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Sample records for low-dose prospectively gated

  1. Low-Dose Prospectively Electrocardiogram-Gated Axial Dual-Source CT Angiography in Patients with Pulsatile Bilateral Bidirectional Glenn Shunt: An Alternative Noninvasive Method for Postoperative Morphological Estimation

    PubMed Central

    Ji, Xiaopeng; Zhao, Bin; Cheng, Zhaoping; Si, Biao; Wang, Zhiheng; Duan, Yanhua; Nie, Pei; Li, Haiou; Yang, Shifeng; Jiao, Hui; Wang, Ximing

    2014-01-01

    Objective To explore the clinical value of low-dose prospectively electrocardiogram-gated axial dual-source CT angiography (low-dose PGA scanning, CTA) in patients with pulsatile bilateral bidirectional Glenn shunt (bBDG) as an alternative noninvasive method for postoperative morphological estimation. Methods Twenty patients with pulsatile bBDG (mean age 4.2±1.6 years) underwent both low-dose PGA scanning and conventional cardiac angiography (CCA) for the morphological changes. The morphological evaluation included the anatomy of superior vena cava (SVC) and pulmonary artery (PA), the anastomotic location, thrombosis, aorto-pulmonary collateral circulation, pulmonary arteriovenous malformations, etc. Objective and subjective image quality was assessed. Bland–Altman analysis and linear regression analyses were used to evaluate the correlation on measurements between CTA and CCA. Effective radiation dose of both modalities was calculated. Results The CT attenuation value of bilateral SVC and PA was higher than 300 HU. The average subjective image quality score was 4.05±0.69. The morphology of bilateral SVC and PA was displayed completely and intuitively by CTA images. There were 24 SVC above PA and 15 SVC beside PA. Thrombosis was found in 1 patient. Collateral vessels were detected in 13 patients. No pulmonary arteriovenous malformation was found in our study. A strong correlation (R2>0.8, P<0.001) was observed between the measurements on CTA images and on CCA images. Bland–Altman analysis demonstrated a systematic overestimation of the measurements by CTA (the mean value of bias>0).The mean effective dose of CTA and CCA was 0.50±0.17 mSv and 4.85±1.34 mSv respectively. Conclusion CT angiography with a low-dose PGA scanning is an accurate and reliable noninvasive examination in the assessment of morphological changes in patients with pulsatile bBDG. PMID:24736546

  2. 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.

  3. 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

  4. 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.

  5. Anti-inflammatory efficacy of low-dose cyclosporin A in psoriatic arthritis. A prospective multicentre study.

    PubMed

    Mahrle, G; Schulze, H J; Bräutigam, M; Mischer, P; Schopf, R; Jung, E G; Weidinger, G; Färber, L

    1996-11-01

    Fifty-five patients with psoriatic arthritis were treated with a low dose of cyclosporin A (CyA) (mean dose 2.7 mg/kg per day) for a period of 6 months to investigate the efficacy of CyA on disease parameters. Significant improvement in the joint complaints and inflammation parameters was observed including a decrease in the number of painful (-46%) and swollen (-45%) joints, tenderness (Ritchie Index: -50%) and degree of swelling (-46%), patient's assessment of pain (-35%), the duration of morning joint stiffness (-37%), as well as a decrease in C-reactive protein (-52%). A 50% reduction of joint complaints required a total of 24 weeks, whereas a 50% reduction of skin involvement was achieved after 5-6 weeks of treatment. Four patients left the study due to adverse events: creatinine level increase in two patients, hypertension in one patient and gastroenteritis in the fourth patient. Joint scintigraphy in 18 patients indicated an improvement or stable condition in 61% of cases after a mean follow-up of approximately 8 months. The results of this prospective study show that low-dose CyA effectively improves not only skin lesions, but also joint complaints in psoriatic arthritis. PMID:8977676

  6. 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

  7. A comparison of conventional /sup 60/Co testing and low dose-accumulation-rate exposure of metal-gate CMOS IC'S

    SciTech Connect

    Roeske, S.B.; Edwards, W.H.; Gammill, P.E.; Puariea, J.W.; Zipay, J.W.

    1984-12-01

    Data are presented for the CD4000 family of Hi-Rel, rad-hard, metal-gate CMOS ICs which show a much greater tolerance to low dose-rate ionizing radiation than that observed with ''conventional rate'' (approximately 10/sup 6/ rad(Si)/hr) /sup 60/Co testing. Data obtained using conventional rate /sup 60/Co irradiations followed by either a 24-hour, high-temperature (100/sup 0/C) anneal or a 65-day, room temperature anneal are in good agreement with data obtained by exposing similar parts at a low dose-accumulation rate (daily 17second, 5000 rad(Si) exposures) for 200 consecutive days. Graphs of thresholds, output drive, and propagation delay for both low doseaccumulation rate and conventional rate exposures are included.

  8. A prospective cohort study on sustained effects of low-dose ecstasy use on the brain in new ecstasy users.

    PubMed

    de Win, Maartje M L; Reneman, Liesbeth; Jager, Gerry; Vlieger, Erik-Jan P; Olabarriaga, Sílvia D; Lavini, Cristina; Bisschops, Ivo; Majoie, Charles B L M; Booij, Jan; den Heeten, Gerard J; van den Brink, Wim

    2007-02-01

    It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.8+/-3.1 years) in two sessions before and after first ecstasy use (1.8+/-1.3 tablets). Interval between baseline and follow-up was on average 8.1+/-6.5 months and time between last ecstasy use and follow-up was 7.7+/-4.4 weeks. Using 1H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (-6.2%), dorsolateral frontal cortex (-4.0%), and superior parietal cortex (-3.0%) (all significant at p<0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity (+3.7% on the Barratt Impulsiveness Scale) and decreased depression (-28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that

  9. 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.

  10. 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.

  11. [Clinical usefulness of 201Tl/99mTc-PYP dual myocardial quantitative gated SPECT program using low-dose dobutamine loading in assessment of myocardial viability in patient with acute myocardial infarction--a case report].

    PubMed

    Irie, Hidekazu; Ito, Kazuki; Koide, Masahiro; Taniguchi, Takuya; Yokoi, Hirokazu; Nakamura, Reo; Kinoshita, Noriyuki; Hashimoto, Tetsuo; Tamaki, Shunichi; Sawada, Takahisa; Azuma, Akihiro; Matsubara, Hiroaki

    2006-05-01

    An 86-year-old man with chest pain was admitted to our hospital. Coronary angiography revealed 99% stenosis of the mid segment of the left anterior descending coronary artery, therefore, a coronary stent was implanted. Immediately after the stent implantation, 99% stenosis occurred at the proximal site of the 1st diagonal artery because of stent jeal. On the 4th hospital day, ECG-gated 201TL/99mTc-PYP dual myocardial quantitative gated SPECT was performed at rest and during low-dose dobutamine loading. The 201Tl scintigraphy revealed moderately reduced uptake in the anterior, septal and apical walls, and 99mTc-PYP uptake was observed in the mid-anterior wall. A three-dimensional surface display of gated 201Tl SPECT images showed severe hypokinesis in the anterior, septal and apical walls at rest. On the other hand, during low-dose dobutamine loading, improved wall motion was observed in the basal anterior and septal walls, while no change was observed in the midanterior and apical wall movements. Three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images revealed similar patterns of wall motion as those of gated 201Tl SPECT images at rest. During low-dose dobutamine loading, on the other hand, a three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images revealed improved wall motion in the basal anterior, septal and apical walls, but worsened wall motion of the mid-anterior wall. After 6 months, a follow-up coronary angiography revealed no re-stenosis of the stent, but 99% stenosis at the proximal aspect of the 1st diagonal artery. Left ventriculography revealed improved wall motion in the apex and akinesis of the mid-anterior wall. These wall motion findings were similar to those visualized in the three-dimensional surface display of gated 201Tl/99mTc-PYP dual SPECT images during low-dose dobutamine loading in the acute phase. These results suggest that 201Tl/99mTc-PYP dual myocardial quantitative gated SPECT using low-dose

  12. 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

  13. Low-Dose Fluvoxamine Treatment of Children and Adolescents with Pervasive Developmental Disorders: A Prospective, Open-Label Study.

    ERIC Educational Resources Information Center

    Martin, Andres; Koenig, Kathleen; Anderson, George M.; Scahill, Lawrence

    2003-01-01

    This prospective open-label study assessed the efficacy and tolerability of low-doze fluvoxamine in 14 children with pervasive developmental disorders (PDDs). Although there was no response for the group as a whole, eight subjects were considered at least partial responders in intent-to-treat analyses. Results suggest fluvoxamine can be beneficial…

  14. Prospective Evaluation of Low-Dose Ketoconazole Plus Hydrocortisone (HC) in Docetaxel Pre-treated Castration-Resistant Prostate Cancer (CRPC) Patients

    PubMed Central

    Lo, Ernest N.; Beckett, Laurel A.; Pan, Chong-Xian; Robles, Daniel; Suga, Jennifer M.; Sands, Jacob M.; Lara, Primo N.

    2015-01-01

    option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy. PMID:25667107

  15. 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

  16. Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome.

    PubMed

    Yakoub-Agha, Ibrahim; Mary, Jean-Yves; Hulin, Cyrille; Doyen, Chantal; Marit, Gérald; Benboubker, Lotfi; Voillat, Laurent; Moreau, Philippe; Berthou, Christian; Stoppa, Anne-Marie; Maloisel, Frédéric; Rodon, Philippe; Dib, Mamoun; Pegourie, Brigitte; Casassus, Philippe; Slama, Borhane; Damaj, Ghandi; Zerbib, Robert; Harousseau, Jean-Luc; Mohty, Mohamad; Facon, Thierry

    2012-03-01

    This multicentre prospective randomised trial compared the efficacy and safety of two doses of thalidomide in patients with relapsed or refractory myeloma. The study was designed to test the non-inferior efficacy and to confirm the better tolerability of low-dose thalidomide as compared to a higher dose. Four hundred patients were randomly assigned to receive either 100 or 400 mg/day of thalidomide. Dexamethasone treatment was added in both arms for patients with stable disease or treatment failure at 12 weeks. The primary endpoint was 1-year overall survival (OS). Thalidomide 100 mg/day was better tolerated than 400 mg/day with less high-grade somnolence, constipation, nausea/vomiting and peripheral neuropathy (P < 0.001, P = 0.007, P = 0.03 and P = 0.007, respectively). In the per-protocol population (PP), the estimated 1-year OS rates were of 74.5% (n = 149) and 67.3% (n = 156) in the 400 and 100 groups, respectively. The upper limit of the difference between these rates was of 15.6% higher than the non-inferiority acceptable limit of 12.75%, and the hypothesis of non-inferiority of 100 could not be established (P = 0.14). On the other hand, when intent-to-treat (ITT) population was analysed, the non-inferiority was demonstrated because the 1-year OS rates were of 72.8% (n = 195) and 68.8% (n = 205) in the same groups, leading to an upper limit of the difference of 11.49% lower than the non-inferiority acceptable limit. In addition, in patients alive 12 weeks postrandomisation and those who received thalidomide plus dexamethasone, there were no significant differences in response rates, time to progression, progression-free survival and OS between the two groups. Collectively, low-dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile and can be a good salvage therapy in combination with dexamethasone. PMID:22023551

  17. Pulmonary Venous Anatomy Imaging with Low-Dose, Prospectively ECG-Triggered, High-Pitch 128-Slice Dual Source Computed Tomography

    PubMed Central

    Thai, Wai-ee; Wai, Bryan; Lin, Kaity; Cheng, Teresa; Heist, E. Kevin; Hoffmann, Udo; Singh, Jagmeet; Truong, Quynh A.

    2012-01-01

    Background Efforts to reduce radiation from cardiac computed tomography (CT) are essential. Using a prospectively triggered, high-pitch dual source CT (DSCT) protocol, we aim to determine the radiation dose and image quality (IQ) in patients undergoing pulmonary vein (PV) imaging. Methods and Results In 94 patients (61±9 years, 71% male) who underwent 128-slice DSCT (pitch 3.4), radiation dose and IQ were assessed and compared between 69 patients in sinus rhythm (SR) and 25 in atrial fibrillation (AF). Radiation dose was compared in a subset of 19 patients with prior retrospective or prospectively triggered CT PV scans without high-pitch. In a subset of 18 patients with prior magnetic resonance imaging (MRI) for PV assessment, PV anatomy and scan duration were compared to high-pitch CT. Using the high-pitch protocol, total effective radiation dose was 1.4 [1.3, 1.9] mSv, with no difference between SR and AF (1.4 vs 1.5 mSv, p=0.22). No high-pitch CT scans were non-diagnostic or had poor IQ. Radiation dose was reduced with high-pitch (1.6 mSv) compared to standard protocols (19.3 mSv, p<0.0001). This radiation dose reduction was seen with SR (1.5 vs 16.7 mSv, p<0.0001) but was more profound with AF (1.9 vs 27.7 mSv, p=0.039). There was excellent agreement of PV anatomy (kappa 0.84, p<0.0001), and a shorter CT scan duration (6 minutes) compared to MRI (41 minutes, p<0.0001). Conclusions Using a high-pitch DSCT protocol, PV imaging can be performed with minimal radiation dose, short scan acquisition, and excellent IQ in patients with SR or AF. This protocol highlights the success of new cardiac CT technology to minimize radiation exposure, giving clinicians a new low-dose imaging alternative to assess PV anatomy. PMID:22586259

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

    PubMed

    Goharian, M; Khan, R F H

    2010-04-01

    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 delivery

  19. 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...

  20. 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

  1. Low-dose bacille Calmette–Guérin for non-muscle-invasive bladder cancer: Results of a prospective study

    PubMed Central

    Nour, Hani H.; Gobashy, Smair E.; Kamal, Ahmad M.; Elbaz, Ahmad G.; Roshdy, Mamdouh A.; Kamel, Ahmad I.

    2015-01-01

    Objective To evaluate the efficacy and safety of low-dose (45 mg) intravesical bacille Calmette–Guérin (BCG) therapy in the treatment of patients with non-muscle-invasive bladder cancer (NMIBC), as intravesical BCG is the most acceptable adjuvant therapy for NMI transitional cell carcinoma of the bladder. However, in the standard regimen, undesirable effects are the main cause of treatment discontinuation. Patients and methods The present study included 37 men with primary NIMBC. All patients underwent complete TURB and 2 weeks later, a 6-week course of 45 mg BCG diluted in 50 mL isotonic saline was instilled into the bladder and retained for 2 h. Patients were evaluated for BCG efficacy (recurrence with or without progression) and safety by documentation of minor and/or major side-effects. Results There were no major or severe side-effects and no treatment discontinuations. Local adverse effects occurred in 20 patients, while systemic effects, in the form of fever, occurred in six patients (16.2%). There was recurrence in 14 patients (37.8%) after 18–34 months, with disease progression (muscle invasion) in four (10.8%) after 6–18 months. The recurrence index was 0.39/100 patients/month and the mean (range) tumour-free period was 30.97 (7–36) months. Conclusion Low-dose BCG intravesical therapy is an effective adjuvant treatment in NMIBC. However, this needs to be validated in future studies and in comparison with other proposed doses and/or regimens. PMID:26609440

  2. Low-dose tacrolimus combined with donor-derived mesenchymal stem cells after renal transplantation: a prospective, non-randomized study

    PubMed Central

    Pan, Guang-hui; Chen, Zheng; Xu, Lu; Zhu, Jing-hui; Xiang, Peng; Ma, Jun-jie; Peng, Yan-wen; Li, Guang-hui; Chen, Xiao-yong; Fang, Jia-li; Guo, Yu-he; Zhang, Lei; Liu, Long-shan

    2016-01-01

    Calcineurin inhibitors, including tacrolimus, are largely responsible for advances in allotransplantation. However, the nephrotoxicity associated with these immunosuppressants impairs patients' long-term survival after renal allograft. Therefore, novel regimens that minimize or even eliminate calcineurin inhibitors could improve transplantation outcomes. In this pilot study, we investigated the use of low-dose tacrolimus in combination with mesenchymal stem cells (MSCs), which are immunosuppressive and prolong allograft survival in experimental organ transplant models. Donor-derived, bone marrow MSCs combined with a sparing dose of tacrolimus (0.04-0.05 mg/kg/day) were administered to 16 de novo living-related kidney transplant recipients; 16 other patients received a standard dose of tacrolimus (0.07-0.08 mg/kg/day). The safety of MSC infusion, acute rejection, graft function, graft survival, and patient survival were evaluated over ≥24 months following kidney transplantation. All patients survived and had stable renal function at the 24 month follow-up. The combination of low-dose tacrolimus and MSCs was as effective as standard dose tacrolimus in maintaining graft survival at least 2 years after transplantation. In addition, both groups had similar urea, urine protein, urinary RBC, urinary WBC, 24-h urine protein, and creatinine clearance rates from 7 days to 24 months after transplantation. Furthermore, no differences in the proportion of lymphocytes, CD19, CD3, CD34, CD38, and natural killer cells were detected between the control and experimental groups. None of the MSC recipients experienced immediate or long-term toxicity from the treatment. This preliminary data suggests that the addition of MSCs permits the use of lower dosages of nephrotoxic calcineurin inhibitors following renal transplantation. PMID:26933811

  3. Comparison and Efficacy of Low-Dose and Standard-Dose Tamsulosin and Alfuzosin in Medical Expulsive Therapy for Lower Ureteral Calculi: Prospective, Randomized, Comparative Study

    PubMed Central

    Cha, Woo Heon; Choi, Jae Duck; Seo, Young Jin; Lee, Kyungseop

    2012-01-01

    Purpose Typically in Korea, for a standard dose (0.4 mg) of tamsulosin, two low doses (0.2 mg) are administered. The aim of this study was to evaluate and compare the efficacy of tamsulosin (0.2 mg and 0.4 mg) and alfuzosin (10 mg) in the treatment of lower ureteral stones. Materials and Methods A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were randomly assigned to 4 groups. Patients in group 1 (n=41) and group 2 (n=30) received an oral dose of 0.2 mg tamsulosin once and twice daily, respectively, and patients in group 3 (n=36) received a daily oral dose of 10 mg alfuzosin. Patients in group 4 (n=34) received trospium chloride only. The spontaneous passage of stones, the stone expulsion time, and adverse effects were evaluated. Results There were no significant differences in patient background, including age, sex, BMI, stone size, stone side, and symptom duration. The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1, 2, and 3 than in group 4. There were no statistically different changes in groups 1, 2, and 3. The adverse effects observed in all groups were comparable and were mild. Conclusions Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin (10 mg) proved to be safe and effective. A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone. PMID:22670195

  4. Comparative evaluation of dexmedetomidine and clonidine with low dose ropivacaine in cervical epidural anesthesia for modified radical mastectomy: A prospective randomized, double-blind study

    PubMed Central

    Channabasappa, Shivakumar M.; Venkatarao, Gopinath H.; Girish, Shobha; Lahoti, Nandakishore K.

    2016-01-01

    Context: Alpha-2 adrenergic agonists clonidine and dexmedetomidine, are well known to produce analgesia through an opioid independent mechanism. Alpha-2 agonists are used as an adjuvant to local anesthetic agents to extend the duration of spinal, epidural and brachial plexus blocks. Aims: We compared clonidine and dexmedetomidine as an adjuvant to Ropivacaine in cervical epidural anesthesia (CEA) with respect to onset and duration of sensory block, duration of analgesia and adverse effects. Subjects and Methods: A total 150 American Society of Anesthesiologists Class I or II adult female patients who were scheduled to undergo modified radical mastectomy were randomly allocated to the following two groups to receive CEA: Group D receive 15 mL of 0.375% ropivacaine combined with 1 μg/kg of dexmedetomidine; Group C received 15 mL of 0.375% ropivacaine combined with 1.5 μg/kg of clonidine. The onset of sensory block, duration of analgesia, mean arterial pressure (MAP), heart rate (HR), sedation scores, and the incidences of adverse effects, such as hypotension, bradycardia, and oxygen desaturation were recorded. Results: The addition of dexmedetomidine to ropivacaine (Group D) resulted in faster onset of sensory block time compared with the addition of clonidine to ropivacaine (Group C) (95% confidence interval [CI]: 14.53 ± 2.96 vs. 16.72 ± 4.43 P = 0.032). The duration of analgesia block in Group D was significantly longer than that in Group C (95% CI: 234.65 ± 23.76 vs. 286.76 ± 34.65; P = 0.037). The Ramsay sedation score at in Group D were significantly higher between 20 and 60 min as compared to Group C (P < 0.022). MAP level and HR level in Group D and Group C were comparable. Conclusion: The addition of dexmedetomidine to low dose ropivacaine for CEA could shorten the onset of sensory block and extend the duration of analgesia with optimum sedation without episodes of hypoxemia as compared to addition of clonidine to ropivacaine. PMID:26957695

  5. Evaluation of a Chest Circumference-Adapted Protocol for Low-Dose 128-Slice Coronary CT Angiography with Prospective Electrocardiogram Triggering

    PubMed Central

    Lu, Chenying; Wang, Zufei; Wang, Hailin; Hu, Xianghua; Chen, Chunmiao

    2015-01-01

    Objective To assess the effect of chest circumference-adapted scanning protocol on radiation exposure and image quality in patients undergoing prospective electrocardiogram (ECG)-triggered coronary CT angiography (CCTA). Materials and Methods One hundred-eighty-five consecutive patients, who had undergone prospective ECG triggering CCTA with a 128-slice CT, were included in the present study. Nipple-level chest circumference, body weight and height were measured before CT examinations. Patients were divided into four groups based on kV/ref·mAs = 100/200, 100/250, 120/200, and 120/250, when patient's chest circumference was ≤ 85.0 (n = 56), 85.0-90.0 (n = 53), 90.0-95.0 (n = 44), and > 95.0 (n = 32), respectively. Image quality per-segment was independently assessed by two experienced observers. Image noise and attenuation were also measured. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The effective radiation dose was calculated using CT dose volume index and the dose-length product. Results A significant correlation was observed between patients' chest circumference and body mass index (r = 0.762, p < 0.001). Chest circumference ranged from 74 to 105 cm, and the mean effective radiation dose was 1.9-3.8 mSv. Diagnostic image quality was obtained in 98.5% (2440/2478) of all evaluated coronary segments without any significant differences among the four groups (p = 0.650). No significant difference in image noise was observed among the four groups (p = 0.439), thus supporting the validity of the chest circumference-adapted scanning protocol. However, vessel attenuation, SNR and CNR were significantly higher in the 100 kV groups than in the 120 kV groups (p < 0.05). Conclusion A measure of chest circumference can be used to adapt tube voltage and current for individualized radiation dose control, with resultant similar image noise and sustained diagnostic image quality. PMID:25598671

  6. Efficacy and Safety of Low-Dose Propiverine in Patients with Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia with Storage Symptoms: A Prospective, Randomized, Single-Blinded and Multicenter Clinical Trial

    PubMed Central

    Bae, Jae Hyun; Kim, Sun Ouck; Yoo, Eun Sang; Moon, Kyung Hyun; Kyung, Yoon Soo

    2011-01-01

    Purpose The aim of this study was to evaluate whether low-dose anticholinergics combined with an α1-receptor antagonist would continue the effect of an alpha-blocker, decrease the side effects of anticholinergics, and improve the symptoms of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Materials and Methods Two hundred nine men with LUTS/BPH with storage symptoms (International Prostate Symptom Score [IPSS] ≥12; storage symptoms ≥4) were randomly assigned in a prospective, multicentered, and single-blind fashion to either the control group (alfuzosin 10 mg, once daily) or the combined group (alfuzosin 10 mg, once daily, and propiverine 10 mg, once daily) for 2 months. IPSS, maximal urinary flow rate (Qmax), and postvoid residual volume (PVR) were used to grade symptoms, side effects, and the impact on quality of life (QoL) at the start of the study and after 1 and 2 months. Results There were no significant differences in patient background, including age, prostate size, Qmax, and PVR, between the control group and the combined group. In the combined group, the IPSS total score and the IPSS storage symptom score were significantly improved compared with the control group. The IPSS voiding symptom score, QoL, Qmax, and PVR did not differ significantly. There were no serious side effects in either group. Conclusions Management with an α1-receptor antagonist combined with a low-dose anticholinergic improved the total score and storage symptom score of the IPSS compared with α1-receptor antagonist only group without causing serious side effects. This initial combination medication can be considered an effective and safe treatment modality for LUTS/BPH patients with storage symptoms. PMID:21556215

  7. Short Term Efficacy and Safety of Low Dose Tolvaptan in Patients with Acute Decompensated Heart Failure with Hyponatremia: A Prospective Observational Pilot Study from a Single Center in South India

    PubMed Central

    Patra, Soumya; Kumar, Basant; Harlalka, Kaushal K.; Jain, Apoorva; Bhanuprakash, H. M.; Sadananda, K. S.; Basappa, Harsha; Santhosh, K.; Rajith, K. S.; Bharathi, K. S.; Manjunath, C. N.

    2014-01-01

    Background: In acute decompensated heart failure (ADHF), diuretic use, the mainstay therapy for congestion, is associated with electrolyte abnormalities and worsening renal function. Vasopressin mediates fluid retention in heart failure. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function. Hyponatremia (serum sodium concentration, <135 mEq/L) is a predictor of death among patients with heart failure. Objective: We prospectively observed the short term efficacy and safety of low dose (15 mg) tolvaptan in admitted patients with hyponatremia and ADHF in Indian population. Methodology: A total of 40 patients with ADHF along with hyponatremia (<125 mEq/L) on standard therapy were treated with 15 mg of tolvaptan at a single oral dose for 7 days. Results: Serum sodium concentrations increased significantly after treatment with tolvaptan from baseline (P < 0.02). There was a significant improvement in symptoms and New York Heart Association (NYHA) class after starting tolvaptan (P ≤ 0.05). Total diuretic dose and mean body weight was reduced non-significantly at 7th day from the baseline. Side-effects associated with tolvaptan included increased thirst, dry mouth and increased urination. Few patients had worsening renal function. However, several patients developed hypernatremia. Conclusion: In this small observational study, tolvaptan initiation in patients with ADHF with hyponatremia in addition to standard therapy may hold promise in improvement in NYHA class and serum sodium. At the same time, we observed that serious adverse events such as renal function deterioration and hypernatremia developed after tolvaptan treatment, which needs to be addressed in future by randomized study with larger sample size. PMID:24949180

  8. Hepatic intra-arterial chemotherapy (HIAC) of high dose mitomycin and epirubicin combined with caval chemofiltration versus prolonged low doses in liver metastases from colorectal cancer: a prospective randomized clinical study.

    PubMed

    Fiorentini, G; Poddie, D B; Cantore, M; Rossi, S; Tumolo, S; Dentico, P; Bernardeschi, P; Guadagni, S; Rossi, G; Valori, V M; De Simone, M

    2004-11-01

    A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22). PMID:15675479

  9. Prospective respiratory-gated micro-CT of free breathing rodents.

    PubMed

    Ford, Nancy L; Nikolov, Hristo N; Norley, Chris J D; Thornton, Michael M; Foster, Paula J; Drangova, Maria; Holdsworth, David W

    2005-09-01

    Microcomputed tomography (Micro-CT) has the potential to noninvasively image the structure of organs in rodent models with high spatial resolution and relatively short image acquisition times. However, motion artifacts associated with the normal respiratory motion of the animal may arise when imaging the abdomen or thorax. To reduce these artifacts and the accompanying loss of spatial resolution, we propose a prospective respiratory gating technique for use with anaesthetized, free-breathing rodents. A custom-made bed with an embedded pressure chamber was connected to a pressure transducer. Anaesthetized animals were placed in the prone position on the bed with their abdomens located over the chamber. During inspiration, the motion of the diaphragm caused an increase in the chamber pressure, which was converted into a voltage signal by the transducer. An output voltage was used to trigger image acquisition at any desired time point in the respiratory cycle. Digital radiographic images were acquired of anaesthetized, free-breathing rats with a digital radiographic system to correlate the respiratory wave form with respiration-induced organ motion. The respiratory wave form was monitored and recorded simultaneously with the x-ray radiation pulses, and an imaging window was defined, beginning at end expiration. Phantom experiments were performed to verify that the respiratory gating apparatus was triggering the micro-CT system. Attached to the distensible phantom were 100 microm diameter copper wires and the measured full width at half maximum was used to assess differences in image quality between respiratory-gated and ungated imaging protocols. This experiment allowed us to quantify the improvement in the spatial resolution, and the reduction of motion artifacts caused by moving structures, in the images resulting from respiratory-gated image acquisitions. The measured wire diameters were 0.135 mm for the stationary phantom image, 0.137 mm for the image gated at end

  10. 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. PMID:27015224

  11. Comparable effect with minimal morbidity of low-dose Tokyo 172 strain compared with regular dose Connaught strain as an intravesical bacillus Calmette–Guérin prophylaxis in nonmuscle invasive bladder cancer: Results of a randomized prospective comparison

    PubMed Central

    Inamoto, Teruo; Ubai, Takanobu; Nishida, Takeshi; Fujisue, Yutaka; Katsuoka, Yoji; Azuma, Haruhito

    2013-01-01

    Aim: The aim was to compare patients' morbidity and response of bacillus Calmette–Guérin (BCG) prophylaxis after the intravesical instillation of low-dose Tokyo 172 strain and regular dose Connaught strain in patients with nonmuscle invasive bladder cancer (NMIBC). Patients and Methods: This was a randomized, active-controlled, open-label, monocenter study. Thirty-eight, NMIBC patients were treated sequentially, in a random order, with low-dose Tokyo 172 strain and regular dose Connaught strain, receiving each therapy for 6 weeks. A total of 18 and 20 patients were randomly assigned to a Tokyo 172 strain arm and a Connaught strain arm, respectively. Complication, morbidity, and recurrence-free survival (RFS) after each treatment were compared. Results: There was no significant difference in the 1-year RFS rate in patients treated with Tokyo 172 strain and Connaught strain (72.2% vs. 83.5%, respectively; P = 0.698). There were no significant differences in adverse events between the arms. Severe adverse events (>Grade 3) were seen in 15% of the Connaught strain group while no severe adverse events were observed as a result of Tokyo 172 strain. Conclusion: Our results indicated that low-dose Tokyo 172 strain decreased adverse events although it was not significant, and the RFS difference was not statistically significant between the two arms. Further investigation is warranted. PMID:23662001

  12. An optical fiber-based gating device for prospective mouse cardiac MRI.

    PubMed

    Sablong, Raphaël; Rengle, A; Ramgolam, A; Saint-Jalmes, H; Beuf, O

    2014-01-01

    Prospective synchronization of MRI acquisitions on living organisms involves the monitoring of respiratory and heart motions. The electrocardiogram (ECG) signal is conventionally used to measure the cardiac cycle. However, in some circumstances, obtaining an uncorrupted ECG signal recorded on small animals with radio frequency (RF) pulses and gradient switching is challenging. To monitor respiratory motion, an air cushion associated with a pressure sensor is commonly used but the system suffers from bulkiness. For many applications, the physiological gating information can also be derived from an MR navigated signal. However, a compact device that can simultaneously provide respiratory and cardiac information, for both prospective gating and physiological monitoring, is desirable. This is particularly valid since small volume coils or dedicated cardiac RF coil arrays placed directly against the chest wall are required to maximize measurement sensitivity. An optic-based device designed to synchronize MRI acquisitions on small animal's respiratory and heart motion was developed using a transmit-receive pair of optical fibers. The suitability of the developed device was assessed on mice ( n = 10) and was based on two sets of experiments with dual cardiac and respiratory synchronization. Images acquired with prospective triggering using the optical-based signal, ECG, and the pressure sensor during the same experiment were compared between themselves in the first set. The second set compared prospective technique using optical-based device and ECG to a retrospective technique. The optical signal that was correlated to both respiratory and heart motion was totally unaffected by radiofrequency pulses or currents induced by the magnetic field gradients used for imaging. Mice heart MR images depict low-visible motion artifacts with all sensors or techniques used. No significant SNR differences were found between each series of image. Full fiber-optic-based signal derived

  13. 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

  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. 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.

  18. Dose reduction of up to 89% while maintaining image quality in cardiovascular CT achieved with prospective ECG gating

    NASA Astrophysics Data System (ADS)

    Londt, John H.; Shreter, Uri; Vass, Melissa; Hsieh, Jiang; Ge, Zhanyu; Adda, Olivier; Dowe, David A.; Sabllayrolles, Jean-Louis

    2007-03-01

    We present the results of dose and image quality performance evaluation of a novel, prospective ECG-gated Coronary CT Angiography acquisition mode (SnapShot Pulse, LightSpeed VCT-XT scanner, GE Healthcare, Waukesha, WI), and compare it to conventional retrospective ECG gated helical acquisition in clinical and phantom studies. Image quality phantoms were used to measure noise, slice sensitivity profile, in-plane resolution, low contrast detectability and dose, using the two acquisition modes. Clinical image quality and diagnostic confidence were evaluated in a study of 31 patients scanned with the two acquisition modes. Radiation dose reduction in clinical practice was evaluated by tracking 120 consecutive patients scanned with the prospectively gated scan mode. In the phantom measurements, the prospectively gated mode resulted in equivalent or better image quality measures at dose reductions of up to 89% compared to non-ECG modulated conventional helical scans. In the clinical study, image quality was rated excellent by expert radiologist reviewing the cases, with pathology being identical using the two acquisition modes. The average dose to patients in the clinical practice study was 5.6 mSv, representing 50% reduction compared to a similar patient population scanned with the conventional helical mode.

  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. Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR)

    PubMed Central

    Clearfield, Michael B; Amerena, John; Bassand, Jean-Pierre; García, Hugo R Hernández; Miller, Sam S; Sosef, Froukje FM; Palmer, Michael K; Bryzinski, Brian S

    2006-01-01

    Background Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg) and atorvastatin (20 mg) in high-risk patients with hypercholesterolemia. Methods A total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or atorvastatin 20 mg. The primary endpoint was the percentage change from baseline in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk ≥ 5% or 3.0 mmol/L for all other patients), changes in other lipids and lipoproteins, cost-effectiveness, and safety. Results Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High-density lipoprotein cholesterol was increased significantly with rosuvastatin 10 mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments were well tolerated, with a similar incidence of adverse events (rosuvastatin 10 mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis

  1. Low Dose Effects: Benefit or Harm?

    PubMed

    Woloschak, Gayle E

    2016-03-01

    This forum article discusses issues related to the effects of low dose radiation, an area that is under intense study but difficult to assess. Experiments with large-scale animal studies are included in this paper; these studies point to the need for international consortia to examine and balance the results of these large-scale studies and databases. PMID:26808889

  2. 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

  3. 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

    Pirard, Céline; Loumaye, Ernest; Laurent, Pascale; 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

  4. 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

  5. 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

  6. 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.’

  7. 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. PMID:26808877

  8. Low doses of cholestyramine in the treatment of hyperthyroidism.

    PubMed

    Kaykhaei, Mahmoud Ali; Shams, Mesbah; Sadegholvad, Abdosamad; Dabbaghmanesh, Mohammad Hossein; Omrani, Gholamhossein Ranjbar

    2008-01-01

    The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis. Bile-salt sequestrants bind thyroid hormones in the intestine and thereby increase their fecal excretion. Based on these observations, the use of cholestyramine has been tried. The present study evaluates the effect of low doses of cholestyramine as an adjunctive therapy in the management of hyperthyroidism. In a prospective, randomized, double-blind, placebo-controlled trial, 45 patients with newly diagnosed hyperthyroid Graves' disease were randomly assigned into the following treatment protocols: group I, cholestyramine 2 g BID, methimazole and propranolol; group II, cholestyramine 1 g BID, methimazole and propranolol; group III, placebo powder, methimazole and propranolol. The fixed dose of methimazole (30 mg/d) and propranolol (40 mg/d) was used. The study period was 4 weeks. Serum total triiodothyronine and free thyroxin were measured at baseline, and at the ends of the second and the fourth week of the study. The serum thyroid hormone levels decreased more rapidly and to a greater extent in the cholestyramine-treated groups. All of the patients in group I had achieved euthyroid state at the end of the study. We conclude that low dose of cholestyramine is an effective and well-tolerated adjunctive agent in the treatment of hyperthyroid Graves' disease. PMID:18946743

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

    PubMed

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

    2015-10-01

    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. PMID:26509454

  10. [Complications of low-dose amiodarone].

    PubMed

    Feigl, D; Gilad, R; Katz, E

    1991-11-15

    Complications of low-dose amiodarone in 83 patients, in whom the drug was effective and who were followed for 1-13 years, are presented. Hypothyroidism was diagnosed in 11 (in 8 by the finding of elevated TSH). In 2 of the 3 in whom clinical signs of hypothyroidism were evident, amiodarone was continued, but thyroxine was also given. In 5 others thyrotoxicosis ensued. Propylthiouracil (PTU) was given and amiodarone was discontinued. PTU was then stopped within 4-8 months, without recurrence of the hyperthyroidism. In 1 patient pneumonitis resolved spontaneously a few weeks after stopping amiodarone. Because of gastrointestinal distress amiodarone was stopped in 1 patient. In none were liver enzymes elevated, nor was the nervous system affected clinically. Photosensitivity in 6 patients and skin discoloration in 2 did not necessitate discontinuation of the drug. Blurred vision was reported by 4, but its connection with amiodarone was not proven. There was sinus bradycardia in 2. There was no arrhythmic effect of amiodarone seen on ECG nor on Holter monitoring, nor was there any mortality. We conclude that amiodarone in low doses causes many complications, most of them mild and transient. However, in only a few cases is discontinuation of the drug indicated. PMID:1752553

  11. 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. PMID:22641644

  12. Comparison Between Prospectively Electrocardiogram-Gated High-Pitch Mode and Retrospectively Electrocardiogram-Gated Mode for Dual-Source CT Coronary Angiography

    PubMed Central

    Koplay, Mustafa; Celik, Mahmut; Avcı, Ahmet; Erdogan, Hasan; Demir, Kenan; Sivri, Mesut; Nayman, Alaaddin

    2015-01-01

    Summary Background We aimed to report the image quality, relationship between heart rate and image quality, amount of contrast agent given to the patients and radiation doses in coronary CT angiography (CTA) obtained by using high-pitch prospectively ECG-gated “Flash Spiral” technique (method A) or retrospectively ECG-gated technique (method B) using 128×2-slice dual-source CT. Material/Methods A total of 110 patients who were evaluated with method A and method B technique with a 128×2-detector dual-source CT device were included in the study. Patients were divided into three groups based on their heart rates during the procedure, and a relationship between heart rate and image quality were evaluated. The relationship between heart rate, gender and radiation dose received by the patients was compared. Results A total of 1760 segments were evaluated in terms of image quality. Comparison of the relationship between heart rate and image quality revealed a significant difference between heart rate <60 beats/min group and >75 beats/min group whereas <60 beats/min and 60–75 beats/min groups did not differ significantly. The average effective dose for coronary CTA was calculated as 1.11 mSv (0.47–2.01 mSv) for method A and 8.22 mSv (2.19–12.88 mSv) for method B. Conclusions Method A provided high quality images with doses as low as <1 mSv in selected patients who have low heart rates with a high negative predictive value to rule out coronary artery disease. Although method B increases the amount of effective dose, it provides high diagnostic quality images for patients who have a high heart rate and arrhythmia which makes it is difficult to obtain images. PMID:26767072

  13. 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.

  14. Ultra-Low Dose Lung CT Perfusion Regularized by a Previous Scan

    PubMed Central

    Yu, Hengyong; Zhao, Shiying; Hoffman, Eric A.; Wang, Ge

    2009-01-01

    Rationale and Objectives Our previous scan regularized reconstruction (PSRR) method is proposed to reduce radiation dose and applied for lung perfusion studies. The normal and ultra-low dose lung CT perfusion studies are compared in terms of estimation accuracy of pulmonary functional parameters. Materials and Methods A sequences of sheep lung scans were performed in three prone, anesthetized sheep at normal and ultra-low doses. A scan protocol was developed for the ultra-low dose studies with ECG gating - time point one for a normal x-ray dose scan (100kV/150mAs) and time points 2–21 for low dose scans (80kV/17mAs). A nonlinear diffusion-based post-filtering (NDPF) method was applied to the difference images between the low-dose images and the high-quality reference image. The final images at 20 time points were generated by fusing the reference image with the filtered difference images. Results The power spectra of perfusion images and coherences with the normal scans show a great improvement in image quality of the ultra-low dose scans with PSRR relative to that without RSRR. The Gamma variate-fitting and the repeatability of the measurements of the mean transit time demonstrate that the key parameters of lung functions can be reliably accessed using PSRR. The variability of the ultra-low dose scan results obtained using PSRR is not substantially different from that between two normal dose scans. Conclusions Our studies have shown that a ~90% reduction in radiation dose is achievable using PSRR without compromising the quantitative CT measurements of regional lung functions. PMID:19201366

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. LINKING MOLECULAR EVENT TO CELLULAR RESPONSES AT LOW DOSE EXPOSURES

    EPA Science Inventory

    Defining low dose radiation cancer risks is limited by our ability to measure and directly correlate relevant cellular and molecular responses occurring at low dose and dose rate with tumor formation. This deficiency has led to conservative risk assessments based on low dose ext...

  20. 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

  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. 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. PMID:12319754

  3. Functional phase-correlated micro-CT imaging of small rodents with low dose

    NASA Astrophysics Data System (ADS)

    Sawall, Stefan; Bergner, Frank; Hess, Andreas; Lapp, Robert; Mronz, Markus; Karolczak, Marek; Kachelriess, Marc

    2011-03-01

    Functional imaging of an animals thoracic region requires cardiac and respiratory gating. The information on respiratory motion and ECG required for double-gating are extracted from the rawdata and used to select the projections appropriate for a given motion phase. A conventional phase-correlated reconstruction (PC) therefore uses only a small amount of the total projections acquired. Thus the resulting images comprise a high noise level unless acquired with very high dose, and streak artifacts may occur due to the sparse angular sampling. Here, we are aiming at getting high fidelity images even for relatively low dose values. To overcome these issues we implemented an iterative reconstruction method encompassing a five-dimensional (spatial, cardiac-temporal, respiratory-temporal) edge-preserving filter. This new phase-correlated low-dose (LDPC) reconstruction method is evaluated using retrospectively-gated, contrast-enhanced micro CT data of mice. The scans performed comprise 7200 projections within 10 rotations over 5 minutes. A tube voltage of 65 kV was used resulting in an administered dose of about 500 mGy. 20 respiratory phases and 10 cardiac phases are reconstructed. Using LDPC reconstruction the image noise is typically reduced by a factor of about six and artifacts are almost removed. Reducing the number of projections available for reconstruction shows that we can get comparable image quality with only 200 mGy. LDPC enables high fidelity low-dose double-gated imaging of free breathing rodents without compromises in image quality. Compared to PC image noise is significantly reduced with LDPC and the administered dose can be reduced accordingly.

  4. Low dose mercury toxicity and human health.

    PubMed

    Zahir, Farhana; Rizwi, Shamim J; Haq, Soghra K; Khan, Rizwan H

    2005-09-01

    Post Minamata incident there has been awareness about mercury toxicity even among the general public. Previous researches contributed a vast amount of data regarding acute mercury exposure, but gradually information about the low dose [Ninomiya, T., Ohmori, H., Hashimoto, K., Tsuruta, K., Ekino, S., 1995. Expansion of methylmercury poisoning outside minamata: an epidemiological study on chronic methylmercury poisoninig outside of Minamata. Environ. Res. 70 (1) 47-50; Lebel, J., Mergler, D., Lucotte, M., Amorim, M., Dolbec, J., Miranda, D., Arantes, G., Rheault, I., Pichet, P., 1996. Evidence of early nervous system dysfunction in Amazonian populations exposed to low-levels of methylmercury. Neurotoxicology 17 (1) 157-167] of mercury toxicity has been trickling in. With mercury contaminating rain-, ground- and sea-water no one is safe. Polluted water leads to mercury laced fish, meat and vegetable. In aquatic environments, inorganic mercury is microbiologically transformed into lipophilic organic compound 'methylmercury'. This transformation makes mercury more prone to biomagnification in food chains. Consequently, populations with traditionally high dietary intake of food originating from fresh or marine environment have highest dietary exposure to mercury. Extensive research done on locals across the globe have already established this, persons who routinely consume fish or a particular species of fish are at an increased risk of methylmercury poisoning. The easy access of the toxicant to man through multiple pathways air, water, food, cosmetic products and even vaccines increase the exposure. Foetus and children are more susceptible towards mercury toxicity. Mothers consuming diet containing mercury pass the toxicant to foetus and to infants through breast milk. Decreased performance in areas of motor function and memory has been reported among children exposed to presumably safe mercury levels. Similarly, disruption of attention, fine motor function and verbal

  5. Coronary Artery Stent Evaluation Using a Vascular Model at 64-Detector Row CT: Comparison between Prospective and Retrospective ECG-Gated Axial Scans

    PubMed Central

    Furui, Shigeru; Kuwahara, Sadatoshi; Mehta, Dhruv; Kaminaga, Tatsuro; Miyazawa, Akiyoshi; Ueno, Yasunari; Konno, Kumiko

    2009-01-01

    Objective We wanted to evaluate the performance of prospective electrocardiogram (ECG)-gated axial scans for assessing coronary stents as compared with retrospective ECG-gated helical scans. Materials and Methods As for a vascular model of the coronary artery, a tube of approximately 2.5-mm inner diameter was adopted and as for stents, three (Bx-Velocity, Express2, and Micro Driver) different kinds of stents were inserted into the tube. Both patent and stenotic models of coronary artery were made by instillating different attenuation (396 vs. 79 Hounsfield unit [HU]) of contrast medium within the tube in tube model. The models were scanned with two types of scan methods with a simulated ECG of 60 beats per minute and using display field of views (FOVs) of 9 and 18 cm. We evaluated the in-stent stenosis visually, and we measured the attenuation values and the diameter of the patent stent lumen. Results The visualization of the stent lumen of the vascular models was improved with using the prospective ECG-gated axial scans and a 9-cm FOV. The inner diameters of the vascular models were underestimated with mean measurement errors of -1.10 to -1.36 mm. The measurement errors were smaller with using the prospective ECG-gated axial scans (Bx-Velocity and Express2, p < 0.0001; Micro Driver, p = 0.0004) and a 9-cm FOV (all stents: p < 0.0001), as compared with the other conditions, respectively. The luminal attenuation value was overestimated in each condition. For the luminal attenuation measurement, the use of prospective ECG-gated axial scans provided less measurement error compared with the retrospective ECG-gated helical scans (all stents: p < 0.0001), and the use of a 9-cm FOV tended to decrease the measurement error. Conclusion The visualization of coronary stents is improved by the use of prospective ECG-gated axial scans and using a small FOV with reduced blooming artifacts and increased spatial resolution. PMID:19412509

  6. 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. PMID:22074737

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

    PubMed Central

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

    2016-01-01

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

  8. 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

  9. Quantification of Adaptive Protection Following Low-dose Irradiation.

    PubMed

    Feinendegen, Ludwig E

    2016-03-01

    The question whether low doses and low dose-rates of ionizing radiation pose a health risk to people is of public, scientific and regulatory concern. It is a subject of intense debate and causes much fear. The controversy is to what extent low-dose effects, if any, cause or protect against damage such as cancer. Even if immediate molecular damage in exposed biological systems rises linearly with the number of energy deposition events (i.e., with absorbed dose), the response of the whole biological system to that damage is not linear. To understand how initial molecular damage affects a complex living system is the current challenge. PMID:26808882

  10. 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.

  11. 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)

  12. Treatment of puberty trichotillomania with low-dose aripiprazole.

    PubMed

    Sasaki, Tsuyoshi; Iyo, Masaomi

    2015-01-01

    The present case is of a 14-year-old female with trichotillomania (TTM) that was treated with a low dose of aripiprazole (ARP) 1.5 mg/day. To our knowledge, this is the first published report to show an improvement of pubertal TTM using an ultra-low dose of ARP. In this case, a 50-mg fluvoxamine monotherapy for 2 years and a subsequent 4-month comprehensive cognitive behavioral therapy (CBT) monotherapy did not improve her hair-pulling symptoms. However, the treatment with a low-dose ARP of 1.5 mg/day dramatically improved her TTM symptoms without extrapyramidal symptoms. In this regard, low-dose ARP treatment for TTM might be a safe alternative to antidepressants, which carry the risk of agitation with suicidal ideation in adolescents. PMID:26089954

  13. 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 Central

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

    2014-01-01

    Purpose 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). Methods 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. Results 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. Conclusions 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. PMID:25546178

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

    PubMed

    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

  15. 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.

  16. 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.

  17. 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

  18. CT angiography of neonates and infants: comparison of radiation dose and image quality of target mode prospectively ECG-gated 320-MDCT and ungated helical 64-MDCT.

    PubMed

    Jadhav, Siddharth P; Golriz, Farahnaz; Atweh, Lamya A; Zhang, Wei; Krishnamurthy, Rajesh

    2015-02-01

    OBJECTIVE. The purpose of this study was to evaluate the radiation dose and image quality of target mode prospectively ECG-gated volumetric CT angiography (CTA) performed with a 320-MDCT scanner compared with the radiation dose and image quality of ungated helical CTA performed with a 64-MDCT scanner. MATERIALS AND METHODS. An experience with CTA for cardiovascular indications in neonates and infants 0-6 months old was retrospectively assessed. Radiation doses and quantitative and qualitative image quality scores of 28 CTA examinations performed with a 320-MDCT scanner and volumetric target mode prospective ECG gating plus iterative reconstruction (target mode) were compared with the doses and scores of 28 CTA examinations performed with a 64-MDCT scanner and ungated helical scanning plus filtered back projection reconstruction (ungated mode). All target mode studies were performed during free breathing. Seven ungated CTA examinations (25%) were performed with general endotracheal anesthesia. The findings of 17 preoperative CTA examinations performed in target mode were also compared with surgical reports for evaluation of diagnostic accuracy. RESULTS. All studies performed with target mode technique were diagnostic for the main clinical indication. Effective doses were significantly lower in the target mode group (0.51 ± 0.19 mSv) compared with the ungated mode group (4.8 ± 1.4 mSv) (p < 0.0001). Quantitative analysis revealed no statistically significant difference between the two groups with respect to signal-to-noise ratio (of pulmonary artery and aorta) and contrast-to-noise ratio. Subjective image quality was significantly better with target mode than with ungated mode (p < 0.0001). CONCLUSION. Target mode prospectively ECG-gated volumetric scanning with iterative reconstruction performed with a 320-MDCT scanner has several benefits in cardiovascular imaging of neonates and infants, including low radiation dose, improved image quality, high diagnostic

  19. Low-Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James; Slovic, Paul

    2001-06-01

    To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email & internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals.

  20. Low doses of arsenic, via perturbing p53, promotes tumorigenesis.

    PubMed

    Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

    2016-09-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure. PMID:27425828

  1. [Low-dose radiation effects and intracellular signaling pathways].

    PubMed

    Suzuki, Keiji; Kodama, Seiji; Watanabe, Masami

    2006-10-01

    Accumulated evidence has shown that exposure to low-dose radiation, especially doses less than 0.1 Gy, induces observable effects on mammalian cells. However, the underlying molecular mechanisms have not yet been clarified. Recently, it has been shown that low-dose radiation stimulates growth factor receptor, which results in a sequential activation of the mitogen-activated protein kinase pathway. In addition to the activation of the membrane-bound pathways, it is becoming evident that nuclear pathways are also activated by low-dose radiation. Ionizing radiation has detrimental effects on chromatin structure, since radiation-induced DNA double-strand breaks result in discontinuity of nucleosomes. Recently, it has been shown that ATM protein, the product of the ATM gene mutated in ataxia-telangiectasia, recognizes alteration in the chromatin structure, and it is activated through intermolecular autophosphorylation at serine 1981. Using antibodies against phosphorylated ATM, we found that the activated and phosphorylated ATM protein is detected as discrete foci in the nucleus between doses of 10 mGy and 1 Gy. Interestingly, the size of the foci induced by low-dose radiation was equivalent to the foci induced by high-dose radiation. These results indicate that the initial signal is amplified through foci growth, and cells evolve a system by which they can respond to a small number of DNA double-strand breaks. From these results, it can be concluded that low-dose radiation is sensed both in the membrane and in the nucleus, and activation of multiple signal transduction pathways could be involved in manifestations of low-dose effects. PMID:17016017

  2. 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. PMID:19820457

  3. LOW-DOSE RISK, DECISIONS, AND RISK COMMUNICATION

    EPA Science Inventory

    This grant application seeks funding for a program of basic research in the areas of risk perception and decision making as applied to the role of communication of biological research results on low-dose radiation exposure. Widespread adverse views about radiation exposure makes...

  4. FINAL REPORT: LOW DOSE RISK, DECISIONS, AND RISK COMMUNICATION

    EPA Science Inventory

    The research project conducted basic research on how people receive, evaluate, and form positions in response to scientific information and its relationship to low-dose radiation exposure. Three major areas of study were addressed in our research program. First was the developmen...

  5. 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.

  6. 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.

  7. PROGRESS REPORT. LOW-DOSE RISK, DECISIONS, AND RISK COMMUNICATION

    EPA Science Inventory

    The objectives of this research are to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development ...

  8. LOW-DOSE RISK, DECISIONS, AND RISK COMMUNICATION: YEAR 3

    EPA Science Inventory

    The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of ...

  9. Glyphosate Applied at Low Doses Can Stimulate Plant Growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glyphosate blocks the shikimic acid pathway, inhibiting the production of aromatic amino acids and several secondary compounds derived from these amino acids. Non-target plants can be exposed to low doses of glyphosate by herbicide drift of spray droplets and contact with treated weeds. Previous s...

  10. Low dose ethanol consumption improves insulin sensitivity in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While chronic consumption of high doses of ethanol is well known to have adverse health consequences, intake of low doses have been reported to improve several markers of health outcomes. Published results from our laboratory using total enteral nutrition (TEN) in rats, in which ethanol-containing d...

  11. 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

  12. 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

  13. 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.

  14. 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. PMID:25429515

  15. 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.

  16. 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.

  17. 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. PMID:23439145

  18. 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.

  19. Torsade de pointes and low-dose oral haloperidol.

    PubMed

    Jackson, T; Ditmanson, L; Phibbs, B

    1997-09-22

    Haloperidol, used to treat patients with psychoses, is considered minimally cardiotoxic. Several cases of torsade de pointes have been reported in association with the use of oral haloperidol. In each of those cases, a prolonged QTc preceded the torsade de pointes episode and thus may be considered a predictor for ventricular arrhythmias in elderly women treated with haloperidol. However, the following case may demonstrate the inability to predict an episode of torsade de pointes with low-dose oral haloperidol use. PMID:9308514

  20. 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.

  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. PMID:21106638

  2. 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. PMID:25355191

  3. 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.

  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. 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. PMID:26774524

  7. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers

    PubMed Central

    Moldovan, Valeriu; Bataga, Simona; Pantea, Monica; Sarkany, Kinga; Tatar, Cristina; Mocan, Simona

    2016-01-01

    Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75–325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06–8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09–30.58) or anticoagulants (OR 4.85, 95% CI 1.33–17.68), male gender (OR 5.2, 95% CI 1.77–15.34), and stroke (OR 7.27, 95% CI 1.40–37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection. PMID:27579036

  8. Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers.

    PubMed

    Negovan, Anca; Iancu, Mihaela; Moldovan, Valeriu; Voidazan, Septimiu; Bataga, Simona; Pantea, Monica; Sarkany, Kinga; Tatar, Cristina; Mocan, Simona; Banescu, Claudia

    2016-01-01

    Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75-325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06-8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09-30.58) or anticoagulants (OR 4.85, 95% CI 1.33-17.68), male gender (OR 5.2, 95% CI 1.77-15.34), and stroke (OR 7.27, 95% CI 1.40-37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection. PMID:27579036

  9. 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

  10. The feasibility of sub-millisievert coronary CT angiography with low tube voltage, prospective ECG gating, and a knowledge-based iterative model reconstruction algorithm.

    PubMed

    Park, Chul Hwan; Lee, Joohee; Oh, Chisuk; Han, Kyung Hwa; Kim, Tae Hoon

    2015-12-01

    We evaluated the feasibility of sub-millisievert (mSv) coronary CT angiography (CCTA) using low tube voltage, prospective ECG gating, and a knowledge-based iterative model reconstruction algorithm. Twenty-four non-obese healthy subjects (M:F 13:11; mean age 50.2 ± 7.8 years) were enrolled. Three sets of CT images were reconstructed using three different reconstruction methods: filtered back projection (FBP), iterative reconstruction (IR), and knowledge-based iterative model reconstruction (IMR). The scanning parameters were as follows: step-and-shoot axial scanning, 80 kVp, and 200 mAs. On the three sets of CT images, the attenuation and image noise values were measured at the aortic root. The signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) were calculated at the proximal right coronary artery and the left main coronary artery. The qualitative image quality of the CCTA with IMR was assessed using a 4-point grading scale (grade 1, poor; grade 4, excellent). The mean radiation dose of the CCTA was 0.89 ± 0.09 mSv. The attenuation values with IMR were not different from those of other reconstruction methods. The image noise with IMR was significantly lower than with IR and FBP. Compared to FBP, the noise reduction rate of IMR was 69 %. The SNR and CNR of CCTA with IMR were significantly higher than with FBP or IR. On the qualitative analysis with IMR, all included segments were diagnostic (grades 2, 3, and 4), and the mean image quality score was 3.6 ± 0.6. In conclusion, CCTA with low tube voltage, prospective ECG gating, and an IMR algorithm might be a feasible method that allows for sub-millisievert radiation doses and good image quality when used with non-obese subjects. PMID:26521066

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Low-dose CT of the lungs: Preliminary observations

    SciTech Connect

    Naidich, D.P.; Marshall, C.H.; Gribbin, C.; Arams, R.S.; McCauley, D.I. )

    1990-06-01

    The potential of low-dose computed tomography (CT) of the lungs was critically evaluated in two patients with normal-appearing lungs and 10 patients with a wide diversity of underlying parenchymal abnormalities. At each of five levels, in addition to routine scans obtained at 120 kVp and 140 mA, a scan at 10 mA and a half scan at 10 mA were obtained, with all other parameters held constant. Each scan was evaluated visually to assess anatomic clarity as well as the presence of artifacts and the extent of graininess. At all levels of the thorax, visualization of parenchymal structures was not affected by decreasing the milliamperage. It appears that high-quality, diagnostic images of the lung can be obtained with a very low radiation dose. Although further evaluation is necessary, the potential of low-dose CT for use in the pediatric population in particular, as well as for screening in patients at high risk for developing lung cancer, is apparent.

  20. Impairment of simulated motorcycle riding performance under low dose alcohol.

    PubMed

    Filtness, A J; Rudin-Brown, C M; Mulvihill, C M; Lenné, M G

    2013-01-01

    Crash statistics that include the blood alcohol concentration (BAC) of vehicle operators reveal that crash involved motorcyclists are over represented at low BACs (e.g., ≤0.05%). This riding simulator study compared riding performance and hazard response under three low dose alcohol conditions (sober, 0.02% BAC, 0.05% BAC). Forty participants (20 novice, 20 experienced) completed simulated rides in urban and rural scenarios while responding to a safety-critical peripheral detection task (PDT). Results showed a significant increase in the standard deviation of lateral position in the urban scenario and PDT reaction time in the rural scenario under 0.05% BAC compared with zero alcohol. Participants were most likely to collide with an unexpected pedestrian in the urban scenario at 0.02% BAC, with novice participants at a greater relative risk than experienced riders. Novices chose to ride faster than experienced participants in the rural scenario regardless of BAC. Not all results were significant, emphasising the complex situation of the effects of low dose BAC on riding performance, which needs further research. The results of this simulator study provide some support for a legal BAC for motorcyclists below 0.05%. PMID:22749316

  1. 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.

  2. Thermoluminescent dosimeters for low dose X-ray measurements.

    PubMed

    Fernández, S Del Sol; García-Salcedo, R; Sánchez-Guzmán, D; Ramírez-Rodríguez, G; Gaona, E; de León-Alfaro, M A; Rivera-Montalvo, T

    2016-01-01

    The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy. PMID:26609683

  3. 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.

  4. 'Low-dose' corticosteroid prophylaxis against fat embolism.

    PubMed

    Kallenbach, J; Lewis, M; Zaltzman, M; Feldman, C; Orford, A; Zwi, S

    1987-10-01

    The effect of 'low-dose' corticosteroids (9 mg/kg methylprednisolone), given after skeletal trauma, on the incidence of the fat embolism syndrome and isolated arterial hypoxemia was studied in 42 controls and 40 steroid-treated subjects. Fat embolism occurred in ten controls (23.8%) and one steroid-treated subject (2.5%) (p = 0.01). A further 44 subjects developed isolated hypoxemia. This was severe (PaO2 less than 50 mm Hg) in seven of 32 controls (21.9%) and one of 39 steroid-treated subjects (2.6%) (p = 0.01). The overall incidence of hypoxemia was 67.1%, affecting 33 controls (78.6%) and 22 steroid-treated patients (55%) (p less than 0.05). The degree of hypoxemia was severe (PaO2 less than 50 mm Hg) in 12 controls (28.6%) and two (5%) of the steroid-treated subjects (p = 0.005). No control subject died or required mechanical ventilation. One steroid-treated subject without fat embolism died of a fulminant infection. Although methylprednisolone in a relatively low dose provides protection against fat embolism and pulmonary dysfunction after skeletal trauma, the safety of this therapy requires further evaluation. PMID:3312625

  5. A New Era of Low-Dose Radiation Epidemiology.

    PubMed

    Kitahara, Cari M; Linet, Martha S; Rajaraman, Preetha; Ntowe, Estelle; Berrington de González, Amy

    2015-09-01

    The last decade has introduced a new era of epidemiologic studies of low-dose radiation facilitated by electronic record linkage and pooling of cohorts that allow for more direct and powerful assessments of cancer and other stochastic effects at doses below 100 mGy. Such studies have provided additional evidence regarding the risks of cancer, particularly leukemia, associated with lower-dose radiation exposures from medical, environmental, and occupational radiation sources, and have questioned the previous findings with regard to possible thresholds for cardiovascular disease and cataracts. Integrated analysis of next generation genomic and epigenetic sequencing of germline and somatic tissues could soon propel our understanding further regarding disease risk thresholds, radiosensitivity of population subgroups and individuals, and the mechanisms of radiation carcinogenesis. These advances in low-dose radiation epidemiology are critical to our understanding of chronic disease risks from the burgeoning use of newer and emerging medical imaging technologies, and the continued potential threat of nuclear power plant accidents or other radiological emergencies. PMID:26231501

  6. 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

  7. Low dose cyclophosphamide: Mechanisms of T cell modulation.

    PubMed

    Madondo, Mutsa Tatenda; Quinn, Michael; Plebanski, Magdalena

    2016-01-01

    Cyclophosphamide is considered one of the most successful chemotherapy drugs and is listed on the World Health Organisations List of Essential Medicines. Since its initial synthesis in 1958, it has been widely used to treat a range of cancers but its use has been declining due to the advent of platinum based and other chemotherapy agents. However, cyclophosphamide is still used either as a single agent or as adjuvant therapy to treat lymphomas, and breast and ovarian cancers at much lower doses. The efficacy of low dose cyclophosphamide is primarily due to its ability to promote anti-tumour immunity, by selectively depleting regulatory T cells and enhancing effector T cell function. Compared to effecter T cells, regulatory T cells have metabolic adaptations that make them more susceptible to cyclophosphamide-mediated cytotoxicity. In this review, we highlight the potential for improving the efficacy of low dose cyclophosphamide by combining insights on the mechanisms of cyclophosphamide-mediated cytotoxicity, and how these cytotoxic effects of cyclophosphamide influence T cell function, thereby contributing to anti-tumour immunity. PMID:26620820

  8. 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.

  9. Low-dose aspirin as treatment for central serous chorioretinopathy

    PubMed Central

    Caccavale, Antonio; Romanazzi, Filippo; Imparato, Manuela; Negri, Angelo; Morano, Anna; Ferentini, Fabio

    2010-01-01

    Purpose: To evaluate the effectiveness of low-dose aspirin for the treatment of central serous chorioretinopathy (CSCR). Patients and methods: Patients with classical or multifocal CSCR were treated with aspirin 100 mg per day orally for 1 month followed by 100 mg on alternate days for 5 months. Treated patients were compared with historic controls consisting of patients with classical or multifocal CSCR previously followed up at our institution. Results: Mean visual acuity in the group treated with aspirin started to improve after the first week of therapy and continued to improve throughout the following 3 months. Visual recovery was slower in the untreated control group than in the treated group and achieved better visual acuity between the first and third month from the onset of the disease. There were no adverse events related to the administration of aspirin. Conclusion: The results indicate that treatment with low-dose aspirin may result in more rapid visual rehabilitation with fewer recurrences in patient with CSCR compared with untreated historic controls. The effectiveness of treatment with aspirin supports our hypothesis regarding the role of impaired fibrinolysis and increased platelet aggregation in the choriocapillaris in the pathogenesis of CSCR. PMID:20714368

  10. 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.

  11. 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.

  12. Synergistic effect of low-dose cucurbitacin B and low-dose methotrexate for treatment of human osteosarcoma

    PubMed Central

    Goff, Catherine; Iwanski, Gabriela B.; Forscher, Charles; Doan, Ngan B.; Said, Jonathan W.; Koeffler, H. Phillip

    2016-01-01

    We investigated the use of cucurbitacin B, a plant-derived tetracyclic triterpenoid, as a single agent or in combination with methotrexate (MTX) for human osteosarcoma (OS) treatment. Cucurbitacin B showed antiproliferative activity against seven human OS cell lines in vitro accompanying G2/M cell cycle arrest, apoptosis, and inhibition of ERK, Akt, and mTOR proteins. Cucurbitacin B in combination with MTX synergistically inhibited OS cell growth in vitro. Low-dose cucurbitacin B (LD-CuB, 0.5 mg/kg body weight) or low-dose MTX (LD-MTX, 150 mg/kg) failed to decrease the size of human OS xenografts in nude mice. However, combined therapy at identical concentrations inhibited tumor growth by 62% vs. LD-CuB and 81% vs. LD-MTX (p < 0.001). Strikingly, the effect persisted even when the dose of MTX was decreased by two thirds (VLD-MTX, 50 mg/kg). In conclusion, cucurbitacin B alone or in combination with MTX shows promising antiproliferative activity against human OS. PMID:21440986

  13. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left After Surgery

    MedlinePlus

    ... of Endocrine & Neuroendocrine Neoplasias Research Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery Adapted from ... NCI Cancer Bulletin . A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) ...

  14. 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.

  15. 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. PMID:27279742

  16. Low-dose digital computed radiography in pediatric chest imaging

    SciTech Connect

    Kogutt, M.S.; Jones, J.P.; Perkins, D.D.

    1988-10-01

    A prototype digital computed radiographic imaging system that uses laser-stimulated luminescence was evaluated for its ability to achieve reproducible, high-detail, low-dose pediatric chest radiographs. Using this system, we performed a total of 401 examinations in infants and children, and achieved an 85% reduction in radiation dose, as compared with that delivered when film-screen techniques were used. We also achieved satisfactory image resolution, and the images obtained were of acceptable diagnostic quality. A direct comparison of analog and digital radiographs showed that comparable quality and clinical acceptability could be readily maintained between the two techniques. This study shows that high-quality images can be produced by this system at radiation doses reduced by 85% when compared with doses from standard radiographic techniques.

  17. [Low dose ketamine for pediatric procedure-related pain].

    PubMed

    Annequin, D

    2012-07-01

    For painful procedures in children, national recommendations are now available in France. When sedation-analgesia with nitrous oxide/oxygen mixture fails, in order to perform a painful procedure under good conditions, low dose ketamine (IV bolus titration 0.5 mg/kg but not more than 2 mg/kg) is the only drug potentially used by a trained physician, without the presence of an anaesthesiologist (Grade A). With these dosages without drug combination, the highest level of security depends largely on the quality of the hospital environment (Grade A). Intramuscular (<4 mg/kg) is an alternative route, but the recovery time is delayed (Grade B). The optimal management is performed by an anesthesiologist, it is necessary to facilitate access to the operating room for children undergoing this type of procedure (Professional consensus). Mainly IV ketamine can be used by pediatric intensive care and emergency physicians who currently have medical skills to detect and treat side effects. PMID:22595625

  18. Hereditary hemorrhagic telangiectasia treated with low dose intravenous bevacizumab

    PubMed Central

    Wee, Jee Wan; Jeon, Young Woo; Eun, Jun Young; Kim, Han Jo; Bae, Sang Byung

    2014-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that leads to mucocutaneous telangiectasias, epistaxis, and gastrointestinal bleeding. Depending on the severity and manifestation of the disease, various therapeutic modalities have been used, from local bleeding control to surgery or concomitant drug therapy. Several articles under review have presented guidelines for treatment of HHT with bevacizumab as a direct anti-angiogenesis strategy. Still, neither the exact optimal dose nor the minimum effective dose of intravenous bevacizumab in patients with severe HHT has been reported. A 55-year-old man presented with long-standing epistaxis, recent melena, dizziness, and a three-generation family history of chronic epistaxis, anemia, and regular blood transfusions. Treatment with argon plasma coagulation (APC) for the gastrointestinal bleeding failed to raise hemoglobin levels, we considered using the bevacizumab. We report a patient with severe HHT, who was treated with low-dose bevacizumab (2 mg/kg) and improved substantially. PMID:25325040

  19. 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.

  20. 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

  1. Extrapyramidal side effects with low doses of amisulpride

    PubMed Central

    Mandal, Nikhiles; Singh, Om P.; Sen, Subrata

    2014-01-01

    Amisulpride, the newly introduced antipsychotic in India, is claimed to be effective in both positive and negative symptom schizophrenia and related disorders, though it has little or no action on serotonergic receptors. Limbic selectivity and lower striatal dopaminergic receptor binding capacity causes very low incidence of EPS. But, in clinical practice, we are getting EPS with this drug even at lower doses. We have reported three cases of akathisia, acute dystonia, and drug-induced Parkinsonism with low doses of amisulpride. So, we should keep this side effect in mind when using amisulpride. In fact, more studies are required in our country to find out the incidence of EPS and other associated mechanism. PMID:24891713

  2. Surrogates of protection in repeated low-dose challenge experiments.

    PubMed

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

    2015-05-10

    A critical step toward developing a successful vaccine to control the human immunodeficiency virus 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 human immunodeficiency virus, 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

  3. 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

  4. 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

  5. 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.

  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. PMID:16235661

  7. 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

  8. 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. PMID:26582164

  9. 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.

  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. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    DOE PAGESBeta

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; et al

    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

  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. PMID:25337914

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain.

    PubMed

    Mao, Xiao Wen; Nishiyama, Nina C; Pecaut, Michael J; Campbell-Beachler, Mary; Gifford, Peter; Haynes, Kristine E; Becronis, Caroline; Gridley, Daila S

    2016-06-01

    Microgravity and radiation are stressors unique to the spaceflight environment that can have an impact on the central nervous system (CNS). These stressors could potentially lead to significant health risks to astronauts, both acutely during the course of a mission or chronically, leading to long-term, post-mission decrements in quality of life. The CNS is sensitive to oxidative injury due to high concentrations of oxidizable, unsaturated lipids and low levels of antioxidant defenses. The purpose of this study was to evaluate oxidative damage in the brain cortex and hippocampus in a ground-based model for spaceflight, which includes prolonged unloading and low-dose radiation. Whole-body low-dose/low-dose-rate (LDR) gamma radiation using (57)Co plates (0.04 Gy at 0.01 cGy/h) was delivered to 6 months old, mature, female C57BL/6 mice (n = 4-6/group) to simulate the radiation component. Anti-orthostatic tail suspension was used to model the unloading, fluid shift and physiological stress aspects of the microgravity component. Mice were hindlimb suspended and/or irradiated for 21 days. Brains were isolated 7 days or 9 months after irradiation and hindlimb unloading (HLU) for characterization of oxidative stress markers and microvessel changes. The level of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation, was significantly elevated in the cortex and hippocampus after LDR + HLU compared to controls (P < 0.05). The combination group also had the highest level of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression compared to controls (P < 0.05). There was a significant decrease in superoxide dismutase (SOD) expression in the animals that received HLU only or combined LDR + HLU compared to control (P < 0.05). In addition, 9 months after LDR and HLU exposure, microvessel densities were the lowest in the combination group, compared to age-matched controls in the cortex (P < 0.05). Our data provide the first evidence

  18. Unexpected behaviour of polystyrene-based scintillating fibers during irradiation at low doses and low dose rates

    NASA Astrophysics Data System (ADS)

    Wick, K.; Zoufal, T.

    2001-12-01

    The time dependence of the optical radiation damage process was studied for different fibers with polystyrene (PS) core. The fibers were irradiated with X-rays. In the present experiment the light guide BCF-98 (Bicron, clear polystyrene) was compared with the two scintillating fibers SCSF-38 and SCSF-81 (Kuraray). The light transmission through the fiber was investigated before, during and after irradiation. All investigated fibers showed unexpected effects depending on the fiber type: (1) at low doses the scintillating fibers are more sensitive to radiation than at high doses, i.e. the optical absorption rises nonlinearly with dose; (2) shortlived optical absorption centers decaying within several hours were detected in all fibers with PS core investigated up to now. Especially for SCSF-81, the annealing part is large and it totally overlaps the emission spectrum of the fiber.

  19. Low dose hydroxylated PCB induces c-Jun expression in PC12 cells.

    PubMed

    Shimokawa, Noriaki; Miyazaki, Wataru; Iwasaki, Toshiharu; Koibuchi, Noriyuki

    2006-03-01

    Polychlorinated biphenyls (PCBs) are known as environmental pollutants that may cause adverse health problems. Recently, accumulating evidence shows that PCBs express neurotoxicity through alteration of gene expression and signal transduction. On the other hand, c-Jun, a component of AP-1, is likely to coordinate transcription programs in response to various extracellular signals. However, little is known about the effects of PCBs on c-Jun expression. Here we investigated the expression of c-Jun in response to PCB. PC12 cells were incubated with hydroxylated PCB (4(OH)-2',3,3',4',5'-penta chlorobiphenyl, OH-PCB) at a final concentration from 10(-8) to 10(-5)M. The level of c-Jun expression was increased by OH-PCB at relatively low-dose; concentration of OH-PCB at 10(-8)M and 10(-7)M produced a 2.4- and 3.5-fold increase of c-Jun expression in respectively, compared with the values without OH-PCB treatment. Thyroid hormone (T3) did not induce such c-Jun expression, indicating that the effect of OH-PCB is not mediated through thyroid hormone signaling pathway. OH-PCB also enhanced phosphorylation of c-Jun NH2-terminal kinases. To determine whether the activation of Ca2+ channel is involved in the OH-PCB-induced c-Jun expression, we examined it using a L-type voltage-gated Ca2+ channel blocker nimodipine. Nimodipine partially inhibited OH-PCB-induced c-Jun expression by 50%. Moreover, Na+ channel antagonist tetrodotoxin inhibited OH-PCB-induced c-Jun expression completely. Taken together, our results indicate that exposure to OH-PCB induces c-Jun expression, and the response may be triggered by depolarization of a plasma membrane via Na+ influx, followed by Ca2+ influx partially through voltage-gated Ca2+ channels. PMID:16300829

  20. 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

  1. 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.

  2. 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

  3. Automatic LV volume measurement in low dose multi-phase CT by shape tracking

    NASA Astrophysics Data System (ADS)

    von Berg, Jens; Begemann, Philipp; Stahmer, Felix; Adam, Gerhard; Lorenz, Cristian

    2006-03-01

    Functional assessment of cardiac ventricular function requires time consuming manual interaction. Some automated methods have been presented that predominantly used cardiac magnet resonance images. Here, an automatic shape tracking approach is followed to estimate left ventricular blood volume from multi-slice computed tomography image series acquired with retrospective ECG-gating. A deformable surface model method was chosen that utilized both shape and local appearance priors to determine the endocardial surface and to follow its motion through the cardiac cycle. Functional parameters like the ejection fraction could be calculated from the estimated shape deformation. A clinical validation was performed in a porcine model with 60 examinations on eight subjects. The functional parameters showed a good correlation with those determined by clinical experts using a commercially available semi-automatic short axes delineation tool. The correlation coefficient for the ejection fraction (EF) was 0.89. One quarter of these acquisitions were done with a low dose protocol. All of these degraded images could be processed well. Their correlation slightly decreases when compared to the normal dose cases (EF: 0.87 versus 0.88).

  4. 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). PMID:27561742

  5. 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

  6. Fibrinolytic response in women on low-dose oral contraceptive.

    PubMed

    Ishak, R; Ahmad, R; Gudum, H R; Hassan, K; Ang, E S

    1992-06-01

    Long term use of low doses of combination oral contraceptives appears to increase plasminogen level, thereby increasing fibrinolytic activity and reducing the risk of thromboembolism. Blood levels of plasminogen, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI), were measured before and after stress (5 minutes of stair climbing) in a group of 30 women, 23-40 years old, who had taken 30 mcg of ethinyl estradiol with 150 mcg of desogestrel or levonorgestrel for at least 1 year. Similar measurements were taken from a control group of 30 women matched for age, height, and weight. Plasminogen and tPA levels in both groups increased significantly after exercise. The level of PAI did not change significantly with stress in either group. The level of plasminogen was significantly higher in the group taking contraceptives, whether before or after exercise, when compared to the control group. Levels of tPA and PAI, although slightly increased in the oral contraceptive group, were not significantly different between the two groups. The increase in plasminogen may be due to the estrogen component of the contraceptives. Stress seems to increase fibrinolytic response. PMID:12345026

  7. Low-dose caffeine physical dependence in humans.

    PubMed

    Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

    1990-12-01

    This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized. PMID:2262896

  8. Risk of cancer subsequent to low-dose radiation.

    PubMed

    Warren, S

    1980-10-01

    Prominent among media items related to the Three Mile Island episode were prophecies of future cancers. The credibility of some of these estimates are discussed. The average person has been exposed by the age of 50 to 2.5 rad (0.025 Gy) from natural background. We define low doses as under 25 rad (0.25 Gy). The most heavily exposed members of the general population during the Three Mile Island event received 83 mrad (0.83 mGy). Those exposed to 2500 mrad (25 mGy) would show no pathologically recognizable effects of radiation though there is evidence that chromosomal damage may occur with doses about 1 rad (0.01 Gy). An official stated among the consequences of the Three Mile Island accident that two additional cancer deaths would result. No epidemiologist could detect such an increase in the population at risk. It has been generally agreed that the linear hypothesis is useful for determining protection standards, not prognosis. Objective criteria for pathologic diagnosis of cause-effect relations are presented. PMID:7430985

  9. Comparison of Image Filters for Low Dose Neutron Imaging

    NASA Astrophysics Data System (ADS)

    Hungler, P. C.; Bennett, L. G. I.; Lewis, W. J.; Bevan, G.; Metzler, J.

    Neutron imaging using low flux sources, such as accelerators or low flux nuclear reactors, produces images which contain significant amounts of noise. The noise indications are a result of high energy gamma radiation and some neutron scattering which hit the CCD detector despite heavy shielding. The amount of noise in an image is a factor of the exposure time required to produce images with adequate dynamic ranges. Minimization of noise and maximization of the dynamic range are inversely proportional and the exposure time is often extended to increase incident neutrons at the expense of noise. The resultant noise can be reduced using image filters; however, these filters usually increase the signal to noise ratio (SNR) at the expense of spatial resolution. Three filters were applied to low dose neutron images acquired at RMC; a median filter, a Z-projection filter and a hybrid PDE filter. The median filter and the hybrid PDE filter showed similar performance in 3D with regards to SNR and spatial resolution, however, the median filter created numerous artefacts in the resultant tomogram. The Z-projection filter using 5 projections had the best performance in 2D improving the SNR of the raw image from 10.2 ± 0.767 to 22.5 ± 1.52 and the spatial resolution from 331 ± 2.89 to 309 ± 0.846, respectively. The Z-projection filter was not evaluated in 3D due to facility induced constraints.

  10. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    PubMed

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals. PMID:24772825

  11. 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.

  12. Analysis of repeated low-dose challenge studies.

    PubMed

    Nolen, Tracy L; Hudgens, Michael G; Senb, Pranab K; Koch, Gary G

    2015-05-30

    Preclinical evaluation of candidate human immunodeficiency virus (HIV) vaccines entails challenge studies whereby non-human primates such as macaques are vaccinated with either an active or control vaccine and then challenged (exposed) with a simian-version of HIV. Repeated low-dose challenge (RLC) studies in which each macaque is challenged multiple times (either until infection or some maximum number of challenges is reached) are becoming more common in an effort to mimic natural exposure to HIV in humans. Statistical methods typically employed for the testing for a vaccine effect in RLC studies include a modified version of Fisher's exact test as well as large sample approaches such as the usual log-rank test. Unfortunately, these methods are not guaranteed to provide a valid test for the effect of vaccination. On the other hand, valid tests for vaccine effect such as the exact log-rank test may not be easy to implement using software available to many researchers. This paper details which statistical approaches are appropriate for the analysis of RLC studies, and how to implement these methods easily in SAS or R. PMID:25752266

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

    PubMed

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

    2016-08-01

    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 (1-10cGy) 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 (5cGy). 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

  18. 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.

  19. [Relationship to Carcinogenesis of Repetitive Low-Dose Radiation Exposure].

    PubMed

    Ootsuyama, Akira

    2016-06-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. PMID:27302731

  20. High versus Low-Dose Rate Brachytherapy for Cervical Cancer

    PubMed Central

    Patankar, Sonali S.; Tergas, Ana I.; Deutsch, Israel; Burke, William M.; Hou, June Y.; Ananth, Cande V.; Huang, Yongmei; Neugut, Alfred I.; Hershman, Dawn L.; Wright, Jason D.

    2015-01-01

    Objectives Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer. Methods Women with stage IB2–IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003–2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival. Results A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (P<0.0001). In a multivariable model, year of diagnosis was the strongest predictor of use of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% 0.83–1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors. Conclusions The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy. PMID:25575481

  1. Small bowel injury in low-dose aspirin users.

    PubMed

    Endo, Hiroki; Sakai, Eiji; Kato, Takayuki; Umezawa, Shotaro; Higurashi, Takuma; Ohkubo, Hidenori; Nakajima, Atsushi

    2015-04-01

    The use of low-dose aspirin (LDA) is well known to be associated with an increased risk of serious upper gastrointestinal complications, such as peptic ulceration and bleeding. Until recently, attention was mainly focused on aspirin-induced damage of the stomach and duodenum. However, recently, there has been growing interest among gastroenterologists on the adverse effects of aspirin on the small bowel, especially as new endoscopic techniques, such as capsule endoscopy (CE) and balloon-assisted endoscopy, have become available for the evaluation of small bowel lesions. Preliminary CE studies conducted in healthy subjects have shown that short-term administration of LDA can induce mild mucosal inflammation of the small bowel. Furthermore, chronic use of LDA results in a variety of lesions in the small bowel, including multiple petechiae, loss of villi, erosions, and round, irregular, or punched-out ulcers. Some patients develop circumferential ulcers with stricture. In addition, to reduce the incidence of gastrointestinal lesions in LDA users, it is important for clinicians to confirm the differences in the gastrointestinal toxicity between different types of aspirin formulations in clinical use. Some studies suggest that enteric-coated aspirin may be more injurious to the small bowel mucosa than buffered aspirin. The ideal treatment for small bowel injury in patients taking LDA would be withdrawal of aspirin, however, LDA is used as an antiplatelet agent in the majority of patients, and its withdrawal could increase the risk of cardiovascular/cerebrovascular morbidity and mortality. Thus, novel means for the treatment of aspirin-induced enteropathy are urgently needed. PMID:25501289

  2. 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

    2015-09-01

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

  3. 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.

  4. Radiobiological Response of Cervical Cancer Cell Line in Low Dose Region: Evidence of Low Dose Hypersensitivity (HRS) and Induced Radioresistance (IRR)

    PubMed Central

    Singh, Rabiraja; George, Daicy; Vijaykumar, T.S.; John, Subhashini

    2015-01-01

    Background Purpose of the present study was to examine the response of cervical cancer cell line (HeLa cell line) to low dose radiation using clonogenic assay and mathematical modeling of the low dose response by Joiner’s induced repair model. Materials and Methods Survival of HeLa cells following exposure to single and fractionated low doses of γ (gamma)-ray, 6 MV, and 15 MV photon was measured by clonogenic assay. Results HeLa cell line demonstrated marked low dose response consisting of an area of HRS and IRR in the dose region of <1 Gy. The two gradients of the low dose region (αs and αr) were distinctly different with a transition dose (Dc) of 0.28-0.40 cGy. Conclusion HeLa cell line demonstrates marked HRS and IRR with distinct transition dose. This may form the biological basis of the clinical study to investigate the chemo potentiating effect of low dose radiation in cervical cancer. PMID:26266200

  5. 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.

  6. 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

  7. Lyssavirus infection: 'low dose, multiple exposure' in the mouse model.

    PubMed

    Banyard, Ashley C; Healy, Derek M; Brookes, Sharon M; Voller, Katja; Hicks, Daniel J; Núñez, Alejandro; Fooks, Anthony R

    2014-03-01

    The European bat lyssaviruses (EBLV-1 and EBLV-2) are zoonotic pathogens present within bat populations across Europe. The maintenance and transmission of lyssaviruses within bat colonies is poorly understood. Cases of repeated isolation of lyssaviruses from bat roosts have raised questions regarding the maintenance and intraspecies transmissibility of these viruses within colonies. Furthermore, the significance of seropositive bats in colonies remains unclear. Due to the protected nature of European bat species, and hence restrictions to working with the natural host for lyssaviruses, this study analysed the outcome following repeat inoculation of low doses of lyssaviruses in a murine model. A standardized dose of virus, EBLV-1, EBLV-2 or a 'street strain' of rabies (RABV), was administered via a peripheral route to attempt to mimic what is hypothesized as natural infection. Each mouse (n=10/virus/group/dilution) received four inoculations, two doses in each footpad over a period of four months, alternating footpad with each inoculation. Mice were tail bled between inoculations to evaluate antibody responses to infection. Mice succumbed to infection after each inoculation with 26.6% of mice developing clinical disease following the initial exposure across all dilutions (RABV, 32.5% (n=13/40); EBLV-1, 35% (n=13/40); EBLV-2, 12.5% (n=5/40)). Interestingly, the lowest dose caused clinical disease in some mice upon first exposure ((RABV, 20% (n=2/10) after first inoculation; RABV, 12.5% (n=1/8) after second inoculation; EBLV-2, 10% (n=1/10) after primary inoculation). Furthermore, five mice developed clinical disease following the second exposure to live virus (RABV, n=1; EBLV-1, n=1; EBLV-2, n=3) although histopathological examination indicated that the primary inoculation was the most probably cause of death due to levels of inflammation and virus antigen distribution observed. All the remaining mice (RABV, n=26; EBLV-1, n=26; EBLV-2, n=29) survived the tertiary and

  8. 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

  9. Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: a comprehensive review.

    PubMed

    Shiotani, Akiko; Manabe, Noriaki; Kamada, Tomoari; Fujimura, Yoshinori; Sakakibara, Takashi; Haruma, Ken

    2012-04-01

    The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA. PMID:22486865

  10. Low-Dose Aspirin-Associated Upper and Mid Gastrointestinal Tract Damage and Gene Polymorphism.

    PubMed

    Shiotani, Akiko; Fujita, Yoshihiko; Nishio, Kazuto

    2015-01-01

    The risk of gastrointestinal (GI) bleeding is increased in association with the use of low-dose aspirin (LDA). There are few studies of the association between genetic polymorphisms and the risks of aspirin-induced ulcer or its complications. Individuals with two single nucleotide polymorphisms (SNPs) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibit increased sensitivity to aspirin and lower prostaglandin synthesis capacity but the polymorphism lacked statistical significance in relation to an association with bleeding peptic ulcer. In our previous Japanese study, SLCO1B1 521TT genotype and the SLCO1B1 *1b haplotype were significantly associated with the risk of peptic ulcer and ulcer bleeding in patients taking LDA, especially in the patients with angiotensin converting enzyme inhibitor (ACEI), angiotensin type 1 receptor blocker (ARB), or statin co-treatment. Protonpump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper GI bleeding. The interaction between PPIs and consequent impaired effectiveness of clopidogrel has caused concern regarding the effect of genetic polymorphisms of the CYP2C19 which mediates conversion of clopidogrel to its active metabolite. The later recent genome-wide analysis of SNPs indicated the association of several SNPs with small bowel bleeding in Japanese patients taking LDA. The data are still lacking and further prospective studies are needed to identify the specific gene polymorphisms as risk or protective factors for GI bleeding associated with LDA. PMID:26369686

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

    PubMed

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

    2015-11-01

    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

  12. 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

  13. Low-dose Vitamin “A” Tablets–treatment of Acne Vulgaris

    PubMed Central

    Kotori, Merita Grajqevci

    2015-01-01

    Background: The efficacy of isotretinoin at 0.5 to 1.0 mg/kg per day in the treatment of acne is well established and considered safe, although it is sometimes not easily tolerated because of its cutaneous side effects. Objective: The purpose of this study was to determine the efficacy of low-dose isotretinoin in the treatment of acne. Methods: In this prospective, non comparative, open-label study, 50 patients, both male and female, with moderate acne were enrolled and treated with isotretinoin at 20 mg/d (approximately 0.3-0.4 mg/kg per day) for 3 months. The patients were divided into two age groups: 12 to 20 and 21 to 35 years old. Patients were evaluated at 2-month intervals by means of clinical and laboratory examinations. A 4-year follow-up was also carried out. Results: At the end of the treatment phase, good results were observed in 90.8% of the patients aged 12 to 20 years, and in 89.6% of the patients aged 21 to 35 years. Failure of the treatment occurred in 5.2% and 7.4% of the two groups, respectively. Three patients dropped out of the study because of lack of compliance, and another patient discontinued participation because of a laboratory side effect. During the 2-year follow-up period, relapses of the acne occurred in 3.9% of the patients aged 12 to 20 years and in 5.9% of the patients aged 21 to 35 years. Elevated serum lipid levels (up to 20% higher than the upper limit of normal value) were found in 4.2% of the patients and abnormal (low-dose isotretinoin (20 mg/d) was found to be effective in the treatment of moderate acne, with a low incidence of severe side effects and at a lower cost than higher doses. PMID:25870473

  14. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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

  17. 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

    2015-10-01

    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 levels

  18. Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA.

    PubMed Central

    Noguchi, M.; Minami, M.; Yagasaki, R.; Kinoshita, K.; Earashi, M.; Kitagawa, H.; Taniya, T.; Miyazaki, I.

    1997-01-01

    We investigated the effects of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the incidence and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat (HF) diet. We also examined the effects of these treatments on the fatty acid composition of tumour and serum. Tumour incidence was significantly decreased by the administration of low-dose EPA and DHA, whereas their inhibitory effects on tumour growth did not reach significance. Serum arachidonic acid (AA) level was decreased by the administration of low-dose EPA and tended to be decreased by the administration of low-dose DHA, whereas tumour AA levels were not changed. The administration of low-dose EPA and DHA may be useful for inhibiting the incidence of breast cancer. PMID:9020478

  19. 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

  20. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium at the EMS 2009 Annual Meeting - September 2006

    SciTech Connect

    Morgan, William F.; von Borstel, Robert C.; Brenner, David; Redpath, J. Leslie; Erickson, Barbra E.; Brooks, Antone L.

    2009-11-12

    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.

  1. 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

    2015-01-01

    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

  2. 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

  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. PMID:26317642

  4. 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.

  5. Extrapyramidal side-effects of low-dose aripiprazole in an 11-year-old child.

    PubMed

    Mohapatra, Satyakam

    2016-01-01

    Partial agonism of D2 and 5-HT1A receptors accounts for the low incidence of extrapyramidal side-effects of aripiprazole. Extrapyramidal symptoms (EPS) during treatment with therapeutical doses of aripiprazole have been reported in adults and children. To the best of our knowledge, no cases of EPS with low doses (5 mg) have been reported until now. In this article, we present an 11-year-old child who developed EPS on low doses (5 mg) aripiprazole. This case emphasizes the need for careful surveillance for the development of EPS in patients treated even with low doses of aripiprazole. PMID:26933364

  6. 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.

  7. Changes in thyroid status of rats after prolonged exposure to low dose dichlorodiphenyltrichloroethane.

    PubMed

    Yaglova, N V; Yaglov, V V

    2014-04-01

    The effect of low dose dichlorodiphenyltrichloroethane (DDT), omnipresent ecotoxicant and endocrine disruptor, on the functioning of the endocrine system is an urgent problem. We studied the effect of low dose DDT on thyroid status in rats. Rats receiving DDT in a dose of 1.890±0.086 μg/kg for 6 weeks showed increased concentrations of thyroid hormones, particularly triiodothyronine, and reduced level of thyrotropin. Longer exposure reduced the production of thyroid hormones. The dynamics of thyroid status parameters during DDT treatment in a low dose was similar to changes observed during the development of hypothyroidism induced by iodine deficiency. PMID:24824690

  8. 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.

  9. Extrapyramidal side-effects of low-dose aripiprazole in an 11-year-old child

    PubMed Central

    Mohapatra, Satyakam

    2016-01-01

    Partial agonism of D2 and 5-HT1A receptors accounts for the low incidence of extrapyramidal side-effects of aripiprazole. Extrapyramidal symptoms (EPS) during treatment with therapeutical doses of aripiprazole have been reported in adults and children. To the best of our knowledge, no cases of EPS with low doses (5 mg) have been reported until now. In this article, we present an 11-year-old child who developed EPS on low doses (5 mg) aripiprazole. This case emphasizes the need for careful surveillance for the development of EPS in patients treated even with low doses of aripiprazole. PMID:26933364

  10. 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.

  11. 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

  12. 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.

  13. Low Dose Dopamine or Low Dose Nesiritide in Acute Heart Failure with Renal Dysfunction: The ROSE Acute Heart Failure Randomized Trial

    PubMed Central

    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.

    2014-01-01

    Importance Small studies suggest 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. Objective To test the two independent hypotheses that when compared to placebo, addition of: (1) low dose dopamine (2 ug/kg/min); or (2) low dose nesiritide (0.005 ug/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Design, Setting and Participants Multicenter, double-blind, placebo-controlled randomized clinical trial (Renal Optimization Strategies Evaluation) of 360 hospitalized participants with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15–60 ml/min/1.73m2), randomized within 24 hours of admission. Participants were randomized from September 2010 to March 2013 across 26 sites in the United States and Canada. Interventions Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategies. 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 to the pooled placebo group (n=119). Main outcome measures Co-primary endpoints included 72-hour cumulative urine volume (decongestion endpoint) and the change in serum cystatin-C from enrollment to 72 hours (renal function endpoint). Results Compared to placebo, low dose dopamine had no significant effect on 72-hour cumulative urine volume (8524 ml [95% CI 7917 to 9131 ml] with dopamine vs. 8296 ml [95% CI 7762 to 8830 ml] with placebo, p=0.59) or on the change in cystatin-C (0.12 mg/L [95% CI 0.06 to 0.18 mg/L] with dopamine vs. 0.11 mg/L [95% CI 0.06 to 0.16 mg/L] with placebo, p=0.72). Similarly, low dose nesiritide had no significant effect on 72-hour cumulative

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Effects of physicochemical forms of phenazepam and Panavir on their action at ultra-low doses.

    PubMed

    Stovbun, S V; Kiselev, A V; Zanin, A M; Kalinina, T S; Voronina, T A; Mikhailov, A I; Berlin, A A

    2012-08-01

    A concept of physicochemical forms of biologically active substances introduced in investigation of the action mechanism of ultra-low doses allows qualitative explanation of the main effects of ultra-low doses, chemical diversity of biologically active substances, and physical boundaries for these effects. Phenazepam was shown to possess activity in ultra-low doses only in disperse state, in the form of nanoparticles with a diameter <100-300 nm; these nanoparticles appear as micelles of surface active substances and solvated. Panavir possesses pharmacological activity in ultra-low doses and appears as nanoparticles with a diameter of 200-300 nm, which have uncompensated negative surface charge and polymer nature. PMID:22977843

  19. Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

    PubMed Central

    Lall, R; Ganapathy, S; Yang, M; Xiao, S; Xu, T; Su, H; Shadfan, M; Asara, J M; Ha, C S; Ben-Sahra, I; Manning, B D; Little, J B; Yuan, Z-M

    2014-01-01

    Because of insufficient understanding of the molecular effects of low levels of radiation exposure, there is a great uncertainty regarding its health risks. We report here that treatment of normal human cells with low-dose radiation induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting in increased radiation resistance. This metabolic change is highlighted by upregulation of genes encoding glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway, concomitant with downregulation of mitochondrial genes, with corresponding changes in metabolic flux through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1α, which is induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed systemically in mice. This highly sensitive metabolic response to low-dose radiation has important implications in understanding and assessing the health risks of radiation exposure. PMID:24583639

  20. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis.

    PubMed

    Ochieng, Josiah; Nangami, Gladys N; Ogunkua, Olugbemiga; Miousse, Isabelle R; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa J; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T; Dong, Chenfang; Zhou, Binhua P; Brown, Dustin G; Colacci, Anna Maria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P; Woodrick, Jordan; Scovassi, A 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

    2015-06-01

    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

  1. The estimation of low-dose hazards by extrapolation from high doses.

    PubMed

    Rossi, H H

    1981-01-01

    Empirical information on the effects of low doses of ionizing radiation is beset by severe limitations. Theoretical considerations of biophysics can guide the analysis of epidemiological data by indicating certain dose-response relations or eliminating others. Thus, it can be shown that at low doses there must be proportionality between dose and effect on non-interacting cells and that one must anticipate different dose-effect relations upon exposure to markedly different types of radiation. PMID:7336764

  2. Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit.

    PubMed

    Gutting, Bradford W; Marchette, David; Sherwood, Robert; Andrews, George A; Director-Myska, Alison; Channel, Stephen R; Wolfe, Daniel; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Rukhin, Andrey

    2013-07-21

    There is a need to advance our ability to conduct credible human risk assessments for inhalational anthrax associated with exposure to a low number of bacteria. Combining animal data with computational models of disease will be central in the low-dose and cross-species extrapolations required in achieving this goal. The objective of the current work was to apply and advance the competing risks (CR) computational model of inhalational anthrax where data was collected from NZW rabbits exposed to aerosols of Ames strain Bacillus anthracis. An initial aim was to parameterize the CR model using high-dose rabbit data and then conduct a low-dose extrapolation. The CR low-dose attack rate was then compared against known low-dose rabbit data as well as the low-dose curve obtained when the entire rabbit dose-response data set was fitted to an exponential dose-response (EDR) model. The CR model predictions demonstrated excellent agreement with actual low-dose rabbit data. We next used a modified CR model (MCR) to examine disease incubation period (the time to reach a fever >40 °C). The MCR model predicted a germination period of 14.5h following exposure to a low spore dose, which was confirmed by monitoring spore germination in the rabbit lung using PCR, and predicted a low-dose disease incubation period in the rabbit between 14.7 and 16.8 days. Overall, the CR and MCR model appeared to describe rabbit inhalational anthrax well. These results are discussed in the context of conducting laboratory studies in other relevant animal models, combining the CR/MCR model with other computation models of inhalational anthrax, and using the resulting information towards extrapolating a low-dose response prediction for man. PMID:23567649

  3. 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.

  4. 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. PMID:27218294

  5. Pulsed low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis

    PubMed Central

    Cline-Smith, Anna; Gibbs, Jesse; Shashkova, Elena; Buchwald, Zachary S.; Novack, Deborah V.; Aurora, Rajeev

    2016-01-01

    A number of studies in model animal systems and in the clinic have established that RANKL promotes bone resorption. Paradoxically, we found that pulsing ovariectomized mice with low-dose RANKL suppressed bone resorption, decreased the levels of proinflammatory effector T cells and led to increased bone mass. This effect of RANKL is mediated through the induction of FoxP3+CD25+ regulatory CD8+ T cells (TcREG) by osteoclasts. Here, we show that pulses of low-dose RANKL are needed to induce TcREG, as continuous infusion of identical doses of RANKL by pump did not induce TcREG. We also show that low-dose RANKL can induce TcREG at 2, 3, 6, and 10 weeks after ovariectomy. Our results show that low-dose RANKL treatment in ovariectomized mice is optimal at once-per-month doses to maintain the bone mass. Finally, we found that treatment of ovariectomized mice with the Cathepsin K inhibitor odanacatib also blocked TcREG induction by low-dose RANKL. We interpret this result to indicate that antigens presented to CD8+ T cells by osteoclasts are derived from the bone protein matrix because Cathepsin K degrades collagen in the bone. Taken together, our studies provide a basis for using low-dose RANKL as a potential therapeutic for postmenopausal osteoporosis. PMID:27570837

  6. Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

    PubMed Central

    Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

    2015-01-01

    Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks. PMID:26029736

  7. 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.

  8. 20. DETAIL VIEW OF NONSUBMERSIBLE TAINTER GATE, SHOWING GATE, GATE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. DETAIL VIEW OF NONSUBMERSIBLE TAINTER GATE, SHOWING GATE, GATE ARM, TRUNNION PIN, PIER AND GATE GAUGE, LOOKING WEST - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 10, Guttenberg, Clayton County, IA

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. LOW DOSE STUDIES WITH FOCUSED X-RAYS IN CELL AND TISSUE MODELS: MECHANISMS OF BYSTANDER AND GENOMIC INSTABILITY RESPONSES

    EPA Science Inventory

    The aims of this and other projects in the DOE's Low-Dose Program are to gain an understanding of the biological actions of low-dose radiation, ultimately to provide information that will lead to more accurate quantification of low-dose risk. Our project is based on the concept t...

  15. 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

  16. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses.

    PubMed

    Vandenberg, Laura N; 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; Myers, John Peterson

    2012-06-01

    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

  17. Low-dose performance of wafer-scale CMOS-based X-ray detectors

    NASA Astrophysics Data System (ADS)

    Maes, Willem H.; Peters, Inge M.; Smit, Chiel; Kessener, Yves; Bosiers, Jan

    2015-03-01

    Compared to published amorphous-silicon (TFT) based X-ray detectors, crystalline silicon CMOS-based active-pixel detectors exploit the benefits of low noise, high speed, on-chip integration and featuring offered by CMOS technology. This presentation focuses on the specific advantage of high image quality at very low dose levels. The measurement of very low dose performance parameters like Detective Quantum Efficiency (DQE) and Noise Equivalent Dose (NED) is a challenge by itself. Second-order effects like defect pixel behavior, temporal and quantization noise effects, dose measurement accuracy and limitation of the x-ray source settings will influence the measurements at very low dose conditions. Using an analytical model to predict the low dose behavior of a detector from parameters extracted from shot-noise limited dose levels is presented. These models can also provide input for a simulation environment for optimizing the performance of future detectors. In this paper, models for predicting NED and the DQE at very low dose are compared to measurements on different CMOS detectors. Their validity for different sensor and optical stack combinations as well as for different x-ray beam conditions was validated.

  18. 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. PMID:24225641

  19. Management of low-dose aspirin and clopidogrel in clinical practice: a gastrointestinal perspective.

    PubMed

    Lanas, Angel; Gargallo, Carla J

    2015-06-01

    Low-dose aspirin, alone or combined with other antiplatelet agents, is increasingly prescribed for cardiovascular prevention. However, the cardiovascular benefits should be evaluated together with the gastrointestinal risks. Low-dose aspirin is associated with upper and lower gastrointestinal injury, although lower gastrointestinal effects are poorly characterized. This gastrointestinal risk differs among antiplatelets drugs users. The most important risk factors are history of peptic ulcer, older age, and concomitant use of non-steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper gastrointestinal prevention strategies are available and should be used in at-risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem to be the best gastroprotective agents, whereas the benefits of Helicobacter pylori eradication are still unclear. Low-dose aspirin has additional effects in the gastrointestinal tract. A large body of evidence indicates that it can protect against different cancers, in particular colorectal cancer. This effect could modify the future indications for use of low-dose aspirin and the risk-benefit balance. PMID:25595209

  20. 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.

  1. 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.

  2. 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. PMID:26945467

  3. Hemiablative Focal Low Dose Rate Brachytherapy: A Phase II Trial Protocol

    PubMed Central

    Bucci, Joseph; Chin, Yaw Sinn; Malouf, David; Howie, Andrew; Enari, Komiti Ese

    2016-01-01

    trial (RCT). Conclusions This protocol is designed to show feasibility in delivering hemigland focal therapy with seed BT. It may answer crucial questions and obtain data which will enable downstream decisions on focal low dose rate (LDR) prostate BT. ClinicalTrial Clinicaltrial.gov NCT02643511; https://www.clinicaltrials.gov/ct2/show/NCT02643511 (Archived by Webcite at http://www.webcitation.org/6ghLCzIhY) PMID:27296781

  4. 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

  5. Safety and Efficacy of Low-Dose Isotretinoin in the Treatment of Moderate to Severe Acne Vulgaris

    PubMed Central

    Rao, Parinitha K; Bhat, Ramesh M; Nandakishore, B; Dandakeri, Sukumar; Martis, Jacintha; Kamath, Ganesh H

    2014-01-01

    Background: Isotretinoin is indicated for moderate to severe cases of acne which are unresponsive to conventional therapy. The classical recommended dose is 0.5 to 1.0 mg/kg/day. As the side effects are dose related, low-dose isotretinoin therapy for acne is an attractive option; however, but little data exists on the safety and efficacy of this strategy. Materials and Methods: In this prospective, non-comparative study, 50 participants, both male and female, having moderate to severe acne vulgaris were enrolled and treated with isotretinoin at a dose of 20 mg/day (approximately 0.3-0.4 mg/kg/day), for a period of 3 months. Participants were evaluated by means of clinical and laboratory investigations before starting isotretinoin. Investigations were repeated at the end of the first and third months following completion of treatment, and participants were followed up for 6 months to look for any relapse. Results: At the end of the treatment, very good results were observed in 90% of participants. Cheilitis was the most common among the side effects observed and was seen in 98% of the participants. One participant developed vitiligo as a side effect, which is a new finding, and has not reported in literature before. Elevated serum lipid levels were observed in 6% of the participants, and relapse occurred in 4% of the participants over a 6 month follow up period. Conclusion: Three months of treatment with low-dose isotretinoin (20 mg/day) was found to be effective in the treatment of moderate to severe acne vulgaris, with a low incidence of serious side effects. This dose also was more economical than the higher doses. PMID:24891681

  6. 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.

  7. Low-dose performance of a whole-body research photon-counting CT scanner

    NASA Astrophysics Data System (ADS)

    Yu, Zhicong; Leng, Shuai; Kappler, Steffen; Hahn, Katharina; Li, Zhoubo; Halaweish, Ahmed F.; Henning, Andre; Ritman, Erik L.; McCollough, Cynthia H.

    2016-04-01

    Photon-counting CT (PCCT) is an emerging technique that may bring new possibilities to clinical practice. Compared to conventional CT, PCCT is able to exclude electronic noise that may severely impair image quality at low photon counts. This work focused on assessing the low-dose performance of a whole-body research PCCT scanner consisting of two subsystems, one equipped with an energy-integrating detector, and the other with a photon-counting detector. Evaluation of the low-dose performance of the research PCCT scanner was achieved by comparing the noise performance of the two subsystems, with an emphasis on examining the impact of electronic noise on image quality in low-dose situations.

  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. 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.

  10. 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.

  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. 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.

  13. Low-dose methotrexate inhibits methionine S-adenosyltransferase in vitro and in vivo.

    PubMed

    Wang, Yi-Cheng; Chiang, En-Pei Isabel

    2012-01-01

    Methionine S-adenosyltransferase (MAT) catalyzes the only reaction that produces the major methyl donor in mammals. Low-dose methotrexate is the most commonly used disease-modifying antirheumatic drug in human rheumatic conditions. The present study was conducted to test the hypothesis that methotrexate inhibits MAT expression and activity in vitro and in vivo. HepG2 cells were cultured under folate restriction or in low-dose methotrexate with and without folate or methionine supplementation. Male C57BL/6J mice received methotrexate regimens that reflected low-dose clinical use in humans. S-adenosylmethionine and MAT genes, proteins and enzyme activity levels were determined. We found that methionine or folate supplementation greatly improved S-adenosylmethionine in folate-depleted cells but not in cells preexposed to methotrexate. Methotrexate but not folate depletion suppressed MAT genes, proteins and activity in vitro. Low-dose methotrexate inhibited MAT1A and MAT2A genes, MATI/II/III proteins and MAT enzyme activities in mouse tissues. Concurrent folinate supplementation with methotrexate ameliorated MAT2A reduction and restored S-adenosylmethionine in HepG2 cells. However, posttreatment folinate rescue failed to restore MAT2A reduction or S-adenosylmethionine level in cells preexposed to methotrexate. Our results provide both in vitro and in vivo evidence that low-dose methotrexate inhibits MAT genes, proteins, and enzyme activity independent of folate depletion. Because polyglutamated methotrexate stays in the hepatocytes, if methotrexate inhibits MAT in the liver, then the efficacy of clinical folinate rescue with respect to maintaining hepatic S-adenosylmethionine synthesis and normalizing the methylation reactions would be limited. These findings raise concerns on perturbed methylation reactions in humans on low-dose methotrexate. Future studies on the clinical physiological consequences of MAT inhibition by methotrexate and the potential benefits of S

  14. 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

  15. Optimum flash lamp annealing conditions for fabrication of low dose ion-implanted Si solar cells

    NASA Astrophysics Data System (ADS)

    Usami, A.; Nishioka, H.; Inoue, Y.

    1984-06-01

    A method to fabricate silicon solar cells was developed around low dose (nonamorphized) ion implantation and Xe flash lamp annealing under assist heating (350-550 C). Solar cells fabricated by low dose B-11/+/ (p+/n-type cell) and P-31/+/ (n+/p-type cell) implantation and flash lamp annealing showing a high efficiency of about 10.4 percent (AM2) without AR coating and BSF structures. The results were compared with those of high dose implanted cells reported previously (in this transaction). Effects of assist heating temperature were also examined.

  16. 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. PMID:23546884

  17. Mechanisms of Low Dose Radiation-induced T helper Cell Function

    SciTech Connect

    Gridley, Daila S.

    2008-10-31

    Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of “dirty bombs” by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset of lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to

  18. [A comparative study between low-dose and high-dose medroxyprogesterone acetate (MPA) in the treatment of advanced and recurrent breast cancer--in relation to dose, serum concentration and response. Osaka Breast Cancer Research Group].

    PubMed

    Furukawa, J; Yayoi, E; Takatsuka, Y; Aikawa, T; Maeura, Y; Kobayashi, T; Miyauchi, K; Kotsuma, Y

    1997-05-01

    A prospective randomized study was carried out to evaluate the effectiveness of MPA in the treatment of breast cancer by comparing low dose (600 mg/day) with high dose (1,200 mg/day) of MPA. In 35 evaluable cases, the response rate to treatment was 40.0% (8/20) with low dose MPA and 26.7% (4/15) with high dose MPA. There was no significant difference between the two groups. The serum MPA concentration measured by high-performance liquid chromatography (HPLC) assay was 23.2 +/- 17.6 ng/ml in the low-dose group and 89.5 +/- 56.7 ng/ml in the high-dose group. Intrapatient variability in serum MPA concentration was relatively stable, but interpatient variability was large. No correlation was found between the response rate and serum MPA concentration. The above results indicate that a low dose of MPA (600 mg/day) is a useful treatment with high effectiveness and safety in advanced and recurrent breast cancer patients. Though no exact data on the optimal serum concentration could not be obtained, it was obvious that a successful response cannot be expected from a serum MPA concentration of less than 17 ng/ml, which was the average serum concentration in NC and PD patients of the low-dose group. PMID:9170519

  19. Concomitant chemoradiotherapy using low-dose weekly gemcitabine versus low-dose weekly paclitaxel in locally advanced head and neck squamous cell carcinoma: a phase III study.

    PubMed

    Halim, Amal Ahmed-Fouad; Wahba, Hanan Ahmed; El-Hadaad, Hend Ahmed; Abo-Elyazeed, Ahmed

    2012-03-01

    The objective of this study was to compare concomitant chemoradiotherapy based on weekly low-dose gemcitabine versus weekly low-dose paclitaxel in locally advanced head and neck squamous cell carcinoma. Previously, untreated patients with locally advanced squamous cell carcinoma of the head and neck were randomly assigned to one of the two concomitant chemoradiation regimens: (1) weekly gemcitabine at a dose of 100 mg/m(2) over 30 min 1-2 h before radiotherapy and (2) weekly paclitaxal at a dose of 20 mg/m(2) over 60 min 4-6 h before radiotherapy. The planned radiotherapy dose was 65 Gy over 6.5 weeks in 32 settings. Two hundred and sixteen patients were randomly divided into 2 groups: group A (110 patients) and group B (106 patients) who received concomitant weekly low-dose gemcitabine and low-dose paclitaxal, respectively, with the radiotherapy protocol. The hematological toxicity was generally mild. On the contrary, non-hematologic toxicities were severe. Grade III mucositis occurred in 36% in group A and in 24% in group B (P = 0.04). Moreover, grade III dermatitis were encountered in 24% in group A and 13% in group B (P = 0.049). Thirty-two (29%) of group A and 18(17%) of group B patients required enteral or parenteral feeding (P = 0.01). Sixteen (15%) of group A and 6 (6%) of group B required enteral or parenteral feeding that lasted for 6 months (P = 0.03). Regarding the late effect on swallowing, 8% of patients in group A and 2% of patients in group B required enteral or parenteral feeding for more than 6 months (P = 0.035). Response rates were 78 and 89% in groups A and B, respectively (P = 0.038). The 2-year progression-free survival figures were 54 and 64% of groups A and B, respectively; however, the 2-year overall survival figures were 56 and 67%, respectively. On the other hand, the 3-year progression-free survival figures were 39 and 48% for groups A and B, respectively, while the 3-year overall survival figures were 45 and 49%, respectively (P = 0

  20. Low-dose preview for patient-specific, task-specific technique selection in cone-beam CT

    PubMed Central

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

    2014-01-01

    Purpose : A method is presented for generating simulated low-dose cone-beam CT (CBCT) preview images from which patient- and task-specific minimum-dose protocols can be confidently selected prospectively in clinical scenarios involving repeat scans. Methods : In clinical scenarios involving a series of CBCT images, the low-dose preview (LDP) method operates upon the first scan to create a projection dataset that accurately simulates the effects of dose reduction in subsequent scans by injecting noise of proper magnitude and correlation, including both quantum and electronic readout noise as important components of image noise in flat-panel detector CBCT. Experiments were conducted to validate the LDP method in both a head phantom and a cadaveric torso by performing CBCT acquisitions spanning a wide dose range (head: 0.8–13.2 mGy, body: 0.8–12.4 mGy) with a prototype mobile C-arm system. After injecting correlated noise to simulate dose reduction, the projections were reconstructed using both conventional filtered backprojection (FBP) and an iterative, model-based image reconstruction method (MBIR). The LDP images were then compared to real CBCT images in terms of noise magnitude, noise-power spectrum (NPS), spatial resolution, contrast, and artifacts. Results : For both FBP and MBIR, the LDP images exhibited accurate levels of spatial resolution and contrast that were unaffected by the correlated noise injection, as expected. Furthermore, the LDP image noise magnitude and NPS were in strong agreement with real CBCT images acquired at the corresponding, reduced dose level across the entire dose range considered. The noise magnitude agreed within 7% for both the head phantom and cadaveric torso, and the NPS showed a similar level of agreement up to the Nyquist frequency. Therefore, the LDP images were highly representative of real image quality across a broad range of dose and reconstruction methods. On the other hand, naïve injection ofuncorrelated noise

  1. Low-dose preview for patient-specific, task-specific technique selection in cone-beam CT

    SciTech Connect

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

    2014-07-15

    Purpose : A method is presented for generating simulated low-dose cone-beam CT (CBCT) preview images from which patient- and task-specific minimum-dose protocols can be confidently selected prospectively in clinical scenarios involving repeat scans. Methods : In clinical scenarios involving a series of CBCT images, the low-dose preview (LDP) method operates upon the first scan to create a projection dataset that accurately simulates the effects of dose reduction in subsequent scans by injecting noise of proper magnitude and correlation, including both quantum and electronic readout noise as important components of image noise in flat-panel detector CBCT. Experiments were conducted to validate the LDP method in both a head phantom and a cadaveric torso by performing CBCT acquisitions spanning a wide dose range (head: 0.8–13.2 mGy, body: 0.8–12.4 mGy) with a prototype mobile C-arm system. After injecting correlated noise to simulate dose reduction, the projections were reconstructed using both conventional filtered backprojection (FBP) and an iterative, model-based image reconstruction method (MBIR). The LDP images were then compared to real CBCT images in terms of noise magnitude, noise-power spectrum (NPS), spatial resolution, contrast, and artifacts. Results : For both FBP and MBIR, the LDP images exhibited accurate levels of spatial resolution and contrast that were unaffected by the correlated noise injection, as expected. Furthermore, the LDP image noise magnitude and NPS were in strong agreement with real CBCT images acquired at the corresponding, reduced dose level across the entire dose range considered. The noise magnitude agreed within 7% for both the head phantom and cadaveric torso, and the NPS showed a similar level of agreement up to the Nyquist frequency. Therefore, the LDP images were highly representative of real image quality across a broad range of dose and reconstruction methods. On the other hand, naïve injection ofuncorrelated noise

  2. Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy.

    PubMed

    Zhang, Yin; Yang, Yunlong; Hosaka, Kayoko; Huang, Guichun; Zang, Jingwu; Chen, Fang; Zhang, Yun; Samani, Nilesh J; Cao, Yihai

    2016-04-12

    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

  3. Efficacy of a Low Dose of Estrogen on Antioxidant Defenses and Heart Rate Variability

    PubMed Central

    Casali, Karina Rabello; Baraldi, Dhãniel; Conzatti, Adriana; Araújo, Alex Sander da Rosa; Khaper, Neelam; Llesuy, Susana; Rigatto, Katya; Belló-Klein, Adriane

    2014-01-01

    This study tested whether a low dose (40% less than the pharmacological dose of 17-β estradiol) would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n = 9/group) were divided in three groups: (1) ovariectomized (Ovx), (2) ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg), and (3) high dose (HE; 0.5 mg) 17-β estradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD) and catalase (CAT) activities, redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP), hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy. PMID:24738017

  4. 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.

  5. 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...

  6. MECHANISMS OF ENHANCED CELL KILLING AT LOW DOSES: IMPLICATIONS FOR RADIATION RISK

    EPA Science Inventory

    We have determined previously that radiation sensitivity can be dose-dependent so that small acute exposures (and possibly exposures at very low dose rates) are more lethal per unit dose than larger exposures above a threshold (typically 5-40 cGy) where radioresistance increases....

  7. ANNUAL PROGRESS REPORT. LOW-DOSE RISK, DECISIONS, AND RISK COMMUNICATION

    EPA Science Inventory

    This report summarizes work after 20 month of a 36-month project. To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research prog...

  8. 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

  9. Analysis of bipolar linear circuit response mechanisms for high and low dose rate total dose irradiations

    SciTech Connect

    Barnaby, H.; Tausch, H.J.; Turfler, R.; Cole, P.; Baker, P.; Pease, R.L.

    1996-12-01

    A methodology is presented for the identification of circuit total dose response mechanisms in bipolar linear microcircuits irradiated at high and low dose rates. This methodology includes manual circuit analysis, circuit simulations with SPICE using extracted device parameters, and selective irradiations of portions of the circuit using a scanning electron microscope.

  10. [The issue of low doses in radiation therapy and impact on radiation-induced secondary malignancies].

    PubMed

    Chargari, Cyrus; Cosset, Jean-Marc

    2013-12-01

    Several studies have well documented that the risk of secondary neoplasms is increasing among patients having received radiation therapy as part of their primary anticancer treatment. Most frequently, radiation-induced neoplasms occur in volume exposed to high doses. However, the impact of "low" doses (<5 Gy) in radiation-induced carcinogenesis should be clinically considered because modern techniques of intensity-modulated radiation therapy (IMRT) or stereotactic irradiation significantly increase tissue volumes receiving low doses. The risk inherent to these technologies remains uncertain and estimates closely depend on the chosen risk model. According to the (debated) linear no-threshold model, the risk of secondary neoplasms could be twice higher with IMRT, as compared to conformal radiation therapy. It seems that only proton therapy could decrease both high and low doses delivered to non-target volumes. Except for pediatric tumors, for which the unequivocal risk of second malignancies (much higher than in adults) should be taken into account, epidemiological data suggest that the risk of secondary cancer related to low doses could be very low, even negligible in some cases. However, clinical follow-up remains insufficient and a marginal increase in secondary tumors could counterbalance the benefit of a highly sophisticated irradiation technique. It therefore remains necessary to integrate the potential risk of new irradiation modalities in a risk-adapted strategy taking into account therapeutic objectives but also associated risk factors, such as age (essentially), chemotherapy, or life style. PMID:24257106

  11. 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…

  12. Low dose titration of copper oxide wire particles for control of gastrointestinal nematodes in weaned kids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to determine whether a low dose of copper oxide wire particles (COWP) would be as effective as a higher dose in reducing gastrointestinal nematodes (GIN) infection. In May 2006, 40 Boer x Spanish doe and wether kids naturally infected with GIN were weaned (97 ± 2 days of age) and ...

  13. 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. PMID:23470804

  14. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

    PubMed

    Kopp, Felix K; Holzapfel, Konstantin; 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

  15. 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.

  16. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  17. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  18. 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.

  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. 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. PMID:22398129

  1. 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

  2. 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

  3. Experimental characterization of the low-dose envelope of spot scanning proton beams

    NASA Astrophysics Data System (ADS)

    Sawakuchi, Gabriel O.; Zhu, X. Ronald; Poenisch, Falk; Suzuki, Kazumichi; Ciangaru, George; Titt, Uwe; Anand, Aman; Mohan, Radhe; Gillin, Michael T.; Sahoo, Narayan

    2010-06-01

    In scanned proton beam radiotherapy, multiple pencil beams are used to deliver the total dose to the target volume. Because the number of such beams can be very large, an accurate dosimetric characterization of every single pencil beam is important to provide adequate input data for the configuration of the treatment planning system. In this work, we present a method to measure the low-dose envelope of single pencil beams, known to play a meaningful role in the dose computation for scanned proton beams. We measured the low-dose proton beam envelope, which extends several centimeters outwards from the center of each single pencil beam, by acquiring lateral dose profile data, down to relative dose levels that were a factor of 104 lower than the central axis dose. The overall effect of the low-dose envelope on the total dose delivered by multiple pencil beams was determined by measuring the dose output as a function of field size. We determined that the low-dose envelope can be influential even for fields as large as 20 cm × 20 cm.

  4. Local low dose streptokinase in the treatment of acute peripheral arterial occlusion.

    PubMed

    Breslau, P J; Van der Linden, C J; Janevski, B; Jörning, P J

    1984-06-01

    Case report of local low dose streptokinase therapy in a patient with acute occlusion of the left branch of an aortobifurcation graft. Objective evidence of complete thrombolysis was demonstrated both by arteriography and hemodynamic parameters. In carefully selected cases this thrombolytic therapy is a promising alternative to surgery. PMID:6738887

  5. 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 for Medicare & Medicaid Services (CMS) are currently evaluating coverage of lung cancer screening for Medicare beneficiaries. Since 70% of lung cancer occurs in patients 65 years or older, CMS should cover low-dose CT, thus avoiding the situation of at-risk patients being screened up to age 64 through private insurers and then abruptly ceasing screening at exactly the ages when their risk for developing lung cancer is increasing. Legitimate concerns include false-positive findings that lead to further testing and invasive procedures, overdiagnosis (detection of clinically unimportant cancers), the morbidity and mortality of surgery, and the overall costs of follow-up tests and procedures. These concerns can be mitigated by clear criteria for screening high-risk patients, disciplined management of abnormalities based on algorithms, and high-quality multidisciplinary care. Lung cancer screening with low-dose CT can lead to early diagnosis and cure for thousands of patients each year. Professional societies can help CMS responsibly implement a program that is patient-centered and minimizes unintended harms and costs. PMID:25317992

  6. Safety and efficacy of low-dose, subacute exposure of mature ewes to sodium chlorate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis

    PubMed Central

    Wells, Alvin F.

    2014-01-01

    Glucocorticosteroids (GCs) have been employed extensively for the treatment of rheumatoid arthritis (RA) and other autoimmune and systemic inflammatory disorders. Their use is supported by extensive literature and their utility is reflected in their incorporation into current treatment guidelines for RA and other conditions. Nevertheless, there is still some concern regarding the long-term use of GCs because of their potential for clinically important adverse events, particularly with an extended duration of treatment and the use of high doses. This article systematically reviews the efficacy for radiological and clinical outcomes for low-dose GCs (defined as ≤10 mg/day prednisone equivalent) in the treatment of RA. Results reviewed indicated that low-dose GCs, usually administered in combination with synthetic DMARDs, most often MTX, significantly improve structural outcomes and decrease symptom severity in patients with RA. Safety data indicate that GC-associated adverse events are dose related, but still occur in patients receiving low doses of these agents. Concerns about side effects associated with GCs have prompted the development of new strategies aimed at improving safety without compromising efficacy. These include altering the structure of existing GCs and the development of delayed-release GC formulations so that drug delivery is timed to match greatest symptom severity. Optimal use of low-dose GCs has the potential to improve long-term outcomes for patients with RA. PMID:24729402

  8. 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...

  9. The prevalence of intolerance for low-dose acetylsalicylacid in the secondary prevention of atherothrombosis.

    PubMed

    Tournoij, E; Peters, R J G; Langenberg, M; Kanhai, K J K; Moll, F L

    2009-05-01

    Daily low-dose acetylsalicylacid (ASA) is prescribed to patients with atherothrombosis frequently to prevent vascular complications. In reports on complications and side effects of low-dose ASA use in the literature there is a range of definitions. We explored the incidence, characteristics and consequences of symptoms suggestive of ASA intolerance in patients on low-dose ASA. General practitioners and specialists in 105 centres were asked to review their patient files for the last 10 consecutive patients who were prescribed ASA. Participating patients completed a questionnaire about their current ASA use (doctors completed the questionnaire together with the patients), use of co-medication and symptoms suggestive of ASA intolerance. A total of 947 patients were included in this study. Sixty patients (6.6%) had ceased ASA treatment, predominantly because of the occurrence of side effects suspected to be caused by ASA use. A quarter of the patients concomitantly used an anti-acid agent. Of the 947 patients, 271 (30.6%) indicated symptoms during ASA intake. The most common symptoms were related to the gastrointestinal tract (25.1%). In patients prescribed a low-dose of ASA monotherapy, side effects suggestive of intolerance are common. More awareness should be created to detect and treat these symptoms, because the occurrence of side effects is the most important reason for patients to discontinue ASA treatment. PMID:19297216

  10. Lack of nontargeted effects in murine bone marrow after low-dose in vivo X irradiation.

    PubMed

    Zyuzikov, Nikolay A; Coates, Philip J; Parry, John M; Lorimore, Sally A; Wright, Eric G

    2011-03-01

    Exposure to high doses of ionizing radiation unequivocally produces adverse health effects including malignancy. At low doses the situation is much less clear, because effects are generally too small to be estimated directly by epidemiology, and extrapolation of risk and establishment of international rules and standards rely on the linear no-threshold (LNT) concept. Claims that low doses are more damaging than would be expected from LNT have been made on the basis of in vitro studies of nontargeted bystander effects and genomic instability, but relevant investigations of primary cells and tissues are limited. Here we show that after low-dose low-LET in vivo radiation exposures in the 0-100-mGy range of murine bone marrow there is no evidence of a bystander effect, assessed by p53 pathway signaling, nor is there any evidence for longer-term chromosomal instability in the bone marrow at doses below 1000 mGy. The data are not consistent with speculations based on in vitro nontargeted effects that low-dose X radiation is more damaging than would be expected from linear extrapolation. PMID:21388275

  11. 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. PMID:24366315

  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. Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method

    SciTech Connect

    Tao, Yinghua; Chen, Guang-Hong; Hacker, Timothy A.; Raval, Amish N.; Van Lysel, Michael S.; Speidel, Michael A.

    2014-07-15

    Purpose: Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. Methods: Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan was performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. Results: Forin vivo studies, the 500 mA FBP maps gave −88.4%, −96.0%, −76.7%, and −65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring −94.7%, −81.6%, −84.0%, and −72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, −11.8%, and −3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was −9.7%, 8.8%, −3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and 937

  14. Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method

    PubMed Central

    Tao, Yinghua; Chen, Guang-Hong; Hacker, Timothy A.; Raval, Amish N.; Van Lysel, Michael S.; Speidel, Michael A.

    2014-01-01

    Purpose: Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. Methods: Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan was performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. Results: Forin vivo studies, the 500 mA FBP maps gave −88.4%, −96.0%, −76.7%, and −65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring −94.7%, −81.6%, −84.0%, and −72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, −11.8%, and −3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was −9.7%, 8.8%, −3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and 937

  15. 18. DETAIL VIEW OF NONSUBMERSIBLE TAINTER GATE, SHOWING GATES, GATE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. DETAIL VIEW OF NON-SUBMERSIBLE TAINTER GATE, SHOWING GATES, GATE ARMS, PIERS AND DAM BRIDGE, LOOKING SOUTHEAST - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 9, Lynxville, Crawford County, WI

  16. 16. DETAIL VIEW OF SUBMERSIBLE TAINTER GATE, SHOWING GATE, GATE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. DETAIL VIEW OF SUBMERSIBLE TAINTER GATE, SHOWING GATE, GATE ARM, TRUNNION PIN AND PIER, LOOKING NORTHEAST - Upper Mississippi River 9-Foot Channel, Lock & Dam No. 8, On Mississippi River near Houston County, MN, Genoa, Vernon County, WI

  17. Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

    PubMed Central

    Kim, Sae-Hoon; Park, Da-Eun; Lee, Hyun-Seung; Kang, Hye-Ryun; Cho, Sang-Heon

    2014-01-01

    Background Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). Methods Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. Results Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. Conclusion Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. PMID:25202911

  18. Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model

    SciTech Connect

    Hengel, Shawna; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.

    2014-07-29

    To assess molecular responses to low doses of radiation that may be encountered during medical diagnostic procedures, nuclear accidents, or terrorist acts, a quantitative global proteomic approach was used to identify protein alterations in a reconstituted human skin tissue treated with 10 cGy of ionizing radiation. Subcellular fractionation was employed to remove highly abundant structural proteins and provide insight on radiation induced alterations in protein abundance and localization. In addition, peptides were post-fractionated using high resolution 2-dimensional liquid chromatography to increase the dynamic range of detection of protein abundance and translocation changes. Quantitative data was obtained by labeling peptides with 8-plex isobaric iTRAQ tags. A total of 207 proteins were detected with statistically significant alterations in abundance and/or subcellular localization compared to sham irradiated tissues. Bioinformatics analysis of the data indicated that the top canonical pathways affected by low dose radiation are related to cellular metabolism. Among the proteins showing alterations in abundance, localization and proteolytic processing was the skin barrier protein filaggrin which is consistent with our previous observation that ionizing radiation alters profilaggrin processing with potential effects on skin barrier functions. In addition, a large number of proteases and protease regulators were affected by low dose radiation exposure indicating that altered proteolytic activity may be a hallmark of low dose radiation exposure. While several studies have demonstrated altered transcriptional regulation occurs following low dose radiation exposures, the data presented here indicates post-transcriptional regulation of protein abundance, localization, and proteolytic processing play an important role in regulating radiation responses in complex human tissues.

  19. Effects of filtering on colorectal polyp detection in ultra low dose CT

    NASA Astrophysics Data System (ADS)

    Schoonenberg, Gert A.; de Vries, Ayso; Grigorescu, Simona; Peters, Joost; Vilanova, Anna; Truyen, Roel; Stoker, Jaap; Gerritsen, Frans

    2006-03-01

    We have evaluated the feasibility of polyp detection on simulated ultra low dose CT Colonography data by a computer aided polyp detection (CAD) algorithm. We compared the results of ultra low dose to normal dose data. Twenty-three extensively prepared patients were scanned in prone and supine position at 25 to 100 mAs (average 70 mAs) depending on their waist circumference. Noise was added and the scans were reconstructed at 6.25 and 1.39 mAs. To evaluate the performance of the CAD system, polyps detected by an experienced reviewer and confirmed at colonoscopy were used as ground truth. Curvature, concavity and sphericity of the colon surface were used to detect polyp candidates. Bilateral filtering was used to reduce noise. We present the results for 40 polyps of 6 mm or larger as measured during colonoscopy. The by-polyp sensitivity was 80% for medium size polyps (6-9 mm) and 97% for large polyps (10 mm or larger) at an average value of 5 false-positives per scan for normal dose data. The by-polyp sensitivity was 81% for medium size polyps and 85% for large size polyps at an average value of 5 false-positives per scan for low dose data (6.25 mAs). Finally for the ultra low dose data (1.39 mAs) we achieved a by-polyp sensitivity of 75% for medium size polyps and 97% for large polyps at an average value of 5 false-positives per scan. The conclusion of our study is that CAD for polyp detection is feasible on ultra low dose CT colonography data.

  20. Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

    SciTech Connect

    Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.; Le, Quynh-Thu; Hoppe, Richard T.; Donaldson, Sarah S.

    2013-08-01

    Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

  1. Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials.

    PubMed

    Charlebois, Audrey; Jacques, Mario; Archambault, Marie

    2014-01-01

    Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. This study was undertaken to address these issues. Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. PMID:24795711

  2. Proteomic-based mechanistic investigation of low-dose radiation-induced cellular responses/effects

    SciTech Connect

    Chen, Xian

    2013-10-23

    The goal of our project is to apply our unique systems investigation strategy to reveal the molecular mechanisms underlying the radiation induction and transmission of oxidative damage, adaptive response, and bystander effect at low-doses. Beginning with simple in vitro systems such as fibroblast or epithelial pure culture, our amino acid-coded mass tagging (AACT) comparative proteomic platform will be used to measure quantitatively proteomic changes at high- or low-dose level with respect to their endogenous damage levels respectively, in which a broad range of unique regulated proteins sensitive to low-dose IR will be distinguished. To zoom in how these regulated proteins interact with other in the form of networks in induction/transmission pathways, these regulated proteins will be selected as baits for making a series of fibroblast cell lines that stably express each of them. Using our newly developed method of ?dual-tagging? quantitative proteomics that integrate the capabilities of natural complex expression/formation, simple epitope affinity isolation (not through tandem affinity purification or TAP), and ?in-spectra? AACT quantitative measurements using mass spectrometry (MS), we will be able to distinguish systematically interacting proteins with each bait in real time. Further, in addition to both proteome-wide (global differentially expressed proteins) and pathway-scale (bait-specific) profiling information, we will perform a computational network analysis to elucidate a global pathway/mechanisms underlying cellular responses to real-time low-dose IR. Similarly, we will extend our scheme to investigate systematically those induction/transmission pathways occurring in a fibroblast-epithelial interacting model in which the bystander cell (fibroblast) monitor the IR damage to the target cell (epithelial cell). The results will provide the proteome base (molecular mechanisms/pathways for signaling) for the low dose radiation-induced essential tissue

  3. A low dose simulation tool for CT systems with energy integrating detectors

    SciTech Connect

    Zabic, Stanislav; Morton, Thomas; Brown, Kevin M.; Wang Qiu

    2013-03-15

    Purpose: This paper introduces a new strategy for simulating low-dose computed tomography (CT) scans using real scans of a higher dose as an input. The tool is verified against simulations and real scans and compared to other approaches found in the literature. Methods: The conditional variance identity is used to properly account for the variance of the input high-dose data, and a formula is derived for generating a new Poisson noise realization which has the same mean and variance as the true low-dose data. The authors also derive a formula for the inclusion of real samples of detector noise, properly scaled according to the level of the simulated x-ray signals. Results: The proposed method is shown to match real scans in number of experiments. Noise standard deviation measurements in simulated low-dose reconstructions of a 35 cm water phantom match real scans in a range from 500 to 10 mA with less than 5% error. Mean and variance of individual detector channels are shown to match closely across the detector array. Finally, the visual appearance of noise and streak artifacts is shown to match in real scans even under conditions of photon-starvation (with tube currents as low as 10 and 80 mA). Additionally, the proposed method is shown to be more accurate than previous approaches (1) in achieving the correct mean and variance in reconstructed images from pure-Poisson noise simulations (with no detector noise) under photon-starvation conditions, and (2) in simulating the correct noise level and detector noise artifacts in real low-dose scans. Conclusions: The proposed method can accurately simulate low-dose CT data starting from high-dose data, including effects from photon starvation and detector noise. This is potentially a very useful tool in helping to determine minimum dose requirements for a wide range of clinical protocols and advanced reconstruction algorithms.

  4. Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials

    PubMed Central

    Charlebois, Audrey; Jacques, Mario; Archambault, Marie

    2014-01-01

    Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. This study was undertaken to address these issues. Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. PMID:24795711

  5. Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.

    PubMed

    Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf

    2015-12-01

    Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks. PMID:26038159

  6. Validation of a Low Dose Simulation Technique for Computed Tomography Images

    PubMed Central

    Muenzel, Daniela; Koehler, Thomas; Brown, Kevin; Žabić, Stanislav; Fingerle, Alexander A.; Waldt, Simone; Bendik, Edgar; Zahel, Tina; Schneider, Armin; Dobritz, Martin; Rummeny, Ernst J.; Noël, Peter B.

    2014-01-01

    Purpose Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT) images from an original higher dose scan. Materials and Methods Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV) of a swine were acquired (approved by the regional governmental commission for animal protection). Simulations of CT acquisition with a lower dose (simulated 10–80 mAs) were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. Results Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was −1.2% (range −9% to 3.2%) and −0.2% (range −8.2% to 3.2%), respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9–10.2 HU (noise) and 1.9–13.4 HU (CT values), without significant differences (p>0.05). Subjective observer evaluation of image appearance showed no visually detectable difference. Conclusion Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques. PMID:25247422

  7. Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease. A randomized controlled trial.

    PubMed

    Abdelkefi, Abderrahman; Ben Othman, Tarek; Kammoun, Leïla; Chelli, Mouna; Romdhane, Neïla Ben; Kriaa, Azza; Ladeb, Saloua; Torjman, Lamia; Lakhal, Amel; Achour, Wafa; Ben Hassen, Assia; Hsaïri, Mohamed; Ladeb, Fethi; Ben Abdeladhim, Abdeladhim

    2004-09-01

    We have conducted a prospective randomized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease. Patients were randomly assigned to receive either prophylactic intravenous unfractionated heparin (continuous infusion of 100 IU/kg/daily) or 50 ml/daily of normal saline solution as a continuous infusion. CVLs were externalized, non tunneled, double lumen catheters. All CVLs were placed percutaneously by the same physician in the subclavian vein. Upper limb veins were systematically examined by ultrasonography just before, or <24 hours after, catheter removal, and in case of clinical signs of thrombosis. One hundred and twenty-eight CVLs were inserted. Catheter-related thrombosis occurred in 1.5% of the catheters inserted in patients of the heparin group, and in 12.6% in the control group (p = 0.03). No other risk factors were found for the development of catheter-related thrombosis. Two and three patients experienced severe bleeding in the heparin group, and in the control group, respectively (p = 0.18). There were no other side-effects clearly ascribable to the use of unfractionated heparin. This is the first prospective, randomized study, which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease. PMID:15351864

  8. Ferroelectric, stacked gate FETs: A prospective for planar CMOS with reduced leakage current and Sub-kT/q subthreshold swing

    NASA Astrophysics Data System (ADS)

    Kumar, Mirgender; Park, Si-Hyun

    2016-07-01

    The planar silicon-on-insulator (SOI) based metal-oxide semiconductor (MOS) structure has been at the center of attention of researchers who are attempting to extend its scalability. This study presents an analysis of ferroelectric MOS field effect transis-tors (Fe-MOSFETs) based on the surface potential, threshold voltage, subthreshold swing, leakage current, ON current and electron temperature. In addition, the electro-static integrity ( EI) factor and the threshold-voltage-to-swing ratio for Fe-MOSFETs were estimated and compared with those of conventional, high-k and double-gate (DG) MOSFETs. The analysis shows that the Fe-MOSFET is able to enhance the scalability and fulfil the expectation of researchers studying planar complementary MOS (CMOS) devices.

  9. Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients

    PubMed Central

    Shih, Chi-Chung; Chuang, Duen-Yau; Chen, Tien-Hsing

    2016-01-01

    Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. PMID:27555669

  10. Low-Dose Steroid Therapy Is Associated with Decreased IL-12 Production in PBMCs of Severe Septic Patients.

    PubMed

    Wu, Huang-Pin; Shih, Chi-Chung; Chuang, Duen-Yau; Chen, Tien-Hsing

    2016-01-01

    Background. Sepsis-induced immunosuppression may result in higher mortality rates in patients. Methods. We examined the relationship of cytokine responses from stimulated peripheral blood mononuclear cells (PBMCs) and monocyte human leukocyte antigen-DR (HLA-DR) expression (days 1 and 7) with low-dose steroid therapy in 29 septic patients. Patients were treated according to the guidelines. Thirty healthy controls were enrolled for validation. Results. Eighteen patients were prescribed low-dose steroids and 11 were not. Interleukin- (IL-) 12 responses in patients without low-dose steroid therapy on days 1 and 7 were higher than those with low-dose steroid therapy. Compared to day 1, IL-12 responses significantly increased on day 7 in patients without low-dose steroid therapy. After regression analysis, the change in the IL-12 response from day 7 to day 1 was found to be independently associated with the low-dose steroid therapy. There was no difference in monocyte HLA-DR expression between patients treated with and without low-dose steroid on day 1 or 7. No change in monocyte HLA-DR expression from day 7 to day 1 was observed in patients with or without low-dose steroid therapy. Conclusion. Decreased IL-12 response was associated with the low-dose steroid therapy in PBMCs of septic patients. PMID:27555669

  11. Final Report - Epigenetics of low dose radiation effects in an animal model

    SciTech Connect

    Kovalchuk, Olga

    2014-10-22

    This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis of induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low

  12. A motion-compensated image filter for low-dose fluoroscopy in a real-time tumor-tracking radiotherapy system.

    PubMed

    Miyamoto, Naoki; Ishikawa, Masayori; Sutherland, Kenneth; Suzuki, Ryusuke; Matsuura, Taeko; Toramatsu, Chie; Takao, Seishin; Nihongi, Hideaki; Shimizu, Shinichi; Umegaki, Kikuo; Shirato, Hiroki

    2015-01-01

    In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory-gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low-dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some trajectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within ±2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction. PMID:25129556

  13. Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension

    PubMed Central

    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

    2016-01-01

    at baseline. 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. PMID:27015224

  14. Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain

    PubMed Central

    Van Bockstaele, Elisabeth J.; Qian, Yaping; Sterling, Robert C.; Page, Michelle E.

    2009-01-01

    The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pretreatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional four hours. At the end of the

  15. Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review.

    PubMed Central

    Melnick, Ronald; Lucier, George; Wolfe, Mary; Hall, Roxanne; Stancel, George; Prins, Gail; Gallo, Michael; Reuhl, Kenneth; Ho, Shuk-Mei; Brown, Terry; Moore, John; Leakey, Julian; Haseman, Joseph; Kohn, Michael

    2002-01-01

    At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. The demonstration that an effect is adverse was not required because in many cases the long-term health consequences of altered endocrine function during development have not been fully characterized. A unique aspect of this peer review was the willing submission of individual animal data by principal investigators of primary research groups active in this field and the independent statistical reanalyses of selected parameters prior to the peer review meeting by a subpanel of statisticians. The expert peer-review panel (the panel) also considered mechanistic data that might influence the plausibility of low-dose effects and identified study design issues or other biologic factors that might account for differences in reported outcomes among studies. The panel found that low-dose effects, as defined for this review, have been demonstrated in laboratory animals exposed to certain endocrine-active agents. In some cases where low-dose effects have been reported, the findings have not been replicated. The shape of the dose-response curves for reported effects varied with the end point and dosing regimen and were low-dose linear, threshold-appearing, or nonmonotonic. The findings of the panel indicate that the current testing paradigm used for assessments of reproductive and developmental toxicity should be revisited to see whether changes are needed regarding dose selection, animal-model selection, age when

  16. Low Dose Gamma Irradiation Potentiates Secondary Exposure to Gamma Rays or Protons in Thyroid Tissue Analogs

    SciTech Connect

    Green, Lora M

    2006-05-25

    We have utilized our unique bioreactor model to produce three-dimensional thyroid tissue analogs that we believe better represent the effects of radiation in vivo than two-dimensional cultures. Our thyroid model has been characterized at multiple levels, including: cell-cell exchanges (bystander), signal transduction, functional changes and modulation of gene expression. We have significant preliminary data on structural, functional, signal transduction and gene expression responses from acute exposures at high doses (50-1000 rads) of gamma, protons and iron (Green et al., 2001a; 2001b; 2002a; 2002b; 2005). More recently, we used our DOE funding (ending Feb 06) to characterize the pattern of radiation modulated gene expression in rat thyroid tissue analogs using low-dose/low-dose rate radiation, plus/minus acute challenge exposures. Findings from these studies show that the low-dose/low-dose rate “priming” exposures to radiation invoked changes in gene expression profiles that varied with dose and time. The thyrocytes transitioned to a “primed” state, so that when the tissue analogs were challenged with an acute exposure to radiation they had a muted response (or an increased resistance) to cytopathological changes relative to “un-primed” cells. We measured dramatic differences in the primed tissue analogs, showing that our original hypothesis was correct: that low dose gamma irradiation will potentiate the repair/adaptation response to a secondary exposure. Implications from these findings are that risk assessments based on classical in vitro tissue culture assays will overestimate risk, and that low dose rate priming results in a reduced response in gene expression to a secondary challenge exposure, which implies that a priming dose provides enhanced protection to thyroid cells grown as tissue analogs. If we can determine that the effects of radiation on our tissue analogs more closely resemble the effects of radiation in vivo, then we can better

  17. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4)

    PubMed Central

    Choi, Philip Young-Ill; Roncolato, Fernando; Badoux, Xavier; Ramanathan, Sundra; Ho, Shir-Jing

    2015-01-01

    Promising reports of combination immunosuppression with high-dose dexamethasone and rituximab for the treatment of primary immune thrombocytopenia (ITP) have recently emerged. They suggest a potential to further optimize the efficacy of therapy. We investigate the use of a novel combination of conventional therapies in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5 to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for days 7, 14, 21, and 28. There were no therapy-related serious adverse side effects, 6-month response rate was 60%, and treatment was well tolerated. Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and 24 months. This study highlights the possibility of achieving an enduring remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au (#ANZCTRN12611000015943). PMID:25972158

  18. Lack of efficacy of low-dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs.

    PubMed

    Schuller, S; Van Israël, N; Vanbelle, S; Clercx, C; McEntee, K

    2011-08-01

    Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment. PMID:20950346

  19. Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions.

    PubMed

    Schwenk, Eric S; Goldberg, Stephen F; Patel, Ronak D; Zhou, Jon; Adams, Douglas R; Baratta, Jaime L; Viscusi, Eugene R; Epstein, Richard H

    2016-01-01

    High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions and which ADEs most frequently led to discontinuation. Spine surgery was chosen because of its association with moderate to severe pain and a relatively high use of ketamine infusions in this population at our hospital. PMID:27281730

  20. Low-dose Amisulpride for Debilitating Clozapine-induced Sialorrhea: Case Series and Review of Literature.

    PubMed

    Kulkarni, Ranganath R

    2015-01-01

    Clozapine-induced sialorrhea (CIS) affects about one-third of patients treated with clozapine, at times can be stigmatizing, socially embarrassing, disabling, affect quality-of-life, cause poor compliance and can be potentially life-threatening adverse effect. Prompt and effective treatment of CIS may assist treatment tolerability, adherence, and better outcomes in patients with treatment nonresponsive schizophrenia. The beneficial effect of amisulpride augmentation of clozapine therapy for such patients may be enhanced by its anti-salivatory effect on CIS. Current series of five subjects who developed CIS that responded poorly to anticholinergic drugs found drastic improvement in daytime and nocturnal CIS with very low-dose (50-100 mg/day) of amisulpride. Low-dose amisulpride augmentation may also provide strong ameliorating effect on CIS. Nevertheless, a long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time. PMID:26702180

  1. Low-dose Amisulpride for Debilitating Clozapine-induced Sialorrhea: Case Series and Review of Literature

    PubMed Central

    Kulkarni, Ranganath R.

    2015-01-01

    Clozapine-induced sialorrhea (CIS) affects about one-third of patients treated with clozapine, at times can be stigmatizing, socially embarrassing, disabling, affect quality-of-life, cause poor compliance and can be potentially life-threatening adverse effect. Prompt and effective treatment of CIS may assist treatment tolerability, adherence, and better outcomes in patients with treatment nonresponsive schizophrenia. The beneficial effect of amisulpride augmentation of clozapine therapy for such patients may be enhanced by its anti-salivatory effect on CIS. Current series of five subjects who developed CIS that responded poorly to anticholinergic drugs found drastic improvement in daytime and nocturnal CIS with very low-dose (50-100 mg/day) of amisulpride. Low-dose amisulpride augmentation may also provide strong ameliorating effect on CIS. Nevertheless, a long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time. PMID:26702180

  2. 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. PMID:25469781

  3. Evaluation of low-dose irradiation on microbiological quality of white carrots and string beans

    NASA Astrophysics Data System (ADS)

    Koike, Amanda C. R.; Santillo, Amanda G.; Rodrigues, Flávio T.; Duarte, Renato C.; Villavicencio, Anna Lucia C. H.

    2012-08-01

    The minimally processed food provided the consumer with a product quality, safety and practicality. However, minimal processing of food does not reduce pathogenic population of microorganisms to safe levels. Ionizing radiation used in low doses is effective to maintain the quality of food, reducing the microbiological load but rather compromising the nutritional values and sensory property. The association of minimal processing with irradiation could improve the quality and safety of product. The purpose of this study was to evaluate the effectiveness of low-doses of ionizing radiation on the reduction of microorganisms in minimally processed foods. The results show that the ionizing radiation of minimally processed vegetables could decontaminate them without several changes in its properties.

  4. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

    PubMed

    Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Van Wettere, Arnaud J; Jung, Kie-Hoon; Dagley, Ashley; Wandersee, Luci; Downs, Brittney; Smee, Donald F; Furuta, Yousuke; Bray, Mike; Gowen, Brian B

    2016-02-01

    Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin. PMID:26711718

  5. Acute necrotising pancreatitis derived from low-dose corticosteroid use: an important reminder of clinical management.

    PubMed

    Sabre, Alexander; Guthrie, Morgan Mary; Maleknia, Reza

    2015-01-01

    Although the exact mechanism is unknown, incidence of drug-induced pancreatitis from corticosteroids is well established in the medical literature. Commonly reported in chronic steroid-dependent individuals who require large doses for a wide array of pathologies, the incidence of damage to the pancreas from low-doses have not been well described. We report a case of a 68-year-old woman who presented with severe abdominal pain, nausea and vomiting, 3 days after the initiation of low-dose methylprednisolone for osteoarthritis. Inpatient laboratory analysis revealed an elevated lipase of 1770 U/L and CT scan showing extensive necrotising pancreatitis involving the head, body and tail. Cessation of the causative medication and conservative treatment successfully led to resolution of symptoms. We present this case to inform clinicians of the precipitance of pancreatitis from modest strength corticosteroid management, so that more accurate and improved performance in pharmacological decisions can be made for patient care. PMID:26150628

  6. Towards robust deconvolution of low-dose perfusion CT: sparse perfusion deconvolution using online dictionary learning.

    PubMed

    Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C

    2013-05-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

  7. An automated system for lung nodule detection in low-dose computed tomography

    NASA Astrophysics Data System (ADS)

    Gori, I.; Fantacci, M. E.; Preite Martinez, A.; Retico, A.

    2007-03-01

    A computer-aided detection (CAD) system for the identification of pulmonary nodules in low-dose multi-detector helical Computed Tomography (CT) images was developed in the framework of the MAGIC-5 Italian project. One of the main goals of this project is to build a distributed database of lung CT scans in order to enable automated image analysis through a data and cpu GRID infrastructure. The basic modules of our lung-CAD system, a dot-enhancement filter for nodule candidate selection and a neural classifier for false-positive finding reduction, are described. The system was designed and tested for both internal and sub-pleural nodules. The results obtained on the collected database of low-dose thin-slice CT scans are shown in terms of free response receiver operating characteristic (FROC) curves and discussed.

  8. Warfarin and low-dose aspirin for stroke prevention from severe intracranial stenosis.

    PubMed

    Bekavac, I; Hanna, J P; Sila, C A; Furland, A J

    1999-01-01

    Management of symptomatic, intracranial, large-arterial atherosclerosis is controversial. We assessed the safety and efficacy of combining warfarin and low-dose aspirin to prevent stroke from intracranial atherosclerotic stenosis failing prior treatment with either aspirin or warfarin. Patients with severe intracranial stenosis were prescribed combination therapy, warfarin (international normalized ratio [INR] 2 to 3) and aspirin 81 mg daily. Ten men and six women treated with combination therapy had one recurrent ischemic event during 382 months of therapy. No patient suffered a myocardial infarction or sudden vascular death. No serious hemorrhagic complication occurred. The combination of warfarin and low-dose aspirin seems safe and effective in preventing recurrent stroke from symptomatic, intracranial, large-arterial occlusive disease after failure with either aspirin or warfarin monotherapy. PMID:17895135

  9. [Treatment of postmenopausal osteoporosis with low doses of calcitonin and a calcitonin-anabolic combination].

    PubMed

    Szücs, J; Horváth, C; Kollin, E; Szathmári, M; Holló, I

    1992-06-01

    Menopausal osteoporotic women (age: 49-69, mean: 59.5 years) with crush fractures of the spine were treated with low doses of calcitonin (Miacalcic, 350 U/month), or with calcitonin + anabolic steroid (Retabolil, 50 mg/month). Efficacy of the therapy was controlled by single foton absorptiometry of midshaft and distal radius, by X-ray morphometry and by registering new crush fractures of the spine. Calcitonin monotherapy stopped further bone loss for two years, but at the end of the third year both absorptiometric values, as well as the radiomorphometrical index of the lumbar spine decreased significantly. In patients on calcitonin+anabolic steroid the decrease was just significant and only at radius midshaft, while at the other measured sites it was not. Two new crush fractures per 1396 patient-months occurred. Intermittent administration of low-dose calcitonin, especially together with an anabolic steroid seems to be a safe and effective therapy in established osteoporosis. PMID:1603585

  10. Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

    PubMed Central

    Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.

    2014-01-01

    Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

  11. [Low dose vasopressin is effective for catecholamine-resistant hypotension after resection of pheochromocytoma].

    PubMed

    Kanazawa, Shinya; Uehara, Naoko; Seo, Hideya; Miyawaki, Ikuko; Yamazaki, Kazuo

    2013-10-01

    The perioperative management of pheochromocytoma is challenging for anesthesiologists and persistent hypotension secondary to cathecholamine depletion after tumor resection can be refractory to treatment. A 64-year-old man underwent right adrenalectomy for treatment of massive pheochromocytoma. Doxazosin administration was started and increased gradually to 12 mg daily. He was premedicated with doxazosin on the day of the surgery. Induction was uneventful but there was a sudden increase of blood pressure with tachycardia on handling of tumor which was controlled by intravenous remifentanil, landiolol, diltiazem, and magnesium sulfate. With dissection of the tumor, the blood pressure dropped to 65/40 mmHg, which was resistant to fluid and cathecholamine treatment. After commencement of low dose vasopressin administration (two boluses of 0.08 U followed by 1.6 U x hr(-1)), blood pressure gradually recovered to normal ranges. Low dose vasopressin can be safely used to treat postadrenalectomy hypotension and also can reduce the cathecholamine dose. PMID:24228460

  12. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    NASA Technical Reports Server (NTRS)

    Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

    2002-01-01

    Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

  13. Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH

    PubMed Central

    Oliu, Carlos J.; Bagci, Ahmet M.; Lee, Sang H.; Kovanlikaya, Ilhami; Adams, David; Katzen, Heather; Ivkovic, Milos; Heier, Linda; Relkin, Norman

    2014-01-01

    Objective: To assess the effects of low-dose acetazolamide treatment on volumetric MRI markers and clinical outcome in idiopathic normal-pressure hydrocephalus (iNPH). Methods: We analyzed MRI and gait measures from 8 patients with iNPH with serial MRIs from an institutional review board–approved imaging protocol who had been treated off-label with low-dose acetazolamide (125–375 mg/day). MRI studies included fluid-attenuated inversion recovery and 3D T1-weighted high-resolution imaging. Automated analyses were employed to quantify each patient's ventricular, global white matter hyperintensities (WMH), and periventricular WMH (PVH) volumes prior to and throughout treatment. Clinical outcome was based on gait changes assessed quantitatively using the Boon scale. Results: Five of 8 patients responded positively to treatment, with median gait improvement of 4 points on the Boon scale. A significant decrease in PVH volume (−6.1 ± 1.9 mL, p = 0.002) was seen in these patients following treatment. One patient's gait was unchanged and 2 patients demonstrated worsened gait and were referred for shunt surgery. No reduction in PVH volume was detected in the latter 2 patients. Nonperiventricular WMH and lateral ventricle volumes remained largely unchanged in all patients. Conclusions: These preliminary findings provide new evidence that low-dose acetazolamide can reduce PVH and may improve gait in iNPH. PVH volume, reflecting transependymal CSF, is shown to be a potential MRI indicator of pharmacologic intervention effectiveness. Further studies of pharmacologic treatment of iNPH are needed and may be enhanced by incorporating quantitative MRI outcomes. Classification of evidence: This study provides Class IV evidence that low-dose acetazolamide reverses PVH volume and, in some cases, improves gait in iNPH. PMID:24634454

  14. Low-dose effects of bisphenol A on mammary gland development in rats.

    PubMed

    Mandrup, K; Boberg, J; Isling, L K; Christiansen, S; Hass, U

    2016-07-01

    Bisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because of small number of animals or few doses investigated these data have not been used by EFSA as point of departure for the newly assessed tolerable daily intake (TDI). We performed a study with perinatal exposure to BPA (0, 0.025, 0.25, 5, and 50 mg/kg bw/day) in rats (n = 22 mated/group). One of the aims was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose-response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg/kg BPA, indicating an increased mammary development at this low dose only. Increased prevalence of intraductal hyperplasia was observed in BPA females exposed to 0.25 mg/kg at PD 400, but not at PD 100, and not at higher or lower doses. The present findings support data from the published literature showing that perinatal exposure to BPA can induce increased mammary growth and proliferative lesions in rodents. Our results indicate that low-dose exposure to BPA can affect mammary gland development in male and female rats, although higher doses show a different pattern of effects. The observed intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may not be sufficiently protected. PMID:27088260

  15. Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine.

    PubMed

    Smith, Tracy T; Rupprecht, Laura E; Cwalina, Samantha N; Onimus, Matthew J; Murphy, Sharon E; Donny, Eric C; Sved, Alan F

    2016-08-01

    The Food and Drug Administration (FDA) has the authority to regulate cigarette smoke constituents, and a reduction in nicotine content might benefit public health by reducing the prevalence of smoking. Research suggests that cigarette smoke constituents that inhibit monoamine oxidase (MAO) may increase the reinforcing value of low doses of nicotine. The aim of the present experiments was to further characterize the impact of MAO inhibition on the primary reinforcing and reinforcement enhancing effects of nicotine in rats. In a series of experiments, rats responded for intravenous nicotine infusions or a moderately-reinforcing visual stimulus in daily 1-h sessions. Rats received pre-session injections of known MAO inhibitors. The results show that (1) tranylcypromine (TCP), a known MAO inhibitor, increases sensitivity to the primary reinforcing effects of nicotine, shifting the dose-response curve for nicotine to the left, (2) inhibition of MAO-A, but not MAO-B, increases low-dose nicotine self-administration, (3) partial MAO-A inhibition, to the degree observed in chronic cigarette smokers, also increases low-dose nicotine self-administration, and (4) TCP decreases the threshold nicotine dose required for reinforcement enhancement. The results of the present experiments suggest cigarette smoke constituents that inhibit MAO-A, in the range seen in chronic smokers, are likely to increase the primary reinforcing and reinforcement enhancing effects of low doses of nicotine. If the FDA reduces the nicotine content of cigarettes, then variability in constituents that inhibit MAO-A could impact smoking. PMID:26955970

  16. Theoretical explanation of enhanced low dose rate sensitivity in erbium-doped optical fibers.

    PubMed

    Gilard, Olivier; Thomas, Jérémie; Troussellier, Laurent; Myara, Mikhael; Signoret, Philippe; Burov, Ekaterina; Sotom, Michel

    2012-05-01

    A new theoretical framework is proposed to explain the dose and dose-rate dependence of radiation-induced absorption in optical fibers. A first-order dispersive kinetics model is used to simulate the growth of the density of color centers during an irradiation. This model succeeds in explaining the enhanced low dose rate sensitivity observed in certain kinds of erbium-doped optical fiber and provides some insight into the physical reasons behind this sensitivity. PMID:22614396

  17. Low-dose photons modify liver response to simulated solar particle event protons.

    PubMed

    Gridley, Daila S; Coutrakon, George B; Rizvi, Asma; Bayeta, Erben J M; Luo-Owen, Xian; Makinde, Adeola Y; Baqai, Farnaz; Koss, Peter; Slater, James M; Pecaut, Michael J

    2008-03-01

    The health consequences of exposure to low-dose radiation combined with a solar particle event during space travel remain unresolved. The goal of this study was to determine whether protracted radiation exposure alters gene expression and oxidative burst capacity in the liver, an organ vital in many biological processes. C57BL/6 mice were whole-body irradiated with 2 Gy simulated solar particle event (SPE) protons over 36 h, both with and without pre-exposure to low-dose/low-dose-rate photons ((57)Co, 0.049 Gy total at 0.024 cGy/h). Livers were excised immediately after irradiation (day 0) or on day 21 thereafter for analysis of 84 oxidative stress-related genes using RT-PCR; genes up or down-regulated by more than twofold were noted. On day 0, genes with increased expression were: photons, none; simulated SPE, Id1; photons + simulated SPE, Bax, Id1, Snrp70. Down-regulated genes at this same time were: photons, Igfbp1; simulated SPE, Arnt2, Igfbp1, Il6, Lct, Mybl2, Ptx3. By day 21, a much greater effect was noted than on day 0. Exposure to photons + simulated SPE up-regulated completely different genes than those up-regulated after either photons or the simulated SPE alone (photons, Cstb; simulated SPE, Dctn2, Khsrp, Man2b1, Snrp70; photons + simulated SPE, Casp1, Col1a1, Hspcb, Il6st, Rpl28, Spnb2). There were many down-regulated genes in all irradiated groups on day 21 (photons, 13; simulated SPE, 16; photons + simulated SPE, 16), with very little overlap among groups. Oxygen radical production by liver phagocytes was significantly enhanced by photons on day 21. The results demonstrate that whole-body irradiation with low-dose-rate photons, as well as time after exposure, had a great impact on liver response to a simulated solar particle event. PMID:18302490

  18. Ventilatory effects of low-dose paraoxon result from central muscarinic effects

    SciTech Connect

    Houze, Pascal; Pronzola, Laetita; Kayouka, Maya; Villa, Antoine; Debray, Marcel; Baud, Frederic J.

    2008-12-01

    Paraoxon induces respiratory toxicity. Atropine completely reversed parathion- and paraoxon-induced respiratory toxicity. The aim of this study was to assess the peripheral or central origin of ventilatory effects of low-dose paraoxon. Male Sprague-Dawley rats were given paraoxon 0.215 mg/kg subcutaneously and treated with either atropine (10 mg/kg sc) or ascending doses of methylatropine of 5.42 (equimolar to that of atropine), 54.2, and 542 mg/kg administered subcutaneously 30 min after paraoxon. Ventilation at rest was assessed using whole-body plethysmography and rat temperature using infra-red telemetry. Results are expressed as mean {+-} SE. Statistical analysis used two-way ANOVA for repeated measurements. Paraoxon induced a significant decrease in temperature 30 min after injection lasting the 90 min of the study period. This effect was partially corrected by atropine, but not by methylatropine whatever the dose. Paraoxon induced a decrease in respiratory rate resulting from an increase in expiratory time associated with an increase in tidal volume. Atropine completely reversed the ventilatory effects of low-dose paraoxon while the equimolar dose of methylatropine had no significant effects. The 54.2 and 542 mg/kg doses of methylatropine had no significant effects. Atropine crosses the blood-brain barrier and reverses peripheral and central muscarinic effects. In contrast, methylatropine does not cross the blood-brain barrier. Atropine completely reversed the ventilatory effects of low-dose paraoxon, while methylatropine had no significant effects at doses up to 100-fold the equimolar dose of atropine. We conclude that the ventilatory effects of low-dose paraoxon are mediated by disrupted muscarinic signaling in the central nervous system.

  19. The road to linearity: why linearity at low doses became the basis for carcinogen risk assessment.

    PubMed

    Calabrese, Edward J

    2009-03-01

    This article assesses the historical foundations of how linearity at low dose became accepted by the scientific/regulatory communities. While the threshold model was used in the 1920s/1930s in establishing radiation health standards, its foundations were challenged by the genetics community who argued that radiation induced mutations in reproductive cells followed a linear response, were cumulative and deleterious. Scientific foundations of linearity for gonadal mutations were based on non-conclusive evidence as well as not being conducted at low doses. Following years of debate, leaders in the genetics community participated in the U.S. National Academy of Sciences (NAS) (1956) Biological Effects of Atomic Radiation (BEAR) BEAR I Committee, getting their perspectives accepted, incorporating linearity for radiation-induced mutational effects in risk assessment. Overtime the concept of linearity was generalized to include somatic effects induced by radiation based on a protectionist philosophy. This affected the course of radiation-induced and later chemically-induced carcinogen risk assessment. Acceptance of linearity at low dose from chemical carcinogens was strongly influenced by the NAS Safe Drinking Water Committee report of 1977 which provided the critical guidance to the U.S. EPA to adopt linear at low dose modeling for risk assessment for chemical carcinogens with little supportive data, much of which has been either discredited or seriously weakened over the past 3 decades. Nonetheless, there has been little practical change of regulatory policy concerning carcinogen risk assessment. These observations suggest that while scientific disciplines are self correcting, that regulatory 'science' fails to display the same self-correcting mechanism despite contradictory data. PMID:19247635

  20. Resource Letter EIRLD-2: Effects of Ionizing Radiation at Low Doses

    NASA Astrophysics Data System (ADS)

    Wilson, Richard

    2012-04-01

    This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer, and non-cancer outcomes), effects of dose rate, relationship to background, supra linearity and hormesis, and policy implications.

  1. Resource Letter EIRLD-1: Effects of ionizing radiation at low doses

    NASA Astrophysics Data System (ADS)

    Wilson, Richard

    1999-05-01

    This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books, and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer and noncancer outcomes), effects of dose rate, relationship to background, supra linearity and homesis, and policy implications.

  2. The biobehavioral and neuroimmune impact of low-dose ionizing radiation

    PubMed Central

    York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

    2011-01-01

    In the clinical setting, repeated exposures (10–30) to low-doses of ionizing radiation (≤ 200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 h and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. PMID:21958477

  3. Inconsistencies and open questions regarding low-dose health effects of ionizing radiation.

    PubMed Central

    Nussbaum, R H; Köhnlein, W

    1994-01-01

    The effects on human health of exposures to ionizing radiation at low doses have long been the subject of dispute. In this paper we focus on open questions regarding the health effects of low-dose exposures that require further investigations. Seemingly contradictory findings of radiation health effects have been reported for the same exposed populations, or inconsistent estimates of radiation risks were found when different populations and exposure conditions were compared. Such discrepancies may be indicative of differences in sensitivities among the applied methods of epidemiological analysis or indicative of significant discrepancies in health consequences after comparable total exposures of different populations under varying conditions. We focus first on inconsistencies and contradictions in presentations of the state of knowledge by different authoritative experts. We then review studies that found positive associations between exposure and risks in dose ranges where traditional notions (generalized primarily from high-dose studies of A-bomb survivors or exposed animals) would have predicted negligible effects. One persistent notion in many reviews of low-dose effects is the hypothesis of reduced biological effectiveness of fractionated low-dose exposures, compared to that of the same acute dose. This assumption is not supported by data on human populations. From studies of populations that live in contaminated areas, more and more evidence is accumulating on unusual rates of various diseases other than radiation-induced malignancies, health effects that are suspected to be associated with relatively low levels of internal exposures originating from radioactive fallout. Such effects include congenital defects, neonatal mortality, stillbirths, and possibly genetically transmitted disease. A range of open questions challenges scientists to test imaginative hypotheses about induction of disease by radiation with novel research strategies. Images Figure 1. PMID

  4. Effects of Low Doses of Bisphenol A on the Metabolome of Perinatally Exposed CD-1 Mice

    PubMed Central

    Cabaton, Nicolas J.; Canlet, Cécile; Wadia, Perinaaz R.; Tremblay-Franco, Marie; Gautier, Roselyne; Molina, Jérôme; Sonnenschein, Carlos; Cravedi, Jean-Pierre; Rubin, Beverly S.; Soto, Ana M.

    2013-01-01

    Background: Bisphenol A (BPA) is a well-known endocrine disruptor used to manufacture polycarbonate plastics and epoxy resins. Exposure of pregnant rodents to low doses of BPA results in pleiotropic effects in their offspring. Objective: We used metabolomics—a method for determining metabolic changes in response to nutritional, pharmacological, or toxic stimuli—to examine metabolic shifts induced in vivo by perinatal exposure to low doses of BPA in CD-1 mice. Methods: Male offspring born to pregnant CD-1 mice that were exposed to vehicle or to 0.025, 0.25, or 25 µg BPA/kg body weight/day, from gestation day 8 through day 16 of lactation, were examined on postnatal day (PND) 2 or PND21. Aqueous extracts of newborns (PND2, whole animal) and of livers, brains, and serum samples from PND21 pups were submitted to 1H nuclear magnetic resonance spectroscopy. Data were analyzed using partial least squares discriminant analysis. Results: Examination of endogenous metabolic fingerprints revealed remarkable discrimination in whole extracts of the four PND2 newborn treatment groups, strongly suggesting changes in the global metabolism. Furthermore, statistical analyses of liver, serum, and brain samples collected on PND21 successfully discriminated among treatment groups. Variations in glucose, pyruvate, some amino acids, and neurotransmitters (γ-aminobutyric acid and glutamate) were identified. Conclusions: Low doses of BPA disrupt global metabolism, including energy metabolism and brain function, in perinatally exposed CD-1 mouse pups. Metabolomics can be used to highlight the effects of low doses of endocrine disruptors by linking perinatal exposure to changes in global metabolism. PMID:23425943

  5. Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice.

    PubMed

    Chandler, Joshua D; Wongtrakool, Cherry; Banton, Sophia A; Li, Shuzhao; Orr, Michael L; Barr, Dana Boyd; Neujahr, David C; Sutliff, Roy L; Go, Young-Mi; Jones, Dean P

    2016-07-01

    Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades-long half-life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low-dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans. Cd-treated mice had increased airway hyperresponsiveness to methacholine challenge, and gene expression array showed that Cd altered the abundance of 443 mRNA transcripts in mouse lung. In contrast to higher doses, low-dose Cd did not elicit increased metallothionein transcripts in lung. To identify pathways most affected by Cd, gene set enrichment of transcripts was analyzed. Results showed that major inducible targets of low-dose Cd were neuronal receptors represented by enriched olfactory, glutamatergic, cholinergic, and serotonergic gene sets. Olfactory receptors regulate chemosensory function and airway hypersensitivity, and these gene sets were the most enriched. Targeted metabolomics analysis showed that Cd treatment also increased metabolites in pathways of glutamatergic (glutamate), serotonergic (tryptophan), cholinergic (choline), and catecholaminergic (tyrosine) receptors in the lung tissue. Protein abundance measurements showed that the glutamate receptor GRIN2A was increased in mouse lung tissue. Together, these results show that in mice, oral low-dose Cd increased lung Cd to levels comparable to humans, increased airway hyperresponsiveness and disrupted neuronal pathways regulating bronchial tone. Therefore, dietary Cd may promote or worsen airway hyperresponsiveness in multiple lung diseases including asthma. PMID:27401458

  6. Low-Dose Isotretinoin: An Option for Difficult-to-Treat Papulopustular Rosacea.

    PubMed

    van Zuuren, Esther J; Fedorowicz, Zbys

    2016-06-01

    Rosacea is a chronic disease with a profound impact on quality of life. Although there are a range of treatments for its many manifestations, some cases are difficult to treat. Sbidian et al. show in this double-blind, randomized, placebo-controlled trial that low-dose isotretinoin can be effective in treating difficult-to-treat and frequently relapsing papulopustular rosacea. PMID:27212646

  7. The biobehavioral and neuroimmune impact of low-dose ionizing radiation.

    PubMed

    York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

    2012-02-01

    In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (≤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. PMID:21958477

  8. Effects of chronic low dose rotenone treatment on human microglial cells

    PubMed Central

    2009-01-01

    Background Exposure to toxins/chemicals is considered to be a significant risk factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is the naturally occurring herbicide rotenone that is now used widely in establishing PD models. We, and others, have shown that chronic low dose rotenone treatment induces excessive accumulation of Reactive Oxygen Species (ROS), inclusion body formation and apoptosis in dopaminergic neurons of animal and human origin. Some studies have also suggested that microglia enhance the rotenone induced neurotoxicity. While the effects of rotenone on neurons are well established, there is little or no information available on the effect of rotenone on microglial cells, and especially cells of human origin. The aim of the present study was to investigate the effects of chronic low dose rotenone treatment on human microglial CHME-5 cells. Methods We have shown previously that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y cells and therefore used these cells as a control for inclusion body formation in this study. SH-SY5Y and CHME-5 cells were treated with 5 nM rotenone for four weeks. At the end of week 4, both cell types were analysed for the presence of inclusion bodies, superoxide dismutases and cell activation (only in CHME-5 cells) using Haematoxylin and Eosin staining, immunocytochemical and western blotting methods. Levels of active caspases and ROS (both extra and intra cellular) were measured using biochemical methods. Conclusion The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others. However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low

  9. Why we need new approaches to low-dose risk modeling

    SciTech Connect

    Alvarez, J.L.; Seiler, F.A.

    1996-06-01

    The linear no-threshold model for radiation effects was introduced as a conservative model for the design of radiation protection programs. The model has persisted not only as the basis for such programs, but has come to be treated as a dogma and is often confused with scientific fact. In this examination a number of serious problems with the linear no-threshold model of radiation carcinogenesis were demonstrated, many of them invalidating the hypothesis. It was shown that the relative risk formalism did not approach 1 as the dose approaches zero. When morality ratios were used instead, the data in the region below 0.3 Sv were systematically below the predictions of the linear model. It was also shown that the data above 0.3 Sv were of little use in formulating a model at low doses. In addition, these data are valid only for doses accumulated at high dose rates, and there is no scientific justification for using the model in low-dose, low-dose-rate extrapolations for purposes of radiation protection. Further examination of model fits to the Japanese survivor data were attempted. Several such models were fit to the data including an unconstrained linear, linear-square root, and Weibull, all of which fit the data better than the relative risk, linear no-threshold model. These fits were used to demonstrate that the linear model systematically over estimates the risk at low doses in the Japanese survivor data set. It is recommended here that an unbiased re-analysis of the data be undertaken and the results used to construct a new model, based on all pertinent data. This model could then form the basis for managing radiation risks in the appropriate regions of dose and dose rate.

  10. Spectrum of early lung cancer presentation in low-dose screening CT: a pictorial review.

    PubMed

    Rampinelli, Cristiano; Calloni, Sonia Francesca; Minotti, Marta; Bellomi, Massimo

    2016-06-01

    The typical presentation of early stage lung cancers on low-dose CT screening are non-calcified pulmonary nodules. However, there is a wide spectrum of unusual focal abnormalities that can be early presentations of lung cancer. These abnormalities include, for example, cancers associated with 'cystic airspaces' or scar-like cancers. The detection of lung cancer with low-dose CT can be affected by the absence of intravenous contrast medium. As a consequence, endobronchial and central lesions can be difficult to recognize, raising the potential for missed cancers. Focal lesions arising within pre-existing lung disease, such as lung fibrosis or apical scars, can also be early lung cancer manifestations and deserve particular consideration as recognition of these lesions may be hindered by the underlying disease. Furthermore, the unpredictable growth rate of lung cancer, which ranges from indolent to aggressive cancers, necessitates attention to the wide spectrum of progression in lung cancer appearance on serial low-dose CT scans. In this pictorial review we discuss the spectrum of early lung cancer presentation in low-dose CT screening, highlighting typical as well as unusual radiological features and the varied growth rates of early lung cancer. Teaching Points • There is a wide spectrum of early presentations of lung cancer on LDCT. • Low radiation dose and the absence of contrast medium injection can affect lung cancer detection. • Lung cancer growth shows various behaviours, ranging from indolent to aggressive cancers. • Familiarity with LDCT technique can improve CT screening effectiveness and avoid missed diagnosis. PMID:27188380

  11. Radiation-induced apoptosis in SCID Mousespleen after a low-dose irration

    NASA Astrophysics Data System (ADS)

    Ohnishi, T.; Takahashi, A.; Ohnishi, K.

    Purpose: To estimate the effects of space radiation on health of space crews, we aimed to clarify whether pre-irradiation at a low-dose interferes in a p53-centered signal transduction pathway induced by radiation. By using a severe combined immunodeficiency (Scid) mouse defective DNA-PK activity, we examined the role of DNA-PK activity in radioadaptation induced by low-dose irradiation. Methodology: Specific pathogen free 5-week-old fe male mice of Scid and the parental mice (CB-17 Icr+/+) were irradiated with X-rays at 3.0 Gy 1, 2, 3 or 4 weeks after conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after irradiation. Bax on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method using HISTOFINE SAB-PO(R) kit (Nichirei Co., Tokyo, Japan). Apoptosis incidence in the sections was measured by staining with HE staining. Results: The frequency of Bax- and apoptosis -positive cells increased up to 12 h after irradiation at 3.0 Gy in the spleen of CB-17 Icr+/+ and Scid mice. However, they were not observed by irradiation with low dose at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before challenging acute irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by irradiation at 3.0 Gy was depressed in the spleen of CB-17 Icr+/+ mice, but not Scid mice. Conclusions: These data suggest that DNA-PKcs (expressed in CB-17 Icr+/+, not Scid mice) might play a major role on radioadaptation induced by pre-irradiation at low dose in mice spleen. We expect that the present findings will provide useful information for the care of space crews' health.

  12. Low-dose X-ray CT reconstruction via dictionary learning.

    PubMed

    Xu, Qiong; Yu, Hengyong; Mou, Xuanqin; Zhang, Lei; Hsieh, Jiang; Wang, Ge

    2012-09-01

    Although diagnostic medical imaging provides enormous benefits in the early detection and accuracy diagnosis of various diseases, there are growing concerns on the potential side effect of radiation induced genetic, cancerous and other diseases. How to reduce radiation dose while maintaining the diagnostic performance is a major challenge in the computed tomography (CT) field. Inspired by the compressive sensing theory, the sparse constraint in terms of total variation (TV) minimization has already led to promising results for low-dose CT reconstruction. Compared to the discrete gradient transform used in the TV method, dictionary learning is proven to be an effective way for sparse representation. On the other hand, it is important to consider the statistical property of projection data in the low-dose CT case. Recently, we have developed a dictionary learning based approach for low-dose X-ray CT. In this paper, we present this method in detail and evaluate it in experiments. In our method, the sparse constraint in terms of a redundant dictionary is incorporated into an objective function in a statistical iterative reconstruction framework. The dictionary can be either predetermined before an image reconstruction task or adaptively defined during the reconstruction process. An alternating minimization scheme is developed to minimize the objective function. Our approach is evaluated with low-dose X-ray projections collected in animal and human CT studies, and the improvement associated with dictionary learning is quantified relative to filtered backprojection and TV-based reconstructions. The results show that the proposed approach might produce better images with lower noise and more detailed structural features in our selected cases. However, there is no proof that this is true for all kinds of structures. PMID:22542666

  13. Low-dose ionising radiation and cardiovascular diseases--Strategies for molecular epidemiological studies in Europe.

    PubMed

    Kreuzer, Michaela; Auvinen, Anssi; Cardis, Elisabeth; Hall, Janet; Jourdain, Jean-Rene; Laurier, Dominique; Little, Mark P; Peters, Annette; Raj, Ken; Russell, Nicola S; Tapio, Soile; Zhang, Wei; Gomolka, Maria

    2015-01-01

    It is well established that high-dose ionising radiation causes cardiovascular diseases. In contrast, the evidence for a causal relationship between long-term risk of cardiovascular diseases after moderate doses (0.5-5 Gy) is suggestive and weak after low doses (<0.5 Gy). However, evidence is emerging that doses under 0.5 Gy may also increase long-term risk of cardiovascular disease. This would have major implications for radiation protection with respect to medical use of radiation for diagnostic purposes and occupational or environmental radiation exposure. Therefore, it is of great importance to gain information about the presence and possible magnitude of radiation-related cardiovascular disease risk at doses of less than 0.5 Gy. The biological mechanisms implicated in any such effects are unclear and results from epidemiological studies are inconsistent. Molecular epidemiological studies can improve the understanding of the pathogenesis and the risk estimation of radiation-induced circulatory disease at low doses. Within the European DoReMi (Low Dose Research towards Multidisciplinary Integration) project, strategies to conduct molecular epidemiological studies in this field have been developed and evaluated. Key potentially useful European cohorts are the Mayak workers, other nuclear workers, uranium miners, Chernobyl liquidators, the Techa river residents and several diagnostic or low-dose radiotherapy patient cohorts. Criteria for informative studies are given and biomarkers to be investigated suggested. A close collaboration between epidemiology, biology and dosimetry is recommended, not only among experts in the radiation field, but also those in cardiovascular diseases. PMID:26041268

  14. Responses of the Rat Basal Ganglia Neurotensin Systems to Low Doses of Methamphetamine

    PubMed Central

    Alburges, Mario E.; Hoonakker, Amanda J.; Cordova, Nathaniel M.; Robson, Christina M.; McFadden, Lisa M.; Martin, Amber L.; Hanson, Glen R.

    2014-01-01

    Rationale Administration of high doses of methamphetamine (METH) in a manner mimicking the bingeing patterns associated with abuse, reduces NT release and causes its accumulation and elevated NT levels in extrapyramidal structures by a D1 mechanism. The relevance of these findings to the therapeutic use of METH needs to be studied. Objectives The effect of low doses (comparable to that used for therapy) of METH on basal ganglia NT systems was examined and compared to high-dose and self-administration effects previously reported. Methods Rats were injected four times (2-h intervals) with either saline or low doses of METH (0.25, 0.50 or 1.00 mg/kg/s.c.). For the DA antagonist studies, animals were pretreated with a D1 (SCH23390) or D2 (eticlopride) antagonist 15 min prior to METH or saline treatments. Rats were sacrificed 5–48 h after last injection. Results METH at doses of 0.25 and 0.50, but not 1.00 mg/kg rapidly and briefly decreased NTLI concentration in all basal ganglia structures studied. In the posterior dorsal striatum, the reduction in NT level after low-dose METH appeared to be caused principally by D2 stimulation, but both D2 and D1 stimulation were required for the NT responses in the other basal ganglia regions. Conclusions A novel finding from the present study was that opposite to abuse-mimicking high doses of METH, the therapeutically relevant low-dose METH treatment reduced NT tissue levels likely reflecting an increase in NT release and a short-term depletion of the levels of this neuropeptide in basal ganglia structures. The possible significance is discussed. PMID:24522333

  15. Low-dose radiation, scientific scrutiny, and requirements for demonstrating effects.

    PubMed

    Møller, Anders Pape; Mousseau, Timothy Alexander

    2013-01-01

    Recent nuclear accidents have prompted renewed interest in the fitness consequences of low-dose radiation. Hiyama et al. provided information on such effects in the Japanese pale grass blue butterfly in a paper that has been viewed more than 300,000 times, prompting a barrage of criticism. These exchanges highlight the role of scrutiny in studies with potential effects on humans, but also raise questions about minimum requirements for demonstrating biological effects. PMID:23987799

  16. [Successful treatment of panarteritis nodosa with low-dose methotrexate therapy].

    PubMed

    Brody, M; Böhm, I; Biwer, E; Bauer, R

    1994-07-01

    We report on a 45-year-old male patient who presented a classic polyarteritis nodosa (PAN). The clinical course extended over 7 years. In spite of 2 years immunosuppressive therapy with azathioprine and methylprednisolone the course was progressive. Low-dose methotrexate therapy was the only treatment that controlled the disease, leading to rapid clinical and histopathological remission. In low concentrations methotrexate acts as an IL-1 inhibitor, and it obviously suppresses the pathogenetic mechanism of PAN. PMID:7928343

  17. Low-Dose X-ray CT Reconstruction via Dictionary Learning

    PubMed Central

    Xu, Qiong; Zhang, Lei; Hsieh, Jiang; Wang, Ge

    2013-01-01

    Although diagnostic medical imaging provides enormous benefits in the early detection and accuracy diagnosis of various diseases, there are growing concerns on the potential side effect of radiation induced genetic, cancerous and other diseases. How to reduce radiation dose while maintaining the diagnostic performance is a major challenge in the computed tomography (CT) field. Inspired by the compressive sensing theory, the sparse constraint in terms of total variation (TV) minimization has already led to promising results for low-dose CT reconstruction. Compared to the discrete gradient transform used in the TV method, dictionary learning is proven to be an effective way for sparse representation. On the other hand, it is important to consider the statistical property of projection data in the low-dose CT case. Recently, we have developed a dictionary learning based approach for low-dose X-ray CT. In this paper, we present this method in detail and evaluate it in experiments. In our method, the sparse constraint in terms of a redundant dictionary is incorporated into an objective function in a statistical iterative reconstruction framework. The dictionary can be either predetermined before an image reconstruction task or adaptively defined during the reconstruction process. An alternating minimization scheme is developed to minimize the objective function. Our approach is evaluated with low-dose X-ray projections collected in animal and human CT studies, and the improvement associated with dictionary learning is quantified relative to filtered backprojection and TV-based reconstructions. The results show that the proposed approach might produce better images with lower noise and more detailed structural features in our selected cases. However, there is no proof that this is true for all kinds of structures. PMID:22542666

  18. Combination therapy with finasteride and low-dose dutasteride in the treatment of androgenetic alopecia.

    PubMed

    Boyapati, Ann; Sinclair, Rodney

    2013-02-01

    We report on a 47-year-old man who was initially treated with finasteride for androgenetic alopecia. Despite continuous treatment, after year 4 his hair density was not as good as at year 2, and low-dose dutasteride at 0.5 mg/week was added to the finasteride therapy. This resulted in a dramatic increase in his hair density, demonstrating that combined therapy with finasteride and dutasteride can improve hair density in patients already taking finasteride. PMID:22686691

  19. 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.

    2015-05-01

    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 hr). 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 were measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 were 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.

  20. Early onset life-threatening myelosuppression after low dose of intravesical thiotepa

    PubMed Central

    Agnelli, Giancarlo; Gresele, Paolo; de Cunto, Maria; del Favero, Albano

    1982-01-01

    Intravesical instillation of thiotepa is a popular treatment for localized bladder carcinoma. The drug can enter the systemic circulation, and such absorption may be enhanced by extensive tumour infiltration or by a recent tumour resection. A case is reported of early onset life-threatening pancytopenia following an unusually low dose of the drug in a patient who had undergone a recent tumour resection. PMID:6812036

  1. [The effect of extremely low doses of the novel regulatory plant proteins ].

    PubMed

    Krasnov, M S; Margasiuk, D V; Iamskov, I A; Iamskova, V P

    2003-01-01

    Searching and study on regulatory proteins, which can keep under control the scope of important processes as like as cell adhesion, proliferation, differentiation and morphogenesis, is an actual aim of the current biochemistry. Recently we have identified S-100 proteins in plants of following species: plantain (Plantago major L.), aloe (Aloe arborescens L.), and bilberry (Vaccinum myrtillus L.). Extraction and purification of S-100 proteins gotten from these plants were performed by the method we developed earlier for adhesion proteins of animal tissues. Homogeneity of the studied plant proteins was evaluated and confirmed by HPLC and SDS-electrophoresis in PAAG. Both, plant and animal proteins have appeared to be biologically active at extremely low doses. The tests were performed by adhesiometrical method in short-term tissue culture of mouse's liver in vitro. As a result it was established that the plant proteins insert a membranotropic effect being added in extremely low doses, corresponding to 10(-10)-10(-13) mg/ml. Keeping in mind that the plantain is well known remedy for wound protection and healing, in several experiments we studied the biological effect of plant S-100 proteins on animal cells. It was found that S-100 proteins obtained from plantain influences proliferation of human fibroblasts in vitro. It was found that after the treatment with this protein in low doses the cell growth rate increases essentially. PMID:12881977

  2. Automated segmentation of cardiac visceral fat in low-dose non-contrast chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2015-03-01

    Cardiac visceral fat was segmented from low-dose non-contrast chest CT images using a fully automated method. Cardiac visceral fat is defined as the fatty tissues surrounding the heart region, enclosed by the lungs and posterior to the sternum. It is measured by constraining the heart region with an Anatomy Label Map that contains robust segmentations of the lungs and other major organs and estimating the fatty tissue within this region. The algorithm was evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets. Based on visual inspection, 343 cases had good cardiac visceral fat segmentation. For quantitative evaluation, manual markings of cardiac visceral fat regions were made in 3 image slices for 45 low-dose scans and the Dice similarity coefficient (DSC) was computed. The automated algorithm achieved an average DSC of 0.93. Cardiac visceral fat volume (CVFV), heart region volume (HRV) and their ratio were computed for each case. The correlation between cardiac visceral fat measurement and coronary artery and aortic calcification was also evaluated. Results indicated the automated algorithm for measuring cardiac visceral fat volume may be an alternative method to the traditional manual assessment of thoracic region fat content in the assessment of cardiovascular disease risk.

  3. Proteomic Analysis of Low Dose Arsenic and Ionizing Radiation Exposure on Keratinocytes

    PubMed Central

    Berglund, Susanne R.; Santana, Alison R.; Li, Dan; Rice, Robert H.; Rocke, David M.; Goldberg, Zelanna

    2008-01-01

    Human exposure to arsenic and ionizing radiation occur environmentally at low levels. While the human health effects of arsenic and ionizing radiation have been examined separately, there is little information regarding their combined effects at doses approaching environmental levels. Arsenic toxicity may be affected by concurrent ionizing radiation especially given their known individual carcinogenic actions at higher doses. We found that keratinocytes responded to either low dose arsenic and/or low dose ionizing radiation exposure, resulting in differential proteomic expression based on 2DGE, immunoblotting and statistical analysis. Seven proteins were identified that passed a rigorous statistical screen for differential expression in 2DGE and also passed a strict statistical screen for follow-up immunoblotting. These included: α-enolase, epidermal-fatty acid binding protein, heat shock protein 27, histidine triad nucleotide-binding protein 1, lactate dehydrogenase A, protein disulfide isomerase precursor and S100A9. Four proteins had combined effects that were different than would be expected based on the response to either individual toxicant. These data demonstrate a possible reaction to the combined insult that is substantially different from that of either separate treatment. Several proteins had different responses than what has been seen from high dose exposures, adding to the growing literature suggesting that the cellular responses to low dose exposures are distinct. PMID:19294697

  4. Treatment of Severe Alopecia Areata: Combination Therapy Using Systemic Cyclosporine A with Low Dose Corticosteroids

    PubMed Central

    Lee, Deborah; Oh, Doo Jin; Kim, Jung Wook; Park, Sung Wook; Oh, Min Kyung; Sung, Ho Suk

    2008-01-01

    Background Combination therapy using cyclosporine A (CsA) together with low-dose corticosteroids has adequate efficacy with little toxicity for the treatment of severe alopecia areata (AA). Objective We wanted to evaluate the clinical efficacy of combination therapy using CsA with low-dose corticosteroid for the treatment of severe AA and we also wanted to determine the safe therapeutic concentration of CsA in the peripheral blood. Methods We treated 34 cases of severe AA with combination therapy for 24 weeks and we evaluated the efficacy at 12 and 24 weeks. We monitored the peripheral blood concentration of CsA to determine the therapeutic range of CsA that has the fewest side effects. Results Of the patients, 77.4% (n=24) and 22.6% (n=10) were classified in the responder and poor-responder groups, respectively. The mean trough concentration of CsA was 95.1 and 101.2 ng/ml in the responder and poor-responder groups, respectively. For the patients with side effects associated with CsA, the mean CsA concentration was 195.8 ng/ml. Conclusion We found that combination therapy with systemic CsA and low-dose corticosteroids effectively treats severe AA and this therapy results in a safe, therapeutic concentration of CsA in the peripheral blood. PMID:27303186

  5. An optimized colony forming assay for low-dose-radiation cell survival measurement

    SciTech Connect

    Zhu J.; Sutherland B.; Hu W.; Ding N.; Ye C.; Usikalu M.; Li S.; Hu B.; Zhou G.

    2011-11-01

    The aim of this study is to develop a simple and reliable method to quantify the cell survival of low-dose irradiations. Two crucial factors were considered, the same number of cells plated in each flask and an appropriate interval between cell plating and irradiation. For the former, we optimized cell harvest with trypsin, diluted cells in one container, and directly seeded cells on the bottom of flasks in a low density before irradiation. Reproducible plating efficiency was obtained. For the latter, we plated cells on the bottom of flasks and then monitored the processing of attachment, cell cycle variations, and the plating efficiency after exposure to 20 cGy of X-rays. The results showed that a period of 4.5 h to 7.5 h after plating was suitable for further treatment. In order to confirm the reliability and feasibility of our method, we also measured the survival curves of these M059K and M059J glioma cell lines by following the optimized protocol and obtained consistent results reported by others with cell sorting system. In conclusion, we successfully developed a reliable and simple way to measure the survival fractions of human cells exposed to low dose irradiation, which might be helpful for the studies on low-dose radiation biology.

  6. Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension

    PubMed Central

    Schmeisser, Sebastian; Schmeisser, Kathrin; Weimer, Sandra; Groth, Marco; Priebe, Steffen; Fazius, Eugen; Kuhlow, Doreen; Pick, Denis; Einax, Jürgen W; Guthke, Reinhard; Platzer, Matthias; Zarse, Kim; Ristow, Michael

    2013-01-01

    Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending capabilities of arsenite, indicating that transiently increased ROS levels act as transducers of arsenite effects on lifespan, a process known as mitohormesis. This requires two transcription factors, namely DAF-16 and SKN-1, which employ the metallothionein MTL-2 as well as the mitochondrial transporter TIN-9.1 to extend lifespan. Taken together, low-dose arsenite extends lifespan, providing evidence for nonlinear dose-response characteristics of toxin-mediated stress resistance and longevity in a multicellular organism. PMID:23534459

  7. Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

    PubMed Central

    Vaiserman, Alexander M.

    2010-01-01

    Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

  8. Investigation of iterative image reconstruction in low-dose breast CT

    NASA Astrophysics Data System (ADS)

    Bian, Junguo; Yang, Kai; Boone, John M.; Han, Xiao; Sidky, Emil Y.; Pan, Xiaochuan

    2014-06-01

    There is interest in developing computed tomography (CT) dedicated to breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence has been found that suggests that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image total-variation minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with a focus on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics.

  9. Theoretical models and simulation codes to investigate bystander effects and cellular communication at low doses

    NASA Astrophysics Data System (ADS)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Mairani, A.; Nano, R.; Ottolenghi, A.

    Astronauts in space are continuously exposed to low doses of ionizing radiation from Galactic Cosmic Rays During the last ten years the effects of low radiation doses have been widely re-discussed following a large number of observations on the so-called non targeted effects in particular bystander effects The latter consist of induction of cytogenetic damage in cells not directly traversed by radiation most likely as a response to molecular messengers released by directly irradiated cells Bystander effects which are observed both for lethal endpoints e g clonogenic inactivation and apoptosis and for non-lethal ones e g mutations and neoplastic transformation tend to show non-linear dose responses This might have significant consequences in terms of low-dose risk which is generally calculated on the basis of the Linear No Threshold hypothesis Although the mechanisms underlying bystander effects are still largely unknown it is now clear that two types of cellular communication i e via gap junctions and or release of molecular messengers into the extracellular environment play a fundamental role Theoretical models and simulation codes can be of help in elucidating such mechanisms In the present paper we will review different available modelling approaches including one that is being developed at the University of Pavia The focus will be on the different assumptions adopted by the various authors and on the implications of such assumptions in terms of non-targeted radiobiological damage and more generally low-dose

  10. Detecting airway remodeling in COPD and emphysema using low-dose CT imaging

    NASA Astrophysics Data System (ADS)

    Rudyanto, R.; Ceresa, M.; Muñoz-Barrutia, A.; Ortiz-de-Solorzano, C.

    2012-03-01

    In this study, we quantitatively characterize lung airway remodeling caused by smoking-related emphysema and Chronic Obstructive Pulmonary Disease (COPD), in low-dose CT scans. To that end, we established three groups of individuals: subjects with COPD (n=35), subjects with emphysema (n=38) and healthy smokers (n=28). All individuals underwent a low-dose CT scan, and the images were analyzed as described next. First the lung airways were segmented using a fast marching method and labeled according to its generation. Along each airway segment, cross-section images were resampled orthogonal to the airway axis. Next 128 rays were cast from the center of the airway lumen in each crosssection slice. Finally, we used an integral-based method, to measure lumen radius, wall thickness, mean wall percentage and mean peak wall attenuation on every cast ray. Our analysis shows that both the mean global wall thickness and the lumen radius of the airways of both COPD and emphysema groups were significantly different from those of the healthy group. In addition, the wall thickness change starts at the 3rd airway generation in the COPD patients compared with emphysema patients, who display the first significant changes starting in the 2nd generation. In conclusion, it is shown that airway remodeling happens in individuals suffering from either COPD or emphysema, with some local difference between both groups, and that we are able to detect and accurately quantify this process using images of low-dose CT scans.

  11. Low-Dose Aronia melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity.

    PubMed

    Case, A J; Agraz, D; Ahmad, I M; Zimmerman, M C

    2016-01-01

    Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated neurotoxicity. Additionally, low doses of the concentrate attenuated the paraquat-induced increase in superoxide, hydrogen peroxide, and oxidized glutathione levels. Interestingly, high doses of aronia berry concentrate increased neuronal superoxide levels independent of paraquat, while at the same time decreasing hydrogen peroxide. Moreover, high-dose aronia berry concentrate potentiated paraquat-induced superoxide production and neuronal cell death. In summary, aronia berry concentrate at low doses restores the homeostatic redox environment of neurons treated with paraquat, while high doses exacerbate the imbalance leading to further cell death. Our findings support that moderate levels of aronia berry concentrate may prevent reactive oxygen species-mediated neurotoxicity. PMID:26770655

  12. Commentary: ethical issues of current health-protection policies on low-dose ionizing radiation.

    PubMed

    Socol, Yehoshua; Dobrzyński, Ludwik; Doss, Mohan; Feinendegen, Ludwig E; Janiak, Marek K; Miller, Mark L; Sanders, Charles L; Scott, Bobby R; Ulsh, Brant; Vaiserman, Alexander

    2014-05-01

    The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are "speculative, unproven, undetectable and 'phantom'." Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation. PMID:24910586

  13. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know.

    PubMed

    Brenner, David J; Doll, Richard; Goodhead, Dudley T; Hall, Eric J; Land, Charles E; Little, John B; Lubin, Jay H; Preston, Dale L; Preston, R Julian; Puskin, Jerome S; Ron, Elaine; Sachs, Rainer K; Samet, Jonathan M; Setlow, Richard B; Zaider, Marco

    2003-11-25

    High doses of ionizing radiation clearly produce deleterious consequences in humans, including, but not exclusively, cancer induction. At very low radiation doses the situation is much less clear, but the risks of low-dose radiation are of societal importance in relation to issues as varied as screening tests for cancer, the future of nuclear power, occupational radiation exposure, frequent-flyer risks, manned space exploration, and radiological terrorism. We review the difficulties involved in quantifying the risks of low-dose radiation and address two specific questions. First, what is the lowest dose of x- or gamma-radiation for which good evidence exists of increased cancer risks in humans? The epidemiological data suggest that it is approximately 10-50 mSv for an acute exposure and approximately 50-100 mSv for a protracted exposure. Second, what is the most appropriate way to extrapolate such cancer risk estimates to still lower doses? Given that it is supported by experimentally grounded, quantifiable, biophysical arguments, a linear extrapolation of cancer risks from intermediate to very low doses currently appears to be the most appropriate methodology. This linearity assumption is not necessarily the most conservative approach, and it is likely that it will result in an underestimate of some radiation-induced cancer risks and an overestimate of others. PMID:14610281

  14. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    SciTech Connect

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  15. Low-Dose Aronia melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity

    PubMed Central

    Case, A. J.; Agraz, D.; Ahmad, I. M.; Zimmerman, M. C.

    2016-01-01

    Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated neurotoxicity. Additionally, low doses of the concentrate attenuated the paraquat-induced increase in superoxide, hydrogen peroxide, and oxidized glutathione levels. Interestingly, high doses of aronia berry concentrate increased neuronal superoxide levels independent of paraquat, while at the same time decreasing hydrogen peroxide. Moreover, high-dose aronia berry concentrate potentiated paraquat-induced superoxide production and neuronal cell death. In summary, aronia berry concentrate at low doses restores the homeostatic redox environment of neurons treated with paraquat, while high doses exacerbate the imbalance leading to further cell death. Our findings support that moderate levels of aronia berry concentrate may prevent reactive oxygen species-mediated neurotoxicity. PMID:26770655

  16. Metabolomic Response of Human Skin Tissue to Low Dose Ionizing Radiation

    SciTech Connect

    Hu, Zeping; Kim, Young-Mo; Sowa, Marianne B.; Robinson, Robert J.; Gao, Xiaoli; Metz, Thomas O.; Morgan, William F.; Zhang, Qibin

    2012-05-18

    Understanding how human organs respond to ionizing radiation (IR) at a systems biology level and identifying biomarkers for IR exposure at low doses can help provide a scientific basis for establishing radiation protection standards. Little is known regarding the physiological responses to low dose IR at the metabolite level, which represents the end-point of biochemical processes inside cells. Using a full thickness human skin tissue model and GC-MS-based metabolomics analysis, we examined the metabolic perturbations at three time points (3, 24 and 48 hr) after exposure to 3, 10 and 200 cGy of X-rays. PLS-DA score plots revealed dose- and time-dependent clustering between sham and irradiated groups. Importantly, a comparable number of metabolites were detected to have significant change 48 hr after exposure to 3 and 10 cGy of irradiation, when compared with the high dose of 200 cGy. Biochemical pathway analysis showed perturbations to DNA/RNA damage and repair, lipid and energy metabolisms, even at low doses of IR.

  17. Promoting Immune Regulation in Type 1 Diabetes Using Low-Dose Interleukin-2.

    PubMed

    Dwyer, Connor J; Ward, Natasha C; Pugliese, Alberto; Malek, Thomas R

    2016-06-01

    Dysregulation of the immune system contributes to the breakdown of immune regulation, leading to autoimmune diseases, such as type 1 diabetes (T1D). Current therapies for T1D include daily insulin, due to pancreatic β-cell destruction to maintain blood glucose levels, suppressive immunotherapy to decrease the symptoms associated with autoimmunity, and islet transplantation. Genetic risks for T1D have been linked to IL-2 and IL-2R signaling pathways that lead to the breakdown of self-tolerance mechanisms, primarily through altered regulatory T cell (Treg) function and homeostasis. In attempt to correct such deficits, therapeutic administration of IL-2 at low doses has gained attention due to the capacity to boost Tregs without the unwanted stimulation of effector T cells. Preclinical and clinical studies utilizing low-dose IL-2 have shown promising results to expand Tregs due to their high selective sensitivity to respond to IL-2. These results suggest that low-dose IL-2 therapy represents a new class of immunotherapy for T1D by promoting immune regulation rather than broadly suppressing unwanted and beneficial immune responses. PMID:27076179

  18. High- and low-dose allergen challenges in asthmatic patients using inhaled corticosteroids

    PubMed Central

    Lee, Wha-Yong; Southworth, Thomas; Booth, Steven; Singh, Dave

    2015-01-01

    Aims The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS. Methods Twenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day−1) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers. Results The high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1, but had no effect on FEV1 at 24 h after challenge or sputum measurements. Conclusions The high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment. PMID:25214200

  19. Effects of low-doses of Bacillus spp. from permafrost on differentiation of bone marrow cells.

    PubMed

    Kalyonova, L F; Novikova, M A; Kostolomova, E G

    2015-01-01

    The effects of a new microorganism species (Bacillus spp., strain M3) isolated from permafrost specimens from Central Yakutia (Mamontova Mountain) on the bone marrow hemopoiesis were studied on laboratory mice. Analysis of the count and immunophenotype of bone marrow cells indicated that even in low doses (1000-5000 microbial cells) these microorganisms modulated hemopoiesis and lymphopoiesis activity. The percentage of early hemopoietic precursors (CD117(+)CD34(-)) increased, intensity of lymphocyte precursor proliferation and differentiation (CD25(+)CD44(-)) decreased, and the percentage of lymphocytes released from the bone marrow (CD25(+)CD44(+)) increased on day 21 after injection of the bacteria. These changes in activity of hemopoiesis were associated with changes in the level of regulatory T lymphocytes (reduced expression of TCRαβ) and were most likely compensatory. The possibility of modulating hemopoiesis activity in the bone marrow by low doses of one microorganism strain isolated from the permafrost could be useful for evaluating the effects of other low dose bacteria on the bone marrow hemopoiesis. PMID:25567196

  20. Perinatal Exposure to Low-Dose Methoxychlor Impairs Testicular Development in C57BL/6 Mice

    PubMed Central

    Du, Xiaohong; Zhang, Hua; Liu, Yuanwu; Yu, Wanpeng; Huang, Chaobin; Li, Xiangdong

    2014-01-01

    Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans. PMID:25048109

  1. Low-Dose Intramuscular Dexmedetomidine as Premedication: A Randomized Controlled Trial

    PubMed Central

    Sun, Yang; Liu, Chaolei; Zhang, Yuehong; Luo, Bin; She, Shouzhang; Xu, Lixin; Ruan, Xiangcai

    2014-01-01

    Background Dexmedetomidine-induced bradycardia or hypotension has recently attracted considerable attention because of potentially grave consequences, including sinus arrest and refractory cardiogenic shock. A route other than intravenous injection or a low dose may help minimize cardiovascular risks associated with dexmedetomidine. However, few studies have addressed the clinical effects of low-dose intramuscular dexmedetomidine as premedication. Material/Methods Forty American Society of Anesthesiologists physical status I adult patients undergoing suspension laryngoscopic surgery were randomized to receive intramuscular dexmedetomidine (1 μg·kg−1) or midazolam (0.02 mg·kg−1) 30 minutes prior to anaesthesia induction. The sedative, hemodynamic, and adjuvant anaesthetic effects of both premedications were assessed. Results The levels of sedation (Observer’s Assessment of Alertness/Sedation scales) and anxiety (visual analog score) at pre-induction, and the times to eye-opening and extubation, were not different between the groups. The heart rate response following tracheal intubation and extubation, and mean arterial pressure responses after extubation, were attenuated in the dexmedetomidine group compared to the midazolam group. No bradycardia or hypotension was noted in any patients. Propofol target concentrations at intubation and at start and completion of surgery were decreased in the dexmedetomidine group, whereas no difference in respective remifentanil levels was detected. Conclusions This study provides further evidence that dexmedetomidine premedication in low dose (1 μg·kg−1) by intramuscular route can induce preoperative sedation and adjuvant anaesthetic effects without clinically significant bradycardia or hypotension. PMID:25529851

  2. Learning from agriculture: understanding low-dose antimicrobials as drivers of resistome expansion

    PubMed Central

    You, Yaqi; Silbergeld, Ellen K.

    2014-01-01

    Antimicrobial resistance is a growing public health challenge worldwide, with agricultural use of antimicrobials being one major contributor to the emergence and dissemination of antimicrobial resistance (AMR). Globally, most antimicrobials are used in industrial food animal production, a major context for microbiomes encountering low-doses or subtherapeutic-levels of antimicrobial agents from all mechanistic classes. This modern practice exerts broad eco-evolutionary effects on the gut microbiome of food animals, which is subsequently transferred to animal waste. This waste contains complex constituents that are challenging to treat, including AMR determinants and low-dose antimicrobials. Unconfined storage or land deposition of a large volume of animal waste causes its wide contact with the environment and drives the expansion of the environmental resistome through mobilome facilitated horizontal genet transfer. The expanded environmental resistome, which encompasses both natural constituents and anthropogenic inputs, can persist under multiple stressors from agriculture and may re-enter humans, thus posing a public health risk to humans. For these reasons, this review focuses on agricultural antimicrobial use as a laboratory for understanding low-dose antimicrobials as drivers of resistome expansion, briefly summarizes current knowledge on this topic, highlights the importance of research specifically on environmental microbial ecosystems considering AMR as environmental pollution, and calls attention to the needs for longitudinal studies at the systems level. PMID:24959164

  3. [Successful treatment of an elderly patient with pretreated recurrent breast cancer using low-dose capecitabine].

    PubMed

    Honma, Hideyuki

    2006-12-01

    The author reports the successful treatment of an 85-year-old recurrent breast cancer patient with low-dose capecitabine. Approximately 20 years ago, the patient received a left mastectomy and 2 years later was treated with unspecified chemotherapy for bone metastasis. In November 2001, metastatic tumors in thoracic vertebrae were removed by emergency laminectomy, followed by radiotherapy plus chemotherapy using mitoxantrone, cyclophosphamide and doxifluridine. In June 2005, abdominal computed tomography revealed a single metastatic tumor 20 mm in diameter in the liver. Treatment with paclitaxel at 70 mg/m(2)/day on days 1 and 14 resulted in no change in tumor size while serum levels of cancer antigen 15-3 increased from 22.1 to 98.1 U/ml. Subsequent daily treatment with capecitabine at 1,000 mg/m(2)/day for 21 days was associated with a 50% decrease in tumor size and a reduction in serum cancer antigen of 15-3 to 18.8 U/ml. Grade 2 hand-foot syndrome was noted,but no severe adverse effects were evident. Five months after the induction of capecitabine treatment, a partial response was obtained. These results suggest that low-dose capecitabine may be a safe and efficacious treatment for elderly patients with pretreated recurrent breast cancer. Clinical trials of low-dose capecitabine in such patients are therefore warranted. PMID:17197750

  4. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

    PubMed Central

    Rodríguez-Gutiérrez, René; Rendon, Adrian; Barrera-Sánchez, Maximiliano; Carlos-Reyna, Kevin Erick Gabriel; Álvarez-Villalobos, Neri Alejandro; González-Saldivar, Gloria; González-González, José Gerardo

    2016-01-01

    Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or

  5. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test.

    PubMed

    Rodríguez-Gutiérrez, René; Rendon, Adrian; Barrera-Sánchez, Maximiliano; Carlos-Reyna, Kevin Erick Gabriel; Álvarez-Villalobos, Neri Alejandro; González-Saldivar, Gloria; González-González, José Gerardo

    2016-01-01

    Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6-12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat

  6. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    SciTech Connect

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  7. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  8. European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

    PubMed

    Landolfi, R; Marchioli, R

    1997-01-01

    Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged < or = 50, and hematocrit < 45% as well as platelet count < 400 x 10(9)/L in patients aged > 50. Randomization will be stratified by participating center. The study is

  9. SOD2-mediated Adaptive Responses Induced by Low Dose Ionizing Radiation via TNF Signaling and Amifostine

    PubMed Central

    Murley, J.S.; Baker, K.L.; Miller, R.C.; Darga, T.E.; Weichselbaum, R.R.; Grdina, D.J.

    2011-01-01

    Manganese superoxide dismutase (SOD2)-mediated adaptive processes that protect against radiation-induced micronuclei formation can be induced in cells following a 2 Gy exposure by previously exposing them to either low dose ionizing radiation (10 cGy) or WR1065 (40 µM), the active thiol form of amifostine. While both adaptive processes culminate with elevated levels of SOD2 enzymatic activities, the underlying pathways differ in complexity, with the tumor necrosis factor α (TNFα) signaling pathway implicated in the low dose radiation-induced response, but not in the thiol-induced pathway. The goal of this study was the characterization of the effects of TNFα receptors1 and 2 (TNFR1, 2) on the adaptive responses induced by low dose irradiation or thiol exposures using micronuclei formation as an endpoint. BFS-1 wild type (WT) cells with functional TNFR1 and 2 were exposed 24 h prior to a 2 Gy dose of ionizing radiation to either 10 cGy or a 40 µM dose of WR1065. BFS2C-SH02 cells defective in TNFR1 and BFS2C-SH22 cells defective in both TNFR1 and 2, generated from BFS2C-SH02 cells by transfection with a murine TNFR2 targeting vector and confirmed to be TNFR2 defective by quantitative PCR, were also exposed under similar conditions for comparison. A 10 cGy dose of radiation induced a significant elevation of SOD2 activity in BFS-1 (P < 0.001) and BFS2C-SH02 (P = 0.005) but not BFS2C-SH22 cells (P = 0.433) as compared to their respective untreated controls. In contrast, WR1065 significantly induced elevations in SOD2 activity in all three cell lines (P = 0.001; P = 0.007; P = 0.020; respectively). A significant reduction in the frequency of radiation-induced micronuclei was observed in each cell line when exposure to a 2 Gy challenge dose of radiation occurred during the period of maximal elevation in SOD2 activity. However, this adaptive effect was completely inhibited if the cells were transfected 24 h prior to low dose radiation or thiol exposure with SOD2 si

  10. Low-dose computed tomography image restoration using previous normal-dose scan

    SciTech Connect

    Ma, Jianhua; Huang, Jing; Feng, Qianjin; Zhang, Hua; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

    2011-10-15

    Purpose: In current computed tomography (CT) examinations, the associated x-ray radiation dose is of a significant concern to patients and operators. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) or kVp parameter (or delivering less x-ray energy to the body) as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and the noise would propagate into the CT image if no adequate noise control is applied during image reconstruction. Since a normal-dose high diagnostic CT image scanned previously may be available in some clinical applications, such as CT perfusion imaging and CT angiography (CTA), this paper presents an innovative way to utilize the normal-dose scan as a priori information to induce signal restoration of the current low-dose CT image series. Methods: Unlike conventional local operations on neighboring image voxels, nonlocal means (NLM) algorithm utilizes the redundancy of information across the whole image. This paper adapts the NLM to utilize the redundancy of information in the previous normal-dose scan and further exploits ways to optimize the nonlocal weights for low-dose image restoration in the NLM framework. The resulting algorithm is called the previous normal-dose scan induced nonlocal means (ndiNLM). Because of the optimized nature of nonlocal weights calculation, the ndiNLM algorithm does not depend heavily on image registration between the current low-dose and the previous normal-dose CT scans. Furthermore, the smoothing parameter involved in the ndiNLM algorithm can be adaptively estimated based on the image noise relationship between the current low-dose and the previous normal-dose scanning protocols. Results: Qualitative and quantitative evaluations were carried out on a physical phantom as well as clinical abdominal and brain perfusion CT scans in terms of accuracy and resolution properties. The gain by the use

  11. A Low-Dose Ipsilateral Lung Restriction Improves 3-D Conformal Planning for Partial Breast Radiation Therapy

    SciTech Connect

    Mitchell, Tracy; Truong, Pauline T.; Salter, Lee; Graham, Cathy; Gaffney, Helene; Beckham, Wayne; Olivotto, Ivo A.

    2011-04-01

    In trials of 3D conformal external beam partial breast radiotherapy (PBRT), the dosimetrist must balance the priorities of achieving high conformity to the target versus minimizing low-dose exposure to the normal structures. This study highlights the caveat that in the absence of a low-dose lung restriction, the use of relatively en-face fields may meet trial-defined requirements but expose the ipsilateral lung to unnecessary low-dose radiation. Adding a low-dose restriction that {<=}20% of the ipsilateral lung should receive 10% of the prescribed dose resulted in successful plans in 88% of cases. This low-dose lung limit should be used in PBRT planning.

  12. Randomized Controlled Trial of Low-Dose Estradiol and the SNRI Venlafaxine for Vasomotor Symptoms

    PubMed Central

    Joffe, Hadine; Guthrie, Katherine A.; LaCroix, Andrea Z.; Reed, Susan D.; Ensrud, Kristine E.; Manson, JoAnn E.; Newton, Katherine M.; Freeman, Ellen W.; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie; Shifren, Jan; Rexrode, Kathryn M.; Caan, Bette; Sternfeld, Barbara; Carpenter, Janet S.; Cohen, Lee

    2014-01-01

    Importance Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine is used widely as a non-hormonal treatment. While clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial. Objective To determine the efficacy and tolerability of low-dose oral 17-beta-estradiol and low-dose venlafaxine XR in alleviating vasomotor symptoms. Design and Participants 339 peri- and postmenopausal women with ≥2 bothersome vasomotor symptoms per day (mean 8.1, SD 5.3/day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites November 2011—October 2012. Interventions Participants were randomized to double-blinded treatment with low-dose oral 17-beta-estradiol 0.5-mg/day (n=97), low-dose venlafaxine XR 75-mg/day (n=96), or placebo (n=146) for 8 weeks. Main Outcomes Primary outcome was the mean daily frequency of vasomotor symptoms after 8 weeks of treatment. Secondary outcomes were vasomotor symptom severity, bother and interference. Intent-to-treat analyses compared change in vasomotor symptom frequency between each active intervention and placebo and between the two active treatments. Results Compared to baseline, mean vasomotor symptom frequency at week 8 decreased by 53% with estradiol, 48% with venlafaxine, and 29% with placebo. Estradiol reduced the frequency of symptoms by 2.3 (95% CI 1.3–3.4) more per day than placebo (p<0.001), and venlafaxine by 1.8 (95% CI 0.8–2.7) more per day than placebo (p=0.005). Results were consistent for VMS severity, bother and interference. Low-dose estradiol reduced symptom frequency by 0.6 more per day than venlafaxine (95% CI, 1.8 more per day to 0.6 fewer per day than

  13. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    SciTech Connect

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  14. Characterization of the role of Fhit in maintenance of genomic integrity following low dose radiation, in vivo and in vitro

    SciTech Connect

    Wang, Ya

    2010-05-14

    The major goal of this study is to determine the effects of the Fhit pathway on low dose (< 0.1 Gy) ionizing radiation (IR)-induced genetic instability. Reduction of Fhit protein expression is observed in most solid tumors particularly in those tumors resulting from exposure to environmental carcinogens. Therefore, characterization of the role of the Fhit-dependent pathway in preventing low dose IR-induced genetic instability will provide useful parameters for evaluating the low dose IR-induced risk of mutagenesis and carcinogenesis. We pursued 3 specific aims to study our hypothesis that the Fhit-dependent pathways maintain genomic integrity through adjusting checkpoint response and repair genes expression following low dose IR. Aim 1: Determine whether Fhit interaction with RPA is necessary for Fhit to affect the cellular response to low dose IR. We combined the approaches of in vitro (GST pull-down and site-directed mutagenesis) and in vivo (observing the co-localization and immunoprecipitation of Fhit and RPA in Fhit knock out mouse cells transfected with mutant Fhit which has lost ability to interact with RPA in vitro). Aim 2: Determine the role of genes whose expression is affected by Fhit in low dose irradiated cells. We analyzed the distinct signature of gene expression in low dose irradiated Fhit-/- cells compared with Fhit+/+ cells by combining microarray, gene transfection and siRNA approaches. Aim 3: Determine the role of Fhit in genetic susceptibility to low dose IR in vivo. We compared the gene mutation frequency and the fragile site stability in the cells isolated from the Fhit+/+ and Fhit-/- mice at 1.5 years following low dose IR. These results determine the role of the Fhit-dependent pathway in maintaining genomic integrity in vitro and in vivo, which provide a basis for choosing surrogate markers in the Fhit-dependent pathway to evaluate low dose IR-induced risk of mutagenesis and carcinogenesis.

  15. Characterization of the role of Fhit in maintenance of genomic integrity following low dose radiation, in vivo and in vitro

    SciTech Connect

    Ya Wang

    2010-05-31

    The major goal of this study is to determine the effects of the Fhit pathway on low dose ({le} 0.1 Gy) ionizing radiation (IR)-induced genetic instability. Reduction of Fhit protein expression is observed in most solid tumors particularly in those tumors resulting from exposure to environmental carcinogens. Therefore, characterization of the role of the Fhit-dependent pathway in preventing low dose IR-induced genetic instability will provide useful parameters for evaluating the low dose IR-induced risk of mutagenesis and carcinogenesis. We pursued 3 specific aims to study our hypothesis that the Fhit-dependent pathways maintain genomic integrity through adjusting checkpoint response and repair genes expression following low dose IR. Aim 1: Determine whether Fhit interaction with RPA is necessary for Fhit to affect the cellular response to low dose IR. We combined the approaches of in vitro (GST pull-down and site-directed mutagenesis) and in vivo (observing the co-localization and immunoprecipitation of Fhit and RPA in Fhit knock out mouse cells transfected with mutant Fhit which has lost ability to interact with RPA in vitro). Aim 2: Determine the role of genes whose expression is affected by Fhit in low dose irradiated cells. We analyzed the distinct signature of gene expression in low dose irradiated Fhit-/- cells compared with Fhit+/+ cells by combining microarray, gene transfection and siRNA approaches. Aim 3: Determine the role of Fhit in genetic susceptibility to low dose IR in vivo. We compared the gene mutation frequency and the fragile site stability in the cells isolated from the Fhit+/+ and Fhit-/- mice at 1.5 years following low dose IR. These results determine the role of the Fhit-dependent pathway in maintaining genomic integrity in vitro and in vivo, which provide a basis for choosing surrogate markers in the Fhit-dependent pathway to evaluate low dose IR-induced risk of mutagenesis and carcinogenesis.

  16. Low dose radiation hypersensitivity and clustered DNA damages in human fibroblasts exposed to low dose and dose rate protons or 137CS y-rays

    SciTech Connect

    Bennett P. V.; Bennett, P.V.; Keszenman, D.J.; Johnson, A.M.; Sutherland, B.M.; Wilson, P.F.

    2013-05-14

    Effective radioprotection for human space travelers hinges upon understanding the individual properties of charged particles. A significant fraction of particle radiation astronauts will encounter in space exploratory missions will come from high energy protons in galactic cosmic radiation (GCR) and/or possible exposures to lower energy proton flux from solar particle events (SPEs). These potential exposures present major concerns for NASA and others, in planning and executing long term space exploratory missions. We recently reported cell survival and transformation (acquisition of anchorage-independent growth in soft agar) frequencies in apparently normal NFF-28 primary human fibroblasts exposed to 0-30 cGy of 50MeV, 100MeV (SPE-like), or 1000 MeV (GCR-like) monoenergetic protons. These were modeled after 1989 SPE energies at an SPE-like low dose-rate (LDR) of 1.65 cGy/min or high dose rate (HDR) of 33.3 cGy/min delivered at the NASA Space Radiation Laboratory (NSRL) at BNL.

  17. Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

    SciTech Connect

    Balajee, A.S.; Meador, J.A.; Su, Y.

    2011-03-24

    It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellular mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the

  18. Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma.

    PubMed

    Kim, Joong Sun; Son, Yeonghoon; Bae, Min Ji; Lee, Seung Sook; Park, Sun Hoo; Lee, Hae June; Lee, Soong In; Lee, Chang Geun; Kim, Sung Dae; Jo, Wol Soon; Kim, Sung Ho; Shin, In Sik

    2015-01-01

    Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation. PMID:26588845

  19. Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma

    PubMed Central

    Kim, Joong Sun; Son, Yeonghoon; Bae, Min Ji; Lee, Seung Sook; Park, Sun Hoo; Lee, Hae June; Lee, Soong In; Lee, Chang Geun; Kim, Sung Dae; Jo, Wol Soon; Kim, Sung Ho; Shin, In Sik

    2015-01-01

    Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation. PMID:26588845

  20. The European initiative on low-dose risk research: from the HLEG to MELODI.

    PubMed

    Belli, Mauro; Tabocchini, Maria Antonella; Jourdain, Jean-René; Salomaa, Sisko; Repussard, Jacques

    2015-09-01

    The importance of low-dose risk research for radiation protection is now widely recognised. The European Commission (EC) and five European Union (EU) Member States involved in the Euratom Programme set up in 2008 a 'High Level and Expert Group on European Low Dose Risk Research' (HLEG) aimed at identifying research needs and proposing a better integration of European efforts in the field. The HLEG revised the research challenges and proposed a European research strategy based on a 'Multidisciplinary European LOw Dose Initiative' (MELODI). In April 2009, five national organisations, with the support of the EC, created the initial core of MELODI (http://www.melodi-online.eu) with a view to integrate the EU institutions with significant programmes in the field, while being open to other scientific organisations and stakeholders, and to develop an agreed strategic research agenda (SRA) and roadmap. Since then, open workshops have been organised yearly, exploring ideas for SRA implementation. As of October 2014, 31 institutions have been included as members of MELODI. HLEG recommendations and MELODI SRA have become important reference points in the radiation protection part of the Euratom Research Programme. MELODI has established close interactions through Memorandum of Understanding with other European platforms involved in radiation protection (Alliance, NERIS and EURADOS) and, together with EURADOS, with the relevant medical European Associations. The role of Joint Programming in priority setting, foreseen in the forthcoming EU Horizon 2020, calls for keeping MELODI an open, inclusive and transparent initiative, able to avoid redundancies and possible conflicts of interest, while promoting common initiatives in radiation protection research. An important issue is the establishment of a proper methodology for managing these initiatives, and this includes the set-up of an independent MELODI Scientific Committee recently extended to Alliance, NERIS and EURADOS, with

  1. Low-dose dual-energy electronic cleansing for fecal-tagging CT Colonography

    NASA Astrophysics Data System (ADS)

    Cai, Wenli; Zhang, Da; Lee, June-Goo; Yoshida, Hiroyuki

    2013-03-01

    Dual-energy electronic cleansing (DE-EC) provides a promising means for cleansing the tagged fecal materials in fecaltagging CT colonography (CTC). However, the increased radiation dose due to the double exposures in dual-energy CTC (DE-CTC) scanning is a major limitation for the use of DE-EC in clinical practice. The purpose of this study was to develop and evaluate a low-dose DE-EC scheme in fecal-tagging DE-CTC. In this study, a custom-made anthropomorphic colon phantom, which was filled with simulated tagged materials by non-ionic iodinated contrast agent (Omnipaque iohexol, GE Healthcare), was scanned by a dual-source CT scanner (SOMATON Definition Flash, Siemens Healthcare) at two photon energies: 80 kVp and 140 kVp with nine different tube current settings ranging from 12 to 74 mAs for 140 kVp, and then reconstructed by soft-tissue reconstruction kernel (B30f). The DE-CTC images were subjected to a low-dose DE-EC scheme. First, our image-space DE-CTC denoising filter was applied for reduction of image noise. Then, the noise-reduced images were processed by a virtual lumen tagging method for reduction of partial volume effect and tagging inhomogeneity. The results were compared with the registered CTC images of native phantom without fillings. Preliminary results showed that our low-dose DE-EC scheme achieved the cleansing ratios, defined by the proportion of the cleansed voxels in the tagging mask, between 93.18% (12 mAs) and 96.62% (74 mAs). Also, the soft-tissue preservation ratios, defined by the proportion of the persevered voxels in the soft-tissue mask, were maintained in the range between 94.67% and 96.41%.

  2. Divergent Modification of Low-Dose 56Fe-Particle and Proton Radiation on Skeletal Muscle

    PubMed Central

    Shtifman, Alexander; Pezone, Matthew J.; Sasi, Sharath P.; Agarwal, Akhil; Gee, Hannah; Song, Jin; Perepletchikov, Aleksandr; Yan, Xinhua; Kishore, Raj; Goukassian, David A.

    2014-01-01

    It is unknown whether loss of skeletal muscle mass and function experienced by astronauts during space flight could be augmented by ionizing radiation (IR), such as low-dose high-charge and energy (HZE) particles or low-dose high-energy proton radiation. In the current study adult mice were irradiated whole-body with either a single dose of 15 cGy of 1 GeV/n 56Fe-particle or with a 90 cGy proton of 1 GeV/n proton particles. Both ionizing radiation types caused alterations in the skeletal muscle cytoplasmic Ca2+ ([Ca2+]i) homeostasis. 56Fe-particle irradiation also caused a reduction of depolarization-evoked Ca2+ release from the sarcoplasmic reticulum (SR). The increase in the [Ca2+]i was detected as early as 24 h after 56Fe-particle irradiation, while effects of proton irradiation were only evident at 72 h. In both instances [Ca2+]i returned to baseline at day 7 after irradiation. All 56Fe-particle irradiated samples revealed a significant number of centrally localized nuclei, a histologic manifestation of regenerating muscle, 7 days after irradiation. Neither unirradiated control or proton-irradiated samples exhibited such a phenotype. Protein analysis revealed significant increase in the phosphorylation of Akt, Erk1/2 and rpS6k on day 7 in 56Fe-particle irradiated skeletal muscle, but not proton or unirradiated skeletal muscle, suggesting activation of pro-survival signaling. Our findings suggest that a single low-dose 56Fe-particle or proton exposure is sufficient to affect Ca2+ homeostasis in skeletal muscle. However, only 56Fe-particle irradiation led to the appearance of central nuclei and activation of pro-survival pathways, suggesting an ongoing muscle damage/recovery process. PMID:24131063

  3. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris.

    PubMed

    Stark, Karolina; Scott, David E; Tsyusko, Olga; Coughlin, Daniel P; Hinton, Thomas G

    2015-01-01

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae. PMID:25927361

  4. A meta-analysis of leukaemia risk from protracted exposure to low-dose gamma radiation

    PubMed Central

    Schubauer-Berigan, M K

    2010-01-01

    Context More than 400 000 workers annually receive a measurable radiation dose and may be at increased risk of radiation-induced leukaemia. It is unclear whether leukaemia risk is elevated with protracted, low-dose exposure. Objective We conducted a meta-analysis examining the relationship between protracted low-dose ionising radiation exposure and leukaemia. Data sources Reviews by the National Academies and United Nations provided a summary of informative studies published before 2005. PubMed and Embase databases were searched for additional occupational and environmental studies published between 2005 and 2009. Study selection We selected 23 studies that: (1) examined the association between protracted exposures to ionising radiation and leukaemia excluding chronic lymphocytic subtype; (2) were a cohort or nested case–control design without major bias; (3) reported quantitative estimates of exposure; and (4) conducted exposure–response analyses using relative or excess RR per unit exposure. Methods Studies were further screened to reduce information overlap. Random effects models were developed to summarise between-study variance and obtain an aggregate estimate of the excess RR at 100 mGy. Publication bias was assessed by trim and fill and Rosenthal's file drawer methods. Results We found an ERR at 100 mGy of 0.19 (95% CI 0.07 to 0.32) by modelling results from 10 studies and adjusting for publication bias. Between-study variance was not evident (p=0.99). Conclusions Protracted exposure to low-dose gamma radiation is significantly associated with leukaemia. Our estimate agreed well with the leukaemia risk observed among exposed adults in the Life Span Study (LSS) of atomic bomb survivors, providing increased confidence in the current understanding of leukaemia risk from ionising radiation. However, unlike the estimates obtained from the LSS, our model provides a precise, quantitative summary of the direct estimates of excess risk from studies of

  5. Automated measurement of pulmonary artery in low-dose non-contrast chest CT images

    NASA Astrophysics Data System (ADS)

    Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2015-03-01

    A new measurement of the pulmonary artery diameter is obtained where the artery may be robustly segmented between the heart and the artery bifurcation. An automated algorithm is presented that can make this pulmonary artery measurement in low-dose non-contrast chest CT images. The algorithm uses a cylinder matching method following geometric constraints obtained from other adjacent organs that have been previously segmented. This new measurement and the related ratio of pulmonary artery to aortic artery measurement are compared to traditional manual approaches for pulmonary artery characterization. The algorithm was qualitatively evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets; 324 out of the 347 cases had good segmentations and in the other 23 cases there was significant boundary inaccuracy. For quantitative evaluation, the comparison was to manually marked pulmonary artery boundary in an axial slice in 45 cases; the resulting average Dice Similarity Coefficient was 0.88 (max 0.95, min 0.74). For the 45 cases with manual markings, the correlation between the automated pulmonary artery to ascending aorta diameter ratio and manual ratio at pulmonary artery bifurcation level was 0.81. Using Bland-Altman analysis, the mean difference of the two ratios was 0.03 and the limits of agreement was (-0.12, 0.18). This automated measurement may have utility as an alternative to the conventional manual measurement of pulmonary artery diameter at the bifurcation level especially in the context of noisy low-dose CT images.

  6. Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

    DOE PAGESBeta

    Stark, Karolina; Scott, David E.; Tsyusko, Olga; Coughlin, Daniel P.; Hinton, Thomas G.; Amendola, Roberto

    2015-04-30

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments did notmore » affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less

  7. Performance of KCl:Eu2+ storage phosphor dosimeters for low dose measurements

    PubMed Central

    Li, H. Harold; Hansel, Rachael; Knutson, Nels; Yang, Deshan

    2013-01-01

    Recent research has demonstrated that europium doped potassium chloride (KCl:Eu2+) storage phosphor material has the potential to become the physical foundation of a novel and reusable dosimetry system using either film-like devices or devices similar to thermoluminescent dosimeter (TLD) chips. The purposes of this work are to quantify the performance of KCl:Eu2+ prototype dosimeters for low dose measurements and to demonstrate how it can be incorporated into clinical application for in vivo peripheral dose measurements. Pellet-style KCl:Eu2+ dosimeters, 6 mm in diameter, and 1 mm thick, were fabricated in-house for this study. The dosimeters were read using a laboratory photostimulated luminescence detection system. KCl:Eu2+ prototype storage phosphor dosimeter was capable of measuring a dose-to-water as low as 0.01 cGy from a 6 MV photon beam with a signal-to-noise ratio greater than 6. A pre-readout thermal annealing procedure enabled the dosimeter to be read within an hour post irradiation. After receiving large accumulated doses (~10 kGy), the dosimeters retained linear response in the low dose region with only a 20 percent loss of sensitivity comparing to a fresh sample (zero Gy history). The energy-dependence encountered during low dose peripheral measurements could be accounted for via a single point outside-field calibration per each beam quality. With further development the KCl:Eu2+− based dosimeter could become a versatile and durable dosimetry tool with large dynamic range (sub-cGy to 100 Gy). PMID:23735856

  8. Diaphragm contractile dysfunction causes by off-target low-dose irradiation

    PubMed Central

    Hsieh, Chen-Hsi; Lin, Yun-Cheng; Chen, Yu-Jen; Wu, Huey-Dong; Wang, Li-Ying

    2016-01-01

    Background: Diaphragm is a primary inspiratory muscle and often receives off-target dose in patients with thoracic radiotherapy, and whether acute effect of low dose irradiation would cause contractile dysfunction of the diaphragm remains unclear. We use a rat model to investigate the effect of low-dose irradiation on diaphragm contractile function in the current study. Methods: The radiation dose distributions in patients with esophageal cancer receiving radiotherapy were calculated to determine the dose received by the off-target diaphragm area. Rats were randomly assigned to an irradiated or a non-irradiated control group (n = 10 per group). A single-fraction of 5 Gy radiation was then delivered to the diaphragms of Sprague-Dawley rats in the irradiated group. The control group received sham irradiation (0 Gy). Rats were sacrificed 24 hours after the irradiation procedures and diaphragms were removed en bloc for contractile function assessment, oxidative injury and DNA damage analysis. Oxidative injury was determined by analyzing concentration of protein carbonyls and DNA damage was determined by analyzing retention of γH2AX foci in nuclei of diaphragmatic tissue. Results: At 24 hours after delivery of a single dose of 5 Gy radiation, specific twitch (p = 0.03) and tetanus tension (p = 0.02) were significantly lower in the irradiated group than in the control group. The relative force-frequency curves showed a significant downward shift in the irradiated group. Protein carbonyl level (p < 0.01) and percentage of γH2AX-positive diaphragm muscle cells were significantly higher in the irradiated group than in the control group 24 hours after irradiation (58% vs. 30%, p = 0.01). Conclusions: Off-target low dose irradiation could induce acute contractile dysfunction of the diaphragm which was related to radiation-induced direct DNA and indirect oxidative damage. PMID:27186277

  9. Low-Dose Neoadjuvant External Beam Radiation Therapy for Soft Tissue Sarcoma

    SciTech Connect

    Devisetty, Kiran; Kobayashi, Wendy; Suit, Herman D.; Goldberg, Saveli I.; Niemierko, Andrzej; Chen, Yen-Lin E.; Raskin, Kevin A.; Schwab, Joseph H.; Springfield, Dempsey S.; Yoon, Sam S.; Hornicek, Francis J.; DeLaney, Thomas F.

    2011-07-01

    Purpose: For soft tissue sarcoma, neoadjuvant external beam radiation therapy (EBRT) to 50 Gy has the same local control (LC) and overall survival as postoperative radiation therapy (PORT) to 60 Gy, but with increased wound complications. We examined whether low-dose neoadjuvant EBRT would decrease acute toxicity while maintaining LC. Methods and Materials: From 1971 to 2008, 1,765 patients with nonmetastatic soft tissue sarcoma were treated with radiation therapy at Massachusetts General Hospital. We identified 42 patients treated with low-dose neoadjuvant EBRT (median, 20 Gy; range, 16-26) followed by surgical resection and PORT. PORT included EBRT (25 patients; median, 40 Gy; range, 20-56.2), brachytherapy (13 patients; median, 42 Gy; range, 26-50), and intraoperative radiation therapy (IORT) (4 patients; median, 12.5 Gy; range, 8-20). The median total dose was 63.3 Gy (range, 28-78.4). Results: Median follow-up was 36 months (range, 4-318). Severe acute wound complications were reported in 15 patients (36%) and correlated to PORT technique (16% EBRT, 69% brachytherapy, 50% IORT, p = 0.004). The 5-year LC was 73% and correlated to PORT technique (68% EBRT, 100% brachytherapy, 50% IORT, p = 0.03) and histology (p = 0.05), with a trend to improvement if >60 Gy (p = 0.10). The 5-year overall survival was 65% and correlated to extent of resection (p < 0.001) and margin status (p < 0.001). Conclusions: Despite using low-dose neoadjuvant EBRT, we report a high rate of severe acute wound complications that was strongly associated with brachytherapy. Modification of the brachytherapy technique may decrease acute toxicity while maintaining excellent local control. Further study must be conducted before recommending broader application.

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

    SciTech Connect

    Eric Y. Chuang

    2006-08-31

    It has been long recognized that a significant fraction of the radiation-induced genetic damage to cells are caused by secondary oxidative species. Internal cellular defense systems against oxidative stress play significant roles in countering genetic damage induced by ionizing radiation. The role of the detoxifying enzymes may be even more prominent in the case of low-dose, low-LET irradiation, as the majority of genetic damage may be caused by secondary oxidative species. In this study we have attempted to decipher the roles of the superoxide dismutase (SOD) genes, which are responsible for detoxifying the superoxide anions. We used adenovirus vectors to deliver RNA interference (RNAi or siRNA) technology to down-regulate the expression levels of the SOD genes. We have also over-expressed the SOD genes by use of recombinant adenovirus vectors. Cells infected with the vectors were then subjected to low dose γ-irradiation. Total RNA were extracted from the exposed cells and the expression of 9000 genes were profiled by use of cDNA microarrays. The result showed that low dose radiation had clear effects on gene expression in HCT116 cells. Both over-expression and down-regulation of the SOD1 gene can change the expression profiles of sub-groups of genes. Close to 200 of the 9000 genes examined showed over two-fold difference in expression under various conditions. Genes with changed expression pattern belong to many categories that include: early growth response, DNA-repair, ion transport, apoptosis, and cytokine response.

  11. Influence of Low-Dose Aspirin on Cerebral Amyloid Angiopathy in Mice.

    PubMed

    Hattori, Yorito; Maki, Takakuni; Saito, Satoshi; Yamamoto, Yumi; Nagatsuka, Kazuyuki; Ihara, Masafumi

    2016-04-12

    Accumulation of amyloid-β peptide (Aβ) in the brain is one of the most important features of Alzheimer's dementia (AD). Cerebral amyloid angiopathy (CAA) is characterized by Aβ accumulation in the walls of cerebral arteries and capillaries, and is present in over 90% of patients with AD. Several novel agents for AD/CAA developed around the amyloid hypothesis have shown positive signs in animal studies but have failed in clinical trials due to adverse events and/or lack of efficiency. As CAA is presumably caused by a failure in Aβ clearance, drugs that promote Aβ clearance may hold promise in the treatment of CAA and possibly AD. With this in mind, cilostazol, an anti-platelet drug with vasodilating action, has been found to promote Aβ clearance along perivascular drainage pathway, reduce Aβ accumulation in the brain, and restore memory impairment in Tg-SwDI mice, an animal model of CAA. We therefore tested whether the most common anti-platelet agent, aspirin, also reduced Aβ and rescued cognitive impairment in Tg-SwDI mice, and also whether aspirin affected hemorrhagic complications that can occur in Tg-SwDI mice. Mice aged 4 months were assigned into vehicle-treated and low-dose aspirin-treated groups. Low-dose aspirin for 8 months did not increase hemorrhagic lesions, nor increase resting cerebral blood flow or cerebral vascular reserve in response to hypercapnia or acetylcholine. Subsequently, aspirin did not restore cognitive dysfunction. These results suggest that low-dose aspirin does not have a direct influence on cerebrovascular Aβ metabolism nor aggravate hemorrhagic complications in CAA. PMID:27079719

  12. Neurocircuitry Underlying the Preferential Sensitivity of Prefrontal Catecholamines to Low-Dose Psychostimulants

    PubMed Central

    Schmeichel, Brooke E; Berridge, Craig W

    2013-01-01

    Low doses of psychostimulants, including methylphenidate (MPH), are highly effective in the treatment of attention-deficit/hyperactivity disorder (ADHD). At these doses, psychostimulants improve prefrontal cortex (PFC)-dependent function. Recent evidence indicates that low and clinically relevant doses of psychostimulants target norepinephrine (NE) and dopamine (DA) signaling preferentially in the PFC. To better understand the neural mechanisms responsible for the regional selectivity of low-dose psychostimulant action, it is important to first identify the underlying neurocircuitry. The current study used reverse microdialysis to test the hypothesis that the preferential targeting of PFC catecholamines by low-dose psychostimulants involves direct action within the PFC, reflecting an intrinsic property of this region. For these studies, the effects of varying concentrations of MPH (0.25, 1.0, and 4.0 μM) on NE and DA efflux were examined within the PFC and select subcortical fields in unanesthetized rats. Low concentrations of MPH elicited significantly larger increases in extracellular levels of NE and DA in the PFC than in subcortical regions linked to motor-activating and arousal-promoting actions of psychostimulants (nucleus accumbens and medial septal area, respectively). The differential action of MPH across regions disappeared at higher concentrations. The enhanced sensitivity of PFC catecholamines to low and clinically relevant doses of psychostimulants, at least in part, reflects a unique sensitivity of this region to NE/DA transporter blockade. Available evidence suggests that the increased sensitivity of PFC catecholamines likely involves DA clearance through the NE transporter within the PFC. PMID:23303075

  13. Consequences of Low Dose Ionizing Radiation Exposure on the Hippocampal Microenvironment

    PubMed Central

    Acharya, Munjal M.; Patel, Neal H.; Craver, Brianna M.; Tran, Katherine K.; Giedzinski, Erich; Tseng, Bertrand P.; Parihar, Vipan K.; Limoli, Charles L.

    2015-01-01

    The response of the brain to irradiation is complex, involving a multitude of stress inducible pathways that regulate neurotransmission within a dynamic microenvironment. While significant past work has detailed the consequences of CNS radiotherapy following relatively high doses (≥ 45 Gy), few studies have been conducted at much lower doses (≤ 2 Gy), where the response of the CNS (like many other tissues) may differ substantially from that expected from linear extrapolations of high dose data. Low dose exposure could elicit radioadaptive modulation of critical CNS processes such as neurogenesis, that provide cellular input into hippocampal circuits known to impact learning and memory. Here we show that mice deficient for chemokine signaling through genetic disruption of the CCR2 receptor exhibit a neuroprotective phenotype. Compared to wild type (WT) animals, CCR2 deficiency spared reductions in hippocampal neural progenitor cell survival and stabilized neurogenesis following exposure to low dose irradiation. While radiation-induced changes in microglia levels were not found in WT or CCR2 deficient animals, the number of Iba1+ cells did differ between each genotype at the higher dosing paradigms, suggesting that blockade of this signaling axis could moderate the neuroinflammatory response. Interestingly, changes in proinflammatory gene expression were limited in WT animals, while irradiation caused significant elevations in these markers that were attenuated significantly after radioadaptive dosing paradigms in CCR2 deficient mice. These data point to the importance of chemokine signaling under low dose paradigms, findings of potential significance to those exposed to ionizing radiation under a variety of occupational and/or medical scenarios. PMID:26042591

  14. Short Communication: Viremic Control Is Independent of Repeated Low-Dose SHIVSF162p3 Exposures

    PubMed Central

    Henning, Tara R.; Hanson, Debra; Vishwanathan, Sundaram A.; Butler, Katherine; Dobard, Charles; Garcia-Lerma, Gerardo; Radzio, Jessica; Smith, James; McNicholl, Janet M.

    2014-01-01

    Abstract The repeat low-dose virus challenge model is commonly used in nonhuman primate studies of HIV transmission and biomedical preventions. For some viruses or challenge routes, it is uncertain whether the repeated exposure design might induce virus-directed innate or adaptive immunity that could affect infection or viremic outcomes. Retrospective cohorts of male Indian rhesus (n=40) and female pigtail (n=46) macaques enrolled in repeat low-dose rectal or vaginal SHIVSF162p3 challenge studies, respectively, were studied to compare the relationship between the number of previous exposures and peak plasma SHIV RNA levels or viral load area under the curve (AUC), surrogate markers of viral control. Repeated mucosal exposures of 10 or 50 TCID50 of virus for rectal and vaginal exposures, respectively, were performed. Virus levels were measured by quantitative reverse-transcriptase real-time PCR. The cumulative number of SHIVSF162p3 exposures did not correlate with observed peak virus levels or with AUC in rectally challenged rhesus macaques [peak: rho (ρ)=0.04, p=0.8; AUC: ρ=0.33, p=0.06] or vaginally challenged pigtail macaques (peak: ρ=−0.09, p=0.7; AUC: ρ=0.11, p=0.6). Infections in these models occur independently of exposure history and provide assurance that neither inoculation route nor number of exposures required for infection correlates with postinfection viremia. These data also indicate that both the vaginal and rectal repeated low-dose virus exposure models using SHIVSF162p3 provide a reliable system for nonhuman primate studies. PMID:25313448

  15. Very-low-dose combination: a first-line choice for the treatment of hypertension?

    PubMed

    Waeber, Bernard

    2003-06-01

    Essential hypertension is a very heterogeneous disease and different pressor mechanisms might interact to increase blood pressure. It is therefore not surprising that antihypertensive drugs given as monotherapies normalize blood pressure in only a proportion of hypertensive patients. This is, for instance, the case for diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor antagonists administered as single agents. The rationale for combining antihypertensive agents relates in part to the concept that the blood pressure-decreasing effect may be enhanced when two classes are coadministered. Also, combination treatment serves to counteract the counter-regulatory mechanisms that are triggered whenever pharmacologic intervention is initiated and act to limit the efficacy of the antihypertensive medication. For example, the compensatory increase in renin secretion induced by sodium depletion may become the predominant factor sustaining high blood pressure. Simultaneous blockade of the renin-angiotensin system, with either an ACE inhibitor or an AT1 receptor blocker, makes this compensatory hyper-reninaemia ineffective and allows maximum benefit from sodium depletion. The increased effectiveness obtained by combining a blocker of the renin-angiotensin system with a low dose of a diuretic is not obtained at the expense of reduced tolerability compared with the individual components administered alone. Fixed very-low-dose combinations containing an ACE inhibitor or an AT1 receptor blocker and a diuretic are therefore likely to become increasingly used, not only as second-line therapy, but also as first-line treatment. This is the case, for instance, for the fixed very-low-dose combination of the ACE inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), as this preparation is very effective in decreasing blood pressure while maintaining a tolerability that is similar to that of placebo. PMID:12929469

  16. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris

    PubMed Central

    Stark, Karolina; Scott, David E.; Tsyusko, Olga; Coughlin, Daniel P.; Hinton, Thomas G.

    2015-01-01

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae. PMID:25927361

  17. Low Dose Parathyroid Hormone Maintains Normal Bone Formation in Adult Male Rats During Rapid Weight Loss

    PubMed Central

    Turner, Russell T.; Iwaniec, Urszula T.

    2011-01-01

    A persistent negative energy balance results in bone loss. It is not clear whether the bone loss associated with chronic negative energy balance can be prevented. The objective of this study was to assess the efficacy of intermittent low dose parathyroid hormone (PTH) treatment in maintaining normal bone formation during severe energy restriction. Six-month-old male Fisher 344 rats were divided into 4 treatment groups: (1) baseline, (2) ad libitum (ad lib)-fed control, (3) energy-restricted (to consume 40% ad lib caloric intake), or (4) energy-restricted + low dose (1 μg/kg/d) PTH. Severe energy restriction for 14 days decreased body weight and serum leptin levels. Compared to ad lib-fed controls, energy-restricted rats had lower cancellous bone formation, higher osteoclast perimeter/bone perimeter and higher bone marrow adiposity in the proximal tibial metaphysis. Also, the energy-restricted rats had a lower periosteal bone formation rate at the tibia-fibula synostosis. Administration of PTH to energy-restricted rats had no effect on weight loss or osteoclast perimeter/bone perimeter. In contrast, energy-restricted rats treated with PTH had higher rates of cancellous and cortical bone formation compared to energy-restricted rats, and did not differ from the ad lib-fed control animals. Furthermore, PTH treatment maintained normal bone marrow adiposity. In conclusion, rapid weight loss in adult male rats was accompanied by decreased bone formation and increased bone marrow adiposity and these changes were prevented by low dose PTH treatment. Taken together, the results suggest that the energy cost of bone formation in adult rats is low and PTH therapy is effective in preventing the reduced bone formation associated with rapid weight loss. PMID:21215827

  18. Efficacy of Low Dose Barbiturate Coma Therapy for the Patients with Intractable Intracranial Hypertension Using the Bispectral™ Index Monitoring

    PubMed Central

    An, Hung-Shik; Kang, Jeong-Han; Kim, Moon-Kyu; Oh, Sae-Moon; Park, Se-Hyuck

    2010-01-01

    Objective Barbiturate coma therapy (BCT) is a useful method to control increased intracranial pressure (IICP) patients. However, the complications such as hypotension and hypokalemia have caused conditions that stopped BCT early. The complications of low dose BCT with Bispectral™ index (BIS) monitoring and those of high dose BCT without BIS monitoring have been compared to evaluate the efficacy of low dose BCT with BIS monitoring. Methods We analyzed 39 patients with high dose BCT group (21 patients) and low dose BCT group (18 patients). Because BIS value of 40-60 is general anesthesia score, we have adjusted the target dose of thiopental to maintain the BIS score of 40-60. Therefore, dose of thiopental was kept 1.3 to 2.6 mg/kg/hour during low dose BCT. However, high dose BCT consisted of 5 mg/kg/hour without BIS monitoing. Results The protocol of BCT was successful in 72.2% and 38.1% of low dose and high dose BCT groups, respectively. The complications such as QT prolongation, hypotension and cardiac arrest have caused conditions that stopped BCT early. Hypokalemia showed the highest incidence rate in complications of both BCT. The descent in potassium level were 0.63 ± 0.26 in low dose group, and 1.31 ± 0.48 in high dose group. The treatment durations were 4.89 ± 1.68 days and 3.38 ± 1.24 days in low dose BCT and high dose BCT, respectively. Conclusion It was proved that low dose BCT showed less severe complications than high dose BCT. Low dose BCT with BIS monitoring provided enough duration of BCT possible to control ICP. PMID:20461164

  19. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue. [Mice

    SciTech Connect

    Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

    1983-04-01

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy.

  20. State of the art low-dose CT angiography of the body.

    PubMed

    Alkadhi, Hatem; Schindera, Sebastian T

    2011-10-01

    This review summarizes current evidence based on pertinent literature on low-dose computed tomography angiography (CTA) of the body. Various strategies for optimizing CTA protocols with the aim to lower the radiation dose while maintaining the diagnostic accuracy of the examination are summarized. To date, various publications have demonstrated that CTA of the body can be performed at a low radiation dose while providing high quality information. Nevertheless, a number of questions still need to be answered, including the optimal combination of tube voltage and tube current settings, as well as the appropriate protocol parameters in relation to the body physiognomy and the specific body region imaged. PMID:21330084

  1. Excess processing of oxidative damaged bases causes hypersensitivity to oxidative stress and low dose rate irradiation.

    PubMed

    Yoshikawa, Y; Yamasaki, A; Takatori, K; Suzuki, M; Kobayashi, J; Takao, M; Zhang-Akiyama, Q-M

    2015-10-01

    Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in Escherichia coli (E. coli) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the effects and the mechanisms of other radiation, such as low dose rate radiation, heavy-ion beams, or hydrogen peroxide (H2O2), are still poorly understood. In the present study, we constructed a stable HeLaS3 cell line overexpressing human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) protein. We determined the survival of HeLaS3 and HeLaS3/hOGG1 cells exposed to UV, heavy-ion beams, γ-rays, and H2O2. The results showed that HeLaS3 cells overexpressing hOGG1 were more sensitive to γ-rays, OH(•), and H2O2, but not to UV or heavy-ion beams, than control HeLaS3. We further determined the levels of 8-oxoG foci and of chromosomal double-strand breaks (DSBs) by detecting γ-H2AX foci formation in DNA. The results demonstrated that both γ-rays and H2O2 induced 8-oxoguanine (8-oxoG) foci formation in HeLaS3 cells. hOGG1-overexpressing cells had increased amounts of γ-H2AX foci and decreased amounts of 8-oxoG foci compared with HeLaS3 control cells. These results suggest that excess hOGG1 removes the oxidatively damaged 8-oxoG in DNA more efficiently and therefore generates more DSBs. Micronucleus formation also supported this conclusion. Low dose-rate γ-ray effects were also investigated. We first found that overexpression of hOGG1 also caused increased sensitivity to low dose rate γ-ray irradiation. The rate of micronucleus formation supported the notion that low dose rate irradiation increased genome instability. PMID:26059740

  2. Fabricating high-density magnetic storage elements by low-dose ion beam irradiation

    SciTech Connect

    Neb, R.; Sebastian, T.; Pirro, P.; Hillebrands, B.; Pofahl, S.; Schaefer, R.; Reuscher, B.

    2012-09-10

    We fabricate magnetic storage elements by irradiating an antiferromagnetically coupled ferromagnetic/nonmagnetic/ferromagnetic trilayer by a low-dose ion beam. The irradiated areas become ferromagnetically coupled and are capable of storing information if their size is small enough. We employ Fe/Cr/Fe trilayers and a 30 keV focused Ga{sup +}-ion beam to demonstrate the working principle for a storage array with a bit density of 7 Gbit/in.{sup 2}. Micromagnetic simulations suggest that bit densities of at least two magnitudes of order larger should be possible.

  3. Algorithm of pulmonary emphysema extraction using low dose thoracic 3D CT images

    NASA Astrophysics Data System (ADS)

    Saita, S.; Kubo, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Omatsu, H.; Tominaga, K.; Eguchi, K.; Moriyama, N.

    2006-03-01

    Recently, due to aging and smoking, emphysema patients are increasing. The restoration of alveolus which was destroyed by emphysema is not possible, thus early detection of emphysema is desired. We describe a quantitative algorithm for extracting emphysematous lesions and quantitatively evaluate their distribution patterns using low dose thoracic 3-D CT images. The algorithm identified lung anatomies, and extracted low attenuation area (LAA) as emphysematous lesion candidates. Applying the algorithm to 100 thoracic 3-D CT images and then by follow-up 3-D CT images, we demonstrate its potential effectiveness to assist radiologists and physicians to quantitatively evaluate the emphysematous lesions distribution and their evolution in time interval changes.

  4. Design and Implementation of a Compact Low-Dose Diffraction Enhanced Medical Imaging System

    SciTech Connect

    Parham, C.; Zhong, Z; Connor, D; Chapman, D; Pisano, E

    2009-01-01

    This paper describes the design, construction, and performance of a new DEI system using a commercially available tungsten anode x-ray tube and includes the first high-quality low-dose diffraction-enhanced images of full-thickness human tissue specimens. Diffraction-enhanced imaging (DEI) is a new x-ray imaging modality that differs from conventional radiography in its use of three physical mechanisms to generate contrast. DEI is able to generate contrast from x-ray absorption, refraction, and ultra-small-angle scatter rejection (extinction) to produce high-contrast images with a much lower radiation dose compared to conventional radiography.

  5. Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole.

    PubMed

    Başay, Ömer; Basay, Burge Kabukcu; Öztürk, Önder; Yüncü, Zeki

    2016-05-31

    The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine prior to the initiation of aripiprazole treatment; thus, this report also discussed the possible mechanisms underlying the manifestation of dystonia from the perspective of neurotransmitter activity. PMID:27121436

  6. Fricke gel dosimeter with improved sensitivity for low-dose-level measurements.

    PubMed

    Valente, Mauro; Molina, Wladimir; Carrizales Silva, Lila; Figueroa, Rodolfo; Malano, Francisco; Pérez, Pedro; Santibañez, Mauricio; Vedelago, José

    2016-01-01

    Fricke solution has a wide range of applications as radiation detector and dosimetry. It is particularly appreciated in terms of relevant comparative advantages, like tissue-equivalence when prepared in aqueous media like gel matrix, continuous mapping capability, independence of dose rate and incident direction, as well as linear dose response. This work presents the development and characterization of an improved Fricke gel system, based on modified chemical compositions, making possible its application in clinical radiology due to its improved sensitivity. Properties of standard Fricke gel dosimeter for high-dose levels are used as a starting point, and suitable chemical modifications are introduced and carefully investigated in order to attain high resolution for low-dose ranges, like those corresponding to radiology interventions. The developed Fricke gel radiation dosimeter system achieves the expected typical dose-dependency, showing linear response in the dose range from 20 up to 4000 mGy. Systematic investigations including several chemical compositions are carried out in order to obtain an adequate dosimeter response for low-dose levels. A suitable composition from among those studied is selected as a good candidate for low-dose-level radiation dosimetry consisting of a modified Fricke solution fixed to a gel matrix containing benzoic acid along with sulfuric acid, ferrous sulfate, Xylenol orange, and tridistilled water. Dosimeter samples are prepared in standard vials for in-phantom irradiation and further characterization by spectrophotometry measuring visible light transmission and absorbance before and after irradiation. Samples are irradiated using typical X-ray tubes for radiology and calibrated Farmer-type ionization chamber is used as reference to measure dose rates inside phantoms at vial locations. Once sensitive material composition is optimized, dose-response curves show significant improvement regarding overall sensitivity for low dose levels

  7. Lung Cancer Screening with Low-Dose Computed Tomography for Primary Care Providers

    PubMed Central

    Richards, Thomas B.; White, Mary C.; Caraballo, Ralph S.

    2015-01-01

    This review provides an update on lung cancer screening with low-dose computed tomography (LDCT) and its implications for primary care providers. One of the unique features of lung cancer screening is the potential complexity in patient management if an LDCT scan reveals a small pulmonary nodule. Additional tests, consultation with multiple specialists, and follow-up evaluations may be needed to evaluate whether lung cancer is present. Primary care providers should know the resources available in their communities for lung cancer screening with LDCT and smoking cessation, and the key points to be addressed in informed and shared decision-making discussions with patients. PMID:24830610

  8. Screening for lung cancer with low-dose computed tomography: a review of current status

    PubMed Central

    Bowman, Rayleen V.; Yang, Ian A.; Fong, Kwun M.; Berg, Christine D.

    2013-01-01

    Screening using low-dose computed tomography (CT) represents an exciting new development in the struggle to improve outcomes for people with lung cancer. Randomised controlled evidence demonstrating a 20% relative lung cancer mortality benefit has led to endorsement of screening by several expert bodies in the US and funding by healthcare providers. Despite this pivotal result, many questions remain regarding technical and logistical aspects of screening, cost-effectiveness and generalizability to other settings. This review discusses the rationale behind screening, the results of on-going trials, potential harms of screening and current knowledge gaps. PMID:24163745

  9. Thromboelastometry in veal calves to detect hemostatic variations caused by low doses of dexamethasone treatment

    PubMed Central

    2013-01-01

    Background The illegal administration of hormones, steroids, β-agonists and other anabolic agents to productive livestock in the European Union continues, despite the long-term ban on their use and despite the measures provided under the directives to monitor certain substances and residues thereof in the interest of protecting consumer health and animal wellbeing. Often administered in low doses in the form of a drug cocktail, these compounds escape detection by common analytical techniques. The aim of this study was to determine whether low-dose dexamethasone administration (0.4 mg orally per day, for 20 days) in white-meat calves produced variations in blood coagulation, as measured by thromboelastometry. A second aim was to determine whether such variations could be valid in detecting illicit low-dose dexamethasone treatment. Results The study population was 42 Friesian calves kept under controlled conditions until 6 months of age. The calves were subdivided into 2 groups: a control group (group A, n = 28) and a group treated with dexamethasone (group B, n = 14) for 20 days beginning at 5 months of age. When compared against the age-matched control group, the dexamethasone-treated calves showed a significant increase in alpha angle, maximum clot firmness and a significant decrease in clot formation time on all thromboelastometric profiles (P < 0.05). The clotting time was significantly decreased on the in-TEM® profile but increased on the ex-TEM® and fib-TEM® profiles (P <0.05). The Receiver Operating Characteristic curves, plotted for the Maximum Clot Elasticity (MCE), had a cut-off value ≥488.23 mm for in-TEM® MCE [Se 85.7%, (95% CI 57.2-98.2); Sp 100% 96.43% (95% CI 81.7-99.9] and a cut-off value ≥63.94 mm for fib-TEM® MCE [Se 92.8 (95% CI 66.1-99.8); Sp 89.3% (95% CI 71.8-97.7)]. In order to increase the sensitivity of the test two parameters (in-TEM® and fib-TEM® MCE) were used as two parallel tests; subsequently, the

  10. Facility for gamma irradiations of cultured cells at low dose rates: design, physical characteristics and functioning.

    PubMed

    Esposito, Giuseppe; Anello, Pasquale; Pecchia, Ilaria; Tabocchini, Maria Antonella; Campa, Alessandro

    2016-09-01

    We describe a low dose/dose rate gamma irradiation facility (called LIBIS) for in vitro biological systems, for the exposure, inside a CO2 cell culture incubator, of cells at a dose rate ranging from few μGy/h to some tens of mGy/h. Three different (137)Cs sources are used, depending on the desired dose rate. The sample is irradiated with a gamma ray beam with a dose rate uniformity of at least 92% and a percentage of primary 662keV photons greater than 80%. LIBIS complies with high safety standards. PMID:27423023

  11. The effects of low doses of ionizing radiation - A question of ethics

    SciTech Connect

    Tschaeche, A.N.

    1996-12-31

    Three ethical questions are asked and answered about the current state of affairs concerning how those in power manipulate public understanding of the effects of low doses of ionizing radiation. The questions are as follows: (1) Is it ethical to frighten people when you do not know that there is anything to be frightened of? (2) Is it ethical to be so conservative that resources are spent to solve a problem that may not exist? (3) Is it ethical not to tell the whole truth about the effects of low levels of ionizing radiation?

  12. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen.

    PubMed

    Chocair, P; Duley, J; Simmonds, H A; Cameron, J S; Ianhez, L; Arap, S; Sabbaga, E

    1993-07-10

    Early rejection can still complicate renal transplantation even with cyclosporin. We added low-dose allopurinol (25 mg on alternative days) to "triple" immunosuppression with cyclosporin, prednisolone, and azathioprine for twelve recipients of cadaver renal grafts. The controls were fifteen patients on triple therapy alone. Only one rejection episode occurred among the allopurinol-treated patients, whereas eleven controls had rejections (seven with more than one episode). Allopurinol may be toxic when combined with azathioprine, yet the bone marrow tolerated the new regimen well. As expected, reduction of the azathioprine dose was necessary in the treated group. PMID:8100914

  13. Effects of low doses of alcohol on delta-9-tetrahydrocannabinol's effects in pregnant rats

    SciTech Connect

    Abel, E.L.; Subramanian, M.G. )

    1990-01-01

    Pregnant rats were intubated with 50 mg/kg of delta-9-tetrahydrocannabinol (THC) or with THC plus alcohol to determine if a low dose of alcohol would significantly increase blood levels of THC. On the basis of this study, a second study was conducted in which pregnant rats were intubated with THC plus alcohol from gestation day six to parturition. THC reduced birth weights but did not significantly affect litter size or passive avoidance learning. Alcohol did not have a significant effect on offspring birth weight nor did it interact with THC to affect offspring.

  14. Seizures associated with low-dose tramadol for chronic pain treatment

    PubMed Central

    Beyaz, Serbülent Gökhan; Sonbahar, Tuğba; Bayar, Fikret; Erdem, Ali Fuat

    2016-01-01

    The management of cancer pain still poses a major challenge for clinicians. Tramadol is a centrally acting synthetic opioid analgesic. Its well-known side effects include nausea, vomiting, and dizziness; seizures are a rare side effect. Some reports have found that tramadol triggers seizure activity at high doses, whereas a few preclinical studies have found that this seizure activity is not dose-related. We herein present a case involving a patient with laryngeal cancer who developed seizures while on low-dose oral tramadol. PMID:27212778

  15. Issues in Low Dose Radiation Biology: The Controversy Continues. A Perspective

    SciTech Connect

    Morgan, William F.; Bair, William J.

    2013-05-01

    Both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a risk to human health. Much of this is unavoidable, e.g., natural background radiation, and as the use of radiation in modern medicine and industry increases so does the potential health risk. This perspective reflects the author’s view of current issues in low dose radiation biology research, highlights some of the controversies therein, and suggests areas of future research to address these issues. The views expressed here are the authors own and do not represent any institution, organization or funding body.

  16. Successful treatment of severe arthralgia associated with palmoplantar pustulosis with low-dose oral cyclosporine A.

    PubMed

    Yamamoto, T; Kimura, K; Katayama, I; Nishioka, K

    1995-07-01

    Two patients with severe arthralgia associated with palmoplantar pustulosis (PPP) were treated with oral cyclosporine A (CsA). Clinical efficacy was assessed on a 0-4 point scale for erythema, desquamation, infiltration, and pustulation, and on a 0-3 point pain scale. Skin lesions and arthralgia improved within twelve weeks with low dose CsA ranging from 2.1 to 2.2 mg/kg/day. High levels of plasma interleukin-6 (IL-6) were reduced to the normal range. PMID:7560444

  17. Reversible keratopathy due to hypertyrosinaemia following intermittent low-dose nitisinone in alkaptonuria: a case report.

    PubMed

    Stewart, R M K; Briggs, M C; Jarvis, J C; Gallagher, J A; Ranganath, L

    2014-01-01

    We describe a patient with ultra-rare disease, alkaptonuria, who developed tyrosine keratopathy following nitisinone therapy of 2 mg on alternate days. His vision became impaired approximately 7 weeks following the commencement of nitisinone and ophthalmological examination at week nine showed characteristic dendritic keratopathy associated with tyrosinaemia. The corneal lesion as well as his visual symptoms normalized completely following discontinuation of nitisinone. This is the first documented report of keratopathy due to acquired tyrosinaemia due to very low-dose nitisinone. PMID:24997710

  18. Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole

    PubMed Central

    Başay, Ömer; Basay, Burge Kabukcu; Öztürk, Önder; Yüncü, Zeki

    2016-01-01

    The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine prior to the initiation of aripiprazole treatment; thus, this report also discussed the possible mechanisms underlying the manifestation of dystonia from the perspective of neurotransmitter activity. PMID:27121436

  19. Radiation-induced apoptosis in SCID mice spleen after low dose irradiation

    NASA Astrophysics Data System (ADS)

    Takahashi, A.; Kondo, N.; Inaba, H.; Uotani, K.; Kiyohara, Y.; Ohnishi, K.; Ohnishi, T.

    To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB-17 Icr +/ + were irradiated with X-ray at 3.0 C3y at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/ + mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.

  20. Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment

    SciTech Connect

    Kataoka, Masateru; Kawamuro, Yuki; Shiraki, Nobuaki; Miki, Rika; Sakano, Daisuke; Yoshida, Tetsu; Yasukawa, Takanori; Kume, Kazuhiko; Kume, Shoen

    2013-01-18

    Highlights: ► We monitored long-term beta cell regeneration in neonatal mice treated with low dose STZ. ► Low-dose STZ neonatal female mice recovered blood glucose in 150 days. ► Glucose intolerance of the STZ treated mice significantly improved in 150 days. -- Abstract: Administration of streptozotocin (STZ) induces destruction of β-cells and is widely used as an experimental animal model of type I diabetes. In neonatal rat, after low-doses of STZ-mediated destruction of β-cells, β-cells regeneration occurs and reversal of hyperglycemia was observed. However, in neonatal mice, β-cell regeneration seems to occur much slowly compared to that observed in the rat. Here, we described the time dependent quantitative changes in β-cell mass during a spontaneous slow recovery of diabetes induced in a low-dose STZ mice model. We then investigated the underlying mechanisms and analyzed the cell source for the recovery of β-cells. We showed here that postnatal day 7 (P7) female mice treated with 50 mg/kg STZ underwent the destruction of a large proportion of β-cells and developed hyperglycemia. The blood glucose increased gradually and reached a peak level at 500 mg/dl on day 35–50. This was followed by a spontaneous regeneration of β-cells. A reversal of non-fasting blood glucose to the control value was observed within 150 days. However, the mice still showed impaired glucose tolerance on day 150 and day 220, although a significant improvement was observed on day 150. Quantification of the β-cell mass revealed that the β-cell mass increased significantly between day 100 and day 150. On day 150 and day 220, the β-cell mass was approximately 23% and 48.5% of the control, respectively. Of the insulin-positive cells, 10% turned out to be PCNA-positive proliferating cells. Our results demonstrated that, β-cell duplication is one of the cell sources for β-cell regeneration.

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

    PubMed

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

    2015-01-01

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

  2. Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress.

    PubMed

    Muthappa, N A; Gupta, Subodh; Yengkokpam, Sona; Debnath, Dipesh; Kumar, Neeraj; Pal, Asim Kumar; Jadhao, Sanjay B

    2014-01-01

    An experiment was conducted to evaluate the role of different lipotropes in modulating immunity and biochemical plasticity under conditions of sublethal low-dose pesticide-induced stress in fish. Labeo rohita fish fingerlings were divided in two sets with one set of fish continuously exposed to low-dose endosulfan (1/10th of 96-h LC50) for 21 days, the other was unexposed, and both sets of fish were fed with practical diets supplemented with either 2 % lecithin, 0.5 % betaine, or 0.1 % choline and compared against unsupplemented diet. Low-dose endosulfan exposure had adverse effects (P < 0.05/P < 0.01) on hematological profile (erythrocyte count, hemoglobin, and hematocrit), serum protein (total protein, albumin, and globulin) and lipid profile (cholesterol and triglyceride), anti-oxidative status (ascorbic acid content of muscle, liver, brain, and kidney and activity of anti-oxidative enzymes: catalase and superoxide dismutase), neurotransmission (acetylcholinesterase activity in muscle and brain), immunological attributes (WBC count, albumin to globulin ratio, phagocytic activity, and serum cortisol), and metabolic plasticity as revealed from enzyme activities (muscle lactate dehydrogenase, liver and kidney glucose-6-phosphatase dehydrogenase-G6PDH activity). Dietary lipotropes prevented these effects completely or partially and the effects were lipotrope dependent. Kinetics (maximum velocity value V max, catalytic efficiency and Michaelis constant K m) of G6PDH enzyme from crude extracts of liver and kidney indicated inhibition due to endosulfan but lipotropes could protect enzyme and showed a stabilizing effect. The supplements also helped maintain integrity of histoarchitecture of the hepatocytes in endosulfan-exposed fish to a great extent. Feeding lipotropes to fish reared in endosulfan-free water also improved hematological and serum protein and lipid profiles and were immunostimulatory. In conclusion, dietary lipotropes, especially betaine and

  3. Biological effects of low doses of ionizing radiations: Particle tracks in radiobiology

    NASA Astrophysics Data System (ADS)

    Katz, Robert; Hofmann, Werner

    1982-12-01

    A radiation field is made up of a tangle of particle tracks, from the primary particle and secondary and higher generation electron interaction, well isolated at low doses and with multiple intersections in cell nuclei at high doses. Low dose effects in multicellular systems are therefore the sum of individual track structures. Until we can state with confidence the structure of a particle track in biological matter for all end-points of interest, at least as well as we can for nuclear emulsions, our knowledge of low dose effects should be regarded as uncertain and inadequate. In this context "track structure" means the response of physical and biological systems along the path of the particle, and depends on the observed end-point as well as on the identity of the particle. For mammalian cell killing and a few other biological end-points track and experimental radiosensitivity parameters allow as to construct schematic models. If we take a particle track to consist of a sequence of inactivated cells strung along the path of a particle, neither electrons nor protons leave a track in a compact mammalian cell structure. At most there is an occasional killed cell at the end of the range of a proton or an electron where the particle stops in the nucleus of a cell, with probability less than 0.3 for a proton, and less than 0.01 for an electron. The variety of potential targets whose size may be compared to the measured inactivation cross-section and the lack of a fully consistent theory of RBE make it possible to decide, from this information alone, whether cell killing is an individual (1-hit) or cooperative (many-hit) phenomenon, especilally for electrons. a siilar analysis of epidemiological data for cancer induction leads to probabilities and action cross-sections so low as to make a linear extrapolation implausible. In assigning quality factors at highest LET values we should consider that heavy ions inactive cells, so that neither mutation nor transformation can

  4. The efficacy of low-dose transdermal fentanyl in opioid-naïve cancer patients with moderate-to-severe pain

    PubMed Central

    Kang, Jung Hun; Oh, Sung Yong; Song, Seo-Young; Lee, Hui-Young; Kim, Jung Han; Lee, Kyoung Eun; Lee, Hye Ran; Hwang, In Gyu; Park, Se Hoon; Kim, Won Seok; Park, Young Suk

    2015-01-01

    Background/Aims Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naïve patients with moderate-to-severe cancer pain. Methods This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 µg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. Results Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean ± SD, 5.10 ± 2.48 vs. 2.48 ± 1.56; p < 0.001). TDF dose (27.8 µg/hr vs. 24.8 µg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). Conclusions Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted. PMID:25589840

  5. Efficacy and safety of low-dose ketamine as an adjunct analgesic and amnesic during caesarean section under general anaesthesia

    PubMed Central

    Rajan, Sunil; Hassain, Anwar; Puthenveettil, Nitu; Kumar, Lakshmi

    2015-01-01

    Background and Aims: The practice of avoiding sedatives or anxiolytics during caesarean section under general anaesthesia (GA) until delivery of the baby could result in exaggerated haemodynamic responses and an increased risk of awareness. We aimed to assess the efficacy and safety of low-dose ketamine, used as an adjunct analgesic and amnesic, in attenuating these responses during caesarean section under GA. Methods: This prospective, randomised study was conducted in 40 patients. Group K (n = 20) received 0.25 mg/kg ketamine, whereas Group C received 5 ml normal saline intravenously (IV) just before induction of anaesthesia. After intubation, patients were ventilated with O2 and N2O (40:60%) with 0.7% end-tidal isoflurane. Fentanyl and midazolam were given following delivery of the baby. Mann–Whitney and Fisher's exact tests were used for statistical analysis. Results: Preinduction haemodynamic parameters and those recorded at 1 min after induction were comparable in both groups. However, heart rate and systolic blood pressure recorded after intubation (at 3, 5, 7, 9, 12, 15, 20, 30 and 45 min after induction) showed significantly high values in Group C (P < 0.05). Mean arterial pressure also showed a similar pattern. Umbilical vein pO2, pCO2 and pH were comparable in both groups. Though Apgar score at 1 min showed a higher scoring in Group K, at 5 min both groups had comparable scores. In Group C, intraoperative lacrimation (50% vs. 0%) and hallucinations/recall of intraoperative events (10% vs. 0%) were high. Conclusion: IV ketamine 0.25 mg/kg can be safely used as an adjunct analgesic and amnesic to attenuate haemodynamic responses during caesarean section under GA without affecting the foetal outcome. PMID:26644613

  6. Allopurinol enhances the activity of hypoxanthine-guanine phosphoribosyltransferase in inflammatory bowel disease patients during low-dose thiopurine therapy: preliminary data of an ongoing series.

    PubMed

    Seinen, Margien L; de Boer, Nanne K H; Smid, Kees; van Asseldonk, Dirk P; Bouma, Gerd; van Bodegraven, Adriaan A; Peters, Godefridus J

    2011-12-01

    Thiopurines are crucial in the treatment of inflammatory bowel disease. The phenotype of pivotal metabolic enzymes determines whether thioguanine nucleotides (6-TGN) are generated in clinically sufficiently high levels. The first step in activation of thiopurine prodrugs to 6-TGN is catalysis by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Often, patients exhibit a clinically unfavorable metabolism, leading to discontinuation of conventional thiopurine therapy. The combination of allopurinol and low-dose thiopurine therapy may optimize this variant metabolism, presumably by affecting enzyme activities. We performed a prospective pharmacodynamic study to determine the effect of combination therapy on the activity of HGPRT. The activity of HGPRT and 6-TGN concentrations was measured in red blood cells during thiopurine monotherapy and after 4 weeks of combination therapy. The activity of HGPRT was also measured after 12 weeks of combination therapy. From the results, we conclude that combination therapy increases the activity of HGPRT and subsequently 6-TGN concentrations. PMID:22132961

  7. FLOW GATING

    DOEpatents

    Poppelbaum, W.J.

    1962-12-01

    BS>This invention is a fast gating system for eiectronic flipflop circuits. Diodes connect the output of one circuit to the input of another, and the voltage supply for the receiving flip-flop has two alternate levels. When the supply is at its upper level, no current can flow through the diodes, but when the supply is at its lower level, current can flow to set the receiving flip- flop to the same state as that of the circuit to which it is connected. (AEC)

  8. Causes of genome instability: the effect of low dose chemical exposures in modern society

    PubMed Central

    Langie, Sabine A.S.; Koppen, Gudrun; Desaulniers, Daniel; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Azqueta, Amaya; Bisson, William H.; Brown, Dustin; Brunborg, Gunnar; Charles, Amelia K.; Chen, Tao; Colacci, Annamaria; Darroudi, Firouz; Forte, Stefano; Gonzalez, Laetitia; Hamid, Roslida A.; Knudsen, Lisbeth E.; Leyns, Luc; Lopez de Cerain Salsamendi, Adela; Memeo, Lorenzo; Mondello, Chiara; Mothersill, Carmel; Olsen, Ann-Karin; Pavanello, Sofia; Raju, Jayadev; Rojas, Emilio; Roy, Rabindra; Ryan, Elizabeth; Ostrosky-Wegman, Patricia; Salem, Hosni K.; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Van Schooten, Frederik J.; Valverde, Mahara; Woodrick, Jordan; Zhang, Luoping; van Larebeke, Nik; Kirsch-Volders, Micheline; Collins, Andrew R.

    2015-01-01

    Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome’s integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis. PMID:26106144

  9. Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.

    PubMed

    Hay, J L; La Vincente, S F; Somogyi, A A; Chapleo, C B; White, J M

    2011-03-01

    Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects. PMID:20728384

  10. In silico modeling of spore inhalation reveals fungal persistence following low dose exposure

    PubMed Central

    Tanaka, Reiko J.; Boon, Neville J.; Vrcelj, Katarina; Nguyen, Anita; Vinci, Carmelina; Armstrong-James, Darius; Bignell, Elaine

    2015-01-01

    The human lung is constantly exposed to spores of the environmental mould Aspergillus fumigatus, a major opportunistic pathogen. The spectrum of resultant disease is the outcome of complex host-pathogen interactions, an integrated, quantitative understanding of which lies beyond the ethical and technical reach permitted by animal studies. Here we construct a mathematical model of spore inhalation and clearance by concerted actions of macrophages and neutrophils, and use it to derive a mechanistic understanding of pathogen clearance by the healthy, immunocompetent host. In particular, we investigated the impact of inoculum size upon outcomes of single-dose fungal exposure by simulated titrations of inoculation dose, from 106 to 102 spores. Simulated low-dose (102) spore exposure, an everyday occurrence for humans, revealed a counter-intuitive prediction of fungal persistence (>3 days). The model predictions were reflected in the short-term dynamics of experimental murine exposure to fungal spores, thereby highlighting the potential of mathematical modelling for studying relevant behaviours in experimental models of fungal disease. Our model suggests that infectious outcomes can be highly dependent upon short-term dynamics of fungal exposure, which may govern occurrence of cyclic or persistent subclinical fungal colonisation of the lung following low dose spore inhalation in non-neutropenic hosts. PMID:26364644

  11. A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

    SciTech Connect

    Liu, Yixun; Summers, Ronald M.; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.; Nacif, Marcelo S.

    2013-10-15

    Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.

  12. Toxic effects of low doses of Bisphenol-A on human placental cells

    SciTech Connect

    Benachour, Nora; Aris, Aziz

    2009-12-15

    Humans are exposed daily to a great number of xenobiotics and their metabolites present as pollutants. Bisphenol-A (BPA) is extensively used in a broad range of products including baby bottles, food-storage containers, medical equipment, and consumer electronics. Thus, BPA is the most common monomer for polycarbonates intended for food contact. Levels of this industrial product are found in maternal blood, amniotic fluid, follicular fluid, placental tissue, umbilical cord blood, and maternal urine. In this study, we investigated toxic effects of BPA concentrations close to levels found in serum of pregnant women on human cytotrophoblasts (CTB). These cells were isolated from fresh placentas and exposed to BPA for 24 h. Our results showed that very low doses of BPA induce apoptosis (2 to 3 times) as assessed using M30 antibody immunofluorescent detection, and necrosis (1.3 to 1.7 times) as assessed through the cytosolic Adenylate Kinase (AK) activity after cell membrane damage. We also showed that BPA increased significantly the tumor-necrosis factor alpha (TNF-alpha) gene expression and protein excretion as measured by real-time RT-PCR and ELISA luminescent test, respectively. Moreover, we observed that induction of AK activation and TNF-alpha gene expression require lower levels of BPA than apoptosis or TNF-alpha protein excretion. Our findings suggest that exposure of placental cells to low doses of BPA may cause detrimental effects, leading in vivo to adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction, prematurity and pregnancy loss.

  13. [HEALTH PREDICTION INDICES OBTAINED WITH LOW-DOSE COMPUTER TOMOGRAPHY SCANS].

    PubMed

    Matkevich, E i; Sinitsyn, V e; Ivanov LV

    2015-01-01

    Purpose of the investigation was to make prognostic estimations of reductions in somatic morbidity and temporal disability, and tumor pathology using low-dose computer tomography (CT) scans and to compare with standard protocols. Mean effective radiation doses were determined based on the results of 1627 diagnostic CT investigations made in 2012-2014 at the Treatment and Rehabilitation Center of the Russian Ministry of Health. Low-dose CT scans of the head and thoracic, abdominal and small pelvis organs were obtained on a GE Discovery CT750 HD, and with the help of the ASIR and MBIR algorithms of iterative reconstruction. In comparison with a standard dose, a single CT scan with a dose reduced by 10-12 mSv predicts a decrease in total morbidity by 0.84-5.52% and temporal disability by 0.55-1.65% per 100 employees over a year; total risk of tumors and genetic effects reduced in 5 to 10 times, which may be equal to 40-90 cases per 100,000 of 30 y.o. males. PMID:26934792

  14. Effects of Low Dose Particle Radiation to Mouse Neonatal Neurons in Culture

    NASA Astrophysics Data System (ADS)

    Nojima, K.; Vazquez, M. E.; Okayasu, R.; Nagaoka, S.

    To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05Gy up to 2.0Gy. The subsequent biological effectswere evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55 -200 keV/μ m) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this repot, a result of memory and learning function to adult mice after whole-body and brainlocal irradiation at carbon ion and iron ion.

  15. Low dose busulfan facilitates chimerism and tolerance in a murine model.

    PubMed

    Anam, Khairul; Black, Alfred T; Hale, Douglas A

    2006-01-01

    T cell depletion, sirolimus and "mega" dose donor specific bone marrow (DSBM) infusion promotes stable multilineage chimerism and indefinite survival of skin allografts in completely mismatched mice. The purpose of this study is to determine whether the addition of low dose busulfan can reduce the amount of DSBM required while preserving efficacy. C57BL/6 recipients of BALB/c skin allografts were treated with alphaCD4 and alphaCD8 monoclonal antibodies, DSBM, sirolimus and various doses of busulfan. The kinetics and phenotype of chimerism and the presence of clonal deletion of alloreactive T-cells were defined using flow cytometry. In vitro reactivity was determined using mixed lymphocyte culture. Second skin grafts confirmed the presence of tolerance. All doses of busulfan resulted in engraftment when combined with this regimen using a reduced dose of donor marrow. The level, kinetics and character of chimerism observed were dose related. Chimerism was associated with indefinite allograft acceptance (>200 days). Tolerance was documented both in vitro/in vivo and was associated with clonal deletion. Addition of a single low dose of busulfan to an established tolerance protocol reduced the required DSBM dose by over 80% while still promoting comparable levels of donor chimerism and donor-specific tolerance. PMID:16431286

  16. A Low-Dose Electron Diffraction Assay for Protection of Protein Structure against Damage from Drying

    NASA Astrophysics Data System (ADS)

    Massover, William H.

    2004-04-01

    A new assay using low-dose electron diffraction to measure the protection of protein structure against damage from drying is described. When thin single crystals of catalase are dried within water alone, low-dose electron diffraction yields no Bragg spots. Drying within an experimental aqueous solution that permits detection of diffraction spots thereby indicates a positive result, and the extent of these Bragg reflections into the high angle range gives a quantitative measure of the degree of protection. Bragg spots out to 3.7 3.9 [Angstrom capital A, ring] are recorded for drying within 100 mM solutions of the known structure-preserving sugars, sucrose, tannin, and trehalose. The ability of trehalose to maintain native protein structure during drying starts between 10 and 25 mM, and changes only slightly at concentrations above this threshold; with drying in 150-mM trehalose, catalase crystals yield diffraction spots out to 3.7 [Angstrom capital A, ring]. Drying within the organic nonsugar polymer polyvinylpyrrolidone gives Bragg spots to 4.0 [Angstrom capital A, ring]. This new assay should be useful to measure the unexamined structure-preserving capabilities of modified sugars, other nonsugars, and mixtures to identify which protective matrix maintains native protein structure to the greatest extent during drying; electron crystallography using that optimal matrix should yield protein structure at improved levels of high resolution.

  17. Neurodegeneration and adaptation in response to low-dose photon irradiation

    SciTech Connect

    Limoli, Charles L.

    2014-10-27

    Neural stem and precursor cells (i.e. multipotent neural cells) are concentrated in the neurogenic regions of the brain (hippocampal dentate gyrus, subventricular zones), and considerable evidence suggests that these cells are important in mediating the stress response of the CNS after damage from ionizing radiation. The capability of these cells to proliferate, migrate and differentiate (i.e. to undergo neurogenesis) suggests they can participate in the repair and maintenance of CNS functions by replacing brain cells damaged or depleted due to irradiation. Importantly, we have shown that multipotent neural cells are markedly sensitive to irradiation and oxidative stress, insults that compromise neurogenesis and hasten the onset and progression of degenerative processes that are likely to have an adverse impact on cognition. Our past and current work has demonstrated that relatively low doses of radiation cause a persistent (weeks-months) oxidative stress in multipotent neural cells that can elicit a range of degenerative sequelae in the CNS. Therefore, our project is focused on determining the extent that endogenous and redox sensitive multipotent neural cells represent important radioresponsive targets for low dose radiation effects. We hypothesize that the activation of redox sensitive signaling can trigger radioadaptive changes in these cells that can be either harmful or beneficial to overall cognitive health.

  18. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation

    PubMed Central

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-01-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  19. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis

    PubMed Central

    Shen, Jian; Song, Ning; Williams, Christopher J.; Brown, Celeste J.; Yan, Zheng; Xu, Chen; Forney, Larry J.

    2016-01-01

    Atrophic vaginitis (AV) is common in postmenopausal women, but its causes are not well understood. The symptoms, which include vaginal itching, burning, dryness, irritation, and dyspareunia, can usually be alleviated by low doses of estrogen given orally or locally. Regrettably, the composition of vaginal bacterial communities in women with AV have not been fully characterized and little is known as to how these communities change over time in response to hormonal therapy. In the present intervention study we determined the response of vaginal bacterial communities in postmenopausal women with AV to low-dose estrogen therapy. The changes in community composition in response to hormonal therapy were rapid and typified by significant increases in the relative abundance of Lactobacillus spp. that were mirrored by a decreased relative abundance of Gardnerella. These changes were paralleled by a significant four-fold increase in serum estradiol levels and decreased vaginal pH, as well as nearly a two-fold increase in the Vaginal Maturation Index (VMI). The results suggest that after menopause a vaginal microbiota dominated by species of Lactobacillus may have a beneficial role in the maintenance of health and these findings that could lead to new strategies to protect postmenopausal women from AV. PMID:27103314

  20. Improving low-dose cardiac CT images using 3D sparse representation based processing

    NASA Astrophysics Data System (ADS)

    Shi, Luyao; Chen, Yang; Luo, Limin

    2015-03-01

    Cardiac computed tomography (CCT) has been widely used in diagnoses of coronary artery diseases due to the continuously improving temporal and spatial resolution. When helical CT with a lower pitch scanning mode is used, the effective radiation dose can be significant when compared to other radiological exams. Many methods have been developed to reduce radiation dose in coronary CT exams including high pitch scans using dual source CT scanners and step-and-shot scanning mode for both single source and dual source CT scanners. Additionally, software methods have also been proposed to reduce noise in the reconstructed CT images and thus offering the opportunity to reduce radiation dose while maintaining the desired diagnostic performance of a certain imaging task. In this paper, we propose that low-dose scans should be considered in order to avoid the harm from accumulating unnecessary X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. Accordingly, in this paper, a 3D dictionary representation based image processing method is proposed to reduce CT image noise. Information on both spatial and temporal structure continuity is utilized in sparse representation to improve the performance of the image processing method. Clinical cases were used to validate the proposed method.

  1. Selective histamine H(1) antagonism: a novel approach to insomnia using low-dose doxepin.

    PubMed

    Owen, Richard T

    2009-04-01

    Doxepin is a tricyclic antidepressant with a subnanomolar affinity for the histamine H(1) (H(1)) receptor. It has a long history of use for depression at doses higher than those needed for antagonism of H(1) receptors. Recent work has focused on its use at low doses (1, 3 and 6 mg) in patients with chronic primary insomnia. Two phase II studies and four phase III studies have investigated its efficacy on both objective and subjective sleep measures in both adults and elderly patients. It was effective on a variety of sleep onset, maintenance and early awakening outcomes and had minimal effects on sleep architecture. There was no signal for tolerance, psychomotor impairment, residual sedation, rebound insomnia or discontinuation symptoms in trials of up to 3 months duration. Doxepin was well tolerated; sedation/sleepiness and headache were the most common adverse events but these were mainly at placebo level or less. Further work is required to establish doxepin's low-dose effect on hypnotic activity. PMID:19499091

  2. Dictionary learning based low-dose x-ray CT reconstruction using a balancing principle

    NASA Astrophysics Data System (ADS)

    Mou, Xuanqin; Wu, Junfeng; Bai, Ti; Xu, Qiong; Yu, Hengyong; Wang, Ge

    2014-09-01

    The high utility and wide applicability of x-ray imaging has led to a rapidly increased number of CT scans over the past years, and at the same time an elevated public concern on the potential risk of x-ray radiation to patients. Hence, a hot topic is how to minimize x-ray dose while maintaining the image quality. The low-dose CT strategies include modulation of x-ray flux and minimization of dataset size. However, these methods will produce noisy and insufficient projection data, which represents a great challenge to image reconstruction. Our team has been working to combine statistical iterative methods and advanced image processing techniques, especially dictionary learning, and have produced excellent preliminary results. In this paper, we report recent progress in dictionary learning based low-dose CT reconstruction, and discuss the selection of regularization parameters that are crucial for the algorithmic optimization. The key idea is to use a "balancing principle" based on a model function to choose the regularization parameters during the iterative process, and to determine a weight factor empirically for address the noise level in the projection domain. Numerical and experimental results demonstrate the merits of our proposed reconstruction approach.

  3. Specific Metabolic Fingerprint of a Dietary Exposure to a Very Low Dose of Endosulfan

    PubMed Central

    Canlet, Cécile; Tremblay-Franco, Marie; Gautier, Roselyne; Molina, Jérôme; Métais, Benjamin; Blas-Y Estrada, Florence; Gamet-Payrastre, Laurence

    2013-01-01

    Like other persistent organochlorine pesticides, endosulfan residues have been detected in foods including fruit, vegetables, and fish. The aim of our study was to assess the impact of a dietary exposure to low doses of endosulfan from foetal development until adult age on metabolic homeostasis in mice and to identify biomarkers of exposure using an 1H-NMR-based metabonomic approach in various tissues and biofluids. We report in both genders an increase in plasma glucose as well as changes in levels of factors involved in the regulation of liver oxidative stress, confirming the prooxidant activities of this compound. Some metabolic changes were distinct in males and females. For example in plasma, a decrease in lipid LDL and choline content was only observed in female. Lactate levels in males were significantly increased. In conclusion, our results show that metabolic changes in liver could be linked to the onset of pathologies like diabetes and insulin resistance. Moreover from our results it appears that the NMR-based metabonomic approach could be useful for the characterization in plasma of a dietary exposure to low dose of pesticide in human. PMID:23431292

  4. Increase of onion yield through low dose of gamma irradiation of its seeds

    NASA Astrophysics Data System (ADS)

    Wiendl, F. M.; Wiendl, F. W.; Wiendl, J. A.; Vedovatto, A.; Arthur, V.

    1995-02-01

    The increase of onions' yield could be achieved by the common farmer through the use of nuclear techniques. This report describes the results obtained with the irradiation of onion seeds, with low doses of gamma radiations (Cobalt-60), at doses of 0 (control), 150, 400 and 700 Gy. Beyond the proper onion's variety also the use of low dose rates of 13.1, 39.2 and 52.3 Gy per hour were of the great importance during irradiation. The results showed to be promising, both in laboratory studies and in the field, resulting in an increase of onions production: A greater number of seedlings, bulbs and a higher yield in weight per hectar were planted. In the field the most promising dose and dose rate to the variety "Super-X" were respectively 150 Gy and 13.1 Gy per hour, yielding an 24.9 percent heavier weight of onions than the control. The other tested variety was "Granex-33", which did not respond so favorable to irradiation. However, also with this variety we harvested a 2.1 percent heavier weight than its control, if the onion seeds were irradiated with the dose of 700 Gy at a dose dose rate of 13.1 Gy per hour.

  5. Symptoms of delusion: the effects of discontinuation of low-dose venlafaxine

    PubMed Central

    Koga, M; Kodaka, F; Miyata, H; Nakayama, K

    2009-01-01

    Objective: We report a patient who experienced delusional symptoms during gradual discontinuation of low-dose venlafaxine and required antipsychotic treatment. Method: Case report. Results: A 31-year-old woman with major depression had been treated abroad with venlafaxine before returning to Japan. Since venlafaxine is unavailable here, we supplemented her regular venlafaxine dosage of 37.5 mg/day with clomipramine 20 mg/day. After 5 weeks we reduced venlafaxine to 18.75 mg/day and uptitrated clomipramine to 40 mg/day. Four days later she developed delusions of reference, palpitations and nausea. Clomipramine was increased to 60 mg/day, and her symptoms subsided. Eight weeks later her supply of venlafaxine ran out, and within 4 days her condition deteriorated into more severe symptoms that required 4 months’ antipsychotic treatment. Conclusion: We speculate that her symptoms were discontinuation syndrome, including psychotic symptoms and physical symptoms, caused by (i) venlafaxine-clomipramine interaction and/or (ii) the serotonin reuptake inhibitor-like effects of low-dose venlafaxine. PMID:19573048

  6. Effect of low-dose scopolamine on autonomic control of the heart

    NASA Technical Reports Server (NTRS)

    Raeder, E. A.; Stys, A.; Cohen, R. J.

    1997-01-01

    Background: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. Methods: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. Results: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. Conclusions: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

  7. Effects of Low-Dose Diethylstilbestrol Exposure on DNA Methylation in Mouse Spermatocytes

    PubMed Central

    Yin, Li; Zheng, Li-juan; Jiang, Xiao; Liu, Wen-bin; Han, Fei; Cao, Jia; Liu, Jin-yi

    2015-01-01

    Evidence from previous studies suggests that the male reproductive system can be disrupted by fetal or neonatal exposure to diethylstilbestrol (DES). However, the molecular basis for this effect remains unclear. To evaluate the effects of DES on mouse spermatocytes and to explore its potential mechanism of action, the levels of DNA methyltransferases (DNMTs) and DNA methylation induced by DES were detected. The results showed that low doses of DES inhibited cell proliferation and cell cycle progression and induced apoptosis in GC-2 cells, an immortalized mouse pachytene spermatocyte-derived cell line, which reproduces primary cells responses to E2. Furthermore, global DNA methylation levels were increased and the expression levels of DNMTs were altered in DES-treated GC-2 cells. A total of 141 differentially methylated DNA sites were detected by microarray analysis. Rxra, an important component of the retinoic acid signaling pathway, and mybph, a RhoA pathway-related protein, were found to be hypermethylated, and Prkcd, an apoptosis-related protein, was hypomethylated. These results showed that low-dose DES was toxic to spermatocytes and that DNMT expression and DNA methylation were altered in DES-exposed cells. Taken together, these data demonstrate that DNA methylation likely plays an important role in mediating DES-induced spermatocyte toxicity in vitro. PMID:26588706

  8. The Radiobiological Basis for Improvements in Radiotherapy and Low Dose Risk Assessment

    SciTech Connect

    Hei, Tom K

    2009-12-09

    Overall Goal: This conference grant was proposed to organize and host an international conference at Columbia University in New York to critically assess the cellular and molecular signaling events and tissue response following radiation damage. The conference would also serve as a venue to play tribute to the more than forty years contributions made by Professor Eric J. Hall to the radiation biology field. The goals of the meeting were to examine tumor hypoxia and sensitizer development; recent advances made in clinical radiotherapy; addressed several low dose phenomena, including genomic instability and bystander effects that are important in radiation risk assessment. Study and Results: The symposium was held on October 13th and 14th, 2008 at the Alfred Lerner Hall in the Morningside campus of Columbia University. The symposium, entitled “From Beans to Genes: A Forty Year Odyssey in Radiation Biology” was attended by more than 120 faculty, scientists, clinicians, fellows and students. The symposium, spanned over a day and a half, covered four scientific themes. These included tumor hypoxia and radiosensitizers; low dose radiation response; radiation biology in the practice of radiotherapy, and radiation hazard in space and genetic predisposition to cancer. The program of the symposium is as follow:

  9. Methods for analyzing combined data from studies of workers exposed to low doses of radiation.

    PubMed

    Gilbert, E S; Fry, S A; Wiggs, L D; Voelz, G L; Cragle, D L; Petersen, G R

    1990-05-01

    Epidemiologic studies of workers exposed occupationally to protracted low doses of radiation provide a direct assessment of health effects resulting from such exposure and thus supplement information provided by studies of populations exposed at high doses of radiation and high dose rates. Analyses based on combined data from several studies can be expected to provide a more thorough assessment of low dose occupational studies and more precise risk estimates than can be obtained from any single study. Statistical methods for conducting such combined analyses are discussed, and different approaches, such as basing analyses on various levels of aggregation of exposure data, are compared and evaluated. Emphasis is given to methods for obtaining risk estimates and confidence limits that can be appropriately compared with estimates that form the basis for current radiation protection standards; these estimates have been obtained through extrapolation from high dose data. Methods are illustrated using combined data on workers at three US Department of Energy facilities: the Hanford Site, Richland, Washington; the Oak Ridge National Laboratory, Oak Ridge, Tennessee; and the Rocky Flats Nuclear Weapons Plant, Denver, Colorado. PMID:2321632

  10. Low-dose prostaglandin E2 analogue for cervical dilatation prior to pregnancy termination.

    PubMed

    Borten, M; DiLeo, L A; Friedman, E A

    1984-11-01

    The trauma of mechanical cervical dilatation preceding abortion is directly related to the degree of cervical resistance. Prostaglandins may reduce cervical rigidity but are accompanied by undesirable side effects. Our aims were to ascertain if a low-dose (10 mg) analogue (9-deoxo-16, 16 dimethyl-9-methylene PGE2) is effective and well tolerated and, if so, to try to determine the possible mechanism by which it works. To this end, we studied 39 women with gestational ages ranging from 7 to 19 weeks who were given a single vaginal suppository 1 to 4 hours before suction curettage. In addition to demographic data on age, gravidity, parity, and previous abortions, we determined progesterone, human chorionic gonadotropin and prostaglandin plasma levels. This low-dose prostaglandin E2 analogue was found to be effective in achieving cervical dilatation and softening with minimal side effects (mild nausea in one patient only). Mean cervical dilatation achieved was 7.8 +/- 2.3 mm. Softening was apparent and facilitated additional instrumental dilatation when required. No correlation was found between drug effectiveness and gravidity, gestational age, or duration of action. There was no detectable trend with regard to baseline progesterone or human chorionic gonadotropin levels. This suggested a specific sensitivity to the local effect by the drug, apparently unrelated to dosage. PMID:6496588

  11. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

    PubMed

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-12-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  12. Effects of chronic low-dose cadmium exposure on selected biochemical and antioxidant parameters in rats.

    PubMed

    Lovásová, Eva; Rácz, Oliver; Cimboláková, Iveta; Nováková, Jaroslava; Dombrovský, Peter; Ništiar, František

    2013-01-01

    The effects of long-term (1 yr) exposure to low doses of cadmium (Cd) dissolved in drinking water on selected biochemical and antioxidant parameters were studied in Wistar rats. Rats were divided into four groups: male control group (C-m), female control group (C-f), male Cd-exposed group (Cd-m), and female Cd-exposed group (Cd-f). Cd groups were exposed to Cd dissolved in drinking water (cadmium dichloride 4.8 mg CdCl2/L, i.e., 2.5 mg Cd/L, 500-fold of maximal allowable concentration for potable water). The experiment was terminated on d 370. In all groups, biochemical parameters (total protein [TP], albumin, alanine aminotransferase, aspartate aminotransferase, glucose, cholesterol, triacylglycerols, urea, and creatinine) and antioxidant parameters (glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) were measured in the blood. Total protein and albumin concentrations were decreased significantly in the Cd-m group. Other biochemical parameters did not change in Cd groups compared to control groups. Superoxide dismutase fell significantly in both male and female Cd-exposed groups. Activity of glutathione peroxidase was markedly lower in Cd-exposed groups. Total antioxidant capacity increased significantly in Cd-f group. These results suggest that chronic low-dose oral Cd exposure induces oxidative stress. PMID:24168039

  13. Low dose 4-MBC effect on neuroendocrine regulation of reproductive axis in adult male rats.

    PubMed

    Carou, Maria E; Ponzo, Osvaldo J; Cardozo Gutierrez, Romina P; Szwarcfarb, Berta; Deguiz, Maria L; Reynoso, Roxana; Carbone, Silvia; Moguilevsky, Jaime A; Scacchi, Pablo

    2008-09-01

    4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats. PMID:21783915

  14. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

    PubMed Central

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-01-01

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images. PMID:26980176

  15. Identifying the health risks from very low-dose sparsely ionizing radiation.

    PubMed Central

    Dreyer, N A; Friedlander, E

    1982-01-01

    The health risks from low-dose sparsely ionizing (low-LET) radiation have been the subject of continued debate. At present, quantitative estimates of risk are extremely uncertain due to the controversy surrounding both the dosimetry for A-bomb survivor data and the choice of mathematical models for extrapolating risk from high to low doses. Nevertheless, much can be learned about the nature of the health risks by reviewing the epidemiologic literature. We present a summary of diseases which have been associated with low-LET radiation (less than 1000 rad) in at least two independent studies, according to the mean cumulative organ dose at which the disease was observed. At organ doses of less than or equal to 50 rad, the only diseases that have been reported consistently are thyroid cancer, salivary gland tumors, and leukemia. The first two diseases were observed in association with x-ray epilation of the scalp for tinea capitis, a therapy which is no longer employed. On the other hand, leukemia has been observed repeatedly to occur at cumulative doses of greater than or equal to 30 rad low-LET radiation. PMID:7041660

  16. Tensile property changes of metals irradiated to low doses with fission, fusion and spallation neutrons

    SciTech Connect

    Heinisch, H.L.; Hamilton, M.L.; Sommer, W.F.; Ferguson, P.D.

    1991-11-01

    Radiation effects due to low doses of spallation neutrons are compared directly to those produced by fission and fusion neutrons. Yield stress changes of pure Cu, alumina-dispersion-strengthened Cu and AISI 316 stainless steel irradiated at 36--55{degrees}C in the Los Alamos Spallation Radiation Effects Facility (LASREF) are compared with earlier results of irradiations at 90{degrees}C using 14 MeV D-T fusion neutrons at the Rotating Target Neutron Source and fission reactor neutrons in the Omega West Reactor. At doses up to 0.04 displacements per atom (dpa), the yield stress changes due to the three quite different neutron spectra correlate well on the basis of dpa in the stainless steel and the Cu alloy. However, in pure Cu, the measured yield stress changes due to spallation neutrons were anomalously small and should be verified by additional irradiations. With the exception of pure Cu, the low dose, low temperature experiments reveal no fundamental differences in radiation hardening by fission, fusion or spallation neutrons when compared on the basis of dpa.

  17. Impacts of low doses of pesticide mixtures on liver cell defence systems.

    PubMed

    Rouimi, Patrick; Zucchini-Pascal, Nathalie; Dupont, Gwendoline; Razpotnik, Andrej; Fouché, Edwin; De Sousa, Georges; Rahmani, Roger

    2012-08-01

    Low amounts of residual pesticides are present in the environment, often as mixtures of chemicals which contaminate drinking water and food, being a source of chronic exposure for humans and a growing matter of concern in public health policy. Despite of the needs and growing investigation, little is known about the impact of low doses and mixtures of these chemicals on human health. The purpose of this study was to enlighten if modifications of liver cell metabolic- and/or defence-related capacities could occur under such exposures. In vitro perturbations of several metabolic, stress and survival pathways in human and mice cultured hepatocytes and liver cells were evaluated under exposure to low doses of single molecules or equimolecular combinations of the three pesticides, atrazine, chlorpyrifos and endosulfan. Mainly phases I and II enzymes of detoxification were found modulated, together with apoptotic process deregulation. Hence, CYP3A4 and CYP3A11 were upregulated in primary cultured human and mouse hepatocytes, respectively. These inductions were correlated to an anti-apoptotic process (increased Bcl-xL/Bax ratio, inhibition of the PARP protein cleavage). Such disturbances in pathways involved in cell protection may possibly account for initiation of pathologies or decrease in drugs efficiency in humans exposed to multiple environmental contaminants. PMID:22515965

  18. Low-dose irradiation as a measure to improve microbial quality of ice cream.

    PubMed

    Kamat, A; Warke, R; Kamat, M; Thomas, P

    2000-12-01

    The present study was undertaken to investigate the efficacy of low-dose irradiation to improve the microbial safety of ice cream. Initially three different flavors (vanilla, strawberry and chocolate) of ice cream were exposed, at -72 degrees C, to doses of 1, 2, 5, 10 and 30 kGy to gamma-radiation. Irradiation at 1 kGy resulted in reduction of microbial population by one log cycle, thus meeting the requirement limits prescribed by Bureau of Indian Standards. Pathogens such as Listeria monocytogenes 036, Yersinia enterocoliticta 5692 and Escherichia coli O157:H19, respectively, showed the D10 values 0.38, 0.15 and 0.2 kGy in ice cream at -72 degrees C suggesting the efficacy of low doses (1 kGy) in eliminating them. Sensory evaluation studies of ice cream irradiated at 1, 2, 3 and 5 kGy by a 15 member panel demonstrated that doses higher than 2 kGy irradiation induced off-odour and an aftertaste was evident in vanilla ice cream. A radiation dose of 1 kGy was sufficient to eliminate the natural number of pathogens present in the ice cream. No statistically significant differences were observed in the sensory attributes of all the three flavours of ice cream either unirradiated or exposed to 1 kGy (P < 0.05). PMID:11139019

  19. The Multifaceted Clinical Readouts of Platelet Inhibition by Low-Dose Aspirin.

    PubMed

    Patrono, Carlo

    2015-07-01

    Inactivation of platelet cyclooxygenase (COX)-1 by low-dose aspirin leads to long-lasting suppression of thromboxane (TX) A2 production and TXA2-mediated platelet activation and aggregation. This e