.01) reduced plasma glucose at the end of 28 days, as compared to the diabetic control group. The reduction in the plasma glucose produced by the CPQ extract was equivalent to that of glibenclamide and significantly more compared to curcumin alone (p<0.01). Furthermore, a significant (p<0.01) reduction in the raised LDL, cholesterol and triglycerides and improvement was observed in the group fed with CPQ compared to diabetic control as well as the alone (p<0.05) curcumin group. There was a significant improvement in the body weight with CPQ compared to diabetes control group. OGTT revealed a significantly high glucose tolerance in CPQ fed rats compared to the diabetic control as well as the rats fed with curcumin alone. Treatment with combinatorial extract of curcumin presented a significantly better therapeutic potential when compared with curcumin alone, which reveals that CPQ, with reduced dose of curcumin may serve as a therapeutic agent in the treatment of type 2 diabetes mellitus.

Measurements of air dose rates in and around houses in the Fukushima Prefecture in Japan after the Fukushima accident.

PubMed

Matsuda, Norihiro; Mikami, Satoshi; Sato, Tetsuro; Saito, Kimiaki

2017-01-01

Measurements of air dose rates for 192 houses in a less contaminated area (<0.5 μSv h -1 ) of the Fukushima Prefecture in Japan were conducted in both living rooms and/or bedrooms using optically stimulated luminescence (OSL) dosimeters and around the houses via a man-borne survey at intervals of several meters. The relation of the two air dose rates (inside and outside) for each house, including the background from natural radionuclides, was divided into several categories, determined by construction materials (light and heavy) and floor number, with the dose reduction factors being expressed as the ratio of the dose inside to that outside the house. For wooden and lightweight steel houses (classed as light), the dose rates inside and outside the houses showed a positive correlation and linear regression with a slope-intercept form due to the natural background, although the degree of correlation was not very high. The regression coefficient, i.e., the average dose reduction factor, was 0.38 on the first floor and 0.49 on the second floor. It was found that the contribution of natural radiation cannot be neglected when we consider dose reduction factors in less contaminated areas. The reductions in indoor dose rates are observed because a patch of ground under each house is not contaminated (this is the so-called uncontaminated effect) since the shielding capability of light construction materials is typically low. For reinforced steel-framed concrete houses (classed as heavy), the dose rates inside the houses did not show a correlation with those outside the houses due to the substantial shielding capability of these materials. The average indoor dose rates were slightly higher than the arithmetic mean value of the outdoor dose rates from the natural background because concrete acts as a source of natural radionuclides. The characteristics of the uncontaminated effect were clarified through Monte Carlo simulations. It was found that there is a great variation in air dose rates even within one house, depending on the height of the area and its closeness to the outside boundary. Measurements of outdoor dose rates required consideration of local variations depending on the environment surrounding each house. The representative value was obtained from detailed distributions of air dose rates around the house, as measured by a man-borne survey. Therefore, it is imperative to recognize that dose reduction factors fluctuate in response to various factors such as the size and shape of a house, construction materials acting as a shield and as sources, position (including height) within a room, floor number, total number of floors, and surrounding environment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genotoxicity testing of peptides: Folate deprivation as a marker of exaggerated pharmacology

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

Guérard, Melanie, E-mail: melanie.guerard@roche.com; Zeller, Andreas; Festag, Matthias

2014-09-15

The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidencemore » of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. - Highlights: • A synthetic peptide has been evaluated for potential genotoxicity • Small increases in an integrated (13-weeks) micronucleus test were observed • Further, animals had a pronounced reductions in food intake and body weight gain • A dose-dependent decrease in plasma folate levels was evident from week 4 onwards • Elevated micronuclei-incidence due to the exaggerated pharmacology.« less

Allopurinol might improve response to azathioprine and 6-mercaptopurine by correcting an unfavorable metabolite ratio.

PubMed

Gardiner, Sharon J; Gearry, Richard B; Burt, Michael J; Chalmers-Watson, Teresa; Chapman, Bruce A; Ross, Alison G; Stedman, Catherine A M; Huelsen, Alexander; Barclay, Murray L

2011-01-01

Allopurinol potentiates azathioprine and 6-mercaptopurine (6-MP) by increasing 6-thioguanine nucleotide (6-TGN) metabolite concentrations. The outcome might also be improved by adding allopurinol in individuals who preferentially produce 6-methylmercaptopurine nucleotides (6-MMPN), rather than 6-TGN. The aim of the present study was to investigate the effect of allopurinol on concentrations of 6-MMPN and 6-TGN in individuals with a high ratio of these metabolites (>20), which is indicative of a poor thiopurine response. Sixteen individuals were identified who were taking azathioprine or 6-MP, and were commenced on allopurinol to improve a high 6-MMPN:TGN ratio. Metabolite concentrations were compared before and after commencing allopurinol, and markers of disease control were compared. The addition of 100-300 mg allopurinol daily and thiopurine dose reduction (17-50% of the original dose) resulted in a reduction of the median (and range) 6-MMPN concentration, from 11,643 (3,365-27,832) to 221 (55-844) pmol/8×10(8) red blood cells (RBC; P=0.0005), increased 6-TGN from 162 (125-300) to 332 (135-923) pmol/8×10(8) RBC (P=0.0005), and reduced the 6-MMPN:6-TGN ratio from 63 (12-199) to 1 (0.1-4.5) (P=0.0005). There was a significant reduction in steroid dose requirements at 12 months (P=0.04) and trends for improvement in other markers of disease control. One patient developed red cell aplasia that resolved upon stopping azathioprine and allopurinol. In those with a high 6-MMPN:6-TGN ratio (>20), response to thiopurine treatment might be improved by the addition of allopurinol, together with a reduced thiopurine dose and close hematological monitoring. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Prescription errors before and after introduction of electronic medication alert system in a pediatric emergency department.

PubMed

Sethuraman, Usha; Kannikeswaran, Nirupama; Murray, Kyle P; Zidan, Marwan A; Chamberlain, James M

2015-06-01

Prescription errors occur frequently in pediatric emergency departments (PEDs).The effect of computerized physician order entry (CPOE) with electronic medication alert system (EMAS) on these is unknown. The objective was to compare prescription errors rates before and after introduction of CPOE with EMAS in a PED. The hypothesis was that CPOE with EMAS would significantly reduce the rate and severity of prescription errors in the PED. A prospective comparison of a sample of outpatient, medication prescriptions 5 months before and after CPOE with EMAS implementation (7,268 before and 7,292 after) was performed. Error types and rates, alert types and significance, and physician response were noted. Medication errors were deemed significant if there was a potential to cause life-threatening injury, failure of therapy, or an adverse drug effect. There was a significant reduction in the errors per 100 prescriptions (10.4 before vs. 7.3 after; absolute risk reduction = 3.1, 95% confidence interval [CI] = 2.2 to 4.0). Drug dosing error rates decreased from 8 to 5.4 per 100 (absolute risk reduction = 2.6, 95% CI = 1.8 to 3.4). Alerts were generated for 29.6% of prescriptions, with 45% involving drug dose range checking. The sensitivity of CPOE with EMAS in identifying errors in prescriptions was 45.1% (95% CI = 40.8% to 49.6%), and the specificity was 57% (95% CI = 55.6% to 58.5%). Prescribers modified 20% of the dosing alerts, resulting in the error not reaching the patient. Conversely, 11% of true dosing alerts for medication errors were overridden by the prescribers: 88 (11.3%) resulted in medication errors, and 684 (88.6%) were false-positive alerts. A CPOE with EMAS was associated with a decrease in overall prescription errors in our PED. Further system refinements are required to reduce the high false-positive alert rates. © 2015 by the Society for Academic Emergency Medicine.

Radiation dose reduction in CT with adaptive statistical iterative reconstruction (ASIR) for patients with bronchial carcinoma and intrapulmonary metastases.

PubMed

Schäfer, M-L; Lüdemann, L; Böning, G; Kahn, J; Fuchs, S; Hamm, B; Streitparth, F

2016-05-01

To compare the radiation dose and image quality of 64-row chest computed tomography (CT) in patients with bronchial carcinoma or intrapulmonary metastases using full-dose CT reconstructed with filtered back projection (FBP) at baseline and reduced dose with 40% adaptive statistical iterative reconstruction (ASIR) at follow-up. The chest CT images of patients who underwent FBP and ASIR studies were reviewed. Dose-length products (DLP), effective dose, and size-specific dose estimates (SSDEs) were obtained. Image quality was analysed quantitatively by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurement. In addition, image quality was assessed by two blinded radiologists evaluating images for noise, contrast, artefacts, visibility of small structures, and diagnostic acceptability using a five-point scale. The ASIR studies showed 36% reduction in effective dose compared with the FBP studies. The qualitative and quantitative image quality was good to excellent in both protocols, without significant differences. There were also no significant differences for SNR except for the SNR of lung surrounding the tumour (FBP: 35±17, ASIR: 39±22). A protocol with 40% ASIR can provide approximately 36% dose reduction in chest CT of patients with bronchial carcinoma or intrapulmonary metastases while maintaining excellent image quality. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Ultralow-dose computed tomography imaging for surgery of midfacial and orbital fractures using ASIR and MBIR.

PubMed

Widmann, G; Dalla Torre, D; Hoermann, R; Schullian, P; Gassner, E M; Bale, R; Puelacher, W

2015-04-01

The influence of dose reductions on diagnostic quality using a series of high-resolution ultralow-dose computed tomography (CT) scans for computer-assisted planning and surgery including the most recent iterative reconstruction algorithms was evaluated and compared with the fracture detectability of a standard cranial emergency protocol. A human cadaver head including the mandible was artificially prepared with midfacial and orbital fractures and scanned using a 64-multislice CT scanner. The CT dose index volume (CTDIvol) and effective doses were calculated using application software. Noise was evaluated as the standard deviation in Hounsfield units within an identical region of interest in the posterior fossa. Diagnostic quality was assessed by consensus reading of a craniomaxillofacial surgeon and radiologist. Compared with the emergency protocol at CTDIvol 35.3 mGy and effective dose 3.6 mSv, low-dose protocols down to CTDIvol 1.0 mGy and 0.1 mSv (97% dose reduction) may be sufficient for the diagnosis of dislocated craniofacial fractures. Non-dislocated fractures may be detected at CTDIvol 2.6 mGy and 0.3 mSv (93% dose reduction). Adaptive statistical iterative reconstruction (ASIR) 50 and 100 reduced average noise by 30% and 56%, and model-based iterative reconstruction (MBIR) by 93%. However, the detection rate of fractures could not be improved due to smoothing effects. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation.

PubMed

Wei, Zhi-Qiang; Zhang, Yong-Hong; Ke, Chang-Zheng; Chen, Hong-Xia; Ren, Pan; He, Yu-Lin; Hu, Pei; Ma, De-Qiang; Luo, Jie; Meng, Zhong-Ji

2017-09-14

To investigate the potential effect of curcumin on hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the underlying mechanism. A HepG2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen (HBsAg) and e antigen (HBeAg) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and cccDNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound cccDNA was detected by chromatin immunoprecipitation (ChIP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs (siRNAs) targeting HBV were tested along with curcumin. Curcumin treatment led to time- and dose-dependent reductions in HBsAg and HBeAg expression and significant reductions in intracellular HBV DNA replication intermediates and HBV cccDNA. After treatment with 20 μmol/L curcumin for 2 d, HBsAg and cccDNA levels in HepG2.2.15 cells were reduced by up to 57.7% ( P < 0.01) and 75.5% ( P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time- and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3- and H4-bound cccDNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of siRNAs targeting HBV enhanced the inhibitory effects of curcumin. Curcumin inhibits HBV gene replication via down-regulation of cccDNA-bound histone acetylation and has the potential to be developed as a cccDNA-targeting antiviral agent for hepatitis B.

Occupational radiation dose to eyes from endoscopic retrograde cholangiopancreatography procedures in light of the revised eye lens dose limit from the International Commission on Radiological Protection.

PubMed

O'Connor, U; Gallagher, A; Malone, L; O'Reilly, G

2013-02-01

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure that combines the use of X-ray fluoroscopy and endoscopy for examination of the bile duct. Published data on ERCP doses are limited, including staff eye dose from ERCP. Occupational eye doses are of particular interest now as the International Commission on Radiological Protection (ICRP) has recommended a reduction in the dose limit to the lens of the eye. The aim of this study was to measure occupational eye doses obtained from ERCP procedures. A new eye lens dosemeter (EYE-D(™), Radcard, Krakow, Poland) was used to measure the ERCP eye dose, H(p)(3), at two endoscopy departments in Ireland. A review of radiation protection practice at the two facilities was also carried out. The mean equivalent dose to the lens of the eye of a gastroenterologist is 0.01 mSv per ERCP procedure with an undercouch X-ray tube and 0.09 mSv per ERCP procedure with an overcouch X-ray tube. Staff eye dose normalised to patient kerma area product is also presented. Staff eye doses in ERCP have the potential to exceed the revised ICRP limit of 20 mSv per annum when an overcouch X-ray tube is used. The EYE-D dosemeter was found to be a convenient method for measuring lens dose. Eye doses in areas outside of radiology departments should be kept under review, particularly in light of the new ICRP eye dose limit. Occupational eye lens doses from ERCP procedures have been established using a new commercially available dedicated H(p)(3) dosemeter.

Impact of Mobile Dose-Tracking Technology on Medication Distribution at an Academic Medical Center.

PubMed

Kelm, Matthew; Campbell, Udobi

2016-05-01

Medication dose-tracking technologies have the potential to improve efficiency and reduce costs associated with re-dispensing doses reported as missing. Data describing this technology and its impact on the medication use process are limited. The purpose of this study is to assess the impact of dose-tracking technology on pharmacy workload and drug expense at an academic, acute care medical center. Dose-tracking technology was implemented in June 2014. Pre-implementation data were collected from February to April 2014. Post-implementation data were collected from July to September 2014. The primary endpoint was the percent of re-dispensed oral syringe and compounded sterile product (CSP) doses within the pre- and post-implementation periods per 1,000 discharges. Secondary endpoints included pharmaceutical expense generated from re-dispensing doses, labor costs, and staff satisfaction with the medication distribution process. We observed an average 6% decrease in re-dispensing of oral syringe and CSP doses from pre- to post-implementation (15,440 vs 14,547 doses; p = .047). However, when values were adjusted per 1,000 discharges, this trend did not reach statistical significance (p = .074). Pharmaceutical expense generated from re-dispensing doses was significantly reduced from pre- to post-implementation ($834,830 vs $746,466 [savings of $88,364]; p = .047). We estimated that $2,563 worth of technician labor was avoided in re-dispensing missing doses. We also saw significant improvement in staff perception of technology assisting in reducing missing doses (p = .0003), as well as improvement in effectiveness of resolving or minimizing missing doses (p = .01). The use of mobile dose-tracking technology demonstrated meaningful reductions in both the number of doses re-dispensed and cost of pharmaceuticals dispensed.

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

PubMed Central

Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

2014-01-01

Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

The Characterization and Treatment of Aggressive Breast Cancer

DTIC Science & Technology

2005-05-01

of a cycle for over 7 days, the carboplatin dose will be decreased by 25% for subsequent cycles. For a second episode of febrile neutropenia , G-CSF...should be given with the next cycle. For an episode of febrile neutropenia despite dose reduction and G-CSF, protocol treatment should be discontinued... neutropenia despite a dose reduction in the previous course. G-CSF may also be used as clinically indicated for neutropenic infection. 4.2.4 The use of

Pediatric CT and radiation: our responsibility

NASA Astrophysics Data System (ADS)

Frush, Donald P.

2009-02-01

In order to discuss the cost-benefit ratio of CT examinations in children, one must be familiar with the reasons why CT can provide a high collective or individual dose. The reasons include increasing CT use as well as lack of attention to dose reduction strategies. While those have been substantial efforts for dose reduction, additional work is necessary to prevent unnecessary radiation exposure. This responsibility is shared between science and medicine, industry, regulatory agencies, and patients as well.

Effectiveness of disinfectant treatments for inactivating Piscirickettsia salmonis.

PubMed

Muniesa, A; Escobar-Dodero, J; Silva, N; Henríquez, P; Bustos, P; Perez, A M; Mardones, F O

2018-03-08

This short communication investigated in vitro differences between commercial disinfectants types (n = 36), doses of application, and time of action in the elimination of Piscirickettsia salmonis, the most important bacterium affecting farmed salmon in Chile. Seven different treatments were examined, including active and inactive chlorine dioxides, glutaraldehyde, hypochlorite disinfectants and detergents, peracetic acid, peroxides and other miscellaneous methods A 3 replicate set of each of the sample groups was stored at 20 °C and 95% relative humidity and retested after 1, 5 and 30 min with varying doses (low, recommended and high doses). Multiple comparison tests were performed for the mean log CFU/ml among different disinfectant types, dose (ppm) and time of exposure (minutes) on the reduction of P. salmonis. Overall, disinfection using peracetic acid, peroxides, and both active and inactive chlorine dioxides caused significantly higher reduction of >7.5 log CFU/ml in samples, compared to other tested sanitizers. The lowest reduction was obtained after disinfection with hypochlorite detergents. As expected, as doses and time of action increase, there was a significant reduction of the overall counts of P. salmonis. However, at lowest doses, only use of paracetic acids resulted in zero counts. Implementation of effective protocols, making use of adequate disinfectants, may enhance biosecurity, and ultimately, mitigate the impact of P. salmonis in farmed salmon. Copyright © 2018. Published by Elsevier B.V.

Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

PubMed

Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M

2017-11-15

Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.

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

Prikhodko, Vitaly Y; Pihl, Josh A; Toops, Todd J

Ethanol is a very effective reductant of nitrogen oxides (NOX) over silver/alumina (Ag/Al2O3) catalysts in lean exhaust environment. With the widespread availability of ethanol/gasoline-blended fuel in the USA, lean gasoline engines equipped with an Ag/Al2O3 catalyst have the potential to deliver higher fuel economy than stoichiometric gasoline engines and to increase biofuel utilization while meeting exhaust emissions regulations. In this work a pre-commercial 2 wt% Ag/Al2O3 catalyst was evaluated on a 2.0-liter BMW lean burn gasoline direct injection engine for the selective catalytic reduction (SCR) of NOX with ethanol/gasoline blends. The ethanol/gasoline blends were delivered via in-pipe injection upstream ofmore » the Ag/Al2O3 catalyst with the engine operating under lean conditions. A number of engine conditions were chosen to provide a range of temperatures and space velocities for the catalyst performance evaluations. High NOX conversions were achieved with ethanol/gasoline blends containing at least 50% ethanol; however, higher C1/N ratio was needed to achieve greater than 90% NOX conversion, which also resulted in significant HC slip. Temperature and HC dosing were important in controlling selectivity to NH3 and N2O. At high temperatures, NH3 and N2O yields increased with increased HC dosing. At low temperatures, NH3 yield was very low, however, N2O levels became significant. The ability to generate NH3 under lean conditions has potential for application of a dual SCR approach (HC SCR + NH3 SCR) to reduce fuel consumption needed for NOX reduction and/or increased NOX conversion, which is discussed in this work.« less

Pharmacokinetics and Abuse Potential of Benzhydrocodone, a Novel Prodrug of Hydrocodone, After Intranasal Administration in Recreational Drug Users.

PubMed

Mickle, Travis C; Guenther, Sven M; Barrett, Andrew C; Roupe, Kathryn Ann; Zhou, Jing; Dickerson, Daniel; Webster, Lynn R

2017-10-28

Developing an acetaminophen-free, immediate-release hydrocodone product remains an unmet medical need; however, new opioid analgesics should not introduce new abuse risks. Benzhydrocodone is a prodrug of hydrocodone that must be metabolized into hydrocodone by enzymes in the intestinal tract to optimally deliver its pharmacologic effects. This study evaluated the intranasal pharmacokinetics and abuse potential of benzhydrocodone active pharmaceutical ingredient (API) compared with hydrocodone bitartrate (HB) API. Single-center, randomized, double-blind, crossover study. Clinical research site. Healthy adult, nondependent, recreational opioid users. Subjects (N = 51 Completers) were randomized to receive 13.34 mg of intranasal benzhydrocodone API and 15.0 mg of intranasal HB API (molar-equivalent doses of hydrocodone). Blood samples were taken, and Drug Liking scores (assessed on a bipolar visual analog scale) were obtained throughout each dosing interval. Nasal irritation and safety were assessed. Peak hydrocodone plasma concentration (Cmax) was 36.0% lower, and total hydrocodone exposures (AUClast and AUCinf) were 20.3% and 19.5% lower, respectively, for benzhydrocodone API compared with HB API (P < 0.0001). All partial AUC values were lower for benzhydrocodone API, with a ≥ 75% reduction in hydrocodone exposure at all time intervals up to one hour postdose (P < 0.0001). Median Tmax of hydrocodone following benzhydrocodone API was delayed by more than one hour compared with HB. Drug Liking score, as assessed by maximal liking (Emax), was significantly lower for benzhydrocodone API vs HB API (P = 0.004), with 45% of subjects showing a ≥ 30% reduction in Drug Liking Emax. Reductions in hydrocodone exposure and associated decreases in Drug Liking relative to HB suggest that the prodrug benzhydrocodone may deter intranasal abuse. © 2017 American Academy of Pain Medicine.

Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens.

PubMed

Chu, Cindy S; Bancone, Germana; Moore, Kerryn A; Win, Htun Htun; Thitipanawan, Niramon; Po, Christina; Chowwiwat, Nongnud; Raksapraidee, Rattanaporn; Wilairisak, Pornpimon; Phyo, Aung Pyae; Keereecharoen, Lily; Proux, Stéphane; Charunwatthana, Prakaykaew; Nosten, François; White, Nicholas J

2017-02-01

Radical cure of Plasmodium vivax malaria with 8-aminoquinolines (primaquine or tafenoquine) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD heterozygous females, because of individual variation in the pattern of X-chromosome inactivation (Lyonisation) in erythroid cells, may have low G6PD activity in the majority of their erythrocytes, yet are usually reported as G6PD "normal" by current phenotypic screening tests. Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized. In a cohort study nested within a randomised clinical trial that compared different treatment regimens for P. vivax malaria, patients with a normal standard NADPH fluorescent spot test result (≳30%-40% of normal G6PD activity) were randomised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine, either the standard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants. Between 21 February 2012 and 04 July 2014, 241 female participants were enrolled, of whom 34 were heterozygous for the G6PD Mahidol variant. Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinically significant haemolysis (fractional haematocrit reduction >25%) in G6PD heterozygotes taking the higher (7 d) primaquine dose (9/17 [53%]) compared with G6PD heterozygotes taking the standard high (14 d) dose (2/16 [13%]; p = 0.022). In heterozygotes, the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose (7-d regimen): -20.4% (95% CI -26.0% to -14.8%) (nadir on day 5) compared with the standard high (14 d) dose: -13.1% (95% CI -17.6% to -8.6%) (nadir day 6). Two heterozygotes taking the higher (7 d) primaquine dose required blood transfusion. In wild-type participants, mean haematocrit reductions were clinically insignificant and similar with both doses: -5.8 (95% CI -7.2% to -4.4%) (nadir day 3) compared with -5.5% (95% CI -7.4% to -3.7%) (nadir day 4), respectively. Limitations to this nested cohort study are that the primary objective of the trial was designed to measure efficacy and not haemolysis in relation to G6PD genotype and that the heterozygote groups were small. Higher daily doses of primaquine have the potential to cause clinically significant haemolysis in G6PD heterozygous females who are reported as phenotypically normal with current point of care tests. ClinicalTrials.gov NCT01640574.

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

2014-01-01

Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). Conclusions. In nonhuman primates, PGJ2 administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ2 is neuroprotective when administered up to 5 hours after induction of pNAION. PMID:25298416

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

PubMed Central

Zarabla, Alessia; Ungania, Sara; Cacciatore, Alessandra; Maialetti, Andrea; Petreri, Gianluca; Mengarelli, Andrea; Spadea, Antonio; Marchesi, Francesco; Renzi, Daniela; Gumenyuk, Svitlana; Strigari, Lidia; Maschio, Marta

2017-01-01

Summary Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the frontoparietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

SU-F-J-17: Patient Localization Using MRI-Guided Soft Tissue for Head-And-Neck Radiotherapy: Indication for Margin Reduction and Its Feasibility

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

Qi, X; Yang, Y; Jack, N

Purpose: On-board MRI provides superior soft-tissue contrast, allowing patient alignment using tumor or nearby critical structures. This study aims to study H&N MRI-guided IGRT to analyze inter-fraction patient setup variations using soft-tissue targets and design appropriate CTV-to-PTV margin and clinical implication. Methods: 282 MR images for 10 H&N IMRT patients treated on a ViewRay system were retrospectively analyzed. Patients were immobilized using a thermoplastic mask on a customized headrest fitted in a radiofrequency coil and positioned to soft-tissue targets. The inter-fraction patient displacements were recorded to compute the PTV margins using the recipe: 2.5∑+0.7σ. New IMRT plans optimized on themore » revised PTVs were generated to evaluate the delivered dose distributions. An in-house dose deformation registration tool was used to assess the resulting dosimetric consequences when margin adaption is performed based on weekly MR images. The cumulative doses were compared to the reduced margin plans for targets and critical structures. Results: The inter-fraction displacements (and standard deviations), ∑ and σ were tabulated for MRI and compared to kVCBCT. The computed CTV-to-PTV margin was 3.5mm for soft-tissue based registration. There were minimal differences between the planned and delivered doses when comparing clinical and the PTV reduced margin plans: the paired t-tests yielded p=0.38 and 0.66 between the planned and delivered doses for the adapted margin plans for the maximum cord and mean parotid dose, respectively. Target V95 received comparable doses as planned for the reduced margin plans. Conclusion: The 0.35T MRI offers acceptable soft-tissue contrast and good spatial resolution for patient alignment and target visualization. Better tumor conspicuity from MRI allows soft-tissue based alignments with potentially improved accuracy, suggesting a benefit of margin reduction for H&N radiotherapy. The reduced margin plans (i.e., 2 mm) resulted in improved normal structure sparing and accurate dose delivery to achieve intended treatment goal under MR guidance.« less

RADIATION PROTECTION CABIN FOR CATHETER-DIRECTED LIVER INTERVENTIONS: OPERATOR DOSE ASSESSMENT.

PubMed

Maleux, Geert; Bergans, Niki; Bosmans, Hilde; Bogaerts, Ria

2016-09-01

The number and complexity of interventional radiological procedures and in particular catheter-directed liver interventions have increased substantially. The current study investigates the reduction of personal doses when using a dedicated radiation protection cabin (RPC) for these procedures. Operator and assistant doses were assessed for 3 series of 20 chemoinfusion/chemoembolisation interventions, including an equal number of procedures with and without RPC. Whole body doses, finger doses and doses at the level of knees and eyes were evaluated with different types of TLD-100 Harshaw dosemeters. Dosemeters were also attached on the three walls of the RPC. The operator doses were significantly reduced by the RPC, but also without RPC, the doses appear to be limited as a result of thorough optimisation with existing radiation protection tools. The added value of the RPC should thus be determined by the outcome of balancing dose reduction and other aspects such as ergonomic benefits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

High-NA optical CD metrology on small in-cell targets enabling improved higher order dose control and process control for logic

NASA Astrophysics Data System (ADS)

Cramer, Hugo; Mc Namara, Elliott; van Laarhoven, Rik; Jaganatharaja, Ram; de la Fuente, Isabel; Hsu, Sharon; Belletti, Filippo; Popadic, Milos; Tu, Ward; Huang, Wade

2017-03-01

The logic manufacturing process requires small in-device metrology targets to exploit the full dose correction potential of the modern scanners and process tools. A high-NA angular resolved scatterometer (YieldStar S-1250D) was modified to demonstrate the possibility of OCD measurements on 5x5µm2 targets. The results obtained on test wafers in a logic manufacturing environment, measured after litho and after core etch, showed a good correlation to larger reference targets and AEI to ADI intra-field CDU correlation, thereby demonstrating the feasibility of OCD on such small targets. The data was used to determine a reduction potential of 55% for the intra-field CD variation, using 145 points per field on a few inner fields, and 33% of the process induced across wafer CD variation using 16 points per field full wafer. In addition, the OCD measurements reveal valuable information on wafer-to-wafer layer height variations within a lot.

Problems associated with digital luminescence radiography in the neonate and young infant. Problems with digital radiography.

PubMed

Arthur, R J; Pease, J N

1992-01-01

An evaluation of the Siemens Digiscan has been undertaken to determine whether digital luminescence radiography (DLR) could replace conventional radiography in the examination of the neonate and young infant. Whilst the overall image quality of the digital radiograph was consistently higher than for conventional radiography the difference was less marked than we had expected. Furthermore, the potential for reduction in radiation dose by reducing the repeat rate due to incorrect exposure was limited. The potential advantages of DLR have been critically examined in relationship to neonatal radiography and a number of problems encountered during the evaluation have been highlighted.

The effects of pre-emptive low-dose X-ray irradiation on MIA induced inflammatory pain in rats

NASA Astrophysics Data System (ADS)

Hahm, Suk-Chan; Lee, Go-Eun; Kim, Eun-Hye; Kim, Junesun; Lee, Taewoong; Lee, Wonho

2013-07-01

This study was performed to determine the effect of pre-emptive low-dose irradiation on the development of inflammatory pain and to characterize the potential mechanisms underlying this effect in osteoarthritis (OA) animal model. Whole-body X-irradiations with 0.1, 0.5, 1 Gy or sham irradiations were performed for 3 days before the induction of ostearthritis with monosodium iodoacetate (MIA) (40 µl, in saline) into the right knee joint in male Sprague Dawley rats. Behavioral tests for arthritic pain including evoked and non-evoked pain were conducted before and after MIA injection and inducible nitric-oxide synthase (iNOS) expression level was measured by western blot. Low-dose radiation significantly prevented the development of mechanical allodynia and thermal hyperalgesia and reduction in weight bearing that is regarded as a behavioral signs of non-evoked pain following MIA injection. Low-dose radiation significantly inhibited the increase in iNOS expression after MIA injection in spinal L3-5 segments in rat. These data suggest that low-dose X-irradiation is able to prevent the development of arthritic pain through modulation of iNOS expression in the spinal cord dorsal horn. Thus, low-dose radiotherapy could be substituted in part for treatment with drugs for patients with chronic inflammatory disease in clinical setting.

Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone.

PubMed

Albers, Lauren N; Arbiser, Jack L; Feldman, Ron J

2017-10-01

Hailey-Hailey disease is a severe genetic blistering disease of intertriginous skin locations that can lead to poor quality of life and increased morbidities. Multiple therapies are available with inconsistent outcomes and potentially severe adverse effects. To determine whether low-dose naltrexone is an effective treatment for Hailey-Hailey disease. This study was a case series performed at a dermatology outpatient clinic of 3 patients with severe Hailey-Hailey disease recalcitrant to at least 4 therapies. Low-dose naltrexone, 3 mg nightly, titrated to 4.5 mg nightly in 2 patients. Reduction in size of lesions as well as subjective improvement of symptoms. All 3 patients noted significant healing of erosions and plaques starting from the peripheral aspect within 1 to 2 weeks of treatment, and clinical resolution of lesions within 2 months. Discontinuation of low-dose naltrexone resulted in flaring of symptoms, which cleared within 2 to 3 days on rechallenge with low-dose naltrexone. We present herein 3 cases of patients with severe Hailey-Hailey disease treated with low-dose naltrexone who achieved clinical resolution of symptoms. The success of these cases suggests low-dose naltrexone as a novel therapy for Hailey-Hailey disease. The possible mechanism may involve low-dose naltrexone influencing opioid or toll-like receptor signaling to improve calcium mobilization and improve keratinocyte differentiation and wound healing. Future studies are needed to clarify the mechanism and to define the role of low-dose naltrexone for treatment of Hailey-Hailey disease.

Comparison of ambulatory blood pressure-lowering effects of higher doses of different calcium antagonists in uncontrolled hypertension: the Calcium Antagonist Controlled-Release High-Dose Therapy in Uncontrolled Refractory Hypertensive Patients (CARILLON) Study.

PubMed

Mizuno, Hiroyuki; Hoshide, Satoshi; Tomitani, Naoko; Kario, Kazuomi

2017-10-01

Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial. Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group. The changes in 24-hr BP were comparable between the groups. The nifedipine group demonstrated a significant decrease in their urinary albumin creatinine ratio, whereas the amlodipine group demonstrated a significant decrease in their NTproBNP level. However, there was no significant difference in any biomarkers between the two groups. Nifedipine showed an almost equal effect on ambulatory blood pressure as amlodipine. Their potentially differential effects on renal protection and NTproBNP should be tested in larger samples.

TH-AB-207A-04: Assessment of Patients’ Cumulative Effective Dose From CT Examinations

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

Bostani, M; Cagnon, C; Sepahdari, A

Purpose: The Joint Commission requires institutions to consider patient’s age and recent imaging exams when deciding on the most appropriate type of imaging exam. Additionally, knowing patient’s imaging history can help prevent duplicate scans. Radiation dose management software affords new opportunities to identify and utilize patients with high cumulative doses as one proxy for subsequent review of imaging history and opportunities in avoiding redundant exams. Methods: Using dose management software (Radimetrics, Bayer Healthcare) a total of 72073 CT examinations performed from Jan 2015 to Jan 2016 were examined to categorize patients with a cumulative effective dose of 100 mSv andmore » above. This threshold was selected based on epidemiological studies on populations exposed to radiation, which demonstrate a statistical increase of cancer risk at doses above 100 mSv. Histories of patients with highest cumulative dose and highest number of exams were further investigated by a Radiologist for appropriateness of recurrent studies and potential opportunities for reduction. Results: Out of 34762 patients, 927 (2.7%) were identified with a cumulative dose of 100 mSv and above. The highest cumulative dose (842 mSv) belonged to an oncology patient who underwent 2 diagnostic exams and 9 interventional ablative CT guided procedures. The patient with highest number of exams (56 counts) and cumulative dose of 170 mSv was a 17 year old trauma patient. An imaging history review of these two patients did not suggest any superfluous scans. Conclusion: Our limited pilot study suggests that recurrent CT exams for patients with oncologic or severe trauma history may be warranted and appropriate. As a result, for future studies we will be focusing on high dose patient cohorts not associated with oncology or severe trauma. Additionally, the review process itself has suggested areas for potential improvement in patient care, including improved documentation and Radiologist involvement in patient management. Dr. McNitt-Gray’s disclosures: Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

SU-F-T-325: On the Use of Bolus in Dosimetry and Dose Reduction for Pacemaker and Defibrillator

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

Liu, W; Kenneth, R; Higgins, S

Purpose: Special attention is required in planning and administering radiation therapy to patients with cardiac implantable electronic devices (CIEDs), such as pacemaker and defibrillator. The range of dose to CIEDs that can induce malfunction is very large among CIEDs. Significant defects have been reported at dose as low as 0.15Gy. Failures causing discomfort have been reported at dose as low as 0.05Gy. Therefore, accurate estimation of dose to CIED and dose reduction are both important even if the dose is expected to be less than the often-used 2Gy limit. We investigate the use of bolus in in vivo dosimetry formore » CIEDs. Methods: In our clinic, high-energy beams (>10MV) are not used for patients with CIED due to neutron production. Solid water phantom measurements of out-of-field dose for a 6MV beam were performed using parallel plate chamber at different depth with and without 2cm bolus covering the chamber. In vivo dosimetry at skin surface above the pacemaker was performed with and without bolus for 3 patients with pacemaker <5cm from the field edge. Results: Chamber measured dose at depth ∼1 to 1.5cm below the skin surface, where the CIED is normally located, was reduced by ∼6% – 20% with bolus. The dose reduction became smaller at deeper depth. In vivo dosimetry at skin surface also yielded ∼20% – 60% lower dose when using bolus for the 3 patients. In general, TPS calculation underestimated the dose. The dose measured with bolus is closer to the dose at the depth of the pacemaker and less affected by contaminant electrons and linac head leakage. Conclusion: In vivo CIED dose measurements should be performed with 1 to 2cm bolus covering the dosimeter on the skin above the CIED for more accurate CIED dose estimation. The use of bolus also reduces the dose delivered to CIED.« less

Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance.

PubMed

Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol ® ATO 5/Transcutol ® HP and tallow fat/Transcutol ® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol ® ATO 5/Transcutol ® HP batch, then 81% and 95% for tallow fat/Transcutol ® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol ® ATO 5/Transcutol ® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol ® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem ® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference ( P <0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms.

Sustained-release liquisolid compact tablets containing artemether–lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

PubMed Central

Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

2016-01-01

The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether–lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (P<0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms. PMID:27932882

Effects of Low-Dose Mindfulness-Based Stress Reduction (MBSR-ld) on Working Adults

ERIC Educational Resources Information Center

Klatt, Maryanna D.; Buckworth, Janet; Malarkey, William B.

2009-01-01

Mindfulness-based stress reduction (MBSR) has produced behavioral, psychological, and physiological benefits, but these programs typically require a substantial time commitment from the participants. This study assessed the effects of a shortened (low-dose [ld]) work-site MBSR intervention (MBSR-ld) on indicators of stress in healthy working…

Radiation dose reduction using a neck detection algorithm for single spiral brain and cervical spine CT acquisition in the trauma setting.

PubMed

Ardley, Nicholas D; Lau, Ken K; Buchan, Kevin

2013-12-01

Cervical spine injuries occur in 4-8 % of adults with head trauma. Dual acquisition technique has been traditionally used for the CT scanning of brain and cervical spine. The purpose of this study was to determine the efficacy of radiation dose reduction by using a single acquisition technique that incorporated both anatomical regions with a dedicated neck detection algorithm. Thirty trauma patients for brain and cervical spine CT were included and were scanned with the single acquisition technique. The radiation doses from the single CT acquisition technique with the neck detection algorithm, which allowed appropriate independent dose administration relevant to brain and cervical spine regions, were recorded. Comparison was made both to the doses calculated from the simulation of the traditional dual acquisitions with matching parameters, and to the doses of retrospective dual acquisition legacy technique with the same sample size. The mean simulated dose for the traditional dual acquisition technique was 3.99 mSv, comparable to the average dose of 4.2 mSv from 30 previous patients who had CT of brain and cervical spine as dual acquisitions. The mean dose from the single acquisition technique was 3.35 mSv, resulting in a 16 % overall dose reduction. The images from the single acquisition technique were of excellent diagnostic quality. The new single acquisition CT technique incorporating the neck detection algorithm for brain and cervical spine significantly reduces the overall radiation dose by eliminating the unavoidable overlapping range between 2 anatomical regions which occurs with the traditional dual acquisition technique.

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

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

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

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

Modeling the Prodromal Effects and Performance Reduction of Astronauts from Exposure to Large Solar Particle Events

NASA Technical Reports Server (NTRS)

Hu, S.; Kim, M. Y.; McClellan, G. E.; Nikjoo, H.; Cucinotta, F. A.

2007-01-01

In space exploration outside the Earth's geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possibility of failure of the mission. Acute risks are especially of concern during spacewalks on the lunar surface because of the rapid onset of SPE's and science goals that involve long distances to crew habitats. Thus assessing the potential of early radiation effect under such adverse conditions is of prime importance. Here we present a biologic based mathematical model which describes the dose and time-dependent early human responses to ionizing radiation. We examine the possible early effects on crew behind various shielding materials from exposure to some historical large SPEs on the lunar and Mars surfaces. The doses and dose rates were calculated using the BRYNTRN code (Kim, M.Y, Hu, X, and Cucinotta, F.A, Effect of Shielding Materials from SPEs on the Lunar and Mars Surface, AIAA Space 2005, paper number AIAA-2005-6653, Long Beach, CA, August 30-September 1, 2005) and the hazard of the early radiation effects and performance reduction were calculated using the RIPD code (Anno, G.H, McClellan, G.E., Dore, M.A, Protracted Radiation-Induced Performance Decrement, Volume 1 Model Development,1996, Defense Nuclear Agency: Alexandria VA). Based on model assumptions we show that exposure to these historical SPEs do cause early effects to crew members and impair their performance if effective shielding and medical countermeasure tactics are not provided. The calculations show multiple occurrence of large SPEs in a short period of time significantly increase the severity of early illness, however early death from failure of the hematopoietic system is very unlikely because of the dose-rate and dose heterogeneity of SPEs. Results from these types of calculations will be a guide in design of protection systems and medical response strategy for astronauts in case of exposure to high dose irradiation during future space missions.

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

PubMed

Mueck, F G; Körner, M; Scherr, M K; Geyer, L L; Deak, Z; Linsenmaier, U; Reiser, M; Wirth, S

2012-03-01

To compare the image quality of dose-reduced 64-row abdominal CT reconstructed at different levels of adaptive statistical iterative reconstruction (ASIR) to full-dose baseline examinations reconstructed with filtered back-projection (FBP) in a clinical setting and upgrade situation. Abdominal baseline examinations (noise index NI = 29; LightSpeed VCT XT, GE) were intra-individually compared to follow-up studies on a CT with an ASIR option (NI = 43; Discovery HD750, GE), n = 42. Standard-kernel images were calculated with ASIR blendings of 0 - 100 % in slice and volume mode, respectively. Three experienced radiologists compared the image quality of these 567 sets to their corresponding full-dose baseline examination (- 2: diagnostically inferior, - 1: inferior, 0: equal, + 1: superior, + 2: diagnostically superior). Furthermore, a phantom was scanned. Statistical analysis used the Wilcoxon - the Mann-Whitney U-test and the intra-class correlation (ICC). The mean CTDIvol decreased from 19.7 ± 5.5 to 12.2 ± 4.7 mGy (p < 0.001). The ICC was 0.861. The total image quality of the dose-reduced ASIR studies was comparable to the baseline at ASIR 50 % in slice (p = 0.18) and ASIR 50 - 100 % in volume mode (p > 0.10). Volume mode performed 73 % slower than slice mode (p < 0.01). After the system upgrade, the vendor recommendation of ASIR 50 % in slice mode allowed for a dose reduction of 38 % in abdominal CT with comparable image quality and time expenditure. However, there is still further dose reduction potential for more complex reconstruction settings. © Georg Thieme Verlag KG Stuttgart · New York.

In vitro and in vivo antibiofilm potential of 2,4-Di-tert-butylphenol from seaweed surface associated bacterium Bacillus subtilis against group A streptococcus.

PubMed

Viszwapriya, Dharmaprakash; Prithika, Udayakumar; Deebika, Sundaresan; Balamurugan, Krishnaswamy; Pandian, Shunmugiah Karutha

2016-10-01

Biofilm formation of Group A Streptococcus (GAS) is recognized as an important virulent determinant. The present study reports the antibiofilm potential of seaweed (Gracilaria gracilis) surface associated Bacillus subtilis against GAS. Purification revealed 2,4-Di-tert-butyl-phenol (DTBP) as the active principle. DTBP exhibited a dose dependent antibiofilm activity against GAS (SF370 & six different clinical M serotypes). Microscopic analysis revealed changes in cell surface architecture and reduced thickness upon DTBP treatment. Results of extracellular polymeric substance quantification, microbial adhesion to hydrocarbon assay and fourier transform infrared spectroscopic analysis suggested that DTBP probably interferes with the initial adhesion stage of biofilm formation cascade. Reduction in hyaluronic acid synthesis goes in unison with blood survival assay wherein, increased susceptibility to phagocytosis was observed. In vivo studies using Caenorhabditis elegans manifested the reduction in adherence and virulence, which prompts further investigation of the potential of DTBP for the treatment of GAS infections. Copyright © 2016 Elsevier GmbH. All rights reserved.

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens

PubMed Central

Annamanedi, Madhavi; Varma, Gajapati Y. N.; Anuradha, K.; Kalle, Arunasree M.

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections. PMID:28533769

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens.

PubMed

Annamanedi, Madhavi; Varma, Gajapati Y N; Anuradha, K; Kalle, Arunasree M

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections.

Toward the development of a one-dose classical swine fever subunit vaccine: antigen titration, immunity onset, and duration of immunity

PubMed Central

Madera, Rachel F.; Wang, Lihua; Gong, Wenjie; Burakova, Yulia; Buist, Sterling; Nietfeld, Jerome; Henningson, Jamie; Cino-Ozuna, Ada G.; Tu, Changchun

2018-01-01

Highly contagious classical swine fever (CSF) remains a major trade and health problem in the pig industry, resulting in large economic losses worldwide. In CSF-endemic countries, attenuated CSF virus (CSFV) vaccines have been routinely used to control the disease. However, eradication of CSFV in a geographical area would require permanent reduction to zero presence of the virus. It is therefore of paramount importance to develop a safe, potent, and non-infectious CSF vaccine. We have previously reported on a cost-effective CSF E2 subunit vaccine, KNB-E2, which can protect against CSF symptoms in a single dose containing 75 µg of recombinant CSFV glycoprotein E2. In this study, we report on a series of animal studies undertaken to elucidate further the efficacy of KNB-E2. We found that pigs vaccinated with a single KNB-E2 dose containing 25 µg of recombinant CSFV glycoprotein E2 were protected from clinical symptoms of CSF. In addition, KNB-E2-mediated reduction of CSF symptoms was observed at two weeks post-vaccination and the vaccinated pigs continued to exhibit reduced CSF clinical signs when virus challenged at two months and four months post-vaccination. These results suggest that KNB-E2 effectively reduces CSF clinical signs, indicating the potential of this vaccine for safely minimizing CSF-related losses. PMID:29510474

Potential of UVC germicidal irradiation in suppressing crown rot disease, retaining postharvest quality and antioxidant capacity of Musa AAA "Berangan" during fruit ripening.

PubMed

S Mohamed, Nuratika Tamimi; Ding, Phebe; Kadir, Jugah; M Ghazali, Hasanah

2017-09-01

Crown rot caused by fungal pathogen is the most prevalent postharvest disease in banana fruit that results significant economic losses during transportation, storage, and ripening period. Antifungal effects of ultraviolet C (UVC) irradiation at doses varied from 0.01 to 0.30 kJ m -2 were investigated in controlling postharvest crown rot disease, maintenance of fruit quality, and the effects on antioxidant capacity of Berangan banana fruit during ripening days at 25 ± 2°C and 85% RH. Fruits irradiated with 0.30 kJ m -2 exhibited the highest (i.e., 62.51%) reduction in disease severity. However, the application of UVC at all doses caused significant browning damages on fruit peel except the dose of 0.01 kJ m -2 . This dose synergistically reduced 46.25% development of postharvest crown and did not give adverse effects on respiration rate, ethylene production, weight loss, firmness, color changes, soluble solids concentration, titratable acidity, and pH in banana as compared to the other treatments and control. Meanwhile, the dose also enhanced a significant higher level of total phenolic content, FRAP, and DPPH values than in control fruits indicating the beneficial impact of UVC in fruit nutritional quality. The results of scanning electron micrographs confirmed that UVC irradiation retarded the losses of wall compartments, thereby maintained the cell wall integrity in the crown tissue of banana fruit. The results suggest that using 0.01 kJ m -2 UVC irradiation dose as postharvest physical treatment, the crown rot disease has potential to be controlled effectively together with maintaining quality and antioxidant of banana fruit.

3,3′,4,4′,5-Pentachlorobiphenyl (PCB 126) Decreases Hepatic and Systemic Ratios of Epoxide to Diol Metabolites of Unsaturated Fatty Acids in Male Rats

PubMed Central

Wu, Xianai; Yang, Jun; Morisseau, Christophe; Robertson, Larry W.; Hammock, Bruce; Lehmler, Hans-Joachim

2016-01-01

Disruption of the homeostasis of oxygenated regulatory lipid mediators (oxylipins), potential markers of exposure to aryl hydrocarbon receptor (AhR) agonists, such as 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), is associated with a range of diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Here we test the hypothesis that PCB 126 exposure alters the levels of oxylipins in rats. Male Sprague-Dawley rats (5-weeks old) were treated over a 3-month period every 2 weeks with intraperitoneal injections of PCB 126 in corn oil (cumulative doses of 0, 19.8, 97.8, and 390 µg/kg b.w.; 6 injections total). PCB 126 treatment caused a reduction in growth rates at the highest dose investigated, a dose-dependent decrease in thymus weights, and a dose-dependent increase in liver weights. Liver PCB 126 levels increased in a dose-dependent manner, while levels in plasma were below or close to the detection limit. The ratios of several epoxides to diol metabolites formed via the cytochrome P450 (P450) monooxygenase/soluble epoxide hydrolase (sEH) pathway from polyunsaturated fatty acids displayed a dose-dependent decrease in the liver and plasma, whereas levels of oxylipins formed by other metabolic pathways were generally not altered by PCB 126 treatment. The effects of PCB 126 on epoxide-to-diol ratios were associated with an increased CYP1A activity in liver microsomes and an increased sEH activity in liver cytosol and peroxisomes. These results suggest that oxylipins are potential biomarkers of exposure to PCB 126 and that the P450/sEH pathway is a therapeutic target for PCB 126-mediated hepatotoxicity that warrants further attention. PMID:27208083

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

PubMed

Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

2015-08-20

Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

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

Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence.

PubMed

Cadoni, Cristina; Pisanu, Augusta; Simola, Nicola; Frau, Lucia; Porceddu, Pier Francesca; Corongiu, Silvia; Dessì, Christian; Sil, Annesha; Plumitallo, Antonio; Wardas, Jadwiga; Di Chiara, Gaetano

2017-09-01

Although MDMA (3,4-methylendioxymethamphetamine, ecstasy) neurotoxicity in serotonin neurons is largely recognized in a wide variety of species including man, neurotoxicity in dopamine (DA) neurons is thought to be species-specific. MDMA is mainly consumed by adolescents, often in conjunction with caffeine (Energy Drinks) and this association has been reported to exacerbate MDMA toxic effects. In order to model these aspects of MDMA use, vis-à-vis their impact on DA neurons, we investigated the effects of adolescent exposure to low doses of MDMA (5 mg/kg for 10 days), alone or in combination with caffeine (10 mg/kg) on neuronal and functional DA indices and on recognition memory in adult rats. MDMA reduced density of tyrosine hydroxylase (TH) positive neurons in the ventral tegmental area and in the substantia nigra pars compacta, and immunoreactivity of TH and DA transporter in the nucleus accumbens (NAc) shell and core, and caudate-putamen. This same treatment caused a reduction of basal dialysate DA in the NAc core. MDMA-pretreated rats also showed behavioral sensitization to a MDMA challenge at adulthood and potentiation of MDMA-induced increase of dialysate DA in the NAc core, but not in the NAc shell. In addition, MDMA-treated rats displayed a deficit in recognition memory. Caffeine co-administration did not affect the above outcomes. Our results show that adolescent exposure of rats to low doses of MDMA induces long-lasting and widespread reduction of DA neurons indicative of a neurotoxic effect on DA neurons and suggestive of a degeneration of the same neurons. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of antiorthostatic unloading and long gamma-irradiation on rat bone marrow (MSCs)

NASA Astrophysics Data System (ADS)

Roe, Maria; Bobyleva, Polina; Shtemberg, Andrey; Buravkova, Ludmila

With the prospect of long interplanetary spaceflight becoming a real possibility there are some important questions that need to be answered regarding the combined effects of microgravity and long gamma-irradiation.The aim of this study was to evaluate the effects of synchronous antiorthostatic unloading and fractional gamma-irradiation on the functional characteristics of rat bone marrow multipotent stromal cells (MSCs).This experiment was carried out following all rules laid out by the Commission on Bioethics at the SSC RF - IBMP RAS. In this experiment the Wistar rats were kept in an unloaded position for a duration of 30 days. They were also subjected to 6 doses of gamma-radiation on the “GOBO-60” with a source of (137) Cs. The dose rate set to 1 meter 50 sGr / H (Total dose of 3 Gr).The study revealed a significant reduction in the number of colonies (CFU-F) in all cultures from the experimental groups when compared to the control groups. The most significant reduction was observed in the group, which had been subject to combined unloading, and radiation. This result was confirmed by examination of cell cultures during 10 days of growth.We found that the CD45 expression was increased in the groups exposed to radiation. At the same time a reduction in the expression of CD90 was observed during combination of radiation and unloading we found.The experimental groups also differed from the control group showing smaller lipid inclusions and decreased expression of alkaline phosphates in the MSCs. This experiment concluded that the bone marrow MSCs after a combination of unloading and multiple radiation sessions, showed a decrease in proliferation and differentiation potential which could reduce the adaption and reparative capacity of the organism.

Prevalence of prescription opioid use disorder among chronic opioid therapy patients after health plan opioid dose and risk reduction initiatives.

PubMed

Von Korff, Michael; Walker, Rod L; Saunders, Kathleen; Shortreed, Susan M; Thakral, Manu; Parchman, Michael; Hansen, Ryan N; Ludman, Evette; Sherman, Karen J; Dublin, Sascha

2017-08-01

No studies have assessed the comparative effectiveness of guideline-recommended interventions to reduce risk of prescription opioid use disorder among chronic opioid therapy (COT) patients. We compared the prevalence of prescription opioid use disorder among COT patients from intervention clinics that had implemented opioid dose and risk reduction initiatives for more than 4 years relative to control clinics that had not. After a healthcare system in Washington State implemented interventions to reduce opioid dose and risks, we surveyed 1588 adult primary care COT patients to compare the prevalence of prescription opioid use disorder among COT patients from the intervention and control clinics. Intervention clinics managed COT patients at lower COT doses and with more consistent use of risk reduction practices. Control clinics cared for similar COT patients but prescribed higher opioid doses and used COT risk reduction practices inconsistently. Prescription opioid use disorder was assessed with the Psychiatric Research Interview for Substance and Mental Disorders. The prevalence of prescription opioid use disorder was 21.5% (95% CI=18.9% to 24.4%) among COT patients in the intervention clinics and 23.9% (95% CI=20.5% to 27.6%) among COT patients in the control clinics. The adjusted relative risk of prescription opioid use disorder was 1.08 (95% CI=0.89, 1.32) among the control clinic patients relative to the intervention clinic patients. Long-term implementation of opioid dose and risk reduction initiatives was not associated with lower rates of prescription opioid use disorder among prevalent COT patients. Extreme caution should be exercised by clinicians considering COT for patients with chronic non-cancer pain until benefits of this treatment and attendant risks are clarified. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-12-01

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

[The determination of the discrepancy between the mathematically ascertained and experimentally provable efficiency of UV facilities for water disinfection].

PubMed

Leuker, G; Hingst, V

1992-10-01

Using three UV-plants of different technical designs for water disinfection, we studied the conformity between experimental germ reduction using standard test organisms and calculated UV-doses under various water flow conditions. Taking into consideration the style of construction of the UV-plants, the irradiation area and the layer thickness were used as constant parameters for dose calculations. This was also employed for the irradiation intensity, since the experiments were performed for a relatively short period compared of the life span of the UV-irradiators. Both exposure time and water transmission were employed as variable parameters in the dose calculations and experimental procedures respectively. The calculated UV-dose and experimentally obtained germ reduction values were comparatively the same for two of the three UV-plants studied. However, no correlation was observed between the reduction of E. coli and the corresponding calculated UV-dose values. Therefore, the calculated UV-dose values for any given UV-plant should be considered to be relative and by no means absolute values. We are of the opinion that within a certain range of water flow rate and transmission, antimicrobial effectiveness of different UV-plants should be demonstrated independent of dose values, technical and other construction characteristics. The applicability of the UV-plants studied is discussed.

Assessment of nicotine withdrawal-induced changes in sucrose preference in mice.

PubMed

Alkhlaif, Yasmin; Bagdas, Deniz; Jackson, Asti; Park, Abigail J; Damaj, Imad M

2017-10-01

Anhedonia, induced by nicotine withdrawal, may serve as an important affective sign that reinforces tobacco use and smoking relapse rates in humans. Animal models provide a way to investigate the underlying neurobiological factors involved in the decrease in responding for positive affective stimuli during nicotine withdrawal and may aid in drug development for nicotine dependence. Thus, we explored the use of the sucrose preference test to measure nicotine withdrawal-induced reduction in response for positive affective stimuli in mice. C57BL/6J and knockout (KO) mice were chronically exposed to different doses of nicotine through surgically implanted subcutaneous osmotic minipumps for 14days and underwent spontaneous nicotine withdrawal on day 15. A sucrose preference time course was performed and the results were compared to another well-established affective sign of nicotine withdrawal, the reduction in time spent in light side, using the Light Dark Box test. Subsequently, our results demonstrated a time-dependent and dose-related reduction in sucrose preference in nicotine withdrawn male C57BL/6J mice, indicative of a decrease in responding for positive affective stimuli. Furthermore, the sucrose preference reduction during nicotine withdrawal was consistent with decrease in time spent in the light side of the Light Dark Box test. We also found the reduction for positive affective stimuli and time spent in the light side was not present in nicotine withdrawn β2 and α6 KO mice, suggesting that these nicotinic subunits are involved in the affective signs of nicotine withdrawal. Thus, this report highlights the potential utility of the sucrose preference test as a useful measure of the decrease in responding for positive affective stimuli during spontaneous nicotine withdrawal. Copyright © 2017 Elsevier Inc. All rights reserved.

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

PubMed

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Evaluation of an iterative model-based reconstruction of pediatric abdominal CT with regard to image quality and radiation dose.

PubMed

Aurumskjöld, Marie-Louise; Söderberg, Marcus; Stålhammar, Fredrik; von Steyern, Kristina Vult; Tingberg, Anders; Ydström, Kristina

2018-06-01

Background In pediatric patients, computed tomography (CT) is important in the medical chain of diagnosing and monitoring various diseases. Because children are more radiosensitive than adults, they require minimal radiation exposure. One way to achieve this goal is to implement new technical solutions, like iterative reconstruction. Purpose To evaluate the potential of a new, iterative, model-based method for reconstructing (IMR) pediatric abdominal CT at a low radiation dose and determine whether it maintains or improves image quality, compared to the current reconstruction method. Material and Methods Forty pediatric patients underwent abdominal CT. Twenty patients were examined with the standard dose settings and 20 patients were examined with a 32% lower radiation dose. Images from the standard examination were reconstructed with a hybrid iterative reconstruction method (iDose 4 ), and images from the low-dose examinations were reconstructed with both iDose 4 and IMR. Image quality was evaluated subjectively by three observers, according to modified EU image quality criteria, and evaluated objectively based on the noise observed in liver images. Results Visual grading characteristics analyses showed no difference in image quality between the standard dose examination reconstructed with iDose 4 and the low dose examination reconstructed with IMR. IMR showed lower image noise in the liver compared to iDose 4 images. Inter- and intra-observer variance was low: the intraclass coefficient was 0.66 (95% confidence interval = 0.60-0.71) for the three observers. Conclusion IMR provided image quality equivalent or superior to the standard iDose 4 method for evaluating pediatric abdominal CT, even with a 32% dose reduction.

Alginate Oligosaccharides Inhibit Fungal Cell Growth and Potentiate the Activity of Antifungals against Candida and Aspergillus spp

PubMed Central

Tøndervik, Anne; Sletta, Håvard; Klinkenberg, Geir; Emanuel, Charlotte; Powell, Lydia C.; Pritchard, Manon F.; Khan, Saira; Craine, Kieron M.; Onsøyen, Edvar; Rye, Phil D.; Wright, Chris; Thomas, David W.; Hill, Katja E.

2014-01-01

The oligosaccharide OligoG, an alginate derived from seaweed, has been shown to have anti-bacterial and anti-biofilm properties and potentiates the activity of selected antibiotics against multi-drug resistant bacteria. The ability of OligoG to perturb fungal growth and potentiate conventional antifungal agents was evaluated using a range of pathogenic fungal strains. Candida (n = 11) and Aspergillus (n = 3) spp. were tested using germ tube assays, LIVE/DEAD staining, scanning electron microscopy (SEM), atomic force microscopy (AFM) and high-throughput minimum inhibition concentration assays (MICs). In general, the strains tested showed a significant dose-dependent reduction in cell growth at ≥6% OligoG as measured by optical density (OD600; P<0.05). OligoG (>0.5%) also showed a significant inhibitory effect on hyphal growth in germ tube assays, although strain-dependent variations in efficacy were observed (P<0.05). SEM and AFM both showed that OligoG (≥2%) markedly disrupted fungal biofilm formation, both alone, and in combination with fluconazole. Cell surface roughness was also significantly increased by the combination treatment (P<0.001). High-throughput robotic MIC screening demonstrated the potentiating effects of OligoG (2, 6, 10%) with nystatin, amphotericin B, fluconazole, miconazole, voriconazole or terbinafine with the test strains. Potentiating effects were observed for the Aspergillus strains with all six antifungal agents, with an up to 16-fold (nystatin) reduction in MIC. Similarly, all the Candida spp. showed potentiation with nystatin (up to 16-fold) and fluconazole (up to 8-fold). These findings demonstrate the antifungal properties of OligoG and suggest a potential role in the management of fungal infections and possible reduction of antifungal toxicity. PMID:25409186

Clarithromycin increases neuronal excitability in CA3 pyramidal neurons through a reduction in GABAergic signaling

PubMed Central

Elder, Courtney C.; García, Paul S.

2016-01-01

Antibiotics are used in the treatment and prevention of bacterial infections, but effects on neuron excitability have been documented. A recent study demonstrated that clarithromycin alleviates daytime sleepiness in hypersomnia patients (Trotti LM, Saini P, Freeman AA, Bliwise DL, García PS, Jenkins A, Rye DB. J Psychopharmacol 28: 697–702, 2014). To explore the potential application of clarithromycin as a stimulant, we performed whole cell patch-clamp recordings in rat pyramidal cells from the CA3 region of hippocampus. In the presence of the antibiotic, rheobase current was reduced by 50%, F-I relationship (number of action potentials as a function of injected current) was shifted to the left, and the resting membrane potential was more depolarized. Clarithromycin-induced hyperexcitability was dose dependent; doses of 30 and 300 μM clarithromycin significantly increased the firing frequency and membrane potential compared with controls (P = 0.003, P < 0.0001). We hypothesized that clarithromycin enhanced excitability by reducing GABAA receptor activation. Clarithromycin at 30 μM significantly reduced (P = 0.001) the amplitude of spontaneous miniature inhibitory GABAergic currents and at 300 μM had a minor effect on action potential width. Additionally, we tested the effect of clarithromycin in an ex vivo seizure model by evaluating its effect on spontaneous local field potentials. Bath application of 300 μM clarithromycin enhanced burst frequency twofold compared with controls (P = 0.0006). Taken together, these results suggest that blocking GABAergic signaling with clarithromycin increases cellular excitability and potentially serves as a stimulant, facilitating emergence from anesthesia or normalizing vigilance in hypersomnia and narcolepsy. However, the administration of clarithromycin should be carefully considered in patients with seizure disorders. NEW & NOTEWORTHY Clinical administration of the macrolide antibiotic clarithromycin has been associated with side effects such as mania, agitation, and delirium. Here, we investigated the adverse effects of this antibiotic on CA3 pyramidal cell excitability. Clarithromycin induces hyperexcitability in single neurons and is related to a reduction in GABAergic signaling. Our results support a potentially new application of clarithromycin as a stimulant to facilitate emergence from anesthesia or to normalize vigilance. PMID:27733592

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

PubMed Central

Häfner, D.; Beume, R.; Kilian, U.; Krasznai, G.; Lachmann, B.

1995-01-01

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 Figure 3 Figure 4 PMID:7582456

Rosewood oil induces sedation and inhibits compound action potential in rodents.

PubMed

de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

2009-07-30

Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients.

PubMed

Turner, Alice M; Stolk, Jan; Bals, Robert; Lickliter, Jason D; Hamilton, James; Christianson, Dawn R; Given, Bruce D; Burdon, Jonathan G; Loomba, Rohit; Stoller, James K; Teckman, Jeffery H

2018-03-21

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder causing pulmonary and liver disease. The PiZ mutation in AAT (SERPINA1) results in mis-folded AAT protein (Z-AAT) accumulating in hepatocytes, leading to fibrosis and cirrhosis. RNAi-based therapeutics silencing production of hepatic Z-AAT might benefit patients with AATD-associated liver disease. This study evaluated an RNAi therapeutic to silence production of AAT. Part A of this double-blind first-in-human study randomized 54 healthy volunteers (HVs) into single dose cohorts (two placebo: four active), receiving escalating doses of the investigational agent ARC-AAT from 0.38 to 8.0 mg/kg or placebo. Part B randomized 11 patients with PiZZ (homozygous for Z-AAT) genotype AATD, who received up to 4.0 mg/kg of ARC-AAT or placebo. Patients with baseline FibroScan® >11 kPa or forced expiratory volume in one second (FEV1) <60% were excluded. Assessments included safety, pharmacokinetics, and change in serum AAT concentrations. A total of 36 HVs received ARC-AAT and 18 received placebo (part A). Seven PiZZ individuals received ARC-AAT and four received placebo (part B). A dose response in serum AAT reduction was observed at doses ≥4 mg/kg with similar relative reductions in PiZZ patients and HVs at 4 mg/kg and a maximum reduction of 76.1% (HVs) vs. 78.8% (PiZZ) at this dose. The time it took for serum AAT to return to baseline was similar for HV and PiZZ. There were no notable differences between HV and PiZZ safety parameters. The study was terminated early because of toxicity findings related to the delivery vehicle (ARC-EX1) seen in a non-human primate study. PiZZ patients and HVs responded similarly to ARC-AAT. Deep and durable knockdown of hepatic AAT production based on observed reduction in serum AAT concentrations was demonstrated. Accumulation of abnormal proteins in the livers of patients with alpha-1 antitrypsin deficiency may lead to decreased liver function and potentially liver failure. Therapeutics targeting the production of these abnormal proteins may be used to prevent or treat liver disease in patients with alpha-1 antitrypsin deficiency. NCT02363946. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effect of x-ray tube parameters and iodine concentration on image quality and radiation dose in cerebral pediatric and adult CT angiography: a phantom study.

PubMed

Papadakis, Antonios E; Perisinakis, Kostas; Raissaki, Maria; Damilakis, John

2013-04-01

The aim of the present phantom study was to investigate the effect of x-ray tube parameters and iodine concentration on image quality and radiation dose in cerebral computed tomographic (CT) angiographic examinations of pediatric and adult individuals. Four physical anthropomorphic phantoms that represent the average individual as neonate, 1-year-old, 5-year-old, and 10-year-old children and the RANDO phantom that simulates the average adult individual were used. Cylindrical vessels were bored along the brain-equivalent plugs of each physical phantom. To simulate the brain vasculature, vessels of 0.6, 1, 2, and 3 mm in diameter were created. These vessels were filled with contrast medium (CM) solutions at different iodine concentrations, that is, 5.6, 4.2, 2.7, and 1.4 mg I/mL. The phantom heads were scanned at 120, 100, and 80 kV. The applied quality reference tube current-time product values ranged from a minimum of 45 to a maximum of 680. The CT acquisitions were performed on a 16-slice CT scanner using the automatic exposure control system. Image quality was evaluated on the basis of image noise and contrast-to-noise ratio (CNR) between the contrast-enhanced iodinated vessels and the unenhanced regions of interest. Dose reduction was calculated as the percentage difference of the CT dose index value at the quality reference tube current-time product and the CT dose index at the mean modulated tube current-time product. Image noise that was measured using the preset tube current-time product settings varied significantly among the different phantoms (P < 0.0001). Hounsfield unit number of iodinated vessels was linearly related to CM concentration (r² = 0.907) and vessel diameter (r² = 0.918). The Hounsfield unit number of iodinated vessels followed a decreasing trend from the neonate phantom to the adult phantom at all kilovoltage settings. For the same image noise level, a CNR improvement of up to 69% and a dose reduction of up to 61% may be achieved when CT acquisition is performed at 80 kV compared with 120 kV. For the same CNR, a reduction by 25% of the administered CM concentration may be achieved when CT acquisition is performed at 80 kV compared with 120 kV. In cerebral CT angiographic studies, appropriate adjustment of the preset tube current-time product settings is required to achieve the same image noise level among participants of different age. Cerebral CT angiography at 80 kV significantly improves CNR and significantly reduces radiation dose. Moreover, at 80 kV, a considerable reduction of the administered amount of the CM may be reached, thus reducing potential risks for contrast-induced nephropathy.

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

PubMed

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

2015-01-01

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

Implementation of a Community-Based Secondhand Smoke Reduction Intervention for Caregivers of Urban Children with Asthma: Process Evaluation, Successes and Challenges

ERIC Educational Resources Information Center

Blaakman, Susan; Tremblay, Paul J.; Halterman, Jill S.; Fagnano, Maria; Borrelli, Belinda

2013-01-01

Many children, including those with asthma, remain exposed to secondhand smoke. This manuscript evaluates the process of implementing a secondhand smoke reduction counseling intervention using motivational interviewing (MI) for caregivers of urban children with asthma, including reach, dose delivered, dose received and fidelity. Challenges,…

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

PubMed Central

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

2017-01-01

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

Dose perturbation effect of metallic spinal implants in proton beam therapy.

PubMed

Jia, Yingcui; Zhao, Li; Cheng, Chee-Wai; McDonald, Mark W; Das, Indra J

2015-09-08

The purpose of this study was to investigate the effect of dose perturbations for two metallic spinal screw implants in proton beam therapy in the perpendicular and parallel beam geometry. A 5.5 mm (diameter) by 45 mm (length) stainless steel (SS) screw and a 5.5 mm by 35 mm titanium (Ti) screw commonly used for spinal fixation were CT-scanned in a hybrid phantom of water and solid water. The CT data were processed with an orthopedic metal artifact reduction (O-MAR) algorithm. Treatment plans were generated for each metal screw with a proton beam oriented, first parallel and then perpendicular, to the longitudinal axis of the screw. The calculated dose profiles were compared with measured results from a plane-parallel ion chamber and Gafchromic EBT2 films. For the perpendicular setup, the measured dose immediately downstream from the screw exhibited dose enhancement up to 12% for SS and 8% for Ti, respectively, but such dose perturbation was not observed outside the lateral edges of the screws. The TPS showed 5% and 2% dose reductions immediately at the interface for the SS nd Ti screws, respectively, and up to 9% dose enhancements within 1 cm outside of the lateral edges of the screws. The measured dose enhancement was only observed within 5 mm from the interface along the beam path. At deeper depths, the lateral dose profiles appeared to be similar between the measurement and TPS, with dose reduction in the screw shadow region and dose enhancement within 1-2 cm outside of the lateral edges of the metals. For the parallel setup, no significant dose perturbation was detected at lateral distance beyond 3 mm away from both screws. Significant dose discrepancies exist between TPS calculations and ion chamber and film measurements in close proximity of high-Z inhomogeneities. The observed dose enhancement effect with proton therapy is not correctly modeled by TPS. An extra measure of caution should be taken when evaluating dosimetry with spinal metallic implants.

Effects of ultrasound-induced inertial cavitation on enzymatic thrombolysis.

PubMed

Chuang, Yueh-Hsun; Cheng, Po-Wen; Chen, Szu-Chia; Ruan, Jia-Ling; Li, Pai-Chi

2010-04-01

Cavitation induced by ultrasound enhances enzymatic fibrinolysis by increasing the transport of reactants. However, the effects of cavitation need to be fully understood before sonothrombolysis can be applied clinically. In order to understand the underlying mechanisms, we examined the effects of combining ultrasound, microbubbles and thrombolytic enzymes on thrombolysis. First, we evaluated the relations between inertial cavitation and the reduction in the weight of a blood clot. Inertial cavitation was varied by changing the amplitude and duration of the transmitted acoustic wave as well as the concentration of microbubbles used to induce cavitation. Second, we studied the combined effects of streptokinase and inertial cavitation on thrombolysis. The results show that inertial cavitation increases the weight reduction of a blood clot by up to 33.9%. With linear regression fitting, the measured differential inertial cavitation dose and the weight reduction had a correlation coefficient of 0.66. Microscopically, enzymatic thrombolysis effects manifest as multiple large cavities within the clot that are uniformly distributed on the side exposed to ultrasound. This suggests that inertial cavitation plays an important role in producing cavities, while microjetting of the microbubbles induces pits on the clot surface. These observations preliminarily demonstrate the clinical potential of sonothrombolysis. The use of the differential inertial cavitation dose as an indicator of blood clot weight loss for controlled sonothrombolysis is also possible and will be further explored.

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988 - 1993: II. In vivo planning and dosimetry

NASA Astrophysics Data System (ADS)

Planskoy, B.; Tapper, P. D.; Bedford, A. M.; Davis, F. M.

1996-11-01

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were within of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of (1 s.d.) and in the lungs (40 patients, five slices) of (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior - posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an increase in treatment set-up times.

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.

A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

PubMed

Ikeda, S; Takano, Y; Cynshi, O; Tanaka, R; Christ, A D; Boerlin, V; Beyer, U; Beck, A; Ciorciaro, C; Meyer, M; Kadowaki, T

2015-10-01

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM. © 2015 John Wiley & Sons Ltd.

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

Perioperative use of selective alpha-2 agonists and antagonists in small animals

PubMed Central

2004-01-01

Abstract Alpha-2 agonists are the only single class of anesthetic drugs that induce reliable, dose-dependent sedation, analgesia, and muscle relaxation in dogs and cats. Used at low doses, as adjuncts to injectable and inhalational anesthetics, selective alpha-2 agonists dramatically reduce the amount of anesthetic drug required to induce and maintain anesthesia. This reduction in anesthetic requirements is achieved without significant depression of pulmonary function and with limited effects on cardiovascular function. Selective alpha-2 agonists can also be used postoperatively to potentiate the analgesic effects of opioids and other drugs. Given the nearly ideal pharmacodynamic profile and reversibility of alpha-2 agonists, these drugs will play a central role in balanced approaches to anesthesia and the management of perioperative pain in healthy dogs and cats. PMID:15283516

Automated size-specific CT dose monitoring program: assessing variability in CT dose.

PubMed

Christianson, Olav; Li, Xiang; Frush, Donald; Samei, Ehsan

2012-11-01

The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CT imaging. The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED(adj)). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED(adj) between scanner models and across institutions. No significant difference was found between computer measurements of patient thickness and observer measurements (p = 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED(adj) that differed by up to 44% from effective dose estimates that were not adjusted by patient size. Additionally, considerable differences were noted in ED(adj) distributions between scanners, with scanners employing iterative reconstruction exhibiting significantly lower ED(adj) (range: 9%-64%). Finally, a significant difference (up to 59%) in ED(adj) distributions was observed between institutions, indicating the potential for dose reduction. The authors developed a robust automated size-specific radiation dose monitoring program for CT. Using this program, significant differences in ED(adj) were observed between scanner models and across institutions. This new dose monitoring program offers a unique tool for improving quality assurance and standardization both within and across institutions.

Automated size-specific CT dose monitoring program: Assessing variability in CT dose

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

Christianson, Olav; Li Xiang; Frush, Donald

2012-11-15

Purpose: The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CTmore » imaging. Methods: The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED{sub adj}). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED{sub adj} between scanner models and across institutions. Results: No significant difference was found between computer measurements of patient thickness and observer measurements (p= 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED{sub adj} that differed by up to 44% from effective dose estimates that were not adjusted by patient size. Additionally, considerable differences were noted in ED{sub adj} distributions between scanners, with scanners employing iterative reconstruction exhibiting significantly lower ED{sub adj} (range: 9%-64%). Finally, a significant difference (up to 59%) in ED{sub adj} distributions was observed between institutions, indicating the potential for dose reduction. Conclusions: The authors developed a robust automated size-specific radiation dose monitoring program for CT. Using this program, significant differences in ED{sub adj} were observed between scanner models and across institutions. This new dose monitoring program offers a unique tool for improving quality assurance and standardization both within and across institutions.« less

[BIOLOGICAL EFFECTIVENESS OF FISSION SPECTRUM NEUTRONS AND PROTONS WITH ENERGIES OF 60-126 MEV DURING ACUTE AND PROLONGED IRRADIATION].

PubMed

Shafirkin, A V

2015-01-01

Neutrons of the fission spectrum are characterized by relatively high values of linear energy transfer (LET). Data about their effects on biological objects are used to evaluate the risk of delayed effects of accelerated ions within the same LET range that serve as an experimental model of the nuclei component of galactic cosmic rays (GCR). Additionally, risks of delayed consequences to cosmonaut's health and average lifetime from certain GCR fluxes and secondary neutrons can be also prognosticated. The article deals with comparative analysis of the literature on reduction of average lifespan (ALS) of animals exposed to neutron reactor spectrum, 60-126 MeV protons, and X- and γ-rays in a broad range of radiation intensity and duration. It was shown that a minimal lifespan reduction by 5% occurs due to a brief exposure to neutrons with the absorbed dose of 5 cGy, whereas same lifespan reduction due to hard X- and γ-radiation occurs after absorption of a minimal dose of 100 cGy. Therefore, according to the estimated minimal ALS reduction in mice, neutron effectiveness is 20-fold higher. Biological effectiveness of protons as regards ALS reduction is virtually equal to that of standard types of radiation. Exposure to X- and γ-radiation with decreasing daily doses, and increasing number of fractions and duration gives rise to an apparent trend toward a less dramatic ALS reduction in mice; on the contrary, exposure to neutrons of varying duration had no effect on threshold doses for the specified ALS reductions. Factors of relative biological effectiveness of neutrons reached 40.

Cardiac dose reduction with deep inspiration breath hold for left-sided breast cancer radiotherapy patients with and without regional nodal irradiation.

PubMed

Yeung, Rosanna; Conroy, Leigh; Long, Karen; Walrath, Daphne; Li, Haocheng; Smith, Wendy; Hudson, Alana; Phan, Tien

2015-09-22

Deep inspiration breath hold (DIBH) reduces heart and left anterior descending artery (LAD) dose during left-sided breast radiation therapy (RT); however there is limited information about which patients derive the most benefit from DIBH. The primary objective of this study was to determine which patients benefit the most from DIBH by comparing percent reduction in mean cardiac dose conferred by DIBH for patients treated with whole breast RT ± boost (WBRT) versus those receiving breast/chest wall plus regional nodal irradiation, including internal mammary chain (IMC) nodes (B/CWRT + RNI) using a modified wide tangent technique. A secondary objective was to determine if DIBH was required to meet a proposed heart dose constraint of Dmean < 4 Gy in these two cohorts. Twenty consecutive patients underwent CT simulation both free breathing (FB) and DIBH. Patients were grouped into two cohorts: WBRT (n = 11) and B/CWRT + RNI (n = 9). 3D-conformal plans were developed and FB was compared to DIBH for each cohort using Wilcoxon signed-rank tests for continuous variables and McNemar's test for discrete variables. The percent relative reduction conferred by DIBH in mean heart and LAD dose, as well as lung V20 were compared between the two cohorts using Wilcox rank-sum testing. The significance level was set at 0.05 with Bonferroni correction for multiple testing. All patients had comparable target coverage on DIBH and FB. DIBH statistically significantly reduced mean heart and LAD dose for both cohorts. Percent reduction in mean heart and LAD dose with DIBH was significantly larger in the B/CWRT + RNI cohort compared to WBRT group (relative reduction in mean heart and LAD dose: 55.9 % and 72.1 % versus 29.2 % and 43.5 %, p < 0.02). All patients in the WBRT group and five patients (56 %) in the B/CWBRT + RNI group met heart Dmean <4 Gy with FB. All patients met this constraint with DIBH. All patients receiving WBRT met Dmean Heart < 4 Gy on FB, while only slightly over half of patients receiving B/CWRT + RNI were able to meet this constraint in FB. DIBH allowed a greater reduction in mean heart and LAD dose in patients receiving B/CWRT + RNI, including IMC nodes than patients receiving WBRT. These findings suggest greatest benefit from DIBH treatment for patients receiving regional nodal irradiation.

Evaluation of the radiation dose in the thyroid gland using different protective collars in panoramic imaging.

PubMed

Hafezi, Ladan; Arianezhad, S Marjan; Hosseini Pooya, Seyed Mahdi

2018-04-25

The value for the use of thyroid shield is one of the issues in radiation protection of patients in dental panoramic imaging. The objective of this research is to investigate the attenuation characteristics of some models of thyroid shielding in dental panoramic examinations. The effects of five different types of lead and lead-free (Pb-equivalent) shields on dose reduction of thyroid gland were investigated using implanted Thermoluminescence Dosemeters (TLDs) in head-neck parts of a Rando phantom. The results show that frontal lead and Pb-equivalent shields can reduce the thyroid dose around 50% and 19%, respectively. It can be concluded that the effective shielding area is an important parameter in thyroid gland dose reduction. Lead frontal collars with large effective shielding areas (>~300 cm 2 but not necessarily very large) are appropriate for an optimized thyroid gland dose reduction particularly for the critical patients in dental panoramic imaging. Regardless of the shape and thickness, using the Pb-equivalent shields is not justifiable in dental panoramic imaging.

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

TU-G-BRA-04: Changes in Regional Lung Function Measured by 4D-CT Ventilation Imaging for Thoracic Radiotherapy

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

Nakajima, Y; Kadoya, N; Kabus, S

Purpose: To test the hypothesis: 4D-CT ventilation imaging can show the known effects of radiotherapy on lung function: (1) radiation-induced ventilation reductions, and (2) ventilation increases caused by tumor regression. Methods: Repeat 4D-CT scans (pre-, mid- and/or post-treatment) were acquired prospectively for 11 thoracic cancer patients in an IRB-approved clinical trial. A ventilation image for each time point was created using deformable image registration and the Hounsfield unit (HU)-based or Jacobian-based metric. The 11 patients were divided into two subgroups based on tumor volume reduction using a threshold of 5 cm{sup 3}. To quantify radiation-induced ventilation reduction, six patients whomore » showed a small tumor volume reduction (<5 cm{sup 3}) were analyzed for dose-response relationships. To investigate ventilation increase caused by tumor regression, two of the other five patients were analyzed to compare ventilation changes in the lung lobes affected and unaffected by the tumor. The remaining three patients were excluded because there were no unaffected lobes. Results: Dose-dependent reductions of HU-based ventilation were observed in a majority of the patient-specific dose-response curves and in the population-based dose-response curve, whereas no clear relationship was seen for Jacobian-based ventilation. The post-treatment population-based dose-response curve of HU-based ventilation demonstrated the average ventilation reductions of 20.9±7.0% at 35–40 Gy (equivalent dose in 2-Gy fractions, EQD2), and 40.6±22.9% at 75–80 Gy EQD2. Remarkable ventilation increases in the affected lobes were observed for the two patients who showed an average tumor volume reduction of 37.1 cm{sup 3} and re-opening airways. The mid-treatment increase in HU-based ventilation of patient 3 was 100.4% in the affected lobes, which was considerably greater than 7.8% in the unaffected lobes. Conclusion: This study has demonstrated that 4D-CT ventilation imaging shows the known effects of radiotherapy on lung function: radiation-induced ventilation reduction and ventilation increase caused by tumor regression, providing validation for 4D-CT ventilation imaging. This study was supported in part by a National Lung Cancer Partnership Young Investigator Research grant.« less

Radiation dose reduction in thoracic and lumbar spine instrumentation using navigation based on an intraoperative cone beam CT imaging system: a prospective randomized clinical trial.

PubMed

Pireau, Nathalie; Cordemans, Virginie; Banse, Xavier; Irda, Nadia; Lichtherte, Sébastien; Kaminski, Ludovic

2017-11-01

Spine surgery still remains a challenge for every spine surgeon, aware of the potential serious outcomes of misplaced instrumentation. Though many studies have highlighted that using intraoperative cone beam CT imaging and navigation systems provides higher accuracy than conventional freehand methods for placement of pedicle screws in spine surgery, few studies are concerned about how to reduce radiation exposure for patients with the use of such technology. One of the main focuses of this study is based on the ALARA principle (as low as reasonably achievable). A prospective randomized trial was conducted in the hybrid operating room between December 2015 and December 2016, including 50 patients operated on for posterior instrumented thoracic and/or lumbar spinal fusion. Patients were randomized to intraoperative 3D acquisition high-dose (standard dose) or low-dose protocol, and a total of 216 pedicle screws were analyzed in terms of screw position. Two different methods were used to measure ionizing radiation: the total skin dose (derived from the dose-area product) and the radiation dose evaluated by thermoluminescent dosimeters on the surgical field. According to Gertzbein and Heary classifications, low-dose protocol provided a significant higher accuracy of pedicle screw placement than the high-dose protocol (96.1 versus 92%, respectively). Seven screws (3.2%), all implanted with the high-dose protocol, needed to be revised intraoperatively. The use of low-dose acquisition protocols reduced patient exposure by a factor of five. This study emphasizes the paramount importance of using low-dose protocols for intraoperative cone beam CT imaging coupled with the navigation system, as it at least does not affect the accuracy of pedicle screw placement and irradiates drastically less.

Standard Pentostatin Dose Reductions in Renal Insufficiency are not Adequate: Selected Patients with Steroid-Refractory Acute Graft-versus-Host Disease

PubMed Central

Poi, Ming J.; Hofmeister, Craig C.; Johnston, Jeffrey S.; Edwards, Ryan B.; Jansak, Buffy S.; Lucas, David M.; Farag, Sherif S.; Dalton, James T.; Devine, Steven M.; Grever, Michael R.; Phelps, Mitch A.

2013-01-01

Background and Objective Pentostatin is an irreversible inhibitor of adenosine deaminase and has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD. Dose reduction equations for patients with renal insufficiency are based on few patients with limited pharmacokinetic and clinical results. This phase II study (NCT00201786) was conducted to assess pentostatin efficacy and infectious complications seen from our previous phase I study in steroid-refractory acute GVHD (aGVHD). Patients and Methods Hospitalized patients with steroid-refractory aGVHD were given pentostatin 1.5 mg/m2/day intravenously on days 1–3 of each 14 day cycle. Prior to each dose, dose modifications were based on Cockcroft-Gault estimated creatinine clearance (eCrCL) with 30–50 ml/min/1.73m2 leading to a 50% dose reduction and eCrCL< 30 ml/min/1.73m2 leading to study removal. Plasma pentostatin area under the concentration-time curve (AUC) and incidence of infectious complications were evaluated. Results Two of the eight patients treated demonstrated excessive pentostatin exposure as determined by measurement of AUC. One of these patients had renal impairment while the other patient demonstrated borderline renal function. Despite dose reduction to 0.75 mg/m2, AUCs were significantly increased compared to the other patients in this study. Seven of eight patients treated with pentostatin had cytomegalovirus (CMV) viremia after pentostatin treatment; however none developed proven CMV disease. Conclusion A 50% dose reduction in patients with eCrCL 30–50 ml/min/1.73m2 seems reasonable. However, the eCrCL should be interpreted with extreme cautions in patients who are critically ill and/or with poor performance status. Renal function assessment based on the Cockcroft-Gault method could be significantly overestimated thus risking pentostatin over-dosing. These results imply a need to closely monitor pentostatin exposure in patients with renal insufficiency. PMID:23588536

TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

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

McGurk, R; Green, R; Lawrence, M

2015-06-15

Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dosemore » data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong Foundation.« less

Irradiation treatment of pharmaceutical and personal care products (PPCPs) in water and wastewater: An overview

NASA Astrophysics Data System (ADS)

Wang, Jianlong; Chu, Libing

2016-08-01

Pharmaceutical and personal care products (PPCPs), especially the pharmaceutically active compounds (PhACs) such as antibiotics and hormones have attracted great concerns worldwide for their persistence and potential threat to ecosystem and public health. This paper presents an overview on the ionizing irradiation-induced degradation of PPCPs in aqueous solution. Parameters that affect PPCPs degradation, such as the absorbed dose, solution pH, dose rate, water matrices and the presence of some inorganic ions and humic acid are evaluated. The mechanism and pathways of radiolytic degradation of PPCPs are reviewed. In many cases, PPCPs such as antibiotics and X-ray contrast agent could be removed completely by radiation, but a higher absorbed dose was needed for their mineralization and toxicity reduction. The combination of ionizing irradiation with other methods such as H2O2, ozonation and TiO2 nanoparticles could improve the degradation efficacy and reduce the cost. Ionizing irradiation is a promising alternative for degradation of PPCPs in aqueous solution.

Radiation dose reduction with the adaptive statistical iterative reconstruction (ASIR) technique for chest CT in children: an intra-individual comparison.

PubMed

Lee, Seung Hyun; Kim, Myung-Joon; Yoon, Choon-Sik; Lee, Mi-Jung

2012-09-01

To retrospectively compare radiation dose and image quality of pediatric chest CT using a routine dose protocol reconstructed with filtered back projection (FBP) (the Routine study) and a low-dose protocol with 50% adaptive statistical iterative reconstruction (ASIR) (the ASIR study). We retrospectively reviewed chest CT performed in pediatric patients who underwent both the Routine study and the ASIR study on different days between January 2010 and August 2011. Volume CT dose indices (CTDIvol), dose length products (DLP), and effective doses were obtained to estimate radiation dose. The image quality was evaluated objectively as noise measured in the descending aorta and paraspinal muscle, and subjectively by three radiologists for noise, sharpness, artifacts, and diagnostic acceptability using a four-point scale. The paired Student's t-test and the Wilcoxon signed-rank test were used for statistical analysis. Twenty-six patients (M:F=13:13, mean age 11.7) were enrolled. The ASIR studies showed 60.3%, 56.2%, and 55.2% reductions in CTDIvol (from 18.73 to 7.43 mGy, P<0.001), DLP (from 307.42 to 134.51 mGy×cm, P<0.001), and effective dose (from 4.12 to 1.84 mSv, P<0.001), respectively, compared with the Routine studies. The objective noise was higher in the paraspinal muscle of the ASIR studies (20.81 vs. 16.67, P=0.004), but was not different in the aorta (18.23 vs. 18.72, P=0.726). The subjective image quality demonstrated no difference between the two studies. A low-dose protocol with 50% ASIR allows radiation dose reduction in pediatric chest CT by more than 55% while maintaining image quality. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study.

PubMed

Stocker, Gertraud; Hacker, Ulrich T; Fiteni, Frédéric; John Mahachie, Jestinah; Roth, Arnaud D; Van Cutsem, Eric; Peeters, Marc; Lordick, Florian; Mauer, Murielle

2018-06-12

Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m 2 ), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model. 13.4% (280 of 2094 patients) had a BMI ≥ 30 kg/m 2 , and 5.3% had both a BMI ≥ 30 kg/m 2 and a body surface area (BSA) ≥2 m 2 . Dose reductions occurred in 16.1% of patients with a BMI ≥ 30 kg/m 2 and 32.4% with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , respectively. In patients with BMI ≥ 30 kg/m 2 , multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥ 30 kg/m 2 and BSA ≥ 2 m 2 , multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men. Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of the time-concentration-mortality responses of Plutella xylostella larvae to the interaction of Isaria fumosorosea with the insecticides beta-cypermethrin and Bacillus thuringiensis.

PubMed

Nian, Xiao-ge; He, Yu-rong; Lu, Li-hua; Zhao, Rui

2015-02-01

Entomopathogenic fungi are potential candidates for controlling Plutella xylostella, a cosmopolitan pest of crucifers. In this study, bioassays were conducted to evaluate the interaction between Isaria fumosorosea and sublethal doses of two insecticides, beta-cypermethrin and Bacillus thuringiensis, against P. xylostella. Data of each assay were in good agreement with the time-concentration-mortality model, indicating a strong dependence of the fungus and insecticide interaction on both concentration and post-exposure time. Using beta-cypermethrin 58-116 µg mL(-1) or B. thuringiensis 222.5-890 µg mL(-1) with the fungus significantly enhanced fungal efficacy. The LC50 values of the fungus declined over a 1-7 day period after exposure, and the LT50 values decreased with increasing concentration. Based on LC50 or LC90 estimates, synergism between the fungus and beta-cypermethrin resulted in a 2.7-28.3-fold reduction in LC50 values and a 12.1-19.6-fold reduction in LC90 values, while synergism of the fungus with B. thuringiensis led to a 2.4-385.0-fold reduction in LC50 values and a 4.4-151.7-fold reduction in LC90 values. Results show that sublethal doses of B. thuringiensis and beta-cypermethrin can synergise I. fumosorosea activity on P. xylostella, suggesting that combination of I. fumosorosea with the two insecticides might offer an integrated approach to controlling P. xylostella in practice. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

Electronic noise in CT detectors: Impact on image noise and artifacts.

PubMed

Duan, Xinhui; Wang, Jia; Leng, Shuai; Schmidt, Bernhard; Allmendinger, Thomas; Grant, Katharine; Flohr, Thomas; McCollough, Cynthia H

2013-10-01

The objective of our study was to evaluate in phantoms the differences in CT image noise and artifact level between two types of commercial CT detectors: one with distributed electronics (conventional) and one with integrated electronics intended to decrease system electronic noise. Cylindric water phantoms of 20, 30, and 40 cm in diameter were scanned using two CT scanners, one equipped with integrated detector electronics and one with distributed detector electronics. All other scanning parameters were identical. Scans were acquired at four tube potentials and 10 tube currents. Semianthropomorphic phantoms were scanned to mimic the shoulder and abdominal regions. Images of two patients were also selected to show the clinical values of the integrated detector. Reduction of image noise with the integrated detector depended on phantom size, tube potential, and tube current. Scans that had low detected signal had the greatest reductions in noise, up to 40% for a 30-cm phantom scanned using 80 kV. This noise reduction translated into up to 50% in dose reduction to achieve equivalent image noise. Streak artifacts through regions of high attenuation were reduced by up to 45% on scans obtained using the integrated detector. Patient images also showed superior image quality for the integrated detector. For the same applied radiation level, the use of integrated electronics in a CT detector showed a substantially reduced level of electronic noise, resulting in reductions in image noise and artifacts, compared with detectors having distributed electronics.

Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure.

PubMed

Armenian, Saro H; Hudson, Melissa M; Chen, Ming Hui; Colan, Steven D; Lindenfeld, Lanie; Mills, George; Siyahian, Aida; Gelehrter, Sarah; Dang, Ha; Hein, Wendy; Green, Daniel M; Robison, Leslie L; Wong, F Lennie; Douglas, Pamela S; Bhatia, Smita

2016-10-04

Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy in pediatric and adult non-oncology populations, yet remains unstudied in the pediatric oncology population. The primary objective of the trial is to determine impact of the intervention on echocardiographic markers of cardiac remodeling and HF risk, including: LV wall thickness/ dimension ratio (LVWT/D; primary endpoint), as well as LV ejection fraction, volume, and blood biomarkers (natriuretic peptides, galectin-3) associated with HF risk. Secondary objectives are to establish safety and tolerability of the 2-year course of carvedilol using: 1) objective measures: hepatic and cardiovascular toxicity, treatment adherence, and 2) subjective measures: participant self-reported outcomes. Two hundred and fifty survivors of childhood cancer (diagnosed <21 years of age), and previously treated with high-dose (≥300 mg/m 2 ) anthracyclines will be enrolled in a randomized, double-blind, placebo controlled trial. After baseline assessments, participants will be randomized in a 1:1 ratio to low-dose carvedilol (maximum dose: 12.5 mg/day) or placebo. Carvedilol or placebo is up-titrated (starting dose: 3.125 mg/day) according to tolerability. When completed, this study will provide much-needed information regarding a physiologically plausible pharmacological risk-reduction strategy for childhood cancer survivors at high risk for developing anthracycline-related HF. ClinicalTrials.gov; NCT02717507.

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers

PubMed Central

Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-01

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step‐and‐shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose <45 Gy to spinal cord and <50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5±2.2 Gy and 36.7±14.0 Gy), without significant changes on the other OARs. A marked difference (−15.9±1.9 Gy and −10.1±5.7 Gy) was obtained at the expense of a small difference (−1.3%±0.9%) from initial PTV195% coverage (96.6%±0.9%). Similar difference (−15.7±2.2 Gy and −10.2±6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (−0.3%±0.3% from the initial 98.3%±0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer. PACS number: 87.55.D PMID:24423836

Joint minimization of uplink and downlink whole-body exposure dose in indoor wireless networks.

PubMed

Plets, D; Joseph, W; Vanhecke, K; Vermeeren, G; Wiart, J; Aerts, S; Varsier, N; Martens, L

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism.

Joint Minimization of Uplink and Downlink Whole-Body Exposure Dose in Indoor Wireless Networks

PubMed Central

Plets, D.; Joseph, W.; Vanhecke, K.; Vermeeren, G.; Wiart, J.; Aerts, S.; Varsier, N.; Martens, L.

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism. PMID:25793213

ALARA at nuclear power plants

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

Baum, J.W.

1990-01-01

Implementation of the As Low As Reasonably Achievable (ALARA) principle at nuclear power plants presents a continuing challenge for health physicists at utility corporate and plant levels, for plant designers, and for regulatory agencies. The relatively large collective doses at some plants are being addressed though a variety of dose reduction techniques. It is planned that this report will include material on historical aspects, management, valuation of dose reduction, quantitative and qualitative aspects of optimization, design, operational considerations, and training. The status of this work is summarized in this report. 30 refs., 1 fig., 6 tabs.

17β-estradiol confers protection after traumatic brain injury in the rat and involves activation of G protein-coupled estrogen receptor 1.

PubMed

Day, Nicole L; Floyd, Candace L; D'Alessandro, Tracy L; Hubbard, William J; Chaudry, Irshad H

2013-09-01

Abstract Traumatic brain injury (TBI) is a significant public health problem in the United States. Despite preclinical success of various drugs, to date all clinical trials investigating potential therapeutics have failed. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. One of these is 17β-estradiol (E2), the most abundant and potent endogenous vertebrate estrogen. The goal of our study was to investigate the acute potential protective effects of E2 or the specific G protein-coupled estrogen receptor 1 (GPER) agonist G-1 when administered in an intravenous bolus dose 1 hour post-injury in the lateral fluid percussion (LFP) rodent model of TBI. The results of this study show that, when assessed at 24 hours post-injury, E2 or G-1 confers protection in adult male rats subjected to LFP brain injury. Specifically, we found that an acute bolus dose of E2 or G-1 administered intravenously 1 hour post-TBI significantly increases neuronal survival in the ipsilateral CA 2/3 region of the hippocampus and decreases neuronal degeneration and apoptotic cell death in both the ipsilateral cortex and CA 2/3 region of the hippocampus. We also report a significant reduction in astrogliosis in the ipsilateral cortex, hilus, and CA 2/3 region of the hippocampus. Finally, these effects were observed to be chiefly dose-dependent for E2, with the 5 mg/kg dose generating a more robust level of protection. Our findings further elucidate estrogenic compounds as a clinically relevant pharmacotherapeutic strategy for treatment of secondary injury following TBI, and intriguingly, reveal a novel potential therapeutic target in GPER.

Obstructive urination problems after high-dose-rate brachytherapy boost treatment for prostate cancer are avoidable.

PubMed

Kragelj, Borut

2016-03-01

Aiming at improving treatment individualization in patients with prostate cancer treated with combination of external beam radiotherapy and high-dose-rate brachytherapy to boost the dose to prostate (HDRB-B), the objective was to evaluate factors that have potential impact on obstructive urination problems (OUP) after HDRB-B. In the follow-up study 88 patients consecutively treated with HDRB-B at the Institute of Oncology Ljubljana in the period 2006-2011 were included. The observed outcome was deterioration of OUP (DOUP) during the follow-up period longer than 1 year. Univariate and multivariate relationship analysis between DOUP and potential risk factors (treatment factors, patients' characteristics) was carried out by using binary logistic regression. ROC curve was constructed on predicted values and the area under the curve (AUC) calculated to assess the performance of the multivariate model. Analysis was carried out on 71 patients who completed 3 years of follow-up. DOUP was noted in 13/71 (18.3%) of them. The results of multivariate analysis showed statistically significant relationship between DOUP and anti-coagulation treatment (OR 4.86, 95% C.I. limits: 1.21-19.61, p = 0.026). Also minimal dose received by 90% of the urethra volume was close to statistical significance (OR = 1.23; 95% C.I. limits: 0.98-1.07, p = 0.099). The value of AUC was 0.755. The study emphasized the relationship between DOUP and anticoagulation treatment, and suggested the multivariate model with fair predictive performance. This model potentially enables a reduction of DOUP after HDRB-B. It supports the belief that further research should be focused on urethral sphincter as a critical structure for OUP.

Optimizing Therapeutic Effect of Aurora B Inhibition in Acute Myeloid Leukemia with AZD2811 Nanoparticles.

PubMed

Floc'h, Nicolas; Ashton, Susan; Taylor, Paula; Trueman, Dawn; Harris, Emily; Odedra, Rajesh; Maratea, Kim; Derbyshire, Nicola; Caddy, Jacqueline; Jacobs, Vivien N; Hattersley, Maureen; Wen, Shenghua; Curtis, Nicola J; Pilling, James E; Pease, Elizabeth J; Barry, Simon T

2017-06-01

Barasertib (AZD1152), a highly potent and selective aurora kinase B inhibitor, gave promising clinical activity in elderly acute myeloid leukemia (AML) patients. However, clinical utility was limited by the requirement for a 7-day infusion. Here we assessed the potential of a nanoparticle formulation of the selective Aurora kinase B inhibitor AZD2811 (formerly known as AZD1152-hQPA) in preclinical models of AML. When administered to HL-60 tumor xenografts at a single dose between 25 and 98.7 mg/kg, AZD2811 nanoparticle treatment delivered profound inhibition of tumor growth, exceeding the activity of AZD1152. The improved antitumor activity was associated with increased phospho-histone H3 inhibition, polyploidy, and tumor cell apoptosis. Moreover, AZD2811 nanoparticles increased antitumor activity when combined with cytosine arabinoside. By modifying dose of AZD2811 nanoparticle, therapeutic benefit in a range of preclinical models was further optimized. At high-dose, antitumor activity was seen in a range of models including the MOLM-13 disseminated model. At these higher doses, a transient reduction in bone marrow cellularity was observed demonstrating the potential for the formulation to target residual disease in the bone marrow, a key consideration when treating AML. Collectively, these data establish that AZD2811 nanoparticles have activity in preclinical models of AML. Targeting Aurora B kinase with AZD2811 nanoparticles is a novel approach to deliver a cell-cycle inhibitor in AML, and have potential to improve on the clinical activity seen with cell-cycle agents in this disease. Mol Cancer Ther; 16(6); 1031-40. ©2017 AACR . ©2017 American Association for Cancer Research.

Toxic effect of acyclovir on testicular tissue in rats

PubMed Central

Movahed, Elham; Nejati, Vahid; Sadrkhanlou, Rajabali; Ahmadi, Abbas

2013-01-01

Background: Acyclovir (ACV), a synthetic purine nucleoside analogue, is known to be toxic to gonads. Objective: The current study evaluated cytotoxicity of ACV on histopathological changes in testis tissue and serum testosterone and lipid peroxidation concentrations of male rats. Materials and Methods: Animals were divided into five groups. One group served as control and one group served as control sham. In the drug treated groups ACV administered for 15 days. 18 days after the last injection, animals were sacrificed. Histopathological and histomorphometrical analysis of the testis was carried out. Serum levels of testosterone and Lipid Peroxidation and potential fertility of animals was evaluated. Results: Male rats exposed to ACV had significant reduction in serum testosterone concentrations at 16 and 48mg/kg dose-levels (p<0.01). ACV induced histopathological changes in the testis and also increase the mean number of mast cells in peritubular or interstitial tissue in the testis at at 16 and 48mg/kg dose-levels (p<0.01). In addition ACV caused increase of serum level of Lipid Peroxidation at 48mg/kg dose-level (p<0.05). As well ACV decreased potential fertility in male rats. Conclusion: The present results highly support the idea that ACV has adverse effect on the reproductive system in male rat. PMID:24639735

Response of optically stimulated luminescence dosimeters subjected to X-rays in diagnostic energy range

NASA Astrophysics Data System (ADS)

Musa, Y.; Hashim, S.; Karim, M. K. A.; Bakar, K. A.; Ang, W. C.; Salehhon, N.

2017-05-01

The use of optically stimulated luminescence (OSL) for dosimetry applications has recently increased considerably due to availability of commercial OSL dosimeters (nanoDots) for clinical use. The OSL dosimeter has a great potential to be used in clinical dosimetry because of its prevailing advantages in both handling and application. However, utilising nanoDot OSLDs for dose measurement in diagnostic radiology can only be guaranteed when the performance and characteristics of the dosimeters are apposite. In the present work, we examined the response of commercially available nanoDot OSLD (Al2O3:C) subjected to X-rays in general radiography. The nanoDots response with respect to reproducibility, dose linearity and signal depletion were analysed using microStar reader (Landauer, Inc., Glenwood, IL). Irradiations were performed free-in-air using 70, 80 and 120 kV tube voltages and tube currents ranging from 10 - 100 mAs. The results showed that the nanoDots exhibit good linearity and reproducibility when subjected to diagnostic X-rays, with coefficient of variations (CV) ranging between 2.3% to 3.5% representing a good reproducibility. The results also indicated average of 1% signal reduction per readout. Hence, the nanoDots showed a promising potential for dose measurement in general X-ray procedure.

Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

PubMed

Godos, Justyna; Micek, Agnieszka; Marranzano, Marina; Salomone, Federico; Rio, Daniele Del; Ray, Sumantra

2017-08-28

A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.

Vinpocetine and piracetam exert antinociceptive effect in visceral pain model in mice.

PubMed

Abdel Salam, Omar M E

2006-01-01

The effect of vinpocetine or piracetam on thermal and visceral pain was studied in mice. In the hot plate test, vinpocetine (0.9 and 1.8 mg/kg), but not piracetam, produced a reduction in nociceptive response. Vinpocetine (0.45-1.8 mg/kg, ip) or piracetam (75-300 mg/kg, ip) caused dose-dependent inhibition of the abdominal constrictions evoked by ip injection of acetic acid. The effect of vinpocetine or piracetam was markedly potentiated by co-administration of propranolol, guanethidine, atropine, naloxone, yohimbine or prazosin. The marked potentiation of antinociception occurred upon a co-administration of vinpocetine and baclofen (5 or 10 mg/kg). In contrast, piracetam antagonized antinociception caused by the low (5 mg/kg), but not the high (10 mg/kg) dose of baclofen. The antinociception caused by vinpocetine was reduced by sulpiride; while that of piracetam was enhanced by haloperidol or sulpiride. Either vinpocetine or piracetam enhanced antinociception caused by imipramine. The antinociceptive effects of vinpocetine or piracetam were blocked by prior administration of theophylline. Low doses of either vinpocetine or piracetam reduced immobility time in the Porsolt's forced-swimming test. This study indicates that vinpocetine and piracetam possess visceral antinociceptive properties. This effect depends on activation of adenosine receptors. Piracetam in addition inhibits GABA-mediated antinociception.