Science.gov

Sample records for low-dose prospectively gated

  1. Low-dose dobutamine gated-SPECT analysis of left ventricular segmental wall thickening in ischemic cardiomyopathy.

    PubMed

    Candell-Riera, Jaume; Romero-Farina, Guillermo; Milá, Marta; Aguadé-Bruix, Santiago

    2008-10-01

    The objective of this study was to use low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) to evaluate segmental thickening of the left ventricle (LV) and its relationship with changes in ejection fraction (EF) and ventricular volumes in patients with ischemic cardiomyopathy. This prospective multicenter study involved 89 patients with ischemic cardiomyopathy (i.e., EF < or =40%) who underwent LDD gated-SPECT at rest. The LV was divided into 17 segments and systolic thickening was assessed in a total of 1513 segments during LDD infusion. RESULTS; A significant increase in LVEF (33.2% vs. 30.8%; P< .001) was observed during LDD infusion and occurred at the expense of a reduction in end-systolic volume (130.5 mL vs. 136.4 mL; P=.005). The increase in EF was > or =5% in 33.7% of patients, while the EF decreased by > or =5% in 5.6% of patients. With LDD infusion, both an improvement in > or =3 segments with severely decreased baseline thickening (odds ratio [OR] = 18.3; 95% confidence interval [CI], 5.3-63) and an improvement in > or =10 segments with mild-to-moderate alterations in baseline thickening (OR = 4.53; 95% CI, 1.26-16.16) were associated with a > or =5% increase in LVEF. During the assessment of global left ventricular contractile reserve by LDD gated-SPECT, attention should be paid not only to the behavior of segments with severely decreased baseline thickening, which are generally regarded as indicating viability, but also to segments with mild-to-moderate alterations and to those in which thickening decreases.

  2. Does low-dose rifaximin ameliorate endotoxemia in patients with liver cirrhosis: a prospective study.

    PubMed

    Zeng, Xin; Tang, Xia Jiao; Sheng, Xia; Ni, Wu; Xin, Hai Guang; Chen, Wei Zhong; Jiang, Cai Feng; Lin, Yong; Shi, Jian; Shi, Bin; Chen, Yue Xiang; Yuan, Zong Li; Xie, Wei Fen

    2015-11-01

    To evaluate the efficacy, safety and tolerability of different doses of rifaximin in Chinese patients with liver cirrhosis. This random prospective study included a screening visit, a 2-week treatment period and a subsequent 4-week observation phase. Patients with liver cirrhosis were randomly assigned to a low-dose rifaximin group, a high-dose rifaximin group and the control group in a ratio of 1:1:1. The low-dose and high-dose groups received 400 mg or 600 mg rifaximin per 12 h for 2 weeks, respectively. All other therapeutic strategies remained unchanged in the three groups as long as possible. In total, 60 patients with liver cirrhosis were screened and 43 of them met the eligibility criteria. After 2-week treatment serum endotoxin levels in the low-dose (1.1 ± 0.8 EU/mL) and high-dose rifaximin groups (1.0 ± 0.8 EU/mL) were significantly lower than that in the control group (2.5 ± 1.8 EU/mL), while no significant difference was found between the two rifaximin-treated groups. The effect of high-dose rifaximin on endotoxemia lasted for at least 4 weeks after drug withdrawal. A significant reduction in the abundance of the Veillonellaceae taxa and an increase in the abundance of Bacteroidaceae were shown after 2 weeks of rifaximin therapy. The incidence of adverse events and severe adverse events was similar among the three groups. Low-dose (800 mg/day) rifaximin could be analogous to high-dose (1200 mg/day) rifaximin to reduce the serum endotoxin level after 2 weeks of treatment. © 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  3. Prospectively gated cardiac computed tomography.

    PubMed

    Moore, S C; Judy, P F; Garnic, J D; Kambic, G X; Bonk, F; Cochran, G; Margosian, P; McCroskey, W; Foote, F

    1983-01-01

    A fourth-generation scanner has been modified to perform prospectively gated cardiac computed tomography (CT). A computer program monitors the electrocardiogram (ECG) and predicts when to initiate the next scan in a gated series in order to acquire all projection data for a desired phase of the heart cycle. The system has been tested with dogs and has produced cross-sectional images of all phases of the cardiac cycle. Eight to ten scans per series were sufficient to obtain reproducible images of each transverse section in the end-diastolic and end-systolic phases. The radiation dose to the skin was approximately 1.4 cGy per scan. The prospectively gated system is more than twice as efficient as a retrospectively gated system in obtaining complete angular projection data for a 10% heart cycle window. A temporal smoothing technique to suppress reconstruction artifacts due to sorting inconsistent projection data was developed and evaluated. Image noise was reduced by averaging together any overlapping projection data. Prospectively gated cardiac CT has also been used to demonstrate that the error in attenuation measured with a single nongated CT scan through the heart can be as large as 50-60 CT numbers outside the heart in the lung field.

  4. Low dose lignocaine + butorphanol vs. low dose bupivacaine for spinal anaesthesia in day care urological surgeries: a prospective randomized control trial.

    PubMed

    Khant, Shahil Rameshbhai; Chaudhari, Rajeev; Kore, Rishikesh Arun; Bhagwat, Shirish; Jakhalekar, Ranjan Purushottam

    2017-06-01

    A local anaesthetic with fast onset, short and reliable duration of anaesthesia may be preferable for day care urological surgeries. Low dose lignocaine is believed to act faster and to have a shorter duration of action than low dose bupivacaine. Use of lignocaine for spinal anesthesia is discouraged now a days because of rare reports of transient neurological symptoms. The purpose of this study was to compare effectiveness and safety of low dose of lignocaine + butorphanol against low dose of bupivacaine for day care urological surgeries. A prospective randomized control trial was conducted between December 2012 to November 2015. After taking ethical committe approval and patient consent, total 990 patients were randomized in two groups. Group A received 0.5 mL of 5% lignocaine (25 mg) + 0.3 mL butorphanol (0.3 mg) and group B received 1 mL of 0.5% bupivacaine (5 mg) for spinal anesthesia. Spinal anesthesia was given at the L3-L4 interspace with the patient in the sitting or lateral position. The criteria for evaluation were time till onset of sensory and motor block, duration of sensory and motor block, time till ambulation, time till fit for discharge and any complications. Both the groups were comparable in terms of age, male to female ratio, American Society of Anesthesiologists (ASA) grade and duration surgery. Group A and Group B were statistically different in terms of mean time till onset of sensory block (120±22 sec and 274±36 sec), onset of motor block (228±34 sec and 372±41 sec), duration of sensory block (100±21 min and 230±28 min), duration of motor block (60±15 min and 152±23 min), time till ambulation (138±24 min and 292±48 min), time till fit for discharge (256±35 min and 428±46 min) respectively (<0.0001). Nausea, vomitings, hypotension, bradycarida and pruritis were less in group A compared to group B (<0.01). None of patient in any group had temporary or permanent neurological defecit. Spinal anaesthesia is an effective as well as a

  5. Influence of ultra-low dose Aprotinin on thoracic surgical operations: a prospective randomized trial

    PubMed Central

    Apostolakis, Efstratios; Panagopoulos, Nikolaos; Koletsis, Efstratios N; Crockett, James; Stamou-Kouki, Helen; Sourgiadaki, Efrosini; Filos, Kriton; Dougenis, Dimitrios

    2008-01-01

    Background The blood saving effect of aprotinin has been well documented in cardiac surgery. In thoracic surgery, very few recent studies, using rather high doses of aprotinin, have shown a similar result. In a randomized prospective trial, we have tested the influence of aprotinin using an ultra-low dose drug regime. Methods Fifty-nine patients, mean age 58 ± 13.25 years (mean ± SD) undergoing general thoracic procedures were randomized into placebo (Group A) and treatment group (Group B). The group B (n = 29) received 500.000 IU of aprotinin after induction to anesthesia and a repeat dose immediately after chest closure. A detailed protocol with several laboratory parameters was recorded. Patients were transfused when perioperative Ht was less than 26%. Results The two groups were similar in terms of age, gender, diagnosis, pathology, co-morbidity and operations performed. The mean drainage of the first and second postoperative day in group B was significantly reduced (412.6 ± 199.2 vs. 764.3 ± 213.9 ml, p < 0.000, and 248.3 ± 178.5 vs. 455.0 ± 274.6, p < 0.001). Similarly, the need for fresh frozen plasma transfusion was lower in group B, p < 0.035. Both the operation time and the hospital stay were also less for group B but without reaching statistical significance (84.6 ± 35.2 vs 101.2 ± 52.45 min. and 5.8 ± 1.6 vs 7.2 ± 3.6 days respectively, p < 0.064). The overall transfusion rate did not differ significantly. No side effects of aprotinin were noted. Conclusion The perioperative ultra-low dose aprotinin administration was associated with a reduction of total blood losses and blood product requirements. We therefore consider the use of aprotinin safe and effective in major thoracic surgery. PMID:18361800

  6. Analysis of low-dose radiation shield effectiveness of multi-gate polymeric sheets

    NASA Astrophysics Data System (ADS)

    Kim, S. C.; Lee, H. K.; Cho, J. H.

    2014-07-01

    Computed tomography (CT) uses a high dose of radiation to create images of the body. As patients are exposed to radiation during a CT scan, the use of shielding materials becomes essential in CT scanning. This study was focused on the radiation shielding materials used for patients during a CT scan. In this study, sheets were manufactured to shield the eyes and the thyroid, the most sensitive parts of the body, against radiation exposure during a CT scan. These sheets are manufactured using silicone polymers, barium sulfate (BaSO4) and tungsten, with the aim of making these sheets equally or more effective in radiation shielding and more cost-effective than lead sheets. The use of barium sulfate drew more attention than tungsten due to its higher cost-effectiveness. The barium sulfate sheets were coated to form a multigate structure by applying the maximum charge rate during the agitator and subsequent mixing processes and creating multilayered structures on the surface. To measure radiation shielding effectiveness, the radiation dose was measured around both eyes and the thyroid gland using sheets in three different thicknesses (1, 2 and 3 mm). Among the 1 and 2 mm sheets, the Pb sheets exhibited greater effectiveness in radiation shielding around both eyes, but the W sheets were more effective in radiation shielding around the thyroid gland. In the 3 mm sheets, the Pb sheet also attenuated a higher amount of radiation around both eyes while the W sheet was more effective around the thyroid gland. In conclusion, the sheets made from barium sulfate and tungsten proved highly effective in shielding against low-dose radiation in CT scans without causing ill-health effects, unlike lead.

  7. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data

    PubMed Central

    Da Silva, J A P; Jacobs, J W G; Kirwan, J R; Boers, M; Saag, K G; Inês, L B S; de Koning, E J P; Buttgereit, F; Cutolo, M; Capell, H; Rau, R; Bijlsma, J W J

    2006-01-01

    Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo. PMID:16107513

  8. Changing Attitude Toward Radiation Carcinogenesis and Prospects for Novel Low-Dose Radiation Treatments.

    PubMed

    Socol, Yehoshua; Welsh, James S

    2016-12-01

    All procedures involving ionizing radiation, whether diagnostic or therapeutic, are subject to strict regulation, and public concerns have been raised about even the low levels of radiation exposures involved in diagnostic imaging. During the last 2 decades, there are signs of more balanced attitude to ionizing radiation hazards, as opposed to the historical "radiophobia." The linear no-threshold hypothesis, based on the assumption that every radiation dose increment constitutes increased cancer risk for humans, is increasingly debated. In particular, the recent memorandum of the International Commission on Radiological Protection admits that the linear no-threshold hypothesis predictions at low doses (that International Commission on Radiological Protection itself has used and continues to use) are "speculative, unproven, undetectable, and 'phantom'." Moreover, numerous experimental, ecological, and epidemiological studies suggest that low doses of ionizing radiation may actually be beneficial to human health. Although these advances in scientific understanding have not yet yielded significant changes in radiation regulation and policy, we are hopeful such changes may happen in the relatively near future. This article reviews the present status of the low-dose radiation hazard debate and outlines potential opportunities in the field of low-dose radiation therapy. © The Author(s) 2015.

  9. Ultra-Low-Dose Fetal CT With Model-Based Iterative Reconstruction: A Prospective Pilot Study.

    PubMed

    Imai, Rumi; Miyazaki, Osamu; Horiuchi, Tetsuya; Asano, Keisuke; Nishimura, Gen; Sago, Haruhiko; Nosaka, Shunsuke

    2017-06-01

    Prenatal diagnosis of skeletal dysplasia by means of 3D skeletal CT examination is highly accurate. However, it carries a risk of fetal exposure to radiation. Model-based iterative reconstruction (MBIR) technology can reduce radiation exposure; however, to our knowledge, the lower limit of an optimal dose is currently unknown. The objectives of this study are to establish ultra-low-dose fetal CT as a method for prenatal diagnosis of skeletal dysplasia and to evaluate the appropriate radiation dose for ultra-low-dose fetal CT. Relationships between tube current and image noise in adaptive statistical iterative reconstruction and MBIR were examined using a 32-cm CT dose index (CTDI) phantom. On the basis of the results of this examination and the recommended methods for the MBIR option and the known relationship between noise and tube current for filtered back projection, as represented by the expression SD = (milliamperes)(-0.5), the lower limit of the optimal dose in ultra-low-dose fetal CT with MBIR was set. The diagnostic power of the CT images obtained using the aforementioned scanning conditions was evaluated, and the radiation exposure associated with ultra-low-dose fetal CT was compared with that noted in previous reports. Noise increased in nearly inverse proportion to the square root of the dose in adaptive statistical iterative reconstruction and in inverse proportion to the fourth root of the dose in MBIR. Ultra-low-dose fetal CT was found to have a volume CTDI of 0.5 mGy. Prenatal diagnosis was accurately performed on the basis of ultra-low-dose fetal CT images that were obtained using this protocol. The level of fetal exposure to radiation was 0.7 mSv. The use of ultra-low-dose fetal CT with MBIR led to a substantial reduction in radiation exposure, compared with the CT imaging method currently used at our institution, but it still enabled diagnosis of skeletal dysplasia without reducing diagnostic power.

  10. A Prospective, Open-Label Study of Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    SciTech Connect

    Kamstrup, Maria R.; Specht, Lena; Skovgaard, Gunhild L.; Gniadecki, Robert

    2008-07-15

    Purpose: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. Methods and Materials: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4 fractions over 4 successive days. Results: Two patients had a complete clinical response but relapsed after 3.5 months. Six patients had partial clinical responses, with a mean duration of 2.0 months. One patient had no clinical response. Median time to relapse was 2.7 months. One patient died of unrelated causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. Conclusion: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration of remission is short. Low-dose total skin electron beam therapy may find application in palliative treatment of mycosis fungoides because of limited toxicity and the possibility of repeating treatments for long-term disease control.

  11. Inhaled low-dose iloprost for pulmonary hypertension: a prospective, multicenter, open-label study.

    PubMed

    Sun, Yun-Juan; Xiong, Chang-Ming; Shan, Guang-Liang; Gu, Qing; Zeng, Wei-Jie; Lu, Xian-Ling; Zhu, Feng; Liu, Zhi-Hong; Ni, Xin-Hai; He, Jian-Guo

    2012-06-01

    Inhaled iloprost (average >30 µg/d) has been considered an effective treatment for severe pulmonary hypertension (PH). Further evidence also showed that low-dose iloprost given intravenously was equally effective as high-dose iloprost in the therapy of systemic sclerosis. Patients with pulmonary hypertension will benefit from inhalation of low-dose iloprost. Sixty-two patients with PH were enrolled and initiated with neubulizedlow-dose iloprost (2.5 µg per inhalation, 6× daily) for 24 weeks in 13 medical centers in China. Efficacy endpoints included changes in 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC), and hemodynamic parameters. Fourteen patients (22.6%) prematurely discontinued the study: 8 due to clinical worsening (6 in WHO-FCIII-IV at baseline), 4 because of protocol change, and 2 patients lost during follow-up. In the remaining 48 patients, 6MWD was increased from 356 ± 98 meters to 414 ± 99 meters (P < 0.001) and WHO-FC improved significantly (P = 0.006) after 24-week inhalation therapy. Cardiac output, cardiac index, and mixed venous oxygen saturation improved significantly compared with baseline (n = 34, P < 0.05). Most of the hemodynamic parameters improved significantly in patients in WHO-FC II (P < 0.05) but not in patients in WHO-FCIII-IV. Low-dose iloprost inhalation significantly improved exercise capacity and functional status in patients with PH. It was well tolerated. The improvement of hemodynamics was confirmed in patients with WHO-FCI-II but not in patients with WHO-FCIII-IV, suggesting the importance of early treatment in patients with advanced disease stages. © 2012 Wiley Periodicals, Inc.

  12. Prospects for quantitative two-dimensional radiochromic film dosimetry for low dose-rate brachytherapy sources

    SciTech Connect

    Le Yi; Ali, Imad; Dempsey, James F.; Williamson, Jeffrey F.

    2006-12-15

    Radiochromic film (RCF) has been shown to be a precise and accurate two-dimensional dosimeter for acute exposure radiation fields. However, ''temporal history'' mismatch between calibration and brachytherapy films due to RCF dose-rate effects could introduce potentially large uncertainties in low dose-rate (LDR) brachytherapy absolute dose measurement. This article presents a quantitative evaluation of the precision and accuracy of a laser scanner-based RCF-dosimetry system and the effect of the temporal history mismatch in LDR absolute dose measurement. MD-55-2 RCF was used to measure absolute dose for a low dose-rate {sup 137}Cs brachytherapy source using both single- and double-exposure techniques. Dose-measurement accuracy was evaluated by comparing RCF to Monte Carlo photon-transport simulation. The temporal history mismatch effect was investigated by examining dependence of RCF accuracy on irradiation-to-densitometry time interval. The predictions of the empirical cumulative dose superposition model (CDSM) were compared with measurements. For the double-exposure technique, the agreement between measurement and Monte Carlo simulation was better than 4% in the 3-60 Gy dose range with measurement precisions (coverage factor k=1) of <2% and <6% for the doses greater or less than 3 Gy, respectively. The overall uncertainty (k=1) of dose rate/air-kerma strength measurements achievable by this dosimetry system for a spatial resolution of 0.1 mm is less than 4% for doses greater than 5 Gy. The measured temporal history mismatch systematic error is about 1.8% for a 48 h postexposure time when using the double exposure technique and agrees with CDSM's prediction qualitatively. This work demonstrates that the model MD-55-2 RCF detector has the potential to support quantitative dose measurements about LDR brachytherapy sources with precision and accuracy better than that of previously described dosimeters. The impacts of this work on the future use of new type of RCF

  13. Comparison of remifentanil and low-dose fentanyl for fast-track cardiac anesthesia: a prospective randomized study.

    PubMed

    Khanykin, Boris; Siddiqi, Rizwan; Jensen, Per F; Bigler, Dennis R; Atroshchenko, Gennady V

    2013-12-01

    Different anesthetic techniques have been used for fast tracking in cardiac anesthesia. Remifentanil, with its unique pharmacokinetic profile, could be an ideal drug for fast tracking. Possible limitations of remifentanil are rapid onset of postoperative pain after discontinuation of the drug infusion, which may increase the risk of an ischemic event. We conducted this randomized study to compare the efficacy of remifentanil versus low doses of fentanyl in fast-track cardiac anesthesia. It has been hypothesized that remifentanil would provide a safe anesthesia with no impact on myocardial function and with positive effects on extubation time and mobilization. We compared the postoperative course of patients, the remifentanil group (RG) and the low-dose fentanyl group (LDFG), in whom remifentanil and low-dose fentanyl, respectively, were used for fast-track cardiac anesthesia. The study was designed as a prospective randomized study. The primary outcomes were changes in the cardiac index and creatine kinase MB fraction (CKMB), extubation times, mobilization times, and lengths of stay in the intensive care unit (ICU) and the hospital. Frequency of myocardial infarction (MI), reoperations due to excessive bleeding, renal impairment, and cerebral complications were registered as well. Seventy-one patients were enrolled in the study, and 7 were excluded due to difficult airway, bleeding, and technical difficulties. The RG comprised 33 patients and the LDFG comprised of 31 patients. There were no differences between the groups in terms of age, Euroscore, types of surgery, extracorporeal circulation, and aortic cross-clamp time. We did not find significant difference in cardiac index, CKMB, extubation times, mobilization times, length of stay in the ICU and in the hospital between the groups. Postoperative complications such as MI, rates of reoperations, renal and cerebral complications and incidence of atrial fibrillation did not show any significant differences

  14. Feasibility of epicardial adipose tissue quantification in non-ECG-gated low-radiation-dose CT: comparison with prospectively ECG-gated cardiac CT.

    PubMed

    Simon-Yarza, Isabel; Viteri-Ramírez, Guillermo; Saiz-Mendiguren, Ramón; Slon-Roblero, Pedro J; Paramo, María; Bastarrika, Gorka

    2012-06-01

    Epicardial adipose tissue (EAT) is an important indicator of cardiovascular risk. This parameter is generally assessed on ECG-gated computed tomography (CT) images. To evaluate feasibility and reliability of EAT quantification on non-gated thoracic low-radiation-dose CT examinations with respect to prospectively ECG-gated cardiac CT acquisition. Sixty consecutive asymptomatic smokers (47 men; mean age 64 ± 9.8 years) underwent low-dose CT of the chest and prospectively ECG-gated cardiac CT acquisitions (64-slice dual-source CT). The two examinations were reconstructed with the same range, field of view, slice thickness, and convolution algorithm. Two independent observers blindly quantified EAT volume using commercially available software. Data were compared with paired sample Student t-test, concordance correlation coefficients (CCC), and Bland-Altman plots. No statistically significant difference was observed for EAT volume quantification with low-dose-CT (141.7 ± 58.3 mL) with respect to ECG-gated CT (142.7 ± 57.9 mL). Estimation of CCC showed almost perfect concordance between the two techniques for EAT-volume assessment (CCC, 0.99; mean difference, 0.98 ± 5.1 mL). Inter-observer agreement for EAT volume estimation was CCC: 0.96 for low-dose-CT examinations and 0.95 for ECG-gated CT. Non-gated low-dose CT allows quantifying EAT with almost the same concordance and reliability as using dedicated prospectively ECG-gated cardiac CT acquisition protocols.

  15. 4D micro-CT using fast prospective gating.

    PubMed

    Guo, Xiaolian; Johnston, Samuel M; Qi, Yi; Johnson, G Allan; Badea, Cristian T

    2012-01-07

    Micro-CT is currently used in preclinical studies to provide anatomical information. But, there is also significant interest in using this technology to obtain functional information. We report here a new sampling strategy for 4D micro-CT for functional cardiac and pulmonary imaging. Rapid scanning of free-breathing mice is achieved with fast prospective gating (FPG) implemented on a field programmable gate array. The method entails on-the-fly computation of delays from the R peaks of the ECG signals or the peaks of the respiratory signals for the triggering pulses. Projection images are acquired for all cardiac or respiratory phases at each angle before rotating to the next angle. FPG can deliver the faster scan time of retrospective gating (RG) with the regular angular distribution of conventional prospective gating for cardiac or respiratory gating. Simultaneous cardio-respiratory gating is also possible with FPG in a hybrid retrospective/prospective approach. We have performed phantom experiments to validate the new sampling protocol and compared the results from FPG and RG in cardiac imaging of a mouse. Additionally, we have evaluated the utility of incorporating respiratory information in 4D cardiac micro-CT studies with FPG. A dual-source micro-CT system was used for image acquisition with pulsed x-ray exposures (80 kVp, 100 mA, 10 ms). The cardiac micro-CT protocol involves the use of a liposomal blood pool contrast agent containing 123 mg I ml(-1) delivered via a tail vein catheter in a dose of 0.01 ml g(-1) body weight. The phantom experiment demonstrates that FPG can distinguish the successive phases of phantom motion with minimal motion blur, and the animal study demonstrates that respiratory FPG can distinguish inspiration and expiration. 4D cardiac micro-CT imaging with FPG provides image quality superior to RG at an isotropic voxel size of 88 μm and 10 ms temporal resolution. The acquisition time for either sampling approach is less than 5 min. The

  16. 4D micro-CT using fast prospective gating

    NASA Astrophysics Data System (ADS)

    Guo, Xiaolian; Johnston, Samuel M.; Qi, Yi; Johnson, G. Allan; Badea, Cristian T.

    2012-01-01

    Micro-CT is currently used in preclinical studies to provide anatomical information. But, there is also significant interest in using this technology to obtain functional information. We report here a new sampling strategy for 4D micro-CT for functional cardiac and pulmonary imaging. Rapid scanning of free-breathing mice is achieved with fast prospective gating (FPG) implemented on a field programmable gate array. The method entails on-the-fly computation of delays from the R peaks of the ECG signals or the peaks of the respiratory signals for the triggering pulses. Projection images are acquired for all cardiac or respiratory phases at each angle before rotating to the next angle. FPG can deliver the faster scan time of retrospective gating (RG) with the regular angular distribution of conventional prospective gating for cardiac or respiratory gating. Simultaneous cardio-respiratory gating is also possible with FPG in a hybrid retrospective/prospective approach. We have performed phantom experiments to validate the new sampling protocol and compared the results from FPG and RG in cardiac imaging of a mouse. Additionally, we have evaluated the utility of incorporating respiratory information in 4D cardiac micro-CT studies with FPG. A dual-source micro-CT system was used for image acquisition with pulsed x-ray exposures (80 kVp, 100 mA, 10 ms). The cardiac micro-CT protocol involves the use of a liposomal blood pool contrast agent containing 123 mg I ml-1 delivered via a tail vein catheter in a dose of 0.01 ml g-1 body weight. The phantom experiment demonstrates that FPG can distinguish the successive phases of phantom motion with minimal motion blur, and the animal study demonstrates that respiratory FPG can distinguish inspiration and expiration. 4D cardiac micro-CT imaging with FPG provides image quality superior to RG at an isotropic voxel size of 88 µm and 10 ms temporal resolution. The acquisition time for either sampling approach is less than 5 min. The

  17. Ultra-low-dose computed tomographic angiography with model-based iterative reconstruction compared with standard-dose imaging after endovascular aneurysm repair: a prospective pilot study.

    PubMed

    Naidu, Sailen G; Kriegshauser, J Scott; Paden, Robert G; He, Miao; Wu, Qing; Hara, Amy K

    2014-12-01

    An ultra-low-dose radiation protocol reconstructed with model-based iterative reconstruction was compared with our standard-dose protocol. This prospective study evaluated 20 men undergoing surveillance-enhanced computed tomography after endovascular aneurysm repair. All patients underwent standard-dose and ultra-low-dose venous phase imaging; images were compared after reconstruction with filtered back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction. Objective measures of aortic contrast attenuation and image noise were averaged. Images were subjectively assessed (1 = worst, 5 = best) for diagnostic confidence, image noise, and vessel sharpness. Aneurysm sac diameter and endoleak detection were compared. Quantitative image noise was 26% less with ultra-low-dose model-based iterative reconstruction than with standard-dose adaptive statistical iterative reconstruction and 58% less than with ultra-low-dose adaptive statistical iterative reconstruction. Average subjective noise scores were not different between ultra-low-dose model-based iterative reconstruction and standard-dose adaptive statistical iterative reconstruction (3.8 vs. 4.0, P = .25). Subjective scores for diagnostic confidence were better with standard-dose adaptive statistical iterative reconstruction than with ultra-low-dose model-based iterative reconstruction (4.4 vs. 4.0, P = .002). Vessel sharpness was decreased with ultra-low-dose model-based iterative reconstruction compared with standard-dose adaptive statistical iterative reconstruction (3.3 vs. 4.1, P < .0001). Ultra-low-dose model-based iterative reconstruction and standard-dose adaptive statistical iterative reconstruction aneurysm sac diameters were not significantly different (4.9 vs. 4.9 cm); concordance for the presence of endoleak was 100% (P < .001). Compared with a standard-dose technique, an ultra-low-dose model-based iterative reconstruction protocol provides

  18. Efficacy of low dose gabapentin in acute herpes zoster for preventing postherpetic neuralgia: a prospective controlled study.

    PubMed

    Lee, Eo G; Lee, Hee J; Hyun, Dong J; Min, Kyunghoon; Kim, Dong H; Yoon, Moon S

    2016-05-01

    Postherpetic neuralgia (PHN) is a sequela of herpes zoster that adversely affects quality of life seriously. The risk factors for PHN are well known but the effective interventions that reduce the incidence of PHN are less studied. The objective of this study is to evaluate the efficacy of treatment with gabapentin in patients with acute herpes zoster for preventing PHN. We performed a prospective randomized controlled study of 120 participants diagnosed with acute herpes zoster, aged 50 and over and complaining moderate to severe pain. All patients were treated with valacyclovir and acetaminophen. Half of the participants were assigned to the gabapentin group and received gabapentin 300 mg three times a day additionally. The intensity of pain at every visit and the incidence of PHN in both groups were measured. Total 52 and 49 patients in the gabapentin group and the control group, respectively, had completed 12 weeks of follow-up period. Although the incidence of PHN was higher in the control group, the difference was not statistically significant (6.1% vs. 3.8%, p = 0.67). Our results indicate that the use of low-dose gabapentin in acute herpes zoster seems not effective in the prevention of PHN. © 2016 Wiley Periodicals, Inc.

  19. Dual-gate photo thin-film transistor: a “smart” pixel for high- resolution and low-dose X-ray imaging

    NASA Astrophysics Data System (ADS)

    Wang, Kai; Ou, Hai; Chen, Jun

    2015-06-01

    Since its emergence a decade ago, amorphous silicon flat panel X-ray detector has established itself as a ubiquitous platform for an array of digital radiography modalities. The fundamental building block of a flat panel detector is called a pixel. In all current pixel architectures, sensing, storage, and readout are unanimously kept separate, inevitably compromising resolution by increasing pixel size. To address this issue, we hereby propose a “smart” pixel architecture where the aforementioned three components are combined in a single dual-gate photo thin-film transistor (TFT). In other words, the dual-gate photo TFT itself functions as a sensor, a storage capacitor, and a switch concurrently. Additionally, by harnessing the amplification effect of such a thin-film transistor, we for the first time created a single-transistor active pixel sensor. The proof-of-concept device had a W/L ratio of 250μm/20μm and was fabricated using a simple five-mask photolithography process, where a 130nm transparent ITO was used as the top photo gate, and a 200nm amorphous silicon as the absorbing channel layer. The preliminary results demonstrated that the photocurrent had been increased by four orders of magnitude due to light-induced threshold voltage shift in the sub-threshold region. The device sensitivity could be simply tuned by photo gate bias to specifically target low-level light detection. The dependence of threshold voltage on light illumination indicated that a dynamic range of at least 80dB could be achieved. The "smart" pixel technology holds tremendous promise for developing high-resolution and low-dose X-ray imaging and may potentially lower the cancer risk imposed by radiation, especially among paediatric patients.

  20. Prospective comparison of conventional radiography, low-dose computed tomography and magnetic resonance imaging in monoclonal gammopathies.

    PubMed

    Minarik, Jiri; Krhovska, Petra; Hrbek, Jan; Pika, Tomas; Bacovsky, Jaroslav; Herman, Miroslav; Scudla, Vlastimil

    2016-06-01

    We carried out a prospective study in order to identify the best imaging approach for patients with newly diagnosed multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). We assessed the extent of myeloma bone disease (MBD) in 112 individuals - 84 patients with MM and 28 individuals with MGUS. For the detection of osteolytic involvement we used whole-body magnetic resonance imaging (WB-MRI), low-dose computed tomography (LD-CT) and conventional radiography (CR). Each method assessed the presence of osteolytic involvement, compressive fractures and extramedullary involvement in the following regions: skull, spine and chest, pelvis and humerus and femur. We compared the difference in the number and extent of osteolytic involvement, especially the findings in CR negative patients. Conventional radiography showed no superiority in any of the evaluated regions, and failed in the detection of extramedullary massess and spine involvement. WB-MRI was best at imaging the spine including extramedullary involvement, however, detection of osteolytic lesions of the skull was limited in comparison with both CR and LD-CT. Both WB-MRI and LD-CT were comparable in imaging of lesions of pelvis, humerus, femur and the presence of extramedullary masses. LD-CT showed superiority in detection of skull lesions but lower sensitivity in spine compared to WB-MRI. Our results confirm that relying solely on CR in the diagnostics of MM is insufficient. We suggest that the most suitable method for primary assessment of osteolytic involvement in monoclonal gammopathies should include either whole-body MRI together with CR of the skull or, with an equivalent sensitivity, whole body LD-CT.

  1. Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.

    PubMed

    Szucs-Farkas, Zsolt; Megyeri, Boglarka; Christe, Andreas; Vock, Peter; Heverhagen, Johannes T; Schindera, Sebastian T

    2014-08-01

    To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. • 80 kVp CTPA is safe in patients weighing <100 kg • Reduced radiation and iodine dose still provide high vessel attenuation • Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.

  2. Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

    PubMed

    Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

    2015-01-01

    Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

  3. Prospective gated chest tomosynthesis using CNT X-ray source array

    NASA Astrophysics Data System (ADS)

    Shan, Jing; Burk, Laurel; Wu, Gongting; Lee, Yueh Z.; Heath, Michael D.; Wang, Xiaohui; Foos, David; Lu, Jianping; Zhou, Otto

    2015-03-01

    Chest tomosynthesis is a low-dose 3-D imaging modality that has been shown to have comparable sensitivity as CT in detecting lung nodules and other lung pathologies. We have recently demonstrated the feasibility of stationary chest tomosynthesis (s-DCT) using a distributed CNT X-ray source array. The technology allows acquisition of tomographic projections without moving the X-ray source. The electronically controlled CNT x-ray source also enables physiologically gated imaging, which will minimize image blur due to the patient's respiration motion. In this paper, we investigate the feasibility of prospective gated chest tomosynthesis using a bench-top s-DCT system with a CNT source array, a high- speed at panel detector and realistic patient respiratory signals captured using a pressure sensor. Tomosynthesis images of inflated pig lungs placed inside an anthropomorphic chest phantom were acquired at different respiration rate, with and without gating for image quality comparison. Metal beads of 2 mm diameter were placed on the pig lung for quantitative measure of the image quality. Without gating, the beads were blurred to 3:75 mm during a 3 s tomosynthesis acquisition. When gated to the end of the inhalation and exhalation phase the detected bead size reduced to 2:25 mm, much closer to the actual bead size. With gating the observed airway edges are sharper and there are more visible structural details in the lung. Our results demonstrated the feasibility of prospective gating in the s-DCT, which substantially reduces image blur associated with lung motion.

  4. Comparison of low-dose oxytocin and dinoprostone for labor induction in postterm pregnancies: a randomized controlled prospective study.

    PubMed

    Akay, Nezahat Öztürk; Hızlı, Deniz; Yılmaz, Saynur Sarıcı; Yalvaç, Serdar; Kandemir, Omer

    2012-01-01

    The aim of this study was to compare the efficacy of oxytocin and dinoprostone in achieving successful labor induction and vaginal delivery in postterm women with an unfavorable cervix. Postterm women with an uncomplicated pregnancy and a Bishop score of ≤6 were randomized to receive either dinoprostone vaginal pessary (Propess®) or low-dose oxytocin. The primary outcomes were the length of the induction-to-delivery period and the incidence of vaginal delivery. A total of 144 women were available for the analysis. The overall vaginal delivery rates were 75% (54/72) for the dinoprostone group and 80.6% (58/72; p = 0.35) for the oxytocin group; the mean induction-to-vaginal delivery interval was 13.3 and 10.3 h in the dinoprostone and the oxytocin group, respectively (p = 0.003). Uterine hyperstimulation was 7.4% compared with 6.8% (p = 0.8), and abnormal fetal heart rate was 26.4% compared with 18% (p = 0.2), respectively. Both oxytocin and dinoprostone seem to have similar obstetric outcomes in postterm pregnancies with an unfavorable cervix, except for a significant superiority of oxytocin for delivery in a shorter period. Copyright © 2012 S. Karger AG, Basel.

  5. Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease

    PubMed Central

    Mucker, Eric M.; Chapman, Jennifer; Huzella, Louis M.; Huggins, John W.; Shamblin, Joshua; Robinson, Camenzind G.; Hensley, Lisa E.

    2015-01-01

    Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox. PMID:26147658

  6. Detection of coronary artery stenoses by low-dose, prospectively ECG-triggered, high-pitch spiral coronary CT angiography.

    PubMed

    Achenbach, Stephan; Goroll, Tobias; Seltmann, Martin; Pflederer, Tobias; Anders, Katharina; Ropers, Dieter; Daniel, Werner G; Uder, Michael; Lell, Michael; Marwan, Mohamed

    2011-04-01

    We sought to evaluate the diagnostic accuracy of a new prospectively electrocardiogram (ECG)-triggered high-pitch scan mode for coronary computed tomography angiography (CTA), which allows an effective dose of less than 1 mSv. Coronary CTA provides increasingly reliable image quality, but the associated radiation exposure can be high. Seventy-five patients with suspected coronary artery disease and in sinus rhythm were screened for participation. After exclusion of 25 patients for body weight >100 kg or failure to lower heart rate to ≤ 60 beats/min, 50 patients were studied by prospectively ECG-triggered high-pitch spiral computed tomography (CT). Coronary CTA was performed using a dual-source CT system with 2 × 128 × 0.6-mm collimation, 0.28-s rotation time, a pitch of 3.4, 100-kVp tube voltage, and current of 320 mA. Data acquisition was prospectively triggered at 60% of the R-R interval and completed within 1 cardiac cycle. Diagnostic accuracy for detection of coronary artery stenoses ≥ 50% diameter stenosis was determined by comparison to invasive coronary angiography. Per-patient diagnostic performance was the primary form of analysis. In all 50 patients (34 males, 59 ± 12 years of age), imaging was successful. For the detection of 16 patients with at least 1 coronary artery stenosis, CT demonstrated a sensitivity of 100% (95% confidence interval [CI]: 79% to 100%) and specificity of 82% (95% CI: 65% to 93%). The positive predictive value was 72% (95% CI: 49% to 89%) and the negative predictive value was 100% (95% CI: 87% to 100%). Sensitivity was 100% (95% CI: 88% to 100%) and specificity was 94% (95% CI: 89% to 97%) on a per-vessel basis. Per-segment sensitivity was 92% (95% CI: 80% to 97%), and specificity was 98% (95% CI: 96% to 98%). Mean dose-length product for coronary CTA was 54 ± 6 mGy · cm, the effective dose was 0.76 ± 0.08 mSv (0.64 to 0.95 mSv). In nonobese patients with a low and stable heart rate, prospectively ECG-triggered high

  7. [Prospective study on the repercussions of low doses of remifentanil on sinoatrial function and in cardiac conduction and refractory period.].

    PubMed

    Leite, Simone Soares; Firme, Elizabeth Bessadas Penna; Bevilaqua, Márcia Santana; Pereira, Leonel Dos Santos; Atié, Jacob

    2007-10-01

    Remifentanil is an opiod with fast onset of action and short acting, and its use in short-duration procedures has increased in the last few years. Bradycardia and asystole are among the side effects reported. The objective of this study was to evaluate the effects of this drug in cardiac conduction and refractory period in human beings. A prospective study with 16 patients, ages 18 to 65, both genders, ASA I to III, undergoing elective intracardiac electrophysiological study, was undertaken. Patients with disorders of the sinoatrial node and those with severe cardiac blocks were excluded. In the laboratory of electrophysiology, patients were sedated with midazolam (0.03 mg.kg-1) after 5 minutes the degree of sedation and degree of pain, systolic and diastolic blood pressure, heart rate and respiratory rate, and oxygen saturation were evaluated. The electrophysiologist evaluated cardiac conduction (duration of the QRS complex, and AA, AH, HV, and PA intervals), duration of sinoatrial node recovery, and cardiac refractory period (refractory period of the right atrium, right ventricle, and atrioventricular node). After the initial measurements, remifentanil was administered (bolus of 0.5 microg.kg-1 + infusion of 0.05 microg.kg-1.min-1) and, after 20 minutes, the same parameters were evaluated. There was a reduction in systolic and diastolic blood pressure (p = 0.0001) between M0 and M1, and significant differences in respiratory rate and oxygen saturation, which were not statistically significant. The atrium-His interval (p = 0.006), recovery time of the sinoatrial node (p = 0.0004), refractory period of the right atrium (p = 0.001), and refractory period of the sinoatrial node (p = 0.0001) were all increased; however, there were no differences in heart rate between M0 and M1. Remifentanil changes cardiac electrophysiological parameters and, in doses higher than the ones used in this study, can cause sinus bradycardia, asystole, and conduction defects.

  8. Evaluation of reperfused myocardial infarction by low-dose multidetector computed tomography using prospective electrocardiography (ECG)-triggering: comparison with magnetic resonance imaging.

    PubMed

    Gweon, Hye Mi; Kim, Sang Jin; Kim, Tae Hoon; Lee, Sang Min; Hong, Yoo Jin; Rim, Se-Joong; Hong, Bum Ki; Min, Phil Ki; Yoon, Young Won; Kwon, Hyuck Moon

    2010-09-01

    To evaluate the potential of prospective electrocardiography (ECG)- gated 64-slice multidetector computed tomography (MDCT) for evaluation of myocardial enhancement, infarct size, and stent patency after percutaneous coronary intervention (PCI) with stenting in patients with myocardial infarction. Seventeen patients who were admitted with acute myocardial infarction were examined with prospective ECG-gated 64-slice cardiac MDCT and magnetic resonance (MR) imaging after reperfusion using PCI with stenting. Cardiac MDCT was performed with two different phases: arterial and delayed phases. We evaluated the stent patency on the arterial phase, and nonviable myocardium on the delayed phase of computed tomography (CT) image, and they were compared with the results from the delayed MR images. Total mean radiation dose was 7.7 +/- 0.5 mSv on the two phases of CT images. All patients except one showed good patency of the stent at the culprit lesion on the arterial phase CT images. All patients had hyperenhanced area on the delayed phase CT images, which correlated well with those on the delayed phase MR images, with a mean difference of 1.6% (20 +/- 10% vs. 22 +/- 10%, r = 0.935, p = 0.10). Delayed MR images had a better contrast-to-noise ratio (CNR) than delayed CT images (27.1 +/- 17.8% vs. 4.3 +/- 2.1%, p < 0.001). Prospective ECG-gated 64-slice MDCT provides the potential to evaluate myocardial viability on delayed phase as well as for stent patency on arterial phase with an acceptable radiation dose after PCI with stenting in patients with myocardial infarction.

  9. A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of  pain in the ED.

    PubMed

    Motov, Sergey; Mai, Mo; Pushkar, Illya; Likourezos, Antonios; Drapkin, Jefferson; Yasavolian, Matthew; Brady, Jason; Homel, Peter; Fromm, Christian

    2017-08-01

    Compare adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED administered either by single intravenous push (IVP) or short infusion (SI). Patients 18-65, presenting to ED with acute abdominal, flank, or musculoskeletal pain with initial pain score≥5, were randomized to ketamine 0.3mg/kg by either IVP or SI with placebo double-dummy. Adverse effects were evaluated by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation-Sedation Scale (RASS) at 5, 15, 30, 60, 90, and 120min post-administration; analgesic efficacy was evaluated by Numerical Rating Scale (NRS). 48 patients enrolled in the study. IVP group had higher overall rates of feeling of unreality on SERSDA scale: 92% versus 54% (difference 37.5%; p=0.008; 95% CI 9.3-59.5%). At 5min median severity of feeling of unreality was 3.0 for IVP versus 0.0 for SI (p=0.001). IVP also showed greater rates of sedation on RASS scale at 5min: median RASS -2.0 versus 0.0 (p=0.01). Decrease in mean pain scores from baseline to 15min was similar across groups: 5.2±3.53 (95% CI 3.7-6.7) for IVP; 5.75±3.48 (95% CI 4.3-7.2) for SI. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication. Low-dose ketamine given as a short infusion is associated with significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Accelerated Partial Breast Irradiation With Low-Dose-Rate Interstitial Implant Brachytherapy After Wide Local Excision: 12-Year Outcomes From a Prospective Trial

    SciTech Connect

    Hattangadi, Jona A.; Powell, Simon N.; MacDonald, Shannon M.; Mauceri, Thomas; Ancukiewicz, Marek; Freer, Phoebe; Lawenda, Brian; Alm El-Din, Mohamed A.; Gadd, Michele A.; Smith, Barbara L.; Taghian, Alphonse G.

    2012-07-01

    Purpose: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). Materials and Methods: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau ({tau}{sub {beta}}) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. Results: The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome ({tau}{sub {beta}} 0.6, p < .0001), lower patient satisfaction ({tau}{sub {beta}} 0.5, p < .001), and worse fibrosis ({tau}{sub {beta}} 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias {>=}1 cm{sup 2}. Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose ({tau}{sub {beta}} 0.3-0.5, p {<=} .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence-free survival

  11. Effect of low-dose citrate anticoagulation on the clinical safety and efficacy of direct adsorption of lipoproteins (DALI apheresis) in hypercholesterolemic patients: a prospective controlled clinical trial.

    PubMed

    Bosch, T; Heinemann, O; Duhr, C; Wendler, T; Keller, C; Fink, E; Kirschner, T; Klebert, S; Samtleben, W

    2000-10-01

    Direct adsorption of lipoproteins (DALI) is the first lipid apheresis system compatible with whole blood with the advantage of a very simple procedure. A mixture of heparin plus citrate (ACD-A) is used for the anticoagulation regimen (AR). A clinical, prospective, controlled crossover study was performed to test the safety and efficacy of low-dose citrate (LDC) anticoagulation in DALI. Five chronic DALI patients suffering from coronary heart disease and hypercholesterolemia underwent 3 DALI sessions each using the LDC anticoagulation regimen (60 IU heparin/kg body weight as initial bolus; 1:40 ACD-A: blood as perfusion). This was compared to 3 sessions per patient with the standard AR (bolus of 20 IU heparin/kg, 1:20 ACD-A as perfusion). Patient blood volumes (1.6; average of 7,040 ml) were treated with 750 ml adsorber gel per session at a blood flow rate of 60 ml/min. Mean LDL and Lp(a) reductions exceeded 60% with both AR. No clinical side effects were observed. Both AR controlled the coagulation well as evidenced by a sufficient prolongation of the partial prothrombin time (PTT) and activated clotting time as well as low thrombin-antithrombin (TAT) formation. Biocompatibility parameters exhibited favorable results (low activation of complement and cells, and only slight formation of C3a, C5a, beta-thromboglobulin, elastase, and TNF-alpha). The asymptomatic bradykinin generation was comparable in both study arms. LDC optimized the ionized calcium levels and pH in the efferent blood postadsorber. LDC anticoagulation was safe and effective, and may further improve the tolerance of DALI apheresis in hypercholesterolemic patients.

  12. Marked reduction of effective radiation dose in patients undergoing CT coronary angiography using prospective ECG gating.

    PubMed

    Freeman, Anthony; Learner, Ruth; Eggleton, Simon; Lambros, John; Friedman, Daniel

    2011-08-01

    Coronary CT angiography (CCTA) is a rapidly evolving technology which can characterise and image sub clinical atherosclerotic plaque and visualise anatomy and quantitate stenosis. Concern about radiation exposure has limited the uptake of this technology. The aim of this study was to review the radiation dose data in 2298 consecutive patients referred to a single centre in an Australian outpatient setting over 27 months using all available radiation dose reduction strategies. Prospective ECG gating ("step and shoot") was used preferentially in 2025 patients with a mean effective dose of 3.39 ± 1.84 mSv (range 0.86-12.6 mSv). For clinical reasons only 273 patients required retrospective ECG gating, mean dose 19.21 ± 5.58 mSv (range 2.4-34.9 mSv) resulting in an 85.7% reduction in dose for the majority of patients with the low dose technique. In conclusion, most patients referred for routine CCTA can be studied with a radiation dose comparable to invasive X-ray angiography and less than radionuclide myocardial perfusion imaging. Copyright © 2011 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.

  13. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  14. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  15. Diagnostic Performance of Ultra-Low-Dose Computed Tomography for Detecting Asbestos-Related Pleuropulmonary Diseases: Prospective Study in a Screening Setting

    PubMed Central

    Schaal, Marysa; Severac, François; Labani, Aissam; Jeung, Mi-Young; Roy, Catherine

    2016-01-01

    Objective To evaluate the diagnostic performance of Ultra-Low-Dose Chest CT (ULD CT) for the detection of any asbestos-related lesions (primary endpoint) and specific asbestos-related abnormalities, i.e. non-calcified and calcified pleural plaques, diffuse pleural thickening, asbestosis and significant lung nodules (secondary endpoints). Material and Methods 55 male patients (55.7±8.1 years old) with occupational asbestos exposure for at least 15 years and where CT screening was indicated were prospectively included. They all underwent a standard unenhanced chest CT (120kV, automated tube current modulation), considered as the reference, and an ULD CT (135kV, 10mA), both with iterative reconstruction. Two chest radiologists independently and blindly read the examinations, following a detailed protocol. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy and error rate of ULD CT were calculated using the exact method of Pearson with a confidence interval of 95%. Results Radiation dose was 17.9±1.2mGy.cm (0.25mSv) for the ULD-CT versus 288.8 ±151mGy.cm (4mSv); p <2.2e-16. Prevalence of abnormalities was 20%. The ULD CT’s diagnostic performance in joint reading was high for the primary endpoint (sensitivity = 90.9%, specificity = 100%, positive predictive value = 100%, negative predictive value = 97.8%), high for lung nodules, diffuse pleural thickening and calcified pleural plaques (sensitivity, specificity, PPV and NPV = 100%) and fair for asbestosis (sensitivity = 75%, specificity = 100%, PPV = 00%, NPV = 98.1%). Intra-reader accuracy between the ULD CT and the reference CT for the primary endpoint was 98% for the senior and 100% for the junior radiologist. Inter-reader agreement for the primary endpoint was almost perfect (Cohen’s Kappa of 0.81). Conclusion ULD CT in the screening of asbestos exposure related diseases has 90.9% sensitivity and 100% specificity, and could therefore be proposed as a first line examination

  16. Reliability analysis of visual ranking of coronary artery calcification on low-dose CT of the thorax for lung cancer screening: comparison with ECG-gated calcium scoring CT.

    PubMed

    Kim, Yoon Kyung; Sung, Yon Mi; Cho, So Hyun; Park, Young Nam; Choi, Hye-Young

    2014-12-01

    Coronary artery calcification (CAC) is frequently detected on low-dose CT (LDCT) of the thorax. Concurrent assessment of CAC and lung cancer screening using LDCT is beneficial in terms of cost and radiation dose reduction. The aim of our study was to evaluate the reliability of visual ranking of positive CAC on LDCT compared to Agatston score (AS) on electrocardiogram (ECG)-gated calcium scoring CT. We studied 576 patients who were consecutively registered for health screening and undergoing both LDCT and ECG-gated calcium scoring CT. We excluded subjects with an AS of zero. The final study cohort included 117 patients with CAC (97 men; mean age, 53.4 ± 8.5). AS was used as the gold standard (mean score 166.0; range 0.4-3,719.3). Two board-certified radiologists and two radiology residents participated in an observer performance study. Visual ranking of CAC was performed according to four categories (1-10, 11-100, 101-400, and 401 or higher) for coronary artery disease risk stratification. Weighted kappa statistics were used to measure the degree of reliability on visual ranking of CAC on LDCT. The degree of reliability on visual ranking of CAC on LDCT compared to ECG-gated calcium scoring CT was excellent for board-certified radiologists and good for radiology residents. A high degree of association was observed with 71.6% of visual rankings in the same category as the Agatston category and 98.9% varying by no more than one category. Visual ranking of positive CAC on LDCT is reliable for predicting AS rank categorization.

  17. Measurement of time delay for a prospectively gated CT simulator

    PubMed Central

    Goharian, M.; Khan, R. F. H.

    2010-01-01

    For the management of mobile tumors, respiratory gating is the ideal option, both during imaging and during therapy. The major advantage of respiratory gating during imaging is that it is possible to create a single artifact-free CT data-set during a selected phase of the patient's breathing cycle. The purpose of the present work is to present a simple technique to measure the time delay during acquisition of a prospectively gated CT. The time delay of a Philips Brilliance BigBore™ (Philips Medical Systems, Madison, WI) scanner attached to a Varian Real-Time Position Management™ (RPM) system (Varian Medical Systems, Palo Alto, CA) was measured. Two methods were used to measure the CT time delay: using a motion phantom and using a recorded data file from the RPM system. In the first technique, a rotating wheel phantom was altered by placing two plastic balls on its axis and rim, respectively. For a desired gate, the relative positions of the balls were measured from the acquired CT data and converted into corresponding phases. Phase difference was calculated between the measured phases and the desired phases. Using period of motion, the phase difference was converted into time delay. The Varian RPM system provides an external breathing signal; it also records transistor-transistor logic (TTL) ‘X-Ray ON’ status signal from the CT scanner in a text file. The TTL ‘X-Ray ON’ indicates the start of CT image acquisition. Thus, knowledge of the start time of CT acquisition, combined with the real-time phase and amplitude data from the external respiratory signal, provides time-stamping of all images in an axial CT scan. The TTL signal with time-stamp was used to calculate when (during the breathing cycle) a slice was recorded. Using the two approaches, the time delay between the prospective gating signal and CT simulator has been determined to be 367 ± 40 ms. The delay requires corrections both at image acquisition and while setting gates for the treatment

  18. Determination of prospective displacement-based gate threshold for respiratory-gated radiation delivery from retrospective phase-based gate threshold selected at 4D CT simulation

    SciTech Connect

    Vedam, S.; Archambault, L.; Starkschall, G.; Mohan, R.; Beddar, S.

    2007-11-15

    Four-dimensional (4D) computed tomography (CT) imaging has found increasing importance in the localization of tumor and surrounding normal structures throughout the respiratory cycle. Based on such tumor motion information, it is possible to identify the appropriate phase interval for respiratory gated treatment planning and delivery. Such a gating phase interval is determined retrospectively based on tumor motion from internal tumor displacement. However, respiratory-gated treatment is delivered prospectively based on motion determined predominantly from an external monitor. Therefore, the simulation gate threshold determined from the retrospective phase interval selected for gating at 4D CT simulation may not correspond to the delivery gate threshold that is determined from the prospective external monitor displacement at treatment delivery. The purpose of the present work is to establish a relationship between the thresholds for respiratory gating determined at CT simulation and treatment delivery, respectively. One hundred fifty external respiratory motion traces, from 90 patients, with and without audio-visual biofeedback, are analyzed. Two respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory gating from the 4D CT-derived tumor motion trajectory. From residual tumor displacements within each such gating phase interval, a simulation gate threshold is defined based on (a) the average and (b) the maximum respiratory displacement within the phase interval. The duty cycle for prospective gated delivery is estimated from the proportion of external monitor displacement data points within both the selected phase interval and the simulation gate threshold. The delivery gate threshold is then determined iteratively to match the above determined duty cycle. The magnitude of the difference between such gate thresholds determined at simulation and treatment delivery is quantified in each case. Phantom motion tests yielded coincidence of simulation

  19. Low-dose radiotherapy as a chemo-potentiator of a chemotherapy regimen with pemetrexed for recurrent non-small-cell lung cancer: a prospective phase II study.

    PubMed

    Mantini, Giovanna; Valentini, Vincenzo; Meduri, Bruno; Margaritora, Stefano; Balducci, Mario; Micciché, Francesco; Nardone, Luigia; De Rose, Fiorenza; Cesario, Alfredo; Larici, Anna Rita; Maggi, Fabio; Calcagni, Maria Lucia; Granone, Pierluigi

    2012-11-01

    Low-dose radiotherapy (LDR) (<50 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon. Aim of this study was to evaluate the safety and efficacy of a palliative regimen combining pemetrexed and LDR (as a chemopotentiator) on patients affected by recurrent non-small-cell lung cancer (NSCLC). Eligible patients had an ECOG performance status ≤2, one prior chemotherapy regimen for advanced NSCLC, adequate organ function, measurable lesions. Patients received pemetrexed (500 mg/m(2) IV) and concurrent LDR (40 cGy bid on days 1 and 2) delivered to target pulmonary or metastatic disease. This cycle was repeated fourfold every 21 days. The accrual was determined by the single proportion powered analysis (α=0.05, power=0.8) with H0 ("bad" response probability, 9% according to literature) and H1 ("good" response probability, 35% ongoing study); 19 is the number required. Nineteen patients with stage III and IV disease were enrolled. Only one patient experienced neutropenia grade 4. All patients are evaluable for clinical response of irradiated lesion: overall response rate was 42%. Low-dose radiotherapy combined with pemetrexed has a similar toxicity profile to chemotherapy alone. The response rate of this novel approach is encouraging, since it was higher than what was reported for pemetrexed alone (42% versus 9.1%). Additional scientific investigation of this new treatment paradigm is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Low dose aprotinin and low dose tranexamic acid in elective cardiac surgery with cardiopulmonary bypass.

    PubMed

    Waldow, Thomas; Krutzsch, Diana; Wils, Michael; Plötze, Katrin; Matschke, Klaus

    2009-01-01

    The antifibrinolytic agents aprotinin and tranexamic acid have both been proven to be efficient in reducing postoperative blood loss and transfusion requirements in patients in cardiac surgery. In light of recent safety issues regarding aprotinin, this single-centre study compared efficacy and safety of low dose aprotinin (2 million KIU, pump-prime volume only) and low dose tranexamic acid (1 g, pump-prime volume) in 708 consecutive patients from two prospective registers undergoing elective cardiac procedures with cardiopulmonary bypass (CPB). Incidences of postoperative complications showed no significant differences between groups. Postoperative blood loss and transfusion requirements were significantly lower in aprotinin compared to tranexamic acid patients. Overall, both antifibrinolytic low dose regimens are safe components of perioperative patient management in elective cardiac surgery with CPB. Cardiac procedures requiring longer CPB times might benefit from the administration of low dose aprotinin.

  1. Acute appendicitis: prospective evaluation of a diagnostic algorithm integrating ultrasound and low-dose CT to reduce the need of standard CT.

    PubMed

    Poletti, Pierre-Alexandre; Platon, Alexandra; De Perrot, Thomas; Sarasin, Francois; Andereggen, Elisabeth; Rutschmann, Olivier; Dupuis-Lozeron, Elise; Perneger, Thomas; Gervaz, Pascal; Becker, Christoph D

    2011-12-01

    To evaluate an algorithm integrating ultrasound and low-dose unenhanced CT with oral contrast medium (LDCT) in the assessment of acute appendicitis, to reduce the need of conventional CT. Ultrasound was performed upon admission in 183 consecutive adult patients (111 women, 72 men, mean age 32) with suspicion of acute appendicitis and a BMI between 18.5 and 30 (step 1). No further examination was recommended when ultrasound was positive for appendicitis, negative with low clinical suspicion, or demonstrated an alternative diagnosis. All other patients underwent LDCT (30 mAs) (step 2). Standard intravenously enhanced CT (180 mAs) was performed after indeterminate LDCT (step 3). No further imaging was recommended after ultrasound in 84 (46%) patients; LDCT was obtained in 99 (54%). LDCT was positive or negative for appendicitis in 81 (82%) of these 99 patients, indeterminate in 18 (18%) who underwent standard CT. Eighty-six (47%) of the 183 patients had a surgically proven appendicitis. The sensitivity and specificity of the algorithm were 98.8% and 96.9%. The proposed algorithm achieved high sensitivity and specificity for detection of acute appendicitis, while reducing the need for standard CT and thus limiting exposition to radiation and to intravenous contrast media.

  2. Lenalidomide and low-dose dexamethasone (Rd) versus bortezomib, melphalan, prednisone (VMP) in elderly newly diagnosed multiple myeloma patients: A comparison of two prospective trials.

    PubMed

    Gentile, Massimo; Magarotto, Valeria; Offidani, Massimo; Musto, Pellegrino; Bringhen, Sara; Teresa Petrucci, Maria; Gay, Francesca; Larocca, Alessandra; Uccello, Giuseppina; Petrungaro, Annamaria; Vigna, Ernesto; Greco, Rosa; Grazia Recchia, Anna; Tripepi, Giovanni; Ria, Roberto; Di Raimondo, Francesco; Palumbo, Antonio; Morabito, Fortunato

    2017-03-01

    There are currently no direct head-to-head clinical trials evaluating bortezomib-melphalan-prednisone (VMP) versus lenalidomide and low-dose dexamethasone (Rd). VMP (257 cases) and Rd (222 cases) arms of two randomized phase III trials were employed to assess the treatment influence on outcome in untreated elderly MM patients. Progression free survival (PFS) and overall survival (OS) were the primary and secondary end-points, respectively, and were investigated according to treatments administered over a 60-months follow-up period. While VMP significantly reduced the disease progression rate between enrolment and 12 months of follow-up, no difference between the two schedules was found between 12 and 32 months. After 32 months, Rd-treated patients had a lower incidence of disease progression. A statistically significant higher OS rate was seen in the VMP arm, which was maintained after data adjustment for potential confounders. Both approaches showed acceptable toxicity profiles. The profound tumor reduction by VMP over Rd justifies the initial higher PFS rate in favor of the bortezomib schedule, while the Rd regimen overcomes this evident initial drawback in reducing the tumor burden by long-term drug administration, gaining a subsequent improved disease control. VMP is associated with a significant reduced risk of death. This study may help physicians make a more informed therapy choice.

  3. Low dose compared to variable dose Warfarin and to Fondaparinux as prophylaxis for thromboembolism after elective hip or knee replacement surgery; a randomized, prospective study.

    PubMed

    Bern, Murray M; Hazel, Diane; Deeran, Elizabeth; Richmond, John R; Ward, Daniel M; Spitz, Damon J; Mattingly, David A; Bono, James V; Berezin, Ronna H; Hou, Laura; Miley, Gerald B; Bierbaum, Benjamin E

    2015-01-01

    Deep vein thrombosis (DVT) and pulmonary emboli (PE), known together as venous thromboembolic (VTE) disease remain major complications following elective hip and knee surgery. This study compares three chemoprophylactic regimens for VTE following elective primary unilateral hip or knee replacement, one of which was designed to minimize risk of post-operative bleeding. Patients were randomized and stratified for hip vs. knee to receive A: variable dose warfarin (first dose on the night preceding surgery with subsequent target INR 2.0-2.5), B: 2.5 mg fondaparinux daily starting 6-18 h postoperatively, or C: fixed 1.0 mg dose warfarin daily starting 7 days preoperatively. All treatments continued until bilateral leg venous ultrasound day 28 ± 2 or earlier upon a VTE event. The study examined primary endpoints including leg DVT, PE or death due to VTE and secondary endpoints including effects on D-dimer, estimated blood loss (EBL) at surgery and hemorrhagic complications. Three hundred fifty-five patients were randomized. None was lost to follow-up. Taking 1.0 mg warfarin for seven days preoperatively did not prolong the prothrombin time (PT). Two patients in Arm C had asymptomatic distal DVT. One major bleed occurred in Arm B and one in Arm C (ischemic colitis). Elevated d-dimer did not predict delayed VTE for one year. Fixed low dose warfarin started preoperatively is equivalent to two other standards of care under study (95 % CI: -0.0428, 0.0067 for both) as VTE prophylaxis for the patients having elective major joint replacement surgery. ClinicalTrials.gov identifier # NCT00767559 FDA IND: 103,716.

  4. Risk of Cataract after Exposure to Low Doses of Ionizing Radiation: A 20-Year Prospective Cohort Study among US Radiologic Technologists

    PubMed Central

    Bekiroglu, Nural; Hauptmann, Michael; Alexander, Bruce H.; Freedman, D. Michal; Doody, Michele Morin; Cheung, Li C.; Simon, Steven L.; Weinstock, Robert M.; Bouville, André; Sigurdson, Alice J.

    2008-01-01

    The study aim was to determine the risk of cataract among radiologic technologists with respect to occupational and nonoccupational exposures to ionizing radiation and to personal characteristics. A prospective cohort of 35,705 cataract-free US radiologic technologists aged 24–44 years was followed for nearly 20 years (1983–2004) by using two follow-up questionnaires. During the study period, 2,382 cataracts and 647 cataract extractions were reported. Cigarette smoking for ≥5 pack-years; body mass index of ≥25 kg/m2; and history of diabetes, hypertension, hypercholesterolemia, or arthritis at baseline were significantly (p ≤ 0.05) associated with increased risk of cataract. In multivariate models, self-report of ≥3 x-rays to the face/neck was associated with a hazard ratio of cataract of 1.25 (95% confidence interval: 1.06, 1.47). For workers in the highest category (mean, 60 mGy) versus lowest category (mean, 5 mGy) of occupational dose to the lens of the eye, the adjusted hazard ratio of cataract was 1.18 (95% confidence interval: 0.99, 1.40). Findings challenge the National Council on Radiation Protection and International Commission on Radiological Protection assumptions that the lowest cumulative ionizing radiation dose to the lens of the eye that can produce a progressive cataract is approximately 2 Gy, and they support the hypothesis that the lowest cataractogenic dose in humans is substantially less than previously thought. PMID:18664497

  5. Low-Dose Sevoflurane May Reduce Blood Loss and Need for Blood Products After Cardiac Surgery: A Prospective, Randomized Pilot Study.

    PubMed

    Tan, Zhaoxia; Zhou, Li; Qin, Zhen; Luo, Ming; Chen, Hao; Xiong, Jiyue; Li, Jian; Liu, Ting; Du, Lei; Zhou, Jing

    2016-04-01

    Patients undergoing cardiac surgery often experience abnormal bleeding, due primarily to cardiopulmonary bypass (CPB)-induced activation of platelets. Sevoflurane may inhibit platelet activation, raising the possibility that administering it during CPB may reduce blood loss.Patients between 18 and 65 years old who were scheduled for cardiac surgery under CPB at our hospital were prospectively enrolled and randomized to receive intravenous anesthetics alone (control group, n = 77) or together with sevoflurane (0.5-1.0 vol/%) from an oxygenator (sevoflurane group, n = 76). The primary outcome was postoperative blood loss, the secondary outcome was postoperative need for blood products.Volume of blood loss was 48% lower in the sevoflurane group than the control group at 4 hours after surgery, and 33% lower at 12 hours after surgery. Significantly fewer patients in the sevoflurane group lost >700 mL blood within 24 hours (9 of 76 vs 28 of 77, P < 0.001). As a result, the sevoflurane group received significantly smaller volumes of packed red blood cells (1.25 ± 2.36 vs 2.23 ± 3.75 units, P = 0.011) and fresh frozen plasma (97 ± 237 vs 236 ± 344 mL, P = 0.004). Thus the sevoflurane group was at significantly lower risk of requiring complex blood products after surgery (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.17-0.68, P = 0.002).Sevoflurane inhalation from an oxygenator during CPB may reduce blood loss and need for blood products after cardiac surgery.

  6. Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma.

    PubMed

    Hauschild, Axel; Weichenthal, Michael; Rass, Knuth; Linse, Ruthild; Ulrich, Jens; Stadler, Rudolf; Volkenandt, Matthias; Grabbe, Stephan; Proske, Ulrike; Schadendorf, Dirk; Brockmeyer, Norbert; Vogt, Thomas; Rompel, Rainer; Kaufmann, Roland; Kaatz, Martin; Näher, Helmut; Mohr, Peter; Eigentler, Thomas; Livingstone, Elisabeth; Garbe, Claus

    2009-07-20

    PURPOSE Interferon alfa (IFN-alpha) has shown clinical efficacy in the adjuvant treatment of patients with high-risk melanoma in several clinical trials, but optimal dosing and duration of treatment are still under discussion. It has been argued that in high-dose IFN-alpha (HDI), the intravenous (IV) induction phase might be critical for the clinical benefit of the regimen. PATIENTS AND METHODS In an attempt to investigate the potential role of a modified high-dose induction phase, lymph node-negative patients with resected primary malignant melanoma of more than 1.5-mm tumor thickness were included in this prospective randomized multicenter Dermatologic Cooperative Oncology Group trial. Six hundred seventy-four patients were randomly assigned to receive 4 weeks of a modified HDI scheme. This schedule consisted of 5 times weekly 10 MU/m(2) IFN-alpha-2b IV for 2 weeks and 5 times weekly 10 MU/m(2) IFN-alpha-2b administered subcutaneously (SC) for another 2 weeks followed by 23 months of low-dose IFN-alpha-2b (LDI) 3 MU SC three times a week (arm A). LDI 3 MU three times a week was given for 24 months in arm B. Results Of 650 assessable patients, there were 92 relapses among the 321 patients receiving high-dose induction as compared with 95 relapses among the 329 patients receiving LDI only. Five-year relapse-free survival rates were 68.0% (arm A) and 67.1% (arm B), respectively. Likewise, melanoma-related fatalities were similar between both groups, resulting in 5-year overall survival rates of 80.2% (arm A) and 82.9% (arm B). CONCLUSION The addition of a 4-week modified HDI induction phase to a 2-year low-dose adjuvant IFN-alpha-2b treatment schedule did not improve the clinical outcome.

  7. High-dose supplements of vitamins C and E, low-dose multivitamins, and the risk of age-related cataract: a population-based prospective cohort study of men.

    PubMed

    Zheng Selin, Jinjin; Rautiainen, Susanne; Lindblad, Birgitta Ejdervik; Morgenstern, Ralf; Wolk, Alicja

    2013-03-15

    We examined the associations of high-dose supplements of vitamins C and E and low-dose multivitamins with the risk of age-related cataract among 31,120 Swedish men, aged 45-79 years, in a population-based prospective cohort. Dietary supplement use was assessed from a questionnaire at baseline in 1998. During follow-up (January 1998-December 2006), 2,963 incident age-related cataract cases were identified. The multivariable-adjusted hazard ratio for men using vitamin C supplements only was 1.21 (95% confidence interval (CI): 1.04, 1.41) in a comparison with that of non-supplement users. The hazard ratio for long-term vitamin C users (≥10 years before baseline) was 1.36 (95% CI: 1.02, 1.81). The risk of cataract with vitamin C use was stronger among older men (>65 years) (hazard ratio = 1.92, 95% CI: 1.41, 2.60) and corticosteroid users (hazard ratio = 2.11, 95% CI: 1.48, 3.02). The hazard ratio for vitamin E use only was 1.59 (95% CI: 1.12, 2.26). Use of multivitamins only or multiple supplements in addition to vitamin C or E was not associated with cataract risk. These results suggest that the use of high-dose (but not low-dose) single vitamin C or E supplements may increase the risk of age-related cataract. The risk may be even higher among older men, corticosteroid users, and long-term users.

  8. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study.

    PubMed

    Piazza, Gregory; Hohlfelder, Benjamin; Jaff, Michael R; Ouriel, Kenneth; Engelhardt, Tod C; Sterling, Keith M; Jones, Noah J; Gurley, John C; Bhatheja, Rohit; Kennedy, Robert J; Goswami, Nilesh; Natarajan, Kannan; Rundback, John; Sadiq, Immad R; Liu, Stephen K; Bhalla, Narinder; Raja, M Laiq; Weinstock, Barry S; Cynamon, Jacob; Elmasri, Fakhir F; Garcia, Mark J; Kumar, Mark; Ayerdi, Juan; Soukas, Peter; Kuo, William; Liu, Ping-Yu; Goldhaber, Samuel Z

    2015-08-24

    This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT

  9. Coronary CT Angiography Incorporating Doppler-Guided Prospective ECG Gating in Patients with High Heart Rate: Comparison with Results of Traditional Prospective ECG Gating

    PubMed Central

    Li, Min; Yu, Bing-bing; Wu, Jian-hua; Xu, Lin; Sun, Gang

    2013-01-01

    Purpose As Doppler ultrasound has been proven to be an effective tool to predict and compress the optimal pulsing windows, we evaluated the effective dose and diagnostic accuracy of coronary CT angiography (CTA) incorporating Doppler-guided prospective electrocardiograph (ECG) gating, which presets pulsing windows according to Doppler analysis, in patients with a heart rate >65 bpm. Materials and Methods 119 patients with a heart rate >65 bpm who were scheduled for invasive coronary angiography were prospectively studied, and patients were randomly divided into traditional prospective (n = 61) and Doppler-guided prospective (n = 58) ECG gating groups. The exposure window of traditional prospective ECG gating was set at 30%–80% of the cardiac cycle. For the Doppler group, the length of diastasis was analyzed by Doppler. For lengths greater than 90 ms, the pulsing window was preset during diastole (during 60%–80%); otherwise, the optimal pulsing intervals were moved from diastole to systole (during 30%–50%). Results The mean heart rates of the traditional ECG and the Doppler-guided group during CT scanning were 75.0±7.7 bpm (range, 66–96 bpm) and 76.5±5.4 bpm (range: 66–105 bpm), respectively. The results indicated that whereas the image quality showed no significant difference between the traditional and Doppler groups (P = 0.42), the radiation dose of the Doppler group was significantly lower than that of the traditional group (5.2±3.4mSv vs. 9.3±4.5mSv, P<0.001). The sensitivities of CTA applying traditional and Doppler-guided prospective ECG gating to diagnose stenosis on a segment level were 95.5% and 94.3%, respectively; specificities 98.0% and 97.1%, respectively; positive predictive values 90.7% and 88.2%, respectively; negative predictive values 99.0% and 98.7%, respectively. There was no statistical difference in concordance between the traditional and Doppler groups (P = 0.22). Conclusion Doppler-guided prospective ECG gating

  10. Prospective timing, attention and the switch. A response to 'Gating or switching? gating is a better model of prospective timing' by Zakay.

    PubMed

    Lejeune, H

    2000-12-07

    In response to the 'Switching or gating' paper (Lejeune, H., 1998. Switching or gating? The attentional challenge in cognitive models of psychological time. Behav. Proc. 44, 127-145), Zakay argued that attention allocation to time should reflect attentional processes in general and suggested that the attentional gate model (AGM) has more explanatory power than the temporal information processing model (TIP) of Church (Church, R.M., 1984. Properties of the internal clock. In: Gibbon, J., Allan, L., (Eds.), Timing and Time Perception, vol. 423. Annals of the New York Academy of Sciences, New York, pp. 566-582). The first point might not be challenged, provided that the specificity of the temporal stimulus is taken into account. Concerning the second point, we argue that the TIP model can account for human prospective timing and discuss differences between attention versus expectancy or motivation. We prefer a 'satellite' attention allocation process, targeting the switch and reference memory (Meck, W.H., 1983. Selective adjustment of the speed of the internal clock and memory processes. J. Exp. Psychol.: Anim. Behav. Proc. 9, 171-201) to an attentional gate serially included in the TIP model of Church.

  11. Effects of local anesthetic on the time between analgesic boluses and the duration of labor in patient-controlled epidural analgesia: prospective study of two ultra-low dose regimens of ropivacaine and sufentanil.

    PubMed

    Costa-Martins, José Manuel; Dias, Cláudia Camila; Pereira, Marco; Tavares, Jorge

    2015-01-01

    Patient-controlled epidural analgesia with low concentrations of anesthetics is effective in reducing labor pain. The aim of this study was to assess and compare two ultra-low dose regimens of ropivacaine and sufentanil (0.1% ropivacaine plus 0.5 μg.ml-1 sufentanil vs. 0.06% ropivacaine plus 0.5 μg.ml-1 sufentanil) on the intervals between boluses and the duration of labor. In this non-randomized prospective study, conducted between January and July 2010, two groups of parturients received patient-controlled epidural analgesia: Group I (n = 58; 1 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil) and Group II (n = 57; 0.6 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil). Rescue doses of ropivacaine at the concentration of the assigned group without sufentanil were administered as necessary. Pain, local anesthetic requirements, neuraxial blockade characteristics, labor and neonatal outcomes, and maternal satisfaction were recorded. The ropivacaine dose was greater in Group I (9.5 [7.7-12.7] mg.h-1 vs. 6.1 [5.1-9.8 mg.h-1], p < 0.001). A time increase between each bolus was observed in Group I (beta = 32.61 min, 95% CI [25.39; 39.82], p < 0.001), whereas a time decrease was observed in Group II (beta = -1.40 min, 95% CI [-2.44; -0.36], p = 0.009). The duration of the second stage of labor in Group I was significantly longer than that in Group II (78 min vs. 65 min, p < 0.001). Parturients receiving 0.06% ropivacaine exhibited less evidence of cumulative effects and exhibited faster second stage progression than those who received 0.1% ropivacaine.

  12. Low-dose hormone therapy in postmenopausal women in China.

    PubMed

    Zang, H; Shi, H; Speroff, L

    2010-12-01

    To review the experience of menopausal symptoms and low-dose hormone therapy (HT) in postmenopausal women in China. Literature review and critical summaries of available prospective, clinical trials (randomized, controlled trials, RCTs). Chinese women experience menopausal symptoms less frequently compared with women in developed countries, and the prevalence of menopausal symptoms is less in women of southern China than in women of northern China. The majority of postmenopausal Chinese women lack knowledge about HT, and the usage rate of HT is low in these women compared to that in women of developed countries. Some RCTs investigated the efficacy and safety of low- or ultra-low-dose HT, including conjugated equine estrogen, estradiol valerate, transdermal estradiol, nylestriol alone or in combination with progesterone, and tibolone in postmenopausal Chinese women. These RCTs reported that low- or ultra-low-dose HT relieved menopausal symptoms and prevented bone loss as well as standard-dose HT and was less likely to induce side-effects, including irregular vaginal bleeding and breast tenderness; there may be dose-dependent effects of HT. No study evaluated the effects of low-dose HT on cardiovascular events or breast mammographic density/risk of breast cancer. More RCTs are required to confirm efficacy and to assess the safety of low- or ultra-low-dose HT for a long-term period in a large group of postmenopausal women.

  13. Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension: A First-in-human, Concept-proven, Prospective, Dose-escalation, Multicenter Study.

    PubMed

    Yin, Wei-Hsian; Chen, Pei; Yeh, Hung-I; Wang, Kuo-Yang; Hung, Yi-Jen; Tseng, Wei-Kung; Wen, Ming-Shien; Wu, Tao-Cheng; Wu, Chau-Chung; Cheng, Shu-Meng; Chen, Jaw-Wen

    2016-03-01

    .Accordingly, the combination with low dose of DXM was feasible to improve BP control in patients who failed to achieve the BP goal by standard AM monotherapy. The benefit effects might be significant especially in patients with impaired endothelial function.

  14. Low Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James

    2002-09-14

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation.

  15. Low Dose Effects in Psychopharmacology: Ontogenetic Considerations

    PubMed Central

    Spear, Linda Patia; Varlinskaya, Elena I.

    2005-01-01

    Low doses of psychoactive drugs often elicit a behavioral profile opposite to that observed following administration of more substantial doses. Our laboratory has observed that these effects are often age-specific in rats. For instance, whereas moderate to high doses of the dopamine agonist apomorphine increase locomotion, suppressed locomotor activity is seen following low dose exposure, with this low dose effect not emerging consistently until adolescence. A somewhat earlier emergence of a low dose “paradoxical” effect is seen with the 5HT1a receptor agonist, 8-OH-DPAT, with late preweanling, but not neonatal, rats showing increases in ingestive behavior at low doses but suppression at higher doses. In contrast to these ontogenetic increases in expression of low dose drug effects, low dose facilitation of social behavior is seen following ethanol only in adolescent rats and not their mature counterparts, although suppression of social interactions at higher doses is seen at both ages. This hormesis-like low dose stimulation appears related in part to overcompensation, with brief social suppression preceding the subsequent stimulation response, and also bears a number of ontogenetic similarities to acute tolerance, a well characterized, rapidly emerging adaptation to ethanol. Implications of these and other ontogenetic findings for studies of hormesis are discussed. PMID:19330157

  16. Automated coronary artery calcification detection on low-dose chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Cham, Matthew D.; Henschke, Claudia; Yankelevitz, David; Reeves, Anthony P.

    2014-03-01

    Coronary artery calcification (CAC) measurement from low-dose CT images can be used to assess the risk of coronary artery disease. A fully automatic algorithm to detect and measure CAC from low-dose non-contrast, non-ECG-gated chest CT scans is presented. Based on the automatically detected CAC, the Agatston score (AS), mass score and volume score were computed. These were compared with scores obtained manually from standard-dose ECG-gated scans and low-dose un-gated scans of the same patient. The automatic algorithm segments the heart region based on other pre-segmented organs to provide a coronary region mask. The mitral valve and aortic valve calcification is identified and excluded. All remaining voxels greater than 180HU within the mask region are considered as CAC candidates. The heart segmentation algorithm was evaluated on 400 non-contrast cases with both low-dose and regular dose CT scans. By visual inspection, 371 (92.8%) of the segmentations were acceptable. The automated CAC detection algorithm was evaluated on 41 low-dose non-contrast CT scans. Manual markings were performed on both low-dose and standard-dose scans for these cases. Using linear regression, the correlation of the automatic AS with the standard-dose manual scores was 0.86; with the low-dose manual scores the correlation was 0.91. Standard risk categories were also computed. The automated method risk category agreed with manual markings of gated scans for 24 cases while 15 cases were 1 category off. For low-dose scans, the automatic method agreed with 33 cases while 7 cases were 1 category off.

  17. [Teamwork for cardiac imaging: coronary computed tomography angiography and low-dose radiation exposure: a cardiology center experience].

    PubMed

    Magnacca, Massimo; Poddighe, Rosa; Del Meglio, Jacopo; Lilli, Alessio; Baratto, Marco Tullio; Canale, Maria Laura; Tessa, Carlo; Salvatori, Luca; Niespolo, Alessandra; Vignali, Claudio; Casolo, Giancarlo

    2017-04-01

    Multidetector coronary computed tomography angiography (CCTA) is increasingly used for noninvasive imaging of the coronary arteries. Radiation exposure, however, is a potential limitation to a more extensive use of this imaging modality. We aimed to demonstrate that a professional teamwork approach, including a cardiologist and a radiologist in performing CCTA, may allow to obtain best quality exams with very low radiation doses. A total of 998 consecutive patients underwent CCTA in accordance with the most recent guidelines. The following procedures were undertaken to reduce the radiation dose: (a) preliminary cardiological evaluation to check for CCTA eligibility; (b) optimized heart rate control with beta-blockers and/or ivabradine; and (c) the use of nonstandardized computed tomography protocols and algorithms for dose reduction. All the patients underwent a preliminary cardiological evaluation; 89% of them were pretreated with oral or intravenous beta-blockers and/or ivabradine; 806 patients (81%) were scanned by means of prospective gating, which allowed a radiation dose exposure of 161 ± 68.64 mGy; 192 patients (19%) underwent a retrospective gating protocol, with a radiation dose exposure of 1135.15 ± 485.87 mGy. In 13 patients (1%) CCTA was uninterpretable because of artifacts. Exam quality was not affected by the use of low-dose computed tomography scanning. Coronary calcium score and/or left ventricular functional analysis were never performed. The preliminary selection and preparation of patients and optimized scanner utilization allow a substantial reduction in radiation dose for most of the patients submitted to CCTA without affecting image quality. In our experience, a team approach was necessary to allow a "low-dose learning curve" and a progressive reduction in radiation doses administered to patients by means of the prospective gating protocol.

  18. Enhancing acupuncture by low dose naltrexone.

    PubMed

    Hesselink, Jan M Keppel; Kopsky, David J

    2011-06-01

    To find appropriate and effective treatment options for chronic pain syndromes is a challenging task. Multimodal treatment approach has been gaining acceptance for chronic pain. However, combining treatments, such as acupuncture, with rational pharmacology is still in its infancy. Acupuncture influences the opioid and cannabinoid system through releasing endogenous receptor ligands. Low dose naltrexone also acts on both these systems, and upregulates the opioid and cannabinoid receptors. The authors hypothesise that low dose naltrexone could enhance the pain-relieving effect of acupuncture.

  19. Radiation Leukemogenesis at Low Dose Rates

    SciTech Connect

    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  20. Low Dose Rapamycin Exacerbates Autoimmune Experimental Uveitis

    PubMed Central

    Zhang, Zili; Wu, Xiumei; Duan, Jie; Hinrichs, David; Wegmann, Keith; Zhang, Gary L.; Hall, Mark; Rosenbaum, James T.

    2012-01-01

    Background Rapamycin, a potent immune modulator, is used to treat transplant rejection and some autoimmune diseases. Uveitis is a potentially severe inflammatory eye disease, and 2 clinical trials of treating uveitis with rapamycin are under way. Unexpectedly, recent research has demonstrated that low dose rapamycin enhances the memory T cell population and function. However, it is unclear how low dose rapamycin influences the immune response in the setting of uveitis. Design and Methods B10.RIII mice were immunized to induce experimental autoimmune uveitis (EAU). Ocular inflammation of control and rapamycin-treated mice was compared based on histological change. ELISPOT and T cell proliferation assays were performed to assess splenocyte response to ocular antigen. In addition, we examined the effect of rapamycin on activation-induced cell death (AICD) using the MitoCapture assay and Annexin V staining. Results Administration of low dose rapamycin exacerbated EAU, whereas treating mice with high dose rapamycin attenuated ocular inflammation. The progression of EAU by low dose rapamycin coincided with the increased frequency of antigen-reactive lymphocytes. Lastly, fewer rapamycin-treated T cells underwent AICD, which might contribute to exaggerated ocular inflammation and the uveitogenic immune response. Conclusion These data reveal a paradoxical role for rapamycin in uveitis in a dose-dependent manner. This study has a potentially important clinical implication as rapamycin might cause unwanted consequences dependent on dosing and pharmacokinetics. Thus, more research is needed to further define the mechanism by which low dose rapamycin augments the immune response. PMID:22574188

  1. Investigation of a breathing surrogate prediction algorithm for prospective pulmonary gating

    SciTech Connect

    White, Benjamin M.; Low, Daniel A.; Zhao Tianyu; Wuenschel, Sara; Lu, Wei; Lamb, James M.; Mutic, Sasa; Bradley, Jeffrey D.; El Naqa, Issam

    2011-03-15

    Purpose: A major challenge of four dimensional computed tomography (4DCT) in treatment planning and delivery has been the lack of respiration amplitude and phase reproducibility during image acquisition. The implementation of a prospective gating algorithm would ensure that images would be acquired only during user-specified breathing phases. This study describes the development and testing of an autoregressive moving average (ARMA) model for human respiratory phase prediction under quiet respiration conditions. Methods: A total of 47 4DCT patient datasets and synchronized respiration records was utilized in this study. Three datasets were used in model development and were removed from further evaluation of the ARMA model. The remaining 44 patient datasets were evaluated with the ARMA model for prediction time steps from 50 to 1000 ms in increments of 50 and 100 ms. Thirty-five of these datasets were further used to provide a comparison between the proposed ARMA model and a commercial algorithm with a prediction time step of 240 ms. Results: The optimal number of parameters for the ARMA model was based on three datasets reserved for model development. Prediction error was found to increase as the prediction time step increased. The minimum prediction time step required for prospective gating was selected to be half of the gantry rotation period. The maximum prediction time step with a conservative 95% confidence criterion was found to be 0.3 s. The ARMA model predicted peak inhalation and peak exhalation phases significantly better than the commercial algorithm. Furthermore, the commercial algorithm had numerous instances of missed breath cycles and falsely predicted breath cycles, while the proposed model did not have these errors. Conclusions: An ARMA model has been successfully applied to predict human respiratory phase occurrence. For a typical CT scanner gantry rotation period of 0.4 s (0.2 s prediction time step), the absolute error was relatively small, 0

  2. Evaluation of exposure dose reduction in multislice CT coronary angiography (MS-CTA) with prospective ECG-gated helical scan

    NASA Astrophysics Data System (ADS)

    Ota, Takamasa; Tsuyuki, Masaharu; Okumura, Miwa; Sano, Tomonari; Kondo, Takeshi; Takase, Shinichi

    2008-03-01

    A novel low-dose ECG-gated helical scan method to investigate coronary artery diseases was developed. This method uses a high pitch for scanning (based on the patient's heart rate) and X-rays are generated only during the optimal cardiac phases. The dose reduction was obtained using a two-level approach: 1) To use a 64-slice CT scanner (Aquilion, Toshiba, Otawara, Tochigi, Japan) with a scan speed of 0.35 s/rot. to helically scan the heart at a high pitch based on the patient's heart rate. By changing the pitch from the conventional 0.175 to 0.271 for a heart rate of 60 bpm, the exposure dose was reduced to 65%. 2) To employ tube current gating that predicts the timing of optimal cardiac phases from the previous cardiac cycle and generates X-rays only during the required cardiac phases. The combination of high speed scanning with a high pitch and appropriate X-ray generation only in the cardiac phases from 60% to 90% allows the exposure dose to be reduced to 5.6 mSv for patients with a heart rate lower than 65 bpm. This is a dose reduction of approximately 70% compared to the conventional scanning method recommended by the manufacturer when segmental reconstruction is considered. This low-dose protocol seamlessly allows for wide scan ranges (e.g., aortic dissection) with the benefits of ECG-gated helical scanning: smooth continuity for longitudinal direction and utilization of data from all cardiac cycles.

  3. Health benefits from low-dose irradiation

    SciTech Connect

    Luckey, T.D.

    1996-12-31

    Whole-body exposures of mice and humans show no harm from low doses of ionizing radiation. Forty reports show statistically significant, p < 0.01, beneficial effects when cancer and total mortality rates were examined in mice. In vitro experiments indicate that radiogenic metabolism, adaptive repair mechanisms, such as DNA repair enzymes, and the essential nature of ionizing radiation are responsible for part of this activity. However, overwhelming evidence shows that low-dose irradiation increases immune competence. Such data negate the linear concept, which has no reliable whole-animal data to support it in the low-dose range. Cell culture data are not pertinent; such cells do not have a complete immune system.

  4. Prospectively ECG gated CT pulmonary angiography versus helical ungated CT pulmonary angiography: impact on cardiac related motion artifacts and patient radiation dose.

    PubMed

    Shuman, William P; Leipsic, Jonathon A; Busey, Janet M; Green, Douglas E; Pipavath, Sudhakar N; Hague, Cameron J; Koprowicz, Kent M

    2012-09-01

    To compare prospectively ECG gated CT pulmonary angiography (CTPA) with routine helical ungated CTPA for cardiac related motion artifacts and patient radiation dose. Twenty patients with signs and symptoms suspicious for pulmonary embolism and who had a heart rate below 85 were scanned with prospectively ECG gated CTPA. These gated exams were matched for several clinical parameters to exams from twenty similar clinical patients scanned with routine ungated helical CTPA. Three blinded independent reviewers subjectively evaluated all exams for overall pulmonary artery enhancement and for several cardiac motion related artifacts, including vessel blurring, intravascular shading, and double line. Reviewers also measured pulmonary artery intravascular density and image noise. Patient radiation dose for each technique was compared. Fourteen clinical prospectively ECG gated CTPA exams from a second institution were evaluated for the same parameters. Prospectively ECG gated CTPA resulted in significantly decreased motion-related image artifact scores in lung segments adjacent to the heart compared to ungated CTPA. Measured image noise was not significantly different between the two types of CTPA exams. Effective dose was 28% less for prospectively ECG gated CTPA (4.9 mSv versus 6.8 mSv, p=0.02). Similar results were found in the prospectively ECG gated exams from the second institution. Compared to routine helical ungated CTPA, prospectively ECG gated CTPA may result in less cardiac related motion artifact in lung segments adjacent to the heart and significantly less patient radiation dose. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Mammography-oncogenecity at low doses.

    PubMed

    Heyes, G J; Mill, A J; Charles, M W

    2009-06-01

    Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 +/- 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 +/- 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low

  6. Low dose naltrexone therapy in multiple sclerosis.

    PubMed

    Agrawal, Y P

    2005-01-01

    The use of low doses of naltrexone for the treatment of multiple sclerosis (MS) enjoys a worldwide following amongst MS patients. There is overwhelming anecdotal evidence, that in low doses naltrexone not only prevents relapses in MS but also reduces the progression of the disease. It is proposed that naltrexone acts by reducing apoptosis of oligodendrocytes. It does this by reducing inducible nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevent the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and oligodendrocytes via activation of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid class of glutamate receptor is prevented. It is crucial that the medical community respond to patient needs and investigate this drug in a clinical trial.

  7. Epigenomic Adaptation to Low Dose Radiation

    SciTech Connect

    Gould, Michael N.

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  8. Genomic Instability Induced by Low Dose Irradiation

    SciTech Connect

    Evans, Helen H. Sedwick, David W. Veigl, Martina L.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  9. Adaption By Low Dose Radiation Exposure

    PubMed Central

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to “as low as reasonably achievable” (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations. PMID:26672725

  10. Prospective ECG triggering reduces prosthetic heart valve-induced artefacts compared with retrospective ECG gating on 256-slice CT.

    PubMed

    Symersky, Petr; Habets, Jesse; Westers, Paul; de Mol, Bas A J M; Prokop, Mathias; Budde, Ricardo P J

    2012-06-01

    Multidetector computed tomography (MDCT) has diagnostic value for the evaluation of prosthetic heart valve (PHV) dysfunction but it is hampered by artefacts. We hypothesised that image acquisition using prospective triggering instead of retrospective gating would reduce artefacts related to pulsating PHV. In a pulsatile in vitro model, a mono- and bileaflet PHV were imaged using 256 MDCT at 60, 75 and 90 beats per minute (BPM) with either retrospective gating (120 kV, 600 mAs, pitch 0.2, CTDI(vol) 39.8 mGy) or prospective triggering (120 kV, 200 mAs, CTDI(vol) 13.3 mGy). Two thresholds (>175 and <-45HU), derived from the density of surrounding structures, were used for quantification of hyper- and hypodense artefacts. Image noise and artefacts were compared between protocols. Prospective triggering reduced hyperdense artefacts for both valves at every BPM (P = 0.001 all comparisons). Hypodense artefacts were reduced for the monoleaflet valve at 60 (P = 0.009), 75 (P = 0.016) and 90 BPM (P = 0.001), and for the bileaflet valves at 60 (P = 0.001), 90 (P = 0.001) but not at 75 BPM (P = 0.6). Prospective triggering reduced image noise at 60 (P = 0.001) and 75 (P < 0.03) but not at 90 BPM. Compared with retrospective gating, prospective triggering reduced most artefacts related to pulsating PHV in vitro. • Computed tomographic images are often degraded by prosthetic heart valve-induced artefacts • Prospective triggering reduces prosthetic heart valve-induced artefacts in vitro • Artefact reduction at 90 beats per minute occurs without image noise reduction • Prospective triggering may improve CT image quality of moving hyperdense structures.

  11. Low-dose 4D myocardial perfusion with x-ray micro-CT

    NASA Astrophysics Data System (ADS)

    Clark, D. P.; Badea, C. T.

    2017-03-01

    X-ray CT is widely used, both clinically and pre-clinically, for fast, high-resolution, anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, temporally-resolved CT data can detail cardiac motion and blood flow dynamics for one-stop cardiovascular CT imaging procedures. In previous work, we demonstrated efficient, low-dose projection acquisition and reconstruction strategies for cardiac micro-CT imaging and for multiple-injection micro-CT perfusion imaging. Here, we extend this previous work with regularization based on rank-sparse kernel regression and on filtration with the Karhunen-Loeve transform. Using a dual source, prospectively gated sampling strategy which produces an approximately uniform distribution of projections, we apply this revised algorithm to the assessment of both myocardial perfusion and cardiac functional metrics from the same set of projection data. We test the algorithm in simulations using a modified version of the MOBY mouse phantom which contains realistic perfusion and cardiac dynamics. The proposed algorithm reduces the reconstruction error by 81% relative to unregularized, algebraic reconstruction. The results confirm our ability to simultaneously solve for cardiac temporal motion and perfusion dynamics. In future work, we will apply the algorithm and sampling protocol to small animal cardiac studies.

  12. Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support—Results of a Prospective, Randomized, Comparative Study

    PubMed Central

    Pirard, Céline; Loumaye, Ernest; Wyns, Christine

    2015-01-01

    Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols. PMID:25945092

  13. Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures.

    PubMed

    Honar, H; Riazi, K; Homayoun, H; Sadeghipour, H; Rashidi, N; Ebrahimkhani, M R; Mirazi, N; Dehpour, A R

    2004-01-01

    Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach in seizure disorders and to examine the differential mechanisms involved in opioid anti- (morphine at 0.5-3 mg/kg) versus pro-convulsant (20-100 mg/kg) effects. Systemic administration of ultra-low doses of naltrexone (100 fg/kg-10 ng/kg) significantly potentiated the anticonvulsant effect of morphine at 0.5 mg/kg while higher degrees of opioid receptor antagonism blocked this effect. Moreover, inhibition of opioid-induced excitatory signaling by naltrexone (1 ng/kg) unmasked a strong anticonvulsant effect for very low doses of morphine (1 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of opioid receptor signaling can exert strong seizure-protective effects even at very low levels of opioid receptor activation. However, ultra-low dose naltrexone could not increase the maximal anticonvulsant effect of morphine (1-3 mg/kg), possibly due to a ceiling effect. The proconvulsant effects of morphine on seizure threshold were minimally altered by ultra-low doses of naltrexone while being completely blocked by a higher dose (1 mg/kg) of the antagonist. The present data suggest that ultra-low doses of opioid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of opioids.

  14. [Low dose naltrexone for treatment of pain].

    PubMed

    Plesner, Karin Bruun; Vægter, Henrik Bjarke; Handberg, Gitte

    2015-10-09

    Recent years have seen an increasing interest in the use of low dose naltrexone (LDN) for off-label treatment of pain in diseases as fibromyalgia, multiple sclerosis and morbus Crohn. The evidence is poor, with only few randomized double-blind placebo-controlled studies. The studies currently available are reviewed in this paper. LDN could be a potentially useful drug in the future for the treatment of pain in fibromyalgia, but more studies are needed to verify that it is superior to placebo, and currently it cannot be recommended as first-line therapy.

  15. Efficacy of two low-dose oral tylosin regimens in controlling the relapse of diarrhea in dogs with tylosin-responsive diarrhea: a prospective, single-blinded, two-arm parallel, clinical field trial

    PubMed Central

    2014-01-01

    Background Despite its wide acceptance as a treatment for canine chronic enteropathies, the macrolide antibiotic tylosin lacks official oral dosage recommendations. Not even textbooks share consensus about the dose; daily recommendations vary from 25 to 80 mg/kg and dosing intervals from one to three times daily. The objective of this prospective, single-blinded, two-arm parallel, clinical field trial was to determine whether doses of 5 mg/kg or 15 mg/kg tylosin administered orally once daily for seven days would have a similar effect on fecal consistency in diarrhea relapses to that of a 25 mg/kg dose of tylosin administered once daily for seven days, a dosage that has proved effective in controlling canine tylosin-responsive diarrhea (TRD). A further objective was to compare the efficacy of the 5 mg/kg and 15 mg/kg tylosin dosages. Fifteen client-owned dogs diagnosed with TRD that had responded to a dose of 25 mg/kg tylosin once daily for seven days were enrolled in the study. After a relapse of diarrhea the dogs were allocated into two groups receiving tylosin orally in doses of either 5 mg/kg or 15 mg/kg once daily for seven days. The owners were blinded to the dosage. The elimination of diarrhea was the main criterion in assessing treatment success. The mean fecal consistency score of the last three treatment days for all dosages, including 25 mg/kg, as evaluated by the owners according to a standardized fecal scoring system, served as the primary outcome measures. Results All eight dogs responded to the 5 mg/kg dose, and six of seven dogs responded to the 15 mg/kg dose. The mean fecal consistency scores at the 25 mg/kg tylosin dosage were no significantly different from scores at the 5 mg/kg or 15 mg/kg tylosin dosages (P = 0.672, P = 0.345). Conclusions Interestingly, 14/15 (93%) of the dogs responding to a dose of 25 mg/kg tylosin once daily for seven days also responded to the lower dosages at diarrhea relapse. The data indicate

  16. Low-dose radiation exposure and carcinogenesis.

    PubMed

    Suzuki, Keiji; Yamashita, Shunichi

    2012-07-01

    Absorption of energy from ionizing radiation by the genetic material in the cell leads to damage to DNA, which in turn leads to cell death, chromosome aberrations and gene mutations. While early or deterministic effects result from organ and tissue damage caused by cell killing, latter two are considered to be involved in the initial events that lead to the development of cancer. Epidemiological studies have demonstrated the dose-response relationships for cancer induction and quantitative evaluations of cancer risk following exposure to moderate to high doses of low-linear energy transfer radiation. A linear, no-threshold model has been applied to assessment of the risks resulting from exposure to moderate and high doses of ionizing radiation; however, a statistically significant increase has hardly been described for radiation doses below 100 mSv. This review summarizes our current knowledge of the physical and biological features of low-dose radiation and discusses the possibilities of induction of cancer by low-dose radiation.

  17. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    PubMed

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully.

  18. Culmination of Low-Dose Pesticide Effects

    PubMed Central

    2013-01-01

    Pesticides applied in agriculture can affect the structure and function of nontarget populations at lower doses and for longer timespans than predicted by the current risk assessment frameworks. We identified a mechanism for this observation. The populations of an aquatic invertebrate (Culex pipiens) exposed over several generations to repeated pulses of low concentrations of the neonicotinoid insecticide (thiacloprid) continuously declined and did not recover in the presence of a less sensitive competing species (Daphnia magna). By contrast, in the absence of a competitor, insecticide effects on the more sensitive species were only observed at concentrations 1 order of magnitude higher, and the species recovered more rapidly after a contamination event. The underlying processes are experimentally identified and reconstructed using a simulation model. We conclude that repeated toxicant pulse of populations that are challenged with interspecific competition may result in a multigenerational culmination of low-dose effects. PMID:23859631

  19. Effects of low doses of radiation.

    PubMed

    Fry, R J

    1996-06-01

    This is a brief review of what is known from experimental studies about the effects of low doses of radiation, and approaches that might improve risk estimates are discussed. The dose-response relationships for cancer induction by radiation vary markedly between tissues. The evidence suggests that 1) the induction of the initial events is dependent on the cell type because the size and/or the number of targets and how the cells handle the initial lesions differs between cell types; and 2) there are marked differences among tissues how initial lesions are expressed and proceed to overt cancer. The recent findings about adaptive responses are discussed in the context of what they contribute to our understanding about the response to irradiation. Lastly, the possibility of extending the approach of determining "The probability of causation," which Vic Bond played such an important role in establishing, is raised.

  20. Low dose neutron late effects: Cataractogenesis

    SciTech Connect

    Worgul, B.V.

    1991-12-01

    The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.

  1. Low Dose Ionizing Radiation Modulates Immune Function

    SciTech Connect

    Nelson, Gregory A.

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  2. Low-Dose Radiotherapy in Indolent Lymphoma

    SciTech Connect

    Rossier, Christine; Schick, Ulrike; Miralbell, Raymond; Mirimanoff, Rene O.; Weber, Damien C.; Ozsahin, Mahmut

    2011-11-01

    Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

  3. Low dose propranolol decreases orthodontic movement.

    PubMed

    de Oliveira, Erika Lira; Freitas, Fabiana Furtado; de Macedo, Cristina Gomes; Clemente-Napimoga, Juliana Trindade; Silva, Milena Bortolotto Felippe; Manhães-Jr, Luiz Roberto Coutinho; Junqueira, José Luiz Cintra; Napimoga, Marcelo Henrique

    2014-10-01

    Low dose propranolol has previously been demonstrated to suppress bone remodelling. Therefore, its effect on orthodontic movement was tested. Rats were assigned as follows (n=5): animals with no orthodontic appliance (G1); the remaining groups were fitted with a Ni-Ti closed-coil spring ligated to the upper left first molar and connected to the incisors using metal and resin and received vehicle only (G2), 0.1mg/kg (G3) or 20mg/kg (G4) of propranolol orally. Cone Beam Computed Tomography was performed using high resolution for image capture. The distance between the first and second upper molars, both with and without the orthodontic appliance, was measured in millimetres. Gingival tissue was harvested and assessed for IL-1β and IL-6 using ELISA and for ICAM-1 and RANKL by Western blotting. The orthodontic appliance induced a significant tooth movement in G2 when compared to the animals without an orthodontic appliance (G1) (p<0.05). The animals from G3 showed a significantly reduction in tooth movement (p<0.05) when compared with rats from G2. Animals treated with 20mg/kg of propranolol (G4) showed tooth movement similar to that of G2. The reduced tooth movement observed in the animals treated with 0.1mg/kg of propranolol (G3) occurred due to decreased amounts of IL-1β and IL-6, in addition to lower ICAM-1 and RANKL expression. Low dose propranolol inhibits bone remodelling and orthodontic movement. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al; Buchner, Stephen; LaBel, Kenneth

    2011-01-01

    We have presented results of ultra-low dose rate irradiations (< or = 10 mrad(Si)/s) for a variety of radiation hardened and commercial linear bipolar devices. We observed low dose rate enhancement factors exceeding 1.5 in several parts. The worst case of dose rate enhancement resulted in functional failures, which occurred after 10 and 60 krad(Si), for devices irradiated at 0.5 and 10 mrad(Si)/s, respectively. Devices fabricated with radiation hardened processes and designs also displayed dose rate enhancement at below 10 mrad(Si)/s. Furthermore, the data indicated that these devices have not reached the damage saturation point. Therefore the degradation will likely continue to increase with increasing total dose, and the low dose rate enhancement will further magnify. The cases presented here, in addition to previous examples, illustrate the significance and pervasiveness of low dose rate enhancement at dose rates lower than 10 mrad(Si). These results present further challenges for radiation hardness assurance of bipolar linear circuits, and raise the question of whether the current standard test dose rate is conservative enough to bound degradations due to ELDRS.

  5. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    SciTech Connect

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  6. Prospectively versus retrospectively ECG-gated 256-slice coronary CT angiography: image quality and radiation dose over expanded heart rates.

    PubMed

    Hou, Yang; Yue, Yong; Guo, Wenli; Feng, Guoqiang; Yu, Tao; Li, Guangwei; Vembar, Mani; Olszewski, Mark E; Guo, Qiyong

    2012-01-01

    To compare image quality and radiation dose estimates for coronary computed tomography angiography (CCTA) obtained with a prospectively gated transaxial (PGT) CT technique and a retrospectively gated helical (RGH) CT technique using a 256-slice multidetector CT (MDCT) scanner and establish an upper limit of heart rate to achieve reliable diagnostic image quality using PGT. 200 patients (135 males, 65 females) with suspected coronary artery disease (CAD) underwent CCTA on a 256-slice MDCT scanner. The PGT patients were enrolled prospectively from January to June, 2009. For each PGT patient, we found the paired ones in retrospective-gating patients database and randomly selected one patient in these match cases and built up the RGH group. Image quality for all coronary segments was assessed and compared between the two groups using a 4-point scale (1: non-diagnostic; 4: excellent). Effective radiation doses were also compared. The average heart rate ± standard deviation (HR ± SD) between the two groups was not significantly different (PGT: 64.6 ± 12.9 bpm, range 45-97 bpm; RGH: 66.7 ± 10.9 bpm, range 48-97 bpm, P = 0.22). A receiver-operating characteristic (ROC) analysis determined a cutoff HR of 75 bpm up to which diagnostic image quality could be achieved using the PGT technique (P < 0.001). There were no significant differences in assessable coronary segments between the two groups for HR ≤ 75 bpm (PGT: 99.9% [961 of 962 segments]; RGH: 99.8% [1038 of 1040 segments]; P = 1.0). At HR > 75 bpm, the performance of the PGT technique was affected, resulting in a moderate reduction of percentage assessable coronary segments using this approach (PGT: 95.5% [323 of 338 segments]; RGH: 98.5% [261 of 265 segments]; P = 0.04). The mean estimated effective radiation dose for the PGT group was 3.0 ± 0.7 mSv, representing reduction of 73% compared to that of the RGH group (11.1 ± 1.6 mSv) (P < 0.001). Prospectively-gated axial coronary computed tomography using a 256

  7. Contraception. Low-dose pill launched.

    PubMed

    1993-01-01

    At a vibrant ceremony in Kampala, Uganda, the Minister of Women in Development, Youth and Culture launched the new low-dose oral contraceptive Pilplan which provides women more options for birth spacing. Diplomats, physicians, government officials, and business leaders attended the ceremony at the Sheraton Hotel Kampala. A dance group did an interpretation of "Women in Uganda: Gaining Momentum." The Minister considered the introduction of this new pill as a turning point for reproductive rights. A baseline survey among Ugandan women has shown that although almost all women were familiar with the pill, only 36% have ever used it and only 15% were currently using it. 80% thought that pill use was preferable to having an unplanned pregnancy. These findings convinced the Minister that ignorance and misconception keep women from using the pill. The government, health providers, and others need to educate women about Pilplan and how to use it correctly. A bilateral agreement between the Ministry of Health and USAID set in motion a social marketing project which has now launched two contraceptive methods: Pilplan in 1993 and the Protector condom in 1990. USAID vowed to continue to support Pilplan, particularly if men could also help in supporting birth spacing. A Uganda-based pharmaceutical firm will distribute Pilplan in Uganda through pharmacies, clinics, and health facilities. Pilplan targets all middle- to low-income women.

  8. STATIC VS PROSPECTIVE GATED, NON-BREATH HOLD VOLUMETRIC MDCT IMAGING OF THE LUNGS

    PubMed Central

    Saba, Osama I.; Chon, Deokiee; Beck, Kenneth; McLennan, Geoffrey; Sieren, Jered; Reinhardt, Joseph; Hoffman, Eric A.

    2005-01-01

    Rationale and Objectives: We seek to establish lung imaging methods which provide for the ability to image the lung under dynamic, non-breath hold conditions while providing “virtual breath hold,” quantifiable volumetric image data sets. We use static, breath hold images as the gold standard for evaluating these virtual breath hold images in both a phantom and sheep. Materials and Methods: We have developed axial methods for gating image acquisition to multiple points in the respiratory cycle interleaved with incremental table stepping during multidetector-row CT (MDCT) scanning. Datasets are generated over multiple breaths, providing volume images representative of multiple points within a respiratory cycle. To determine the reproducibility and accuracy of the methods , 6 anesthetized sheep were studied by MDCT in non-gated and airway-pressure (Pawy)-gated modes where Pawy was 0, 7 and 15 cmH2O. Results: No significant differences were found between the coefficient of variation in air volume measured from repeated static scans (1.74±1.78%), gated scans: Inspiratory gated (1.2±0.44%) or expiratory-gated (1.39±0.98%), or between static (1.74±1.78%) and gated (1.39+/-0.98%) scanning at similar Pawy (p>0.1). Measured air volumes were larger from static vs. gated scans by 5.85±3.77% at 7cmH2O and 4.45±3.6% at 15cmHL2O Pawy (p<0.05) consistent with hysteresis. Differences between air volumes at 7 and 15 cmH2O measured from either static or gated scans or that delivered by a supersyringe were insignificant (p<0.05). Visual accuracy of 3D anatomic geometry was achieved, and landmark certainty was within 1mm across respiratory cycles. Conclusion: A method has been demonstrated which provides for accurate gating to respiratory signals during axial scanning. High resolution volumetric image datasets are achievable while the scanned subject is breathing.Images are quantitatively similar to breath hold images with differences likely explained by known P-V hysteresis

  9. Whole-Chest 64-MDCT of Emergency Department Patients with Nonspecific Chest Pain: Radiation Dose and Coronary Artery Image Quality with Prospective ECG Triggering Versus Retrospective ECG Gating

    PubMed Central

    Shuman, William P.; Branch, Kelley R.; May, Janet M.; Mitsumori, Lee M.; Strote, Jared N.; Warren, Bill H.; Dubinsky, Theodore J.; Lockhart, David W.; Caldwell, James H.

    2012-01-01

    Objective The purpose of this study was to compare the patient radiation dose and coronary artery image quality of long-z-axis whole-chest 64-MDCT performed with retrospective ECG gating with those of CT performed with prospective ECG triggering in the evaluation of emergency department patients with nonspecific chest pain. Subjects and Methods Consecutively registered emergency department patients with nonspecific low-to-moderate-risk chest pain underwent whole-chest CT with retrospective gating (n = 41) or prospective triggering (n = 31). Effective patient radiation doses were estimated and compared by use of unpaired Student's t tests. Two reviewers independently scored the quality of images of the coronary arteries, and the scores were compared by use of ordinal logistic regression. Results Age, heart rate, body mass index, and z-axis coverage were not statistically different between the two groups. For retrospective gating, the mean effective radiation dose was 31.8 ± 5.1 mSv; for prospective triggering, the mean effective radiation dose was 9.2 ± 2.2 mSv (prospective triggering 71% lower, p < 0.001). Two of 512 segments imaged with retrospective gating were nonevaluable (0.4%), and two of 394 segments imaged with prospective triggering were nonevaluable (0.5%). Prospectively triggered images were 2.2 (95% CI, 1.1–4.5) times as likely as retrospectively gated images to receive a high image quality score for each segment after adjustment for segment differences (p < 0.05). Conclusion For long-z-axis whole-chest 64-MDCT of emergency department patients with nonspecific chest pain, use of prospective ECG triggering may result in substantially lower patient radiation doses and better coronary artery image quality than is achieved with retrospective ECG gating. PMID:19457832

  10. Whole-chest 64-MDCT of emergency department patients with nonspecific chest pain: Radiation dose and coronary artery image quality with prospective ECG triggering versus retrospective ECG gating.

    PubMed

    Shuman, William P; Branch, Kelley R; May, Janet M; Mitsumori, Lee M; Strote, Jared N; Warren, Bill H; Dubinsky, Theodore J; Lockhart, David W; Caldwell, James H

    2009-06-01

    The purpose of this study was to compare the patient radiation dose and coronary artery image quality of long-z-axis whole-chest 64-MDCT performed with retrospective ECG gating with those of CT performed with prospective ECG triggering in the evaluation of emergency department patients with nonspecific chest pain. Consecutively registered emergency department patients with nonspecific low-to-moderate-risk chest pain underwent whole-chest CT with retrospective gating (n = 41) or prospective triggering (n = 31). Effective patient radiation doses were estimated and compared by use of unpaired Student's t tests. Two reviewers independently scored the quality of images of the coronary arteries, and the scores were compared by use of ordinal logistic regression. Age, heart rate, body mass index, and z-axis coverage were not statistically different between the two groups. For retrospective gating, the mean effective radiation dose was 31.8 +/- 5.1 mSv; for prospective triggering, the mean effective radiation dose was 9.2 +/- 2.2 mSv (prospective triggering 71% lower, p < 0.001). Two of 512 segments imaged with retrospective gating were nonevaluable (0.4%), and two of 394 segments imaged with prospective triggering were nonevaluable (0.5%). Prospectively triggered images were 2.2 (95% CI, 1.1-4.5) times as likely as retrospectively gated images to receive a high image quality score for each segment after adjustment for segment differences (p < 0.05). For long-z-axis whole-chest 64-MDCT of emergency department patients with nonspecific chest pain, use of prospective ECG triggering may result in substantially lower patient radiation doses and better coronary artery image quality than is achieved with retrospective ECG gating.

  11. Patient radiation dose in prospectively gated axial CT coronary angiography and retrospectively gated helical technique with a 320-detector row CT scanner

    SciTech Connect

    Seguchi, Shigenobu; Aoyama, Takahiko; Koyama, Shuji; Fujii, Keisuke; Yamauchi-Kawaura, Chiyo

    2010-11-15

    Purpose: The aim of this study was to evaluate radiation dose to patients undergoing computed tomography coronary angiography (CTCA) for prospectively gated axial (PGA) technique and retrospectively gated helical (RGH) technique. Methods: Radiation doses were measured for a 320-detector row CT scanner (Toshiba Aquilion ONE) using small sized silicon-photodiode dosimeters, which were implanted at various tissue and organ positions within an anthropomorphic phantom for a standard Japanese adult male. Output signals from photodiode dosimeters were read out on a personal computer, from which organ and effective doses were computed according to guidelines published in the International Commission on Radiological Protection Publication 103. Results: Organs that received high doses were breast, followed by lung, esophagus, and liver. Breast doses obtained with PGA technique and a phase window width of 16% at a simulated heart rate of 60 beats per minute were 13 mGy compared to 53 mGy with RGH technique using electrocardiographically dependent dose modulation at the same phase window width as that in PGA technique. Effective doses obtained in this case were 4.7 and 20 mSv for the PGA and RGH techniques, respectively. Conversion factors of dose length product to the effective dose in PGA and RGH were 0.022 and 0.025 mSv mGy{sup -1} cm{sup -1} with a scan length of 140 mm. Conclusions: CTCA performed with PGA technique provided a substantial effective dose reduction, i.e., 70%-76%, compared to RGH technique using the dose modulation at the same phase windows as those in PGA technique. Though radiation doses in CTCA with RGH technique were the same level as, or some higher than, those in conventional coronary angiography (CCA), the use of PGA technique reduced organ and effective doses to levels less than CCA except for breast dose.

  12. Estimation of radiation exposure of retrospective gated and prospective triggered 128-slice triple-rule-out CT angiography.

    PubMed

    Ketelsen, Dominik; Fenchel, Michael; Thomas, Christoph; Buchgeister, Markus; Boehringer, Nadine; Tsiflikas, Ilias; Kaempf, Michael; Claussen, Claus D; Heuschmid, Martin

    2011-09-01

    CT has become an important role in the differential diagnosis of acute chest pain to exclude an aortic dissection, pulmonary embolism and acute coronary artery syndrome. However, the additional radiation exposure is a cause of concern and dose saving strategies should be applied, if possible. To estimate effective dose of retrospective gated and prospective ECG-triggered triple-rule-out computed tomography angiography (TRO-CTA). An Alderson-Rando-phantom equipped with thermoluminescent dosimeters was used for dose measurements. Exposure was performed on a 128-slice single source scanner. The following scan parameters were used (retrospective ECG-gated): 120 kV, 190 mAs/rot., collimation 128x0.6 mm, rotation time 0.3 s. Protocols with a simulated heart rate (HR) of 60 and 100 bpm were performed using the standard ECG-pulsing as well as MinDose. Additionally, a prospective triggered TRO-CTA was acquired (HR 60 bpm). The estimated effective dose of retrospective ECG-gated TRO-CTA ranged from 7.4-13.4 mSv and from 10.1-17.5 mSv for men and women, respectively. Due to radiosensitive breast tissue, women received a significant increased effective dose of up to 64.7% ± 0.03% (p = 0.028) compared to men. MinDose reduces radiation exposure of up to 33.0% ± 6.5% in comparison to standard ECG-pulsing (p < 0.001). The effective dose increased significantly with lower heart rates (p < 0.001). Prospective ECG-triggered TRO-CTA showed an effective dose of 5.9 mSv and 8.2 mSv for men and women, respectively. Compared to retrospective ECG-gated TRO-CTA a significant dose reduction was observed (p < 0.001). Due to the significant different dose exposure, scan protocols should be specifically adapted in a patient- and problem-oriented manner.

  13. Application of low dose radiation and low concentration contrast media in enhanced CT scans in children with congenital heart disease.

    PubMed

    Liu, Zhimin; Song, Lei; Yu, Tong; Gao, Jun; Zhang, Qifeng; Jiang, Ling; Liu, Yong; Peng, Yun

    2016-09-01

    The aim of this study was to explore the feasibility of using low dose radiation and low concentration contrast media in enhanced CT examinations in children with congenital heart disease. Ninety patients with congenital heart disease were randomly divided into three groups of 30 patients each who underwent contrast-enhanced cardiac scans on a Discovery CT750 HD scanner. Group A received 270 mg I/mL iodixanol, and group B received 320 mg I/mL iodixanol contrast media and was scanned with prospective ECG triggering mode. Group C received 320 mg I/mL iodixanol and was scanned with conventional retrospective ECG gating mode. The same weight-based contrast injection protocol was used for all three groups. Images were reconstructed using a 30% adaptive statistical iterative reconstruction (ASIR) algorithm and a 50% ASIR in groups A and B and a 30% ASIR in group C. The subjective and objective image quality evaluations, diagnostic accuracies, radiation doses and amounts of contrast media in the three groups were measured and compared. All images in the three groups met the diagnostic requirements, with the same diagnostic accuracy and image quality scores greater than 3 in a 4-point scoring system. However, ventricular enhancement and the objective noise, signal-to-noise ratio, contrast-to-noise ratio and subjective image quality scores in group C were better than those in groups A and B (all P<.001). The effective radiation dose in groups A and B was 84% lower than that in group C (P<.001); group A received the lowest contrast dose (14% lower than that of groups B and C). Enhanced CT scan images with low dose radiation and low concentration contrast media can meet the diagnostic requirements for examining children with congenital heart disease while reducing the potential risk of radiation damage and contrast-induced nephropathy. © 2016 John Wiley & Sons Ltd.

  14. The tolerability and efficacy of low-dose simvastatin in statin-intolerant patients.

    PubMed

    Degreef, L E; Opdam, F L; Teepe-Twiss, I M; Jukema, J W; Guchelaar, H J; Tamsma, J T

    2010-08-01

    Statin intolerance is increasingly recognized as a therapy limiting factor in the primary and secondary prevention of cardiovascular disease. Since vulnerability to dose related adverse events differ between subjects treated with statins we hypothesized low-dose simvastatin would be tolerated and effective in statin-intolerant patients. A single center open label prospective observational study was performed assessing tolerability and efficacy of low-dose simvastatin treatment in 35 statin-intolerant patients. Statin intolerance was defined as not being able to tolerate a registered dose statin due to myalgia-myopathy, myositis, or elevation of serum liver enzyme levels. These statin-intolerant patients were treated with simvastatin with an initial dose of 2.5mg every other day. The dose was titrated upwards if possible. Tolerability was defined as remaining on treatment. Efficacy was defined as change of LDL-cholesterol compared to baseline. The reached simvastatin dose ranged from 0.825 to 8.75mg/day with a mean dose of 4mg/day. Fifty-seven percent of the patients tolerated low-dose therapy and remained on treatment. Of these patients, 30% noted recurrent myalgia. Low-dose simvastatin significantly decreased mean(SD) LDL-cholesterol levels with 25.9(12.1)% (p<0.001). Eleven percent of the patients reached LDL-cholesterol target levels (<2.6mmol/l) in an intention to treat analysis and in 20% of patients that tolerated low-dose simvastatin. Low-dose simvastatin therapy is tolerated in a considerable proportion of statin-intolerant patients with significant lipid lowering efficacy. Low-dose statin therapy can be considered in multidrug regimens in statin-intolerant patients.

  15. Low-dose effects of hormones and endocrine disruptors.

    PubMed

    Vandenberg, Laura N

    2014-01-01

    Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately. © 2014 Elsevier Inc. All rights reserved.

  16. Low-dose-rate, low-dose irradiation delays neurodegeneration in a model of retinitis pigmentosa.

    PubMed

    Otani, Atsushi; Kojima, Hiroshi; Guo, Congrong; Oishi, Akio; Yoshimura, Nagahisa

    2012-01-01

    The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (LD) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a condition using 650 mGy irradiation and a 26 mGy/minute dose rate. Multiple rounds of irradiation strengthened this neuroprotective effect. A characteristic up-regulation (563%) of antioxidative gene peroxiredoxin-2 (Prdx2) in the LDR-LD-irradiated retina was observed compared to the sham-treated control retina. Silencing the Prdx2 using small-interfering RNA administration reduced the LDR-LD rescue effect on the photoreceptors. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved.

  17. [Indications for low-dose CT in the emergency setting].

    PubMed

    Poletti, Pierre-Alexandre; Andereggen, Elisabeth; Rutschmann, Olivier; de Perrot, Thomas; Caviezel, Alessandro; Platon, Alexandra

    2009-08-19

    CT delivers a large dose of radiation, especially in abdominal imaging. Recently, a low-dose abdominal CT protocol (low-dose CT) has been set-up in our institution. "Low-dose CT" is almost equivalent to a single standard abdominal radiograph in term of dose of radiation (about one sixth of those delivered by a standard CT). "Low-dose CT" is now used routinely in our emergency service in two main indications: patients with a suspicion of renal colic and those with right lower quadrant pain. It is obtained without intravenous contrast media. Oral contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is used in the frame of well defined clinical algorithms, and does only replace standard CT when it can reach a comparable diagnostic quality.

  18. Low-dose or low-dose-rate ionizing radiation–induced bioeffects in animal models

    PubMed Central

    Loke, Weng Keong; Khoo, Boo Cheong

    2017-01-01

    Abstract Animal experimental studies indicate that acute or chronic low-dose ionizing radiation (LDIR) (≤100 mSv) or low-dose-rate ionizing radiation (LDRIR) (<6 mSv/h) exposures may be harmful. It induces genetic and epigenetic changes and is associated with a range of physiological disturbances that includes altered immune system, abnormal brain development with resultant cognitive impairment, cataractogenesis, abnormal embryonic development, circulatory diseases, weight gain, premature menopause in female animals, tumorigenesis and shortened lifespan. Paternal or prenatal LDIR/LDRIR exposure is associated with reduced fertility and number of live fetuses, and transgenerational genomic aberrations. On the other hand, in some experimental studies, LDIR/LDRIR exposure has also been reported to bring about beneficial effects such as reduction in tumorigenesis, prolonged lifespan and enhanced fertility. The differences in reported effects of LDIR/LDRIR exposure are dependent on animal genetic background (susceptibility), age (prenatal or postnatal days), sex, nature of radiation exposure (i.e. acute, fractionated or chronic radiation exposure), type of radiation, combination of radiation with other toxic agents (such as smoking, pesticides or other chemical toxins) or animal experimental designs. In this review paper, we aimed to update radiation researchers and radiologists on the current progress achieved in understanding the LDIR/LDRIR-induced bionegative and biopositive effects reported in the various animal models. The roles played by a variety of molecules that are implicated in LDIR/LDRIR-induced health effects will be elaborated. The review will help in future investigations of LDIR/LDRIR-induced health effects by providing clues for designing improved animal research models in order to clarify the current controversial/contradictory findings from existing studies. PMID:28077626

  19. Low-dose or low-dose-rate ionizing radiation-induced bioeffects in animal models.

    PubMed

    Tang, Feng Ru; Loke, Weng Keong; Khoo, Boo Cheong

    2017-03-01

    Animal experimental studies indicate that acute or chronic low-dose ionizing radiation (LDIR) (≤100 mSv) or low-dose-rate ionizing radiation (LDRIR) (<6 mSv/h) exposures may be harmful. It induces genetic and epigenetic changes and is associated with a range of physiological disturbances that includes altered immune system, abnormal brain development with resultant cognitive impairment, cataractogenesis, abnormal embryonic development, circulatory diseases, weight gain, premature menopause in female animals, tumorigenesis and shortened lifespan. Paternal or prenatal LDIR/LDRIR exposure is associated with reduced fertility and number of live fetuses, and transgenerational genomic aberrations. On the other hand, in some experimental studies, LDIR/LDRIR exposure has also been reported to bring about beneficial effects such as reduction in tumorigenesis, prolonged lifespan and enhanced fertility. The differences in reported effects of LDIR/LDRIR exposure are dependent on animal genetic background (susceptibility), age (prenatal or postnatal days), sex, nature of radiation exposure (i.e. acute, fractionated or chronic radiation exposure), type of radiation, combination of radiation with other toxic agents (such as smoking, pesticides or other chemical toxins) or animal experimental designs. In this review paper, we aimed to update radiation researchers and radiologists on the current progress achieved in understanding the LDIR/LDRIR-induced bionegative and biopositive effects reported in the various animal models. The roles played by a variety of molecules that are implicated in LDIR/LDRIR-induced health effects will be elaborated. The review will help in future investigations of LDIR/LDRIR-induced health effects by providing clues for designing improved animal research models in order to clarify the current controversial/contradictory findings from existing studies. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research

  20. Practical dosimetry methods for the determination of effective skin and breast dose for a modern CT system, incorporating partial irradiation and prospective cardiac gating.

    PubMed

    Loader, R J; Gosling, O; Roobottom, C; Morgan-Hughes, G; Rowles, N

    2012-03-01

    For CT coronary angiography (CTCA), a generic chest conversion factor returns a significant underestimate of effective dose. The aim of this manuscript is to communicate new dosimetry methods to calculate weighted CT dose index (CTDIw), effective dose, entrance surface dose (ESD) and organ dose to the breast for prospectively gated CTCA. CTDIw in 32 cm diameter Perspex phantom was measured using an adapted technique, accounting for the segmented scan characteristic. Gafchromic XRCT film (International Speciality Products, New Jersey, NJ) was used to measure the distribution and magnitude of ESD. Breast dose was measured using high sensitivity metal oxide semiconductor field-effect transistors and compared to the computer based imaging performance assessment of CT scanners (ImPACT) dosimetry calculations. For a typical cardiac scan the mean ESD remained broadly constant (7-9 mGy) when averaged over the circumference of the Perspex phantom. Typical absorbed dose to the breast with prospectively gated protocols was within the range 2-15 mGy. The subsequent lifetime attributable risk (LAR) of cancer incidence to the breast was found at 0.01-0.06 for a 20-year-old female. This compares favourably to 100 mGy (LAR ~0.43) for a retrospectively gated CTCA. Care must be taken when considering radiation dosimetry associated with prospectively gated scanning for CTCA and a method has been conveyed to account for this. Breast doses for prospectively gated CTCA are an order of magnitude lower than retrospectively gated scans. Optimisation of cardiac protocols is expected to show further dose reduction.

  1. Practical dosimetry methods for the determination of effective skin and breast dose for a modern CT system, incorporating partial irradiation and prospective cardiac gating

    PubMed Central

    Loader, R J; Gosling, O; Roobottom, C; Morgan-Hughes, G; Rowles, N

    2012-01-01

    Objective For CT coronary angiography (CTCA), a generic chest conversion factor returns a significant underestimate of effective dose. The aim of this manuscript is to communicate new dosimetry methods to calculate weighted CT dose index (CTDIw), effective dose, entrance surface dose (ESD) and organ dose to the breast for prospectively gated CTCA. Methods CTDIw in 32 cm diameter Perspex phantom was measured using an adapted technique, accounting for the segmented scan characteristic. Gafchromic XRCT film (International Speciality Products, New Jersey, NJ) was used to measure the distribution and magnitude of ESD. Breast dose was measured using high sensitivity metal oxide semiconductor field-effect transistors and compared to the computer based imaging performance assessment of CT scanners (ImPACT) dosimetry calculations. Results For a typical cardiac scan the mean ESD remained broadly constant (7–9 mGy) when averaged over the circumference of the Perspex phantom. Typical absorbed dose to the breast with prospectively gated protocols was within the range 2–15 mGy. The subsequent lifetime attributable risk (LAR) of cancer incidence to the breast was found at 0.01–0.06 for a 20-year-old female. This compares favourably to 100 mGy (LAR ∼0.43) for a retrospectively gated CTCA. Conclusions Care must be taken when considering radiation dosimetry associated with prospectively gated scanning for CTCA and a method has been conveyed to account for this. Breast doses for prospectively gated CTCA are an order of magnitude lower than retrospectively gated scans. Optimisation of cardiac protocols is expected to show further dose reduction. PMID:21896660

  2. Low-dose propranolol for infantile haemangioma.

    PubMed

    Tan, Swee T; Itinteang, Tinte; Leadbitter, Philip

    2011-03-01

    In 2008, propranolol was serendipitously observed to cause accelerated involution of infantile haemangioma. However, the mechanism by which it causes this dramatic effect is unknown, the dosage empirical and the optimal duration of treatment unexplored. This study determines the minimal dosage and duration of propranolol treatment to achieve accelerated involution of problematic infantile haemangioma. Consecutive patients with problematic proliferating infantile haemangioma treated with propranolol were culled from our prospective vascular anomalies database. The patients were initially managed as inpatients and commenced on propranolol at 0.25 mg kg(-1) twice daily, and closely monitored. The dosage was increased to 0.5 mg kg(-1) twice daily after 24 h, if there was no cardiovascular or metabolic side effect. The dosage was increased further by 0.5 mg kg(-1) day(-1) until a visible effect was noticed or up to a maximum of 2 mg kg(-1) day(-1), and was maintained until the lesion had fully involuted or the child was 12-months old. A total of 15 patients aged 3 weeks to 8.5 months (mean, 11 weeks) underwent propranolol treatment for problematic proliferating infantile haemangioma, which threatened life (n=1) or vision (n=2) or nasal obstruction (n=3) and/or caused ulceration (n=6) and/or bleeding (n=2) and/or significant tissue distortion (n=12). The minimal dosage required to achieve accelerated involution was 1.5-2.0 mg kg(-1) day(-1). Rebound growth occurred in the first patient when the dose was withdrawn at 7.5 months of age requiring reinstitution of treatment. No rebound growth was observed in the remaining patients. No other complications were observed. Propranolol at 1.5-2.0 mg kg(-1) day(-1), administered in divided doses with gradual increase in the dose, is effective and safe for treating problematic proliferating infantile haemangioma in our cohort of patients. Treatment should be maintained until the lesion is completely involuted or the child is 12

  3. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice

    PubMed Central

    Lim, S.; Jatakanon, A.; Gordon, D.; Macdonald, C.; Chung, K. F.; Barnes, P.

    2000-01-01

    BACKGROUND—Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.
METHODS—In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 µg beclomethasone dipropionate (BDP) daily and inhaled β2 agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 µg BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 µg BDP) over a six month period was examined.
RESULTS—One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.
CONCLUSION—There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.

 PMID:10992535

  4. Ultra-Low-Dose CT of the Thorax Using Iterative Reconstruction: Evaluation of Image Quality and Radiation Dose Reduction.

    PubMed

    Kim, Yookyung; Kim, Yoon Kyung; Lee, Bo Eun; Lee, Seok Jeong; Ryu, Yon Ju; Lee, Jin Hwa; Chang, Jung Hyun

    2015-06-01

    The purpose of this study is to assess the image quality and radiation dose reduction of ultra-low-dose CT using sinogram-affirmed iterative reconstruction (SAFIRE). This prospective study enrolled 25 patients who underwent three consecutive unenhanced CT scans including low-dose CT (120 kVp and 30 mAs) and two ultra-low-dose CT protocols (protocol A, 100 kVp and 20 mAs; protocol B, 80 kVp and 30 mAs) with image reconstruction using SAFIRE. The image quality and radiation dose reduction were assessed. The mean (± SD) effective radiation dose was 1.06 ± 0.11, 0.44 ± 0.05, and 0.31 ± 0.03 mSv for low-dose CT, ultra-low-dose CT protocol A, and ultra-low-dose CT protocol B, respectively. Overall image quality was determined as diagnostic in 100% of low-dose CT scans, 96% of ultra-low-dose CT protocol A scans, and 88% of ultra-low-dose CT protocol B scans. All patients with nondiagnostic quality images had a body mass index (weight in kilograms divided by the square of height in meters) greater than 25. There was no statistically significant difference in detection frequencies of 14 lesion types among the three CT protocols, but pulmonary emphysema was detected in fewer patients (3/25) in ultra-low-dose CT protocol B scans compared with ultra-low-dose CT protocol A scans (5/25) or low-dose CT scans (6/25). We measured the longest dimensions of 33 small solid nodules (3.8-12.4 mm in long diameter) and found no statistically significant difference in the values afforded by the three CT protocols (p = 0.135). Iterative reconstruction allows ultra-low-dose CT and affords acceptable image quality, allowing size measurements of solid pulmonary nodules to be made.

  5. Fibrinolytic activity and bleeding after cardiac surgery with cardiopulmonary bypass and low-dose aprotinin therapy.

    PubMed

    Kuepper, Frank; Dangas, George; Mueller-Chorus, Ansgar; Kulka, Peter M; Zenz, Michael; Wiebalck, Albrecht

    2003-02-01

    Low-dose aprotinin inhibits hyperfibrinolysis in cardiac surgery. However, excessive postoperative bleeding and increased fibrinolysis may occur despite low dose-aprotinin administration. We investigated (i) whether fibrinolytic activity significantly rises under low-dose aprotinin administration, and (ii) whether this is associated with excessive postoperative bleeding (> or = 1000 ml/24 h). In a prospective single-blind trial, 120 consecutive patients were randomized to receive 280 mg aprotinin or no aprotinin before skin incision. D-dimer levels increased significantly to the end of surgery, reaching higher levels in the control group. The risk for excessive bleeding was lower in the aprotinin group (12 versus 37%, = 0.001). Fifteen minutes after heparin reversal, patients were at risk for excessive bleeding, when enhanced fibrinolysis was documented (aprotinin group, D-dimer > or = 1.0 micro g/ml, odds ratio = 9.1, = 0.047; control group, D-dimer > or = 3.0 micro g/ml, odds ratio = 4.6, = 0.014). Ninety-seven per cent of the aprotinin group and 81% of control group patients had no excessive bleeding when the D-dimer plasma level was below these values. We conclude that (i) fibrinolytic activity significantly rises under low-dose aprotinin administration, and (ii) plasma D-dimer levels at end of surgery may help to identify patients who are unlikely to develop excessive postoperative bleeding.

  6. Risk of cancer subsequent to low-dose radiation

    SciTech Connect

    Warren, S.

    1980-01-01

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident. (PCS)

  7. Low-Dose Hyper-Radiosensitivity: Past, Present, and Future

    SciTech Connect

    Marples, Brian Collis, Spencer J.

    2008-04-01

    This review article discusses the biology of low-dose hyper-radiosensitivity (HRS) with reference to the molecular regulation of DNA repair and cell cycle control processes. Particular attention is paid to the significance of G2-phase cell cycle checkpoints in overcoming low-dose hyper-radiosensitivity and the impact of HRS on low-dose rate radiobiology. The history of HRS from the original in vivo discovery to the most recent in vitro and clinical data are examined to present a unifying hypothesis concerning the molecular control and regulation of this important low dose radiation response. Finally, preclinical and clinical data are discussed, from a molecular viewpoint, to provide theoretical approaches to exploit HRS biology for clinical gain.

  8. Low-dose naltrexone therapy improves active Crohn's disease.

    PubMed

    Smith, Jill P; Stock, Heather; Bingaman, Sandra; Mauger, David; Rogosnitzky, Moshe; Zagon, Ian S

    2007-04-01

    Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. In an open-labeled pilot prospective trial, the safety and efficacy of low-dose naltrexone (LDN), an opioid antagonist, were tested in patients with active Crohn's disease. Eligible subjects with histologically and endoscopically confirmed active Crohn's disease activity index (CDAI) score of 220-450 were enrolled in a study using 4.5 mg naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior to study initiation. Other therapy for Crohn's disease that was at a stable dose for 4 wk prior to enrollment was continued at the same doses. Patients completed the inflammatory bowel disease questionnaire (IBDQ) and the short-form (SF-36) quality of life surveys and CDAI scores were assessed pretreatment, every 4 wk on therapy and 4 wk after completion of the study drug. Drug was administered by mouth each evening for a 12-wk period. Seventeen patients with a mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased significantly (P= 0.01) with LDN, and remained lower than baseline 4 wk after completing therapy. Eighty-nine percent of patients exhibited a response to therapy and 67% achieved a remission (P < 0.001). Improvement was recorded in both quality of life surveys with LDN compared with baseline. No laboratory abnormalities were noted. The most common side effect was sleep disturbances, occurring in seven patients. LDN therapy appears effective and safe in subjects with active Crohn's disease. Further studies are needed to explore the use of this compound.

  9. Bradycardia following a single low dose of trazodone.

    PubMed

    Li, Tien-Chun; Chiu, Hsiu-Wen; Ho, Kai-Jen; Tzeng, Dong-Sheng

    2011-03-01

    Symptomatic bradycardia following a single low dose of oral trazodone is rare. Herein, we report the case of a patient with major depressive disorder who developed and was able to resolve symptomatic bradycardia following administration of a single low dose of trazodone 50mg, and then discontinuation. This is the first case report of symptomatic bradycardia which might be attributed to a single lowest dose of trazodone in the world.

  10. Low-dose cyclophosphamide-induced acute hepatotoxicity

    PubMed Central

    Subramaniam, S. Ravih; Cader, Rizna Abdul; Mohd, Rozita; Yen, Kong Wei; Ghafor, Halim Abdul

    2013-01-01

    Patient: Male, 48 Final Diagnosis: Low dose cyclophosphamide-induced acute hepatotoxicity Symptoms: Epigastric pain Medication: Withdrawal of cyclophosphamide Clinical Procedure: — Specialty: Nephrology • Hepatology • Gastroenterology • Toxicology Objective: Unexpected drug reaction Background: Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis). Acute adverse effects include bone marrow suppression, hemorrhagic cystitis, nausea, vomiting, and hair loss. Hepatotoxicity with high dose cyclophosphamide is well recognized but hepatitis due to low dose cyclophosphamide has rarely been described. Case Report: We report the case of a 48-year-old Chinese man with a rapidly progressive glomerulonephritis secondary to granulomatosis with polyangiitis who developed severe acute hepatic failure within 24 hours of receiving low-dose intravenous cyclophosphamide. The diagnosis of granulomatosis with polyangiitis was supported with a positive c-ANCA serology. The patient was treated with high dose methylprednisolone, plasmapheresis, intermittent hemodialysis, and low-dose intravenous cyclophosphamide. Conclusions: Hepatotoxicity may occur even after low-dose intravenous cyclophosphamide treatment. To the best of our knowledge, this is the first report of severe, non-viral, liver inflammation developing within 24 hours of administration of low-dose intravenous cyclophosphamide (200 mg). Physicians should be aware of this serious adverse reaction and should not repeat the cyclophosphamide dose when there is hepatotoxicity caused by the first dose. Initial and follow-up liver function tests should be monitored in all patients receiving cyclophosphamide treatment. PMID:24023976

  11. Gate bias symmetry dependency of electron mobility and prospect of velocity modulation in double-gate silicon-on-insulator transistors

    NASA Astrophysics Data System (ADS)

    Prunnila, M.; Ahopelto, J.; Henttinen, K.; Gamiz, F.

    2004-11-01

    We report on detailed room-temperature transport properties of a 17nm thick double-gate silicon-on-insulator (DGSOI) transistor. We find that when the electron gas is transferred between the top and the bottom of the silicon-on-insulator (SOI) layer by changing the gate bias symmetry (i.e., applying the gate biases in a push-pull fashion), while keeping the carrier density constant the maximum mobility occurs when the electron gas symmetrically occupies the whole SOI slab. The observed mobility behavior is the fingerprint of volume inversion/accumulation. This gate bias symmetry dependency of the mobility suggests that DGSOI devices intrinsically can be operated in a velocity modulation transistor (VMT) mode. In the experimental gate bias window, the maximum velocity/mobility modulation is ˜40%. The VMT transconductance exceeds conventional single-gate transconductance when electron density is above ˜5.3×1016m-2. Improvements of the observed VMT operation in thin DGSOI devices are discussed.

  12. Design, optimization and evaluation of a "smart" pixel sensor array for low-dose digital radiography

    NASA Astrophysics Data System (ADS)

    Wang, Kai; Liu, Xinghui; Ou, Hai; Chen, Jun

    2016-04-01

    Amorphous silicon (a-Si:H) thin-film transistors (TFTs) have been widely used to build flat-panel X-ray detectors for digital radiography (DR). As the demand for low-dose X-ray imaging grows, a detector with high signal-to-noise-ratio (SNR) pixel architecture emerges. "Smart" pixel is intended to use a dual-gate photosensitive TFT for sensing, storage, and switch. It differs from a conventional passive pixel sensor (PPS) and active pixel sensor (APS) in that all these three functions are combined into one device instead of three separate units in a pixel. Thus, it is expected to have high fill factor and high spatial resolution. In addition, it utilizes the amplification effect of the dual-gate photosensitive TFT to form a one-transistor APS that leads to a potentially high SNR. This paper addresses the design, optimization and evaluation of the smart pixel sensor and array for low-dose DR. We will design and optimize the smart pixel from the scintillator to TFT levels and validate it through optical and electrical simulation and experiments of a 4x4 sensor array.

  13. Preliminary Study of Prospective ECG-Gated 320-Detector CT Coronary Angiography in Patients with Ventricular Premature Beats

    PubMed Central

    Wang, Wei; Wang, Dan; Shen, Baozhong

    2012-01-01

    Background To study the applicability of prospective ECG-gated 320-detector CT coronary angiography (CTCA) in patients with ventricular premature beats(VPB), and determine the scanning mode that best maximizes image quality and reduces radiation dose. Methods: 110 patients were divided into a VPB group (60 cases) and a control group (50 cases) using CTCA.All the patients then underwent coronary angiography (CAG) within one month. CAG served as a reference standard through which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CTCA in diagnosing significant coronary artery stenosis (luminal stenosis ≥50%) could be analyzed. The two radiologists with more than 3 years’ experience in cardiac CT each finished the image analysis after consultation. A personalized scanning mode was adopted to compare image quality and radiation dose between the two groups. Methodology/Principal Findings At the coronary artery segment level, sensitivity, specificity, PPV, and NPV in the premature beat group were 92.55%, 98.21%, 88.51%, and 98.72% respectively. In the control group these values were found to be 95.79%, 98.42%, 90.11%, and 99.28% respectively. Between the two groups, specificity, sensitivity PPV, NPV was no significant difference. The two groups had no significant difference in image quality score (P>0.05). Heart rate (77.20±12.07 bpm) and radiation dose (14.62±1.37 mSv) in the premature beat group were higher than heart rate (58.72±4.73 bpm) and radiation dose (3.08±2.35 mSv) in the control group. In theVPB group, the radiation dose (34.55±7.12 mSv) for S-field scanning was significantly higher than the radiation dose (15.10±1.12 mSv) for M-field scanning. Conclusions/Significance With prospective ECG-gated scanning for VPB, the diagnostic accuracy of coronary artery stenosis is very high. Scanning field adjustment can reduce radiation dose while maintaining good image quality. For patients with slow heart

  14. Low Dose Suppression of Neoplastic Transformation in Vitro

    SciTech Connect

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  15. [Prevention of psychedelic side effects associated with low dose continuous intravenous ketamine infusion].

    PubMed

    Remerand, Francis; Couvret, Claude; Pourrat, Xavier; Le Tendre, Charlotte; Baud, Annick; Fusciardi, Jacques

    2007-01-01

    Continuous low dose infusion of intravenous ketamine for postoperative analgesia was often associated with frightening acute psychodysleptic experiences in our patients. We hypothesized they were due to boluses of ketamine accumulated in the infusion line. We evaluated on two successive groups the impact of perfusion line modifications on psychodysleptic side effects occurrence. We compared a reference historic group (in which ketamine line was connected to perfusion line) to a second prospective group (in which ketamine line was connected to the venous catheter via an unidirectional valve). Psychodysleptic experiences occurrence decreased from 4 patients of 26 (15%) to 2 of 116 (2%, p = 0.01). Moreover, these experiences were no longer associated with severe anxious symptoms like near death experiences. An unidirectional valve must be considered to limit the occurrence of low dose intravenous ketamine infusion associated psychedelic side effects, during postoperative analgesia.

  16. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    PubMed Central

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  17. Screening for lung cancer with low-dose CT.

    PubMed

    Coche, E

    2008-01-01

    Lung cancer represents the leading cause of cancer-related mortality in the world. In the past, many attempts were made to detect the disease at an early stage and subsequently reduce its mortality. Chest X-ray was abandoned for this purpose. For several years low-dose computed tomography has been introduced as a potential tool for early screening in a high-risk population. As demonstrated in several papers, the task is not easy and researchers are faced with many difficulties. This paper reviews mainly the role of low-dose CT for early cancer screening. Results of past and current trials, controversies related to the high rate of lung nodules, cost-effectiveness, and delivered radiation dose to the patient are presented. Finally some limitations of low dose CT for lung cancer detection are explained.

  18. [Mechanism of cytogenetic adaptive response induced by low dose radiation].

    PubMed

    Cai, L; Liu, S

    1990-11-01

    Cytogenetic observation on human lymphocytes indicated that pre-exposure of 10, 50 and 75 mGy X-rays could induced the adaptive response. Experimental results with different temperature treatment showed that the adaptive response induced by low dose radiation could be enhanced by 41 degrees C and 43 degrees C, but inhibited by 4 degrees C in addition the treatment by 41 degrees C for one hour could also cause the adaptive response as did low dose radiation. Results showed that adaptive response induced by low dose radiation (10 or 50 mGy X-rays) could be eliminated by the protein synthesis inhibitor, implying that the adaptive response is related with the metabolism of cells, especially with the production of certain protective proteins.

  19. Health Benefits of Exposure to Low-dose Radiation.

    PubMed

    Rithidech, Kanokporn Noy

    2016-03-01

    Although there is no doubt that exposure to high doses of radiation (delivered at a high dose-rate) induces harmful effects, the health risks and benefits of exposure to low levels (delivered at a low dose-rate) of toxic agents is still a challenging public health issue. There has been a considerable amount of published data against the linear no-threshold (LNT) model for assessing risk of cancers induced by radiation. The LNT model for risk assessment creates "radiophobia," which is a serious public health issue. It is now time to move forward to a paradigm shift in health risk assessment of low-dose exposure by taking the differences between responses to low and high doses into consideration. Moreover, future research directed toward the identification of mechanisms associated with responses to low-dose radiation is critically needed to fully understand their beneficial effects.

  20. Low-dose CT via convolutional neural network

    PubMed Central

    Chen, Hu; Zhang, Yi; Zhang, Weihua; Liao, Peixi; Li, Ke; Zhou, Jiliu; Wang, Ge

    2017-01-01

    In order to reduce the potential radiation risk, low-dose CT has attracted an increasing attention. However, simply lowering the radiation dose will significantly degrade the image quality. In this paper, we propose a new noise reduction method for low-dose CT via deep learning without accessing original projection data. A deep convolutional neural network is here used to map low-dose CT images towards its corresponding normal-dose counterparts in a patch-by-patch fashion. Qualitative results demonstrate a great potential of the proposed method on artifact reduction and structure preservation. In terms of the quantitative metrics, the proposed method has showed a substantial improvement on PSNR, RMSE and SSIM than the competing state-of-art methods. Furthermore, the speed of our method is one order of magnitude faster than the iterative reconstruction and patch-based image denoising methods. PMID:28270976

  1. Low-dose radiation epidemiology studies: status and issues.

    PubMed

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes.

  2. Low-dose vaporized cannabis significantly improves neuropathic pain.

    PubMed

    Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-02-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

  3. ["Dose-risk" relationships at low doses of radiation].

    PubMed

    Stefanou, E P

    1988-01-01

    The ionizing radiation is inherently harmful to human beings, and people must be protected from unnecessary or excessive exposure to it. The harmful nature of high doses of x rays has been known for many years. However, for low doses such as those commonly employed in dental radiographic procedures the magnitude of the risk (or even if there is a risk) remains uncertain. The purpose of this paper is to do an analysis of the Dose-risk relationships at low doses of radiation according to the latest recommendations and philosophy of the International Commission on Radiological Protection (ICRP).

  4. High-resolution low-dose scanning transmission electron microscopy.

    PubMed

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  5. Very low-dose lenalidomide therapy for elderly multiple myeloma patients.

    PubMed

    Minagawa, Kentaro; Kawano, Hiroki; Suzuki, Takuma; Inagaki, Tadahiro; Kishi, Minoru; Hirata, Tamaki; Kimura, Sachiko; Takechi, Miho; Koide, Toru; Iwai, Masahide; Katayama, Yoshio; Matsui, Toshimitsu

    2013-05-01

    Lenalidomide treatment for refractory or relapsed multiple myeloma in elderly patients may be feasible in an outpatient setting. However, difficulties have been associated with the management of adverse effects. Therefore, a dose reduction in lenalidomide has been recommended in some cases. In this report, we encountered the successful treatment of myeloma in 6 elderly patients (aged above 70 years) with very low-dose lenalidomide (5 mg daily). Four patients exhibited more than a partial response with an 8.6 months median follow-up period, which was comparable with previous findings. The major adverse effect observed was infection, which occurred during the first several cycles. Others were less toxic, especially the absence of grade 3/4 toxicities for hematological adverse effects.Although a dose reduction in lenalidomide therapy for elderly patients is controversial, a very low dose could be safe and effective. Our group is currently conducting a multi-center prospective trial to evaluate the efficacy of low-dose lenalidomide therapy.

  6. Coronary artery bypass surgery with heparin-coated perfusion circuits and low-dose heparinization

    PubMed Central

    Mullen, John C.; Bentley, Michael J.; Gelfand, Elliot T.; Koshal, Arvind; Modry, Dennis L.; Guenther, Craig R.; Etches, Wai S.; Stang, Linda J.; Lopushinsky, Steven R.

    2002-01-01

    Objective To evaluate the safety and efficacy of heparin-coated perfusion circuits with low-dose heparinization and centrifugal pumping compared with the standard method during coronary artery bypass grafting. Design Prospective, randomized, single-blind clinical trial. Setting A primary care institution. Patients Ninety patients who underwent first-time elective coronary artery bypass grafting were eligible for the study. After giving informed consent, they were randomly assigned to 1 of 3 groups (30/group). Interventions Perfusion on regular uncoated bypass equipment with a roller pump and full-dose heparinization (300 IU/kg bolus, activated clotting time [ACT] > 400 s) (group 1), on a heparin-coated oxygenator with a centrifugal pump and full-dose heparinization (group 2) and on fully heparin-coated bypass equipment with a centrifugal pump and low-dose heparinization (100 IU/kg bolus, ACT of 180–400 s) (group 3). Standard coronary artery bypass grafting was performed. Outcome measures Postoperative bleeding, transfusion requirements and clinical outcomes. Results There were no complications related to the study protocol. Study groups were similar in terms of postoperative bleeding, transfusion requirements and clinical outcomes. Conclusions Heparin-coated cardiopulmonary bypass with low-dose heparinization and centrifugal pumping is a safe practice but showed no advantages over the use of regular uncoated bypass circuits for coronary bypass surgery. PMID:12067167

  7. [Clinical study of a low-dose contraceptive--Femodene].

    PubMed

    Rachev, E; Damianov, L; Dukovski, A; Katsarova, M

    1995-01-01

    The authors present their clinical experience with a low-dose monophasic contraceptive consisting of 30 mcg ethinylestradiol and 75 mcg a gestagen--gestodene (Femoden, Schering). 112 menstrual cycles of 22 women in fertile age were followed. The results show 100% contraception, a good control of the menstrual cycle and tolerance of the preparation.

  8. Low-dose high-resolution CT of lung parenchyma

    SciTech Connect

    Zwirewich, C.V.; Mayo, J.R.; Mueller, N.L. )

    1991-08-01

    To evaluate the efficacy of low-dose high-resolution computed tomography (HRCT) in the assessment of lung parenchyma, three observers reviewed the scans of 31 patients. The 1.5-mm-collimation, 2-second, 120-kVp scans were obtained at 20 and 200 mA at selected identical levels in the chest. The observers evaluated the visualization of normal pulmonary anatomy, various parenchymal abnormalities and their distribution, and artifacts. The low-dose and conventional scans were equivalent in the evaluation of vessels, lobar and segmental bronchi, and anatomy of secondary pulmonary lobules, and in characterizing the extent and distribution of reticulation, honeycomb cysts, and thickened interlobular septa. The low-dose technique failed to demonstrate ground-glass opacity in two of 10 cases (20%) and emphysema in one of nine cases (11%), in which they were evident but subtle on the high-dose scans. These differences were not statistically significant. Linear streak artifact was more prominent on images acquired with the low-dose technique, but the two techniques were judged equally diagnostic in 97% of cases. The authors conclude that HRCT images acquired at 20 mA yield anatomic information equivalent to that obtained with 200-mA scans in the majority of patients, without significant loss of spatial resolution or image degradation due to linear streak artifact.

  9. Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.

    PubMed

    Paquette, Jay; Olmstead, Mary C; Olmstead, Mary

    2005-12-01

    Both opioids and cannabinoids have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid systems interact, this study investigated whether ultra-low dose naltrexone also influences cannabinoid-induced antinociception. Separate groups of Long-Evans rats were tested for antinociception following an injection of vehicle, a sub-maximal dose of the cannabinoid agonist WIN 55 212-2, naltrexone (an ultra-low or a high dose) or a combination of WIN 55 212-2 and naltrexone doses. Tail-flick latencies were recorded for 3 h, at 10-min intervals for the first hour, and at 15-min intervals thereafter. Ultra-low dose naltrexone elevated WIN 55 212-2-induced tail flick thresholds without extending its duration of action. This enhancement was replicated in animals receiving intraperitoneal or intravenous injections. A high dose of naltrexone had no effect on WIN 55 212-2-induced tail flick latencies, but a high dose of the cannabinoid 1 receptor antagonist SR 141716 blocked the elevated tail-flick thresholds produced by WIN 55 212-2+ultra-low dose naltrexone. These data suggest a mechanism of cannabinoid-opioid interaction whereby activated opioid receptors that couple to Gs-proteins may attenuate cannabinoid-induced antinociception and/or motor functioning.

  10. Malignant melanoma of the tongue following low-dose radiation

    SciTech Connect

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  11. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    EPA Science Inventory

    Carcinogenic Effects of Low Doses of Ionizing Radiation

    R Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

    The form of the dose-response curve for radiation-induced cancers, particu...

  12. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    EPA Science Inventory

    Carcinogenic Effects of Low Doses of Ionizing Radiation

    R Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

    The form of the dose-response curve for radiation-induced cancers, particu...

  13. Low dose quetiapine induced galactorrhoea: a case report

    PubMed Central

    2007-01-01

    Background Quetiapine causes less prolactin elevation and/or galactorrhoea than other atypical antipsychotics. Case Presentation Ms AB had galactorrhoea and raised prolactin levels at only 100 mg of quetiapine daily. Conclusion Low dose quetiapine can also cause galactorrhoea. PMID:17650327

  14. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    SciTech Connect

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

  15. The impact of breathing guidance and prospective gating during thoracic 4DCT imaging: an XCAT study utilizing lung cancer patient motion

    NASA Astrophysics Data System (ADS)

    Pollock, Sean; Kipritidis, John; Lee, Danny; Bernatowicz, Kinga; Keall, Paul

    2016-09-01

    Two interventions to overcome the deleterious impact irregular breathing has on thoracic-abdominal 4D computed tomography (4DCT) are (1) facilitating regular breathing using audiovisual biofeedback (AVB), and (2) prospective respiratory gating of the 4DCT scan based on the real-time respiratory motion. The purpose of this study was to compare the impact of AVB and gating on 4DCT imaging using the 4D eXtended cardiac torso (XCAT) phantom driven by patient breathing patterns. We obtained simultaneous measurements of chest and abdominal walls, thoracic diaphragm, and tumor motion from 6 lung cancer patients under two breathing conditions: (1) AVB, and (2) free breathing. The XCAT phantom was used to simulate 4DCT acquisitions in cine and respiratory gated modes. 4DCT image quality was quantified by artefact detection (NCCdiff), mean square error (MSE), and Dice similarity coefficient of lung and tumor volumes (DSClung, DSCtumor). 4DCT acquisition times and imaging dose were recorded. In cine mode, AVB improved NCCdiff, MSE, DSClung, and DSCtumor by 20% (p  =  0.008), 23% (p  <  0.001), 0.5% (p  <  0.001), and 4.0% (p  <  0.003), respectively. In respiratory gated mode, AVB improved NCCdiff, MSE, and DSClung by 29% (p  <  0.001), 34% (p  <  0.001), 0.4% (p  <  0.001), respectively. AVB increased the cine acquisitions by 15 s and reduced respiratory gated acquisitions by 31 s. AVB increased imaging dose in cine mode by 10%. This was the first study to quantify the impact of breathing guidance and respiratory gating on 4DCT imaging. With the exception of DSCtumor in respiratory gated mode, AVB significantly improved 4DCT image analysis metrics in both cine and respiratory gated modes over free breathing. The results demonstrate that AVB and respiratory-gating can be beneficial interventions to improve 4DCT for cancer radiation therapy, with the biggest gains achieved when these interventions are used

  16. Prospective-gated cardiac micro-CT imaging of free-breathing mice using carbon nanotube field emission x-ray.

    PubMed

    Cao, Guohua; Burk, Laurel M; Lee, Yueh Z; Calderon-Colon, Xiomara; Sultana, Shabana; Lu, Jianping; Zhou, Otto

    2010-10-01

    Carbon nanotube (CNT) based field emission x-ray source technology has recently been investigated for diagnostic imaging applications because of its attractive characteristics including electronic programmability, fast switching, distributed source, and multiplexing. The purpose of this article is to demonstrate the potential of this technology for high-resolution prospective-gated cardiac micro-CT imaging. A dynamic cone-beam micro-CT scanner was constructed using a rotating gantry, a stationary mouse bed, a flat-panel detector, and a sealed CNT based microfocus x-ray source. The compact single-beam CNT x-ray source was operated at 50 KVp and 2 mA anode current with 100 microm x 100 microm effective focal spot size. Using an intravenously administered iodinated blood-pool contrast agent, prospective cardiac and respiratory-gated micro-CT images of beating mouse hearts were obtained from ten anesthetized free-breathing mice in their natural position. Four-dimensional cardiac images were also obtained by gating the image acquisition to different phases in the cardiac cycle. High-resolution CT images of beating mouse hearts were obtained at 15 ms temporal resolution and 6.2 lp/mm spatial resolution at 10% of system MTF. The images were reconstructed at 76 microm isotropic voxel size. The data acquisition time for two cardiac phases was 44 +/- 9 min. The CT values observed within the ventricles and the ventricle wall were 455 +/- 49 and 120 +/- 48 HU, respectively. The entrance dose for the acquisition of a single phase of the cardiac cycle was 0.10 Gy. A high-resolution dynamic micro-CT scanner was developed from a compact CNT microfocus x-ray source and its feasibility for prospective-gated cardiac micro-CT imaging of free-breathing mice under their natural position was demonstrated.

  17. Prospective-gated cardiac micro-CT imaging of free-breathing mice using carbon nanotube field emission x-ray

    SciTech Connect

    Cao Guohua; Burk, Laurel M.; Lee, Yueh Z.; Calderon-Colon, Xiomara; Sultana, Shabana; Lu Jianping; Zhou, Otto

    2010-10-15

    Purpose: Carbon nanotube (CNT) based field emission x-ray source technology has recently been investigated for diagnostic imaging applications because of its attractive characteristics including electronic programmability, fast switching, distributed source, and multiplexing. The purpose of this article is to demonstrate the potential of this technology for high-resolution prospective-gated cardiac micro-CT imaging. Methods: A dynamic cone-beam micro-CT scanner was constructed using a rotating gantry, a stationary mouse bed, a flat-panel detector, and a sealed CNT based microfocus x-ray source. The compact single-beam CNT x-ray source was operated at 50 KVp and 2 mA anode current with 100 {mu}mx100 {mu}m effective focal spot size. Using an intravenously administered iodinated blood-pool contrast agent, prospective cardiac and respiratory-gated micro-CT images of beating mouse hearts were obtained from ten anesthetized free-breathing mice in their natural position. Four-dimensional cardiac images were also obtained by gating the image acquisition to different phases in the cardiac cycle. Results: High-resolution CT images of beating mouse hearts were obtained at 15 ms temporal resolution and 6.2 lp/mm spatial resolution at 10% of system MTF. The images were reconstructed at 76 {mu}m isotropic voxel size. The data acquisition time for two cardiac phases was 44{+-}9 min. The CT values observed within the ventricles and the ventricle wall were 455{+-}49 and 120{+-}48 HU, respectively. The entrance dose for the acquisition of a single phase of the cardiac cycle was 0.10 Gy. Conclusions: A high-resolution dynamic micro-CT scanner was developed from a compact CNT microfocus x-ray source and its feasibility for prospective-gated cardiac micro-CT imaging of free-breathing mice under their natural position was demonstrated.

  18. Low dose naltrexone: side effects and efficacy in gastrointestinal disorders.

    PubMed

    Ploesser, Jennifer; Weinstock, Leonard B; Thomas, Erin

    2010-01-01

    Use of low dose naltrexone has been advocated for a variety of medical problems. Only a few articles published in peer review journals have documented side effects of low dose naltrexone. The purpose of this study was to determine the frequency of adverse effects of low dose naltrexone in patients who have been treated for a variety of gastrointestinal disorders. The secondary purpose was to determine global efficacy in a retrospective survey. Patients (206) form a single gastroenterologist's clinical practice who had been prescribed naltrexone were mailed a survey to evaluate the side effects and efficacy of naltrexone. Patients had either irritable bowel syndrome without evidence for small intestinal bacterial overgrowth, chronic idiopathic constipation, or inflammatory bowel disease. Patients with diarrhea were given 2.5 mg daily, constipation 2.5 mg twice daily, and inflammatory bowel disease 4.5 mg daily. In the patients who returned the survey, 47/121 (38.8%) had no side effects. Of the 74/121 (61.2%) patients who had side effects, 58 had one or more neurological complaints, and 32 had one or more gastrointestinal side effects. In the patients with side effects, 24/74 (32.4%) had short lived symptoms. Low dose naltrexone was terminated owing to side effects in 20/74 patients (27.0%). In 13 patients with idiopathic irritable bowel syndrome, 2 were markedly worse. In 85 patients with irritable bowel syndrome-small intestinal bacterial overgrowth, 15 were markedly improved, 32 were moderately worse, and 1 was markedly worse. In 12 patients with chronic constipation, 7 were markedly improved, 1 was moderately improved, 1 was mildly improved, and 4 were unchanged. Low dose naltrexone frequently has side effects but in most is tolerable. It appears to be helpful for a member of patients with gastrointestinal disorders.

  19. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection.

    PubMed

    Goh, Duck-Ho; Jin, Sung-Chul; Jeong, Hae Woong; Ha, Sam Yeol

    2016-09-01

    Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications.

  20. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection

    PubMed Central

    Goh, Duck-Ho; Jeong, Hae Woong; Ha, Sam Yeol

    2016-01-01

    Purpose Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Materials and Methods Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Results Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Conclusion Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications. PMID:27621948

  1. Comparison of colloid preload versus coload under low dose spinal anesthesia for cesarean delivery

    PubMed Central

    Varshney, Rohit; Jain, Gaurav

    2013-01-01

    Background: Although fluid bolus is considered as a conventional prophylactic measure to prevent spinal-induced hypotension; vasopressors are nevertheless required. Low dose spinal anesthetics could markedly reduce such episodes of hypotension, by minimizing sympathetic blockade. Aims: We chose to compare the relative efficacy of colloid preload versus coload under low dose spinal anesthesia, for elective cesarean delivery. Settings and Design: A prospective, randomized, double-blinded study. Materials and Methods: In total, 42 parturients were randomized to receive a preload (Group P) of hydroxyl ethyl starch (10 ml/kg) over 20 min before initiation of low dose spinal anesthesia (hyperbaric bupivacaine 5.5 mg with fentanyl 25 μg) or coload (Group C) of an identical fluid over 5 min, starting at the time of identification of cerebrospinal fluid. Our primary outcome included hemodynamic parameters and the incidence of hypotension. The neonatal outcome and side-effects were also monitored. Statistical Analysis: Mann-Whitney U test and Fisher's exact/Chi-square test, whichever appropriate. A P < 0.05 was considered to be significant. Results: The incidence of hypotension was lower in Group P (10%) when compared with Group C (25%), though insignificant statistically. The hemodynamic parameters were better in Group P, though intergroup statistical differences were not observed. The time to the first episode of hypotension was longer in the Group P (17 min) as compared with Group C (14 min). No notable side-effects or adverse neonatal outcome was noted. Conclusion: Colloid preload has a clinical advantage over the coload strategy, in reducing hypotensive episodes under low dose spinal anesthesia. Preload is better under large hemodynamic fluctuations while coload is preferable for emergency scenarios. PMID:25885987

  2. Low-Dose CT of the Paranasal Sinuses: Minimizing X-Ray Exposure with Spectral Shaping.

    PubMed

    Wuest, Wolfgang; May, Matthias; Saake, Marc; Brand, Michael; Uder, Michael; Lell, Michael

    2016-11-01

    Shaping the energy spectrum of the X-ray beam has been shown to be beneficial in low-dose CT. This study's aim was to investigate dose and image quality of tin filtration at 100 kV for pre-operative planning in low-dose paranasal CT imaging in a large patient cohort. In a prospective trial, 129 patients were included. 64 patients were randomly assigned to the study protocol (100 kV with additional tin filtration, 150mAs, 192x0.6-mm slice collimation) and 65 patients to the standard low-dose protocol (100 kV, 50mAs, 128 × 0.6-mm slice collimation). To assess the image quality, subjective parameters were evaluated using a five-point scale. This scale was applied on overall image quality and contour delineation of critical anatomical structures. All scans were of diagnostic image quality. Bony structures were of good diagnostic image quality in both groups, soft tissues were of sufficient diagnostic image quality in the study group because of a high level of noise. Radiation exposure was very low in both groups, but significantly lower in the study group (CTDIvol 1.2 mGy vs. 4.4 mGy, p < 0.001). Spectral optimization (tin filtration at 100 kV) allows for visualization of the paranasal sinus with sufficient image quality at a very low radiation exposure. • Spectral optimization (tin filtration) is beneficial to low-dose parasinus CT • Tin filtration at 100 kV yields sufficient image quality for pre-operative planning • Diagnostic parasinus CT can be performed with an effective dose <0.05 mSv.

  3. Comparison of infusion or low-dose proton pump inhibitor treatments in upper gastrointestinal system bleeding.

    PubMed

    Songür, Yildiran; Balkarli, Ayşe; Acartürk, Gürsel; Senol, Altug

    2011-04-01

    The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain. To compare the treatment effects of continuous infusion and low-dose esomeprazole therapies in patients with non-variceal upper gastrointestinal (GI) bleeding. This prospective clinical study compared continuous infusion of esomeprazole (80 mg bolus followed by 8 mg∕h continuous infusion for 72 h) and low-dose esomeprazole (40 mg twice daily IV) treatments in GI bleeding patients with peptic ulcer presenting a high risk of re-bleeding, who were administered a successful endoscopic homeostasis. The primary end point was the occurrence of re-bleeding during hospitalization and within one month of discharge. Secondary outcomes were defined as duration of hospitalization, need of transfusion, surgical treatment, and mortality rate. After 72 h, both groups were switched to oral esomeprazole therapy for one-month. A hundred thirty-two subjects were enrolled. Re-bleeding occurred in 11 (16.7%) patients in the infusion therapy group and in 12 (18.2%) patients in the low-dose group (P=0.819) within the first 72 h. No patient experienced re-bleeding in the first month following discharge. There was no statistical significant difference between the two groups in terms of transfusion need, durations of hospitalization, need for surgery and mortality rate. PPI infusion therapy following endoscopic hemostasis treatment was not found superior to low-dose PPI therapy in the terms of re-bleeding, need of surgery and mortality. Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  4. Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography

    PubMed Central

    Pompe, E.; van der Bruggen, T.; van Rhenen, A.; Lammers, J. W. J.; Wessels, F.; Sprengers, R. W.; de Jong, P. A.; Minnema, M. C.

    2017-01-01

    We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose. PMID:28235014

  5. Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

    PubMed

    Gerritsen, M G; Willemink, M J; Pompe, E; van der Bruggen, T; van Rhenen, A; Lammers, J W J; Wessels, F; Sprengers, R W; de Jong, P A; Minnema, M C

    2017-01-01

    We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

  6. Application of prospective ECG-gated high-pitch 128-slice dual-source CT angiography in the diagnosis of congenital extracardiac vascular anomalies in infants and children.

    PubMed

    Nie, Pei; Yang, Guangjie; Wang, Ximing; Duan, Yanhua; Xu, Wenjian; Li, Haiou; Cao, Ting; Liu, Xuejun; Ji, Xiaopeng; Cheng, Zhaoping; Wang, Anbiao

    2014-01-01

    To investigate the value of prospective ECG-gated high-pitch 128-slice dual-source CT (DSCT) angiography in the diagnosis of congenital extracardiac vascular anomalies in infants and children in comparison with transthoracic echocardiography (TTE). Eighty consecutive infants or children clinically diagnosed of congenital heart disease and suspected with extracardiac vascular anomaly were enrolled, and 75 patients were finally included in this prospective study. All patients underwent prospective ECG-gated high-pitch DSCT angiography after TTE with an interval of 1-7 days. The diagnostic accuracy and sensitivity of high-pitch DSCT angiography and TTE were compared according to the surgical/CCA findings. The image quality of DSCT was assessed using a five-point scale. The effective radiation dose (ED) was calculated. A total of 17 congenital heart diseases and 162 separate extracardiac vascular anomalies were confirmed by surgical/CCA findings in 75 patients. The diagnostic accuracy of high-pitch DSCT angiography and TTE was 99.67% and 97.89%, respectively. The sensitivity of high-pitch DSCT angiography and TTE was 97.53% and 79.62%, respectively. There was significant difference regarding to the diagnostic accuracy and the sensitivity between high-pitch DSCT angiography and TTE (χ2 = 23.561 and 28.013, P<0.05). The agreement on the image quality scoring of DSCT between the two observers was excellent (κ = 0.81), and the mean score of image quality was 4.1±0.7. The mean ED of DSCT was 0.29±0.08 mSv. Prospective ECG-gated high-pitch 128-slice DSCT angiography with low radiation dose and high diagnostic accuracy has higher sensitivity compared to TTE in the detection of congenital extracardiac vascular anomalies in infants and children.

  7. Automated aortic calcification detection in low-dose chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Htwe, Yu Maw; Padgett, Jennifer; Henschke, Claudia; Yankelevitz, David; Reeves, Anthony P.

    2014-03-01

    The extent of aortic calcification has been shown to be a risk indicator for vascular events including cardiac events. We have developed a fully automated computer algorithm to segment and measure aortic calcification in low-dose noncontrast, non-ECG gated, chest CT scans. The algorithm first segments the aorta using a pre-computed Anatomy Label Map (ALM). Then based on the segmented aorta, aortic calcification is detected and measured in terms of the Agatston score, mass score, and volume score. The automated scores are compared with reference scores obtained from manual markings. For aorta segmentation, the aorta is modeled as a series of discrete overlapping cylinders and the aortic centerline is determined using a cylinder-tracking algorithm. Then the aortic surface location is detected using the centerline and a triangular mesh model. The segmented aorta is used as a mask for the detection of aortic calcification. For calcification detection, the image is first filtered, then an elevated threshold of 160 Hounsfield units (HU) is used within the aorta mask region to reduce the effect of noise in low-dose scans, and finally non-aortic calcification voxels (bony structures, calcification in other organs) are eliminated. The remaining candidates are considered as true aortic calcification. The computer algorithm was evaluated on 45 low-dose non-contrast CT scans. Using linear regression, the automated Agatston score is 98.42% correlated with the reference Agatston score. The automated mass and volume score is respectively 98.46% and 98.28% correlated with the reference mass and volume score.

  8. Influence of low-dose and low-dose-rate ionizing radiation on mutation induction in human cells

    NASA Astrophysics Data System (ADS)

    Yatagai, F.; Umebayashi, Y.; Suzuki, M.; Abe, T.; Suzuki, H.; Shimazu, T.; Ishioka, N.; Iwaki, M.; Honma, M.

    This is a review paper to introduce our recent studies on the genetic effects of low-dose and low-dose-rate ionizing radiation (IR). Human lymphoblastoid TK6 cells were exposed to γ-rays at a dose-rate of 1.2 mGy/h (total 30 mGy). The frequency of early mutations (EMs) in the thymidine kinase ( TK) gene locus was determined to be 1.7 × 10 -6, or 1.9-fold higher than the level seen in unirradated controls [Umebayashi, Y., Honma, M., Suzuki, M., Suzuki, H., Shimazu, T., Ishioka, N., Iwaki, M., Yatagai, F., Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation: detection by LOH analysis. J. Radiat. Res., 48, 7-11, 2007]. These mutants were then analyzed for loss of heterozygosity (LOH) events. Small interstitial-deletion events were restricted to the TK gene locus and were not observed in EMs in unirradated controls, but they comprised about half of the EMs (8/15) after IR exposure. Because of the low level of exposure to IR, this specific type of event cannot be considered to be the direct result of an IR-induced DNA double strand break (DSB). To better understand the effects of low-level IR exposure, the repair efficiency of site-specific chromosomal DSBs was also examined. The pre γ-irradiation under the same condition did not largely influence the efficiency of DSB repair via end-joining, but enhanced such efficiency via homologous recombination to an about 40% higher level (unpublished data). All these results suggest that DNA repair and mutagenesis can be indirectly influenced by low-dose/dose-rate IR.

  9. Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects.

    PubMed

    Abraham, Renny; Nirogi, Ramakrishna; Shinde, Anil; Irupannanavar, Shantaveer

    2015-01-01

    An extensive amount of research has focused on the development of new pharmacological agents to treat schizophrenia. Varying from person to person, schizophrenia is a heterogeneous disease with symptoms of positive, negative, and cognitive deficits. PRX-07034, a 5-hydroxytryptamine6 (5-HT6) receptor antagonist has been evaluated for its potential in treating obesity and cognitive deficits. This study evaluated PRX-07034 (0.1, 0.3, and 1.0 mg/kg body mass, by intraperitoneal (i.p.) injection), in combination with a low dose of prazosin (0.3 mg/kg, i.p.), for its antipsychotic potential. The research utilized a stereotypy assay, an open field test, an object recognition task, and prepulse inhibition. Dizocilpine, a non-competitive N-methyl-d-aspartate (NMDA) antagonist, was also administered in the above-mentioned assays as a psychomimetic. The combination of PRX-07034 and prazosin alleviated stereotypy and hyperlocomotor activity while enhancing memory in an object recognition task, and reversed sensory-gating deficits induced by dizocilpine. Examination of the medial prefrontal cortex revealed that a combination of PRX-07034 and prazosin reduced the dizocilpine-mediated increase of 5-HT. These results suggest that the combination of a 5-HT6 antagonist with low doses of prazosin could have therapeutic potential in the treatment of schizophrenia.

  10. Low Dose Naltrexone in the Treatment of Fibromyalgia.

    PubMed

    Metyas, Samy K; Yeter, Karen; Solyman, John; Arkfeld, Daniel

    2017-03-21

    Fibromyalgia is a chronic pain disorder characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance and cognitive impairment. A significant number of fibromyalgia patients do not respond adequately to the current drugs (pregabalin, milnacipran, duloxetine) approved for fibromyalgia treatment by the Food and Drug Administration (FDA). Thus, there is still a need for adjunctive therapies. Naltrexone is an opioid receptor antagonist used to treat alcohol and opioid dependence. It is hypothesized that low dose naltrexone causes transient blockade of opioid receptors centrally resulting in a rebound of endorphin function which may attenuate pain in fibromyalgia. Treatment with low dose naltrexone may be an effective, highly tolerable and inexpensive treatment for fibromyalgia. Further controlled trials are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Low Dose, Low Energy 3d Image Guidance during Radiotherapy

    NASA Astrophysics Data System (ADS)

    Moore, C. J.; Marchant, T.; Amer, A.; Sharrock, P.; Price, P.; Burton, D.

    2006-04-01

    Patient kilo-voltage X-ray cone beam volumetric imaging for radiotherapy was first demonstrated on an Elekta Synergy mega-voltage X-ray linear accelerator. Subsequently low dose, reduced profile reconstruction imaging was shown to be practical for 3D geometric setup registration to pre-treatment planning images without compromising registration accuracy. Reconstruction from X-ray profiles gathered between treatment beam deliveries was also introduced. The innovation of zonal cone beam imaging promises significantly reduced doses to patients and improved soft tissue contrast in the tumour target zone. These developments coincided with the first dynamic 3D monitoring of continuous body topology changes in patients, at the moment of irradiation, using a laser interferometer. They signal the arrival of low dose, low energy 3D image guidance during radiotherapy itself.

  12. Response of human fibroblasts to low dose rate gamma irradiation

    SciTech Connect

    Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

    1984-11-01

    Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to ..gamma.. radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D/sub 0/) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury.

  13. Gamma regularization based reconstruction for low dose CT.

    PubMed

    Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis

    2015-09-07

    Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l0-norm and l1-norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms.

  14. Patient release criteria for low dose rate brachytherapy implants.

    PubMed

    Boyce, Dale E; Sheetz, Michael A

    2013-04-01

    A lack of consensus regarding a model governing the release of patients following sealed source brachytherapy has led to a set of patient release policies that vary from institution to institution. The U.S. Nuclear Regulatory Commission has issued regulatory guidance on patient release in NUREG 1556, Volume 9, Rev. 2, Appendix U, which allows calculation of release limits following implant brachytherapy. While the formalism presented in NUREG is meaningful for the calculation of release limits in the context of relatively high energy gamma emitters, it does not estimate accurately the effective dose equivalent for the common low dose rate brachytherapy sources Cs, I, and Pd. NUREG 1556 states that patient release may be based on patient-specific calculations as long as the calculation is documented. This work is intended to provide a format for patient-specific calculations to be used for the consideration of patients' release following the implantation of certain low dose rate brachytherapy isotopes.

  15. Responses of astrocytes in culture after low dose laser irradiation

    SciTech Connect

    Yew, D.T.; Zheng, D.R.; Au, C.; Li, W.W. )

    1990-03-01

    The effect of Helium-Neon low dose laser on astrocytes was investigated in cultures of isolated astrocytes from albino neonatal rats. The laser appeared to inhibit the growth of astrocytes as exemplified by the smaller sizes of the cells and the decreased leucine uptake in each cell after treatment. Temporary decrease in the number of mitoses was also observed, but this trend was reversed soon after. Electron microscopic studies revealed an increase in buddings from cell bodies and processes (branches) after irradiation.

  16. Role of animal studies in low-dose extrapolation

    SciTech Connect

    Fry, R.J.M.

    1981-01-01

    Current data indicate that in the case of low-LET radiation linear, extrapolation from data obtained at high doses appears to overestimate the risk at low doses to a varying degree. In the case of high-LET radiation, extrapolation from data obtained at doses as low as 40 rad (0.4 Gy) is inappropriate and likely to result in an underestimate of the risk.

  17. Secondary infertility due to use of low-dose finasteride.

    PubMed

    Şalvarci, Ahmet; Istanbulluoğlu, Okan

    2013-02-01

    Herein, we present an unusual case of secondary infertility after prolonged use of low-dose finasteride for androgenetic alopecia in a 40-year-old man. We detected sperm DNA damage in the patient. Despite such a long-term use, we observed that impairment in semen parameters and sperm DNA fragmentation index regressed after the drug was discontinued. Consequently, pregnancy occurred and resulted in live birth.

  18. Exercise and sport performance with low doses of caffeine.

    PubMed

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  19. Therapeutic rationale for low dose doxepin in insomnia patients

    PubMed Central

    Katwala, Jigar; Kumar, Ananda K; Sejpal, Jaykumar J; Terrence, Marcelle; Mishra, Manish

    2013-01-01

    Histamine is an excitatory neurotransmitter in central nervous system. It plays an important role in the regulation of the sleep-wake cycle. Antidepressant with sleep-promoting effects, for example, doxepin, promotes sleep not through a sedative action but through resynchronisation of circadian cycle. The stimulation of the H1 receptor is thought to play an important role in mediating arousal. Doxepin has a high affinity for the H1 receptor, making it a selective H1 antagonist at low dose and it has been shown to display sedating properties. Compared to other sedative antidepressant, low dose doxepin is the only tricyclic drug which has been evaluated by well-designed, randomised, double blind, placebo controlled studies in both adult and elderly patients. Doxepin is not designated as controlled substance/unscheduled drugs and thus may be of special advantage to use in patients with a history of substance abuse. Hence, well-documented therapeutic efficacy, tolerability and lack of important adverse effects make the low dose doxepin as a unique, rational drug for the treatment of insomnia in adult and elderly patients.

  20. Low-dose dasatinib rescues cardiac function in Noonan syndrome

    PubMed Central

    Yi, Jae-Sung; Huang, Yan; Kwaczala, Andrea T.; Kuo, Ivana Y.; Ehrlich, Barbara E.; Campbell, Stuart G.; Giordano, Frank J.; Bennett, Anton M.

    2016-01-01

    Noonan syndrome (NS) is a common autosomal dominant disorder that presents with short stature, craniofacial dysmorphism, and cardiac abnormalities. Activating mutations in the PTPN11 gene encoding for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) causes approximately 50% of NS cases. In contrast, NS with multiple lentigines (NSML) is caused by mutations that inactivate SHP2, but it exhibits some overlapping abnormalities with NS. Protein zero-related (PZR) is a SHP2-binding protein that is hyper-tyrosyl phosphorylated in the hearts of mice from NS and NSML, suggesting that PZR and the tyrosine kinase that catalyzes its phosphorylation represent common targets for these diseases. We show that the tyrosine kinase inhibitor, dasatinib, at doses orders of magnitude lower than that used for its anticancer activities inhibited PZR tyrosyl phosphorylation in the hearts of NS mice. Low-dose dasatinib treatment of NS mice markedly improved cardiomyocyte contractility and functionality. Remarkably, a low dose of dasatinib reversed the expression levels of molecular markers of cardiomyopathy and reduced cardiac fibrosis in NS and NSML mice. These results suggest that PZR/SHP2 signaling is a common target of both NS and NSML and that low-dose dasatinib may represent a unifying therapy for the treatment of PTPN11-related cardiomyopathies. PMID:27942593

  1. MELODI: the 'Multidisciplinary European Low-Dose Initiative'.

    PubMed

    Belli, M; Salomaa, S; Ottolenghi, A

    2011-02-01

    The importance of research to reduce uncertainties in risk assessment of low and protracted exposures is now recognised globally. In Europe a new initiative, called 'Multidisciplinary European LOw Dose Initiative' (MELODI), has been proposed by a 'European High Level and Expert Group on low-dose risk research' (www.hleg.de), aimed at integrating national and EC (Euratom) efforts. Five national organisations: BfS (DE), CEA (FR), IRSN (FR), ISS (IT) and STUK (FI), with the support of the EC, have initiated the creation of MELODI by signing a letter of intent. In the forthcoming years, MELODI will integrate in a step-by-step approach EU institutions with significant programmes in the field and will be open to other scientific organisations and stakeholders. A key role of MELODI is to develop and maintain over time a strategic research agenda (SRA) and a road map of scientific priorities within a multidisciplinary approach, and to transfer the results for the radiation protection system. Under the coordination of STUK a network has been proposed in the 2009 Euratom Programme, called DoReMi (Low-Dose Research towards Mutidisciplinary Integration), which can help the integration process within the MELODI platform. DoReMi and the First MELODI Open Workshop, organised by BfS in September 2009, are now important inputs for the European SRA.

  2. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

    SciTech Connect

    Schoenfeld, Gordon O.; Amdur, Robert J. . E-mail: amdurrj@ufl.edu; Schmalfuss, Ilona M.; Morris, Christopher G.; Keole, Sameer R.; Mendenhall, William M.; Marcus, Robert B.

    2006-06-01

    Purpose: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Methods and Materials: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. Results: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Conclusions: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element.

  3. Biological-Based Modeling of Low Dose Radiation Risks

    SciTech Connect

    Scott, Bobby R., Ph.D.

    2006-11-08

    The objective of this project was to refine a biological-based model (called NEOTRANS2) for low-dose, radiation-induced stochastic effects taking into consideration newly available data, including data on bystander effects (deleterious and protective). The initial refinement led to our NEOTRANS3 model which has undergone further refinement (e.g., to allow for differential DNA repair/apoptosis over different dose regions). The model has been successfully used to explain nonlinear dose-response curves for low-linear-energy-transfer (LET) radiation-induced mutations (in vivo) and neoplastic transformation (in vitro). Relative risk dose-response functions developed for neoplastic transformation have been adapted for application to cancer relative risk evaluation for irradiated humans. Our low-dose research along with that conducted by others collectively demonstrate the following regarding induced protection associated with exposure to low doses of low-LET radiation: (1) protects against cell killing by high-LET alpha particles; (2) protects against spontaneous chromosomal damage; (3) protects against spontaneous mutations and neoplastic transformations; (4) suppresses mutations induced by a large radiation dose even when the low dose is given after the large dose; (5) suppresses spontaneous and alpha-radiation-induced cancers; (6) suppresses metastasis of existing cancer; (7) extends tumor latent period; (8) protects against diseases other than cancer; and (9) extends life expectancy. These forms of radiation-induced protection are called adapted protection as they relate to induced adaptive response. Thus, low doses and dose rates of low-LET radiation generally protect rather than harm us. These findings invalidate the linear not threshold (LNT) hypothesis which is based on the premise that any amount of radiation is harmful irrespective of its type. The hypothesis also implicates a linear dose-response curve for cancer induction that has a positive slope and no

  4. Induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia: effects of low doses and low dose rates

    SciTech Connect

    van Buul, P.P.; Richardson, J.F. Jr.; Goudzwaard, J.H.

    1986-01-01

    The induction of reciprocal translocation in rhesus monkey spermatogonial stem cells was studied following exposure to low doses of acute X rays (0.25 Gy, 300 mGy/min) or to low-dose-rate X rays (1 Gy, 2 mGy/min) and gamma rays (1 Gy, 0.2 mGy/min). The results obtained at 0.25 Gy of X rays fitted exactly the linear extrapolation down from the 0.5 and 1.0 Gy points obtained earlier. Extension of X-ray exposure reduced the yield of translocations similar to that in the mouse by about 50%. The reduction to 40% of translocation rate after chronic gamma exposure was clearly less than the value of about 80% reported for the mouse over the same range of dose rates. Differential cell killing with ensuing differential elimination of aberration-carrying cells is the most likely explanation for the differences between mouse and monkey.

  5. Arsenic, mode of action at biologically plausible low doses: What are the implications for low dose cancer risk?

    SciTech Connect

    Snow, Elizabeth T. . E-mail: esnow@deakin.edu.au; Sykora, Peter; Durham, Troy R.; Klein, Catherine B.

    2005-09-01

    Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to {<=}60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 {mu}M arsenite (As{sup III}) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase {beta} and DNA ligase I. At higher concentrations (> 10 {mu}M), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

  6. Animal Studies of Residual Hematopoietic and Immune System Injury from Low Dose/Low Dose Rate Radiation and Heavy Metals.

    DTIC Science & Technology

    1998-09-01

    accidents and industrial accidents (e.g., Chernobyl ) who receive high doses of radiation over a relatively short period of time, there are thousands of...several years after exposure may have been terminated. Examples of such groups include those affected by the fallout near Chernobyl , those living near...cohorts (e.g., Chernobyl victims) particular damage from low dose irradiation, especially membrane damage and mismatched DNA repair. Dosimetric Problems

  7. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

    PubMed

    Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

    2016-04-01

    A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  8. European low-dose radiation risk research strategy: future of research on biological effects at low doses.

    PubMed

    Salomaa, Sisko; Averbeck, Dietrich; Ottolenghi, Andrea; Sabatier, Laure; Bouffler, Simon; Atkinson, Michael; Jourdain, Jean-René

    2015-04-01

    In 2009, the European High Level and Expert Group identified key policy and scientific questions to be addressed through a strategic research agenda for low-dose radiation risk. This initiated the establishment of a European Research Platform, called MELODI (Multidisciplinary European Low Dose Research Initiative). In 2010, the DoReMi Network of Excellence was launched in the Euratom 7th Framework Programme. DoReMi has acted as an operational tool for the sustained development of the MELODI platform during its early years. A long-term Strategic Research Agenda for European low-dose radiation risk research has been developed by MELODI. Strategic planning of DoReMi research activities is carried out in close collaboration with MELODI. The research priorities for DoReMi are designed to focus on objectives that are achievable within the 6-y lifetime of the project and that are in areas where stimulus and support can help progress towards the longer-term strategic objectives.

  9. Comparison of two different strategies for human monocyte subsets gating within the large-scale prospective CARE FOR HOMe Study.

    PubMed

    Zawada, Adam M; Fell, Lisa H; Untersteller, Kathrin; Seiler, Sarah; Rogacev, Kyrill S; Fliser, Danilo; Ziegler-Heitbrock, Loems; Heine, Gunnar H

    2015-08-01

    Monocytes are heterogeneous cells consisting of (at least) three subsets: classical, intermediate, and nonclassical monocytes. Correct enumeration of cell counts necessitates well-defined gating strategies, which are essentially based upon CD14 and CD16 expression. For the delineation of intermediate from nonclassical monocytes, a "rectangular gating (RG) strategy" and a "trapezoid gating (TG) strategy" have been proposed. We compared the two gating strategies in a well-defined clinical cohort of patients with chronic kidney disease (CKD). Within the ongoing CARE FOR HOMe study, monocyte subsets were reanalyzed in 416 CKD patients, who were followed 3.6 ± 1.6 years for the occurrence of a cardiovascular event. Gating was performed by either RG or TG. We analyzed the expression of surface markers, and compared the predictive role of cell counts of monocyte subsets, as defined by RG and TG, respectively. With both gating strategies, higher intermediate monocyte counts predicted the cardiovascular endpoint in Kaplan-Meier analyses (P < 0.001 with RG; P < 0.001 with TG). After correction for confounders, intermediate monocyte counts remained independent predictors in Cox-Regression analyses (HR = 1.013 [95% CI: 1.006-1.020; P < 0.001] with RG; HR = 1.015 [95% CI: 1.006-1.024; P = 0.001] with TG). NRI was 3.9% when reclassifying patients from quartiles of intermediate monocyte counts with RG strategy toward quartiles of intermediate monocytes counts with TG strategy. In expression analysis, those monocytes which are defined as intermediate monocytes by the RG strategy and as nonclassical monocytes by the TG strategy share characteristics of both subsets. In conclusion, intermediate monocytes were independent predictors of cardiovascular outcome irrespective of the applied gating strategy. Future studies should aim to identify markers that allow for an unequivocal definition of intermediate monocytes, which may further improve their power to

  10. Evaluation of in vivo low-dose mouse irradiation system

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Kim, H. J.; Kim, H.; Kye, Y.-U.; Kim, J. K.; Son, T. G.; Lee, M. W.; Jeong, D. H.; Yang, K. M.; Nam, S.-H.; Kang, Y.-R.

    2016-03-01

    This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

  11. Low doses and thresholds in genotoxicity: from theories to experiments.

    PubMed

    Zito, R

    2001-09-01

    The absence of threshold in the action of genotoxic carcinogens was theoretically postulated more than thirty years ago, but continuously challenged for scientific and practical reasons. The direct experimental demonstration of the presence of a threshold for genotoxic damage is precluded by the insufficient sensitivity of the biological methods presently available. In the last twenty years the sensitivity of the methods for quantitative determination of the DNA adducts of the carcinogens was enormously improved, demonstrating linearity of the dose/adducts pattern over dose intervals of more than million-fold. The arguments more often advanced for the presence of a threshold for genotoxic carcinogens were mainly based on the action of intracellular scavengers, detoxification enzymes and repair systems, being able to block completely the genotoxic carcinogens at very low doses. This hypothesis is disproved by the constant presence of DNA adducts at extremely low doses of different carcinogens, whatever their chemical structure can be. On the other hand if genotoxic damage results from damage to proteins involved in cell division, like tubulin, there is a threshold dose for such genotoxic effects. The detailed knowledge of the genotoxicity mechanism is therefore needed for a sound carcinogenic risk assessment. Most of the genotoxic carcinogens, or their metabolites, damage directly the DNA. In this case the absence of threshold must be assumed, not only for theoretical reasons, but for the results of the experiments quantitatively relating DNA damage and very low doses of carcinogens. For the sake of clarity the "adjectivated" thresholds, like practical pragmatic, apparent and operational, must disappear from documents analysing the carcinogenic risk.

  12. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    SciTech Connect

    Yuan, Zhi-Min

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

  13. Water Intoxication Following Low-Dose Intravenous Cyclophosphamide

    PubMed Central

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung

    2007-01-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention. PMID:24459501

  14. Water intoxication following low-dose intravenous cyclophosphamide.

    PubMed

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung; Kim, Gheun-Ho

    2007-06-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention.

  15. Mild Hypothermia in a Child with Low-Dose Risperidone.

    PubMed

    Grau, Katharina; Plener, Paul L; Gahr, Maximilian; Denzer, Christian; Freudenmann, Roland W

    2017-07-01

    Risperidone is a widely used, second-generation antipsychotic approved for treating schizophrenia as well as for treating aggression in children and adolescents with mental retardation. The substance has a well-established risk profile including alterations of body temperature. Apart from hyperthermia with and without full-blown malignant neuroleptic syndrome, low body temperatures (hypothermia) have also been reported anecdotally, usually appearing in the context of comedication. Here, we report a case of hypothermia associated with a low-dose risperidone monotherapy in a child.

  16. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    PubMed

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  17. Low-dose insulin treatment of hyperosmolar diabetic coma.

    PubMed

    Wright, A D; Walsh, C H; Fitzgerald, M G; Malins, J M

    1981-09-01

    The effect of low-dose hourly i.m. injections of insulin has been studied in the treatment of 17 episodes of hyperosmolar non-ketoacidotic diabetic coma compared with 26 episode of hyperosmolar ketoacidosis occurring in patients over 40 years of age. The fall in blood sugar was satisfactory in the majority of episodes of both types of coma and there was no evidence that patients with hyperosmolar non-ketoacidotic coma were more sensitive to insulin. The excess mortality in the non-ketotic group (47%) compared with the ketoacidotic group (16%) was not due to uncontrolled diabetes.

  18. Low-dose insulin treatment of hyperosmolar diabetic coma.

    PubMed Central

    Wright, A. D.; Walsh, C. H.; Fitzgerald, M. G.; Malins, J. M.

    1981-01-01

    The effect of low-dose hourly i.m. injections of insulin has been studied in the treatment of 17 episodes of hyperosmolar non-ketoacidotic diabetic coma compared with 26 episode of hyperosmolar ketoacidosis occurring in patients over 40 years of age. The fall in blood sugar was satisfactory in the majority of episodes of both types of coma and there was no evidence that patients with hyperosmolar non-ketoacidotic coma were more sensitive to insulin. The excess mortality in the non-ketotic group (47%) compared with the ketoacidotic group (16%) was not due to uncontrolled diabetes. PMID:6799948

  19. Optimized source selection for intracavitary low dose rate brachytherapy

    SciTech Connect

    Nurushev, T.; Kim, Jinkoo

    2005-05-01

    A procedure has been developed for automating optimal selection of sources from an available inventory for the low dose rate brachytherapy, as a replacement for the conventional trial-and-error approach. The method of optimized constrained ratios was applied for clinical source selection for intracavitary Cs-137 implants using Varian BRACHYVISION software as initial interface. However, this method can be easily extended to another system with isodose scaling and shaping capabilities. Our procedure provides optimal source selection results independent of the user experience and in a short amount of time. This method also generates statistics on frequently requested ideal source strengths aiding in ordering of clinically relevant sources.

  20. Harderian Gland Tumorigenesis: Low-Dose and LET Response

    SciTech Connect

    Chang, Polly Y.; Cucinotta, Francis A.; Bjornstad, Kathleen A.; Bakke, James; Rosen, Chris J.; Du, Nicholas; Fairchild, David G.; Cacao, Eliedonna; Blakely, Eleanor A.

    2016-04-19

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  1. Low-dose fixed-target serial synchrotron crystallography

    PubMed Central

    Owen, Robin L.; Axford, Danny; Sherrell, Darren A.; Kuo, Anling; Ernst, Oliver P.; Schulz, Eike C.; Miller, R. J. Dwayne; Mueller-Werkmeister, Henrike M.

    2017-01-01

    The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption. PMID:28375148

  2. Low-dose fixed-target serial synchrotron crystallography.

    PubMed

    Owen, Robin L; Axford, Danny; Sherrell, Darren A; Kuo, Anling; Ernst, Oliver P; Schulz, Eike C; Miller, R J Dwayne; Mueller-Werkmeister, Henrike M

    2017-04-01

    The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.

  3. Lung cancer screening with low-dose computed tomography.

    PubMed

    Chiles, Caroline

    2014-01-01

    Current guidelines endorse low-dose computed tomography (LDCT) screening for smokers and former smokers aged 55 to 74, with at least a 30-pack-year smoking history. Adherence to published algorithms for nodule follow-up is strongly encouraged. Future directions for screening research include risk stratification for selection of the screening population and improvements in the diagnostic follow-up for indeterminate pulmonary nodules. Screening for lung cancer with LDCT has revealed that there are indolent lung cancers that may not be fatal. More research is necessary if the risk-benefit ratio in lung cancer screening is to be maximized. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Low-dose docetaxel, estramustine and prednisolone combination chemotherapy for castration-resistant prostate cancer

    PubMed Central

    NAKANO, MAYURA; SHOJI, SUNAO; HIGURE, TARO; KAWAKAMI, MASAYOSHI; TOMONAGA, TETSURO; TERACHI, TOSHIRO; UCHIDA, TOYOAKI

    2016-01-01

    The objective of this study was to report our experience with weekly low-dose docetaxel (DOC) chemotherapy for patients with castration-resistant prostate cancer (CRPC). From 2007 to 2014, 39 consecutive patients received weekly low-dose DOC; the oncological effectiveness, side effects and tolerability were prospectively analyzed. The median patient age, serum prostate-specific antigen (PSA) level and Gleason score at diagnosis of prostate cancer were 71 years (range, 55–83 years), 187 ng/ml (range, 2.0–1711 ng/ml) and 8 (range, 5–10), respectively. The median number of cycles of DOC was 7 (range, 1–45 cycles). Of the 39 patients, the PSA level decreased by >50% in 13 (33%). In the multivariate analysis of prediction of patient overall survival, a decrease of the PSA level to <50% was a significant predictor (hazard ratio = 6.913; 95% confidence interval: 1.147–41.669; P=0.035). The median cancer-specific overall survival from the diagnosis of CRPC was 16.7 months (range, 2–54 months). Grade 3 toxicities were observed in 5 patients (13%); specifically, limb edema, nausea and hepatic disorders were detected in 2 (5%), 2 (5%) and 1 patient (3%), respectively. Treatment-related death (grade 5) occurred in 1 patient due to interstitial pneumonia after two courses of chemotherapy. The chemotherapy was completed in the majority of the patients (n=37, 94.8%) in the outpatient department, without interruption. These findings suggest that weekly low-dose DOC is feasible and safe for selected patients with CRPC, without treament with novel agents, such as abiraterone, enzalutamide and cabazitaxel. PMID:27284427

  5. Low-dose endotoxemia and human neuropsychological functions.

    PubMed

    Krabbe, Karen Suárez; Reichenberg, Abraham; Yirmiya, Raz; Smed, Annelise; Pedersen, Bente Klarlund; Bruunsgaard, Helle

    2005-09-01

    Epidemiological data demonstrate an association between systemic low-grade inflammation defined as 2- to 3-fold increases in circulating inflammatory mediators and age-related decline in cognitive function. However, it is not known whether small elevations of circulating cytokine levels cause direct effects on human neuropsychological functions. We investigated changes in emotional, cognitive, and inflammatory parameters in an experimental in vivo model of low-grade inflammation. In a double-blind crossover study, 12 healthy young males completed neuropsychological tests before as well as 1.5, 6, and 24 h after an intravenous injection of Escherichia coli endotoxin (0.2 ng/kg) or saline in two experimental sessions. Endotoxin administration had no effect on body temperature, cortisol levels, blood pressure or heart rate, but circulating levels of tumor necrosis factor (TNF) and interleukin (IL)-6 increased 2- and 7-fold, respectively, reaching peak values at 3 h, whereas soluble TNF-receptors and IL-1 receptor antagonist peaked at 4.5 h. The neutrophil count increased and the lymphocyte count declined. In this model, low-dose endotoxemia did not affect cognitive performance significantly but declarative memory performance was inversely correlated with cytokine increases. In conclusion, our findings demonstrate a negative association between circulating IL-6 and memory functions during very low-dose endotoxemia independently of physical stress symptoms, and the hypothalamo-pituitary-adrenal axis.

  6. Transfer of Low Dose Aspirin Into Human Milk.

    PubMed

    Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

    2017-05-01

    Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

  7. Low-dose computed tomography to diagnose fetal bone dysplasias.

    PubMed

    Montoya Filardi, A; Guasp Vizcaíno, M; Gómez Fernández-Montes, J; Llorens Salvador, R

    We present a case of cleidocranial dysplasia diagnosed by low-dose fetal computed tomography (CT) in the 25th week of gestation. Severe bone dysplasia was suspected because of the fetus' low percentile in long bones length and the appearance of craniosynostosis on sonography. CT found no abnormalities incompatible with life. The effective dose was 5 mSv, within the recommended range for this type of examination. Low-dose fetal CT is a new technique that makes precision study of the bony structures possible from the second trimester of pregnancy. In Spain, abortion is legal even after the 22nd week of gestation in cases of severe fetal malformations. Therefore, in cases in which severe bone dysplasia is suspected, radiologists must know the strategies for reducing the dose of radiation while maintaining sufficient diagnostic quality, and they must also know which bony structures to evaluate. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Non linear processes modulated by low doses of radiation exposure

    NASA Astrophysics Data System (ADS)

    Mariotti, Luca; Ottolenghi, Andrea; Alloni, Daniele; Babini, Gabriele; Morini, Jacopo; Baiocco, Giorgio

    The perturbation induced by radiation impinging on biological targets can stimulate the activation of several different pathways, spanning from the DNA damage processing to intra/extra -cellular signalling. In the mechanistic investigation of radiobiological damage this complex “system” response (e.g. omics, signalling networks, micro-environmental modifications, etc.) has to be taken into account, shifting from a focus on the DNA molecule solely to a systemic/collective view. An additional complication comes from the finding that the individual response of each of the involved processes is often not linear as a function of the dose. In this context, a systems biology approach to investigate the effects of low dose irradiations on intra/extra-cellular signalling will be presented, where low doses of radiation act as a mild perturbation of a robustly interconnected network. Results obtained through a multi-level investigation of both DNA damage repair processes (e.g. gamma-H2AX response) and of the activation kinetics for intra/extra cellular signalling pathways (e.g. NFkB activation) show that the overall cell response is dominated by non-linear processes - such as negative feedbacks - leading to possible non equilibrium steady states and to a poor signal-to-noise ratio. Together with experimental data of radiation perturbed pathways, different modelling approaches will be also discussed.

  9. Low doses of neutrons induce changes in gene expression

    SciTech Connect

    Woloschak, G.E.; Chang-Liu, C.M.; Panozzo, J.; Libertin, C.R.

    1993-06-01

    Studies were designed to identify genes induced following low-dose neutron but not following {gamma}-ray exposure in fibroblasts. Our past work had shown differences in the expression of {beta}-protein kinase C and c-fos genes, both being induced following {gamma}-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not {gamma}-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to {gamma} rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  10. Adaptively Tuned Iterative Low Dose CT Image Denoising

    PubMed Central

    Hashemi, SayedMasoud; Paul, Narinder S.; Beheshti, Soosan; Cobbold, Richard S. C.

    2015-01-01

    Improving image quality is a critical objective in low dose computed tomography (CT) imaging and is the primary focus of CT image denoising. State-of-the-art CT denoising algorithms are mainly based on iterative minimization of an objective function, in which the performance is controlled by regularization parameters. To achieve the best results, these should be chosen carefully. However, the parameter selection is typically performed in an ad hoc manner, which can cause the algorithms to converge slowly or become trapped in a local minimum. To overcome these issues a noise confidence region evaluation (NCRE) method is used, which evaluates the denoising residuals iteratively and compares their statistics with those produced by additive noise. It then updates the parameters at the end of each iteration to achieve a better match to the noise statistics. By combining NCRE with the fundamentals of block matching and 3D filtering (BM3D) approach, a new iterative CT image denoising method is proposed. It is shown that this new denoising method improves the BM3D performance in terms of both the mean square error and a structural similarity index. Moreover, simulations and patient results show that this method preserves the clinically important details of low dose CT images together with a substantial noise reduction. PMID:26089972

  11. Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation.

    PubMed

    Webster, Lynn R

    2007-08-01

    Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. To evaluate the safety and efficacy of the oxycodone/naltrexone combination, three clinical studies have been conducted, one in healthy volunteers and the other two in patients with chronic pain. The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.

  12. [Low dose naltrexone in the treatment of dissociative symptoms].

    PubMed

    Pape, W; Wöller, W

    2015-03-01

    Following the hypothesis that blocking opioid receptors leads to a decline in opiate-modulated dissociative phenomena, experiences with naltrexone as medication for dissociative symptoms have been gained since 1999 (mainly in doses of 25-100 mg/day). In this study patients with severe trauma-related and dissociative disorders were treated with naltrexone in doses of 2-6 mg/day (0.06 mg/kg body weight). The low dose treatment with naltrexone proved to be effective whereby 11 out of 15 patients reported immediate positive effects and 7 described a lasting helpful effect. The majority of patients who felt positive effects reported a clearer perception of both their surroundings and their inner life. Assessment of reality and dealing with it improved as did the perception of their own body and affects as well as self-regulation. The treatment was very low in side effects. Treatment with low-dose naltrexone may be a helpful element in the treatment of patients with complex posttraumatic stress disorder. However, it has to be realized that the decrease of dissociation may lead patients to a not yet resolvable challenge, in as much as dissociation had previously been a necessary mechanism of self-protection.

  13. Low dose scatter correction for digital chest tomosynthesis

    NASA Astrophysics Data System (ADS)

    Inscoe, Christina R.; Wu, Gongting; Shan, Jing; Lee, Yueh Z.; Zhou, Otto; Lu, Jianping

    2015-03-01

    Digital chest tomosynthesis (DCT) provides superior image quality and depth information for thoracic imaging at relatively low dose, though the presence of strong photon scatter degrades the image quality. In most chest radiography, anti-scatter grids are used. However, the grid also blocks a large fraction of the primary beam photons requiring a significantly higher imaging dose for patients. Previously, we have proposed an efficient low dose scatter correction technique using a primary beam sampling apparatus. We implemented the technique in stationary digital breast tomosynthesis, and found the method to be efficient in correcting patient-specific scatter with only 3% increase in dose. In this paper we reported the feasibility study of applying the same technique to chest tomosynthesis. This investigation was performed utilizing phantom and cadaver subjects. The method involves an initial tomosynthesis scan of the object. A lead plate with an array of holes, or primary sampling apparatus (PSA), was placed above the object. A second tomosynthesis scan was performed to measure the primary (scatter-free) transmission. This PSA data was used with the full-field projections to compute the scatter, which was then interpolated to full-field scatter maps unique to each projection angle. Full-field projection images were scatter corrected prior to reconstruction. Projections and reconstruction slices were evaluated and the correction method was found to be effective at improving image quality and practical for clinical implementation.

  14. The Effects of ELDRS at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al

    2011-01-01

    We present results on the effects on ELDRS at dose rates of 10, 5, 1, and 0.5 mrad(Si)/s for a variety of radiation hardened and commercial devices. We observed low dose rate enhancement below 10 mrad(Si)/s in several different parts. The magnitudes of the dose rate effects vary. The TL750L, a commercial voltage regulator, showed dose rate dependence in the functional failures, with initial failures occurring after 10 krad(Si) for the parts irradiated at 0.5 mrad(Si)/s. The RH1021 showed an increase in low dose rate enhancement by 2x at 5 mrad(Si)/s relative to 8 mrad(Si)/s and high dose rate, and parametric failure after 100 krad(Si). Additionally the ELDRS-free devices, such as the LM158 and LM117, showed evidence of dose rate sensitivity in parametric degradations. Several other parts also displayed dose rate enhancement, with relatively lower degradations up to approx.15 to 20 krad(Si). The magnitudes of the dose rate enhancement will likely increase in significance at higher total dose levels.

  15. Low doses of neutrons induce changes in gene expression

    SciTech Connect

    Woloschak, G.E.; Chang-Liu, C.M. ); Panozzo, J.; Libertin, C.R. )

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following [gamma]-ray exposure in fibroblasts. Our past work had shown differences in the expression of [beta]-protein kinase C and c-fos genes, both being induced following [gamma]-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not [gamma]-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to [gamma] rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  16. Sinogram smoothing with bilateral filtering for low-dose CT

    NASA Astrophysics Data System (ADS)

    Yu, Lifeng; Manduca, Armando; Trzasko, Joshua D.; Khaylova, Natalia; Kofler, James M.; McCollough, Cynthia M.; Fletcher, Joel G.

    2008-03-01

    Optimal noise control is critical for dose reduction in CT. In this work, we investigated the use of a locally-adaptive method for noise reduction in low-dose CT. This method is based upon bilateral filtering, which smoothes the projection data using a weighted average in a local neighborhood, where the weights are determined according to both the spatial proximity and intensity similarity between the center pixel and the neighboring pixels. This filtering is locally adaptive and can preserve important edge information in the sinogram, thus without significantly sacrificing the spatial resolution. It is closely related to anisotropic diffusion, but is significantly faster. More importantly, a CT noise model can be readily incorporated in the filtering and denoising process. We have evaluated the noise-resolution properties of the bilateral filtering in a phantom study and a preliminary patient study with contrast-enhanced abdominal CT exams. The results demonstrated that bilateral filtering can achieve a better noise-resolution tradeoff than a series of commercial reconstruction kernels. This improvement on noise-resolution properties can be used for improving the image quality in low-dose CT and can also be translated to substantial dose reduction.

  17. Adaptively Tuned Iterative Low Dose CT Image Denoising.

    PubMed

    Hashemi, SayedMasoud; Paul, Narinder S; Beheshti, Soosan; Cobbold, Richard S C

    2015-01-01

    Improving image quality is a critical objective in low dose computed tomography (CT) imaging and is the primary focus of CT image denoising. State-of-the-art CT denoising algorithms are mainly based on iterative minimization of an objective function, in which the performance is controlled by regularization parameters. To achieve the best results, these should be chosen carefully. However, the parameter selection is typically performed in an ad hoc manner, which can cause the algorithms to converge slowly or become trapped in a local minimum. To overcome these issues a noise confidence region evaluation (NCRE) method is used, which evaluates the denoising residuals iteratively and compares their statistics with those produced by additive noise. It then updates the parameters at the end of each iteration to achieve a better match to the noise statistics. By combining NCRE with the fundamentals of block matching and 3D filtering (BM3D) approach, a new iterative CT image denoising method is proposed. It is shown that this new denoising method improves the BM3D performance in terms of both the mean square error and a structural similarity index. Moreover, simulations and patient results show that this method preserves the clinically important details of low dose CT images together with a substantial noise reduction.

  18. Low-dose growth hormone supplementation increases clinical pregnancy rate in poor responders undergoing in vitro fertilisation.

    PubMed

    Lattes, Karinna; Brassesco, Mario; Gomez, Manuel; Checa, Miguel A

    2015-07-01

    Poor ovarian response (POR) often means low success rates after in vitro fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH) supplementation in pregnancy rates in poor responders in a prospective, self-controlled study of 64 poor responders to previous IVF cycles, who failed to achieve pregnancy and were supplemented with low-doses of GH in a subsequent cycle using the same gonadotropin dose and protocol. Our primary endpoint was the clinical pregnancy rate (CPR), considering secondary endpoints, the number of retrieved oocytes, embryos, embryo quality and the proportion of cycles with embryo transfer. CPR in the GH group was 34.4%. Significant differences were observed for the GH group both in the number of top quality embryos (0.64 ± 0.88 versus 1.03 ± 1.17, p < 0.05) and cryopreserved embryos (0.3 ± 0.81 versus 0.85 ± 1.49, p < 0.05). This is, to our knowledge, the first clinical trial to use a low dose of GH as a supplement for IVF in POR patients. Despite this low dose, we achieved excellent success rates in patients with a very poor prognosis, at a reasonable cost and without side effects, which makes this a safe and cost-effective alternative.

  19. Recurrent miscarriage associated with antiphospholipid antibodies: prophylactic treatment with low-dose aspirin and fish oil derivates.

    PubMed

    Carta, G; Iovenitti, P; Falciglia, K

    2005-01-01

    The aim of this study was to evaluate the effects of two different prophylactic protocols, low-dose aspirin and fish oil derivates, in the treatment of patients with recurrent pregnancy loss associated with antiphospholipid antibodies (APA) syndrome. A prospective study included 30 patients who were alternately assigned to treatment. Each patient had had at least two consecutive spontaneous abortions, positive antiphospholipid antibodies on two occasions, and a complete evaluation. Among patients treated with low-dose aspirin, 12 out of the 15 (80%) pregnancies ended in live births. In the fish oil derivate group 11 out of the 15 (73.3%) ended in live births (p > 0.05). There were no significant differences between the low-dose aspirin and the fish oil derivates groups with respect to gestational age at delivery (39.9 +/- 0.4 vs 39 +/- 1.5 weeks), fetal birth weight (3290 +/- 200g vs 3560 +/- 100 g), number of cesarean sections (25% vs 18%), or complications. There were no significant differences in terms of pregnancy outcome between women with recurrent pregnancy loss associated with APA syndrome treated with low-dose aspirin or fish oil derivates.

  20. Efficacy of rebamipide for low-dose aspirin-related gastrointestinal symptoms.

    PubMed

    Mizukami, Kazuhiro; Murakami, Kazunari; Hirashita, Yuka; Hisamatsu, Akari; Ogawa, Ryo; Uchida, Masahiro; Nakagawa, Yoshifumi; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio

    2012-11-01

    Gastrointestinal symptoms are a problematic issue for patients who take low-dose aspirin for long time. We conducted a pilot study to investigate the efficacy of combination therapy with proton pump inhibitor and rebamipide. This was a prospective, randomized, double-blind, placebo-controlled cross-over study. All the subjects received aspirin 100 mg and omeprazole 20 mg. The subjects were divided into two groups and received either rebamipide 300 mg or placebo, which was prescribed for 4 weeks. The subjects were instructed to record their gastrointestinal symptom rating scale before the study and 1 and 4 weeks after beginning the protocol. These scores of the groups were compared before and after the treatment to evaluate the severity of their symptoms and the number of symptom items present in each group. For the subjects receiving rebamipide, the total prevalence of lower gastrointestinal symptoms was significantly different from the placebo group (p=0.0093) at week 4. No troublesome symptoms were observed in the rebamipide group. Inconclusion, the administration of rebamipide prevented the occurrence of troublesome symptoms, especially lower gastrointestinal symptoms, in patients taking aspirin and omeprazole. Rebamipide is a candidate drug for combination therapy with proton pump inhibitors to prevent low-dose aspirin-induced gastrointestinal symptoms.

  1. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery.

    PubMed

    Choi, Eun-Su; Jeong, Woo-Jin; Ahn, Soon-Hyun; Oh, Ah-Young; Jeon, Young-Tae; Do, Sang-Hwan

    2017-02-01

    We evaluated the effect of magnesium sulfate-an enhancer of neuromuscular blockade-on onset and duration of low dose of rocuronium, and on operating conditions during laryngeal microsurgery. Randomized, prospective, double-blinded study. Eighty-four patients scheduled for elective laryngeal microsurgery. Patients were randomly allocated to receive different doses of rocuronium: 0.6 mg/kg (group C, n=28), 0.45 mg/kg (group LR, n=28), or 0.45 mg/kg plus magnesium sulfate 30 mg/kg (group LM, n=28). We measured the onset time and duration of action of rocuronium, and evaluated the surgeon's satisfaction with the operating conditions. Group LR showed significantly delayed onset time (group C: 87±22 seconds, group LR: 127±47 seconds, and group LM: 89±32 seconds; P=.001) and maximal suppression than did other groups (group C: 102±30 seconds, group LR: 155±66 seconds, and group LM: 105±36 seconds; P=.002). Duration of action of rocuronium was significantly longer in group C than in other groups (group C: 39±7 minutes, group LR: 28±8 minutes, group LRM: 31±8 minutes; P<.001). Laryngoscope placement score (P=.002), surgeon's satisfaction (P=.005), and sore throat (P=.035) were significantly worse in group LR. Magnesium sulfate 30 mg/kg accelerated the onset and improved operating conditions of low-dose rocuronium without prolongation of action. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The effect of intravenous low dose ketamine for reducing postoperative sore throat.

    PubMed

    Park, Sun Young; Kim, Sang Hyun; Noh, Jung Il; Lee, Su Myoung; Kim, Mun Gyu; Kim, Sang Ho; Ok, Si Young; Kim, Soon Im

    2010-07-01

    This study was performed to evaluate the effectiveness of intravenous low dose ketamine for reducing the incidence and severity of postoperative sore throat (POST). This was a prospective, randomized, double-blind clinical trial. The study population consisted of 70 patients between 20 and 70 years old who were classified as American Society of Anesthesiologists I-II and were scheduled for elective laparoscopic cholecystectomy. The patients were divided randomly into two groups. Patients in the ketamine group received an intravenous injection of 0.5 mg/kg of ketamine just before induction, followed by 10 microg/kg/min throughout the operation. Patients in the control group received intravenous saline instead of ketamine. The patients were interviewed 1, 6, and 24 h after the operation. The incidence and severity of POST were recorded. No significant differences in the incidence and severity of POST during the 24 h after the operation were found between the two groups (21/31 in the ketamine group vs. 26/34 in the control group, P = 0.398). Intravenous injection of low dose ketamine was not effective for reducing POST.

  3. The effect of intravenous low dose ketamine for reducing postoperative sore throat

    PubMed Central

    Kim, Sang Hyun; Noh, Jung Il; Lee, Su Myoung; Kim, Mun Gyu; Kim, Sang Ho; Ok, Si Young; Kim, Soon Im

    2010-01-01

    Background This study was performed to evaluate the effectiveness of intravenous low dose ketamine for reducing the incidence and severity of postoperative sore throat (POST). Methods This was a prospective, randomized, double-blind clinical trial. The study population consisted of 70 patients between 20 and 70 years old who were classified as American Society of Anesthesiologists I-II and were scheduled for elective laparoscopic cholecystectomy. The patients were divided randomly into two groups. Patients in the ketamine group received an intravenous injection of 0.5 mg/kg of ketamine just before induction, followed by 10 µg/kg/min throughout the operation. Patients in the control group received intravenous saline instead of ketamine. The patients were interviewed 1, 6, and 24 h after the operation. The incidence and severity of POST were recorded. Results No significant differences in the incidence and severity of POST during the 24 h after the operation were found between the two groups (21/31 in the ketamine group vs. 26/34 in the control group, P = 0.398). Conclusions Intravenous injection of low dose ketamine was not effective for reducing POST. PMID:20651994

  4. Low-dose (2.5 mg/day) finasteride treatment in hirsutism.

    PubMed

    Bayram, F; Müderris, I; Güven, M; Ozçelik, B; Keleştimur, F

    2003-10-01

    This study was performed to confirm the therapeutic effects of low-dose, (2.5 mg/day) finasteride in hirsute women. Our study was a non-randomized prospective clinical trial. Twenty-nine patients with hirustism were included in the study. The patients received 2.5 mg finasteride once a day over a period of 12 months. Follicle stimulating hormone, luteinizing hormone, sex hormone binding globulin, 17 alpha-hydroxyprogesterone, estradiol, androstenedione, total and free testosterone, dehydroepiandrosterone sulfate levels and hirsutism scores were determined in all patients before treatment and at every 6 months during the therapy. The hirsutism score decreased from a mean of 18.4 +/- 4.6 to 8.4 +/- 4.2 during the study. The per cent reduction in hirsutism score (mean +/- SD) at 6 and 12 months was 29.2 +/- 14.5 and 55.7 +/- 14.9%, respectively. There were no significant differences in any of the hormone levels and no serious side-effects were observed during the treatment. In conclusion, low-dose finasteride (2.5 mg/day) is a cost-effective, well-tolerated therapeutic agent without significant abnormal biochemical findings and can be used in place of high-dose (5 mg/day) finasteride in the treatment of hirsutism.

  5. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients.

    PubMed

    Tschirch, Frank T C; Göpfert, Kerstin; Fröhlich, Johannes M; Brunner, Genevieve; Weishaupt, Dominik

    2007-06-01

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form.

  6. Heart region segmentation from low-dose CT scans: an anatomy based approach

    NASA Astrophysics Data System (ADS)

    Reeves, Anthony P.; Biancardi, Alberto M.; Yankelevitz, David F.; Cham, Matthew D.; Henschke, Claudia I.

    2012-02-01

    Cardiovascular disease is a leading cause of death in developed countries. The concurrent detection of heart diseases during low-dose whole-lung CT scans (LDCT), typically performed as part of a screening protocol, hinges on the accurate quantification of coronary calcification. The creation of fully automated methods is ideal as complete manual evaluation is imprecise, operator dependent, time consuming and thus costly. The technical challenges posed by LDCT scans in this context are mainly twofold. First, there is a high level image noise arising from the low radiation dose technique. Additionally, there is a variable amount of cardiac motion blurring due to the lack of electrocardiographic gating and the fact that heart rates differ between human subjects. As a consequence, the reliable segmentation of the heart, the first stage toward the implementation of morphologic heart abnormality detection, is also quite challenging. An automated computer method based on a sequential labeling of major organs and determination of anatomical landmarks has been evaluated on a public database of LDCT images. The novel algorithm builds from a robust segmentation of the bones and airways and embodies a stepwise refinement starting at the top of the lungs where image noise is at its lowest and where the carina provides a good calibration landmark. The segmentation is completed at the inferior wall of the heart where extensive image noise is accommodated. This method is based on the geometry of human anatomy and does not involve training through manual markings. Using visual inspection by an expert reader as a gold standard, the algorithm achieved successful heart and major vessel segmentation in 42 of 45 low-dose CT images. In the 3 remaining cases, the cardiac base was over segmented due to incorrect hemidiaphragm localization.

  7. Low-dose vs standard-dose insulin in pediatric diabetic ketoacidosis: a randomized clinical trial.

    PubMed

    Nallasamy, Karthi; Jayashree, Muralidharan; Singhi, Sunit; Bansal, Arun

    2014-11-01

    The standard recommended dose (0.1 U/kg per hour) of insulin in diabetic ketoacidosis (DKA) guidelines is not backed by strong clinical evidence. Physiologic dose-effect studies have found that even lower doses could adequately normalize ketonemia and acidosis. Lowering the insulin dose may be advantageous in the initial hours of therapy when a gradual decrease in glucose, electrolytes, and resultant osmolality is desired. To compare the efficacy and safety of low-dose insulin against the standard dose in children with DKA. This was a prospective, open-label randomized clinical trial conducted in the pediatric emergency department and intensive care unit of a tertiary care teaching hospital in northern India from November 1, 2011, through December 31, 2012. A total of 50 consecutive children 12 years or younger with a diagnosis of DKA were randomized to low-dose (n = 25) and standard-dose (n = 25) groups. Low-dose (0.05 U/kg per hour) vs standard-dose (0.1 U/kg per hour) insulin infusion. The primary outcome was the rate of decrease in blood glucose until a level of 250 mg/dL or less is reached (to convert to millimoles per liter, multiply by 0.0555). The secondary outcomes included time to resolution of acidosis, episodes of treatment failures, and incidences of hypokalemia and hypoglycemia. The mean (SD) rate of blood glucose decrease until a level of 250 mg/dL or less is reached (45.1 [17.6] vs 52.2 [23.4] mg/dL/h) and the mean (SD) time taken to achieve this target (6.0 [3.3] vs 6.2 [2.2] hours) were similar in the low- and standard-dose groups, respectively. Mean (SD) length of time to achieve resolution of acidosis (low vs standard dose: 16.5 [7.2] vs 17.2 [7.7] hours; P = .73) and rate of resolution of acidosis were also similar in the groups. Hypokalemia was seen in 12 children (48%) receiving the standard dose vs 5 (20%) of those receiving the low dose (P = .07); the tendency was more pronounced in malnourished children (7 [88%] vs 2 [28%]). Five children

  8. Comparison of image quality and radiation dose between prospectively ECG-triggered and retrospectively ECG-gated CT angiography: Establishing heart rate cut-off values in first-generation dual-source CT.

    PubMed

    Ünal, Emre; Yıldız, A Elçin; Güler, Ezgi; Karcaaltıncaba, Muşturay; Akata, Deniz; Kılınçer, Abidin; Atlı, Eray; Topçuoğlu, Melih; Hazırolan, Tuncay

    2015-09-01

    To evaluate radiation dose and image quality of prospectively electrocardiography (ECG)-triggered and retrospectively ECG-gated coronary computed tomography (CT) angiography and to establish cut-off values of heart rates (HRs) for each technique in first-generation dual-source CT. A total of 200 consecutive patients with suspected coronary artery disease were accepted into the study. Patients were selected randomly for each technique (prospective triggering group n=99, mean age 55.85±10.74 and retrospective gating group n=101, mean age 53.38±11.58). Two independent radiologists scored coronary artery segments for image quality using a 5-point scale. Also, attenuation values of each coronary artery segment and dose-length product values were measured. For each technique, cut-off HR values were determined for the best image quality. Mean image quality scores and attenuation values were found to be higher in the prospective triggering group (p<0.05). Mean radiation dose was 73% lower for the prospective triggering group (p<0.01). The cut-off HR values for good image quality scores were ≤67 beats per minute (bpm) and ≤80 bpm for the prospective triggering and retrospective gating groups, respectively (p<0.05). Increased HR (≥68 and ≥81 bpm, respectively) had negative effects on image quality (p<0.05). The prospective ECG triggering technique has better image quality scores than retrospective ECG gating, particularly in patients who have an HR of less than 68 bpm. Also, a 73% radiation dose reduction can be achieved with prospective ECG triggering. In patients with higher heart rates, retrospective ECG gating is recommended.

  9. Choosing populations to study the health effects of low-dose ionizing radiation.

    PubMed Central

    Dreyer, N A; Loughlin, J E; Friedlander, E R; Clapp, R W; Fahey, F H

    1981-01-01

    In January 1978, the United States Congress requested information about the utility of additional epidemiologic studies for quantifying the health effects of low-dose ionizing radiation. In our judgment, no single population can be recommended for study on purely scientific grounds, since the largest group offers only a small chance to obtain a definitive result. On the other hand, if social pressures and regulatory agencies mandate that such studies be attempted, we would recommend prospective cohort studies of occupational populations. We propose that a national worker registry be developed using ionizing radiation as the prototype for studying other occupational exposures. The problems related to studying low-level radiation are not unique, but apply equally to investigations dealing with a great variety of toxic agents. A national plan for collecting information on workers' exposure and health could provide a cost-efficient means to answer public health questions posed by the Congress, scientists and the public. PMID:7294269

  10. The spectrum of mutation produced by low dose radiation

    SciTech Connect

    Morley,Alexander,A; Turner, David,R

    2004-10-31

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  11. Low-dose aripiprazole for refractory burning mouth syndrome.

    PubMed

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS.

  12. Optical fiber sensor for low dose gamma irradiation monitoring

    NASA Astrophysics Data System (ADS)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  13. Surrogates of Protection in Repeated Low-Dose Challenge Experiments

    PubMed Central

    Long, Dustin M.; Hudgens, Michael G.; Wu, Chih-Da

    2015-01-01

    A critical step toward developing a successful vaccine to control the human immunodeficiency virus (HIV) pandemic entails evaluation of vaccine candidates in non-human primates (NHPs). Historically, these studies have usually entailed challenges (i.e., exposures) with very high doses of a simian version of HIV, resulting in infection of all NHPs in the experiment after a single challenge. More recently, researchers have begun to conduct repeated low-dose challenge (RLC) studies in NHPs that are believed to more closely mimic typical exposure in natural human transmission settings. One objective of RLC studies is to assess whether measured immune responses to vaccination can serve as surrogate endpoints for the primary endpoint of interest, namely infection. In this paper, different designs of RLC studies for assessing a binary surrogate of protection are considered. PMID:25628249

  14. Low-dose aripiprazole for refractory burning mouth syndrome

    PubMed Central

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  15. Early outcomes following low dose naltrexone enhancement of opioid detoxification.

    PubMed

    Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Gottheil, Edward; Wu, Li-Tzy; Gorelick, David A

    2009-01-01

    Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence.

  16. Use of very low-dose naltrexone during opiate detoxification.

    PubMed

    Mannelli, Paolo; Gottheil, Edward; Buonanno, Antonio; De Risio, Sergio

    2003-01-01

    The use of antagonist drugs to reduce the duration of opiate detoxification severely enhances withdrawal symptoms. To investigate the feasibility of administering antagonists with opiates without intense withdrawal during detoxification, 5 methadone maintained patients were evaluated while tapering methadone and receiving at the same time very low (0.125 mg), then increasing daily doses of naltrexone in the course of a 6-day, day hospital treatment. Reduced quantities of adjunctive medications were administered, as compared to the standard protocols, the treatment was completed without incidents or particular discomfort and all patients were easily induced to naltrexone maintenance by the day of discharge. Controlled studies will clarify whether very low-dose naltrexone provides a safe and comfortable detoxification technique to reduce withdrawal intensity and duration without the problems of heavy sedation, as suggested by the description of these clinical cases.

  17. Low-dose naltrexone for pruritus in systemic sclerosis.

    PubMed

    Frech, Tracy; Novak, Kirsten; Revelo, Monica P; Murtaugh, Maureen; Markewitz, Boaz; Hatton, Nathan; Scholand, Mary Beth; Frech, Edward; Markewitz, David; Sawitzke, Allen D

    2011-01-01

    Pruritus is a common symptom in systemic sclerosis (SSc), an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT). Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN) for pruritus, pain, and quality of life (QOL) in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms as measured by the 10-point faces scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) questionnaire. This small case series suggests LDN may be an effective, highly tolerable, and inexpensive treatment for pruritus and GIT symptoms in SSc.

  18. Early Outcomes Following Low Dose Naltrexone Enhancement of Opioid Detoxification

    PubMed Central

    Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Gottheil, Edward; Wu, Li-Tzy; Gorelick, David A

    2011-01-01

    Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence. PMID:19283561

  19. Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

    PubMed Central

    Frech, Tracy; Novak, Kirsten; Revelo, Monica P.; Murtaugh, Maureen; Markewitz, Boaz; Hatton, Nathan; Scholand, Mary Beth; Frech, Edward; Markewitz, David; Sawitzke, Allen D.

    2011-01-01

    Pruritus is a common symptom in systemic sclerosis (SSc), an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT). Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN) for pruritus, pain, and quality of life (QOL) in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms as measured by the 10-point faces scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) questionnaire. This small case series suggests LDN may be an effective, highly tolerable, and inexpensive treatment for pruritus and GIT symptoms in SSc. PMID:21918649

  20. Abnormal thallium 201 scintigraphy during low-dose vasopressin infusions

    SciTech Connect

    Davison, R.; Kaplan, K.; Bines, A.; Spies, S.; Reed, M.T.; Lesch, M.

    1986-12-01

    Thallium 201 (/sup 201/Tl) myocardial scans were obtained in 16 patients just prior to the discontinuation of a vasopressin infusion (.1 to .2 units/min) administered for the treatment of upper gastrointestinal bleeding. Repeat scintigraphy was performed two to three hours after the vasopressin was stopped. Eleven of the 16 patients (69 percent) demonstrated areas of decreased myocardial /sup 201/Tl uptake that resolved after the infusion was stopped. Heart rate-blood pressure product was significantly lower at the time of the second scan. Autopsies were secured in three of 11 scan-positive patients: one had severe coronary artery obstruction, one nonsignificant disease, and another had normal coronary arteries. Vasopressin, even at low doses, can induce abnormalities in myocardial perfusion that are probably mediated by a direct effect on the coronary circulation. They are usually not detectable by routine monitoring techniques and conceivably form the basis for the cardiovascular morbidity associated with the use of this agent.

  1. Radiobiological evaluation of low dose-rate prostate brachytherapy implants

    NASA Astrophysics Data System (ADS)

    Knaup, Courtney James

    Low dose-rate brachytherapy is a radiation therapy treatment for men with prostate cancer. While this treatment is common, the use of isotopes with varying dosimetric characteristics means that the prescription level and normal organ tolerances vary. Additionally, factors such as prostate edema, seed loss and seed migration may alter the dose distribution within the prostate. The goal of this work is to develop a radiobiological response tool based on spatial dose information which may be used to aid in treatment planning, post-implant evaluation and determination of the effects of prostate edema and seed migration. Aim 1: Evaluation of post-implant prostate edema and its dosimetric and biological effects. Aim 2: Incorporation of biological response to simplify post-implant evaluation. Aim 3: Incorporation of biological response to simplify treatment plan comparison. Aim 4: Radiobiologically based comparison of single and dual-isotope implants. Aim 5: Determine the dosimetric and radiobiological effects of seed disappearance and migration.

  2. Quantifying exploratory low dose compounds in humans with AMS

    PubMed Central

    Dueker, Stephen R.; Vuong, Le T.; Lohstroh, Peter N.; Giacomo, Jason A.; Vogel, John S.

    2010-01-01

    Accelerator Mass Spectrometry is an established technology whose essentiality extends beyond simply a better detector for radiolabeled molecules. Attomole sensitivity reduces radioisotope exposures in clinical subjects to the point that no population need be excluded from clinical study. Insights in human physiochemistry are enabled by the quantitative recovery of simplified AMS processes that provide biological concentrations of all labeled metabolites and total compound related material at non-saturating levels. In this paper, we review some of the exploratory applications of AMS 14C in toxicological, nutritional, and pharmacological research. This body of research addresses the human physiochemistry of important compounds in their own right, but also serves as examples of the analytical methods and clinical practices that are available for studying low dose physiochemistry of candidate therapeutic compounds, helping to broaden the knowledge base of AMS application in pharmaceutical research. PMID:21047543

  3. Quantifying exploratory low dose compounds in humans with AMS.

    PubMed

    Dueker, Stephen R; Vuong, Le T; Lohstroh, Peter N; Giacomo, Jason A; Vogel, John S

    2011-06-19

    Accelerator Mass Spectrometry is an established technology whose essentiality extends beyond simply a better detector for radiolabeled molecules. Attomole sensitivity reduces radioisotope exposures in clinical subjects to the point that no population need be excluded from clinical study. Insights in human physiochemistry are enabled by the quantitative recovery of simplified AMS processes that provide biological concentrations of all labeled metabolites and total compound related material at non-saturating levels. In this paper, we review some of the exploratory applications of AMS (14)C in toxicological, nutritional, and pharmacological research. This body of research addresses the human physiochemistry of important compounds in their own right, but also serves as examples of the analytical methods and clinical practices that are available for studying low dose physiochemistry of candidate therapeutic compounds, helping to broaden the knowledge base of AMS application in pharmaceutical research.

  4. Low dose ionizing radiation detection using conjugated polymers

    SciTech Connect

    Silva, E.A.B.; Borin, J.F.; Nicolucci, P.; Graeff, C.F.O.; Netto, T. Ghilardi; Bianchi, R.F.

    2005-03-28

    In this work, the effect of gamma radiation on the optical properties of poly[2-methoxy-5-(2{sup '}-ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV) is studied. The samples were irradiated at room temperature with different doses from 0 Gy to 152 Gy using a {sup 60}Co gamma ray source. For thin films, significant changes in the UV-visible spectra were only observed at high doses (>1 kGy). In solution, shifts in absorption peaks are observed at low doses (<10 Gy), linearly dependent on dose. The shifts are explained by conjugation reduction, and possible causes are discussed. Our results indicate that MEH-PPV solution can be used as a dosimeter adequate for medical applications.

  5. Low-dose radiation: a cause of breast cancer

    SciTech Connect

    Land, C.E.

    1980-08-15

    It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause.

  6. Personalized body segment parameters from biplanar low-dose radiography.

    PubMed

    Dumas, Raphaël; Aissaoui, Rachid; Mitton, David; Skalli, Wafa; de Guise, Jacques A

    2005-10-01

    Body segment parameters are essential data in biomechanics. They are usually computed with population-specific predictive equations from literature. Recently, medical imaging and video-based methods were also reported for personalized computation. However, these methods present limitations: some of them provide only two-dimensional measurements or external measurements, others require a lot of tomographic images for a three-dimensional (3-D) reconstruction. Therefore, an original method is proposed to compute personalized body segment parameters from biplanar radiography. Simultaneous low-dose frontal and sagittal radiographs were obtained with EOS system. The upper leg segments of eight young males and eight young females were studied. The personalized parameters computed from the biplanar radiographic 3-D reconstructions were compared to literature. The biplanar radiographic method was consistent with predictive equations based on gamma-ray scan and dual energy X-ray absorptiometry.

  7. Restless Legs Syndrome After Single Low Dose Quetiapine Administration.

    PubMed

    Soyata, Ahmet Z; Celebi, Fahri; Yargc, Lutfi I

    2016-01-01

    Restless legs syndrome is an underdiagnosed sensori-motor disorder and psychotropic drugs are one of the main secondary causes of the illness. The most common psychotropic agents that cause restless legs syndrome are antidepressants; however, antipsychotics have also been reported to induce restless legs syndrome. The prevalence, vulnerability factors and the underlying mechanism of antipsychotic-induced restless legs syndrome are unclear. A possible explanation is that dopaminergic blockade is the main precipitator of the syndrome. Quetiapine-induced restless legs syndrome is another point of interest because of its low binding to D2 receptors. We herein report the case of a restless legs syndrome that emerged after a single low dose quetiapine administration.

  8. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    PubMed Central

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-01-01

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy. PMID:25337914

  9. Evaluation of a low-dose progestagen as a contraceptive.

    PubMed

    Iizuka, R; Hayashi, M; Kamouchi, Y; Yamanaka, K

    1971-01-01

    In order to evaluate the safety and effectiveness of a low-dose progestagen oral contraceptive, 46 women were administered 0.25 mg daily of a synthetic gestagen, R-2453 (17alpha-methyl delta 9-19 norprogesterone) for 1-12 months for a total of 189 cycles. The pill was found to be safe and completely effective with no pregnancies occurring in the study group. The length of the bleeding cycle was found to be prolonged under this treatment, to an average of 40 days . Bleeding duration and amount were generally the same as those before treatment, except in 3 cases where irregular bleeding prompted discontinuance of the pill use. Basal body temperature patterns were measured and found to be atypical biphasic in 17.3% of the cases, high temperature monophasic in 47.2%, and irregular in 34.6%. Routine blood, kidney and liver function tests were normal. Pregnandiol excretion before withdrawal bleeding was low in all but 1 case. Cervical mucus was also low and no crystal formation was observed. In the nidation menstrual stage the endometrial glands were few in number and adenomeres were small in size. In glandular cells, supranuclear vacuoles were found and interstices were coarse and edematous. Histological examinations in the implantation phase showed some alterations but their relationship to the contraceptive mechanism of this pill is not clear. Low-dose progestagens appear to be highly effective contraceptive agents that do not suppress ovulatory activity but their prescription must take careful note of dosage and formulas.

  10. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  11. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    SciTech Connect

    Kleiman, Norman Jay

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  12. Cardiovascular risks associated with low dose ionizing particle radiation.

    PubMed

    Yan, Xinhua; Sasi, Sharath P; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A

    2014-01-01

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1)H; 0.5 Gy, 1 GeV) and iron ion ((56)Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56)Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56)Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  13. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    DOE PAGES

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; ...

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initiallymore » improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less

  14. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    SciTech Connect

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  15. Transcriptome profiling of mice testes following low dose irradiation

    PubMed Central

    2013-01-01

    Background Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis. Methods Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). Results We identified a subset of transcripts (n = 988) where changes in expression pi can be explained by changes in cellularity. We separated the transcripts into five unique clusters that we associated with spermatogonia, spermatocytes, early spermatids, late spermatids and somatic cells, respectively. Transcripts in the somatic cell cluster showed large changes in expression pi, mainly caused by changes in cellularity. Further investigations revealed that the low dose irradiation seemed to cause Leydig cell hyperplasia, which contributed to the detected expression changes in the somatic cell cluster. Conclusions The five clusters represent gene expression in distinct cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production and inadequate inhibin signalling due to missing germ cells. PMID:23714422

  16. Low-Dose Hyperradiosensitivity: Is There a Place for Future Investigation in Clinical Settings?

    SciTech Connect

    Valentini, Vincenzo; Massaccesi, Mariangela; Balducci, Mario; Mantini, Giovanna; Micciche, Francesco; Mattiucci, Gian Carlo; Dinapoli, Nicola; Meduri, Bruno; D'Agostino, Giuseppe Roberto; Salvi, Giovanna; Nardone, Luigia

    2010-02-01

    Background and Purpose: In vitro radiation doses of below 0.5 Gy have been shown to be more effective than higher doses per unit dose in killing clonogenic cells of many epithelial tumor cell lines. This phenomenon is known as low-dose hyperradiosensitivity. Preclinical studies have now suggested that there is synergism between chemotherapy and low-dose fractionated radiotherapy (LD-FRT). To test the clinical efficacy of this approach, we prospectively evaluated concurrent palliative chemotherapy and LD-FRT in patients with various types of epithelial tumors. Methods and Materials: Patients suffering from relapses or metastases of epithelial tumors were scheduled to receive concurrent LD-FRT (two fractions of 0.4 Gy per day) and chemotherapy. Radiologic assessments were performed after three cycles of chemotherapy plus LD-FRT. Results: Between June 2006 and October 2007, 12 patients with lung cancer, 7 patients with head-and-neck tumors, 2 patients with breast cancer, and 1 patient with esophageal carcinoma, for a total patient population of 22, underwent concomitant LD-FRT and chemotherapy. All patients but 3 (86%) had received previous treatments for their cancer. The median total dose of LD-FRT delivered was 800 cGy (range, 320-1280 cGy). The overall response rate was 45% (42% in previously treated patients). Grade 3-4 hematologic toxicities (Radiation Therapy Oncology Group ratings) were observed in 2 patients. At a median follow-up of 6.5 months, however, no local toxicity was observed. Conclusion: In our experience, concurrent LD-FRT and chemotherapy was well tolerated. Because the response rate seems promising, prospective Phase II studies of the strategy are now under way.

  17. TU-A-12A-09: Absolute Blood Flow Measurement in a Cardiac Phantom Using Low Dose CT

    SciTech Connect

    Ziemer, B; Hubbard, L; Lipinski, J; Molloi, S

    2014-06-15

    Purpose: To investigate a first pass analysis technique to measure absolute flow from low dose CT images in a cardiac phantom. This technique can be combined with a myocardial mass assignment to yield absolute perfusion using only two volume scans and reduce the radiation dose to the patient. Methods: A four-chamber cardiac phantom and perfusion chamber were constructed from poly-acrylic and connected with tubing to approximate anatomical features. The system was connected to a pulsatile pump, input/output reservoirs and power contrast injector. Flow was varied in the range of 1-2.67 mL/s with the pump operating at 60 beats/min. The system was imaged once a second for 14 seconds with a 320-row scanner (Toshiba Medical Systems) using a contrast-enhanced, prospective-gated cardiac perfusion protocol. Flow was calculated by the following steps: subsequent images of the perfusion volume were subtracted to find the contrast entering the volume; this was normalized by an upstream, known volume region to convert Hounsfield (HU) values to concentration; this was divided by the subtracted images time difference. The technique requires a relatively stable input contrast concentration and no contrast can leave the perfusion volume before the flow measurement is completed. Results: The flow calculated from the images showed an excellent correlation with the known rates. The data was fit to a linear function with slope 1.03, intercept 0.02 and an R{sup 2} value of 0.99. The average root mean square (RMS) error was 0.15 mL/s and the average standard deviation was 0.14 mL/s. The flow rate was stable within 7.7% across the full scan and served to validate model assumptions. Conclusion: Accurate, absolute flow rates were measured from CT images using a conservation of mass model. Measurements can be made using two volume scans which can substantially reduce the radiation dose compared with current dynamic perfusion techniques.

  18. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    SciTech Connect

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  19. Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury

    PubMed Central

    Ota, Kazuhiro; Takeuchi, Toshihisa; Nouda, Sadaharu; Ozaki, Haruhiko; Kawaguchi, Shinpei; Takahashi, Yoshiaki; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Kuramoto, Takanori; Higuchi, Kazuhide

    2016-01-01

    Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20–65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary. PMID:27895392

  20. Determination of the adequate dosage of rebamipide, a gastric mucoprotective drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury.

    PubMed

    Ota, Kazuhiro; Takeuchi, Toshihisa; Nouda, Sadaharu; Ozaki, Haruhiko; Kawaguchi, Shinpei; Takahashi, Yoshiaki; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Kuramoto, Takanori; Higuchi, Kazuhide

    2016-11-01

    Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20-65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group). Esophagogastroduodenoscopy and video capsule endoscopy were performed, and the fecal occult blood reaction and fecal calprotectin levels were measured before and two weeks after drug administration. Although the fecal calprotectin levels increased significantly in Group A, they did not increase in Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among the three groups. In conclusion, standard-dose rebamipide is sufficient for preventing mucosal injury of the small intestine induced by low-dose aspirin, indicating that high-dose rebamipide is not necessary.

  1. Ultra low-dose CT attenuation correction in PET SPM

    NASA Astrophysics Data System (ADS)

    Wang, Shyh-Jen; Yang, Bang-Hung; Tsai, Chia-Jung; Yang, Ching-Ching; Lee, Jason J. S.; Wu, Tung-Hsin

    2010-07-01

    The use of CT images for attenuation correction (CTAC) allows significantly shorter scanning time and a high quality noise-free attenuation map compared with conventional germanium-68 transmission scan because at least 10 4 times greater of photon flux would be generated from a CT scan under standard operating condition. However, this CTAC technique would potentially introduce more radiation risk to the patients owing to the higher radiation exposure from CT scan. Statistic parameters mapping (SPM) is a prominent technique in nuclear medicine community for the analysis of brain imaging data. The purpose of this study is to assess the feasibility of low-dose CT (LDCT) and ultra low-dose CT (UDCT) in PET SPM applications. The study was divided into two parts. The first part was to evaluate of tracer uptake distribution pattern and quantity analysis by using the striatal phantom to initially assess the feasibility of AC for clinical purpose. The second part was to examine the group SPM analysis using the Hoffman brain phantom. The phantom study is to simulate the human brain and to reduce the experimental uncertainty of real subjects. The initial studies show that the results of PET SPM analysis have no significant differences between LDCT and UDCT comparing to the current used default CTAC. Moreover, the dose of the LDCT is lower than that of the default CT by a factor of 9, and UDCT can even yield a 42 times dose reduction. We have demonstrated the SPM results while using LDCT and UDCT for PET AC is comparable to those using default CT setting, suggesting their feasibility in PET SPM applications. In addition, the necessity of UDCT in PET SPM studies to avoid excess radiation dose is also evident since most of the subjects involved are non-cancer patients or children and some normal subjects are even served as a comparison group in the experiment. It is our belief that additional attempts to decrease the radiation dose would be valuable, especially for children and

  2. Information content of low-dose radiographs: Part 2

    SciTech Connect

    Morris, R.A.

    1997-10-01

    The previous paper described the concept of using the net number of information bits transmitted in a radiographic image as a measure of the contrast parameter of image quality. The concept is particularly useful when the image contrast is limited by the statistics of the photon fluence incident on the detector (low doses). The Wolfram Research Mathematica program (described in Ref. 1) that was used to simulate a noisy image of an object with two thicknesses and to calculate the resulting IC (information content). The only noise source in the simulation was fluctuations in the photon fluence incident on the detector. The results from the simulation were compared to data obtained from actual radiographs of a copper step wedge radiographed with 10 and 50 pulses from a 150-p, V x-ray machine. Good agreement between the simulation and experiment was obtained when the photon fluence was considered a free, adjustable parameter. This report extends the simulation described in Ref. 1 and shows how IC varies as the following radiographic parameters change: object thickness; object Z number; x-ray energy; and incident x-ray fluence.

  3. Personalized low dose CT via variable kVp

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Jin, Yannan; Yao, Yangyang; Wu, Mingye; Yan, Ming; Tao, Kun; Yin, Zhye; De Man, Bruno

    2015-03-01

    Computerized Tomography (CT) is a powerful radiographic imaging technology but the health risk due to the exposure of x-ray radiation has drawn wide concern. In this study, we propose to use kVp modulation to reduce the radiation dose and achieve the personalized low dose CT. Two sets of simulation are performed to demonstrate the effectiveness of kVp modulation and the corresponding calibration. The first simulation used the helical body phantom (HBP) that is an elliptical water cylinder with high density bone inserts. The second simulation uses the NCAT phantom to emulate the practical use of kVp modulation approach with region of interest (ROI) selected in the cardiac region. The kVp modulation profile could be optimized view by view based on the knowledge of patient attenuation. A second order correction is applied to eliminate the beam hardening artifacts. To simplify the calibration process, we first generate the calibration vectors for a few representative spectra and then acquire other calibration vectors with interpolation. The simulation results demonstrate the beam hardening artifacts in the images with kVp modulation can be eliminated with proper beam hardening correction. The results also show that the simplification of calibration did not impair the image quality: the calibration with the simplified and the complete vectors both eliminate the artifacts effectively and the results are comparable. In summary, this study demonstrates the feasibility of kVp modulation and gives a practical way to calibrate the high order beam hardening artifacts.

  4. Sensitivity to low-dose radiation in radiosensitive wasted mice

    SciTech Connect

    Paunesku, T.; Protic, M.; Woloschak, G. E.

    1999-11-12

    Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T-cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T-lymphocytes and motor neuron cells afflicted by the 3-bp deletion in the PCNA promoter. The model is as follows: Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis; this absence of expression is mediated by a positive transactor that can bind to the wild-type but not the wasted mutant PCNA promoter; the bound protein induces late expression of PCNA in T-lymphocytes and prevents onset of radiation sensitivity in the cells.

  5. Pb low doses induced genotoxicity in Lactuca sativa plants.

    PubMed

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

    2017-03-01

    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L(-1). In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO3)2 up to 20 mg L(-1). The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L(-1) significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L(-1) and presence of micronuclei (MN) were detected for 20 mg L(-1). Also, cell cycle impairment was observed for doses as low as 0.05 mg L(-1) and 0.5 mg L(-1) (mostly G2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays.

  6. Low dose CT perfusion using k-means clustering

    NASA Astrophysics Data System (ADS)

    Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

    2016-03-01

    We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.

  7. Discriminative stimulus properties of low doses of ethanol in humans.

    PubMed

    Duka, T; Stephens, D N; Russell, C; Tasker, R

    1998-04-01

    Discriminative stimulus properties of low doses of ethanol were evaluated in humans using established behavioural drug discrimination procedures. Twenty-five moderate drinkers (12 females and 13 males) were trained to discriminate placebo from 0.2 g/kg ethanol in 200 ml tonic water mixed with Tabasco sauce and drunk in portions of 50 ml every 15 s. Seventeen of the subjects (ten females and seven males) were able to reach criterion performance (at least 80% correct responses). Generalisation responding across ethanol doses of 0 (placebo), 0.025, 0.05, 0.1 and 0.2 g/kg was examined the day after training using a procedure in which subjects reported the extent to which the test stimulus resembled the training dose. At the end of each generalisation session, self ratings of mood changes, physiological responses and performance in a working memory and a time estimation task were evaluated. Subjects were able to distinguish the three higher doses of ethanol from placebo. Self ratings indicated that subjects' ability to distinguish ethanol from placebo was related, at the highest dose, to change of taste, but to feelings of light-headedness at the lower doses. Ethanol administration influenced skin conductance measurements but there was no relationship found between changes in skin conductance and the ethanol discriminative stimulus. These data suggest a difference in the nature of the discriminative stimulus of ethanol between high (training) and low (generalising) doses as indicated in the subjective reports.

  8. Dosimetric Study of a Low-Dose-Rate Brachytherapy Source

    NASA Astrophysics Data System (ADS)

    Rodríguez-Villafuerte, M.; Arzamendi, S.; Díaz-Perches, R.

    Carcinoma of the cervix is the most common malignancy - in terms of both incidence and mortality - in Mexican women. Low dose rate (LDR) intracavitary brachytherapy is normally prescribed for the treatment of this disease to the vast majority of patients attending public hospitals in our country. However, most treatment planning systems being used in these hospitals still rely on Sievert integral dose calculations. Moreover, experimental verification of dose distributions are hardly ever done. In this work we present a dosimetric characterisation of the Amersham CDCS-J 137Cs source, an LDR brachytherapy source commonly used in Mexican hospitals. To this end a Monte Carlo simulation was developed, that includes a realistic description of the internal structure of the source embedded in a scattering medium. The Monte Carlo results were compared to experimental measurements of dose distributions. A lucite phantom with the same geometric characteristics as the one used in the simulation was built. Dose measurements were performed using thermoluminescent dosimeters together with commercial RadioChromic dye film. A comparison between our Monte Carlo simulation, the experimental data, and results reported in the literature is presented.

  9. Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

    NASA Astrophysics Data System (ADS)

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enikő; Lumniczky, Katalin; Sáfrány, Géza

    We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent's whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300-500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

  10. Functional modulation on macrophage by low dose naltrexone (LDN).

    PubMed

    Yi, Zhe; Guo, Shengnan; Hu, Xu; Wang, Xiaonan; Zhang, Xiaoqing; Griffin, Noreen; Shan, Fengping

    2016-10-01

    Previously it was confirmed that naltrexone, a non-peptide δ-opioid receptor selective antagonist is mainly used for alcoholic dependence and opioid addiction treatment. However, there is increasing data on immune regulation of low dose naltrexone (LDN). The aim of this work was to explore the effect of LDN on the phenotype and function of macrophage. The changes of macrophage after treatment with LDN were examined using flow cytometry (FCM); FITC-dextran phagocytosis and enzyme-linked immunosorbent assay (ELISA). We have found that LDN enhances function of macrophage as confirmed by up-regulating MHC II molecule and CD64 on macrophage while down-regulating CD206 expression. Furthermore the productions of TNF-α, IL-6, IL-1β, increased significantly. Macrophages in LDN treated group performed the enhanced phagocytosis. Therefore it is concluded that LDN could promote function of macrophage and this work has provided concrete data of impact on immune system by LDN. Especially the data would support interaction between CD4+T cell and macrophage in AIDS treatment with LDN in Africa (LDN has already been approved in Nigeria for the use in AIDS treatment). Copyright © 2016. Published by Elsevier B.V.

  11. Chronic very low dose naltrexone administration attenuates opioid withdrawal expression.

    PubMed

    Mannelli, Paolo; Gottheil, Edward; Peoples, James F; Oropeza, Veronica C; Van Bockstaele, Elisabeth J

    2004-08-15

    Different regimens of agonist and antagonist drugs have been used in opioid withdrawal management, with variable results. We examined whether administering extremely small quantities of opiate antagonists in the presence of opiate agonist drugs reduces withdrawal expression. Forty-one male Sprague-Dawley rats were implanted with morphine or placebo pellets for eight days. Starting on day 3, some rats received naltrexone in their drinking water (5 mg/L), or unadulterated water. On day 8, rats were injected with saline or naltrexone (100 mg/kg) and evaluated for behavioral signs of withdrawal. Next, sections through the locus coeruleus (LC) and nucleus of the solitary tract (NTS), brainstem areas exhibiting cellular activation following opiate withdrawal, were processed for c-Fos to detect early gene expression. Finally, the same nuclei were examined for protein kinase A regulatory subunit II (PKA) and phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB), using Western blot analysis. Withdrawal was attenuated and c-Fos, PKA, and pCREB expression was decreased in the NTS and LC of rats receiving chronic very low doses of naltrexone. Reduction of withdrawal upon chronic very low naltrexone administration may be due in part to decreased activation of brainstem noradrenergic neurons in morphine dependent rats.

  12. Benzodiazepine dependence and its treatment with low dose flumazenil.

    PubMed

    Hood, Sean David; Norman, Amanda; Hince, Dana Adelle; Melichar, Jan Krzysztof; Hulse, Gary Kenneth

    2014-02-01

    Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future.

  13. Low dose radiation adaptive protection to control neurodegenerative diseases.

    PubMed

    Doss, Mohan

    2014-05-01

    Concerns have been expressed recently regarding the observed increased DNA damage from activities such as thinking and exercise. Such concerns have arisen from an incomplete accounting of the full effects of the increased oxidative damage. When the effects of the induced adaptive protective responses such as increased antioxidants and DNA repair enzymes are taken into consideration, there would be less endogenous DNA damage during the subsequent period of enhanced defenses, resulting in improved health from the thinking and exercise activities. Low dose radiation (LDR), which causes oxidative stress and increased DNA damage, upregulates adaptive protection systems that may decrease diseases in an analogous manner. Though there are ongoing debates regarding LDR's carcinogenicity, with two recent advisory committee reports coming to opposite conclusions, data published since the time of the reports have overwhelmingly ruled out its carcinogenicity, paving the way for consideration of its potential use for disease reduction. LDR adaptive protection is a promising approach to control neurodegenerative diseases, for which there are no methods of prevention or cure. Preparation of a compelling ethics case would pave the way for LDR clinical studies and progress in dealing with neurodegenerative diseases.

  14. Low dose radiation damage effects in silicon strip detectors

    NASA Astrophysics Data System (ADS)

    Wiącek, P.; Dąbrowski, W.

    2016-11-01

    The radiation damage effects in silicon segmented detectors caused by X-rays have become recently an important research topic driven mainly by development of new detectors for applications at the European X-ray Free Electron Laser (E-XFEL). However, radiation damage in silicon strip is observed not only after extreme doses up to 1 GGy expected at E-XFEL, but also at doses in the range of tens of Gy, to which the detectors in laboratory instruments like X-ray diffractometers or X-ray spectrometers can be exposed. In this paper we report on investigation of radiation damage effects in a custom developed silicon strip detector used in laboratory diffractometers equipped with X-ray tubes. Our results show that significant degradation of detector performance occurs at low doses, well below 200 Gy, which can be reached during normal operation of laboratory instruments. Degradation of the detector energy resolution can be explained by increasing leakage current and increasing interstrip capacitance of the sensor. Another observed effect caused by accumulation of charge trapped in the surface oxide layer is change of charge division between adjacent strips. In addition, we have observed unexpected anomalies in the annealing process.

  15. Low-dose techniques in CT-guided interventions.

    PubMed

    Sarti, Marc; Brehmer, William P; Gay, Spencer B

    2012-01-01

    Computed tomography (CT)-guided interventions such as biopsy, drainage, and ablation may be significant sources of radiation exposure in both patients and radiologists. Simple CT techniques to reduce radiation dose may be employed without increasing the procedure time or significantly degrading image quality. To develop low-dose protocols, it is important to understand the key concepts of delivered radiation dose to patients and physicians during CT-guided interventions. Patient dose estimates are easily followed and are provided at CT workstations. Familiarity with dose estimates, which are expressed as CT dose index and dose-length product, is also important. Methods to reduce radiation exposure in patients and physicians include performing proper preprocedure planning and paying careful attention to technique during the planning stage, making use of personal protective equipment, performing CT fluoroscopy intermittently instead of in real time, and optimizing needle visualization. Representative examples of these techniques have resulted in dose reductions of as much as 89%. Alternative imaging technologies that do not use ionizing radiation, such as virtual and ultrasonographic guidance, may also be used to reduce radiation dose. Understanding dose contribution strategies to reduce radiation dose provides a safer, more efficient environment for patients and the radiology team.

  16. Algorithm-enabled Low-dose Micro-CT Imaging

    PubMed Central

    Han, Xiao; Bian, Junguo; Eaker, Diane R.; Kline, Timothy L.; Sidky, Emil Y.; Ritman, Erik L.; Pan, Xiaochuan

    2013-01-01

    Micro-CT is an important tool in biomedical research and preclinical applications that can provide visual inspection of and quantitative information about imaged small animals and biological samples such as vasculature specimens. Currently, micro-CT imaging uses projection data acquired at a large number (300 – 1000) of views, which can limit system throughput and potentially degrade image quality due to radiation-induced deformation or damage to the small animal or specimen. In this work, we have investigated low-dose micro-CT and its application to specimen imaging from substantially reduced projection data by using a recently developed algorithm, referred to as the adaptive-steepest-descent-projection-onto-convex-sets (ASD-POCS) algorithm, which reconstructs an image through minimizing the image total-variation and enforcing data constraints. To validate and evaluate the performance of the ASD-POCS algorithm, we carried out quantitative evaluation studies in a number of tasks of practical interest in imaging of specimens of real animal organs. The results show that the ASD-POCS algorithm can yield images with quality comparable to that obtained with existing algorithms, while using one-sixth to one quarter of the 361-view data currently used in typical micro-CT specimen imaging. PMID:20977983

  17. Standardization and optimization of CT protocols to achieve low dose.

    PubMed

    Trattner, Sigal; Pearson, Gregory D N; Chin, Cynthia; Cody, Dianna D; Gupta, Rajiv; Hess, Christopher P; Kalra, Mannudeep K; Kofler, James M; Krishnam, Mayil S; Einstein, Andrew J

    2014-03-01

    The increase in radiation exposure due to CT scans has been of growing concern in recent years. CT scanners differ in their capabilities, and various indications require unique protocols, but there remains room for standardization and optimization. In this paper, the authors summarize approaches to reduce dose, as discussed in lectures constituting the first session of the 2013 UCSF Virtual Symposium on Radiation Safety and Computed Tomography. The experience of scanning at low dose in different body regions, for both diagnostic and interventional CT procedures, is addressed. An essential primary step is justifying the medical need for each scan. General guiding principles for reducing dose include tailoring a scan to a patient, minimizing scan length, use of tube current modulation and minimizing tube current, minimizing tube potential, iterative reconstruction, and periodic review of CT studies. Organized efforts for standardization have been spearheaded by professional societies such as the American Association of Physicists in Medicine. Finally, all team members should demonstrate an awareness of the importance of minimizing dose.

  18. Role of heme Oxygenase-1 in low dose Radioadaptive response

    PubMed Central

    Bao, Lingzhi; Ma, Jie; Chen, Guodong; Hou, Jue; Hei, Tom K.; Yu, K.N.; Han, Wei

    2016-01-01

    Radioadaptive response (RAR) is an important phenomenon induced by low dose radiation. However, the molecular mechanism of RAR is obscure. In this study, we focused on the possible role of heme oxygenase 1 (HO-1) in RAR. Consistent with previous studies, priming dose of X-ray radiation (1–10 cGy) induced significant RAR in normal human skin fibroblasts (AG 1522 cells). Transcription and translation of HO-1 was up-regulated more than two fold by a priming dose of radiation (5 cGy). Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, could mimic priming dose of X-rays to induce RAR. Knocking down of HO-1 by transfection of HO-1 siRNA significantly attenuated RAR. Furthermore, the expression of HO-1 gene was modulated by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which translocated from cytoplasm to nucleus after priming dose radiation and enhance the antioxidant level of cells. PMID:26966892

  19. Low dose radiation-induced endothelial cell retraction.

    PubMed

    Kantak, S S; Diglio, C A; Onoda, J M

    1993-09-01

    We characterized in vitro the effects of gamma-radiation (12.5-100 cGy) on pulmonary microvascular endothelial cell (PMEC) morphology and F-actin organization. Cellular retraction was documented by phase-contrast microscopy and the organization of actin microfilaments was determined by immunofluorescence. Characterization included radiation dose effects, their temporal duration and reversibility of the effects. A dose-dependent relationship between the level of exposure (12.5-100 cGy) and the rate and extent of endothelial retraction was observed. Moreover, analysis of radiation-induced depolymerization of F-actin microfilament stress fibres correlated positively with the changes in PMEC morphology. The depolymerization of the stress fibre bundles was dependent on radiation dose and time. Cells recovered from exposure to reform contact inhibited monolayers > or = 24 h post-irradiation. Concomitantly, the depolymerized microfilaments reorganized to their preirradiated state as microfilament stress fibres arrayed parallel to the boundaries of adjacent contact-inhibited cells. The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Our data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema.

  20. Pharmacogenetics of Low Dose Clonidine in Irritable Bowel Syndrome

    PubMed Central

    Camilleri, Michael; Busciglio, Irene; Carlson, Paula; McKinzie, Sanna; Burton, Duane; Baxter, Kari; Ryks, Michael; Zinsmeister, Alan R.

    2009-01-01

    Objectives Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) sensorimotor functions. We aimed to determine whether candidate ADR-SER genes affect GI responses to low dose clonidine (CLO) in humans. Methods Forty healthy and 120 irritable bowel syndrome (IBS) participants received CLO, 0.1mg or 0.15mg b.i.d., for 6 days. At baseline and post-clonidine, we measured: gastric volume (GV); satiation volume; rectal compliance, sensation thresholds and ratings with distensions. Genetic variations tested were: α2A (C-1291G), α2C (Del 332-325), GNβ3 (C825T) and SLC6A4 (5-HTT-LPR). Results CLO reduced volume to satiation (p=0.002), postprandial GV (p<0.001), sensation threshold for pain (<0.001); CLO increased rectal compliance (p=0.024). There were significant associations between post-CLO responses and gene variations for Δ GV (α2A and SLC6A4), rectal sensation of gas (α2A, GNβ3), urgency (α2A); and pain (GNβ3 and SLC6A4); and rectal compliance (SLC6A4). Conclusion α2A, GNβ3 and SLC6A4 genotypes significantly modify responses to clonidine on sensory and motor GI functions in health and IBS. PMID:19309415

  1. Ergogenic effects of low doses of caffeine on cycling performance.

    PubMed

    Jenkins, Nathan T; Trilk, Jennifer L; Singhal, Arpit; O'Connor, Patrick J; Cureton, Kirk J

    2008-06-01

    The purpose of this experiment was to learn whether low doses of caffeine have ergogenic, perceptual, and metabolic effects during cycling. To determine the effects of 1, 2, and 3 mg/kg caffeine on cycling performance, differentiated ratings of perceived exertion (D-RPE), quadriceps pain intensity, and metabolic responses to cycling exercise, 13 cyclists exercised on a stationary ergometer for 15 min at 80% VO, then, after 4 min of active recovery, completed a 15-min VO2peak performance ride 60 min after ingesting caffeine or placebo. Work done (kJ/kg) during the performance ride was used as a measure of performance. D-RPE, pain ratings, and expired-gas data were obtained every 3 min, and blood lactate concentrations were obtained at 15 and 30 min. Compared with placebo, caffeine doses of 2 and 3 mg/kg increased performance by 4% (95% CI: 1.0-6.8%, p = .02) and 3% (95% CI: -0.4% to 6.8%, p = .077), respectively. These effects were ergogenic, on average, but varied considerably in magnitude among individual cyclists. There were no effects of caffeine on D-RPE or pain throughout the cycling task. Selected metabolic variables were affected by caffeine, consistent with its known actions. The authors conclude that caffeine preparations of 2 and 3 mg/kg enhanced performance, but future work should aim to explain the considerable interindividual variability of the drug's ergogenic properties.

  2. Coronary CT angiography with single-source and dual-source CT: comparison of image quality and radiation dose between prospective ECG-triggered and retrospective ECG-gated protocols.

    PubMed

    Sabarudin, Akmal; Sun, Zhonghua; Yusof, Ahmad Khairuddin Md

    2013-09-30

    This study is conducted to investigate and compare image quality and radiation dose between prospective ECG-triggered and retrospective ECG-gated coronary CT angiography (CCTA) with the use of single-source CT (SSCT) and dual-source CT (DSCT). A total of 209 patients who underwent CCTA with suspected coronary artery disease scanned with SSCT (n=95) and DSCT (n=114) scanners using prospective ECG-triggered and retrospective ECG-gated protocols were recruited from two institutions. The image was assessed by two experienced observers, while quantitative assessment was performed by measuring the image noise, the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). Effective dose was calculated using the latest published conversion coefficient factor. A total of 2087 out of 2880 coronary artery segments were assessable, with 98.0% classified as of sufficient and 2.0% as of insufficient image quality for clinical diagnosis. There was no significant difference in overall image quality between prospective ECG-triggered and retrospective gated protocols, whether it was performed with DSCT or SSCT scanners. Prospective ECG-triggered protocol was compared in terms of radiation dose calculation between DSCT (6.5 ± 2.9 mSv) and SSCT (6.2 ± 1.0 mSv) scanners and no significant difference was noted (p=0.99). However, the effective dose was significantly lower with DSCT (18.2 ± 8.3 mSv) than with SSCT (28.3 ± 7.0 mSv) in the retrospective gated protocol. Prospective ECG-triggered CCTA reduces radiation dose significantly compared to retrospective ECG-gated CCTA, while maintaining good image quality. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Randomized, double-blind, pilot study of geranylgeranylacetone versus placebo in patients taking low-dose enteric-coated aspirin. Low-dose aspirin-induced small bowel damage.

    PubMed

    Shiotani, Akiko; Haruma, Ken; Nishi, Ryuji; Fujita, Minoru; Kamada, Tomoari; Honda, Keisuke; Kusunoki, Hiroaki; Hata, Jiro; Graham, David Y

    2010-03-01

    Low-dose enteric-coated aspirin is increasingly being used for prevention of cardiovascular disease. The aim of this study was to evaluate whether geranylgeranylacetone (GGA) could prevent aspirin-induced small bowel injury. This was a prospective, randomized, double-blind, pilot study of GGA versus placebo in subjects taking low-dose enteric-coated aspirin. Young healthy volunteers were enrolled and each received 100 mg of enteric-coated aspirin per day plus either GGA (150 mg/day) or matching placebo for 7 days. Video capsule endoscopy of the small bowel and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire were performed before and after the administration of aspirin. Twenty volunteers were evaluated. There was no significant difference in the number of lesions in any category between those receiving or not receiving GGA. Large erosions or ulcers were observed in 12 (60%; 95% confidence interval 36%- 80%) aspirin users. Mucosal breaks were most frequently found in the latter half of the proximal small bowel. Short-term administration of low-dose enteric-coated aspirin was associated with visible small bowel damage in the majority of users. We could not prove that aspirin-induced small bowel mucosal injury was prevented by GGA.

  4. Low-dose recombinant factor VIIa for reversing coagulopathy in patients with isolated traumatic brain injury.

    PubMed

    Yuan, Qiang; Wu, Xing; Du, Zhuo-Ying; Sun, Yi-Rui; Yu, Jian; Li, Zhi-Qi; Wu, Xue-Hai; Mao, Ying; Zhou, Liang-Fu; Hu, Jin

    2015-02-01

    The purpose of this study was to investigate the role of low-dose recombinant factor VIIa (rFVIIa) (20 μg/kg) in reversing coagulopathy in patients with isolated traumatic brain injury (TBI). Patients with isolated TBI and coagulopathy at admission were enrolled prospectively from January 2010 to December 2011. The patients were divided into 2 groups: the rFVIIa and the no-rFVIIa groups. In the rFVIIa group, patients received a single dose of 20 μg/kg rFVIIa intravenously to reverse their coagulopathy in addition to blood products. Patients in the no-rFVIIa group received only blood products to correct the coagulopathy. The clinical outcome variables evaluated included changes in coagulation parameters after administration for reversing coagulopathy, the occurrence of progressive hemorrhagic injury (PHI), intensive care unit length of stay, the incidence of thromboembolic complications, inhospital mortality, and 90-day Glasgow Outcome Scale. Eighty-seven patients were ultimately included in this study. Of them, 49 patients were treated with blood products alone, whereas 38 patients also received rFVIIa to reverse their coagulopathy. The improvement in international normalized ratio was greater in the rFVIIa group (0.26 [0.18-0.39]) than in the no-rFVIIa group (0.06 [-0.11 to 0.30]) (P = .001). In addition, the improvement in lactate was also greater in the rFVIIa group (0.33 [-0.18 to 0.54]) than in the no-rFVIIa group (0.04 [-0.25 to 0.20]) (P = .029). During the period after we began to correct the coagulopathy, PHI occurred in 19 patients (38.8%) in the no-rFVIIa group, which was significantly higher than that in the rFVIIa group (7, 18.4%; P = .040). The rate of cerebral infarction was similar in both groups (10.2% vs 5.3%). There was a trend indicating that low-dose rFVIIa therapy was associated with a lower mortality, but the association was not statistically significant (P = .266). The use of low-dose rFVIIa (20 μg/kg) is effective for correcting

  5. Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group.

    PubMed

    Lowes, B D; Higginbotham, M; Petrovich, L; DeWood, M A; Greenberg, M A; Rahko, P S; Dec, G W; LeJemtel, T H; Roden, R L; Schleman, M M; Robertson, A D; Gorczynski, R J; Bristow, M R

    2000-08-01

    This study was designed to evaluate the effects of low-dose enoximone on exercise capacity. At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. This is a prospective, double-blind, placebo-controlled, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased arrhythmias by Holter monitoring. By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups. Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events.

  6. Effects of perioperative intravenous low dose of ketamine on postoperative analgesia in children.

    PubMed

    Bazin, Véronique; Bollot, Julie; Asehnoune, Karim; Roquilly, Antoine; Guillaud, Christian; De Windt, Ariane; Nguyen, Jean-Michel; Lejus, Corinne

    2010-01-01

    Low dose of ketamine reduces postoperative pain and opioid consumption in adult studies. However, there are only a few data with controversial results in the paediatric population. The aim of this randomized controlled trial was to evaluate the use of low doses of intravenous ketamine on postoperative pain in children after surgery on the lower part of the body. Thirty-seven children with ASA 1 or 2 from 6 to 60 months of age, undergoing scheduled surgery, were prospectively enrolled in a double blind sequential trial using a triangular test, with analysis every 10 patients treated. The children were randomly assigned to intravenously receive saline or 0.15 mg kg(-1) ketamine before surgery, followed by a continuous infusion of 1.4 microg kg(-1) min(-1) over 24 h. After sevoflurane induction and tracheal intubation, a caudal anaesthesia was performed in all children (1 ml kg(-1) of bupivacaine 0.25% with epinephrine). The postoperative analgesic technique was standardized with intravenous paracetamol 15 mg kg(-1) 6 h(-1), rectal morniflumate (20 mg kg(-1) 12 h(-1)) and intravenous nalbuphine infusion 1.2 mg kg(-1) 24 h(-1) for 24 h. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, additional bolus of nalbuphine (if CHEOPS >7) and side effects were recorded from eye opening every 2 h over 24 h. The primary endpoint was the CHEOPS area under the curve. There was no difference in terms of additional bolus of nalbuphine as well as CHEOPS score area under the curve between groups, that is, 76 +/- 10 in the ketamine group versus 74 +/- 7 in the control group. No psychomimetic side effects were noted. The study failed to show any evidence of benefit of ketamine to improve analgesia in children when given in addition to a multimodal analgesic therapy with paracetamol, a NSAID and an opiate.

  7. Low-dose thallium-201 protocol with a cadmium-zinc-telluride cardiac camera.

    PubMed

    Songy, Bernard; Guernou, Mohamed; Lussato, David; Queneau, Mathieu; Geronazzo, Ricardo

    2012-05-01

    Thallium-201 is efficient for myocardial perfusion imaging, but leads to relatively high radiation exposure in patients. The purpose of this study was to compare the efficiency of low-dose thallium-201 imaging with cadmium-zinc-telluride (CZT) cameras with regular-dose thallium-201 imaging with conventional cameras. We prospectively studied 137 consecutive patients referred for stress myocardial perfusion imaging who had previously had a myocardial single-photon emission computed tomography with thallium-201. We injected at stress a low dose of thallium-201 (1.1 MBq/kg, 28 µCi/kg), performed a 5-7 min scan with a CZT camera (GE DNM 530c), and assessed redistribution imaging when the initial images were abnormal. We compared the CZT scan with the conventional dual-head tomographic camera scan taken previously with a regular dose of thallium-201. The average delay between both scans was 22 months. The stress dose was 88 ± 16 (2.38 ± 0.43 mCi) versus 125 ± 13 MBq (3.38 ± 0.34 mCi; a 30% reduction). The time for camera acquisition was 6 versus 13 min (a 54% reduction). The myocardial counts were increased two-fold with CZT (mean: 446 Kcounts). The quality of CZT images was better in 69% of the cases. There were 59 artifacts with conventional cameras and 29 artifacts with CZT (P<0.01). The diagnostic agreement was calculated in patients without clinical or angiographic changes between both scans (115 patients) and was high (97%). The effective dose at stress was less than 12 mSv. High myocardial counting allowed for further decrease in the injected activity, leading to an effective dose as low as 8 mSv. With reduced activities of thallium-201 and low effective doses, the CZT camera provides reliable, high-quality imaging.

  8. Pharmacodynamic Effects of Low-Dose Pioglitazone in Patients with the Metabolic Syndrome without Diabetes Mellitus.

    PubMed

    Vu, Anh; Kosmiski, Lisa A; Beitelshees, Amber L; Prigeon, Ronald; Sidhom, Maha S; Bredbeck, Brooke; Predhomme, Julie; Deininger, Kimberly M; Aquilante, Christina L

    2016-03-01

    To determine the effects of low-dose pioglitazone on plasma adipocyte-derived cytokines, high-sensitivity C-reactive protein (hs-CRP), and components of the metabolic syndrome in adults with the metabolic syndrome without diabetes mellitus. Prospective, randomized, double-blind, placebo-controlled study. University of Colorado Clinical and Translational Research Center. Thirty-two men and women, aged 30-60 years, without diabetes who had a clinical diagnosis of the metabolic syndrome, as defined by the American Heart Association/National Heart, Lung, and Blood Institute criteria. Patients were randomly assigned to receive oral pioglitazone 7.5 mg daily or matching placebo for 8 weeks. The primary end point was the change in plasma high-molecular-weight (HMW) adiponectin level from baseline to week 8. Other end points were changes in plasma total adiponectin, omentin, and hs-CRP levels, and changes in components of the metabolic syndrome (e.g., insulin sensitivity) from baseline to week 8. Pioglitazone was associated with a significant increase in plasma HMW adiponectin from baseline to week 8 compared with placebo (+47% vs -10%, p<0.001). Insulin sensitivity increased significantly from baseline to week 8 in the pioglitazone group (+88%, p=0.02) but not in the placebo group (+15%, p=0.14). Change in HMW adiponectin was significantly correlated with the change in insulin sensitivity in the pioglitazone group (r = 0.784, p=0.003). No significant differences in mean percentage changes in plasma total adiponectin, omentin, and hs-CRP levels were observed between the pioglitazone and placebo groups. Likewise, changes in body weight, insulin sensitivity, glucose, lipids, and blood pressure did not differ significantly between the groups. Low-dose pioglitazone favorably modulates plasma HMW adiponectin, which was associated with an improvement in insulin sensitivity, in patients with the metabolic syndrome without diabetes. © 2016 Pharmacotherapy Publications, Inc.

  9. An exploratory study of responses to low-dose lithium in African Americans and Hispanics.

    PubMed

    Gonzalez Arnold, Jodi; Salcedo, Stephanie; Ketter, Terrence A; Calabrese, Joseph R; Rabideau, Dustin J; Nierenberg, Andrew A; Bazan, Melissa; Leon, Andrew C; Friedman, Edward S; Iosifescu, Dan; Sylvia, Louisa G; Ostacher, Michael; Thase, Michael; Reilly-Harrington, Noreen A; Bowden, Charles L

    2015-06-01

    Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS). LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) vs. OPT alone in outpatients with bipolar disorder. Of 283 participants, 47 African Americans, 39 Hispanics, and 175 non-Hispanic whites were examined. We predicted minority groups would have more negative medication attitudes and higher attrition rates, but better clinical outcomes. African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study. African Americans in the OPT only group had marginal improvement on depression symptoms. For Hispanics, satisfaction with life did not significantly improve in the OPT only group, in contrast to whites and African Americans who improved over time on all measures. Attitudes toward medications did not differ across ethnic/racial groups. African Americans show some greater improvements with lithium than non-Hispanic whites, and Hispanics showed more consistent improvements in the lithium group. The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics. Given that the control group (regardless of ethnicity/race) had significant improvements, optimized treatment may be beneficial for any ethnic group. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Low doses of prophylactic cranial irradiation effective in limited stage small cell carcinoma of the lung

    SciTech Connect

    Rubenstein, J.H.; Dosoretz, D.E.; Katin, M.J. |

    1995-09-30

    Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses. One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI. Patients receiving PCI exhibited brain failure in 15%, while 38 of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS {ge} 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018). In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials. 44 refs., 4 figs., 2 tabs.

  11. An Exploratory Study of Responses to Low-Dose Lithium in African Americans and Hispanics

    PubMed Central

    Arnold, Jodi Gonzalez; Salcedo, Stephanie; Ketter, Terrence A.; Calabrese, Joseph R.; Rabideau, Dustin J.; Nierenberg, Andrew A.; Bazan, Melissa; Leon, Andrew C.; Friedman, Edward S.; Iosifescu, Dan; Sylvia, Louisa G.; Ostacher, Michael; Thase, Michael; Reilly-Harrington, Noreen A.; Bowden, Charles L.

    2015-01-01

    Objectives Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic Whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS). Methods LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) versus OPT alone in outpatients with bipolar disorder. Of 283 participants, 47 African Americans, 39 Hispanics, and 175 non-Hispanic whites were examined. We predicted minority groups would have more negative medication attitudes and higher attrition rates, but better clinical outcomes. Results African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study. African Americans in the OPT only group had marginal improvement on depression symptoms. For Hispanics, satisfaction with life did not significantly improve in the OPT only group, in contrast to whites and African Americans who improved over time on all measures. Attitudes toward medications did not differ across ethnic/racial groups. Conclusions African Americans show some greater improvements with lithium than non-Hispanic whites, and Hispanics showed more consistent improvements in the lithium group. The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics. Given that the control group (regardless of ethnicity/race) had significant improvements, optimized treatment may be beneficial for any ethnic group. PMID:25827507

  12. Intrathecal sufentanil or fentanyl as adjuvants to low dose bupivacaine in endoscopic urological procedures

    PubMed Central

    Gupta, Shikha; Sampley, Supriya; Kathuria, Suneet; Katyal, Sunil

    2013-01-01

    Context: Opioids are being increasingly used these days as adjuvants to local anesthetics in spinal anesthesia. Aim: The aim of this study is to compare the effects of adding sufentanil or fentanyl to low dose bupivacaine in spinal anesthesia for endoscopic urological procedures. Settings and Design: Prospective, randomized, double-blind study. Materials and Methods: A total of 90 elective endoscopic urological surgery patients, 40-80 years old, received spinal anesthesia with 7.5 mg hyperbaric bupivacaine 0.5% (Group A) or by adding sufentanil 10 g (Group B) or fentanyl 25 g (Group C) to 5 mg hyperbaric bupivacaine 0.5%. These groups were compared in terms of the quality of spinal anesthesia as well as analgesia. Results: The onset of sensory and motor blockade was significantly rapid in Group A as compared with Groups B and C. The maximum upper level of sensory block was higher in Group A patients than Groups B and C patients. Quality of analgesia was significantly better and prolonged in sufentanil group as compared with other two groups. Motor block was more intense and prolonged in Group A as compared with Groups B and C patients. Request for post-operative analgesic was significantly delayed in Group B patients. Conclusions: Spinal anesthesia for endoscopic urological procedures in elderly patients using low dose bupivacaine (5 mg) combined with 10 μg sufentanil is associated with a lower incidence of hemodynamic instability, better quality and prolonged duration as compared to that by adding 25 μg fentanyl. PMID:24249989

  13. Effect of low dose oral contraceptives on exercise performance.

    PubMed Central

    Bryner, R W; Toffle, R C; Ullrich, I H; Yeater, R A

    1996-01-01

    OBJECTIVE--to examine the effect of cycle phase or a low dose oral contraceptive on exercise performance in young women. METHODS--As controls, 15 men were tested twice by a maximal treadmill test (Vo2 max) and by an endurance run 14 d apart to determine performance variability from causes other than hormonal fluctuations. Ten women ages 18-30 were then tested for Vo2 max and endurance in the same way in both the follicular and the luteal phase (random order, ovulation assessed by sonography). They were then randomly assigned to placebo (n = 3) or oral contraceptive (1 mg norethindrone and 35 micrograms ethinyl oestradiol) (n = 7) for 21 days. Tests were repeated during the first and third weeks of treatment. Vo2 max and endurance tests were compared in the men and control cycle of the women by using independent t tests on percent change. The data for both cycles in the women were analysed by repeated measures ANOVA. RESULTS--There was no difference in per cent change in total test time, Vo2 max, or breathing frequency between the men and women in either test. Data obtained during the Vo2 max test revealed no difference between the follicular and luteal phases of the menstrual cycle for total test time [11.8 (SD 2.3) v 12.6 (2.3) min], Vo2 [41.6 (12.1) v 39.7 (11.4) ml.kg-1.min-1], or breathing frequency [26.8 (3.5) v 27.3 (9.9) breaths.min-1] respectively, or during the first and third weeks of treatment [total test time 12.0 (2.5) v 12.8 (2.4) min; Vo2 37.3 (7.4) v 41.0 (12.4) ml.kg-1.min-1; breathing frequency 27.8 (4.2) v 27.7 (3.4) breaths.min-1, respectively]. Data obtained during the endurance test revealed no difference between the follicular and luteal phase of the menstrual cycle for total test time [20.5 (15.7) v 16.2 (8.5) min], Vo2 [37.5 (9.4) v 32.9 (8.1) ml.kg-1.min-1], or breathing frequency [32.0 (6.0) v 33.2 (5.1) breaths.min-1, respectively], or during the first and third weeks of treatment [total test time 32.3 (34.9) v 30.6 (30.1) min; Vo2 33

  14. Effect of low-dose gaseous ozone on pathogenic bacteria

    PubMed Central

    2012-01-01

    Background Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes. Methods A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99) mixture, applied for 5min under atmospheric pressure was selected. In the 2nd phase, eight bacterial strains with well characterized resistance patterns were evaluated in vitro using agar-blood in adapted Petri dishes (105 bacteria/dish). The cultures were divided into 3 groups: 1- ozone-oxygen gaseous mixture containing 20 μg of O3/mL for 5 min; 2- 100% oxygen for 5 min; 3- baseline: no gas was used. Results The selected ozone dose was applied to the following eight strains: Escherichia coli, oxacillin-resistant Staphylococcus aureus, oxacillin-susceptible Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, Acinetobacter baumannii susceptible only to carbapenems, and Pseudomonas aeruginosa susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups. Conclusion A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents. PMID:23249441

  15. Evaluation of a low-dose neonatal chest radiographic system

    SciTech Connect

    Burton, E.M.; Kirks, D.R.; Strife, J.L.; Henry, G.C.; Kereiakes, J.G.

    1988-11-01

    A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad (0.009 vs 0.029 mGy)) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad (0.009 vs 0.037 mGy)). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness.

  16. Low dose TBT exposure decreases amphipod immunocompetence and reproductive fitness.

    PubMed

    Jacobson, Therese; Sundelin, Brita; Yang, Gongda; Ford, Alex T

    2011-01-17

    The antifouling agent tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Despite of regulations on the usage of TBT, it remains in high concentrations in sediments both in harbors and in off-shore sites. The toxicity of TBT in mollusks is well documented. However, adverse effects in other aquatic organisms, such as crustaceans, are less well known. This study is an effort to assess the effects of environmentally realistic concentrations of TBT on an ecologically important species in Swedish fresh and brackish water ecosystems, the benthic amphipod Monoporeia affinis. Field collected animals were exposed during gonad maturation to TBT (70 and 170 ng/g sediment d wt) for five weeks in static microcosms with natural sediment. Exposure concentrations were chosen to reflect effects at concentrations found in Swedish coastal sediment, but below expected effects on survival. TBT exposure resulted in a statistically significant adverse effect on oocyte viability and a doubling of the prevalence of microsporidian parasites in females, from 17% in the control to 34% in the 170 ng TBT/g sediment d wt exposure. No effects on survival were observed. Borderline significant effects were observed on male sexual maturation in the 70 ng TBT/g d wt exposure and on ecdysteroid levels in the 170 ng/g sediment d wt exposure. Both reproduction and parasite infection effects are of ecological importance since they have the potential to affect population viability in the field. This study gives further evidence to the connection between low dose contaminant exposure and increases in microsporidian parasite infection.

  17. Low-dose ethanol aggravates allergic dermatitis in mice.

    PubMed

    Sakazaki, Fumitoshi; Ogino, Hirofumi; Arakawa, Tomohiro; Okuno, Tomofumi; Ueno, Hitoshi

    2014-08-01

    Alcohol injures dendritic cells and suppresses cellular immunity, while some evidence indicates that drinking alcohol aggravates allergic asthma. This study investigated the effect of low doses of ethanol in enhancing allergic reactions in the skin of mice. Liquid food containing alcohol was administered to conventional NC/Nga mice to induce alcoholic hepatic steatosis, and spontaneous dermatitis was evaluated. BALB/c mice were administered approximately 1 g/kg body weight of ethanol by gavage, and contact hypersensitivity (CHS) or active cutaneous anaphylaxis (ACA) was induced. Spleens were collected 24 h after the elicitation of CHS and mRNA expressions of interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-10, and IL-18 were measured by quantitative RT-PCR. Alcohol-containing diet exaggerated spontaneous dermatitis in conventional NC/Nga mice and contact hypersensitivity in BALB/c mice. Ethanol administered by gavage for 5 days enhanced contact hypersensitivity in BALB/c mice. Ethanol administration with gavage also enhanced ACA of BALB/c mice. Ethanol did not affect mRNA expression of IFN-γ and IL-4, but did enhance IL-6, IL-10, and IL-18 mRNA expression. Histological evaluation revealed an absence of hepatic steatosis in mice administered ethanol by gavage for 5 days. In ethanol-administered mice, inflamed areas presented as lesions or a local extreme accumulation of mononuclear cells in the epidermis. These findings suggest that ethanol enhances the expression of inflammatory cytokines independently from T helper (Th)1/Th2 cytokine phenotypes, causing abnormalities in the epidermis resulting in exacerbated allergic reactivity.

  18. Low dose acute alcohol effects on GABAA receptor subtypes

    PubMed Central

    Wallner, Martin; Hanchar, H. Jacob; Olsen, Richard W.

    2010-01-01

    GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (≥100 mM) of ethanol have been reported to enhance activity of most GABAAR subtypes, most abundant synaptic GABAARs are essentially insensitive to ethanol concentrations that occur during social ethanol consumption (<30 mM). However, extrasynaptic δ and β3 subunit-containing GABAARs, associated in the brain with α4or α6 subunits, are sensitive to low millimolar ethanol concentrations, as produced by drinking half a glass of wine. Additionally, we found that a mutation in the cerebellar α6 subunit (α6R100Q), initially reported in rats selectively bred for increased alcohol sensitivity, is sufficient to produce increased alcohol-induced motor impairment and further increases of alcohol sensitivity in recombinant α6β3δ receptors. Furthermore, the behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement on α4/6/β3δ receptors, without reducing GABA-induced currents. In binding assays α4β3δ GABAARs bind [3H] Ro15-4513 with high affinity, and this binding is inhibited, in an apparently competitive fashion, by low ethanol concentrations, as well as analogs of Ro15-4513 that are active to antagonize ethanol or Ro15-4513’s block of ethanol. We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABAAR subtypes. PMID:16814864

  19. Low dose naltrexone for induction of remission in Crohn's disease.

    PubMed

    Segal, Dan; Macdonald, John K; Chande, Nilesh

    2014-02-21

    Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. A systematic search of MEDLINE, EMBASE, CENTRAL, and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Register was performed from inception to February 2013 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also reviewed. Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.2). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed

  20. Variability of repeated coronary artery calcium scoring and radiation Dose on 64- and 16-slice computed tomography by prospective electrocardiographically-triggered axial and retrospective electrocardiographically-gated spiral computed tomography: a phantom study.

    PubMed

    Horiguchi, Jun; Kiguchi, Masao; Fujioka, Chikako; Arie, Ryuichi; Shen, Yun; Sunasaka, Kenichi; Kitagawa, Toshiro; Yamamoto, Hideya; Ito, Katsuhide

    2008-08-01

    We sought to compare coronary artery calcium (CAC) scores, the variability and radiation doses on 64- and 16-slice computed tomography (CT) scanners by both prospective electrocardiographically (ECG)-triggered and retrospective ECG-gated scans. Coronary artery models (n = 3) with different plaque CT densities (approximately 240 Hounsfield units [HU], approximately 600 HU, and approximately 1000 HU) of four sizes (1, 3, 5, and 10 mm in length) on a cardiac phantom were scanned three times in five heart rate sequences. The tube current-time products were set to almost the same on all four protocols (32.7 mAs for 64-slice prospective and retrospective scans, 33.3 mAs for 16-slice prospective and retrospective scans). Slice thickness was set to 2.5 mm to keep the radiation dose low. Overlapping reconstruction with a 1.25-mm increment was applied on the retrospective ECG-gated scan. The CAC scores were not different between the four protocols (one-factor analysis of variance: Agatston, P = .32; volume, P = .19; and mass, P = .09). Two-factor factorial analysis of variance test revealed that the interscan variability was different between protocols (P < .01) and scoring algorithms (P < .01). The average variability of Agatston/volume/mass scoring and effective doses were as follows: 64-slice prospective scan: 16%/15%/11% and 0.5 mSv; 64-slice retrospective scan: 11%/11%/8% and 3.7 mSv; 16-slice prospective scan: 20%/18%/13% and 0.6 mSv; and 16-slice retrospective scan: 16%/15%/11% and 2.9 to 3.5 mSv (depending on the pitch). Retrospective ECG-gated 64-slice CT showed the lowest variability. Prospective ECG-triggered 64-slice CT, with low radiation dose, shows low variability on CAC scoring comparable to retrospective ECG-gated 16-slice CT.

  1. Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma.

    PubMed

    Fiorito, Filomena; Cantiello, Antonietta; Granato, Giovanna Elvira; Navas, Luigi; Diffidenti, Carmine; De Martino, Luisa; Maharajan, Veeramani; Olivieri, Fabio; Pagnini, Ugo; Iovane, Giuseppe

    2016-10-01

    Feline herpesvirus 1 (FHV-1) is a widespread cat pathogen inducing rhinitis, conjunctivitis and corneal ulcers. To alleviate acute FHV-1-induced disease, antiviral agents are used often with antibiotics. But sometimes, these treatments, as well as conventional doses of cytokines have moderate efficacy and/or collateral effects. Herein we have investigated the effects of low dose interleukin (IL)-12 plus interferon (IFN)-gamma, prepared by Sequential Kinetic Activated (SKA), on the treatment of FHV-1 infection. Twenty-five, unvaccinated FHV-1-positive cats were recruited into a prospective, randomized, placebo-controlled, double-blinded clinical trial. Fifteen cats were treated for 6 months with oral low doses of SKA IL-12 plus IFN-gamma and 10 cats were treated with placebo. At 1, 6 and 12 months (follow-up) after the beginning of treatment, clinical assessment, PCR assay and blood count were carried out. At follow-up, in treated group, we observed significant (p<0.05) improvements in clinical signs and PCR became negative in 12/15 cats (80%). In placebo, 10/10 cats were PCR-positive, with improvements (30%) or worsening (70%) in clinical signs. Blood values were normal in both groups. Our results show that the low dose therapy, based on activated solutions of IL-12 plus IFN-gamma, represents a novel approach to treat FHV-1 infection in cats.

  2. Anatomical-based partial volume correction for low-dose dedicated cardiac SPECT/CT

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R.; Sinusas, Albert J.; Liu, Chi

    2015-09-01

    count cardiac SPECT studies, typically obtained from low-dose protocols, gated studies, and dynamic applications.

  3. Anatomical-based partial volume correction for low-dose dedicated cardiac SPECT/CT.

    PubMed

    Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R; Sinusas, Albert J; Liu, Chi

    2015-09-07

    for low count cardiac SPECT studies, typically obtained from low-dose protocols, gated studies, and dynamic applications.

  4. Anatomical-based Partial Volume Correction for Low-dose Dedicated Cardiac SPECT/CT

    PubMed Central

    Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R.; Sinusas, Albert J.; Liu, Chi

    2016-01-01

    for low count cardiac SPECT studies, typically obtained from low-dose protocols, gated studies, and dynamic applications. PMID:26296043

  5. Evaluation of dose reduction and image quality in CT colonography: comparison of low-dose CT with iterative reconstruction and routine-dose CT with filtered back projection.

    PubMed

    Nagata, Koichi; Fujiwara, Masanori; Kanazawa, Hidenori; Mogi, Tomohiro; Iida, Nao; Mitsushima, Toru; Lefor, Alan T; Sugimoto, Hideharu

    2015-01-01

    To prospectively evaluate the radiation dose and image quality comparing low-dose CT colonography (CTC) reconstructed using different levels of iterative reconstruction techniques with routine-dose CTC reconstructed with filtered back projection. Following institutional ethics clearance and informed consent procedures, 210 patients underwent screening CTC using automatic tube current modulation for dual positions. Examinations were performed in the supine position with a routine-dose protocol and in the prone position, randomly applying four different low-dose protocols. Supine images were reconstructed with filtered back projection and prone images with iterative reconstruction. Two blinded observers assessed the image quality of endoluminal images. Image noise was quantitatively assessed by region-of-interest measurements. The mean effective dose in the supine series was 1.88 mSv using routine-dose CTC, compared to 0.92, 0.69, 0.57, and 0.46 mSv at four different low doses in the prone series (p < 0.01). Overall image quality and noise of low-dose CTC with iterative reconstruction were significantly improved compared to routine-dose CTC using filtered back projection. The lowest dose group had image quality comparable to routine-dose images. Low-dose CTC with iterative reconstruction reduces the radiation dose by 48.5 to 75.1% without image quality degradation compared to routine-dose CTC with filtered back projection. • Low-dose CTC reduces radiation dose ≥ 48.5% compared to routine-dose CTC. • Iterative reconstruction improves overall CTC image quality compared with FBP. • Iterative reconstruction reduces overall CTC image noise compared with FBP. • Automated exposure control with iterative reconstruction is useful for low-dose CTC.

  6. A comparison of thoracic spinal anesthesia with low-dose isobaric and low-dose hyperbaric bupivacaine for orthopedic surgery: A randomized controlled trial

    PubMed Central

    Imbelloni, Luiz Eduardo; Gouveia, Marildo A.

    2014-01-01

    Background: The thoracic spinal anesthesia was first described in 1909 and recently revised for various surgical procedures. This is a prospective study aims to evaluate the parameters of the thoracic spinal anesthesia (latency, motor block and paresthesia), the incidence of cardiovascular changes and complications comparing low doses of isobaric and hyperbaric bupivacaine. Materials and Methods: A total of 200 orthopedic patients operated under spinal anesthesia were included in this study. Spinal anesthesia was between T9-T10, with a 27G cutting point or pencil tip in lateral or sitting. Spinal anesthesia was performed with 0.5% bupivacaine isobaric or hyperbaric. Patients remained in cephalad or head down position 10-20° for 10 minutes. We evaluated the demographics, analgesia, and degree of motor block, incidence of paresthesia, bradycardia, hypotension, anesthesia success and neurological complications. Results: All patients developed spinal and there was no failure. The solution did not affect the onset of the blockade. The duration of motor block was greater than the sensitive with isobaric. The duration of sensory block was greater than the motor block with hyperbaric solution. The incidence of paresthesia was 4%, with no difference between the needles. The incidence of hypotension was 12.5% with no difference between the solutions. There was no neurological damage in all patients. Conclusion: The beginning of the block is fast regardless of the solution used. By providing a sensory block of longer duration than the motor block hyperbaric bupivacaine is reflected in a better indication. Thoracic spinal anesthesia provides excellent anesthesia for lower limb orthopedic surgery PMID:25886099

  7. Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction

    NASA Astrophysics Data System (ADS)

    Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

    2015-03-01

    Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

  8. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    SciTech Connect

    Al-Qaisieh, Bashar; Mason, Josh; Bownes, Peter; Henry, Ann; Dickinson, Louise; Ahmed, Hashim U.; Emberton, Mark; Langley, Stephen

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  9. Speech Articulation of Low-Dose Oral Contraceptive Users.

    PubMed

    Meurer, Eliséa Maria; Fontoura, Giana Valeria Fagundez; Corleta, Helena von Eye; Capp, Edison

    2015-11-01

    In the female life cycle, hormonal fluctuations may result in impaired verbal efficiency and vocal worsening during the premenstrual phase. Oral contraceptives may interfere with vocal range. Voice, resonance, and articulation variations clarify speech content. To investigate the phonoarticulatory sounds produced by oral contraceptive users aged between 20 and 30 years. This is a cross-sectional study. Our study included four groups of women (n = 66): two groups used low-dose oral contraceptives and two groups did not use any oral contraceptives. Questionnaires and sound records were used. Acoustic analysis was performed using the Computerized Speech Laboratory program, Model 4341 (Kay Elemetrics Corp, Lincoln Park, New Jersey). The statistical analysis of the SPPS database, version 13.0, was performed by means of generalized estimating equation. In the groups that did not use oral contraceptives, sustained vowel tones were more acute in the two phases and cycles of women older than 25 years (w/oOC1, 175 ± 74 to 190 ± 55 Hz; w/oOC2, 194 ± 56 to 210 ± 32 Hz). At the midfollicular phase (Fph) and midluteal phase (Lph) of the two cycles, the speed of the speech was slower in this group (w/oOC1: Fph, 5.3 ± 1.6/s and Lph, 5.4 ± 1.4/s; w/oOC2: Fph, 4.5 ± 1.7/s and Lph, 4.8 ± 1.1/s). In both groups that used oral contraceptives, there was a higher modulation frequency in the sentences when compared with nonusers (OC1, 33 ± 10 Hz; w/oOC1, 28 ± 10 Hz; OC2, 34 ± 10 Hz; w/oOC2, 27 ± 10 Hz). Vocal intensity was closer between the OC1 (62 ± 4 dB), w/oOC1 (61 ± 3 dB), and OC2 (63 ± 4 dB) groups when compared with the w/oOC2 (67 ± 6 dB) group. We demonstrated hormonal influences on speech articulation of contraceptive users and nonusers. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  10. Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter?

    PubMed

    Morgan, William F

    2016-03-01

    Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered.

  11. Early interim FDG PET/CT prediction of treatment response and prognosis in pediatric Hodgkin disease-added value of low-dose CT.

    PubMed

    Ilivitzki, Anat; Radan, Lea; Ben-Arush, Miriam; Israel, Ora; Ben-Barak, Ayelet

    2013-01-01

    Interim 18F-FDG PET helps predict outcome and tailor treatment in adults with Hodgkin disease (HD). The purpose of this study was to assess predictive values of interim 18F-FDG PET/CT in children with HD and to define the potential added value to interim PET of low-dose CT. Children were prospectively enrolled August 2002-April 2007. PET/low-dose CT was performed at staging, after 2 cycles, at the end of treatment and during follow-up (mean 45 months). Treatment was unchanged regardless of interim results. PET and low-dose CT were read independently. Of 34 enrolled children (ages 3-17 years), 27 achieved complete response, 4 had progressive disease and 3 had relapse. Interim PET alone had positive and negative predictive values of 67% and 89%, respectively. Interim low-dose CT alone had positive and negative predictive values of 35% and 100%, respectively. Interim PET/CT had positive and negative predictive values of 75% and 96%, respectively. Early interim PET/CT was a good predictor of outcome. Integrated PET and low-dose CT improved the predictive value in children with HD.

  12. Low-dose gefitinib treatment for patients with advanced non-small cell lung cancer harboring sensitive epidermal growth factor receptor mutations.

    PubMed

    Satoh, Hironori; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

    2011-08-01

    Although standard schedule of gefitinib was the administration of 250 mg tablet every day, many patients need dose reduction because of toxicities. However, the efficacy of such low-dose gefitinib for patients with epidermal growth factor receptor-mutated non-small cell lung cancer has rarely been evaluated. A post hoc comparison of the efficacy (response rate and survival) in patients treated with gefitinib with or without any dose reduction in NEJ002 study was performed. Among 114 patients treated with first-line gefitinib in NEJ002, 61 (54%) continued gefitinib without any dose reduction until their diseases progressed, and 53 (46%) reduced their dose of gefitinib because of some toxicities. There was no significant difference of patient characteristics between the two groups. The progression-free survival of low-dose group tended to be better than that of standard-dose group (median progression-free survival, 11.8 versus 9.9 months; p = 0.144), and the overall survival of low-dose group was also better than that of standard-dose group (median survival time, 32.7 versus 25.3 months; p = 0.049). The results suggest that low-dose gefitinib may be clinically not inferior to standard-dose gefitinib for non-small cell lung cancer with sensitive epidermal growth factor receptor mutations. Prospective study of low-dose gefitinib is warranted especially for frail patients who need less toxic treatment.

  13. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder.

    PubMed

    Gris, Jean-Christophe; Mercier, Eric; Quéré, Isabelle; Lavigne-Lissalde, Géraldine; Cochery-Nouvellon, Eva; Hoffet, Médéric; Ripart-Neveu, Sylvie; Tailland, Marie-Laure; Dauzat, Michel; Marès, Pierre

    2004-05-15

    The prospective evaluation of the effect of thromboprophylaxis in women with one unexplained pregnancy loss from the 10th week of amenorrhea was performed. A total of 160 patients with heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency were given 5 mg folic acid daily before conception, to be continued during pregnancy, and low-dose aspirin 100 mg daily or low-molecular-weight heparin enoxaparin 40 mg was taken from the 8th week. Twenty-three of the 80 patients treated with low-dose aspirin and 69 of the 80 patients treated with enoxaparin had a healthy live birth (odds ratio [OR], 15.5; 95% confidence interval [CI], 7-34, P <.0001). Enoxaparin was superior to low-dose aspirin in each subgroup defined according to the underlying constitutional thrombophilic disorder. An associated protein Z deficiency and/or positive antiprotein Z antibodies were associated with poorer outcomes. The neonate weight was higher in the women successfully treated with enoxaparin, and neonates small for gestational age were more frequent in patients treated with low-dose aspirin. No significant side effects of the treatments could be evidenced in patients or newborns. As there is no argument to prove that low-dose aspirin may have been deleterious, these results support enoxaparin use during such at-risk pregnancies.

  14. Proposed Criteria for the Use of Low-Dose Vitamin K Supplementation in Patients Using Vitamin K Antagonists: A Literature Review of a Clinical Controversy.

    PubMed

    Evans, Christy E; Getchell, Katerine E; Ivy, Delaney R

    2017-01-01

    Vitamin K antagonists (VKAs) have been used for decades to prevent thromboembolic events, but can be burdensome to patients based on numerous factors impacting anticoagulation control. Low-dose vitamin K supplementation has been theorized to improve anticoagulation control in patients on VKAs that may be vitamin K deficient. The objective of this literature review is to propose criteria for implementing low-dose vitamin K supplementation in patients on VKAs. The CHEST 2012 antithrombotic guidelines recommended against routine use of vitamin K supplementation in patients on VKAs. An observational study and three randomized controlled trials pertaining to this recommendation were evaluated. A literature review was also performed on other studies looking at the impact of low-dose vitamin K supplementation on anticoagulation control through a search in PubMed and the Cochrane Database of Systematic Reviews. One retrospective and two prospective studies were reviewed. Six of the seven studies demonstrated a non-statistically significant trend in data supporting improvement in anticoagulation control with low-dose vitamin K supplementation. While many of the studies did not achieve significant results, the majority demonstrated a trend in support of the improvement of anticoagulation control with low-dose vitamin K supplementation in patients on VKAs.

  15. [Epidemiology of digestive complications associated with use of low-dose aspirin].

    PubMed

    Czernichow, Pierre; Merle, Véronique

    2004-04-01

    Low-dose aspirin (< 330 mg/d) is recommended for the prevention of myocardial infarction or ischemic stroke. Six to 12% of the general population is exposed to low-dose aspirin. The most frequently studied digestive complications are bleeding peptic ulcers, whose risk is increased twofold by low-dose aspirin treatment, and non-complicated peptic ulcers. History of bleeding or non-complicated peptic ulcer, alcohol intake, concomitant treatment with NSAID or calcic inhibitors are demonstrated risk factors of bleeding ulcer associated with low-dose aspirin. The role of enteric coating, of low-dose aspirin dose, of delay since low-dose aspirin treatment onset, and of Helicobacter pylori infection, remains controversial. Antisecretory drugs (H2 inhibitors, proton pump inhibitors), and nitroglycerin are associated with a decreased risk of bleeding ulcer. The protective effect of COX-2 inhibitors on the risk of bleeding ulcer is suppressed by concomitant treatment with low-dose aspirin. The risk of no- complicated peptic ulcer was increased by low-dose aspirin intake by a factor 2.9 in one study. Low-dose aspirin dose, infection by Helicobacter pylori, NSAID intake, and absence of enteric coating, are possible risk factors for non-complicated peptic ulcer. No association was retrieved with alcohol intake and peptic ulcer history.

  16. A Simple Low-dose X-ray CT Simulation from High-dose Scan.

    PubMed

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong; Ma, Jianhua

    2015-10-01

    Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low-dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements.

  17. A knowledge-based iterative model reconstruction algorithm: can super-low-dose cardiac CT be applicable in clinical settings?

    PubMed

    Oda, Seitaro; Utsunomiya, Daisuke; Funama, Yoshinori; Katahira, Kazuhiro; Honda, Keiichi; Tokuyasu, Shinichi; Vembar, Mani; Yuki, Hideaki; Noda, Katsuo; Oshima, Shuichi; Yamashita, Yasuyuki

    2014-01-01

    To investigate whether "full" iterative reconstruction, a knowledge-based iterative model reconstruction (IMR), enables radiation dose reduction by 80% at cardiac computed tomography (CT). A total of 23 patients (15 men, eight women; mean age 64.3 ± 13.4 years) who underwent retrospectively electrocardiography-gated cardiac CT with dose modulation were evaluated. We compared full-dose (FD; 730 mAs) images reconstructed with filtered back projection (FBP) technique and the low-dose (LD; 146 mAs) images reconstructed with FBP and IMR techniques. Objective and subjective image quality parameters were compared among the three different CT images. There was no significant difference in the CT attenuation among the three reconstructions. The mean image noise of LD-IMR (18.3 ± 10.6 Hounsfield units [HU]) was significantly lowest among the three reconstructions (41.9 ± 15.3 HU for FD-FBP and 109.9 ± 42.6 HU for LD-FBP; P < .01). The contrast-to-noise ratio of LD-IMR was better than that of FD-FBP and LD-FBP (P < .01). Visual evaluation score was also highest for LD-IMR. The IMR can provide improved image quality at super-low-dose cardiac CT with 20% of the standard tube current. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  18. The effects of repeated low-dose sarin exposure

    SciTech Connect

    Shih, T.-M. . E-mail: tsungming.a.shih@us.army.mil; Hulet, S.W.; McDonough, J.H.

    2006-09-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD{sub 5} dose of sarin (42 {mu}g/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD{sub 5} of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD{sub 5} of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD{sub 5} sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD{sub 5} sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD{sub 5} sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD{sub 5} sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0

  19. The effect of low-dose oxytocin infusion on cerebral hemodynamics in pregnant women.

    PubMed

    van Veen, Teelkien R; Belfort, Michael A; Zeeman, Gerda G

    2011-08-01

    We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive, nonsmoking patients undergoing induction of labor. No vasoactive drugs were used before or during the study period. Measurements were made at baseline and 15, 30, 60, and 120 minutes after oxytocin initiation. Mean arterial pressure, cerebral perfusion pressure, resistance index, resistance area product, and cerebral flow index at different times were calculated and compared using one-way analysis of variance (ANOVA) for repeated measures or Friedman repeated-measures ANOVA as appropriate, with P<0.05 regarded as significant. No significant systemic or cerebrovascular changes were noted after oxytocin initiation, and there was no correlation between the dosage administered and any hemodynamic parameter. Induction-dose oxytocin does not significantly affect selected cerebral hemodynamic parameters in the first 2 hours after initiation. © Thieme Medical Publishers.

  20. Pulmonary function in patients with trophoblastic disease treated with low-dose methotrexate.

    PubMed Central

    Gillespie, A. M.; Lorigan, P. C.; Radstone, C. R.; Waterhouse, J. C.; Coleman, R. E.; Hancock, B. W.

    1997-01-01

    The Sheffield Trophoblastic Disease Centre treats about 25 patients with persistent trophoblastic disease each year. A total of 75% of patients are classified as low risk according to the Charing Cross Hospital prognostic scoring system and receive methotrexate (MTX) 50 mg, i.m., on days 1, 3, 5, 7 with folinic acid 7.5 mg orally 24 h after each methotrexate injection. There is a 7-day rest between treatment cycles. Remission is achieved in 85% of cases. Approximately 20% of patients experienced pleuritic chest pain and dyspnoea. We have evaluated prospectively lung function in 16 low-risk patients receiving methotrexate. All patients had pulmonary function tests [spirometry-forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and transfer factor - TLCO, kCO] performed before and after completed treatment. A mean of 7.5 cycles of MTX were administered (range 4-11). There was a significant reduction in the mean TLCO (mean pre/post 8.15/7.38 mmol min-1 kPa-1, P = 0.01), but there were no other statistically significant changes. Three patients experienced respiratory symptoms and were found to have a 39%, 28%, and 11% reduction in TLCO from baseline, improving on follow up to pretreatment levels. Low-dose MTX is an effective therapy but may cause troublesome pulmonary toxicity. PMID:9374387

  1. Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

    PubMed

    Cook, S D; Devereux, C; Troiano, R; Wolansky, L; Guarnaccia, J; Haffty, B; Bansil, S; Goldstein, J; Sheffet, A; Zito, G; Jotkowitz, A; Boos, J; Dowling, P; Rohowsky-Kochan, C; Volmer, T

    1997-11-25

    In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

  2. Low-dose fenfluramine in the treatment of neurologic disorders: experience in Dravet syndrome

    PubMed Central

    Schoonjans, An-Sofie; Lagae, Lieven; Ceulemans, Berten

    2015-01-01

    In this paper, we review the experience with fenfluramine in epileptic and other paroxysmal disorders. Since the best available data are from the treatment of Dravet syndrome, we will focus primarily on this condition. Originally fenfluramine was launched as an anorectic agent. As early as 1985, seizure reduction in children could be demonstrated in a few cases with photosensitive, self-induced epilepsy. Hereafter, a small study was launched in patients with self-induced epilepsy. Results showed a significant seizure reduction, and review of the patient data showed that 5 of the 12 patients had Dravet syndrome. During that observation period, fenfluramine was withdrawn from the market because of cardiovascular side effects associated with prescribing higher doses in combination with phentermine for weight loss. In March 2002, a Belgian Royal Decree was issued permitting further study of fenfluramine in pediatric patients with intractable epilepsy. In 2011 under the Royal Decree, a prospective study of patients with Dravet syndrome treated with low-dose fenfluramine was initiated and is currently ongoing. The initial results are promising in terms of reduction of seizure frequency and overall tolerability. PMID:26600876

  3. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  4. [Risk and prevention of gastrointestinal complications due to low-dose aspirin and other antiplatelet agents].

    PubMed

    Bretagne, Jean-François

    2008-09-15

    Upper and lower gastrointestinal (GI) haemorrhages are the main complications associated with low-dose aspirin or anti-thrombotic drugs. In France, low-dose aspirin or anti-thrombotic agents use has been found in 30% of upper GI and 40% of lower GI bleeding episodes. Main causes of GI bleeding with low-dose aspirin are gastroduodenal peptic ulcer and colonic diverticulosis. Recent cohort studies have shown that the relative risk of GI bleeding with low-dose aspirin was comprised between 2 and 4 and the absolute risk comprised between 1 per 100 and 1 per 1000 aspirin users per year. Main risk factors for upper GI bleeding with low-dose aspirin are concomitant antiplatelet agents, anticoagulants, non steroidal anti-inflammatory drugs or steroids use, and recent history of complicated or non-complicated gastroduodenal ulcer. Helicobacter pylori infection increases the risk for upper GI bleeding with low-dose aspirin, but infection should be searched and treated only in patients with peptic ulcer. Despite eradication of H. pylori in the latter patients, gastroprotection with PPI is strongly recommended. In patients presenting with peptic ulcer bleeding with low-dose aspirin, aspirin should be continued in association with PPI rather than replaced with clopidogrel. Discontinuation of low-dose aspirin which exposes to increased cardiovascular complications and mortality should be avoided, even in cases of peptic ulcer bleeding.

  5. Low doses of glyphosate change the response of soybean to later glyphosate exposures

    USDA-ARS?s Scientific Manuscript database

    The stimulatory effect of low doses of toxic substances is known as hormesis. Many herbicides that cause severe injury to plants at recommended rates, promote growth or have other stimulatory effects at very low doses. The objective of this study was to evaluate glyphosate-induced hormesis in soyb...

  6. Detection and size measurements of pulmonary nodules in ultra-low-dose CT with iterative reconstruction compared to low dose CT.

    PubMed

    Sui, Xin; Meinel, Felix G; Song, Wei; Xu, Xiaoli; Wang, Zixing; Wang, Yuyan; Jin, Zhengyu; Chen, Jiuhong; Vliegenthart, Rozemarijn; Schoepf, U Joseph

    2016-03-01

    In this study, the accuracy of ultra-low-dose computed tomography (CT) with iterative reconstruction (IR) for detection and measurement of pulmonary nodules was evaluated. Eighty-four individuals referred for lung cancer screening (mean age: 54.5±10.8 years) underwent low-dose computed tomography (LDCT) and ultra-low-dose CT. CT examinations were performed with attenuation-based tube current modulation. Reference tube voltage and current were set to 120kV/25mÅs for LDCT and 80kV/4mÅs for ultra-low-dose CT. CT images were reconstructed with filtered back projection (FBP) for LDCT, and with FBP and IR for ultra-low-dose CT datasets. A reference standard was established by a consensus panel of 2 different radiologists on LDCT. Volume and diameter of the solid nodules were measured on LDCT with FBP and ultra-low dose CT with FBP and IR. Interobserver and interscan variability were analyzed and compared by the Bland-Altman method. A total of 127 nodules were identified, including 105 solid nodules, 15 part solid nodules, 7 ground glass nodules. On ultra-low-dose CT scans, the effective radiation dose was 0.13±0.11mSv. A total of 113 (88.9%) and 110 (86.6%) true-positive nodules with FBP versus 117 (92.1%) and 118(92.9%) with IR were detected by two observers, respectively. The volume and size of the 105 solid nodules were measured, with mean volume/diameter of 46.5±46.6 mm(3)/5.1±1.6mm. There was no significant difference in nodule volume or diameter measurements between ultra-low-dose CT and LDCT protocols for solid nodules. Ultra-low-dose CT with iterative reconstruction has high sensitivity for lung nodule detection without significant difference in nodule size and volume measurement compared to LDCT. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms

    NASA Astrophysics Data System (ADS)

    Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M.; Asma, Evren; Kinahan, Paul E.; De Man, Bruno

    2015-09-01

    For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition. We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 s. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.043 75 mAs, were investigated. Both the analytical Feldkamp, Davis and Kress (FDK) algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality. With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose

  8. Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms.

    PubMed

    Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M; Asma, Evren; Kinahan, Paul E; De Man, Bruno

    2015-10-07

    For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition.We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 s. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.043 75 mAs, were investigated. Both the analytical Feldkamp, Davis and Kress (FDK) algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality.With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose levels

  9. Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms

    PubMed Central

    Rui, Xue; Cheng, Lishui; Long, Yong; Fu, Lin; Alessio, Adam M.; Asma, Evren; Kinahan, Paul E.; De Man, Bruno

    2015-01-01

    For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition. Methods We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 seconds. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.04375 mAs, were investigated. Both the analytical FDK algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean-squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality. Results With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose levels

  10. New feasible treatment for refractory autoimmune encephalitis: Low-dose interleukin-2.

    PubMed

    Lim, Jung-Ah; Lee, Soon-Tae; Moon, Jangsup; Jun, Jin-Sun; Park, Byeong-Su; Byun, Jung-Ick; Sunwoo, Jun-Sang; Park, Kyung-Il; Jung, Keun-Hwa; Jung, Ki-Young; Lee, Sang Kun; Chu, Kon

    2016-10-15

    Low-dose interleukin-2 (IL-2) restores the balance of regulatory and effector T cells. We aimed to determine the feasibility of low-dose IL-2 as a treatment for refractory autoimmune encephalitis (AE). Ten patients who had received low-dose IL-2 were retrospectively identified. We observed an improvement in the modified Rankin Scale scores of six patients at the last follow-up compared with the scores at the initiation of low-dose IL-2 (p=0.014). One patient experienced treatment-related grade 3 neutropenia. Overall, low-dose IL-2 is a feasible and relatively safe treatment for AE patients who are refractory to the first- and second-line immunotherapies. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. A prospective, randomised trial of preoperative rectal diclofenac: are we closing the gate after the horse has gone?

    PubMed

    Lyons, J B; Niazi, A; Lowe, D; Sheehan, S J; Moriarty, J

    2003-01-01

    Diclofenac sodium is a non-steroidal anti-inflammatory agent commonly used to provide analgesia post-surgery. It is common clinical practice to administer a diclofenac suppository at induction to contribute to pre-emptive analgesia (PEA). Diclofenac takes up to 30 minutes to attain maximal plasma level after rectal administration. To compare post-operative analgesia in patients who received diclofenac 30-45 minutes preoperatively, or at induction of anaesthesia. A prospective, randomised, double-blind controlled trial in 157 patients undergoing varicose vein surgery. Group A (control) received a rectal placebo 30-45 minutes preoperatively, group B received diclofenac 100 mg 30-45 minutes preoperatively and group C received placebo 30-45 minutes preoperatively and diclofenac 100 mg at induction. Outcome measures were Visual Analogue Scores (VAS) and requirement for rescue analgesia. Patients in group A had significantly poorer analgesia than patients in groups B and C. There were no significant differences in VAS values and requirements for rescue analgesia between groups B and C 3-4 hours and 18-22 hours postoperatively. For patients undergoing varicose vein surgery preoperative administration of rectal diclofenac significantly improves post-operative analgesia and this effect is independent of whether it is given at induction or 30-45 minutes preoperatively.

  12. Quantitative Evaluation of Acute Renal Transplant Dysfunction with Low-Dose Three-dimensional MR Renography

    PubMed Central

    Zhang, Jeff L.; Rusinek, Henry; Chandarana, Hersh; Vivier, Pierre-Hugues; Babb, James S.; Diflo, Thomas; John, Devon G.; Benstein, Judith A.; Barisoni, Laura; Stoffel, David R.; Lee, Vivian S.

    2011-01-01

    Purpose: To assess prospectively the ability of quantitative low-dose three-dimensional magnetic resonance (MR) renography to help identify the cause of acute graft dysfunction. Materials and Methods: This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained. Between December 2001 and May 2009, sixty patients with transplanted kidneys (41 men and 19 women; mean age, 49 years; age range, 22–71 years) were included. Thirty-one patients had normal function and 29 had acute dysfunction due to acute rejection (n = 12), acute tubular necrosis (ATN) (n = 8), chronic rejection (n = 6), or drug toxicity (n = 3). MR renography was performed at 1.5 T with three-dimensional gradient-echo imaging. With use of a multicompartment renal model, the glomerular filtration rate (GFR) and the mean transit time (MTT) of the tracer for the vascular compartment (MTTA), the tubular compartment (MTTT), and the collecting system compartment (MTTC) were calculated. Also derived was MTT for the whole kidney (MTTK = MTTA + MTTT + MTTC) and fractional MTT of each compartment (MTTA/K = MTTA/MTTK, MTTT/K = MTTT/MTTK, MTTC/K = MTTC/MTTK). These parameters were compared in patients in the different study groups. Statistical analysis was performed by using analysis of covariance. Results: There were significant differences in GFR and MTTK between the acute dysfunction group (36.4 mL/min ± 20.8 [standard deviation] and 177.1 seconds ± 46.8, respectively) and the normal function group (65.9 mL/min ± 27.6 and 140.5 seconds ± 51.8, respectively) (P < .001 and P = .004). The MTTA/K was significantly higher in the acute rejection group (mean, 12.7% ± 2.9) than in the normal function group (mean, 8.3% ± 2.2; P < .001) or in the ATN group (mean, 7.1% ± 1.4; P < .001). The MTTT/K was significantly higher in the ATN group (mean, 83.2% ± 9.2) than in the normal function group (mean, 72.4% ± 10.2; P = .031) or in the acute rejection group

  13. Maternal and neonatal effects of adding morphine to low-dose bupivacaine for epidural labor analgesia.

    PubMed

    Dostbil, A; Celik, M; Alici, H A; Erdem, A F; Aksoy, M; Ahiskalioglu, A

    2014-01-01

    Labor is one of the most painful experiences a woman may face during her lifetime. One of the most effective methods used for eliminating this pain is epidural analgesia. The aim of this study to determine the impact of adding morphine to low-dose bupivacaine epidural anesthesia on labor and neonatal outcomes, and maternal side effects. This is a prospective randomized double-blind study comparing two regimens of anesthetic agents used for epidural anesthesia in labor. A total of 120 pregnant women were randomized into two groups with 60 subjects in each study arm. A catheter was inserted, and 0.1% bupivacaine + 2 μg/mL fentanyl in 15 mL saline were given to Group bupivacaine-fentanyl (Group BF), while 0.0625% bupivacaine + 2 μg/ml fentanyl + 2 mg morphine in 15 mL saline were given to Group bupivacaine-fentanyl-morphine (Group BFM) with no test dosing from the needle. No morphine was added to the subsequent epidural injections in Group BFM. The total dose of bupivacaine was significantly lower in Group BFM relative to Group BF (P = 0.0001). The visual analogu scalescores at 15, 30, and 45 min were significantly lower in Group BF compared to thosein Group BFM (P = 0.0001, P = 0.001, and P = 0.006, respectively). The second stage of labor was significantly shorter in Group BFM relative to Group BF (P = 0.027 and P = 0.003, respectively). The satisfaction with analgesia following the first dose was higher in the nonmorphine group (P = 0.0001). However, maternal postpartum satisfaction was similar in both groups. Either nausea or vomiting was recorded in eight patients in Group BFM. We believe that epidural analgesia comprised of a low-dose local anaesthetic and 2 mg morphine provides a painless labor that significantly reducesthe use of local anesthetic without changing the efficiency of the analgesic, ensuring the mother's satisfaction without leading to an adverse effect on the mother or foetus, while mildly (but significantly) shortening the second stage of

  14. Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury.

    PubMed

    Westphal, Martin; Rehberg, Sebastian; Maybauer, Marc O; Maybauer, Dirk M; Enkhbaatar, Perenlei; Westphal-Varghese, Beena B; Schmalstieg, Frank C; Morita, Naoki; Cox, Robert A; Traber, Lillian D; Hawkins, Hal; Whorton, Elbert; Traber, Daniel L

    2011-02-01

    To elucidate the effects of low-dose arginine vasopressin on cardiopulmonary functions and nitrosative stress using an established model of acute lung injury. Prospective, randomized, controlled laboratory experiment. Investigational intensive care unit. Eighteen chronically instrumented sheep. Sheep were randomly assigned to a sham group without injury or treatment, an injury group without treatment (40% total body surface area third-degree burn and 48 breaths of cold cotton smoke), or an injured group treated with arginine vasopressin (0.02 IU·min⁻¹) from 1 hr after injury until the end of the 24-hr study period (each n = 6). All sheep were mechanically ventilated and fluid resuscitated using an established protocol. There were no differences among groups at baseline. The injury was characterized by a severe deterioration of cardiopulmonary function (left ventricular stroke work indexes and Pao2/Fio2 ratio; p < .01 each vs. sham). Compared with controls, arginine vasopressin infusion improved myocardial function, as suggested by higher stroke volume indexes and left ventricular stroke work indexes (18-24 hrs and 6-24 hrs, respectively; p < .05 each). In addition to an improved gas exchange (higher Pao2/Fio2 ratios from 6 to 24 hrs, p < .01 each), pulmonary edema (bloodless wet-to-dry-weight ratio; p = .018), bronchial obstruction (p = .01), and pulmonary shunt fraction (12-24 hrs; p ≤ .001 each) were attenuated in arginine vasopressin-treated animals compared with controls. These changes occurred along with reduced nitrosative stress, as indicated by lower plasma levels of nitrate/nitrite (12-24 hrs, p < .01 each), as well as lower myocardial and pulmonary tissue concentrations of 3-nitrotyrosine (p = .041 and p = .042 vs. controls, respectively). At 24 hrs, pulmonary 3-nitrotyrosine concentrations were negatively correlated with Pao2/Fio2 ratio (r = -.882; p < .001) and myocardial 3-nitrotyrosine content with stroke volume indexes (r = -.701; p = .004

  15. Prospectively versus Retrospectively ECG-Gated 256-Slice CT Angiography to Assess Coronary Artery Bypass Grafts — Comparison of Image Quality and Radiation Dose

    PubMed Central

    Lee, Yi-Wei; Yang, Ching-Ching; Mok, Greta S. P.; Law, Wei-Yip; Su, Cheng-Tau; Wu, Tung-Hsin

    2012-01-01

    Objective In this retrospective non-randomized cohort study, the image quality and radiation dose were compared between prospectively electrocardiogram (ECG)-gated axial (PGA) and retrospectively ECG-gated helical (RGH) techniques for the assessment of coronary artery bypass grafts using 256-slice CT. Methods We studied 124 grafts with 577 segments in 64 patients with a heart rate (HR) <85 bpm who underwent CT coronary angiography (CTCA); 34 patients with RGH-CTCA and 30 patients with PGA-CTCA. The image quality of the bypass grafts was assessed by a 5-point scale (1 = excellent to 5 = non-diagnostic) for each segment (proximal anastomosis, proximal, middle, distal course of graft body, and distal anastomosis). Other objective image quality indices such as noise, signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR) were assessed. Radiation doses were also compared. Results Patient characteristics of the two groups were well matched except HR. The HR of the PGA group was lower than that of the RGH group (62.0±5.0 vs. 65.7±7.4). For both groups, over 90% of segments received excellent or good image quality scores and none was non-evaluative. The image quality generally degraded as graft segment approached to distal anastomosis regardless of techniques and graft types. Image quality scores of the PGA group were better than those of the RGH group (1.51±0.53 vs. 1.73±0.62; p<0.001). There was no significantly difference of objective image quality between two techniques, and the effective radiation dose was significantly lower in the PGA group (7.0±1.2 mSv) than that of the RGH group (20.0±4.6 mSv) (p<0.001), with a 65.0% dose reduction. Conclusions Following bypass surgery, 256-slice PGA-CTCA is superior to RGH-CTCA in limiting the radiation dose and obtaining better image quality for bypass grafts. PMID:23145126

  16. Detection of bladder cancer: comparison of low-dose scans with AIDR 3D and routine-dose scans with FBP on the excretory phase in CT urography

    PubMed Central

    Tsuboyama, Takahiro; Kumano, Seishi; Inada, Yuki; Koyama, Mitsuhiro; Azuma, Haruhito; Narumi, Yoshifumi

    2016-01-01

    Objective: To prospectively compare the detection of bladder cancer between low-dose scans with adaptive iterative dose reduction three dimensional projection (AIDR 3D) and routine-dose scans with filtered back projection (FBP) on the excretory phase (EP) in CT urography. Methods: 42 patients were included. Routine- and low-dose EP were performed in each patient. Routine-dose images were reconstructed with FBP, and low-dose images were reconstructed with AIDR 3D. Two radiologists scored confidence levels for the presence or absence of bladder cancer using a 5-point scale. The CT dose index of each EP was measured, and the dose reduction was calculated. Results: Sensitivity, specificity and accuracy were 86.4%, 95.0% and 90.5% on routine-dose scans and were 86.4%, 90.0% and 88.1% on low-dose scans, respectively. There was no significant difference (p; not significant, 1.00 and 1.00, respectively). The average CT dose index was 8.07 and 2.63 mGy on routine- and low-dose scans, and the ratio of dose reduction was 67.6%. Conclusion: The detection of bladder cancer on low-dose scans with AIDR 3D is almost equal to that on routine-dose scans with FBP on the EP, with nearly 70% dose reduction. Advances in knowledge: Using AIDR 3D, the radiation dose may be reduced on the EP in CT urography for the detection of bladder cancer. PMID:26642306

  17. Prevalence and independent factors for gastroduodenal ulcers/erosions in asymptomatic patients taking low-dose aspirin and gastroprotective agents: the OITA-GF study.

    PubMed

    Tamura, A; Murakami, K; Kadota, J

    2011-02-01

    Although it is well known that aspirin causes gastroduodenal mucosal injury and that aspirin-induced gastroduodenal mucosal injury is often asymptomatic, the prevalence and independent factors for gastroduodenal mucosal injury have not been clarified in asymptomatic patients taking low-dose aspirin and gastroprotective agents. To clarify the prevalence and independent factors for gastroduodenal ulcers/erosions in asymptomatic patients taking low-dose aspirin and gastroprotective agents. Prospective observational study. We performed endoscopy in 150 asymptomatic patients taking low-dose aspirin and gastroprotective agents for at least 3 months. Gastroduodenal ulcers/erosions were observed in 37.3% [ulcers (4.0%); erosions (34.0%)]. Univariate logistic regression analyses showed that proton-pump inhibitor (PPI) use was negatively associated with gastroduodenal ulcers/erosions [odds ratio (OR) 0.35, 95% confidence interval (95% CI) 0.17-0.75, P=0.007]. A multivariate logistic regression analysis selected PPI use as the only independent factor for gastroduodenal ulcers/erosions (OR 0.35, 95% CI 0.14-0.86, P=0.02). None of the 53 patients with PPI use had any gastroduodenal ulcers, and 11 with standard-dose PPI use tended to have a lower prevalence of gastroduodenal erosions than 42 with low-dose PPI use (0% vs. 28.6%, P=0.052). Gastroduodenal ulcers/erosions were observed in about one-third of asymptomatic patients taking low-dose aspirin and gastroprotective agents, and PPI use was a negative independent factor for gastroduodenal ulcers/erosions in those patients. In addition, standard-dose PPI therapy might be more effective in the prevention of aspirin-induced gastroduodenal mucosal injury than low-dose PPI therapy.

  18. Low-dose colchicine for secondary prevention of cardiovascular disease.

    PubMed

    Nidorf, Stefan M; Eikelboom, John W; Budgeon, Charley A; Thompson, Peter L

    2013-01-29

    The objective of this study was to determine whether colchicine 0.5 mg/day can reduce the risk of cardiovascular events in patients with clinically stable coronary disease. The presence of activated neutrophils in culprit atherosclerotic plaques of patients with unstable coronary disease raises the possibility that inhibition of neutrophil function with colchicine may reduce the risk of plaque instability and thereby improve clinical outcomes in patients with stable coronary disease. In a clinical trial with a prospective, randomized, observer-blinded endpoint design, 532 patients with stable coronary disease receiving aspirin and/or clopidogrel (93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and followed for a median of 3 years. The primary outcome was the composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke. The primary analysis was by intention-to-treat. The primary outcome occurred in 15 of 282 patients (5.3%) who received colchicine and 40 of 250 patients (16.0%) assigned no colchicine (hazard ratio: 0.33; 95% confidence interval [CI] 0.18 to 0.59; p < 0.001; number needed to treat: 11). In a pre-specified secondary on-treatment analysis that excluded 32 patients (11%) assigned to colchicine who withdrew within 30 days due to intestinal intolerance and a further 7 patients (2%) who did not start treatment, the primary outcome occurred in 4.5% versus 16.0% (hazard ratio: 0.29; 95% CI: 0.15 to 0.56; p < 0.001). Colchicine 0.5 mg/day administered in addition to statins and other standard secondary prevention therapies appeared effective for the prevention of cardiovascular events in patients with stable coronary disease. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

    PubMed Central

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-01-01

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen. PMID:26515758

  20. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation.

    PubMed

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-10-30

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen.

  1. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses

    PubMed Central

    Nam, Seon Young; Yang, Kwang Hee; Kim, Cha Soon; Lee, In Kyung; Kim, Ji Young

    2015-01-01

    Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro. PMID:26317642

  2. Ultra-low dose (+)-naloxone restores the thermal threshold of morphine tolerant rats.

    PubMed

    Chou, Kuang-Yi; Tsai, Ru-Yin; Tsai, Wei-Yuan; Wu, Ching-Tang; Yeh, Chun-Chang; Cherng, Chen-Hwan; Wong, Chih-Shung

    2013-12-01

    As known, long-term morphine infusion leads to tolerance. We previously demonstrated that both co-infusion and post-administration of ultra-low dose (±)-naloxone restores the antinociceptive effect of morphine in morphine-tolerant rats. However, whether the mechanism of the action of ultra-low dose (±)-naloxone is through opioid receptors or not. Therefore, in the present study, we further investigated the effect of ultra-low dose (+)-naloxone, it does not bind to opioid receptors, on the antinociceptive effect of morphine. Male Wistar rats were implanted with one or two intrathecal (i.t.) catheters; one catheter was connected to a mini-osmotic pump, used for morphine (15 μg/h), ultra-low dose (+)-naloxone (15 pg/h), morphine plus ultra-low dose (+)-naloxone (15 pg/h) or saline (1 μl/h) infusion for 5 days. On day 5, either ultra-low dose (+)-naloxone (15 pg) or saline (5 μl) was injected via the other catheter immediately after discontinued morphine or saline infusion. Three hours later, morphine (15 μg in 5 μl saline) or saline were given intrathecally. All rats received nociceptive tail-flick test every 30 minutes for 120 minutes after morphine challenge at different temperature (45-52°C, respective). Our results showed that, both co-infusion and post-treatment of ultra-low dose (+)-naloxone with morphine preserves the antinociceptive effect of morphine. Moreover, in the post administration rats, ultra-low dose (+)-naloxone further enhances the antinociceptive effect of morphine. This study provides an evidence for ultra-low dose (+)-naloxone as a therapeutic adjuvant for patients who need long-term opioid administration for pain management. Copyright © 2013. Published by Elsevier B.V.

  3. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    PubMed

    Joo, Hae Mi; Kang, Su Jin; Nam, Seon Young; Yang, Kwang Hee; Kim, Cha Soon; Lee, In Kyung; Kim, Ji Young

    2015-01-01

    Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  4. Initial Performance of Radiologists and Radiology Residents in Interpreting Low-Dose (2-mSv) Appendiceal CT.

    PubMed

    Yang, Hyun Kyung; Ko, Yousun; Lee, Min Hee; Woo, Hyunsik; Ahn, Soyeon; Kim, Bohyoung; Pickhardt, Perry J; Kim, Mi Sung; Park, Sung Bin; Lee, Kyoung Ho

    2015-12-01

    The objective of our study was to prospectively evaluate the initial diagnostic performance and learning curve of a community of radiologists and residents in interpreting 2-mSv appendiceal CT. We included 46 attending radiologists and 153 radiology residents from 22 hospitals who completed an online training course of 30 2-mSv CT cases. Appendicitis was confirmed in 14 cases. Most of the readers had limited (≤ 10 cases, n = 32) or no (n = 118) prior experience with low-dose appendiceal CT. The order of cases was randomized for each reader. A multireader multicase ROC analysis was performed. Generalized estimating equations were used to model the learning curves in diagnostic performance. Diagnostic performance gradually improved with years of training. The average AUC was 0.94 (95% CI, 0.90-0.98), 0.92 (0.88-0.96), 0.90 (0.85-0.96), and 0.86 (0.80-0.92) for the attending radiologists, senior residents, 2nd-year residents, and 1st-year residents, respectively. We did not observe any notable intrareader learning curves over the training course of the 30 cases except a decrease in reading time. Diagnostic accuracy and sensitivity were significantly affected by the reader training level and prior overall experience with appendiceal CT but not by the prior specific experience with low-dose appendiceal CT. The learning curve is likely prolonged and forms gradually over years by overall radiology training and clinical experience in general rather than by experience with low-dose appendiceal CT specifically.

  5. Sedation with ketamine and low-dose midazolam for short-term procedures requiring pharyngeal manipulation in young children.

    PubMed

    Novak, Helena; Karlsland Akeson, Pia; Akeson, Jonas

    2008-01-01

    Pediatric intestinal biopsy procedures including considerable transpharyngeal manipulation of a wire-guided metal capsule require adequate sedation or anesthesia. This retrospective cohort study was designed to evaluate intravenous sedation with ketamine and low-dose midazolam in young children undergoing these procedures before and also after discharge from the hospital. A total of 244 biopsy procedures in 217 children under the age of 16 years were evaluated. All anesthesia records were reviewed according to a defined study protocol and in 145 cases the parents were also interviewed by telephone to obtain further information on possible adverse effects before and after discharge. Ketamine and low-dose midazolam were carefully titrated by an experienced anesthesia team at an approximate dose ratio of 40 : 1 (total doses 2.3 and 0.05 mg.kg(-1)) in continuously monitored spontaneously breathing children. Possibly associated problems before discharge were salivation (5.7%), vomiting (4.9%), oxygen desaturation (3.3%), laryngospasm (2.5%) and rash (1.2%) according to the patient records and blurred vision (27%), nausea and vomiting (19%), vertigo (13%) and hallucinations or nightmares (3.5%) according to telephone interviews. Few, mild and transient problems remained after discharge from the hospital. Careful titration of ketamine and low-dose midazolam provides adequate sedation for nonsurgical pediatric short-term procedures also requiring considerable pharyngeal manipulation, particularly considering the low number of serious airway problems such as laryngospasm. The high incidence of late postoperative problems suggests that prospective studies should be designed for long-term follow-up of young children subjected to sedation or anesthesia.

  6. Different effects of tibolone and low-dose EPT in the management of postmenopausal women with primary headaches.

    PubMed

    Nappi, Rossella E; Sances, Grazia; Sommacal, Arianna; Detaddei, Silvia; Facchinetti, Fabio; Cristina, Silvano; Polatti, Franco; Nappi, Giuseppe

    2006-01-01

    The present randomized prospective study aimed to compare the effect of tibolone (T) with conventional low-dose estrogen-progestogen therapy (EPT) administered in a combined continuous regimen on the course of primary headaches in postmenopausal women requesting hormone therapy (HT) for climacteric complaints. Forty women presenting for clinical evaluation of headache (migraine without aura and episodic tension-type headache) were enrolled. The observational period lasted 7 months during which women kept a diary of the clinical characteristics of headache attacks and analgesic use. Climacteric symptoms and both anxiety and depression were also measured. After a 1-month run-in period, women received two different HT regimens: 1 mg 17beta-estradiol + 0.5 mg norethisterone acetate (EPT) or 2.5 mg T. Follow-up evaluations were planned after 3 and 6 months of treatment. Although T did not affect the number of days with migraine without aura, it significantly reduced the number of hours during which pain intensity prohibited daily activities (P < 0.001) and the number of analgesics (P < 0.001) after 3 months. Conventional low-dose EPT administered in a combined continuous regimen was confirmed to have a mild, but negative, effect on the course of migraine without aura by increasing the number of days with head pain (P < 0.001) and the number of analgesics (P < 0.001). Interestingly, both treatments were effective in the management of episodic tension-type headache, significantly reducing the number of days with head pain, severity, and analgesic consumption. In postmenopausal headache sufferers, analgesics are more effective in alleviating severe head pain when women are treated with T in comparison with low-dose EPT for climacteric complaints.

  7. Low-Dose High-Pitch CT Angiography of the Supraaortic Arteries Using Sinogram-Affirmed Iterative Reconstruction

    PubMed Central

    Beitzke, Dietrich; Nolz, Richard; Unterhumer, Sylvia; Plank, Christina; Weber, Michael; Schernthaner, Rüdiger; Schöpf, Veronika; Wolf, Florian; Loewe, Christian

    2014-01-01

    Objective To prospectively evaluate image quality and radiation dose using a low-dose computed tomography angiography protocol and iterative image reconstruction for high-pitch dual-source CT-angiography (DSCTA) of the supraaortic arteries. Material and Methods DSCTA was performed in 42 patients, using either 120 kVp tube voltage, 120 mAS tube current, 2.4 pitch and filtered back projection, or 100 kVp tube voltage, 100 mAs tube current, 3.2 pitch, and sinogram affirmed iterative reconstruction. Measurements of vessel attenuation, of the contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) were performed to objectively evaluate image quality. Two readers evaluated subjective image quality and image noise, using a four-point scale. Effective dose was used to compare the differences in radiation dose. Results Low-dose protocol application showed significantly higher vessel opacification (p = 0.013), and non-significantly higher CNR and SNR values. There was no difference in the subjective image quality and image noise reading between the protocols. Effective dose was significantly lower using the low-dose protocol (1.29±0.21 mSv vs. 2.92±0.72 mSv; p<0.001). Conclusion The combined use of reduced tube voltage, reduced tube current, and iterative reconstruction reduces radiation dose by 55.4% in high-pitch DSCTA of the supraaortic arteries without impairment of image quality. PMID:24919195

  8. Low Dose of Some Persistent Organic Pollutants Predicts Type 2 Diabetes: A Nested Case–Control Study

    PubMed Central

    Lee, Duk-Hee; Steffes, Michael W.; Sjödin, Andreas; Jones, Richard S.; Needham, Larry L.; Jacobs, David R.

    2010-01-01

    Background Low doses of some persistent organic pollutants (POPs) associate cross-sectionally with type 2 diabetes, whereas associations with high POP exposures are inconsistent. Objectives We investigated whether several POPs prospectively predict type 2 diabetes within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Methods Participants in this nested case–control study were diabetes free in 1987–1988. By 2005–2006, the 90 controls remained free of diabetes, whereas the 90 cases developed diabetes. Using serum collected in 1987–1988, we measured 8 organochlorine pesticides, 22 polychlorinated biphenyl congeners (PCBs), and 1 polybrominated biphenyl (PBB). We compared POP concentrations from CARDIA and the National Health and Nutrition Examination Survey (NHANES) in 2003–2004. We computed odds ratios (ORs) for incident diabetes using logistic regression analysis. Results Chlorinated POPs in CARDIA in 1987–1988 were much higher than corresponding NHANES 2003-2004 concentrations. POPs showed nonlinear associations with diabetes risk. The highest risk was observed in the second quartiles of trans-nonachlor, oxychlordane, mirex, highly chlorinated PCBs, and PBB153—a finding that suggests low-dose effects. We concentrated risk by summing these POPs and isolated very low concentrations of multiple POPs in the lowest sextile of the sum. The adjusted OR in the second sextile vs. the lowest sextile was 5.3 overall and 20.1 for body mass index ≥ 30 kg/m2. Conclusions Several POPs at low doses similar to current exposure levels may increase diabetes risk, possibly through endocrine disruption. Certain POPs may a play a role in the current epidemic of diabetes, which has been attributed to obesity. PMID:20444671

  9. Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

    2012-01-01

    We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

  10. Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

    NASA Technical Reports Server (NTRS)

    Johnston, A.; Barnes, C.

    1995-01-01

    Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

  11. Modeling Low-Dose-Rate Effects in Irradiated Bipolar-Base Oxides

    SciTech Connect

    Cirba, C.R.; Fleetwood, D.M.; Graves, R.J.; Michez, A.; Milanowski, R.J.; Saigne, F.; Schrimpf, R.D.; Witczak, S.C.

    1998-10-26

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in bipolar junction transistors. Multiple-trapping simulations show that space charge limited transport is partially responsible for low-dose-rate enhancement. At low dose rates, more holes are trapped near the silicon-oxide interface than at high dose rates, resulting in larger midgap voltage shifts at lower dose rates. The additional trapped charge near the interface may cause an exponential increase in excess base current, and a resultant decrease in current gain for some NPN bipolar technologies.

  12. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yin, Xindao; Shi, Luyao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis; Toumoulin, Christine

    2013-08-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors.

  13. Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

    NASA Technical Reports Server (NTRS)

    Johnston, A.; Barnes, C.

    1995-01-01

    Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

  14. Noise reduction with low dose CT data based on a modified ROF model.

    PubMed

    Zhu, Yining; Zhao, Mengliu; Zhao, Yunsong; Li, Hongwei; Zhang, Peng

    2012-07-30

    In order to reduce the radiation exposure caused by Computed Tomography (CT) scanning, low dose CT has gained much interest in research as well as in industry. One fundamental difficulty for low dose CT lies in its heavy noise pollution in the raw data which leads to quality deterioration for reconstructed images. In this paper, we propose a modified ROF model to denoise low dose CT measurement data in light of Poisson noise model. Experimental results indicate that the reconstructed CT images based on measurement data processed by our model are in better quality, compared to the original ROF model or bilateral filtering.

  15. Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia.

    PubMed

    Crain, S M; Shen, K F

    2001-01-05

    Our previous electrophysiologic studies on nociceptive types of dorsal root ganglion (DRG) neurons in culture demonstrated that extremely low fM-nM concentrations of morphine and many other bimodally-acting mu, delta and kappa opioid agonists can elicit direct excitatory opioid receptor-mediated effects, whereas higher (microM) opioid concentrations evoked inhibitory effects. Cotreatment with pM naloxone or naltrexone (NTX) plus fM-nM morphine blocked the excitatory effects and unmasked potent inhibitory effects of these low opioid concentrations. In the present study, hot-water-immersion tail-flick antinociception assays at 52 degrees C on mice showed that extremely low doses of morphine (ca. 0.1 microg/kg) can, in fact, elicit acute hyperalgesic effects, manifested by rapid onset of decreases in tail-flick latency for periods >3 h after drug administration. Cotreatment with ultra-low-dose NTX (ca. 1-100 pg/kg) blocks this opioid-induced hyperalgesia and unmasks potent opioid analgesia. The consonance of our in vitro and in vivo evidence indicates that doses of morphine far below those currently required for clinical treatment of pain may become effective when opioid hyperalgesic effects are blocked by coadministration of appropriately low doses of opioid antagonists. This low-dose-morphine cotreatment procedure should markedly attenuate morphine tolerance, dependence and other aversive side-effects.

  16. A comparative study of paediatric oral premedication: midazolam, ketamine and low dose combination of midazolam and ketamine.

    PubMed

    Banerjee, Bhakti; Bose, Anjana; Pahari, Subrata; Dan, Amit Kumar

    2011-06-01

    In a prospective randomised double-blind trial, 90 patients aged 1-7 years (ASA I) undergoing elective surgery less than 90 minutes duration were allocated into three separate groups to compare the safety and effectiveness of oral midazolam, ketamine, and low dose combination of midazolam and ketamine for premedication in paediatric patients. Group M received midazolam 0.5 mg kg(-1), group K received ketamine 6mg kg(-1) and group C received combination of ketamine 2.5 mg kg(-1) and midazolam 0.25 mg kg(-1) orally in 0.2ml kg(-1) of sugar syrup to make it palatable. The sedation score and emotional state on a four -point scale, ease of parental separation, cooperation for venepuncture, ease of mask acceptance and peri-operative cardiorespiratory status were evaluated. Peri-operative incidence of vomiting, nystagmus, emergence phenomenon and postanesthetic recovery time were noted. In the present study it was found that C group was more effective in sedating the children within 10 minutes and 20 minutes, whereas, the combination and midazolam groups are comparable in sedating the children at 30 minutes. Side-effects and recovery time were more in ketamine group. The recovery time was significantly less in group C. In conclusion oral combination of low dose ketamine and midazolam produced quick onset of satisfactory conscious sedation and more rapid recovery without significant side-effects, so that more children could be separated easily from their parents and provides smooth induction than the individual drug.

  17. Sexual behavior of women taking low-dose oral contraceptive containing 15 microg ethinylestradiol/60 microg gestodene.

    PubMed

    Caruso, Salvatore; Agnello, Carmela; Intelisano, Giorgia; Farina, Marco; Di Mari, Lucia; Cianci, Antonio

    2004-03-01

    The objective of this prospective study was to assess the effects of a low-dose oral contraceptive (OC) containing 15 microg ethinylestradiol and 60 microg gestodene on sexuality. Forty-eight healthy volunteers (age range, 18-35 years), having regular menstrual cycles with ovulation, participated in the study. Sexual behavior was assessed using the self-administered Personal Experience Questionnaire, at baseline, and at 3, 6 and 9 months of pill use. Women reported decreased sexual desire (p < 0.005) and sexual activity (p < 0.05) at the 9th month of pill use, and diminished sexual arousal at the 3rd month of pill intake (p < 0.05), with respect to baseline. The frequency of orgasm did not change during OC use (p = NS). Moreover, sexual enjoyment was worse at the 3rd, 6th and 9th month with respect to baseline (p < 0.001). The low dose of ethinylestradiol could cause decreased vaginal lubrication, and diminished sexual arousal could be due to hypoandrogenism. Women may expect increased sexual performance when they take the pill, as compared to before starting contraception. Consequently, they could have an unexpected effect with pill use, though sexuality may remain the same.

  18. Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies.

    PubMed

    Barcellini, Wilma; Zaja, Francesco; Zaninoni, Anna; Imperiali, Francesca Guia; Battista, Marta Lisa; Di Bona, Eros; Fattizzo, Bruno; Consonni, Dario; Cortelezzi, Agostino; Fanin, Renato; Zanella, Alberto

    2012-04-19

    This prospective study investigated the efficacy, safety, and response duration of low-dose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first- or second-line therapy in 23 patients with primary autoimmune hemolytic anemia (AIHA). The overall response was 82.6% at month +2, and subsequently stabilized to ∼ 90% at months +6 and +12; the response was better in warm autoimmune hemolytic anemia (WAIHA; overall response, 100% at all time points) than in cold hemagglutinin disease (CHD; average, 60%); the relapse-free survival was 100% for WAIHA at +6 and +12 months versus 89% and 59% in CHD, respectively, and the estimated relapse-free survival at 2 years was 81% and 40% for the warm and cold forms, respectively. The risk of relapse was higher in CHD and in patients with a longer interval between diagnosis and enrollment. Steroid administration was reduced both as cumulative dose (∼ 50%) and duration compared with the patient's past history. Treatment was well tolerated and no adverse events or infections were recorded; retreatment was also effective. The clinical response was correlated with amelioration biologic markers such as cytokine production (IFN-γ, IL-12, TNF-α, and IL-17), suggesting that low-dose rituximab exerts an immunomodulating activity. This study is registered at www.clinicaltrials.gov as NCT01345708.

  19. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Cancer.gov

    A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

  20. Enhanced charge trapping in bipolar spacer oxides during low-dose-rate irradiation

    SciTech Connect

    Fleetwood, D.M.; Reber, R.A. Jr.; Winokur, P.S.; Kosier, S.L.; Schrimpf, R.D.; Nowlin, R.N.; Pease, R.L.; DeLaus, M.

    1994-03-01

    Thermally-stimulated-current and capacitance-voltage measurements reveal enhanced hole trapping in bipolar spacer-oxide capacitors irradiated at 0 V at low dose rates. Possible mechanisms and implications for bipolar low-rate response are discussed.

  1. An evaluation of low-dose simvastatin in achieving LDL goal: a retrospective chart review.

    PubMed

    Schnee, David M; Bogdanski, Laura; Zaiken, Kathy; McCloskey, William W

    2007-05-01

    Treatment for hyperciholesterolemia targets low-density lipoprotein (LDL) cholesterol. In July 2004, an update to the existingcholesterol guidelines was published that recommended more intense lowering of LDL levels. This study, a retrospective chart review conducted at a multispecialty medical group practice, aimed to determine iflow-dose simvastatin (5 or 10 mg) was effective at achieving LDL goal, in light of these more aggressive guidelines. Demographic data, including risk factors and LDL levels, were collected on 173 patients identified as taking low-dose simvastatin. The review indicated that 66% of patients with low-to-rnoderate cardiovascular risk treated with low-dose simvastatin achieved their risk-appropriate LDL goalMore than 50% of patients who achieved this LDL goal on low-dose simvastatin fell into lower-risk cattegories. Therefore, low-dose simvastatin may be a beneficial treatment option for patients in lower cardiovascular-risk categories.

  2. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    PubMed Central

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  3. 20 percent lower lung cancer mortality with low-dose CT vs chest X-ray

    Cancer.gov

    Scientists have found a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray.

  4. Low dose intrathecal clonidine and fentanyl added to hyperbaric bupivacaine prolongs analgesia in gynecological surgery

    PubMed Central

    Chopra, Pooja; Talwar, Vandana

    2014-01-01

    Background: We undertook this study to ascertain if a small dose of clonidine (30 μg) when added to a bupivacaine-fentanyl mixture improves spinal analgesia, without producing side effects, as compared to a bupivacaine-fentanyl or a bupivacaine-clonidine mixture. Materials and Methods: In this prospective, randomized, double-blind study, 75 (American Society of Anesthesiologists) ASA grade I-II patients, aged between 45 and 65 years, who were scheduled for vaginal hysterectomy with pelvic floor repair or non-descent vaginal hysterectomy under spinal anesthesia were recruited. The patients received hyperbaric bupivacaine (2.3 ml) with fentanyl 15 μg (Group BF) or clonidine 30 μg (Group BC) or both fentanyl (15 μg) and clonidine (30 μg) (Group BCF). The total amount of intrathecal mixture was constant (2.8 ml) in all the groups. Duration of sensory, motor block and effective analgesia, hemodynamic profile, postoperative pain score and analgesic requirements were recorded. Results: The duration of effective analgesia, mean time till two-segment regression, and duration of sensory and motor block were significantly longer in group BCF as compared to group BC (P ~ 0.002), and in group BC as compared to group BF (P ~ 0.01). The incidence of intraoperative pain and requirement of postoperative analgesics in the first 24 hours was significantly more in group BF as compared to the other groups (P ~ 0.01). There was no difference in the hemodynamic profile between the groups. Conclusion: Low-dose clonidine (30 μg) when added to a bupivacaine-fentanyl mixture increased the duration of effective analgesia and the duration of sensory and motor block in gynecological surgery. The incidence of intraoperative pain and requirement of postoperative analgesics was significantly less when clonidine was added to intrathecal bupivacaine with or without fentanyl. PMID:24803764

  5. Quality of Life of Oral Cancer Patients After Low-Dose-Rate Interstitial Brachytherapy

    SciTech Connect

    Yoshimura, Ryo-ichi Shibuya, Hitoshi; Miura, Masahiko; Watanabe, Hiroshi; Ayukawa, Fumio; Hayashi, Keiji; Toda, Kazuma

    2009-03-01

    Purpose: To assess the quality of life (QOL) of oral cancer patients treated with low-dose-rate interstitial brachytherapy (LDR-BT) alone. Methods and Materials: Between June 2005 and July 2006, a total of 56 patients with oral cancer were enrolled in this prospective study. QOL was assessed by means of the core questionnaire and head and neck questionnaire module of the European Organization for Research and Treatment of Cancer (EORTC Quality of Life Questionnaire-Core 30 [QLQ-C30] and QLQ Head and Neck 35 [H and N35]). The questionnaires were distributed to the patients before the start of treatment and 3 months, 6 months, and 12 months after the start of LDR-BT. Results: It was possible to analyze the results for 20 of the initial 56 patients because they did not experience metastasis or recurrence during this study. No functions or symptoms asked about in the QLQ-C30 deteriorated during the first year. The emotional function score steadily and significantly increased. No symptoms in the QLQ-H and N35 significantly deteriorated. The scores for pain, trouble with social eating, and weight loss on the QLQ-H and N35 steadily and significantly decreased. Age, gender, and LDR-BT source had no effect on the change in QOL during the first year, but T-stage significantly affected the change in global health status, tumor site affected the changes in swallowing, sensory problems, sticky saliva, and complications affected the changes in pain, swallowing, and mouth opening. Conclusions: QOL of oral cancer patients treated with LDR-BT is high. However, tumor stage, tumor site, and complications affected the changes in a few functions and symptoms during the first year.

  6. [Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery].

    PubMed

    Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

    2015-01-01

    The aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. In this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25μg fentanyl. All the patients remained in the seated position for 5min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. Motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. Spinal saddle block using hyperbaric levobupivacaine with both 12.5μg and 25μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  7. Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery.

    PubMed

    Honca, Mehtap; Dereli, Necla; Kose, Emine Arzu; Honca, Tevfik; Kutuk, Selcen; Unal, Selma Savas; Horasanli, Eyup

    2015-01-01

    the aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. in this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5 μg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25 μg fentanyl. All the patients remained in the seated position for 5 min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. spinal saddle block using hyperbaric levobupivacaine with both 12.5 μg and 25 μg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  8. An evaluation of human ADME and mass balance studies using regular or low doses of radiocarbon.

    PubMed

    Roffel, A F; van Marle, S P; van Lier, J J; Hartstra, J; van Hoogdalem, E-J

    2016-12-01

    There has been increased interest in conducting human absorption, distribution, metabolism, and excretion (ADME) studies with low doses (up to 0.1 MBq) as opposed to regular doses (1.85-3.7 MBq) of radiocarbon ((14) C). This is due to the fact that low-dose human ADME studies may be conducted without dosimetry calculations and will lead to lower human radiation exposure. Here, we sought to compare the outcomes of low-dose versus regular-dose human ADME studies in healthy volunteers. Forty oral human ADME studies conducted at PRA were surveyed, among which 12 were low-dose studies. The fraction of drug material absorbed was 67% ± 7% in the regular-dose studies (data for 13 studies) versus 39% ± 16% in the low-dose studies (data for 5 studies). The average total recovery of (14) C in excreta was 93% ± 5% for regular-dose studies, and 21 of 28 such studies showed recoveries more than 90%. For low-dose studies, average total recovery was 89% ± 9%, and 6 of 12 studies showed recoveries more than 90%. Metabolite profiling was successful in all cases reported (13 regular-dose studies and 5 low-dose studies). There was no obvious relationship between the total recoveries of (14) C in excreta and the proportion of (14) C excreted in feces, or between the total recoveries and the plasma elimination half-lives for parent or total (14) C, neither in the low-dose nor the regular-dose studies. A significant correlation was found between the fraction absorbed and the recovery in feces in the low-dose but not in the regular-dose studies, and no correlation was found between the fractions absorbed and the total recoveries in both types of studies. Low-dose studies were more often conducted on drugs that had a plasma elimination half-life of parent drug more than 100 hours (5 of 12 studies) than regular-dose studies (1 of 26 studies). We conclude that both low-dose as well as regular-dose human ADME studies provide adequate data to support decision making for further

  9. Reduced lung-cancer mortality with low-dose computed tomographic screening.

    PubMed

    Aberle, Denise R; Adams, Amanda M; Berg, Christine D; Black, William C; Clapp, Jonathan D; Fagerstrom, Richard M; Gareen, Ilana F; Gatsonis, Constantine; Marcus, Pamela M; Sicks, JoRean D

    2011-08-04

    The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer

  10. Tacrolimus combined with low-dose corticosteroids is an effective and safe therapeutic option for refractory IgA nephropathy

    PubMed Central

    Wan, Qi-Jun; Hu, Hao-Fei; He, Yong-Cheng; Luan, Shao-Dong; Chen, Hong-Tao; Li, Tong; Xu, Yi; Xu, Hui-Li; Liao, Ying

    2016-01-01

    Tacrolimus (TAC) has been shown to improve remission from proteinuria in patients with refractory IgA nephropathy (IgAN); however, the efficacy and safety of TAC in such patients have not been fully explored. Therefore, the present study was conducted to evaluate the tolerance to and efficacy of TAC combined with low-dose corticosteroids in patients with refractory IgAN. This was a single-center retrospective study. A total of 28 patients with refractory IgAN were randomly included and received TAC plus corticosteroid; 26 patients received TAC and prednisone, and 2 patients received TAC and methylprednisolone. In addition, all patients were treated with an angiotensin inhibitor. Total urinary protein excretion, serum albumin, blood glucose, complete remission (CR), partial remission (PR), cholesterol, low-density lipoprotein (LDL), serum creatinine (Scr) and estimated GFR (eGFR) were tested at baseline and at 3, 6 and 12 months after the initiation of treatment in all patients. The primary endpoints were CR and PR. Secondary endpoints included changes of Scr, eGFR, clinical data and adverse events. After 12 months, CR was achieved in 40.1% of patients and PR in 43.4%, yielding a total response rate of 83.5%, and the total urinary protein excretion, serum albumin, cholesterol and LDL results were improved significantly compared with those at baseline. Proteinuria and serum albumin results were significantly improved by month 3 of treatment. Two patients relapsed during months 3–6 of follow-up. At the 12-month follow-up, renal function was improved compared with the baseline level as evidenced by eGFR and Scr, respectively. The blood glucose level was stable. One case of pneumococcal pneumonia developed in a patient treated with TAC plus low-dose methylprednisolone and one case of upper gastrointestinal hemorrhage was found in a patient treated with TAC plus low-dose prednisone; both cases completely recovered after treatment. In conclusion, TAC combined with low-dose

  11. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial.

    PubMed

    Ogawa, Hisao; Nakayama, Masafumi; Morimoto, Takeshi; Uemura, Shiro; Kanauchi, Masao; Doi, Naofumi; Jinnouchi, Hideaki; Sugiyama, Seigo; Saito, Yoshihiko

    2008-11-12

    Previous trials have investigated the effects of low-dose aspirin on primary prevention of cardiovascular events, but not in patients with type 2 diabetes. To examine the efficacy of low-dose aspirin for the primary prevention of atherosclerotic events in patients with type 2 diabetes. Multicenter, prospective, randomized, open-label, blinded, end-point trial conducted from December 2002 through April 2008 at 163 institutions throughout Japan, which enrolled 2539 patients with type 2 diabetes without a history of atherosclerotic disease and had a median follow-up of 4.37 years. Patients were assigned to the low-dose aspirin group (81 or 100 mg per day) or the nonaspirin group. Primary end points were atherosclerotic events, including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease. Secondary end points included each primary end point and combinations of primary end points as well as death from any cause. A total of 154 atherosclerotic events occurred: 68 in the aspirin group (13.6 per 1000 person-years) and 86 in the nonaspirin group (17.0 per 1000 person-years) (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58-1.10; log-rank test, P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient (stroke) in the aspirin group and 10 patients (5 fatal myocardial infarctions and 5 fatal strokes) in the nonaspirin group (HR, 0.10; 95% CI, 0.01-0.79; P = .0037). A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause (HR, 0.90; 95% CI, 0.57-1.14; log-rank test, P = .67). The composite of hemorrhagic stroke and significant gastrointestinal bleeding was not significantly different between the aspirin and nonaspirin groups. In this study of patients with type 2 diabetes, low-dose aspirin as primary prevention did not reduce the risk of cardiovascular events. clinicaltrials.gov Identifier: NCT00110448.

  12. [The advance of model of action in low-dose chronic benzene exposure induced hematotoxicity].

    PubMed

    Gao, Chen; Zhang, Zhengbao; Chen, Liping; Chen, Wen

    2015-09-01

    Benzene is classified as Group 1 carcinogen by IARC. It has been found that benzene induces hematotoxicity even in low dose exposure. The identification of key events during benzene induced hematotoxicty leads to adjustment of occupational exposure limits of benzene. In this review, we focus on the exposure, metabolism, target organs, key epigenetic changes, toxicty effects and end points of low-dose chronic benzene exposure induced hematotoxicity and finally discuss the perspectives on the future study of this area.

  13. Use of MOS structures for the investigation of low-dose-rate effects in bipolar transistors

    SciTech Connect

    Belyakov, V.V.; Pershenkov, V.S.; Shalnov, A.V.; Shvetzov-Shilovsky, I.N.

    1995-12-01

    A possible physical mechanism for bipolar transistor low-dose-rate irradiation response is discussed. This mechanism is described in terms of shallow electron traps in oxide. The experimental results on positive charge build-up at low dose-rates and small electric field in oxide are presented. The use of MOS transistor in bipolar mode for investigation of surface peripheral recombination current in bipolar transistor and extraction of MOS structure physical parameters is described.

  14. Low-dose versus standard-dose CT protocol in patients with clinically suspected renal colic.

    PubMed

    Poletti, Pierre-Alexandre; Platon, Alexandra; Rutschmann, Olivier T; Schmidlin, Franz R; Iselin, Christophe E; Becker, Christoph D

    2007-04-01

    The purpose of our study was to compare a low-dose abdominal CT protocol, delivering a dose of radiation close to the dose delivered by abdominal radiography, with standard-dose unenhanced CT in patients with suspected renal colic. One hundred twenty-five patients (87 men, 38 women; mean age, 45 years) who were admitted with suspected renal colic underwent both abdominal low-dose CT (30 mAs) and standard-dose CT (180 mAs). Low-dose CT and standard-dose CT were independently reviewed, in a delayed fashion, by two radiologists for the characterization of renal and ureteral calculi (location, size) and for indirect signs of renal colic (renal enlargement, pyeloureteral dilatation, periureteral or renal stranding). Results reported for low-dose CT, with regard to the patients' body mass indexes (BMIs), were compared with those obtained with standard-dose CT (reference standard). The presence of non-urinary tract-related disorders was also assessed. Informed consent was obtained from all patients. In patients with a BMI < 30, low-dose CT achieved 96% sensitivity and 100% specificity for the detection of indirect signs of renal colic and a sensitivity of 95% and a specificity of 97% for detecting ureteral calculi. In patients with a BMI < 30, low-dose CT was 86% sensitive for detecting ureteral calculi < 3 mm and 100% sensitive for detecting calculi > 3 mm. Low-dose CT was 100% sensitive and specific for depicting non-urinary tract-related disorders (n = 6). Low-dose CT achieves sensitivities and specificities close to those of standard-dose CT in assessing the diagnosis of renal colic, depicting ureteral calculi > 3 mm in patients with a BMI < 30, and correctly identifying alternative diagnoses.

  15. Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone.

    PubMed

    Albers, Lauren N; Arbiser, Jack L; Feldman, Ron J

    2017-08-02

    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.

  16. Cytogenetic Low-Dose Hyperradiosensitivity Is Observed in Human Peripheral Blood Lymphocytes

    SciTech Connect

    Seth, Isheeta; Joiner, Michael C.; Tucker, James D.

    2015-01-01

    Purpose: The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations. Methods and Materials: Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above. Results: HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy. Conclusions: These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.

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

    PubMed

    Madas, Balázs G

    2016-07-01

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

  18. Multidisciplinary European low dose initiative: an update of the MELODI program.

    PubMed

    Salomaa, Sisko; Jourdain, Jean-René; Kreuzer, Michaela; Jung, Thomas; Repussard, Jacques

    2017-10-01

    This paper provides an update and summary on the organization of European research in the field of low dose risk and radiation protection. To address declining resources and competence in radiation protection and related research across European countries, a High Level and Expert Group (HLEG) was established in 2007. The HLEG identified key policy and scientific questions to be addressed through a strategic research agenda for low dose radiation risk. This initiated the establishment of a European Research Platform, called MELODI (Multidisciplinary European Low Dose Research Initiative). Dr Bill Morgan closely followed the European low dose programme and chaired the international Advisory Boards of DoReMi Network of Excellence and the MELODI platform. The MELODI research platform is dedicated to low dose ionizing radiation risk. In 2010, MELODI was founded as a registered association with 15 members. As of September 2016, the association´s membership increased to 46. A major activity of MELODI is the establishment and updating of a long-term Strategic Research Agenda (SRA) for research on low dose risk in Europe. The SRA is intended to guide the priorities for national and European research programmes and the preparation of competitive calls at the European level. A key priority for radiation protection research is to improve health risk estimates for exposures corresponding to the dose limits for occupational exposures and to reference levels for the exposure of the population in emergency situations.

  19. Low-Dose Radiation and Genotoxic Chemicals Can Protect Against Stochastic Biological Effects

    PubMed Central

    Scott, Bobby R.; Walker, Dale M.; Walker, Vernon E.

    2004-01-01

    A protective apoptosis-mediated (PAM) process that is turned on in mammalian cells by low-dose photon (X and γ) radiation and appears to also be turned on by the genotoxic chemical ethylene oxide is discussed. Because of the PAM process, exposure to low-dose photon radiation (and possibly also some genotoxic chemicals) can lead to a reduction in the risk of stochastic effects such as problematic mutations, neoplastic transformation (an early step in cancer occurrence), and cancer. These findings indicate a need to revise the current low-dose risk assessment paradigm for which risk of cancer is presumed to increase linearly with dose (without a threshold) after exposure to any amount of a genotoxic agent such as ionizing radiation. These findings support a view seldom mentioned in the past, that cancer risk can actually decrease, rather than increase, after exposure to low doses of photon radiation and possibly some other genotoxic agents. The PAM process (a form of natural protection) may contribute substantially to cancer prevention in humans and other mammals. However, new research is needed to improve our understanding of the process. The new research could unlock novel strategies for optimizing cancer prevention and novel protocols for low-dose therapy for cancer. With low-dose cancer therapy, normal tissue could be spared from severe damage while possibly eliminating the cancer. PMID:19330143

  20. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.

    PubMed

    Chen, Horng H; Anstrom, Kevin J; Givertz, Michael M; Stevenson, Lynne W; Semigran, Marc J; Goldsmith, Steven R; Bart, Bradley A; Bull, David A; Stehlik, Josef; LeWinter, Martin M; Konstam, Marvin A; Huggins, Gordon S; Rouleau, Jean L; O'Meara, Eileen; Tang, W H Wilson; Starling, Randall C; Butler, Javed; Deswal, Anita; Felker, G Michael; O'Connor, Christopher M; Bonita, Raphael E; Margulies, Kenneth B; Cappola, Thomas P; Ofili, Elizabeth O; Mann, Douglas L; Dávila-Román, Víctor G; McNulty, Steven E; Borlaug, Barry A; Velazquez, Eric J; Lee, Kerry L; Shah, Monica R; Hernandez, Adrian F; Braunwald, Eugene; Redfield, Margaret M

    2013-12-18

    Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo

  1. Comparison of the Effects of Low-Dose Midazolam, Magnesium Sulfate, Remifentanil and Low-Dose Etomidate on Prevention of Etomidate-Induced Myoclonus in Orthopedic Surgeries

    PubMed Central

    Sedighinejad, Abbas; Naderi Nabi, Bahram; Haghighi, Mohammad; Biazar, Gelareh; Imantalab, Vali; Rimaz, Siamak; Zaridoost, Zahra

    2016-01-01

    Background Etomidate is a potent hypnotic agent with several desirable advantages such as providing a stable cardiovascular profile with minimal respiratory adverse effects and better hemodynamic stability compared with other induction agents. This drug is associated, however, with myoclonic movements which is characterized by a sudden, brief muscle contractions as a disturbing side-effect. Objectives The present study was designed to compare the effectiveness of low- dose midazolam, magnesium sulfate, remifentanil and low-dose etomidate to suppress etomidate-induced myoclonus in orthopedic surgery. Patients and Methods A double-blind clinical trial study was conducted in an academic hospital from September 2014 to August 2015. Two hundred and eighty-four eligible patients, American society of anesthesiologists class I - II, scheduled for elective orthopedic surgery were randomly allocated into four equal groups (n = 71). They received premedication with intravenous low-dose midazolam 0.015 mg/kg, magnesium sulfate 30 mg/kg, remifentanil 1 μg/kg and low-dose etomidate 0.03 mg/kg two minutes before induction of anesthesia with 0.3 mg/kg intravenous etomidate. Then the incidence and intensity of myoclonus were evaluated on a scale of 0 - 3; 0 = no myoclonus; 1 = mild (movement at wrist); 2 = moderate (movement at arm only, elbow or shoulder); and 3 = severe, generalized response or movement in more than one extremity, within ninety seconds. Any adverse effect due to these premedication agents was recorded. Results The incidence and intensity of myoclonus were significantly lower in the low-dose etomidate group. The incidence rates of myoclonus were 51 (71.85%), 61 (85.9%), 30 (42.3%) and 41 (57.7%), and the percentages of patients who experienced grade III of myoclonus were 30 (58.8%), 32 (52.5%), 9 (30%) and 14 (34.1%) in the midazolam, magnesium sulfate, etomidate and remifentanil groups, respectively. The incidence and intensity of myoclonus were significantly

  2. Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis.

    PubMed

    Xu, Ying; Hackett, Maree; Carter, Gregory; Loo, Colleen; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A; Mitchell, Philip B; Rodgers, Anthony

    2016-04-01

    Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5 mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50 mg intra-nasal spray, another assessed 0.1-0.4 mg/kg i.v., and another assessed 0.1-0.5 mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6-7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2-5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. © The Author 2015. Published by Oxford University

  3. Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis

    PubMed Central

    Xu, Ying; Hackett, Maree; Carter, Gregory; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A.; Mitchell, Philip B.; Rodgers, Anthony

    2016-01-01

    Background: Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. Methods: A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Results: Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50mg intra-nasal spray, another assessed 0.1–0.4mg/kg i.v., and another assessed 0.1–0.5mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6–7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2–5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Conclusion: Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety. PMID

  4. Comparison of retrospectively self-gated and prospectively triggered FLASH sequences for cine imaging of the aorta in mice at 9.4 Tesla.

    PubMed

    Fries, Peter; Massmann, Alexander; Seidel, Roland; Müller, Andreas; Stroeder, Jonas; Custodis, Florian; Reil, Jan; Schneider, Günther; Buecker, Arno

    2012-04-01

    A critical problem in cardiovascular MRI in small rodents is adjusting the sequence acquisition to the high heart and respiratory rates. The aim of this study was to compare a retrospectively self-gated fast low angle shot navigator (RSG-FLASH) sequence with a conventional prospectively triggered (PT-FLASH) sequence for cine imaging of the ascending aorta in mice at 9.4 T. Ten C57/BL6 mice were examined with a horizontal bore 9.4 Tesla MRI animal scanner using a dedicated 2 × 2 phased-array surface coil. We acquired a RSG-FLASH sequence (RSG-FLASH sequences (repetition time (TR) / echo time (TE) = 6.5/2.5 ms, flip angle (FA) = 10 degrees, field of view (FOV) = 2 × 2 cm, matrix = 384 × 384, slice thickness = 1 mm, 25 movie frames) perpendicular to the ascending aorta using the IntraGate technique. At the same position, we performed a PT-FLASH sequence (TR/TE = 6.5/2.1 ms, FA = 10 degrees, FOV = 2 × 2 cm, matrix = 384 × 384, slice thickness = 1 mm) in which the maximum number of movie frames had to be adjusted to the interval between two R-peaks (RR interval) of the electrocardiogram (ECG) with: number of frames = RR interval / TR." Cross-sectional vessel areas at end-systole (AES) and end-diastole (AED) were measured to determine the aortic strain (ΔA = (AES-AED)/AED). Two blinded readers rated the sequences for presence of flow and trigger artifacts and their influence on the depiction of the blood/vessel-wall interface. Irregularities in displaying the cardiac cycle and the overall suitability of the sequence for aortic strain evaluation were assessed using a 5-level ordinal scale. Statistical differences were analyzed using Student t test and Wilcoxon signed rank test (P < 0.05). Intra- and interobserver variability was evaluated using Bland-Altman analyses. No significant differences were noted between techniques regarding the measured vessel areas (AED: P = 0.07, AES: P = 0.34), ΔA: P = 0.1). Similarly, there were no significant differences in heart (P

  5. 20. DETAIL VIEW OF SUBMERSIBLE GATE, SHOWING GATE ARMS, GATE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. DETAIL VIEW OF SUBMERSIBLE GATE, SHOWING GATE ARMS, GATE PIERS, TRUNNION PIN AND GATE GAUGE, LOOKING NORTHEAST - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 8, On Mississippi River near Houston County, MN, Genoa, Vernon County, WI

  6. 21. DETAIL VIEW OF SUBMERSIBLE TAINTER GATE, SHOWING GATE, GATE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. DETAIL VIEW OF SUBMERSIBLE TAINTER GATE, SHOWING GATE, GATE ARM, TRUNNION PIN, PIER AND GATE GAUGE, LOOKING EAST - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 10, Guttenberg, Clayton County, IA

  7. 17. DETAIL VIEW OF NONSUBMERSIBLE TAINTER GATE, SHOWING GATES, GATE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. DETAIL VIEW OF NON-SUBMERSIBLE TAINTER GATE, SHOWING GATES, GATE ARMS, PIERS AND DAM BRIDGE, WITH ROLLER GATE HEADHOUSE IN BACKGROUND, LOOKING SOUTHEAST - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 9, Lynxville, Crawford County, WI

  8. 17. DETAIL VIEW OF TAINTER GATE, SHOWING GATES, GATE ARMS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. DETAIL VIEW OF TAINTER GATE, SHOWING GATES, GATE ARMS, PIERS, GATE CHAINS AND SWITCHES, AND BRIDGE GIRDERS, LOOKING SOUTHWEST - Upper Mississippi River 9-Foot Channel Project, Lock & Dam No. 5, Minneiska, Winona County, MN

  9. 18. DETAIL VIEW OF TAINTER GATE, SHOWING GATES, GATE ARMS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. DETAIL VIEW OF TAINTER GATE, SHOWING GATES, GATE ARMS, PIERS, GATE CHAINS AND SWITCHES, AND BRIDGE GIRDERS, LOOKING NORTHWEST - Upper Mississippi River 9-Foot Channel Project, Lock & Dam No. 5, Minneiska, Winona County, MN

  10. Motion-compensated PET image reconstruction with respiratory-matched attenuation correction using two low-dose inhale and exhale CT images.

    PubMed

    Nam, Woo Hyun; Ahn, Il Jun; Kim, Kyeong Min; Kim, Byung Il; Ra, Jong Beom

    2013-10-21

    Positron emission tomography (PET) is widely used for diagnosis and follow up assessment of radiotherapy. However, thoracic and abdominal PET suffers from false staging and incorrect quantification of the radioactive uptake of lesion(s) due to respiratory motion. Furthermore, respiratory motion-induced mismatch between a computed tomography (CT) attenuation map and PET data often leads to significant artifacts in the reconstructed PET image. To solve these problems, we propose a unified framework for respiratory-matched attenuation correction and motion compensation of respiratory-gated PET. For the attenuation correction, the proposed algorithm manipulates a 4D CT image virtually generated from two low-dose inhale and exhale CT images, rather than a real 4D CT image which significantly increases the radiation burden on a patient. It also utilizes CT-driven motion fields for motion compensation. To realize the proposed algorithm, we propose an improved region-based approach for non-rigid registration between body CT images, and we suggest a selection scheme of 3D CT images that are respiratory-matched to each respiratory-gated sinogram. In this work, the proposed algorithm was evaluated qualitatively and quantitatively by using patient datasets including lung and/or liver lesion(s). Experimental results show that the method can provide much clearer organ boundaries and more accurate lesion information than existing algorithms by utilizing two low-dose CT images.

  11. Motion-compensated PET image reconstruction with respiratory-matched attenuation correction using two low-dose inhale and exhale CT images

    NASA Astrophysics Data System (ADS)

    Nam, Woo Hyun; Ahn, Il Jun; Kim, Kyeong Min; Kim, Byung Il; Ra, Jong Beom

    2013-10-01

    Positron emission tomography (PET) is widely used for diagnosis and follow up assessment of radiotherapy. However, thoracic and abdominal PET suffers from false staging and incorrect quantification of the radioactive uptake of lesion(s) due to respiratory motion. Furthermore, respiratory motion-induced mismatch between a computed tomography (CT) attenuation map and PET data often leads to significant artifacts in the reconstructed PET image. To solve these problems, we propose a unified framework for respiratory-matched attenuation correction and motion compensation of respiratory-gated PET. For the attenuation correction, the proposed algorithm manipulates a 4D CT image virtually generated from two low-dose inhale and exhale CT images, rather than a real 4D CT image which significantly increases the radiation burden on a patient. It also utilizes CT-driven motion fields for motion compensation. To realize the proposed algorithm, we propose an improved region-based approach for non-rigid registration between body CT images, and we suggest a selection scheme of 3D CT images that are respiratory-matched to each respiratory-gated sinogram. In this work, the proposed algorithm was evaluated qualitatively and quantitatively by using patient datasets including lung and/or liver lesion(s). Experimental results show that the method can provide much clearer organ boundaries and more accurate lesion information than existing algorithms by utilizing two low-dose CT images.

  12. An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis.

    PubMed

    Martin-Martin, L S; Giovannangeli, F; Bizzi, E; Massafra, U; Ballanti, E; Cassol, M; Migliore, A

    2017-01-01

    Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA). One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA). The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA) IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL) in patients affected by RA in maintaining LDA or remission obtained after biological therapy. This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28), clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs) therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA cytokines may be an opportunity to explore in the management of RA.

  13. An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis

    PubMed Central

    Martin-Martin, LS; Giovannangeli, F; Bizzi, E; Massafra, U; Ballanti, E; Cassol, M; Migliore, A

    2017-01-01

    Background Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA). One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA). The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA) IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL) in patients affected by RA in maintaining LDA or remission obtained after biological therapy. Method This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28), clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs) therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. Results The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. Conclusion This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA cytokines may be an opportunity to explore in the management of RA. PMID:28408798

  14. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium Annual Meeting of the Environmental Mutagen Society: Agenda and Abstracts

    SciTech Connect

    Veigl, Martina L.; Morgan, William F.; Schwartz, Jeffrey L.

    2009-11-11

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects. This report shows the agenda and abstracts for this symposium.

  15. Low-dose methotrexate inhibits lung metastasis and lengthens survival in rat osteosarcoma.

    PubMed

    Tomoda, Ryota; Seto, Masashi; Hioki, Yasunari; Sonoda, Jun; Matsumine, Akihiko; Kusuzaki, Katsuyuki; Uchida, Atsumasa

    2005-01-01

    Lung metastasis is the most crucial event affecting the treatment of osteosarcoma and is dependent on tumor angiogenesis. To improve the prognosis for patients with osteosarcoma, prevention of lung metastasis is essential. Low-dose methotrexate is a useful drug for treating a variety of diseases. Low-dose methotrexate reportedly plays a role in antiangiogenesis for the synovial blood vessels in rheumatoid arthritis. However, whether low-dose methotrexate is correlated with tumor angiogenesis and metastasis is unclear. We investigated the inhibitory effect of methotrexate on lung metastasis in a rat osteosarcoma cell line with high metastatic potential, S-SLM. Two weeks after inoculation of S-SLM cells into male Fischer 344 rats, low-dose methotrexate (1.2 mg/kg once or twice a week) or saline was intraperitonealy injected for 4 weeks and the antimetastatic effect was evaluated. Low-dose methotrexate significantly reduced the number of lung metastatic nodules and the wet weight of the lungs. Immunohistochemical staining showed a decrease in microvessel density in the metastatic nodules. We also evaluated the effect of methotrexate on the proliferation of endothelial cells and S-SLM osteosarcoma cells in vitro. Methotrexate significantly inhibited the proliferation of endothelial cells at a lower concentration than that of S-SLM osteosarcoma cells. These data suggest that low-dose methotrexate inhibited lung metastasis of osteosarcoma through its antiangiogenic activity. Our results indicate that low-dose methotrexate is a promising drug for tumor dormancy therapy in patients with osteosarcoma and lung metastasis.

  16. Randomized Trial of Low-Dose Morphine Versus Weak Opioids in Moderate Cancer Pain.

    PubMed

    Bandieri, Elena; Romero, Marilena; Ripamonti, Carla Ida; Artioli, Fabrizio; Sichetti, Daniela; Fanizza, Caterina; Santini, Daniele; Cavanna, Luigi; Melotti, Barbara; Conte, Pier Franco; Roila, Fausto; Cascinu, Stefano; Bruera, Eduardo; Tognoni, Gianni; Luppi, Mario

    2016-02-10

    The WHO guidelines on cancer pain management recommend a sequential three-step analgesic ladder. However, conclusive data are lacking as to whether moderate pain should be treated with either step II weak opioids or low-dose step III strong opioids. In a multicenter, 28-day, open-label randomized controlled study, adults with moderate cancer pain were assigned to receive either a weak opioid or low-dose morphine. The primary outcome was the number of responder patients, defined as patients with a 20% reduction in pain intensity on the numerical rating scale. A total of 240 patients with cancer (118 in the low-dose morphine and 122 in the weak-opioid group) were included in the study. The primary outcome occurred in 88.2% of the low-dose morphine and in 57.7% of the weak-opioid group (odds risk, 6.18; 95% CI, 3.12 to 12.24; P < .001). The percentage of responder patients was higher in the low-dose morphine group, as early as at 1 week. Clinically meaningful (≥ 30%) and highly meaningful (≥ 50%) pain reduction from baseline was significantly higher in the low-dose morphine group (P < .001). A change in the assigned treatment occurred more frequently in the weak-opioid group, because of inadequate analgesia. The general condition of patients, which was based on the Edmonton Symptom Assessment System overall symptom score, was better in the morphine group. Adverse effects were similar in both groups. In patients with cancer and moderate pain, low-dose morphine reduced pain intensity significantly compared with weak opioids, with a similarly good tolerability and an earlier effect. © 2015 by American Society of Clinical Oncology.

  17. Local application of low-dose insulin in improving wound healing after deep burn surgery

    PubMed Central

    Wang, Chejiang; Wang, Jiazhe; Feng, Jianke

    2016-01-01

    The clinical effects of local application of low-dose insulin in improving wound healing after deep burn self-skin transplantation surgery were examined. Fifty-eight patients with deep burns were selected and randomly divided into 3 groups. In the blank control group, normal saline was injected to the subcutaneous tissue of wounds; in large dose insulin group, 1.0 µ long-term suspended zinc insulin was locally injected; and in the low-dose insulin group, 0.1 µ long-term suspended zinc insulin was locally injected. The healing effects were compared. After 7 and 14 days of treatments, wound surface area in the low-dose group was significantly smaller than in the other groups, and differences were statistically significant (P<0.05); wound healing duration and infection rate for patients in the low-dose group were significantly lower, class A healing rate was significantly improved, and the differences were statistically significant (P<0.05). Insulin resistance index (HOMA-IR) in the low-dose group was significantly lower, insulin secretion index (HOMA-β) and the insulin sensitivity index (HOMA-ISI) significantly increased. The expression levels of vascular endothelial growth factor and tumor necrosis factor-α in local tissue for the low-dose group were significantly higher than those in the other two groups. Differences were statistically significant (P<0.05). In conclusion, local application of low-dose insulin can effectively improve wound healing after deep burn surgeries. PMID:27698753

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

    PubMed Central

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

    2012-01-01

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

  19. Convolutional auto-encoder for image denoising of ultra-low-dose CT.

    PubMed

    Nishio, Mizuho; Nagashima, Chihiro; Hirabayashi, Saori; Ohnishi, Akinori; Sasaki, Kaori; Sagawa, Tomoyuki; Hamada, Masayuki; Yamashita, Tatsuo

    2017-08-01

    The purpose of this study was to validate a patch-based image denoising method for ultra-low-dose CT images. Neural network with convolutional auto-encoder and pairs of standard-dose CT and ultra-low-dose CT image patches were used for image denoising. The performance of the proposed method was measured by using a chest phantom. Standard-dose and ultra-low-dose CT images of the chest phantom were acquired. The tube currents for standard-dose and ultra-low-dose CT were 300 and 10 mA, respectively. Ultra-low-dose CT images were denoised with our proposed method using neural network, large-scale nonlocal mean, and block-matching and 3D filtering. Five radiologists and three technologists assessed the denoised ultra-low-dose CT images visually and recorded their subjective impressions of streak artifacts, noise other than streak artifacts, visualization of pulmonary vessels, and overall image quality. For the streak artifacts, noise other than streak artifacts, and visualization of pulmonary vessels, the results of our proposed method were statistically better than those of block-matching and 3D filtering (p-values < 0.05). On the other hand, the difference in the overall image quality between our proposed method and block-matching and 3D filtering was not statistically significant (p-value = 0.07272). The p-values obtained between our proposed method and large-scale nonlocal mean were all less than 0.05. Neural network with convolutional auto-encoder could be trained using pairs of standard-dose and ultra-low-dose CT image patches. According to the visual assessment by radiologists and technologists, the performance of our proposed method was superior to that of large-scale nonlocal mean and block-matching and 3D filtering.

  20. Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

    PubMed

    Park, Jeong Bae; Shin, Joon-Han; Kim, Dong-Soo; Youn, Ho-Joong; Park, Seung Woo; Shim, Wan Joo; Park, Chang Gyu; Kim, Dong-Woon; Lee, Hae-Young; Choi, Dong-Ju; Rim, Se-Joong; Lee, Sung-Yun; Kim, Ju-Han

    2016-04-01

    Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition

  1. Clofarabine plus Low-Dose Cytarabine Followed by Clofarabine plus Low-Dose Cytarabine Alternating with Decitabine in AML Frontline Therapy of Older Patients

    PubMed Central

    Faderl, Stefan; Ravandi, Farhad; Huang, Xuelin; Wang, Xuemei; Jabbour, Elias; Garcia-Manero, Guillermo; Kadia, Tapan; Ferrajoli, Alessandra; Konopleva, Marina; Borthakur, Gautam; Burger, Jan; Feliu, Jennie; Kantarjian, Hagop M.

    2014-01-01

    Background Standard therapy for older patients with AML has a poor outcome. We have designed a combination of clofarabine plus low-dose cytarabine followed by a prolonged consolidation alternating with decitabine. Methods Sixty patients with a median age of 70 years (range 60-81) with newly diagnosed AML were included. They received clofarabine 20mg/m2 intravenously daily × 5 days plus cytarabine 20mg subcutaneously twice daily × 10 days. Responding patients continued for up to 17 courses of consolidation therapy including decitabine. Results Forty of 59 evaluable patients responded (66%). Complete remission rate was 58%. Median relapse-free survival (RFS) was 14.1 (95% CI: 6.9-not estimable) and median overall survival (OS) 12.7 months (95% CI: 8.8-not estimable). Median OS of responding patients (CR/CRp) was 24.2 months (95% CI: 17-not estimable). Compared to a historical group of patients who received clofarabine plus low-dose cytarabine with a shorter consolidation, RFS was not statistically different. Induction mortality was low (7% at 8 weeks) and toxicities manageable. Conclusions Clofarabine plus low-dose cytarabine alternating with decitabine in consolidation is active in older patients with newly diagnosed AML. The benefits of a prolonged consolidation remain unproven. PMID:22282348

  2. Low-dose serotherapy improves early immune reconstitution after cord blood transplantation for primary immunodeficiencies.

    PubMed

    Lane, Jonathan P; Evans, Philippa T G; Nademi, Zohreh; Barge, Dawn; Jackson, Anthony; Hambleton, Sophie; Flood, Terry J; Cant, Andrew J; Abinun, Mario; Slatter, Mary A; Gennery, Andrew R

    2014-02-01

    Cord blood transplantation (CBT) is curative for many primary immunodeficiencies (PIDs) but is associated with risks of viral infection and graft-versus-host disease (GvHD). Serotherapy reduces GvHD but potentially increases the risk of viral infection by delaying immune reconstitution. Because many PID patients have pre-existing viral infections, the optimal dose of serotherapy is unclear. We performed a retrospective analysis in 34 consecutive PID patients undergoing CBT and compared immune reconstitution, viral infection, GvHD, mortality, and long-term immune function between high-dose (n = 11) and low-dose (n = 9) serotherapy. Serotherapy dose had no effect on neutrophil engraftment. Median CD3(+) engraftment occurred at 92.5 and 97 days for high- and low-dose serotherapy, respectively. The low-dose serotherapy group had higher CD3(+), CD4(+), and early thymic emigrant counts at 4 months compared with the high-dose group. GvHD severity and number of viral infections did not differ between serotherapy doses. Survival from the transplantation process was 90.9% for high-dose and 100% for low-dose groups. In conclusion, low-dose serotherapy enhanced T cell reconstitution and thymopoiesis during the first year after CBT with no increase in GvHD. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Irradiation with low-dose gamma ray enhances tolerance to heat stress in Arabidopsis seedlings.

    PubMed

    Zhang, Liang; Zheng, Fengxia; Qi, Wencai; Wang, Tianqi; Ma, Lingyu; Qiu, Zongbo; Li, Jingyuan

    2016-06-01

    Gamma irradiation at low doses can stimulate the tolerance to environmental stress in plants. However, the knowledge regarding the mechanisms underlying the enhanced tolerance induced by low-dose gamma irradiation is far from fully understood. In this study, to investigate the physiological and molecular mechanisms of heat stress alleviated by low-dose gamma irradiation, the Arabidopsis seeds were exposed to a range of doses before subjected to heat treatment. Our results showed that 50-Gy gamma irradiation maximally promoted seedling growth in response to heat stress. The production rate of superoxide radical and contents of hydrogen peroxide and malondialdehyde in the seedlings irradiated with 50-Gy dose under heat stress were significantly lower than those of controls. The activities of antioxidant enzymes, glutathione (GSH) content and proline level in the gamma-irradiated seedlings were significantly increased compared with the controls. Furthermore, transcriptional expression analysis of selected genes revealed that some components related to heat tolerance were stimulated by low-dose gamma irradiation under heat shock. Our results suggest that low-dose gamma irradiation can modulate the physiological responses as well as gene expression related to heat tolerance, thus alleviating the stress damage in Arabidopsis seedlings. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. What can be learned from epidemiologic studies of persons exposed to low doses of radiation?

    SciTech Connect

    Gilbert, E.S.

    1993-04-01

    The main objective of radiation risk assessment is to determine the risk of various adverse health effects associated with exposure to low doses and low dose rates. Extrapolation of risks from studies of persons exposed at high doses (generally exceeding 1 Sv) and dose rates has been the primary approach used to achieve this objective. The study of Japanese atomic bomb survivors in Hiroshima and Nagasaki has played an especially important role in risk assessment efforts. A direct assessment of the dose-response function based on studies of persons exposed at low doses and dose rates is obviously desirable. This paper focuses on the potential of both current and future nuclear workers studies for investigating the dose-response functions at low doses, and also discusses analyses making use of the low dose portion of the atomic bomb survivor data. Difficulties in using these data are the statistical imprecision of estimated dose-response parameters, and potential bias resulting from confounding factors and from uncertainties in dose estimates.

  5. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.

    PubMed

    Younger, Jarred; Mackey, Sean

    2009-01-01

    Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial, we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia. Participants completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks). Ten women meeting criteria for fibromyalgia and not taking an opioid medication. Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation. Participants completed reports of symptom severity everyday, using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity. Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone. We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.

  6. Bromocriptine and low dose cyclosporine in the treatment of experimental autoimmune uveitis in the rat.

    PubMed Central

    Palestine, A G; Muellenberg-Coulombre, C G; Kim, M K; Gelato, M C; Nussenblatt, R B

    1987-01-01

    The immunologic effects of bromocriptine and low dose cyclosporine on experimental autoimmune uveitis (EAU) induced in Lewis rats by S-antigen immunization were studied. Rats treated with a sub-optimal dose (low dose) of cyclosporine (2 mg/kg per d), bromocriptine (1.8 mg/kg per d), or both drugs were compared with untreated rats in regard to the development of EAU, lymphocyte proliferative responses, and anti-S-antigen serum antibodies. Bromocriptine alone decreased the incidence of EAU only in female rats (P less than 0.01), did not effect the lymphocyte proliferative response, but did significantly decrease antibody titers in both males (P less than 0.004) and females (P less than 0.0005). Low dose cyclosporine also partially decreased the incidence of EAU in female rats, but did not decrease antibody titers or lymphocyte proliferative responses. Bromocriptine plus low-dose cyclosporine led to more marked decreases in the incidence of EAU and anti-S-antigen antibody titers as well as in the lymphocyte proliferative assay (P less than 0.01 for males, P less than 0.0005 for females). This study suggests that bromocriptine can enhance the immunosuppression of low dose cyclosporine. PMID:3494043

  7. Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction

    NASA Astrophysics Data System (ADS)

    Bauer, G.

    2011-01-01

    Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.

  8. Final Technical Report for the grant entitled "Genetic Factors Affecting Susceptibility to Low-Dose Radiation"

    SciTech Connect

    Morgan, William, F., Ph.D., D.Sc.

    2006-11-22

    The goal of this proposal was to test the hypothesis that mice heterozygous for the Nijmegen Breakage Syndrome (NBS1) gene are genetically susceptible to low doses of ionizing radiation. The rationale for this is that patients with NBS are radiation sensitive, because of defects in cellular responses to radiation induced genetic damage and haploinsufficiency at this genetic locus provides the potential for genetic susceptibility to low doses of ionizing radiation. Wild type and heterozygous NBS1 mice were irradiated and followed over their lifetime for radiation induced genomic instability, carcinogenesis and non-specific life shortening. No differences in cytogenetic damage, cancer induction or life span were observed between the hypomorphic mice indicating that genetic imbalance at the NBS1 loci does not modulate low dose radiation sensitivity.

  9. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  10. Ultra Low-Dose Radiation: Stress Responses and Impacts Using Rice as a Grass Model

    PubMed Central

    Rakwal, Randeep; Agrawal, Ganesh Kumar; Shibato, Junko; Imanaka, Tetsuji; Fukutani, Satoshi; Tamogami, Shigeru; Endo, Satoru; Sahoo, Sarata Kumar; Masuo, Yoshinori; Kimura, Shinzo

    2009-01-01

    We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model) exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot) and secondary metabolites (LC-MS/MS) in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (γ) rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s. PMID:19399245

  11. Data integration reveals key homeostatic mechanisms following low dose radiation exposure

    SciTech Connect

    Tilton, Susan C.; Matzke, Melissa M.; Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J.; Morgan, William F.; Waters, Katrina M.

    2015-05-15

    The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time — with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24–72 h). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress was measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 was experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation. - Highlights: • Low dose ionizing radiation altered homeostasis in 3D skin tissue model. • Global gene/protein/metabolite data integrated using complementary statistical approaches • Time and location-specific change in matrix regulation

  12. SU-E-P-03: Implementing a Low Dose Lung Screening CT Program Meeting Regulatory Requirements

    SciTech Connect

    LaFrance, M; Marsh, S; O'Donnell, G

    2014-06-01

    Purpose: To provide information pertaining to IROC Houston QA Center's (RPC) credentialing process for institutions participating in NCI-sponsored clinical trials. Purpose: Provide guidance to the Radiology Departments with the intent of implementing a Low Dose CT Screening Program using different CT Scanners with multiple techniques within the framework of the required state regulations. Method: State Requirements for the purpose of implementing a Low Dose CT Lung Protocol required working with the Radiology and Pulmonary Department in setting up a Low Dose Screening Protocol designed to reduce the radiation burden to the patients enrolled. Radiation dose measurements (CTDIvol) for various CT manufacturers (Siemens16, Siemens 64, Philips 64, and Neusoft128) for three different weight based protocols. All scans were reviewed by the Radiologist. Prior to starting a low dose lung screening protocol, information had to be submitted to the state for approval. Performing a Healing Arts protocol requires extensive information. This not only includes name and address of the applicant but a detailed description of the disease, the x-ray examination and the population to be examined. The unit had to be tested by a qualified expert using the technique charts. The credentials of all the operators, the supervisors and the Radiologists had to be submitted to the state. Results: All the appropriate documentation was sent to the state for review. The measured results between the Low Dose Protocol versus the default Adult Chest Protocol showed that there was a dose reduction of 65% for small (100-150 lb.) patient, 75% for the Medium patient (151-250 lbs.), and a 55% reduction for the Large patient ( over 250 lbs.). Conclusion: Measured results indicated that the Low Dose Protocol indeed lowered the screening patient's radiation dose and the institution was able to submit the protocol to the State's regulators.

  13. Low Dose Radiation Hypersensitivity is Caused by p53-dependent Apoptosis

    SciTech Connect

    Enns, L; Bogen, K; Wizniak, J; Murtha, A; Weinfeld, M

    2004-04-08

    Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses below 50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times post irradiation, we examined the response of human A549 lung carcinoma, T98G glioma and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (annexin-V binding). We observed that caspase-3 activation and annexin-V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and annexin-V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no HRS and apoptosis was not detectable by annexin-V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.

  14. Low-dose total-body γ irradiation modulates immune response to acute proton radiation.

    PubMed

    Luo-Owen, Xian; Pecaut, Michael J; Rizvi, Asma; Gridley, Daila S

    2012-03-01

    Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate γ rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with ⁵⁷Co (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to γ rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to γ rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+ T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with γ radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate γ rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations.

  15. Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats

    PubMed Central

    2010-01-01

    Background The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Results Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Conclusion Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with

  16. Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

    PubMed

    Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

    2010-04-16

    The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone

  17. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    NASA Astrophysics Data System (ADS)

    Acheva, A.; Georgieva, R.; Rupova, I.; Boteva, R.; Lyng, F.

    2008-02-01

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy.

  18. Micro RNA responses to chronic or acute exposures to low dose ionizing radiation

    PubMed Central

    Chaudhry, M. Ahmad; Omaruddin, Romaica A.; Kreger, Bridget; de Toledo, Sonia M.; Azzam, Edouard I.

    2014-01-01

    Human health risks of exposure to low dose ionizing radiation remain ambiguous and are the subject of intense debate. A wide variety of biological effects are induced after cellular exposure to ionizing radiation, but the underlying molecular mechanism(s) remain to be completely understood. We hypothesized that low dose c-radiation-induced effects are controlled by the modulation of micro RNA (miRNA) that participate in the control of gene expression at the posttranscriptional level and are involved in many cellular processes. We monitored the expression of several miRNA in human cells exposed to acute or chronic low doses of 10 cGy or a moderate dose of 400 cGy of 137Cs γ-rays. Dose, dose rate and time dependent differences in the relative expression of several miRNA were investigated. The expression patterns of many miRNA differed after exposure to either chronic or acute 10 cGy. The expression of miRNA let-7e, a negative regulator of RAS oncogene, and the c-MYC miRNA cluster were upregulated after 10 cGy chronic dose but were downregulated after 3 h of acute 10 cGy. The miR-21 was upregulated in chronic or acute low dose and moderate dose treated cells and its target genes hPDCD4, hPTEN, hSPRY2, and hTPM1 were found to be downregulated. These findings provide evidence that low dose and dose rate c-irradiation dictate the modulation of miRNA, which can result in a differential cellular response than occurs at high doses. This information will contribute to understanding the risks to human health after exposure to low dose radiation. PMID:22367372

  19. Is bacterial luminescence response to low-dose radiation associated with mutagenicity?

    PubMed

    Rozhko, T V; Guseynov, O A; Guseynova, V E; Bondar, A A; Devyatlovskaya, A N; Kudryasheva, N S

    2017-10-01

    Luminous marine bacteria are widely used in bioassays with luminescence intensity being a physiological parameter tested. The purpose of the study was to determine whether bacterial genetic alteration is responsible for bioluminescence kinetics change under low-dose radiation exposure. The alpha-emitting radionuclide (241)Am and beta-emitting radionuclide (3)H were used as the sources of low-dose ionizing radiation. Changes of bioluminescence kinetics of Photobacterium phosphoreum in solutions of (241)Am(NO3)3, 7 kBq/L, and tritiated water, 100 MBq/L, were studied; bioluminescence kinetics stages (absence of effect, activation, and inhibition) were determined. Bacterial suspension was sampled at different stages of the bioluminescent kinetics; the doses accumulated by the samples were close or a little higher than a tentative limit of a low-dose interval: 0.10 and 0.85 Gy for (241)Am, or 0.11 and 0.18 Gy for (3)H. Sequence analysis of the 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose alpha and beta radiation in the bacterial samples. Previous results on bacterial DNA exposed to low-dose gamma radiation (0.25 Gy) were analyzed and compared to those for alpha and beta irradiation. It is concluded that bioluminescence activation and/or inhibition under the applied conditions of low-dose alpha, beta and gamma radioactive exposure is not associated with DNA mutations in the gene sequences tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    SciTech Connect

    Shin, Suk Chul; Lee, Kyung-Mi; Kang, Yu Mi; Kim, Kwanghee; Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo; Kim, Chong Soon; Kim, Hee Sun

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  1. Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer.

    PubMed

    Gestaut, Matthew M; Cai, Wendi; Vyas, Shilpa; Patel, Belur J; Hasan, Salman A; MunozMaldonado, Yolanda; Deb, Niloyjyoti; Swanson, Gregory

    2017-05-01

    Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL. A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression-free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001). The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was -35°C (range, -96°C to -6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection

  2. [Cerebral hemorrhage induced by low-dose streptokinase: a pharmacologic paradox? Report of a clinical case].

    PubMed

    Fedeli, F; Skouse, D; Messina, A

    1997-01-01

    A case of an important intracranial hemorrhage after a low dose (approx. 500,000 UI) of streptokinase in a 60 year-old woman suffering from myocardial infarction is presented. Clinical, electrocardiographic, echocardiographic, lab and tomographic findings are described. The authors suggest a pharmacokinetic mechanism which could be responsible of a "paradox effect" (a powerful and dangerous effect of the drug when given in low dose) and they wonder whether in case of allergic reactions should it be better not to stop the infusion of the thrombolytic drug and be more liberal with the "symptomatic" drugs. Tha patient is still alive and the clinical conditions slowly progressing.

  3. Opioid-induced myoclonus and hyperalgesia following a short course of low-dose oral morphine

    PubMed Central

    Woodward, Owen Bleddyn; Naraen, Sangeeta; Naraen, Akriti

    2016-01-01

    A 76-year-old man was admitted to hospital with a right-sided fractured neck of femur requiring repair via a cemented hemiarthroplasty. Intraoperatively he received 10 mg of intravenous morphine. Post-operatively he received a short course of low-dose oral opioids and subsequently developed myoclonic jerks and hyperalgesia. The opioids were discontinued and both adverse effects resolved. This case report discusses the concurrent development of myoclonus and hyperalgesia following a low dose of opioids and explores possible management options. PMID:28386402

  4. Severe compensatory hyperhidrosis following thoracic sympathectomy successfully treated with low doses of botulinum toxin A.

    PubMed

    Santana-Rodríguez, Norberto; Clavo, Bernardino; Calatayud-Gastardi, Joaquín; García-Castellano, José Manuel; Ponce-González, Miguel A; Olmo-Quintana, Vicente; Llontop, Pedro; Alvarez-Prats, Alejandro; Yordi, Nagib Atallah; Ruíz-Caballero, José Antonio

    2012-12-01

    Compensatory hyperhidrosis is an adverse effect of thoracic sympathectomy that can be debilitating, which is why an efficient treatment is demanded. Botulinum toxin is an emerging treatment, not well known yet. We report two cases of compensatory hyperhidrosis following thoracic sympathectomy which were both treated with low doses of botulinum toxin A. The patients, a male and a female, noted a high level of satisfaction with the abolishment of sweating that was maintained up to 10 months. We consider that low doses of botulinum toxin A is a well tolerated, safe and effective treatment for compensatory hyperhidrosis and should be offered as an alternative treatment.

  5. Low-Dose Naltrexone: A New Therapy Option for Complex Regional Pain Syndrome Type I Patients.

    PubMed

    Sturn, Kayla M; Collin, Michael

    2016-01-01

    Naltrexone (an opioid antagonist) has long been used in patients overcoming alcohol and opioid dependency. However, at doses one-tenth of those commonly prescribed for the above conditions, an unexpected effect occurs that aids in alleviating pain. Although there are currently no randomized clinical trials supporting the use of low-dose naltrexone, we present a case study describing the impact of compounding low-dose naltrexone that has dramatically improved the patient's pain symptoms which were refractory to other treatments. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  6. Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone.

    PubMed

    Roshanpour, Maryam; Ghasemi, Mehdi; Riazi, Kiarash; Rafiei-Tabatabaei, Neda; Ghahremani, Mohammad Hossein; Dehpour, Ahmad Reza

    2009-02-01

    The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a mouse model of clonic seizures induced by pentylenetetrazole, and whether ultra-low doses of the opioid receptor antagonist naltrexone which selectively block G(s) opioid receptors were capable of preventing the observed tolerance. The results showed that the morphine anticonvulsant effect could be subject to tolerance after repeated administration. Both the development and expression of tolerance were inhibited by ultra-low doses of naltrexone, suggesting the possible involvement of G(s)-coupled opioid receptors in the development of tolerance to the anticonvulsant effect of morphine.

  7. Treatment of Complex Regional Pain Syndrome (CRPS) using low dose naltrexone (LDN).

    PubMed

    Chopra, Pradeep; Cooper, Mark S

    2013-06-01

    Complex Regional Pain Syndrome (CRPS) is a neuropathic pain syndrome, which involves glial activation and central sensitization in the central nervous system. Here, we describe positive outcomes of two CRPS patients, after they were treated with low-dose naltrexone (a glial attenuator), in combination with other CRPS therapies. Prominent CRPS symptoms remitted in these two patients, including dystonic spasms and fixed dystonia (respectively), following treatment with low-dose naltrexone (LDN). LDN, which is known to antagonize the Toll-like Receptor 4 pathway and attenuate activated microglia, was utilized in these patients after conventional CRPS pharmacotherapy failed to suppress their recalcitrant CRPS symptoms.

  8. Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer.

    PubMed

    Matsuo, Koji; Cahoon, Sigita S; Yoshihara, Kosuke; Shida, Masako; Kakuda, Mamoru; Adachi, Sosuke; Moeini, Aida; Machida, Hiroko; Garcia-Sayre, Jocelyn; Ueda, Yutaka; Enomoto, Takayuki; Mikami, Mikio; Roman, Lynda D; Sood, Anil K

    2016-07-01

    To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81-100 mg/d). A multicenter retrospective study was conducted examining patients with stage I-IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival. One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8-11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all P<.001). Low-dose aspirin users were more likely to take other antihypertensive, antiglycemic, and anticholesterol agents (all P<.05). Low-dose aspirin use was not associated with histologic subtype, tumor grade, nodal metastasis, or cancer stage (all P>.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25-0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08-0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared

  9. Current trends in estimating risk of cancer from exposure to low doses of ionising radiation.

    PubMed

    Majer, Marija; Knežević, Zeljka; Saveta, Miljanić

    2014-09-29

    Although ionising radiation has proven beneficial in the diagnosis and therapy of a number of diseases, one should keep in mind that irradiating healthy tissue may increase the risk of cancer. In order to justify an exposure to radiation, both the benefits and the risks must be evaluated and compared. The deleterious effects of medium and high doses are well known, but it is much less clear what effects arise from low doses (below 0.1 Gy), which is why such risk estimates are extremely important. This review presents the current state, important assumptions and steps being made in deriving cancer risk estimates for low dose exposures.

  10. Enteric coating can lead to reduced antiplatelet effect of low-dose acetylsalicylic acid.

    PubMed

    Haastrup, Peter Fentz; Grønlykke, Thor; Jarbøl, Dorte Ejg

    2015-03-01

    Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric-coated ASA has been developed to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically been assessed. This MiniReview demonstrates that data from clinical trials indicate that enteric coating can reduce the antiplatelet effect of ASA compared to plain ASA. This is possibly due to decreased bioavailability of ASA caused by prolonged solvation and absorption of the enteric-coated formulations. Therefore, low-dose enteric-coated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis.

  11. Incidental renal tumours on low-dose CT lung cancer screening exams.

    PubMed

    Pinsky, Paul F; Dunn, Barbara; Gierada, David; Nath, P Hrudaya; Munden, Reginald; Berland, Lincoln; Kramer, Barnett S

    2017-06-01

    Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P < 0.001). Cases with abnormalities below the diaphragms had shorter median time to diagnosis than those without (71 vs. 160 days, P = 0.004). In the reader study, 64% of renal cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P < 0.001). Conclusion Low-dose computed tomography screens can potentially detect renal cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

  12. Behavioral Effects of Low Doses of Cholinesterase Inhibitors in Robot- Tested Marmosets

    DTIC Science & Technology

    1989-10-01

    IJW hL l !2Y r GRANT NO.: DAMDI7-88-Z-8020 TITLE: Behavioral effects of low doses of cholinesterase inhibitors in robot-tested marmosets ...Behavioral effects of low doses of cholinesterase inhibitors in robot-tested marmosets 12Z. PERSONAL AUfl4R() Otto L. Wolt huts, Bap Groen. Raymond Vanwerech...mg/kg) and 20 min after i.m. physostigmine (0.02-0.08 mg/kg) in experimentally naive marmosets . The behavioral tasks in series 1 were hand-eye

  13. Low dose weekly methotrexate in early pregnancy. A case series and review of the literature.

    PubMed

    Ostensen, M; Hartmann, H; Salvesen, K

    2000-08-01

    To assess the teratogenic risk of low dose weekly pulses of methotrexate (MTX) inadvertently taken during the first trimester of pregnancy. We assessed pregnancy and neonatal outcome of 4 patients with rheumatic disease treated with weekly pulses of 5 to 15 mg of MTX for a mean duration of 4 years. The 4 patients had continued MTX treatment from one to 6 weeks of gestation. One patient miscarried at Week 6, the other pregnancies ended with the delivery of healthy children. Chromosome analysis of one child was normal. In spite of the absence of congenital anomalies in our cases, safe contraception in fertile patients who start low dose weekly MTX is mandatory.

  14. Low-dose imipramine for treatment of panic disorder during pregnancy: a retrospective chart review.

    PubMed

    Uguz, Faruk; Sahingoz, Mine; Gungor, Buket; Askin, Rustem

    2014-08-01

    Although imipramine is one of the antidepressants that could be effective in the treatment of panic disorder, data on its usage for this diagnosis in the pregnancy period are limited. This report presents the results of 16 pregnant women with panic disorder without comorbid diagnosis who underwent low-dose imipramine (10-40 mg/d) treatment. According to the Clinical Global Impression-Improvement Scale, 12 (75%) of 16 women responded to the treatment. The results suggest that low-dose imipramine may be useful for the treatment of panic disorder during pregnancy.

  15. Application of Low-dose Stereoradiography in In Vivo Vertebral Morphologic Measurements: Comparison With Computed Tomography.

    PubMed

    Pasha, Saba; Schlösser, Tom; Zhu, Xiaowei; Mellor, Xochitl; Castelein, René; Flynn, John

    2017-06-30

    Though computed tomography (CT) and 3 dimensional (3D) reconstruction of the spine and ribcage are powerful techniques for detailed monitoring of spinal growth and surgical planning of patients, drawbacks can arise. We explored the application of low-dose stereoradiography of the spine to calculate distinct morphologic parameters of the vertebral body in a juvenile patient population with early-onset scoliosis or congenital scoliosis. This study compares the 3D vertebral morphology measurements using low-dose stereoradiography with the currently accepted imaging modality for such measurements, CT scans. A total of 86 vertebrae of 6 patients with early-onset scoliosis and 3 patients with congenital scoliosis, age ranged between 7.8 and 12.5 years, who had both thoracic spine CT scan and low-dose stereoradiography of the spine were included. 3D reconstructions of CT and low-dose stereoradiography were generated. Using previously validated image processing techniques, vertebral anterior (A), posterior (P), left (L), and right (R) heights, superior and inferior endplates depth and width (S-D, I-D, S-W, I-W) were measured on the CTs' 3D reconstructions and were compared with the same parameters measured on low-dose stereoradiography reconstructions using a postprocessing custom code. The agreement between the 2 techniques in measurement of the vertebral morphology was assessed using the Bland-Altman plots. No significant difference was observed in the A, P, L, R, S-W, and I-W between the stereoradiography and CT measurements (P>0.05). S-D and I-D were significantly greater in low-dose stereoradiography measurements P<0.05. Bland-Altman plots showed an agreement between the stereoradiography and CT techniques in vertebral height measurements (A, P, L, R); however, larger measurement bias and greater limits of agreement in S-D, I-D, S-W, and I-W measurements were shown. In vivo measurements of the vertebral heights using low-dose stereoradiography 3D reconstructions were

  16. Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

    PubMed Central

    García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

    2016-01-01

    Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin

  17. Low-dose spinal anesthesia for urgent laparotomy in severe myasthenia gravis

    PubMed Central

    Rodríguez, Miguel Angel Palomero; Mencía, Teresa Pérez; Álvarez, Felipe Villar; Báez, Yolanda Laporta; Pérez, Gloria María Santos; García, Andrés López

    2013-01-01

    Myasthenia gravis (MG) is an autoimmune disease with an incidence of 2-10/100,000 cases per year, characterized by muscle weakness secondary to destruction of postsynaptic acetylcholine receptors. In these patients, important perioperative issues remain unresolved, namely, optimal administration of cholinesterase inhibitors, risks of regional anesthesia, and prediction of need of postoperative mechanical ventilation. We describe the use of a low-dose spinal anesthesia in a patient with MG who was submitted for emergence exploratory laparotomy. The utilization of low-dose spinal anesthesia allowed us to perform surgery with no adverse respiratory or cardiovascular events in this patient. PMID:23717241

  18. Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

    PubMed Central

    Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

    2016-01-01

    Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. Trial registration numbers http://www.clinicaltrials.gov (NCT01278082) and http

  19. Low-Dose Hydroxychloroquine is as Effective as Phlebotomy in Treatment of Patients with Porphyria Cutanea Tarda

    PubMed Central

    Singal, Ashwani K.; Kormos-Hallberg, Csilla; Lee, Chul; Sadagoparamanujam, V.-M.; Grady, James J.; Freeman, Daniel H.; Anderson, Karl E.

    2012-01-01

    Background & Aims Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase (UROD); it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. Methods We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. Results The time to remission was a median 6.9 months for patients that received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 months for randomized patients), a difference that was not significant (Log Rank P=.06 and P=.95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 0.95–5.06) for all patients. Patients that received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. Conclusions Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. PMID:22985607

  20. Gabapentin vs. low-dose transdermal estradiol for treating post-menopausal women with moderate to very severe hot flushes.

    PubMed

    Aguirre, Wellington; Chedraui, Peter; Mendoza, Jose; Ruilova, Ivan

    2010-05-01

    Gabapentin (GPT), a widely used drug in neurology, has been proposed as a non-hormonal option for the management of hot flushes in menopausal women with contraindications for estrogen therapy. To compare GPT versus low-dose transdermal estradiol (E(2)) for treating post-menopausal women with moderate to very severe hot flushes. A total of 45 post-menopausal women with moderate to very severe hot flushes were prospectively and single-blinded randomised to receive oral GPT 600 mg/night or transdermal 25 microg/day E(2) per week. Hot flush intensity and frequency were assessed with the Menopause Rating Scale and a numeric scale respectively at baseline and at 1, 4 and 8 weeks. Side effects were also assessed. Hot flush intensity and frequency significantly decreased for both groups at 1, 4 and 8 weeks of treatment as compared to baseline; however, this decrease was statistically more evident for the E(2) group. Although the percentage of hot flush intensity and frequency reduction at the end of the treatment was higher for E2, this was not statistically significant (68.2% vs. 60.6% for intensity and 70.1% vs. 58.9% for frequency, respectively, p > 0.05, NS). Encountered side effects included: drowsiness, dizziness, fatigue (GPT group) and mastodynia, vaginal spotting and a local allergic reaction (E(2) group). Compliance to treatment was 95.6% (GPT group) as compared to 90.9% for the E(2) group. Despite statistical significant differences, from a clinical point of view oral GPT 600 mg was as effective as low-dose transdermal E(2) in controlling moderate to severe hot flushes in post-menopausal women, and should be recommended as an alternative option in those with contraindications to estrogen therapy. More research is warranted in this regard.

  1. Heparin-coated extracorporeal circulation in combination with low dose systemic heparinization reduces early postoperative blood loss in cardiac surgery.

    PubMed

    Mirow, N; Zittermann, A; Koertke, H; Maleszka, A; Knobl, H; Coskun, T; Kleesiek, K; Koerfer, R

    2008-04-01

    According to a recently performed meta-analysis, heparin-bonded circuits do not reduce blood loss in cardiac surgery patients compared to nonheparin-bonded circuits within the first 24 h postoperatively. We investigated the effects of heparin-coated circuits in combination with a reduced systemic heparin dose on early postoperative blood loss (first 12 h), platelet function, and postoperative complications. Patients who underwent their first coronary artery bypass graft surgery were included in a randomized prospective study. Group A (n=149) was perfused with an uncoated extracorporeal circulation (ECC)-set and groups B (n=152) and C (n=149) with heparin-coated ECC-sets. In groups A and B, conventional dose systemic heparin was given, whereas group C received low dose systemic heparin. Blood loss was assessed within the first 12 h postoperatively. Moreover, biochemical parameters of pro-coagulant activity and immunological function were measured. None of the pro-coagulant activity markers and immunological parameters measured differed preoperatively or postoperatively between study groups. However, intraoperative platelet counts and maximal intraoperative concentrations of platelet factor 4, ss-thromboglobulin, and poly-morpho-nuclear (PMN)-elastase were lowest in group C, whereas group C also had the highest concentrations of thrombin-antithrombin complex (P<0.018-0.001). Blood loss within the first 12 h postoperatively was 457 +/- 204 mL in group A, 431 +/- 178 mL in group B, and 382 +/- 188 mL in group C (P<0.01). Complication rates and 30-day mortality did not differ between study groups. The combined use of heparin-coated circuits and low dose systemic heparinization is able to reduce early postoperative blood loss without enhancing the risk of complications.

  2. Assessment of dose and DNA damages in individuals exposed to low dose and low dose rate ionizing radiations during computed tomography imaging.

    PubMed

    Kanagaraj, Karthik; Abdul Syed Basheerudeen, Safa; Tamizh Selvan, G; Jose, M T; Ozhimuthu, Annalakshmi; Panneer Selvam, S; Pattan, Sudha; Perumal, Venkatachalam

    2015-08-01

    Computed tomography (CT) is a frequently used imaging modality that contributes to a tenfold increase in radiation exposure to the public when compared to other medical imaging modalities. The use of radiation for therapeutic need is always rationalized on the basis of risk versus benefit thereby increasing concerns on the dose received by patients undergoing CT imaging. Therefore, it was of interest to us to investigate the effects of low dose and low dose-rate X-irradiation in patients who underwent CT imaging by recording the doses received by the eye, forehead and thyroid, and to study the levels of damages in the lymphocytes in vivo. Lithium manganese borate doped with terbium (LMB:Tb) thermo luminescence dosimeters (TLD) were used to record the doses in the patient's (n = 27) eye, forehead, and thyroid and compared with the dose length product (DLP) values. The in vivo DNA damages measured were compared before and after CT imaging using chromosomal aberration (CA) and micronucleus (MN) assays. The overall measured organ dose ranged between 2 ± 0.29 and 520 ± 41.63 mGy for the eye, 0.84 ± 0.29 and 210 ± 20.50 mGy for the forehead, and 1.79 ± 0.43 and 185 ± 0.70 mGy for the thyroid. The in vivo damages measured from the blood lymphocytes of the subjects showed an extremely significant (p < 0.0001) increase in CA frequency and significant (p < 0.001) increase in MN frequency after exposure, compared to before exposure. The results suggest that CT imaging delivers a considerable amount of radiation dose to the eye, forehead, and thyroid, and the observed increase in the CA and MN frequencies show low dose radiation effects calling for protective regulatory measures to increase patient's safety. This study is the first attempt to indicate the trend of doses received by the patient's eye, forehead and thyroid and measured directly in contrast to earlier values obtained by extrapolation from phantoms, and to assess the in vivo low dose effects in an Indian

  3. Safety and efficacy of low-dose, subacute exposure of mature ewes to sodium chlorate

    USDA-ARS?s Scientific Manuscript database

    The objective was to determine the safety and efficacy of low-dose, subacute exposure of mature ewes to NaClO3 in the drinking water. Twenty-five ewes (BW = 62.5 ± 7.3 kg) were placed indoors in individual pens with ad libitum access to water and feed. After 7 d of adaptation, ewes were assigned ran...

  4. 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…

  5. Clinical use of a low-dose medetomidine infusion in healthy dogs undergoing ovariohysterectomy.

    PubMed

    Rioja, Eva; Gianotti, Giacomo; Valverde, Alexander

    2013-09-01

    Eight healthy dogs undergoing elective ovariohysterectomy were anesthetized with a standard protocol and received a low-dose medetomidine constant rate infusion during surgery. Cardiorespiratory parameters, including non-invasive cardiac output, were measured at various times. This protocol resulted in acceptable and stable cardiovascular performance, allowed low isoflurane concentrations, and provided smooth recoveries.

  6. Clinical use of a low-dose medetomidine infusion in healthy dogs undergoing ovariohysterectomy

    PubMed Central

    Rioja, Eva; Gianotti, Giacomo; Valverde, Alexander

    2013-01-01

    Eight healthy dogs undergoing elective ovariohysterectomy were anesthetized with a standard protocol and received a low-dose medetomidine constant rate infusion during surgery. Cardiorespiratory parameters, including non-invasive cardiac output, were measured at various times. This protocol resulted in acceptable and stable cardiovascular performance, allowed low isoflurane concentrations, and provided smooth recoveries. PMID:24155491

  7. Low Doses of Camptothecin Induced Hormetic and Neuroprotective Effects in PC12 Cells

    PubMed Central

    Zhang, Chao; Chen, Shenghui; Bao, Jiaolin; Zhang, Yulin; Huang, Borong; Jia, Xuejing; Chen, Meiwan; Wan, Jian-Bo; Su, Huanxing; Wang, Yitao

    2015-01-01

    Hormetic response is an adaptive mechanism for a cell or organism surviving in an unfavorable environment. It has been an intriguing subject of researches covering a broad range of biological and medical disciplines, in which the underlying significance and molecular mechanisms are under intensive investigation. In the present study, we demonstrated that topoisomerase I inhibitor camptothecin (CPT), a potent anticancer agent, induced an obvious hormetic response in rat pheochromocytoma PC12 cells. Camptothecin inhibited PC12 cell growth at relative high doses as generally acknowledged while stimulated the cell growth by as much as 39% at low doses. Moreover, low doses of CPT protected the cells from hydrogen peroxide (H2O2)-induced cell death. Phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways were reported playing pivotal roles in protecting cells from oxidative stress. We observed that these 2 pathways were upregulated by low doses of CPT, as evidenced by increased levels of phosphorylated PI3K, phosphorylated Akt, phosphorylated mammalian target of rapamycin, Nrf2, and HO-1; and abolishment of the growth-promoting and neuroprotective effects of CPT by LY294002, a PI3K inhibitor. These results suggest that the hormetic and neuroprotective effects of CPT at low doses on PC12 cells were attributable, at least partially, to upregulated PI3K/Akt and Nrf2/HO-1 pathways. PMID:26674066

  8. Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy

    PubMed Central

    Zhang, Yin; Yang, Yunlong; Hosaka, Kayoko; Huang, Guichun; Zang, Jingwu; Chen, Fang; Zhang, Yun; Samani, Nilesh J.; Cao, Yihai

    2016-01-01

    Anti-VEGF–based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects. PMID:27035988

  9. CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

    EPA Science Inventory

    Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?

    Abstract
    High doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

  10. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  11. Low-Dose Valacyclovir for Cytomegalovirus Infection Prophylaxis After a Heart Transplant.

    PubMed

    Kervan, Umit; Kucuker, Seref Alp; Kocabeyoglu, Sinan Sabit; Unal, Ertekin Utku; Ozatik, Mehmet Ali; Sert, Dogan Emre; Kavasoglu, Kemal; Tezer, Ayse Yasemin; Pac, Mustafa

    2016-10-01

    Cytomegalovirus infection is a major cause of morbidity and mortality in solid-organ transplant. Low doses of valacyclovir have been administered as cytomegalovirus prophylaxis in our institution for years. To the best of our knowledge, there is no published study of a low-dose regimen for cytomegalovirus prophylaxis in heart transplant patients. Therefore, our aim was to determine the results of low doses of valacyclovir in heart transplant. Between September 2006 and December 2014, sixty-eight patients underwent orthotopic heart transplants. All of the patients received triple immunosuppressive therapy after surgery. During the next 6 months, sulfamethoxazole/trimethoprim was administered for Pneumocystis jiroveci pneumonia, and toxoplasmosis. Additionally all patients received valacyclovir hydrochloride (1000 mg/d, oral) for cytomegalovirus prophylaxis and nystatin oral rinse for prophylaxis of fungal infections. There was only 1 cytomegalovirus infection at follow-up. The patient had cytomegalovirus pneumonia at 17-month follow-up. In response to treatment with 1-week intravenous ganciclovir, the patient was discharged with a further 6-month oral valacyclovir therapy (1000 mg/d). In this study, we hypothesized that daily use of low-dose valacyclovir (1000 mg/d) is not only sufficient for cytomegalovirus prophylaxis but also beneficial in terms of cost.

  12. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

    PubMed Central

    Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

    2014-01-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. PMID:24366315

  13. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    PubMed

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

  14. Evaluation of small bowel blood flow in healthy subjects receiving low-dose aspirin

    PubMed Central

    Nishida, Urara; Kato, Mototsugu; Nishida, Mutsumi; Kamada, Go; Yoshida, Takeshi; Ono, Shouko; Shimizu, Yuichi; Asaka, Masahiro

    2011-01-01

    AIM: To investigate the relationship between low-dose aspirin-induced small bowel mucosal damage and blood flow, and the effect of rebamipide. METHODS: Ten healthy volunteers were enrolled in this study. The subjects were divided into two groups: a placebo group given low-dose aspirin plus placebo and a rebamipide group given low-dose aspirin plus rebamipide for a period of 14 d. Capsule endoscopy and contrast-enhanced ultrasonography were performed before and after administration of drugs. Areas under the curves and peak value of time-intensity curve were calculated. RESULTS: Absolute differences in areas under the curves were -1102.5 (95% CI: -1980.3 to -224.7, P = 0.0194) in the placebo group and -152.7 (95% CI: -1604.2 to 641.6, P = 0.8172) in the rebamipide group. Peak values of time intensity curves were -148.0 (95% CI: -269.4 to -26.2, P = 0.0225) in the placebo group and 28.3 (95% CI: -269.0 to 325.6, P = 0.8343) in the rebamipide group. Capsule endoscopy showed mucosal breaks only in the placebo group. CONCLUSION: Short-term administration of low-dose aspirin is associated with small bowel injuries and blood flow. PMID:21245996

  15. Alteration of Lysosome Fusion and Low-grade Inflammation Mediated by Super-low-dose Endotoxin*

    PubMed Central

    Baker, Bianca; Geng, Shuo; Chen, Keqiang; Diao, Na; Yuan, Ruoxi; Xu, Xiguang; Dougherty, Sean; Stephenson, Caroline; Xiong, Huabao; Chu, Hong Wei; Li, Liwu

    2015-01-01

    Subclinical super-low-dose endotoxin LPS is a risk factor for the establishment of low-grade inflammation during the pathogenesis and progression of chronic diseases. However, the underlying mechanisms are not well understood. At the cellular level, a disruption of lysosome fusion with endosomes or autophagosomes may contribute to the potentiation of low-grade inflammation. In this study, we identified that subclinical super-low-dose endotoxin LPS can potently inhibit the process of endosome acidification and lysosome fusion with endosomes or autophagosomes in primary macrophages. Super-low-dose LPS induced the inhibitory phosphorylation of VPS34, thus leading to the disruption of endosome-lysosome fusion. This effect may depend upon the clearance and relocation of Tollip in macrophages by super-low-dose LPS. Consistent with this notion, Tollip-deficient macrophages had constitutively elevated levels of VPS34 inhibitory phosphorylation and constitutive disruption of endosome-lysosome fusion. By employing a skin excision wound-healing model, we observed that Tollip-deficient mice had significantly elevated levels of cell stress and reduced wound repair. This study reveals a novel mechanism responsible for the modulation of endosome-lysosome fusion and low-grade inflammation in innate macrophages. PMID:25586187

  16. Low dose irradiation profoundly affects transcriptome and microRNAme in rat mammary gland tissues

    PubMed Central

    Luzhna, Lidia; Kovalchuk, Olga

    2014-01-01

    Ionizing radiation has been successfully used in medical tests and treatment therapies for a variety of medical conditions. However, patients and health-care workers are greatly concerned about overexposure to medical ionizing radiation and possible cancer induction due to frequent mammographies and/or CT scans. Diagnostic imaging involves the use of low doses of ionizing radiation, and its potential carcinogenic role creates a cancer risk concern for exposed individuals. In this study, the effects of X-ray exposure of different doses on the gene expression patterns and the micro-RNA expression patterns in normal breast tissue were investigated in rats. Our results revealed the activation of immune response pathways upon low dose of radiation exposure. These included natural killer mediated cytotoxicity pathways, antigen processing and presentation pathways, chemokine signaling pathways, and T- and B-cell receptor signaling pathways. Both high and low doses of radiation led to miRNA expression alterations. Increased expression of miR-34a may be linked to cell cycle arrest and apoptosis. Up-regulation of miR-34a was correlated with down-regulation of its target E2F3 and up-regulation of p53. This data suggests that ionizing radiation at specific high and low doses leads to cell cycle arrest and a possible initiation of apoptosis. PMID:25594002

  17. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  18. Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

    SciTech Connect

    Neelis, Karen J. Schimmel, Erik C.; Vermeer, Maarten H.; Senff, Nancy J.; Willemze, Rein; Noordijk, Evert M.

    2009-05-01

    Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.

  19. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    PubMed Central

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation. PMID:26795421

  20. Efficacy and safety of add on low-dose mirtazapine in depression.

    PubMed

    Matreja, Prithpal S; Badyal, Dinesh K; Deswal, Randhir S; Sharma, Arvind

    2012-03-01

    Although antidepressant medications are effective, they have a delayed onset of effect. Mirtazapine, an atypical antidepressant is an important option for add-on therapy in major depression. There is insufficient data on mirtazapine in Indian population; hence this study was designed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD) in Indian population. In an open, randomized study, 60 patients were divided into two groups. In Group A (n=30) patients received conventional SSRIs for 6 weeks. In Group B (n=30) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks. There was significant improvement in Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) scores (P<0.05) in both groups. Mirtazapine in low dose as add on therapy showed improvement in scores, had earlier onset of action, and more number of responders and remitters as compared to conventional treatment (P<0.05). No serious adverse event was reported in either of the groups. Low-dose mirtazapine as add-on therapy has shown better efficacy, earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patients.

  1. Low-dose computed tomography screening for lung cancer: how strong is the evidence?

    PubMed

    Woolf, Steven H; Harris, Russell P; Campos-Outcalt, Doug

    2014-12-01

    In 2013, the US Preventive Services Task Force (USPSTF) recommended low-dose computed tomographic (CT) screening for high-risk current and former smokers with a B recommendation (indicating a level of certainty that it offered moderate to substantial net benefit). Under the Affordable Care Act, the USPSTF recommendation requires commercial insurers to fully cover low-dose CT. The Centers for Medicare & Medicaid Services (CMS) is now considering whether to also offer coverage for Medicare beneficiaries. Although the National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose CT, implementation of national screening may be premature. The magnitude of benefit from routine screening is uncertain; estimates are based on data from a single study and simulation models commissioned by the USPSTF. The potential harms-which could affect a large population-include false-positive results, anxiety, radiation exposure, diagnostic workups, and the resulting complications. It is unclear if routine screening would result in net benefit or net harm. The NLST may not be generalizable to a national screening program for the Medicare age group because 73% of NLST participants were younger than 65 years. Moreover, screening outside of trial conditions is less likely to be restricted to high-risk smokers and qualified imaging centers with responsible referral protocols. Until better data are available for older adults who are screened in ordinary (nontrial) community settings, CMS should postpone coverage of low-dose CT screening for Medicare beneficiaries.

  2. Acute, Low-dose CO Inhalation does not Alter Energy Expenditure during Submaximal Exercise.

    PubMed

    Kane, L A; Ryan, B J; Schmidt, W; Byrnes, W C

    2016-01-01

    Carbon monoxide, a gas known most widely for its toxic effects at high doses, is receiving increased attention for its role as a physiological signaling molecule and potential therapeutic agent when administered in low doses. We sought to quantify any changes to oxygen consumption and energy expenditure during submaximal exercise after low-dose CO inhalation. 9 active individuals completed 4 graded submaximal exercise tests, with each test occurring during a separate visit. For their first exercise test, subjects inhaled CO or room air (1.2 mL·kg(-1) body mass) in a randomized, subject-blind fashion. A second test was repeated 24 h later when the inhaled gas should have cleared the system. Subjects repeated study procedures with the alternate dose after a washout period of at least 2 days. Low-dose CO administration did not affect oxygen consumption or energy expenditure during submaximal exercise immediately or 24 h following its administration. Increases in heart rate, blood [lactate], and perceived exertion were observed following acute CO inhalation but these effects were absent after 24 h. The results of this study suggest that low-dose CO administration does not influence the energetics of submaximal exercise, but it acutely increases the relative intensity associated with absolute workloads below the lactate threshold. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    SciTech Connect

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  4. The debate on the use of linear no threshold for assessing the effects of low doses.

    PubMed

    Tubiana, M; Aurengo, A; Averbeck, D; Masse, R

    2006-09-01

    From December 2004 to July 2005, three reports on the effects of low doses of ionising radiation were released: ICRP (2004), the joint report of the French Academies of Science and Medicine (Tubiana et al 2005), and a report from the American Academy of Sciences (BEIR VII 2005). These reports quote the same recent articles on the biological effects of low doses, yet their conclusions diverge. The French report concludes that recent biological data show that the efficacy of defense mechanisms is modulated by dose and dose rate and that linear no threshold (LNT) is no longer plausible. The ICRP and the BEIR VII reports recognise that there are biologic arguments against LNT but feel that there are not sufficient biological proofs against it to change risk assessment methodology and subsequent regulatory policy based on LNT. They point out the remaining uncertainties and the lack of mechanistic explanations of phenomena such as low dose hyperlethality or the adaptive response. In this context, a critical analysis of the available data is necessary. The epidemiological data and the experimental data challenge the validity of the LNT hypothesis for assessing the carcinogenic effect of low doses, but do not allow its exclusion. Therefore, the main criteria for selecting the most reliable dose-effect relationship from a scientific point of view should be based on biological data. Their analysis should help one to understand the current controversy.

  5. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation.

    PubMed

    Zhao, Yuchao; Ricci, Paolo F

    2010-03-18

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health.

  6. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment

    PubMed Central

    Baum, Thomas; Nasirudin, Radin A.; Mei, Kai; Garcia, Eduardo G.; Burgkart, Rainer; Rummeny, Ernst J.; Kirschke, Jan S.; Noël, Peter B.

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods. PMID:27447827

  7. Low doses of alcohol have a selective effect on the recognition of happy facial expressions.

    PubMed

    Kano, Michiko; Gyoba, Jiro; Kamachi, Miyuki; Mochizuki, Hideki; Hongo, Michio; Yanai, Kazuhiko

    2003-03-01

    Alcohol is one of the most widely used recreational drugs, yet it is associated with undesirable social behaviour. It is used primarily for its psychoactive properties, increasing sociability and talkativeness. We hypothesize that low doses of alcohol can improve the performance related to positive emotional cognition. In this experiment, we examined the effect of low doses of alcohol on the processing of emotional facial expressions. Fifteen young male volunteers drank alcohol at volumes of 30, 60, 120 ml (0.14, 0.28, 0.56 g/kg) and performed discrimination tasks on morphed facial emotion expressions of anger, happiness, sadness and surprise-neutral. One-way ANOVA co-varying pretreatment performances revealed significant differences between alcohol levels in happy face discrimination ( p<0.01). Bonferroni correction demonstrated that low doses of alcohol caused a significantly better discrimination of happy faces, and that the performances were worse with higher doses ( p<0.001). No significance was observed with the other three emotional faces. These results indicate that low doses of alcohol affect positive emotional cognition of happy facial expressions.

  8. Adverse reproductive effects of maternal low-dose melamine exposure during pregnancy in rats.

    PubMed

    Chu, Ching Yan; Tang, Ling Ying; Li, Lu; Shum, Alisa Sau Wun; Fung, Kwok Pui; Wang, Chi Chiu

    2017-01-01

    Melamine is a heterocyclic, aromatic amine and nitrogen-enriched environmental toxicant, found in not only adulterated foodstuffs but also industrial household tableware and paints. Previous studies demonstrated adverse effects of high-dose melamine on human infants and pregnant animals, but effects of low-dose melamine on pregnancy have not been reported. In this study, reproductive effects of low-dose melamine were investigated in pregnant rats. Melamine in the range of 12.5-50 mg/kg was administered to pregnant rats at different gestational stages. Maternal weight gain was not significantly affected, and other maternal morbidity was not observed. Low-dose melamine exposure during pregnancy increased fetal size but reduced somite number in gastrulation (GD8.5-GD10.5) and organogenesis (GD10.5-GD16.5) periods, and increased incidence of stillbirth in whole gestational period (GD0.5 to delivery). Embryotoxicity of melamine was further confirmed by whole embryo culture in vitro that melamine retarded embryonic growth, impaired development of brain and heart, and induced open neural tube and atrioventricular defects with increased apoptosis. In conclusion, adverse reproductive effects of low-dose melamine during pregnancy were identified in the developing rat embryos and the perinatal effects of melamine were gestational and developmental stage dependent. Detailed hazard and risk assessment of melamine in reproduction system are warrant. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 131-138, 2017.

  9. [Prevention of preeclampsia with low-dose acetyl salicylic acid: critical assessment].

    PubMed

    Verrotti, C; Fieni, S; Gualdi, M; Cavatorta, E

    1999-01-01

    The Authors present a critical review of the published literature about the effect of low dose of acido acetilsalicilico on prevention and treatment of preeclampic. Beginning from the effects of low daily dose of acido acetilsalicilico on the pregnancy, the Authors present the published datas from 1970 until today, and suggest the present directions for use of acido acetilsalicilico in pregnancy.

  10. Accelerated tests for bounding the low dose rate radiation response of lateral PNP bipolar junction transistors

    SciTech Connect

    Witczak, S.C.; Schrimpf, R.D.; Galloway, K.F.; Schmidt, D.M.; Fleetwood, D.M.; Pease, R.L.; Coombs, W.E.; Suehle, J.S.

    1996-03-01

    Low dose rate gain degradation of lateral pnp bipolar transistors can be simulated by accelerated irradiations performed at approximately 135 degrees C. Degradation enhancement is explained by temperature- dependent radiation-induced interface trap formation above the transistor`s base.

  11. Mechanism of an exaggerated locomotor response to a low-dose challenge of methamphetamine

    PubMed Central

    Frankel, Paul S.; Hoonakker, Amanda J.; Danaceau, Jonathan P.; Hanson, Glen R.

    2008-01-01

    Previous studies using phenylethylamine psychostimulants such as amphetamine (AMPH) have demonstrated that pretreatment with a high dose of drug followed by a low-dose challenge injection (3h later) results in an exaggerated behavioral response. In order to explore the mechanism of this exaggerated or what has been suggested to be a “sensitized” response, we investigated the effects of methamphetamine (METH) in a similar treatment paradigm. The current study found that, as suggested by previous studies, a low-dose challenge with METH substantially increased the locomotor response in animals that received a high-dose pretreatment (3.5 h prior to challenge). We also observed that rats displayed an increase in the concentrations of METH and its metabolite AMPH in the striatum following the low-dose challenge of METH if they were pretreated with METH versus saline. A similar pattern for METH and AMPH levels were measured in the plasma. Taken together, these results suggest that the accumulation of drug in animals pretreated with high-dose METH contributes to the overall enhanced behavioral response following challenges with low doses of METH. PMID:17303233

  12. Rewarding effects of ethanol combined with low doses of morphine through dopamine D1 receptors.

    PubMed

    Ise, Yuya; Mori, Tomohisa; Katayama, Shirou; Nagase, Hiroshi; Suzuki, Tsutomu

    2013-01-01

    This study investigated whether ethanol combined with low doses of morphine produces rewarding effects in rats. Ethanol (0.075-1.2 g/kg, intraperitoneal [i.p.]) alone did not induce place preference. A moderate dose (1 mg/kg, s.c.), but not a low dose (0.1 mg/kg), of morphine induced a significant place preference. The combination of ethanol (0.075-0.6 g/kg, i.p.) and 0.1 mg/kg of morphine, as well as low doses of morphine (0.03-0.1 mg/kg, subcutaneous [s.c.]) combined with ethanol (0.3 g/kg, i.p.), induced a significant place preference. The combined effect of ethanol and morphine was significantly attenuated by naloxone (0.3 mg/kg, s.c.), naltrindole (1.0 mg/kg, s.c.), or long-term administration of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, s.c.). These results suggest that the rewarding effect induced by ethanol and a low dose of morphine is mediated by activation of the central opioidergic and dopaminergic systems through dopamine D1 receptors.

  13. CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

    EPA Science Inventory

    Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?

    Abstract
    High doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

  14. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.

    PubMed

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-22

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  15. Antinociceptive effects of low dose lumbosacral epidural ropivacaine in healthy ponies.

    PubMed

    van Loon, Johannes P A M; Menke, Eveline S; Doornenbal, Arie; Back, Willem; Hellebrekers, Ludo J

    2012-07-01

    The objective of this study was to evaluate the safety and efficacy of low dose lumbosacral epidural ropivacaine in ponies. Antinociceptive effects of epidural ropivacaine were evaluated by means of mechanical nociceptive thresholds (MNTs) at several spinal levels in conscious ponies. The effects of ropivacaine on nociceptive afferent transmission to the spinal cord were also assessed by measuring spinal cord somatosensory evoked potentials (SSEPs) in anaesthetised ponies. Ataxia scores were determined in conscious ponies to assess the effects on motor function. A randomised, placebo controlled, double blind cross-over design was used. Low dose lumbosacral epidural ropivacaine led to increases in MNTs at various anatomical locations with a maximum effect at the lumbosacral and sacrococcygeal regions, both with respect to increase in threshold and duration of effect. Analysis of SSEPs showed that epidural ropivacaine influenced both Aβ- and Aδ-mediated afferent transmission to the spinal cord at the level of the lumbosacral junction. Ponies showed mild ataxia after low dose lumbosacral epidural ropivacaine, but all ponies remained standing. Application of low dose lumbosacral epidural ropivacaine provided safe and efficacious antinociceptive effects in conscious and anaesthetised ponies, and could therefore be a valuable addition to multimodal analgesic protocols in Equidae.

  16. The importance of lung cancer screening with low-dose computed tomography for Medicare beneficiaries.

    PubMed

    Wood, Douglas E

    2014-12-01

    The National Lung Screening Trial has provided convincing evidence of a substantial mortality benefit of lung cancer screening with low-dose computed tomography (CT) for current and former smokers at high risk. The United States Preventive Services Task Force has recommended screening, triggering coverage of low-dose CT by private health insurers under provisions of the Affordable Care Act. The Centers fo