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Sample records for high-dose stabilized chlorite

  1. Formulation and stability of busulfan for intravenous administration in high-dose chemotherapy.

    PubMed

    Bhagwatwar, H P; Phadungpojna, S; Chow, D S; Andersson, B S

    1996-01-01

    The bifunctional alkylating agent busulfan (Bu) was solubilized in a cosolvent mixture of anhydrous dimethylacetamide (DMA), polyethylene glycol 400 (PEG400), and water at a ratio of 1:2:2 (v/v/v), to achieve a Bu concentration of 3 mg/ml, a preparation that would be suitable for parenteral administration in high-dose chemotherapy preceding bone marrow transplantation. The complete formulation was stable for more than 54 h at room temperature (RT, 22 degrees C). An accelerated stability study of Bu in anhydrous DMA or DMA/PEG400 (1:2) as stock solutions indicated shelf-lives of 191 and 180 days respectively, at RT, and 8.2 and 7.5 years, respectively, at 4 degrees C. Although the complete formulation with Bu was very hypertonic, hemolysis studies indicated that the formulation would be safe for intravenous (i.v.) administration, since it would be rapidly diluted to harmless tonicity levels in the blood. Cytotoxicity studies of the complete formulation in vitro proved that Bu retained its activity when dissolved in the complete vehicle. A preliminary pharmacokinetic study in a rodent model after the i.v. administration of Bu at a dose of 1 mg/kg body weight yielded high plasma concentrations of Bu for at least 5 h after injection. PMID:8599861

  2. Structural, optical and compositional stability of MoS2 multi-layer flakes under high dose electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Rotunno, E.; Fabbri, F.; Cinquanta, E.; Kaplan, D.; Longo, M.; Lazzarini, L.; Molle, A.; Swaminathan, V.; Salviati, G.

    2016-06-01

    MoS2 multi-layer flakes, exfoliated from geological molybdenite, have been exposed to high dose electron irradiation showing clear evidence of crystal lattice and stoichiometry modifications. A massive surface sulfur depletion is induced together with the consequent formation of molybdenum nanoislands. It is found that a nanometric amorphous carbon layer, unwillingly deposited during the transmission electron microscope experiments, prevents the formation of the nanoislands. In the absence of the carbon layer, the formation of molybdenum grains proceeds both on the top and bottom surfaces of the flake. If carbon is present on both the surfaces then the formation of Mo grains is completely prevented.

  3. Chlorite (sodium salt)

    Integrated Risk Information System (IRIS)

    Chlorite ( sodium salt ) ; CASRN 7758 - 19 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarc

  4. Studies of carcinogenicity of sodium chlorite in B6C3F1 mice

    SciTech Connect

    Yokose, Y.; Uchida, K.; Nakae, D.; Shiraiwa, K.; Yamamoto, K.; Konishi, Y.

    1987-12-01

    The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentration of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose) in female mice, and 46% (control), 57% (low dose), and 53% (high dose) in male mice. The types and incidence of neoplasms that occurred frequently in each group of both sexes were similar to those observed spontaneously in B6C3F1 mice. The incidence of lymphomas/leukemias in the high dose group of females (2%), however, was lower than that in the control group (15%). Furthermore, the incidence of pulmonary adenomas in the high dose group of males (12%) was higher than that in the control group (0%), but neither dose-related increases in the adenoma incidences nor increased incidences of the adenocarcinomas were observed. These results indicated no clear evidence of a carcinogenic potential of sodium chlorite in B6C3F1 mice.

  5. 21 CFR 186.1750 - Sodium chlorite.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium chlorite. 186.1750 Section 186.1750 Food... of Specific Substances Affirmed as GRAS § 186.1750 Sodium chlorite. (a) Sodium chlorite (NaCLO2, CAS... passing chlorine dioxide into a solution of sodium hydroxide and hydrogen peroxide. (b) the ingredient...

  6. 21 CFR 186.1750 - Sodium chlorite.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium chlorite. 186.1750 Section 186.1750 Food... of Specific Substances Affirmed as GRAS § 186.1750 Sodium chlorite. (a) Sodium chlorite (NaCLO2, CAS... passing chlorine dioxide into a solution of sodium hydroxide and hydrogen peroxide. (b) the ingredient...

  7. 21 CFR 186.1750 - Sodium chlorite.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium chlorite. 186.1750 Section 186.1750 Food... of Specific Substances Affirmed as GRAS § 186.1750 Sodium chlorite. (a) Sodium chlorite (NaCLO2, CAS... passing chlorine dioxide into a solution of sodium hydroxide and hydrogen peroxide. (b) the ingredient...

  8. 21 CFR 186.1750 - Sodium chlorite.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium chlorite. 186.1750 Section 186.1750 Food... GRAS § 186.1750 Sodium chlorite. (a) Sodium chlorite (NaCLO2, CAS Reg. No. 7758-19-2) exists as... solution of sodium hydroxide and hydrogen peroxide. (b) the ingredient is used at levels from 125 to...

  9. Interlayer bonding in IIb chlorite

    SciTech Connect

    Bish, D.L.; Giese, R.F. Jr.

    1981-01-01

    The interlayer bond energy of a IIb-4 chlorite has been calculated as a function of layer charge, the site of the charge and the selective replacement of hydroxyl groups by fluoride ions. Long hydrogen bonds between the hydroxide sheet and the adjacent oxygens are strong and by themselves sufficient to create a stable structure. Coupled substitutions giving the 2:1 layer a negative charge and the hydroxide sheet a positive charge increase substantially the interlayer bond energy. 3 figures.

  10. Mechanism of reaction of chlorite with mammalian heme peroxidases

    PubMed Central

    Jakopitsch, Christa; Pirker, Katharina F.; Flemmig, Jörg; Hofbauer, Stefan; Schlorke, Denise; Furtmüller, Paul G.; Arnhold, Jürgen; Obinger, Christian

    2014-01-01

    This study demonstrates that heme peroxidases from different superfamilies react differently with chlorite. In contrast to plant peroxidases, like horseradish peroxidase (HRP), the mammalian counterparts myeloperoxidase (MPO) and lactoperoxidase (LPO) are rapidly and irreversibly inactivated by chlorite in the micromolar concentration range. Chlorite acts as efficient one-electron donor for Compound I and Compound II of MPO and LPO and reacts with the corresponding ferric resting states in a biphasic manner. The first (rapid) phase is shown to correspond to the formation of a MPO-chlorite high-spin complex, whereas during the second (slower) phase degradation of the prosthetic group was observed. Cyanide, chloride and hydrogen peroxide can block or delay heme bleaching. In contrast to HRP, the MPO/chlorite system does not mediate chlorination of target molecules. Irreversible inactivation is shown to include heme degradation, iron release and decrease in thermal stability. Differences between mammalian peroxidases and HRP are discussed with respect to differences in active site architecture and heme modification. PMID:24632343

  11. 21 CFR 186.1750 - Sodium chlorite.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium chlorite. 186.1750 Section 186.1750 Food and... Substances Affirmed as GRAS § 186.1750 Sodium chlorite. (a) Sodium chlorite (NaCLO2, CAS Reg. No. 7758-19-2... into a solution of sodium hydroxide and hydrogen peroxide. (b) the ingredient is used at levels...

  12. A dimeric chlorite dismutase exhibits O2-generating activity and acts as a chlorite antioxidant in Klebsiella pneumoniae MGH 78578.

    PubMed

    Celis, Arianna I; Geeraerts, Zachary; Ngmenterebo, David; Machovina, Melodie M; Kurker, Richard C; Rajakumar, Kumar; Ivancich, Anabella; Rodgers, Kenton R; Lukat-Rodgers, Gudrun S; DuBois, Jennifer L

    2015-01-20

    Chlorite dismutases (Clds) convert chlorite to O2 and Cl(-), stabilizing heme in the presence of strong oxidants and forming the O═O bond with high efficiency. The enzyme from the pathogen Klebsiella pneumoniae (KpCld) represents a subfamily of Clds that share most of their active site structure with efficient O2-producing Clds, even though they have a truncated monomeric structure, exist as a dimer rather than a pentamer, and come from Gram-negative bacteria without a known need to degrade chlorite. We hypothesized that KpCld, like others in its subfamily, should be able to make O2 and may serve an in vivo antioxidant function. Here, it is demonstrated that it degrades chlorite with limited turnovers relative to the respiratory Clds, in part because of the loss of hypochlorous acid from the active site and destruction of the heme. The observation of hypochlorous acid, the expected leaving group accompanying transfer of an oxygen atom to the ferric heme, is consistent with the more open, solvent-exposed heme environment predicted by spectroscopic measurements and inferred from the crystal structures of related proteins. KpCld is more susceptible to oxidative degradation under turnover conditions than the well-characterized Clds associated with perchlorate respiration. However, wild-type K. pneumoniae has a significant growth advantage in the presence of chlorate relative to a Δcld knockout strain, specifically under nitrate-respiring conditions. This suggests that a physiological function of KpCld may be detoxification of endogenously produced chlorite. PMID:25437493

  13. A Dimeric Chlorite Dismutase Exhibits O2-Generating Activity and Acts as a Chlorite Antioxidant in Klebsiella pneumoniae MGH 78578

    PubMed Central

    2015-01-01

    Chlorite dismutases (Clds) convert chlorite to O2 and Cl–, stabilizing heme in the presence of strong oxidants and forming the O=O bond with high efficiency. The enzyme from the pathogen Klebsiella pneumoniae (KpCld) represents a subfamily of Clds that share most of their active site structure with efficient O2-producing Clds, even though they have a truncated monomeric structure, exist as a dimer rather than a pentamer, and come from Gram-negative bacteria without a known need to degrade chlorite. We hypothesized that KpCld, like others in its subfamily, should be able to make O2 and may serve an in vivo antioxidant function. Here, it is demonstrated that it degrades chlorite with limited turnovers relative to the respiratory Clds, in part because of the loss of hypochlorous acid from the active site and destruction of the heme. The observation of hypochlorous acid, the expected leaving group accompanying transfer of an oxygen atom to the ferric heme, is consistent with the more open, solvent-exposed heme environment predicted by spectroscopic measurements and inferred from the crystal structures of related proteins. KpCld is more susceptible to oxidative degradation under turnover conditions than the well-characterized Clds associated with perchlorate respiration. However, wild-type K. pneumoniae has a significant growth advantage in the presence of chlorate relative to a Δcld knockout strain, specifically under nitrate-respiring conditions. This suggests that a physiological function of KpCld may be detoxification of endogenously produced chlorite. PMID:25437493

  14. Thermodynamic properties of chlorite and berthierine derived from calorimetric measurements

    NASA Astrophysics Data System (ADS)

    Blanc, Philippe; Gailhanou, Hélène; Rogez, Jacques; Mikaelian, Georges; Kawaji, Hitoshi; Warmont, Fabienne; Gaboreau, Stéphane; Grangeon, Sylvain; Grenèche, Jean-Marc; Vieillard, Philippe; Fialips, Claire I.; Giffaut, Eric; Gaucher, Eric C.; Claret, F.

    2014-09-01

    In the context of the deep waste disposal, we have investigated the respective stabilities of two iron-bearing clay minerals: berthierine ISGS from Illinois [USA; (Al0.975FeIII0.182FeII1.422Mg0.157Li0.035Mn0.002)(Si1.332Al0.668)O5(OH)4] and chlorite CCa-2 from Flagstaff Hill, California [USA; (Si2.633Al1.367)(Al1.116FeIII0.215Mg2.952FeII1.712Mn0.012Ca0.011)O10(OH)8]. For berthierine, the complete thermodynamic dataset was determined at 1 bar and from 2 to 310 K, using calorimetric methods. The standard enthalpies of formation were obtained by solution-reaction calorimetry at 298.15 K, and the heat capacities were measured by heat-pulse calorimetry. For chlorite, the standard enthalpy of formation is measured by solution-reaction calorimetry at 298.15 K. This is completing the entropy and heat capacity obtained previously by Gailhanou et al. (Geochim Cosmochim Acta 73:4738-4749, 2009) between 2 and 520 K, by using low-temperature adiabatic calorimetry and differential scanning calorimetry. For both minerals, the standard entropies and the Gibbs free energies of formation at 298.15 K were then calculated. An assessment of the measured properties could be carried out with respect to literature data. Eventually, the thermodynamic dataset allowed realizing theoretical calculations concerning the berthierine to chlorite transition. The latter showed that, from a thermodynamic viewpoint, the main factor controlling this transition is probably the composition of the berthierine and chlorite minerals and the nature of the secondary minerals rather than temperature.

  15. Experimental determination of chlorite dissolution rates

    SciTech Connect

    Rochelle, C.A.; Bateman, K.; MacGregor, R.; Pearce, J.M.; Wetton, P.D.; Savage, D.

    1995-12-31

    Current concepts of the geological disposal of low- and intermediate-level radioactive wastes in the UK envisage the construction of a mined facility (incorporating cementitious engineered barriers) in chlorite-bearing rocks. To model accurately the fluid-rock reactions within the disturbed zone surrounding a repository requires functions that describe mineral dissolution kinetics under pH conditions that vary from near neutral to highly alkaline. Therefore, an experimental study to determine the dissolution rates of Fe-rich chlorite has been undertaken as part of the Nirex Safety Assessment Research Program. Four experiments have been carried out at 25 C and four at 70 C, both sets using a range of NaCl/NaOH solutions of differing pH (of nominal pH 9.0, 10.3, 11.6 and 13.0 [at 25 C]). Dissolution rates have been calculated and were found to increase with increasing pH and temperature. However, increased pH resulted in non-stoichiometric dissolution possibly due to preferential dissolution of part of the chlorite structure relative to another, or reprecipitation of some elements as thin hydroxide or oxyhydroxide surface coatings on the chlorite. These results also show that chlorite dissolution is appreciably slower than that of albite and quartz at both 25 and 70 C, but slightly faster than that of muscovite at 70 C.

  16. The smectite to chlorite transition in the Chipilapa geothermal system, El Salvador

    SciTech Connect

    Robinson, D.; Santana de Zamora, A.

    1999-04-01

    Clay mineralogical, X-ray diffraction and electron microprobe studies have been carried out on separated <2 {micro}m fractions from cutting and core material from three wells in the Chipilapa geothermal system in El Salvador. The data indicate that the smectite to chlorite transition is prevalent, but a secondary smectite to illite transition is also present. At depths approximately <750 m, smectite with very minor chlorite mixed-layers (approximately <15%) is dominant, and has a composition midway between a di- and tri-smectite. At {approximately}750 m there is a very clear distinction and sharp transition into discrete chlorite with very minor smectite mixed-layers (approximately <10%). Corrensite is recorded only as a rare and minor phase. Smectite occurs in abundance at temperatures up to {approximately}200 C, and the transition from a smectite-dominant to chlorite-dominant assemblage takes place over a narrow temperature range ({approximately}150 to 200 C). The stability range of smectite is very similar to that recorded in other geothermal systems, whereas the smectite to chlorite transition differs greatly from that recorded in other systems. The transition does not involve continuous chlorite/smectite mixed-layering but a marked step: It is the sharpest and most discontinuous stepped sequence of this mineralogical transition recorded.

  17. TOXICOLOGICAL EFFECTS OF CHLORITE IN THE MOUSE

    EPA Science Inventory

    When exposed to a maximum level of 100 ppm chlorine dioxide in their drinking water, neither A/J or C57L/J mice exhibited any hematologic changes. Chlorite exposure under similar conditions produced increases for red blood cells in osmotic fragility, mean corpuscular volume, and ...

  18. Mechanism of chlorite degradation to chloride and dioxygen by the enzyme chlorite dismutase.

    PubMed

    Schaffner, Irene; Hofbauer, Stefan; Krutzler, Michael; Pirker, Katharina F; Furtmüller, Paul G; Obinger, Christian

    2015-05-15

    Heme b containing chlorite dismutase (Cld) catalyses the conversion of chlorite to chloride and dioxygen which includes an unusual OO bond formation. This review summarizes our knowledge about the interaction of chlorite with heme enzymes and introduces the biological role, phylogeny and structure of functional chlorite dismutases with differences in overall structure and subunit architecture. The paper sums up the available experimental and computational studies on chlorite degradation by water soluble porphyrin complexes as well as a model based on the active site of Cld. Finally, it reports the available biochemical and biophysical data of Clds from different organisms which allow the presentation of a general reaction mechanism. It includes binding of chlorite to ferric Cld followed by subsequent heterolytic OCl bond cleavage leading to the formation of Compound I and hypochlorite, which finally recombine for production of chloride and O2. The role of the Cld-typical distal arginine in catalysis is discussed together with the pH dependence of the reaction and the role of transiently produced hypochlorite in irreversible inactivation of the enzyme. PMID:25748001

  19. The homopentameric chlorite dismutase from Magnetospirillum sp.

    PubMed

    Freire, Diana M; Rivas, Maria G; Dias, André M; Lopes, Ana T; Costa, Cristina; Santos-Silva, Teresa; Van Doorslaer, Sabine; González, Pablo J

    2015-10-01

    Chlorite dismutase (Cld) is a b-type heme containing enzyme that catalyzes the reduction of chlorite into chloride plus dioxygen. This enzyme has gained attention because it can be used in the development of bioremediation processes, biosensors, and controlled dioxygen production. In the present work, Cld was purified from Magnetospirillum sp. cells cultured anaerobically with acetate/perchlorate until stationary phase. Biochemical, spectroscopic and X-ray crystallography methods showed that Cld from Magnetospirillum sp. is a ~140 kDa homopentamer comprising ~27.8 kDa monomers. Preliminary X-ray crystallography studies confirmed the quaternary structure and the presence of one b-type heme per monomer. The EPR spectroscopic signature of the as-purified Cld samples is affected by the buffer composition used during the purification. Potassium phosphate buffer is the only buffer that affected neither the spectral nor the kinetic properties of Cld. Kinetic studies in solution revealed that Cld from Magnetospirillum sp. decomposes chlorite at high turnover rates with optimal pH6.0. A temperature below 10 °C is required to avoid enzyme inactivation due to cofactor bleaching during turnover, and to achieve full substrate consumption. Cld kinetic parameters were not affected when kinetic assays were performed in the presence of air or under argon atmosphere, but chloride is a weak mixed inhibitor that modifies the EPR signal of as-prepared samples. PMID:26218477

  20. Ligand Binding to Chlorite Dismutase from Magnetospirillum sp.

    PubMed

    De Schutter, Amy; Correia, Hugo D; Freire, Diana M; Rivas, María G; Rizzi, Alberto; Santos-Silva, Teresa; González, Pablo J; Van Doorslaer, Sabine

    2015-10-29

    Chlorite dismutase (Cld) catalyzes the reduction of chlorite to chloride and dioxygen. Here, the ligand binding to Cld of Magnetospirillum sp. (MaCld) is investigated with X-ray crystallography and electron paramagnetic resonance (EPR). EPR reveals a large heterogeneity in the structure of wild-type MaCld, showing a variety of low- and high-spin ferric heme forms. Addition of an axial ligand, such as azide or imidazole, removes this heterogeneity almost entirely. This is in line with the two high resolution crystal structures of MaCld obtained in the presence of azide and thiocyanate that show the coordination of the ligands to the heme iron. The crystal structure of the MaCld-azide complex reveals a single well-defined orientation of the azide molecule in the heme pocket. EPR shows, however, a pH-dependent heme structure, probably due to acid-base transitions of the surrounding amino-acid residues stabilizing azide. For the azide and imidazole complex of MaCld, the hyperfine and nuclear quadrupole interactions with the close-by (14)N and (1)H nuclei are determined using pulsed EPR. These values are compared to the corresponding data for the low-spin forms observed in the ferric wild-type MaCld and to existing EPR data on azide and imidazole complexes of other heme proteins. PMID:26287794

  1. Dehydration of chlorite explains anomalously high electrical conductivity in the mantle wedges.

    PubMed

    Manthilake, Geeth; Bolfan-Casanova, Nathalie; Novella, Davide; Mookherjee, Mainak; Andrault, Denis

    2016-05-01

    Mantle wedge regions in subduction zone settings show anomalously high electrical conductivity (~1 S/m) that has often been attributed to the presence of aqueous fluids released by slab dehydration. Laboratory-based measurements of the electrical conductivity of hydrous phases and aqueous fluids are significantly lower and cannot readily explain the geophysically observed anomalously high electrical conductivity. The released aqueous fluid also rehydrates the mantle wedge and stabilizes a suite of hydrous phases, including serpentine and chlorite. In this present study, we have measured the electrical conductivity of a natural chlorite at pressures and temperatures relevant for the subduction zone setting. In our experiment, we observe two distinct conductivity enhancements when chlorite is heated to temperatures beyond its thermodynamic stability field. The initial increase in electrical conductivity to ~3 × 10(-3) S/m can be attributed to chlorite dehydration and the release of aqueous fluids. This is followed by a unique, subsequent enhancement of electrical conductivity of up to 7 × 10(-1) S/m. This is related to the growth of an interconnected network of a highly conductive and chemically impure magnetite mineral phase. Thus, the dehydration of chlorite and associated processes are likely to be crucial in explaining the anomalously high electrical conductivity observed in mantle wedges. Chlorite dehydration in the mantle wedge provides an additional source of aqueous fluid above the slab and could also be responsible for the fixed depth (120 ± 40 km) of melting at the top of the subducting slab beneath the subduction-related volcanic arc front. PMID:27386526

  2. Dehydration of chlorite explains anomalously high electrical conductivity in the mantle wedges

    PubMed Central

    Manthilake, Geeth; Bolfan-Casanova, Nathalie; Novella, Davide; Mookherjee, Mainak; Andrault, Denis

    2016-01-01

    Mantle wedge regions in subduction zone settings show anomalously high electrical conductivity (~1 S/m) that has often been attributed to the presence of aqueous fluids released by slab dehydration. Laboratory-based measurements of the electrical conductivity of hydrous phases and aqueous fluids are significantly lower and cannot readily explain the geophysically observed anomalously high electrical conductivity. The released aqueous fluid also rehydrates the mantle wedge and stabilizes a suite of hydrous phases, including serpentine and chlorite. In this present study, we have measured the electrical conductivity of a natural chlorite at pressures and temperatures relevant for the subduction zone setting. In our experiment, we observe two distinct conductivity enhancements when chlorite is heated to temperatures beyond its thermodynamic stability field. The initial increase in electrical conductivity to ~3 × 10−3 S/m can be attributed to chlorite dehydration and the release of aqueous fluids. This is followed by a unique, subsequent enhancement of electrical conductivity of up to 7 × 10−1 S/m. This is related to the growth of an interconnected network of a highly conductive and chemically impure magnetite mineral phase. Thus, the dehydration of chlorite and associated processes are likely to be crucial in explaining the anomalously high electrical conductivity observed in mantle wedges. Chlorite dehydration in the mantle wedge provides an additional source of aqueous fluid above the slab and could also be responsible for the fixed depth (120 ± 40 km) of melting at the top of the subducting slab beneath the subduction-related volcanic arc front. PMID:27386526

  3. Ocular toxicity following high dose chemotherapy and autologous transplant.

    PubMed

    Rubin, P; Hulette, C; Khawly, J A; Elkordy, M; Hussein, A; Vredenburgh, J J; Jaffe, G J; Peters, W P

    1996-07-01

    A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful. PMID:8832031

  4. Periodic and nonperiodic interstratification in the chlorite-biotite series

    SciTech Connect

    Hu, Huifang; Zhang, Yiqiang; Veblen, D.R.

    1996-11-01

    A systematic TEM investigation of interstratified chlorite-biotite crystals showed that the crystals are composed of domains of periodically interstratified chlorite-biotite, non-periodically interstratified chlorite-biotite, biotite, and chlorite. The interstratified chlorite-biotite occurs as a vein filling and was apparently crystallized from a hydrothermal solution. The complex structure of the interstratified chlorite-biotite presumably results from a nonlinear growth phenomenon occurring under a nonequilibrium state. A simple nonlinear dynamics model derived from Duffing`s equation was constructed with an additional chemical potential that accounts for the variation of structural configuration of tetrahedral sheets or 2:1 layers in chlorite and biotite, a simple periodic fluctuation of hydrothermal fluid composition, and a simple damping force for two-dimensional lattice misfit on (001) resulting from the intergrowth of different types of layers with different structural configurations and other dissipation effects. Solutions to the equations of the model show that periodic interstratification, nonperiodic interstratification, and domains of the two end-member components (biotite, chlorite) can be formed during crystallization under various conditions. The nonperiodic sequences of biotite and chlorite layers along the c axis in the interstratified crystals produced by this model are chaotic rather than random. The calculations suggest that both periodic and nonperiodic interstratifications can result from periodic external force, e.g., compositional fluctuation of the fluid.

  5. Structural features promoting dioxygen production by Dechloromonas aromatica chlorite dismutase

    SciTech Connect

    Goblirsch, Brandon R.; Streit, Bennett R.; DuBois, Jennifer L.; Wilmot, Carrie M.

    2010-08-12

    Chlorite dismutase (Cld) is a heme enzyme capable of rapidly and selectively decomposing chlorite (ClO{sub 2}{sup -}) to Cl{sup -} and O{sub 2}. The ability of Cld to promote O{sub 2} formation from ClO{sub 2}{sup -} is unusual. Heme enzymes generally utilize ClO{sub 2}{sup -} as an oxidant for reactions such as oxygen atom transfer to, or halogenation of, a second substrate. The X-ray crystal structure of Dechloromonas aromatica Cld co-crystallized with the substrate analogue nitrite (NO{sub 2}{sup -}) was determined to investigate features responsible for this novel reactivity. The enzyme active site contains a single b-type heme coordinated by a proximal histidine residue. Structural analysis identified a glutamate residue hydrogen-bonded to the heme proximal histidine that may stabilize reactive heme species. A solvent-exposed arginine residue likely gates substrate entry to a tightly confined distal pocket. On the basis of the proposed mechanism of Cld, initial reaction of ClO{sub 2}{sup -} within the distal pocket generates hypochlorite (ClO{sup -}) and a compound I intermediate. The sterically restrictive distal pocket probably facilitates the rapid rebound of ClO{sup -} with compound I forming the Cl{sup -} and O{sub 2} products. Common to other heme enzymes, Cld is inactivated after a finite number of turnovers, potentially via the observed formation of an off-pathway tryptophanyl radical species through electron migration to compound I. Three tryptophan residues of Cld have been identified as candidates for this off-pathway radical. Finally, a juxtaposition of hydrophobic residues between the distal pocket and the enzyme surface suggests O{sub 2} may have a preferential direction for exiting the active site.

  6. Methane oxidation linked to chlorite dismutation

    PubMed Central

    Miller, Laurence G.; Baesman, Shaun M.; Carlström, Charlotte I.; Coates, John D.; Oremland, Ronald S.

    2014-01-01

    We examined the potential for CH4 oxidation to be coupled with oxygen derived from the dissimilatory reduction of perchlorate, chlorate, or via chlorite (ClO−2) dismutation. Although dissimilatory reduction of ClO−4 and ClO−3 could be inferred from the accumulation of chloride ions either in spent media or in soil slurries prepared from exposed freshwater lake sediment, neither of these oxyanions evoked methane oxidation when added to either anaerobic mixed cultures or soil enriched in methanotrophs. In contrast, ClO−2 amendment elicited such activity. Methane (0.2 kPa) was completely removed within several days from the headspace of cell suspensions of Dechloromonas agitata CKB incubated with either Methylococcus capsulatus Bath or Methylomicrobium album BG8 in the presence of 5 mM ClO−2. We also observed complete removal of 0.2 kPa CH4 in bottles containing soil enriched in methanotrophs when co-incubated with D. agitata CKB and 10 mM ClO−2. However, to be effective these experiments required physical separation of soil from D. agitata CKB to allow for the partitioning of O2 liberated from chlorite dismutation into the shared headspace. Although a link between ClO−2 and CH4 consumption was established in soils and cultures, no upstream connection with either ClO−4 or ClO−3 was discerned. This result suggests that the release of O2 during enzymatic perchlorate reduction was negligible, and that the oxygen produced was unavailable to the aerobic methanotrophs. PMID:24987389

  7. Methane oxidation linked to chlorite dismutation

    USGS Publications Warehouse

    Miller, Laurence G.; Baesman, Shaun M.; Carlström, Charlotte I.; Coates, John D.; Oremland, Ronald S.

    2014-01-01

    We examined the potential for CH4 oxidation to be coupled with oxygen derived from the dissimilatory reduction of perchlorate, chlorate, or via chlorite (ClO−2) dismutation. Although dissimilatory reduction of ClO−4 and ClO−3 could be inferred from the accumulation of chloride ions either in spent media or in soil slurries prepared from exposed freshwater lake sediment, neither of these oxyanions evoked methane oxidation when added to either anaerobic mixed cultures or soil enriched in methanotrophs. In contrast, ClO−2 amendment elicited such activity. Methane (0.2 kPa) was completely removed within several days from the headspace of cell suspensions of Dechloromonas agitata CKB incubated with either Methylococcus capsulatus Bath or Methylomicrobium album BG8 in the presence of 5 mM ClO−2. We also observed complete removal of 0.2 kPa CH4 in bottles containing soil enriched in methanotrophs when co-incubated with D. agitata CKB and 10 mM ClO−2. However, to be effective these experiments required physical separation of soil from D. agitata CKB to allow for the partitioning of O2 liberated from chlorite dismutation into the shared headspace. Although a link between ClO−2 and CH4 consumption was established in soils and cultures, no upstream connection with either ClO−4 or ClO−3 was discerned. This result suggests that the release of O2 during enzymatic perchlorate reduction was negligible, and that the oxygen produced was unavailable to the aerobic methanotrophs.

  8. Methane oxidation linked to chlorite dismutation.

    PubMed

    Miller, Laurence G; Baesman, Shaun M; Carlström, Charlotte I; Coates, John D; Oremland, Ronald S

    2014-01-01

    We examined the potential for CH4 oxidation to be coupled with oxygen derived from the dissimilatory reduction of perchlorate, chlorate, or via chlorite (ClO(-) 2) dismutation. Although dissimilatory reduction of ClO(-) 4 and ClO(-) 3 could be inferred from the accumulation of chloride ions either in spent media or in soil slurries prepared from exposed freshwater lake sediment, neither of these oxyanions evoked methane oxidation when added to either anaerobic mixed cultures or soil enriched in methanotrophs. In contrast, ClO(-) 2 amendment elicited such activity. Methane (0.2 kPa) was completely removed within several days from the headspace of cell suspensions of Dechloromonas agitata CKB incubated with either Methylococcus capsulatus Bath or Methylomicrobium album BG8 in the presence of 5 mM ClO(-) 2. We also observed complete removal of 0.2 kPa CH4 in bottles containing soil enriched in methanotrophs when co-incubated with D. agitata CKB and 10 mM ClO(-) 2. However, to be effective these experiments required physical separation of soil from D. agitata CKB to allow for the partitioning of O2 liberated from chlorite dismutation into the shared headspace. Although a link between ClO(-) 2 and CH4 consumption was established in soils and cultures, no upstream connection with either ClO(-) 4 or ClO(-) 3 was discerned. This result suggests that the release of O2 during enzymatic perchlorate reduction was negligible, and that the oxygen produced was unavailable to the aerobic methanotrophs. PMID:24987389

  9. Sensitivity of antioxidant-deficient yeast to hypochlorite and chlorite.

    PubMed

    Kwolek-Mirek, Magdalena; Bartosz, Grzegorz; Spickett, Corinne M

    2011-08-01

    Sodium hypochlorite and sodium chlorite are commonly used as disinfectants, and understanding the mechanisms of microbial resistance to these compounds is of considerable importance. In this study, the role of oxidative stress and antioxidant enzymes in the sensitivity of the yeast Saccharomyces cerevisiae to hypochlorite and chlorite was studied. Yeast mutants lacking Cu-Zn superoxide dismutase, but not mutants deficient in cytoplasmic and peroxisomal catalase, were hypersensitive to the action of both hypochlorite and chlorite. Both compounds depleted cellular glutathione, induced the production of reactive oxygen species and decreased the viability of the cells. The toxicity of hypochlorite and chlorite was abolished by hypoxic and anoxic conditions and ameliorated by thiol antioxidants and ascorbate. The results demonstrated that the action of hypochlorite and chlorite involves the formation of superoxide and peroxide and that SOD1 is protective, probably by limiting the formation of hydroxyl radicals and damage to proteins. PMID:21761455

  10. Evidence for multi-stage metasomatism of chlorite-amphibole peridotites (Ulten Zone, Italy): Constraints from trace element compositions of hydrous phases

    NASA Astrophysics Data System (ADS)

    Marocchi, Marta; Hermann, Jörg; Morten, Lauro

    2007-11-01

    Peridotites from the Ulten Zone (Upper Austroalpine Domain, Central-Eastern Alps, Italy) derive from a mantle wedge environment and record a complex metamorphic history. This study focuses on amphibole-spinel peridotites and chlorite-tremolite peridotites. Chlorite is generally closely intergrown with Cr-spinel, indicating that it grew at the expense of former Al-spinel. No garnet relics or chlorite pseudomorphs after garnet have been found. Moreover, amphibole and chlorite trace element patterns display no fractionation in HREE, suggesting that these chlorite peridotites never equilibrated in the garnet stability field. On the basis of textures, bulk rock and mineral major and trace element compositions three stages of metasomatism are documented in the mantle rocks. We propose that the earliest stage represents melt impregnation at plagioclase peridotite conditions and is unrelated to subduction. The metasomatism leading to spinel- and chlorite-amphibole peridotites is related to the progressive influx of a fluid with crustal signature, derived from neighbouring subducted continental crust as the mantle wedge peridotites approach the slab. The observation that garnet peridotites and chlorite peridotites, which never equilibrated in the garnet stability field, are hosted within the same gneisses, suggests that slices of mantle wedge peridotite with different P-T trajectories can be sampled by subducted and exhumed crust.

  11. Redox kinetics and colloid formation during water-chlorite interactions

    NASA Astrophysics Data System (ADS)

    Kim, E. G.; Ahn, H.; Ryu, J. H.; Jo, H. Y.

    2014-12-01

    For the isolation of high-level radioactive wastes from biosphere, the deep geological repository should be maintained reducing conditions. Surface groundwater can flow along fractures into the deep geological repository, which may cause oxic conditions. In the oxic conditions, uranium can be oxidized from U(Ⅳ) to U(Ⅵ) and U(Ⅵ) can easily migrate in groundwater due to its high mobility. Chlorite with Fe(Ⅱ), which is a phyllosilicate minerals generally occurred in fractures, can help maintenance of the reducing condition because chlorite can consume oxidizing agents by redox reactions. In this study, redox kinetics of chlorite were investigated by conducting redox batch kinetic tests at various conditions (i.e., concentration of oxidizing agent, pH, and presence of NaCl). Colloidal particle formation during redox reactions of chlorite was also investigated. Two types of chlorite samples: low iron content (CCa-2) and high iron content (Chlorite from Daejeon, South Korea) were used. Redox batch kinetic tests were conducted for 60 days. The solutions, reactants, and colloidal particles collected from the redox batch kinetic tests every 10 days were characterized. Results show that the concentration of oxidizing agent decreased more in the chlorite sample having higher Fe(Ⅱ) content than that having lower Fe(Ⅱ) content. After 10 days, both the chlorite samples tend to be reached steady-state conditions and then no changes in the concentration of oxidizing agent were observed. SEM analysis shows that surface and edge of the chlorite samples tend to be crispy and smoothy with increasing reaction time. SEM-EDS analysis on colloidal particles shows that colloidal particles consisted of Fe and O, which were identified as ferrihydrite.

  12. Interaction of the chlorite-based drug WF10 and chlorite with hemoglobin, methemoglobin and ferryl hemoglobin.

    PubMed

    Pichert, Annelie; Arnhold, Jürgen

    2015-11-01

    The interaction of the chlorite-based drug solution WF10 with human oxyhemoglobin and oxidized hemoglobin forms was investigated monitoring the corresponding spectral changes in heme states. The chlorite component of WF10 converts oxyhemoglobin into methemoglobin with a rate of 35.4 M(-1)s(-1). Methemoglobin is also formed upon the interaction of ferryl hemoglobin and WF10/chlorite. The rate of this interconversion depends on the oxidation state of ferryl hemoglobin. This rate is 114 M(-1)s(-1), when ferryl hemoglobin was generated upon reaction of oxyhemoglobin and hydrogen peroxide. A considerable higher rate (6600 M(-1)s(-1)) is measured between the chlorite components of WF10 and ferryl hemoglobin after formation of the latter species from methemoglobin. WF10/chlorite inactivates also methemoglobin as evidenced by the continuous decrease of the Soret band and all other absorbances with a rate of 8.3 M(-1)s(-1). In all interconversions, the chlorite component of WF10 was the active principle as shown in experiments applying pure chlorite at the same concentration as in WF10. Thus, WF10 is able to diminish efficiently the yield of cytotoxic hemoglobin species that might appear after excessive hemolysis of red blood cells under pathologic situations. PMID:26391926

  13. Serpentines, talc, chlorites, and their high-pressure phase transitions: a Raman spectroscopic study

    NASA Astrophysics Data System (ADS)

    Reynard, Bruno; Bezacier, Lucile; Caracas, Razvan

    2015-09-01

    Raman spectra of magnesian phyllosilicates belonging to the serpentine, talc, and chlorite groups have been obtained at ambient conditions, and at high pressures and up to 200 °C in order to study high-pressure transformations in the 10 GPa range. The complex and distinct Raman spectra of these minerals allow straightforward identification, which may otherwise be difficult from optical microscopy. High-pressure measurements are in good agreement with DFT calculations for talc and lizardite. Pressure-induced displacive modifications are identified in lizardite and antigorite serpentines, and in chlorite at ~4, 7 and 8 GPa, respectively, while talc shows no transition up to ~11 GPa. At high temperature, the high-pressure distortions of serpentines shift to higher pressures. Given the stability limits of these minerals, and the natural range of P-T conditions, none of the high-pressure distortions observed at high pressure are likely to occur at depth in the Earth.

  14. “Development of an Automated On-line Electrochemical Chlorite Ion Sensor”

    PubMed Central

    Myers, John N.; Steinecker, William H.; Sandlin, Zechariah D.; Cox, James A.; Gordon, Gilbert; Pacey, Gilbert E.

    2012-01-01

    A sensor system for the automatic, in-line, determination of chlorite ion is reported. Electroanalytical measurements were performed in electrolyte-free liquids by using an electrochemical probe (EC), which enables in-line detection in high-resistance media such as disinfected water. Cyclic voltammetry scan rate studies suggest that the current arising from the oxidation of chlorite ion at an EC probe is mass-transfer limited. By coupling FIA with an EC probe amperometric cell, automated analysis was achieved. This sensor is intended to fulfill the daily monitoring requirements of the EPA DBP regulations for chlorite ion. Detection limits of 0.02-0.13 mg/L were attained, which is about one order of magnitude below the MRDL. The sensor showed no faradaic signal for perchlorate, chlorate, or nitrate. The lifetime and stability of the sensor were investigated by measuring calibration curves over time under constant-flow conditions. Detection limits of <0.1 mg/L were repeatedly achieved over a period of three weeks. PMID:22608440

  15. Three-dimensional convection-driven fronts of the exothermic chlorite-tetrathionate reaction.

    PubMed

    Schuszter, Gábor; Pótári, Gábor; Horváth, Dezső; Tóth, Ágota

    2015-06-01

    Horizontally propagating autocatalytic reaction fronts in fluids are often accompanied by convective motion in the presence of gravity. We experimentally and numerically investigate the stable complex three-dimensional pattern arising in the exothermic chlorite-tetrathionate reaction as a result of the antagonistic thermal and solutal contribution to the density change. By particle image velocimetry measurements, we construct the flow field that stabilizes the front structure. The calculations applied for incompressible fluids using the empirical rate-law model reproduce the experimental observations with good agreement. PMID:26117124

  16. Three-dimensional convection-driven fronts of the exothermic chlorite-tetrathionate reaction

    NASA Astrophysics Data System (ADS)

    Schuszter, Gábor; Pótári, Gábor; Horváth, Dezső; Tóth, Ágota

    2015-06-01

    Horizontally propagating autocatalytic reaction fronts in fluids are often accompanied by convective motion in the presence of gravity. We experimentally and numerically investigate the stable complex three-dimensional pattern arising in the exothermic chlorite-tetrathionate reaction as a result of the antagonistic thermal and solutal contribution to the density change. By particle image velocimetry measurements, we construct the flow field that stabilizes the front structure. The calculations applied for incompressible fluids using the empirical rate-law model reproduce the experimental observations with good agreement.

  17. S-oxygenation of thiocarbamides V: oxidation of tetramethylthiourea by chlorite in slightly acidic media.

    PubMed

    Chigwada, Tabitha; Mbiya, Wilbes; Chipiso, Kudzanai; Simoyi, Reuben H

    2014-08-01

    The reaction between tetramethylthiourea (TTTU) and slightly acidic chlorite has been studied. The reaction is much faster than comparable oxidations of the parent thiourea compound as well as other substituted thioureas. The stoichiometry of the reaction in excess oxidant showed a complete desulfurization of the thiocarbamide to yield the corresponding urea and sulfate: 2ClO2(-) + (Me2N)2C ═ S + H2O → (Me2N)2C ═ O + SO4(2-) + 2Cl(-) + 2H(+). The reaction mechanism is unique in that the most stable metabolite before formation of the corresponding urea is the S-oxide. This is one of the rare occasions in which a low-molecular-weight S-oxide has been stabilized without the aid of large steric groups. ESI-MS data show almost quantitative formation of the S-oxide and negligible formation of the sulfinic and sulfonic acids. TTTU, in contrast to other substituted thioureas, can only stabilize intermediate oxoacids, before formation of sulfate, in the form of zwitterions. With a stoichiometric excess of TTTU over oxidant, the TTTU dimer is the predominant product. Chlorine dioxide, which is formed from the reaction of excess chlorite and HOCl, is a very important reactant in the overall mechanism. It reacts rapidly with TTTU to reform ClO2(-). Oxidation of TTTU by chlorite has a complex dependence on acid as a result of chlorous acid dissociation and protonation of the thiol group on TTTU in high-acid conditions, which renders the thiol center a less effective nucleophile. PMID:24922053

  18. Chlorites in reservoir sandstones of the Guadalupian Delaware Mountain Group

    SciTech Connect

    Walling, S.D. )

    1992-04-01

    Late-stage authigenic clay minerals are pervasive in the very fine-grained, subarkosic sandstones of the Guadalupian Delaware Mountain Group, comprising up to 10% of the bulk rock. Thus, reservoir rock properties are influenced by these minerals. Samples selected from cored intervals, ranging from 600 to 2500 m, were studied using optical and electron microscopy and x-ray diffraction methods to determine the distribution and nature of occurrence of the authigenic clay minerals. In thin sections, the clay minerals are recognizable as grain coatings, with thickness varying from a few micrometers to tens of micrometers. A correlation between the morphology and the amount of interstratification has been observed, with more interstratification corresponding to the formless chlorite variety. The structural and morphological evidence suggests that the chlorites represent different stages of development, possibly evolving from a smectite component through an interstratified intermediate, to a more well-ordered form. There appears to be no systematic trends vertically or laterally in clay mineralogy. The importance of understanding the clay mineralogy and chemistry in these sandstones is evident when considering enhanced recovery procedures. Different clay structures and chemistries may respond differently to production and stimulation techniques. The proposed chlorite diagenetic sequence suggests that drastic changes in borehole fluid chemistry may cause retrogression of chlorite to some expansive forms, which may be water sensitive or inclined to migration.

  19. Elastic stability of high dose neutron irradiated spinel

    SciTech Connect

    Li, Z.; Chan, S.K.; Garner, F.A.

    1995-04-01

    The objective of this effort is to identify ceramic materials that are suitable for fusion reactor applications. Elastic constants (C{sub 11}, C{sub 12}, and C{sub 44}) of spinel (MgAl{sub 2}O{sub 4}) single crystals irradiated to very high neutron fluences have geen measured by an ultrasonic technique. Although results of a neutron diffraction study show that cation occupation sites are significantly changed in the irradiated samples, no measurable differences occurred in their elastic properties. In order to understand such behavior, the elastic properties of a variety of materials with either normal or inverse spinel structures were studied. The cation valence and cation distribution appear to have little influence on the elastic properties of spinel materials.

  20. High-dose naloxone in tardive dyskinesia.

    PubMed

    Lindenmayer, J P; Gardner, E; Goldberg, E; Opler, L A; Kay, S R; van Praag, H M; Weiner, M; Zukin, S

    1988-10-01

    Tardive dyskinesia (TD) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure. Preclinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state. In a trial of high-dose naloxone, 20 patients with TD received i.v. naloxone (20 mg, 40 mg, and placebo) under double-blind conditions. At baseline and at regular postdrug intervals, patients were evaluated using a battery of motor, clinical, and neuropsychological measures to study effects on neurological, behavioral, and cognitive functions. There was a significant improvement in involuntary movements at 30 min postnaloxone, together with improvement in clinical ratings at that time point, as well as some cognitive changes. The implications of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed. PMID:3070611

  1. [High-dose intravenous immunoglobulin treatment].

    PubMed

    Taneichi, Hiromichi; Miyawaki, Toshio

    2011-03-01

    Intravenous immunoglobulin treatment was introduced as replacement therapy for patients with congenital agammaglobulinemia. For the last three decades, high-dose intravenous immunoglobulin (HD-IVIg) has been used for autoimmune diseases and systemic inflammatory diseases, such as idiopathic thrombocytopenic purpura, Kawasaki disease, myasthenia gravis and Guillain-Barré/syndrome. Although the immunomodulatory mechanisms of HD-IVIg remains unclear. Its use in many other diseases have been expected. Acute encephalitis/encephalopathy is a complex neurological syndrome associated with significant morbidity and mortality. The pathogenicity of brain dysfunction is still unknown. This review provides an overview and discussion of mechanisms that may be responsible for HD-IVIg effects in acute encephalitis/encephalopathy. PMID:21400848

  2. A thermodynamic model for di-trioctahedral chlorite from experimental and natural data in the system MgO-FeO-Al2O3-SiO2-H2O: applications to P- T sections and geothermometry

    NASA Astrophysics Data System (ADS)

    Lanari, Pierre; Wagner, Thomas; Vidal, Olivier

    2014-02-01

    We present a new thermodynamic activity-composition model for di-trioctahedral chlorite in the system FeO-MgO-Al2O3-SiO2-H2O that is based on the Holland-Powell internally consistent thermodynamic data set. The model is formulated in terms of four linearly independent end-members, which are amesite, clinochlore, daphnite and sudoite. These account for the most important crystal-chemical substitutions in chlorite, the Fe-Mg, Tschermak and di-trioctahedral substitution. The ideal part of end-member activities is modeled with a mixing-on-site formalism, and non-ideality is described by a macroscopic symmetric (regular) formalism. The symmetric interaction parameters were calibrated using a set of 271 published chlorite analyses for which robust independent temperature estimates are available. In addition, adjustment of the standard state thermodynamic properties of sudoite was required to accurately reproduce experimental brackets involving sudoite. This new model was tested by calculating representative P- T sections for metasediments at low temperatures (<400 °C), in particular sudoite and chlorite bearing metapelites from Crete. Comparison between the calculated mineral assemblages and field data shows that the new model is able to predict the coexistence of chlorite and sudoite at low metamorphic temperatures. The predicted lower limit of the chloritoid stability field is also in better agreement with petrological observations. For practical applications to metamorphic and hydrothermal environments, two new semi-empirical chlorite geothermometers named Chl(1) and Chl(2) were calibrated based on the chlorite + quartz + water equilibrium (2 clinochlore + 3 sudoite = 4 amesite + 4 H2O + 7 quartz). The Chl(1) thermometer requires knowledge of the (Fe3+/ΣFe) ratio in chlorite and predicts correct temperatures for a range of redox conditions. The Chl(2) geothermometer which assumes that all iron in chlorite is ferrous has been applied to partially recrystallized

  3. Modern trends and development in high-dose luminescent measurements

    NASA Astrophysics Data System (ADS)

    Kortov, V.

    2014-11-01

    Main application areas of high-dose dosimetry are described. The requirements to the materials for high-dose luminescent detectors are set. The examples of successful high-dose measurements using radiation-resistant phosphors are given. Viability of using materials with deep traps to detect intensive radiation flows is grounded. Characteristics of high-dose measurements using highly sensitive detectors TLD-500 (Al2O3:C) and LiF:Mg,Cu,P are discussed.

  4. 40 CFR 180.1070 - Sodium chlorite; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Sodium chlorite; exemption from the... Exemptions From Tolerances § 180.1070 Sodium chlorite; exemption from the requirement of a tolerance. Sodium chlorite is exempted from the requirement of a tolerance for residues when used in accordance with...

  5. 40 CFR 180.1070 - Sodium chlorite; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Sodium chlorite; exemption from the... Exemptions From Tolerances § 180.1070 Sodium chlorite; exemption from the requirement of a tolerance. Sodium chlorite is exempted from the requirement of a tolerance for residues when used in accordance with...

  6. 40 CFR 180.1070 - Sodium chlorite; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Sodium chlorite; exemption from the... Exemptions From Tolerances § 180.1070 Sodium chlorite; exemption from the requirement of a tolerance. Sodium chlorite is exempted from the requirement of a tolerance for residues when used in accordance with...

  7. 40 CFR 180.1070 - Sodium chlorite; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Sodium chlorite; exemption from the... Exemptions From Tolerances § 180.1070 Sodium chlorite; exemption from the requirement of a tolerance. Sodium chlorite is exempted from the requirement of a tolerance for residues when used in accordance with...

  8. 40 CFR 180.1070 - Sodium chlorite; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Sodium chlorite; exemption from the... Exemptions From Tolerances § 180.1070 Sodium chlorite; exemption from the requirement of a tolerance. Sodium chlorite is exempted from the requirement of a tolerance for residues when used in accordance with...

  9. Variations of chlorites and illites and porosity in Mississippian sandstone reservoirs in the Illinois basin

    SciTech Connect

    Moore, D.M.; Hughes, R.E. )

    1991-03-01

    Shallow marine, Mississippian, siliclastics in the Illinois basin, although predominantly quartz, contain other minerals that directly influence the porosity and permeability of these reservoir rocks. These sandstones contain more chlorite and kaolinite, relative to illite, than the authors have observed for shales from other Chesterian and Valmeyeran strata. Clay mineral suites in reservoirs appear to be diagenetic. The Aux Vases Sandstone contains illite, illite/smectite, and chlorite; kaolinite is absent. The Cypress Sandstone contains illite, illite/smectite, chlorite, and kaolinite. Chlorite in the Aux Vases Sandstone varies from moderately Fe-rich to Mg-rich, whereas the chlorite in the Cypress Sandstone is uniformly Fe-rich. As the percentage of clay minerals in these rocks decreases, the proportion of chlorite to other clay minerals increases. In some chlorites, the width of the 003 and 005 peaks at half-height is greater than that of the 002 and 004 peaks. This suggests an interlayering of a 7{angstrom} mineral, probably berthierine- or serpentine-like. SEM photos show chlorite coating quartz grains. In some samples there are quartz overgrowths in spite of the presence of a coating of chlorite; in others, chlorite interlayered with the 7{angstrom} phase seems to have interfered with or suppressed overgrowths. Correspondingly, there is a correlation between the 7{angstrom} phase/chlorite and porosity. Therefore, identification of the type of chlorite in a potential reservoir may be an indicator of porosity, as well as a guide for selecting completion and stimulation treatments.

  10. Electrical conductivity of chlorite at high pressures and high temperatures

    NASA Astrophysics Data System (ADS)

    Eymard, I.; Mibe, K.; Reynard, B.

    2012-12-01

    In the mantle wedge of subduction zones, high electrical-conductivity bodies have been observed. In order to understand the cause of high-conductivity body in subduction zones, we measured the electrical conductivity of polycrystalline chlorite, at pressures from 2 to 4 GPa and at high temperatures up to 850K using complex impedance spectroscopy in a multi-anvil high-pressure apparatus. The electrical conductivity increased slightly with increasing pressure. The obtained electrical conductivity values are higher than serpentine and talc (Reynard et al., 2011; Guo et al., 2011) and are slightly lower than brucite (Fujita et al., 2007). Although the obtained values are higher compared to serpentine, the presence of chlorite alone is not high enough to explain high-conductivity bodies in subduction-zones. Instead, the presence of some amount of saline fluids is inferred.

  11. Preliminary evaluation of oxygen isotopic exchange between chlorite and water

    SciTech Connect

    Cole, D.R.

    1985-01-01

    Variations in the oxygen isotopic composition of biotites altering to chlorite have been monitored as a function of time from 16 hydrothermal granite-water experiments conducted at the following conditions: T = 170/sup 0/ - 300/sup 0/C; P = 100-300 bars; mNaCl = 0.1-1.0; water/biotite mass ratio = 1-60 for periods up to 900 hours. The magnitude of delta/sup 18/O depletion in biotite increased with increasing temperature and time. Detailed thin section, x-ray and SEM studies demonstrated that biotite is altered exclusively to chlorite in 11 of the 16 experiments. The amounts of chlorite formed in these experiments increased with increasing temperature as well as time. The isotopic compositions of chlorite were calculated from mass balance, and compared with the final measured delta/sup 18/O of the fluids. These fractionations (..delta..Ch1-w) average 0.26, 0.77, and 3.74 per thousand for T = 300/sup 0/, 250/sup 0/, and 200/sup 0/C, respectively. Several lines of evidence will be discussed that suggest these data may represent equilibrium values. A least-squares regression of the data yields the following preliminary equation: 1000 ln ..cap alpha../sub/ Chl-W/ = 08.38 (10/sup 3//T) + 4.81 (10/sup 6//T/sup 2/). The error about this curve is at least +/-0.5 per thousand at 250/sup 0/ and 300/sup 0/C, and +/- 1 per thousand at 200/sup 0/C. There is excellent agreement between this curve and the curve given by Wenner and Taylor (1971) for the temperature range of 250/sup 0/ to 300/sup 0/C. However, below 250/sup 0/C, the new chloride-water results predict consistently higher temperatures compared to previous estimates.

  12. Redox Thermodynamics of High-Spin and Low-Spin Forms of Chlorite Dismutases with Diverse Subunit and Oligomeric Structures

    PubMed Central

    2012-01-01

    Chlorite dismutases (Clds) are heme b-containing oxidoreductases that convert chlorite to chloride and dioxygen. In this work, the thermodynamics of the one-electron reduction of the ferric high-spin forms and of the six-coordinate low-spin cyanide adducts of the enzymes from Nitrobacter winogradskyi (NwCld) and Candidatus “Nitrospira defluvii” (NdCld) were determined through spectroelectrochemical experiments. These proteins belong to two phylogenetically separated lineages that differ in subunit (21.5 and 26 kDa, respectively) and oligomeric (dimeric and pentameric, respectively) structure but exhibit similar chlorite degradation activity. The E°′ values for free and cyanide-bound proteins were determined to be −119 and −397 mV for NwCld and −113 and −404 mV for NdCld, respectively (pH 7.0, 25 °C). Variable-temperature spectroelectrochemical experiments revealed that the oxidized state of both proteins is enthalpically stabilized. Molecular dynamics simulations suggest that changes in the protein structure are negligible, whereas solvent reorganization is mainly responsible for the increase in entropy during the redox reaction. Obtained data are discussed with respect to the known structures of the two Clds and the proposed reaction mechanism. PMID:23126649

  13. Kinetics and Mechanism of Oxidation of Methimazole by Chlorite in Slightly Acidic Media.

    PubMed

    Chipiso, Kudzanai; Simoyi, Reuben H

    2016-06-01

    The kinetics and mechanism of the oxidation of methimazole (1-methyl-3H-imidazole), MMI, by chlorite in mildly acidic environments were studied. It is a complex reaction that gives oligo-oscillations in chlorine dioxide concentrations in excess chlorite conditions. The stoichiometry is strictly 2:1, with the sulfur center being oxidized to sulfate and the organic moiety being hydrolyzed to several indeterminate species. In excess MMI conditions over chlorite, the sulfinic acid and sulfonic acid were observed as major intermediates. The sulfenic acid, which was observed in the electrochemical oxidation of MMI, was not observed with chlorite oxidations. Initial reduction of chlorite produced HOCl, an autocatalytic species in chlorite oxidations. HOCl rapidly reacts with chlorite to produce chlorine dioxide, which, in turn, reacts rapidly with MMI to produce more chlorite. The reaction of chlorine dioxide with MMI is competitive, in rate, with the chlorite-MMI and HOCl-ClO2(-) reactions. This explains the oligo-oscillations in ClO2 concentrations. PMID:27126471

  14. Fe-SAPONITE and Chlorite Growth on Stainless Steel in Hydrothermal Engineered Barrier Experiments

    NASA Astrophysics Data System (ADS)

    Cheshire, M. C.; Caporuscio, F. A.; McCarney, M.

    2012-12-01

    The United States recently has initiated the Used Fuel Disposition campaign to evaluate various generic geological repositories for the disposal of high-level, spent nuclear fuel within environments ranging from hard-rock, salt/clay, to deep borehole settings. Previous work describing Engineered Barrier Systems (EBS) for repositories focused on low temperature and pressure conditions. The focus of this experimental work is to characterize the stability and alteration of a bentonite-based EBS with different waste container materials in brine at higher heat loads and pressures. All experiments were run at ~150 bar and 125 to 300 C for ~1 month. Unprocessed bentonite from Colony, Wyoming was used in the experiments as the clay buffer material. The redox conditions for each system were buffered along the magnetite-iron oxygen fugacity univariant curve using Fe3O4 and Feo filings. A K-Na-Ca-Cl-based salt solution was chosen to replicate deep groundwater compositions. The experimental mixtures were 1) salt solution-clay; 2) salt solution -clay-304 stainless steel; and 3) salt solution -clay-316 stainless steel with a water/bentonite ratio of ~9. Mineralogy and aqueous geochemistry of each experiment was evaluated to monitor the reactions that took place. No smectite illitization was observed in these reactions. However, it appears that K-smectite was produced, possibly providing a precursor to illitization. It is unclear whether reaction times were sufficient for bentonite illitization at 212 and 300 C or whether conditions conducive to illite formation were obtained. The more notable clay mineral reactions occurred at the stainless steel surfaces. Authigenic chlorite and Fe-saponite grew with their basal planes near perpendicular to the steel plate, forming a 10 - 40 μm thick 'corrosion' layer. Partial dissolution of the steel plates was the likely iron source for chlorite/saponite formation; however, dissolution of the Feo/Fe3O4 may also have acted as an iron source

  15. The EORTC GI group experience with high-dose infusional 5-FU in colorectal cancer.

    PubMed

    Blijham, G H

    1996-01-01

    The EORTC Gastrointestinal Tract Cancer Cooperative Group has conducted a randomized trial of high-dose infusional 5-fluorouracil (FU) with or without Methotrexate (MTX). FU was given as a 48-horus infusion of 60 mg/kg every week x 4, biweekly x 4, and subsequently every 3 weeks. Half of the patients also received 40 mg/m2 MTX as a bolus injection just prior to the FU infusion. A total of 312 patients were randomized. High-dose infusional FU was very well tolerated with virtually no haematological, renal, hepatic or cutaneous toxicity. Nausea and vomiting occurred in 35% and diarrhea in 24% of patients but was almost never severe. Cardiac toxicity and ataxia were seen in less than 5% of patients. Methotrexate lead to a significantly higher incidence of stomatitis, which was severe in 10% of patients. Eleven percent of the high-dose infusional FU patients showed an objective response with stabilization in an additional 35%; median survival was 9.3 months. With the addition of methotrexate a 23% response rate was seen (p = 0.025) and survival was 12.5 months (n.s.). We demonstrated the favorable therapeutic index tolaribility of high-dose (60 mg/kg), short-term (48 hours), frequent (weekly-biweekly) infusional FU and the ability of low-dose MTX to positivity modulate this FU treatment. PMID:9229320

  16. Water incorporation in NAMs after antigorite and chlorite dehydration reactions

    NASA Astrophysics Data System (ADS)

    Padrón-Navarta, José Alberto; Hermann, Jörg

    2014-05-01

    Subduction zones play a fundamental role in the deep water cycle making the Earth unique among other terrestrial planets. Water is incorporated into hydrous minerals during seafloor alteration of the oceanic lithosphere. During subduction of the oceanic lithosphere, dehydration of these hydrous minerals produces a fluid phase. A part of this fluid phase will be recycled back to the Earth's surface through hydrothermal aqueous fluids or through hydrous arc magmas, whereas another part of the water will be transported to the deep mantle by Nominally Anhydrous Minerals (NAMs) such as olivine, pyroxene and garnet. The partitioning of water between these two processes is crucial for our understanding of the mantle-scale water recycling in the Earth. This can be investigated experimentally under water-saturated conditions because this situation is met during dehydration reactions. However relatively low temperature conditions for such reactions make challenging these experiments. An alternative can be found in the natural record. The Alpine Betic-Rif orogen together with Central and Western Alps offer an invaluable diversity of ultramafic lenses that record a significant range of pressure-temperature and cooling rates. Hence these samples portray an excellent data set of 24 samples to survey the transfer of fluids from hydrous phases (brucite, antigorite and chlorite) to NAMs (olivine, orthopyroxene, clinopyroxene and garnet). Well-studied samples from these localities have been selected for water measurement using FTIR spectroscopy. The selected suite comprises the following high-pressure peridotite outcrops: Malenco serpentinite, Cerro del Almirez (1.6-1.9 GPa and 680-710ºC), Alpe Arami (3.2 GPa and 840ºC), Cima di Gagnone (3.0 GPa and 750-800ºC) and Alpe Albion (0.6 GPa and 730ºC). The infrared signature of olivine in all localities contains water (hydroxyl groups) associated to intrinsic defects (mostly point defects related to Ti4+) and extrinsic submicroscopic

  17. Geochemistry of sericite and chlorite in well 14-2 Roosevelt Hot Springs geothermal system and in mineralized hydrothermal systems

    SciTech Connect

    Ballantyne, J.M.

    1980-06-01

    Chemical compositions of chlorite and sericite from one production well in the Roosevelt geothermal system have been determined by electron probe methods and compared with compositions of chlorite and sericite from porphyry copper deposits. Modern system sericite and chlorite occur over a depth interval of 2 km and a temperature interval of 250/sup 0/C.

  18. Investigation of ion binding in chlorite dismutases by means of molecular dynamics simulations.

    PubMed

    Sündermann, Axel; Reif, Maria M; Hofbauer, Stefan; Obinger, Christian; Oostenbrink, Chris

    2014-07-29

    Chlorite dismutases are prokaryotic heme b oxidoreductases that convert chlorite to chloride and dioxygen. It has been postulated that during turnover hypochlorite is formed transiently, which might be responsible for the observed irreversible inactivation of these iron proteins. The only charged distal residue in the heme cavity is a conserved and mobile arginine, but its role in catalysis and inactivation is not fully understood. In the present study, the pentameric chlorite dismutase (Cld) from the bacterium Candidatus Nitrospira defluvii was probed for binding of the low spin ligand cyanide, the substrate chlorite, and the intermediate hypochlorite. Simulations were performed with the enzyme in the ferrous, ferric, and compound I state. Additionally, the variant R173A was studied. We report the parametrization for the GROMOS force field of the anions ClO(-), ClO2(-), ClO3(-), and ClO4(-) and describe spontaneous binding, unbinding, and rebinding events of chlorite and hypochlorite, as well as the dynamics of the conformations of Arg173 during simulations. The findings suggest that (i) chlorite binding to ferric NdCld occurs spontaneously and (ii) that Arg173 is important for recognition and to impair hypochlorite leakage from the reaction sphere. The simulation data is discussed in comparison with experimental data on catalysis and inhibition of chlorite dismutase. PMID:24988286

  19. Authigenic chlorites in sandstones as indicators of high-temperature diagenesis, Arkoma Foreland Basin, USA

    SciTech Connect

    Spoetl, C.; Houseknecht, D.W. ); Longstaffe, F.J. . Dept. of Earth Sciences)

    1994-07-01

    Abundant authigenic chamosite associated with higher-than-average porosities is present in a deep gas reservoir (Spiro sandstone) of the Arkoma Basin, east-central Oklahoma. Three types of chlorite can be distinguished petrographically, all of which appear texturally to have formed early: chlorite peloids, diffuse matrix, and grain coatings. X-ray diffraction, scanning electron microscopy, and electron microprobe studies show that most chlorites are composed of two distinct polytypes, Ib ([beta] = 90[degree]) and IIb. A third structure, Ia[prime] polytype, was identified in only one sample. The relative percentage of the high-temperature IIb structure increases gradually with increasing thermal maturity, from [le] 10% at 2.0% R[sub o] up to [le] 40% at 3.5% R[sub o]. IIb chlorite forms rather thick, blocky crystals distinct from the thin, pseudohexagonal plates typical of low-temperature Ib chlorite. Temperature estimates based on data on vitrinite reflectance and fluid inclusions suggest that IIb chlorite formed at burial temperatures [ge] 150--180 C. Higher contents of tetrahedral Al[sup 3+] and slightly higher Fe/[Fe+Mg] ratios in IIb chlorite are consistent with precipitation temperatures higher than those of the Ib structure. A higher-temperature origin for the IIb structure is also consistent with oxygen isotope data.

  20. Investigation of Ion Binding in Chlorite Dismutases by Means of Molecular Dynamics Simulations

    PubMed Central

    2014-01-01

    Chlorite dismutases are prokaryotic heme b oxidoreductases that convert chlorite to chloride and dioxygen. It has been postulated that during turnover hypochlorite is formed transiently, which might be responsible for the observed irreversible inactivation of these iron proteins. The only charged distal residue in the heme cavity is a conserved and mobile arginine, but its role in catalysis and inactivation is not fully understood. In the present study, the pentameric chlorite dismutase (Cld) from the bacterium Candidatus Nitrospira defluvii was probed for binding of the low spin ligand cyanide, the substrate chlorite, and the intermediate hypochlorite. Simulations were performed with the enzyme in the ferrous, ferric, and compound I state. Additionally, the variant R173A was studied. We report the parametrization for the GROMOS force field of the anions ClO–, ClO2–, ClO3–, and ClO4– and describe spontaneous binding, unbinding, and rebinding events of chlorite and hypochlorite, as well as the dynamics of the conformations of Arg173 during simulations. The findings suggest that (i) chlorite binding to ferric NdCld occurs spontaneously and (ii) that Arg173 is important for recognition and to impair hypochlorite leakage from the reaction sphere. The simulation data is discussed in comparison with experimental data on catalysis and inhibition of chlorite dismutase. PMID:24988286

  1. Investigation of U(VI) Adsorption in Quartz-Chlorite Mineral Mixtures

    SciTech Connect

    Wang, Zheming; Zachara, John M.; Shang, Jianying; Jeon, Choong; Liu, Juan; Liu, Chongxuan

    2014-08-25

    A batch and cryogenic laser-induced time-resolved fluorescence spectroscopy investigation of U(VI) adsorbed on quartz-chlorite mixtures with variable mass ratios have been performed under field-relevant uranium concentrations (5x10-7 M and 5x10-6 M) in pH 8.1 synthetic groundwater. The U(VI) adsorption Kd values steadily increased as the mass fraction of chlorite increased, indicating preferential sorption to chlorite. For all mineral mixtures, U(VI) adsorption Kd values were lower than that calculated from the assumption of component additivity; The largest deviation occurred when the mass fractions of the two minerals were equal. U(VI) adsorbed on quartz and chlorite displayed characteristic individual fluorescence spectra that were not affected by mineral mixing. The spectra of U(VI) adsorbed within the mixtures could be simulated by one surface U(VI) species on quartz and two on chlorite. The fluorescence intensity decreased in a nonlinear manner as the adsorbed U(VI) concentration increased with increasing chlorite mass fraction – likely due to ill-defined fluorescence quenching by both structural Fe/Cr in chlorite, and trace amounts of solubilized and re-precipitated Fe/Cr in the aqueous phase. However, the fractional spectral intensities of U(VI) adsorbed on quartz and chlorite followed the same trend of fractional adsorbed U(VI) concentration in each mineral phase; approximate linear correlations in the quartz:chlorite mass ratio ranges of 0.0 - 0.2 and 0.2 - 1.0, offering a method to estimate of U(VI) concentration distribution between the mineral components.

  2. Inhibition of apple polyphenol oxidase activity by sodium chlorite.

    PubMed

    Lu, Shengmin; Luo, Yaguang; Feng, Hao

    2006-05-17

    Sodium chlorite (SC) was shown to have strong efficacy both as a sanitizer to reduce microbial growth on produce and as a browning inhibitor on fresh-cut apples in previous experiments. This study was undertaken to investigate the inhibitory effect of SC on polyphenol oxidase (PPO) and the associated mechanisms. The experiment showed that SC had a strong inhibition of apple PPO. The extent of inhibition was influenced by SC concentration and pH. Inhibition was most prominent at pH 4.5, at which approximately 30% of enzyme activity was lost in the presence of 10 mM SC, followed closely by that at pH 4.0 with a 26% reduction in PPO activity. The inhibition mode was determined using Dixon and Lineweaver-Burk plots, which established SC to be a mixed inhibitor of apple PPO for the oxidation of catechol. Preincubation of PPO with 8 mM SC for 8 min caused a maximum of 46% activity reduction compared to noninhibited control. However, preincubation of SC with catechol for 8 min resulted in no additional loss of PPO activity. These findings provide further evidence that the inhibition of PPO activity by SC is due to the inhibition of the enzyme itself rather than removal of the substrate. PMID:19127746

  3. Relative safety profiles of high dose statin regimens

    PubMed Central

    Escobar, Carlos; Echarri, Rocio; Barrios, Vivencio

    2008-01-01

    Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses. PMID:18827903

  4. Determination of Chlorine Dioxide and Chlorite in Water Supply Systems by Verified Methods

    NASA Astrophysics Data System (ADS)

    Tkáčová, Jana; Božíková, Jarmila

    2014-07-01

    This work is dedicated to the development and optimization of appropriate analytical methods for the determination of chlorine dioxide and chlorite in drinking water in order to obtain accurate and correct results in the quality control of drinking water. The work deals with the development and optimization of a method for the determination of chlorine dioxide using chlorophenol red. Furthermore, a new spectrophotometric method for the determination of chlorite via bromometry using methyl orange was developed, optimized and validated. An electrochemical method for the determination of chlorite by flow coulometry was also developed, optimized and validated.

  5. The distribution of Fe and Mn between chlorite and fluid: Evidence from fluid inclusions

    SciTech Connect

    Bottrell, S.H.; Yardley, B.W.D. )

    1991-01-01

    The Fe/Mn ratio of fluid inclusions from low-grade metamorphic quartz veins has been analyzed by an improved crush-leach method. When compared with Fe and Mn in coexisting vein chlorites, exchange between fluid and chlorite is shown to vary with the redox state of the wall rocks, but is independent of the salinity of the fluid. Agreement between our results and theoretical predictions of Fe/Mn partitioning between fluid and chlorite are good for veins from relatively oxidized rocks, but vein fluids from reduced hosts are enriched in Fe.

  6. Understanding How the Distal Environment Directs Reactivity in Chlorite Dismutase: Spectroscopy and Reactivity of Arg183 Mutants

    PubMed Central

    Blanc, Béatrice; Mayfield, Jeffery A.; McDonald, Claudia A.; Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.; DuBois, Jennifer L.

    2012-01-01

    The chlorite dismutase from Dechloromonas aromatica (DaCld) catalyzes the highly efficient decomposition of chlorite to O2 and chloride. Spectroscopic, equilibrium thermodynamic, and kinetic measurements have indicated that Cld has two pH sensitive moieties; one is the heme, and Arg183 in the distal heme pocket has been hypothesized to be the second. This active site residue has been examined by site-directed mutagenesis to understand the roles of positive charge and hydrogen bonding in O–O bond formation. Three Cld mutants, Arg183 to Lys (R183K), Arg183 to Gln (R183Q), and Arg183 to Ala (R183A), were investigated to determine their respective contributions to the decomposition of chlorite ion, the spin state and coordination states of their ferric and ferrous forms, their cyanide and imidazole binding affinities, and their reduction potentials. UV–visible and resonance Raman spectroscopies showed that DaCld(R183A) contains five-coordinate high-spin (5cHS) heme, the DaCld(R183Q) heme is a mixture of five-coordinate and six-coordinate high spin (5c/6cHS) heme, and DaCld(R183K) contains six-coordinate low-spin (6cLS) heme. In contrast to wild-type (WT) Cld, which exhibits pKa values of 6.5 and 8.7, all three ferric mutants exhibited pH-independent spectroscopic signatures and kinetic behaviors. Steady state kinetic parameters of the chlorite decomposition reaction catalyzed by the mutants suggest that in WT DaCld the pKa of 6.5 corresponds to a change in the availability of positive charge from the guanidinium group of Arg183 to the heme site. This could be due to either direct acid–base chemistry at the Arg183 side chain or a flexible Arg183 side chain that can access various orientations. Current evidence is most consistent with a conformational adjustment of Arg183. A properly oriented Arg183 is critical for the stabilization of anions in the distal pocket and for efficient catalysis. PMID:22313119

  7. Chloritization of Late Ordovician K-bentonites from the northern Baltic Palaeobasin influence from source material or diagenetic environment?

    NASA Astrophysics Data System (ADS)

    Hints, Rutt; Kirsimäe, Kalle; Somelar, Peeter; Kallaste, Toivo; Kiipli, Tarmo

    2006-09-01

    The Baltic Ordovician-Silurian sedimentary succession embodies numerous altered volcanic ash beds that are illite-smectite dominated. Only a few beds rich in chlorite-smectite are known from the Upper Ordovician Pirgu Stage of Estonia. Mixed-layer chlorite-smectite occurs commonly in low-grade metamorphic and hydrothermal environments. However, chloritic K-bentonites of the Pirgu Stage have never been buried deeply and lack signs of metamorphic overprinting. In order to understand the origin of chloritization, three distinct beds were sampled in 14 drillcores from Estonia and Latvia and analysed by means of XRD and SEM. The principal authigenic assemblage of the bulk samples consists of chlorite-smectite (corrensite) together with illite-smectite and K-feldspar. The actual mineral composition of K-bentonites though varies from sample to sample. The clay mineral assemblages range from virtually pure chlorite-smectite to illite-smectite dominated assemblages with minor or no chlorite-smectite. The proportion of chlorite-smectite in K-bentonites shows systematic lateral variations: the share of chloritic phases is highest in the shallower-water part of the palaeobasin and decreases towards the deeper part of the basin. Such regular lateral variations suggest a possible link between chloritization and the configuration of ancient palaeobasin. The present study suggests that the chloritization of primary felsic ashes occurred during early diagenesis and that it was caused by an influx of Mg-rich water probably from a marine sabkha-type environment.

  8. Unusually large shear wave anisotropy for chlorite in subduction zone settings

    NASA Astrophysics Data System (ADS)

    Mookherjee, Mainak; Mainprice, David

    2014-03-01

    Using first principle simulations we calculated the elasticity of chlorite. At a density ρ~ 2.60 g cm-3, the elastic constant tensor reveals significant elastic anisotropy: VP ~27%, VS1 ~56%, and VS2 ~43%. The shear anisotropy is exceptionally large for chlorite and enhances upon compression. Upon compression, the shear elastic constant component C44 and C55 decreases, whereas C66 shear component stiffens. The softening in C44 and C55 is reflected in shear modulus, G, and the shear wave velocity, VS. Our results on elastic anisotropy at conditions relevant to the mantle wedge indicates that a 10-20 km layer of hydrated peridotite with serpentine and chlorite could account for the observed shear polarization anisotropy and associated large delay times of 1-2 s observed in some subduction zone settings. In addition, chlorite could also explain the low VP/VS ratios that have been observed in recent high-resolution seismological studies.

  9. The effect of sodium chlorite solutions on zebra mussel mortality

    SciTech Connect

    Dion, J.; Richer, Y.; Messer, R.

    1995-06-01

    The effect of four dilutions, 8 ppm, 40 ppm, 120 ppm and 473 ppm of the stock solution of a first product, Z-8, on zebra mussel mortality was investigated in static continuous exposure systems and compared to controls. The entire size class spectrum of the mussel population present at the sampling site was tested by leaving mussels attached to their original rock substrata. Two size class grouping of mussels, 13 mm and less and more than 13 mm in length, were exposed in the same test chambers but were analyzed separately. No mortality occurred in the controls. Concentration 8 ppm had no effect after 166 hours on both size class groupings. Concentrations 40, 120 and 473 ppm had observable killing effect within the 331 hours of experiment for both size groupings. The smaller mussels died faster than the larger ones. Another product, Z-11, was similarly tested during fall 1994 with dilutions 8, 40, 80 and 120 ppm. At 8 ppm dilution, Z-11 had induced only little mortality on both size class groupings after 739 hours. At 40, 80 and 120 ppm dilutions, Z-11 had interesting killing effect for both mussel size groupings within the 739 hours of experiment considering the somehow intermittent treatment used. The results already appear to show that sodium chlorite solutions have the potential for eventually becoming a surrogate to the use of chlorine for the control of zebra mussels. That is because they already show a good killing efficiency without being involved in the formation of undesired by-products such as the use of chlorine is. On this purpose, the product is engaged in the process of homologation by Agriculture Canada for it use as treatment against zebra mussels.

  10. The reactivity of chlorite surfaces: Microscopic alteration processes and the transport behaviour of uranium(VI)

    NASA Astrophysics Data System (ADS)

    Bosbach, D.; Brandt, F.; Arnold, T.; Krawczyk-Baersch, E.; Bernhard, G.

    2003-04-01

    The transport of U(VI) in phyllite rocks or on granitic fractures is significantly affected by the dissolution of chlorite and the re-precipitation of various secondary phases. However, in order to be able to predict the behaviour of radionuclides in these systems a sound understanding of the reaction kinetics of chlorite alteration/dissolution processes as well as the precipitation of secondary phases is required. We have studied the dissolution of chlorite with mixed-flow reactor experiments and in-situ AFM observations far from equilibrium over a broad pH range. Key parameters such as the reactive surface area as well as the stoichiometry and pH dependency of the dissolution reaction were determined. Speciation calculations indicate that no secondary phases have formed (except under neutral pH conditions). Under acidic conditions the brucite-like layer of the chlorite structure dissolves faster than the 2:1 TOT layer whereas above pH 8 a reverse dissolution behaviour was observed. Under acidic conditions (pH < 5) chlorite transforms to a vermiculite-like clay mineral, which has also been identified in field studies. In addition, static batch dissolution experiments with chlorite were performed in order to mimic more closely natural systems. In these experiments various secondary phases including hydrous ferrous oxides (HFO) were formed as coatings on chlorite surfaces and as colloids in solution. Batch adsorption experiments indicate that U(VI) has a strong affinity to HFO and that retardation of U(VI) occurs via adsorption to immobile HFO coatings on chlorite surfaces. Heterogeneous HFO formation seems to be favoured on {hk0} edge surfaces in the near neutral pH range. The formation mechanism of HFO coatings was studied systematically with titration experiments, in order to be able to quantify the homogeneous and heterogeneous formation of these secondary phases as a function of the geochemical conditions.

  11. High-dose methotrexate with leucovorin rescue, vinblastine, and bleomycin with or without tamoxifen in metastatic renal cell carcinoma.

    PubMed

    Bell, D R; Aroney, R S; Fisher, R J; Levi, J A

    1984-04-01

    A regimen of high-dose methotrexate with leucovorin rescue, vinblastine, and bleomycin with or without tamoxifen was administered to 34 patients with metastatic renal cell carcinoma. No complete remissions were observed, but ten patients (30%) achieved partial remission and an additional 13 patients (39%) had stabilization of disease. The median survival of responding patients (110 weeks) was significantly longer than that of nonresponding patients. The addition of tamoxifen did not influence response or survival. This regimen was tolerated without significant toxicity. A prospective randomized study of the vinblastine and high-dose methotrexate regimen compared to the respective single agents seem to be indicated. PMID:6201268

  12. High-dose secondary calibration laboratory accreditation program

    SciTech Connect

    Humphreys, J.C.

    1993-12-31

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

  13. High-dose thiamine as initial treatment for Parkinson's disease

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Compagnoni, Laura; Colangeli, Marco

    2013-01-01

    Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23986125

  14. Finnish spectrolite as high-dose gamma detector

    NASA Astrophysics Data System (ADS)

    Antonio, Patrícia L.; Caldas, Linda V. E.

    2015-11-01

    A natural material called spectrolite, from Finland, was studied in this work. The purpose was to test it in gamma radiation beams to verify its performance as a high-dose detector. From this material, pellets were manufactured with two different concentrations of Teflon and spectrolite, and their responses were verified using two luminescent techniques: thermoluminescence (TL) and optically stimulated luminescence (OSL). The TL and OSL signals were evaluated by means of characterization tests of the material response, after exposure to a nominal absorbed dose interval of 5 Gy to 10 kGy. The results obtained, for both concentrations, showed a good performance of this material in beams of high-dose gamma radiation. Both techniques were utilized in order to investigate the properties of the spectrolite+Teflon samples for different applications.

  15. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    SciTech Connect

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  16. High-Dose Intravenous Corticosteroids for Ocular Inflammatory Diseases

    PubMed Central

    Charkoudian, Leon D.; Ying, Gui-shuang; Pujari, Siddharth S.; Gangaputra, Sapna; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Suhler, Eric B.; Kempen, John H.

    2011-01-01

    Purpose To evaluate the effectiveness and risk of complications of high-dose intravenous pulsed corticosteroids for non-infectious ocular inflammatory diseases. Methods Retrospective cohort study. One hundred four eyes of seventy patients who received high-dose intravenous corticosteroids for treatment of active ocular inflammation were identified from five centers. The main outcome measures were control of inflammation and occurrence of ocular or systemic complications within one month after treatment. Results Within ≤1 month of starting treatment, 57% of eyes achieved complete control of inflammation (95% confidence interval (CI): 33-83%), improving to 82% when near-complete control was included (95% CI: 61-96%). Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in anterior chamber inflammation. One patient developed a colon perforation during treatment. No other major complications were recorded. Conclusions Treatment of ocular inflammation with high-dose intravenous corticosteroids resulted in substantial clinical improvement for most cases within one month. Complications of therapy were infrequent. PMID:22409561

  17. From chlorite dismutase towards HemQ–the role of the proximal H-bonding network in haeme binding

    PubMed Central

    Hofbauer, Stefan; Howes, Barry D.; Flego, Nicola; Pirker, Katharina F.; Schaffner, Irene; Mlynek, Georg; Djinović-Carugo, Kristina; Furtmüller, Paul G.; Smulevich, Giulietta; Obinger, Christian

    2016-01-01

    Chlorite dismutase (Cld) and HemQ are structurally and phylogenetically closely related haeme enzymes differing fundamentally in their enzymatic properties. Clds are able to convert chlorite into chloride and dioxygen, whereas HemQ is proposed to be involved in the haeme b synthesis of Gram-positive bacteria. A striking difference between these protein families concerns the proximal haeme cavity architecture. The pronounced H-bonding network in Cld, which includes the proximal ligand histidine and fully conserved glutamate and lysine residues, is missing in HemQ. In order to understand the functional consequences of this clearly evident difference, specific hydrogen bonds in Cld from ‘Candidatus Nitrospira defluvii’ (NdCld) were disrupted by mutagenesis. The resulting variants (E210A and K141E) were analysed by a broad set of spectroscopic (UV–vis, EPR and resonance Raman), calorimetric and kinetic methods. It is demonstrated that the haeme cavity architecture in these protein families is very susceptible to modification at the proximal site. The observed consequences of such structural variations include a significant decrease in thermal stability and also affinity between haeme b and the protein, a partial collapse of the distal cavity accompanied by an increased percentage of low-spin state for the E210A variant, lowered enzymatic activity concomitant with higher susceptibility to self-inactivation. The high-spin (HS) ligand fluoride is shown to exhibit a stabilizing effect and partially restore wild-type Cld structure and function. The data are discussed with respect to known structure–function relationships of Clds and the proposed function of HemQ as a coprohaeme decarboxylase in the last step of haeme biosynthesis in Firmicutes and Actinobacteria. PMID:26858461

  18. From chlorite dismutase towards HemQ - the role of the proximal H-bonding network in haeme binding.

    PubMed

    Hofbauer, Stefan; Howes, Barry D; Flego, Nicola; Pirker, Katharina F; Schaffner, Irene; Mlynek, Georg; Djinović-Carugo, Kristina; Furtmüller, Paul G; Smulevich, Giulietta; Obinger, Christian

    2016-01-01

    Chlorite dismutase (Cld) and HemQ are structurally and phylogenetically closely related haeme enzymes differing fundamentally in their enzymatic properties. Clds are able to convert chlorite into chloride and dioxygen, whereas HemQ is proposed to be involved in the haeme b synthesis of Gram-positive bacteria. A striking difference between these protein families concerns the proximal haeme cavity architecture. The pronounced H-bonding network in Cld, which includes the proximal ligand histidine and fully conserved glutamate and lysine residues, is missing in HemQ. In order to understand the functional consequences of this clearly evident difference, specific hydrogen bonds in Cld from 'Candidatus Nitrospira defluvii' (NdCld) were disrupted by mutagenesis. The resulting variants (E210A and K141E) were analysed by a broad set of spectroscopic (UV-vis, EPR and resonance Raman), calorimetric and kinetic methods. It is demonstrated that the haeme cavity architecture in these protein families is very susceptible to modification at the proximal site. The observed consequences of such structural variations include a significant decrease in thermal stability and also affinity between haeme b and the protein, a partial collapse of the distal cavity accompanied by an increased percentage of low-spin state for the E210A variant, lowered enzymatic activity concomitant with higher susceptibility to self-inactivation. The high-spin (HS) ligand fluoride is shown to exhibit a stabilizing effect and partially restore wild-type Cld structure and function. The data are discussed with respect to known structure-function relationships of Clds and the proposed function of HemQ as a coprohaeme decarboxylase in the last step of haeme biosynthesis in Firmicutes and Actinobacteria. PMID:26858461

  19. Chloritization and associated alteration at the Jabiluka unconformity-type uranium deposit, Northern Territory, Australia

    USGS Publications Warehouse

    Nutt, Constance J.

    1989-01-01

    Jabiluka is the largest of four known uncomformity-type uranium deposits that are hosted by brecciated and altered metasedimentary rocks in the Pine Creek geosyncline, Northern Territory, Australia. The alteration zone at Jabiluka is dominated by chlorite, but also contains white mica, tourmaline and apatite; hematite is present, but only in minor amounts. Added quartz is mainly restricted to fractures and breccias. Chlorite, which formed during episodic fluid movement, partly to totally replaced all pre-existing minerals. Chloritized rocks are enriched in Mg, and depleted in K, Ca, Na and Si. Five types of chlorite are optically and chemically distinguishable in the rocks at Jabiluka. Chloritization is proposed as a mechanism that lowered the pH of the circulating fluid, and also caused significant loss of silica from the altered rocks. The proposed constraints on alteration, and presumably on at least part of the uranium mineralization, neither require nor preclude the existence of the unconformity as necessary for the formation of ore.

  20. Vanadium chlorite from a sandstone-hosted vanadium-uranium deposit, Henry basin, Utah.

    USGS Publications Warehouse

    Whitney, G.; Northrop, H.R.

    1986-01-01

    This ore deposit formed by reduction and precipitation of U and V in the presence of organic matter at the interface between a stagnant brine and overlying circulating meteoric water. Some samples of the vanadium chlorite (heated before analysis) contain = or >10% V2O5; in fresh samples most of the V is in the V3+ state. XRD data suggest that Fe and V are concentrated preferentially in the interlayer hydroxide sheets of the chlorite. A d060 value of 1.52 A indicates that the chlorite probably has a dioctahedral structure distended by the presence of octahedral Fe and V; it is a IIb polytype. The V ore zone is flanked by peripheral zones with perfectly ordered chlorite/smectite containing much less V than the pure chlorite. Chemical analysis of a sample heated to 900oC before analysis gave SiO2 44.89, Al2O3 25.14, TiO2 0.35, Fe2O3 8.29, MgO 8.47, CaO 0.84, Na2O 0.27, K2O 2.18, Li2O 0.16, UO3 0.92, V2O5 9.14, = 100.65, together with Cr 10, Mn 200, Co 150, Ni 5.8, Cu 10, Zn 140 ppm; XRD, DTG, TG and IR curves are presented. -R.A.H.

  1. Unexpected Diversity of Chlorite Dismutases: a Catalytically Efficient Dimeric Enzyme from Nitrobacter winogradskyi ▿ †

    PubMed Central

    Mlynek, Georg; Sjöblom, Björn; Kostan, Julius; Füreder, Stephanie; Maixner, Frank; Gysel, Kira; Furtmüller, Paul Georg; Obinger, Christian; Wagner, Michael; Daims, Holger; Djinović-Carugo, Kristina

    2011-01-01

    Chlorite dismutase (Cld) is a unique heme enzyme catalyzing the conversion of ClO2− to Cl− and O2. Cld is usually found in perchlorate- or chlorate-reducing bacteria but was also recently identified in a nitrite-oxidizing bacterium of the genus Nitrospira. Here we characterized a novel Cld-like protein from the chemolithoautotrophic nitrite oxidizer Nitrobacter winogradskyi which is significantly smaller than all previously known chlorite dismutases. Its three-dimensional (3D) crystal structure revealed a dimer of two identical subunits, which sharply contrasts with the penta- or hexameric structures of other chlorite dismutases. Despite a truncated N-terminal domain in each subunit, this novel enzyme turned out to be a highly efficient chlorite dismutase (Km = 90 μM; kcat = 190 s−1; kcat/Km = 2.1 × 106 M−1 s−1), demonstrating a greater structural and phylogenetic diversity of these enzymes than was previously known. Based on comparative analyses of Cld sequences and 3D structures, signature amino acid residues that can be employed to assess whether uncharacterized Cld-like proteins may have a high chlorite-dismutating activity were identified. Interestingly, proteins that contain all these signatures and are phylogenetically closely related to the novel-type Cld of N. winogradskyi exist in a large number of other microbes, including other nitrite oxidizers. PMID:21441524

  2. Transiently Produced Hypochlorite Is Responsible for the Irreversible Inhibition of Chlorite Dismutase

    PubMed Central

    2014-01-01

    Chlorite dismutases (Clds) are heme b-containing prokaryotic oxidoreductases that catalyze the reduction of chlorite to chloride with the concomitant release of molecular oxygen. Over time, they are irreversibly inactivated. To elucidate the mechanism of inactivation and investigate the role of the postulated intermediate hypochlorite, the pentameric chlorite dismutase of “Candidatus Nitrospira defluvii” (NdCld) and two variants (having the conserved distal arginine 173 exchanged with alanine and lysine) were recombinantly produced in Escherichia coli. Exchange of the distal arginine boosts the extent of irreversible inactivation. In the presence of the hypochlorite traps methionine, monochlorodimedone, and 2-[6-(4-aminophenoxy)-3-oxo-3H-xanthen-9-yl]benzoic acid, the extent of chlorite degradation and release of molecular oxygen is significantly increased, whereas heme bleaching and oxidative modifications of the protein are suppressed. Among other modifications, hypochlorite-mediated formation of chlorinated tyrosines is demonstrated by mass spectrometry. The data obtained were analyzed with respect to the proposed reaction mechanism for chlorite degradation and its dependence on pH. We discuss the role of distal Arg173 by keeping hypochlorite in the reaction sphere for O–O bond formation. PMID:24754261

  3. High-dose chemotherapy in small-cell lung cancer.

    PubMed

    Pasini, F; Durante, E; De Manzoni, D; Rosti, G; Pelosi, G

    2002-01-01

    Small cell lung cancer (SCLC) is highly sensitive both to radiotherapy and chemotherapy. Given its high chemo sensitivity, even two decades ago, SCLC was one of the first malignancies deemed suitable for maximising the dose and dose intensity with the support of autologous bone marrow (ABMT). On the whole, results were disappointing and the procedure was practically abandoned. Nowadays some interest is again emerging due to improvements in supportive care, such as the availability of hematopoietic growth factors and the peripheral blood progenitor cells (PBPC). Data of 505 patients included in 26 studies were reviewed. About two thirds of these patients had LD (limited disease). Late intensification protocols were used in 311 patients who, however, represented only the 30% of the population initially given conventional chemotherapy. Of the patients not achieving complete remission (CR) after induction, high-dose induced a CR in 39% of the cases. The use of early intensification was reported in 8 studies including 194 patients. The CR rate was 51.5%. Overall, the probability of achieving the CR was 2-3 times higher in LD than in ED (extensive disease). Relapses occurred at the site of the primary in more than half of the cases, showing that the course of the disease was not modified by the use of high-dose chemotherapy. Toxic deaths occurred in 7% of the treated patients, without difference in the two treatment methods. Though the schedules were too variable to draw firm conclusions, the ICE (ifosfamide, carboplatin, etoposide) and the CBP (cyclophosphamide, cisplatin, carmustine) regimens apparently provided better results, with a 2-year survival rate of 30-50% in the LD subset. An european multicenter randomized trial is ongoing. At the present time high-dose chemotherapy is still to be considered experimental treatment, since major problems such as the selection of the patients, doses and timing of chemotherapy and radiotherapy remain unsolved. PMID:12552940

  4. High dose rate intraluminal irradiation in recurrent endobronchial carcinoma

    SciTech Connect

    Seagren, S.L.; Harrell, J.H.; Horn, R.A.

    1985-12-01

    Palliative therapy for previously irradiated patients with symptomatic recurrent endobronchial malignancy is a difficult problem. We have had the opportunity to treat 20 such patients with high dose rate (50-100 rad/min) endobronchial brachytherapy. Eligible patients had received previous high dose thoracic irradiation (TDF greater than or equal to 90), a performance status of greater than or equal to 50, and symptoms caused by a bronchoscopically defined and implantable lesion. The radiation is produced by a small cobalt-60 source (0.7 Ci) remotely afterloaded by cable control. The source is fed into a 4 mm diameter catheter which is placed with bronchoscopic guidance; it may oscillate if necessary to cover the lesion. A dose of 1,000 rad at 1 cm from the source is delivered. We have performed 22 procedures in 20 patients, four following YAG laser debulking. Most had cough, some with hemoptysis. Eight had dyspnea secondary to obstruction and three had obstructive pneumonitis. In 12, symptoms recurred with a mean time to recurrence of 4.3 months (range 1-9 months). Eighteen patients were followed-up and reexamined via bronchoscope 1-2.5 months following the procedure; two were lost to follow-up. All had at least 50 percent clearance of tumor, and six had complete clearance; most regressions were documented on film or videotape. In six, the palliation was durable. The procedure has been well tolerated with no toxicity. We conclude that palliative endobronchial high dose rate brachytherapy is a useful palliative modality in patients with recurrent endobronchial symptomatic carcinoma.

  5. High-dose enzyme replacement therapy in murine Hurler syndrome.

    PubMed

    Ou, Li; Herzog, Tyler; Koniar, Brenda L; Gunther, Roland; Whitley, Chester B

    2014-02-01

    Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease that is systemic, including progressive neurodegeneration, mental retardation and death before the age of 10 years. MPS I results from deficiency of α-L-iduronidase (IDUA) in lysosomes and subsequent accumulation of glycosaminoglycans (GAG). Clinical enzyme replacement therapy (ERT) with intravenous laronidase reverses some aspects of MPS I disease (e.g., hepatomegaly, splenomegaly, glycosaminoglycanuria) and ameliorates others (e.g., pulmonary function, cardiac disease, arthropathy, exercise tolerance). However, neurologic benefits are thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from reaching the central nervous system (CNS). We considered the possibility that a very high dose of intravenous laronidase might be able to traverse the BBB in small quantities, and provide some metabolic correction in the brain. To address this question, high-dose laronidase was administered (11.6 mg/kg, once per week, 4 weeks) to adult MPS I mice. IDUA enzyme activity in the cortex of treated mice increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were reduced by 63% of that from untreated MPS I mice (p<0.05). Further, immunohistochemical analysis showed that treatment reduced secondary GM3-ganglioside accumulation in treated MPS I mice. Water T-maze tests showed that the learning abnormality in MPS I mice was reduced (p<0.0001). In summary, repeated, high-dose ERT facilitated laronidase transit across the BBB, reduced GAG accumulation within the CNS, and rescued cognitive impairment. PMID:24100243

  6. On carbon nitride synthesis at high-dose ion implantation

    NASA Astrophysics Data System (ADS)

    Romanovsky, E. A.; Bespalova, O. V.; Borisov, A. M.; Goryaga, N. G.; Kulikauskas, V. S.; Sukharev, V. G.; Zatekin, V. V.

    1998-04-01

    Rutherford backscattering spectrometry was used for the study of high dose 35 keV nitrogen ions implantation into graphites and glassy carbon. Quantitative data on depth profiles and its dependencies on irradiation fluence and ion beam density were obtained. The stationary dome-shaped depth profile with maximum nitrogen concentration 22-27 at.% and half-width more than twice exceeding projected range of ions is reached at fluence Φ ˜10 18 cm -2. The dependence of the maximum concentration in the profile on ion current density was studied. The largest concentration was obtained at reduced ion current density.

  7. High dose calcitriol may reduce thrombosis in cancer patients.

    PubMed

    Beer, Tomasz M; Venner, Peter M; Ryan, Christopher W; Petrylak, Daniel P; Chatta, Gurkamal; Dean Ruether, J; Chi, Kim N; Curd, John G; DeLoughery, Thomas G

    2006-11-01

    The incidence of venous and arterial thrombosis in a placebo-controlled randomised trial of DN-101 (high dose calcitriol) with docetaxel versus docetaxel was compared. Of the 13 thrombotic events observed in the 250 patients enroled in this study, two occurred in DN-101 and 11 in placebo-treated patients (P = 0.01). This difference remained significant after adjustment for baseline history of thrombosis, atrial fibrillation and use of anti-thrombotic agents. In vitro and vitamin D receptor (VDR) knockout mouse studies predict that nanomolar concentrations of calcitriol may act as an antithrombotic agent. We report the first clinical observation that supports this hypothesis in humans. PMID:16984385

  8. Pharmacokinetic interaction between high-dose methotrexate and oxacillin.

    PubMed

    Titier, Karine; Lagrange, Fabrice; Péhourcq, Fabienne; Moore, Nicholas; Molimard, Mathieu

    2002-08-01

    An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate. PMID:12142645

  9. Compatible mechanism to characterize three independent but cross-coupled reactions of chlorite ion

    NASA Astrophysics Data System (ADS)

    Nagypál, István; Horváth, Attila K.

    2015-06-01

    Individually proposed kinetic models of the key subsystems of the chlorite-thiosulfate reaction, such as the hypochlorous acid-chlorite, tetrathionate-chlorite, and tetrathionate-chlorine dioxide reactions, have been unified to be able to describe all the main characteristics of these systems simultaneously. A complex 38-step kinetic model is composed in which the subsystems are coupled by the necessary short-lived intermediates and such species that is products or reactants in one system but transients in the other. Such a cross-coupling between the individual systems as well as the sound agreement between the measured and calculated absorbance-time profiles in 367 experimental curves strongly validates the proposed kinetic model.

  10. Compatible mechanism to characterize three independent but cross-coupled reactions of chlorite ion.

    PubMed

    Nagypál, István; Horváth, Attila K

    2015-06-01

    Individually proposed kinetic models of the key subsystems of the chlorite-thiosulfate reaction, such as the hypochlorous acid-chlorite, tetrathionate-chlorite, and tetrathionate-chlorine dioxide reactions, have been unified to be able to describe all the main characteristics of these systems simultaneously. A complex 38-step kinetic model is composed in which the subsystems are coupled by the necessary short-lived intermediates and such species that is products or reactants in one system but transients in the other. Such a cross-coupling between the individual systems as well as the sound agreement between the measured and calculated absorbance-time profiles in 367 experimental curves strongly validates the proposed kinetic model. PMID:26117129

  11. A chlorite solid solution geothermometer the Los Azufres (Mexico) geothermal system

    NASA Astrophysics Data System (ADS)

    Cathelineau, Michel; Nieva, David

    1985-11-01

    Chlorite constitutes a major hydrothermal alteration product of metamorphism of andesites, in the active geothermal system of Los Azufres (Mexico). Electron microprobe analyses performed on a set of crystals from each sample show wide variations in composition. Correlation coefficients among chemical constituents were calculated. It is shown that the tetrahedral charge is positively correlated with the octahedral vacancy and negatively with the iron content, and there is almost no correlation with the octahedral aluminium and magnesium content. A procedure is proposed to select end-members and substitution vectors, and to give a general formula for these chlorites. Their formation temperatures are estimated with great accuracy, combining results of microthermometric data on fluid inclusions from gangue minerals of chlorites (quartz, calcite), direct measurements in wells (Kuster equipment), and chemical geothermometers. Correlations between chlorite compositions, range and nature of site occupancy, and temperature are good. Formation temperatures of chlorites range from 130° C to 300° C. As no other thermodynamic parameter varies significantly in the studied field (composition of the host rocks, nature of the geothermal fluids, pressure, ...), these variations of site occupancy (mainly Al(IV) and the octahedral occupancy (6-Al(VI)-(Mg+Fe(2+)) = VAC) are considered mainly as temperature dependent. Molar fractions of each end-member show very different variations with increasing temperature: X-kaolinite decreases, and X-chamosite increases, while X-talc-3 brucite does not show significant change. From these data, activity coefficients and standard state chemical potential of major components, and molar free energy formation of chlorite have been calculated for each temperature of crystallisation.

  12. [Clinical trials of ultra-high-dose methylcobalamin in ALS].

    PubMed

    Izumi, Yuishin; Kaji, Ryuji

    2007-10-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both upper and lower motor neurons. Weakness may begin in the legs, hands, proximal arms, or pharynx. The course is relentless and progressive without remissions, relapses, or even stable plateaus. There is no effective drug therapy for ALS, although riluzole has been shown to prolong life in sufferers, without tracheostomy. A vitamin B12 analog, methylcobalamin, has a protective effect on cultured cortical neurons against glutamate-induced cytotoxicity. We have shown the ultra-high-dose methylcobalamin (25 mg/day i.m.) slows down the progressive reduction of the CMAP (compound muscle action potential) amplitudes in ALS in the short term (4 weeks). The latencies of SSR (sympathetic skin response) were shorter after treatment (50 mg/day i.v., 2 weeks). In the long-term effect of methylcobalamin (50 mg/day i.m., twice a week), the survival time (or the period to become respirator-bound) was significantly longer in the treated group than in the untreated. Larger-scale randomized double blind trial was started in Japan in order to evaluate the long-term efficacy and the safety of ultra-high-dose methylcobalamin for sporadic or familial cases of ALS. PMID:17969354

  13. Pharmacokinetics of high-dose busulfan in children.

    PubMed

    Vassal, G; Gouyette, A; Hartmann, O; Pico, J L; Lemerle, J

    1989-01-01

    The pharmacokinetics of high-dose busulfan given orally at 1 mg/kg every 6 h over 4 days (total dose, 16 mg/kg) in combined chemotherapy followed by autologous bone marrow transplantation was studied in 12 children with a mean age of 7 years (range, 4-14 years). Busulfan levels in biological fluids were measured by a gas chromatographic assay with mass fragmentographic detection, using a deuterated analogue as the internal standard. In a high-dose regimen, busulfan followed one-compartment model kinetics with zero-order absorption. A mean maximal concentration of 803 +/- 228 ng/ml was achieved at 92-255 min after dosing. The mean elimination half-life was 2.33 h, and the mean total clearance was 119 +/- 54 ml/min per m2, with an apparent distribution volume of 27.10 +/- 11.50 l/m2. A mean trough level of 370 ng/ml was found throughout the 4 days of the chemotherapy course. There were no significant variations in pharmacokinetic parameters measured after the first and last doses. Busulfan was monitored in the CSF of nine children at 3.25-7 h after the last dose and was detected in all patients, with a mean CSF-to-plasma concentration ratio of 0.95 (range, 0.5-1.4). PMID:2791192

  14. ELDRS Characterization for a Very High Dose Mission

    NASA Technical Reports Server (NTRS)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  15. Total rod ERG suppression with high dose compassionate Fenretinide usage.

    PubMed

    Marmor, Michael F; Jain, Atul; Moshfeghi, Darius

    2008-11-01

    Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability. PMID:18523815

  16. Spectroscopic gamma camera for use in high dose environments

    NASA Astrophysics Data System (ADS)

    Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Kometani, Yutaka; Suzuki, Yasuhiko; Umegaki, Kikuo

    2016-06-01

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  17. Kikuchi-Fujimoto disease presenting after consumption of 'Miracle Mineral Solution' (sodium chlorite).

    PubMed

    Loh, John Ming Ren; Shafi, Humaira

    2014-01-01

    We present a case report of a 41-year-old woman of Malay ethnicity who presented with an 11-day history of fever and left-sided lymphadenopathy after consuming 'Miracle Mineral Solution' (sodium chlorite solution) for the first time. A diagnosis of Kikuchi-Fujimoto disease was established via lymph node biopsy after other differentials were excluded. The aetiology of Kikuchi-Fujimoto disease remains controversial, but viral, autoimmune and physicochemical causes have been suggested as possibilities. In this case, we hypothesise that oxidative injury from sodium chlorite initiated an inflammatory response, which triggered the onset of Kikuchi-Fujimoto disease. PMID:25422331

  18. Structure and heme-binding properties of HemQ (chlorite dismutase-like protein) from Listeria monocytogenes

    PubMed Central

    Hofbauer, Stefan; Hagmüller, Andreas; Schaffner, Irene; Mlynek, Georg; Krutzler, Michael; Stadlmayr, Gerhard; Pirker, Katharina F.; Obinger, Christian; Daims, Holger; Djinović-Carugo, Kristina; Furtmüller, Paul G.

    2015-01-01

    Chlorite dismutase-like proteins are structurally closely related to functional chlorite dismutases which are heme b-dependent oxidoreductases capable of reducing chlorite to chloride with simultaneous production of dioxygen. Chlorite dismutase-like proteins are incapable of performing this reaction and their biological role is still under discussion. Recently, members of this large protein family were shown to be involved in heme biosynthesis in Gram-positive bacteria, and thus the protein was renamed HemQ in these organisms. In the present work the structural and heme binding properties of the chlorite dismutase-like protein from the Gram-positive pathogen Listeria monocytogenes (LmCld) were analyzed in order to evaluate its potential role as a regulatory heme sensing protein. The homopentameric crystal structure (2.0 Å) shows high similarity to chlorite-degrading chlorite dismutases with an important difference in the structure of the putative substrate and heme entrance channel. In solution LmCld is a stable hexamer able to bind the low-spin ligand cyanide. Heme binding is reversible with KD-values determined to be 7.2 μM (circular dichroism spectroscopy) and 16.8 μM (isothermal titration calorimetry) at pH 7.0. Both acidic and alkaline conditions promote heme release. Presented biochemical and structural data reveal that the chlorite dismutase-like protein from L. monocytogenes could act as a potential regulatory heme sensing and storage protein within heme biosynthesis. PMID:25602700

  19. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of chlorite dismutase: a detoxifying enzyme producing molecular oxygen

    SciTech Connect

    Geus, Daniël C. de Thomassen, Ellen A. J.; Feltz, Clarisse L. van der; Abrahams, Jan Pieter

    2008-08-01

    Preliminary X-ray data collection and analysis for crystals of chlorite dismutase, a haem-based enzyme that very effectively reduces chlorite to chloride while producing molecular oxygen, is reported to 2.1 Å resolution. Chlorite dismutase, a homotetrameric haem-based protein, is one of the key enzymes of (per)chlorate-reducing bacteria. It is highly active (< 2 kU mg{sup −1}) in reducing the toxic compound chlorite to the innocuous chloride anion and molecular oxygen. Chlorite itself is produced as the intermediate product of (per)chlorate reduction. The chlorite dismutase gene in Azospira oryzae strain GR-1 employing degenerate primers has been identified and the active enzyme was subsequently overexpressed in Escherichia coli. Chlorite dismutase was purified, proven to be active and crystallized using sitting drops with PEG 2000 MME, KSCN and ammonium sulfate as precipitants. The crystals belonged to space group P2{sub 1}2{sub 1}2 and were most likely to contain six subunits in the asymmetric unit. The refined unit-cell parameters were a = 164.46, b = 169.34, c = 60.79 Å. The crystals diffracted X-rays to 2.1 Å resolution on a synchrotron-radiation source and a three-wavelength MAD data set has been collected. Determination of the chlorite dismutase structure will provide insights into the active site of the enzyme, for which no structures are currently available.

  20. Structure and heme-binding properties of HemQ (chlorite dismutase-like protein) from Listeria monocytogenes.

    PubMed

    Hofbauer, Stefan; Hagmüller, Andreas; Schaffner, Irene; Mlynek, Georg; Krutzler, Michael; Stadlmayr, Gerhard; Pirker, Katharina F; Obinger, Christian; Daims, Holger; Djinović-Carugo, Kristina; Furtmüller, Paul G

    2015-05-15

    Chlorite dismutase-like proteins are structurally closely related to functional chlorite dismutases which are heme b-dependent oxidoreductases capable of reducing chlorite to chloride with simultaneous production of dioxygen. Chlorite dismutase-like proteins are incapable of performing this reaction and their biological role is still under discussion. Recently, members of this large protein family were shown to be involved in heme biosynthesis in Gram-positive bacteria, and thus the protein was renamed HemQ in these organisms. In the present work the structural and heme binding properties of the chlorite dismutase-like protein from the Gram-positive pathogen Listeria monocytogenes (LmCld) were analyzed in order to evaluate its potential role as a regulatory heme sensing protein. The homopentameric crystal structure (2.0Å) shows high similarity to chlorite-degrading chlorite dismutases with an important difference in the structure of the putative substrate and heme entrance channel. In solution LmCld is a stable hexamer able to bind the low-spin ligand cyanide. Heme binding is reversible with KD-values determined to be 7.2μM (circular dichroism spectroscopy) and 16.8μM (isothermal titration calorimetry) at pH 7.0. Both acidic and alkaline conditions promote heme release. Presented biochemical and structural data reveal that the chlorite dismutase-like protein from L. monocytogenes could act as a potential regulatory heme sensing and storage protein within heme biosynthesis. PMID:25602700

  1. High doses of corticosteroids in the treatment of septic shock.

    PubMed

    Hellman, A; Alestig, K

    1985-01-01

    High doses of corticosteroids are reported to be beneficial in the treatment of septic shock in many animal species, e.g. dog, rat and rabbit. Recent findings in baboons subjected to E. coli shock indicate that early treatment with a combination of antibiotics and steroids strongly enhance survival rate. In clinical studies the protective effects of steroids are more ambiguous, however. In part this may be explained by variations in the amount of steroids used or by the fact that in some studies the steroid is administered late in shock. The dose recommended, 30 mg/kg bw of methylprednisolone or an equivalent amount of another glucocorticoid given once or twice, is based on animal as well as clinical documentation. PMID:3911703

  2. High-dose thiamine improves the symptoms of fibromyalgia.

    PubMed

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-01-01

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients' history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms. PMID:23696141

  3. High-dose thiamine improves the symptoms of Friedreich's ataxia

    PubMed Central

    Costantini, Antonio; Giorgi, Rafaela; D'Agostino, Sonia; Pala, Maria Immacolata

    2013-01-01

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3–5  days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease. PMID:23704441

  4. High dose thiamine improves fatigue in multiple sclerosis

    PubMed Central

    Costantini, Antonio; Nappo, Agostino; Pala, Maria Immacolata; Zappone, Antonietta

    2013-01-01

    The majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23861280

  5. High-dose thiamine improves the symptoms of fibromyalgia

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-01-01

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients’ history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms. PMID:23696141

  6. High dose bystander effects in spatially fractionated radiation therapy

    PubMed Central

    Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

    2014-01-01

    Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

  7. Oxidation of silicon implanted with high-dose aluminum

    SciTech Connect

    Yang, Zunde; Du, Honghua; Withrow, S.P.

    1994-12-31

    Si(100) wafers were implanted with Al at 500 C to high doses at multi-energies and were oxidized in 1 atm flowing oxygen at 1000-1200 C. Morphology, structure, and oxidation behavior of the implanted and oxidized Si were studied using optical microscopy, atomic force microscopy, and cross-sectional transmission electron microscopy in conjunction with selected area electron diffraction and energy dispersive x-ray analysis. Large Al precipitates were formed and embedded near the surface region of the implanted Si. Oxidation rate of the Al-implanted Si wafers was lower than that of virgin Si. The unique morphology of the implanted Si results from rpaid Al diffusion and segregation promoted by hot implantation. Reduction of the oxidation rate of Si by Al implantation is attributed to preferential oxidation of Al and formation of a continuous diffusion barrier of Al{sub 2}O{sub 3}.

  8. Anti-angiogenic effect of high doses of ascorbic acid

    PubMed Central

    Mikirova, Nina A; Ichim, Thomas E; Riordan, Neil H

    2008-01-01

    Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA. PMID:18789157

  9. High dose intravenous ciprofloxacin in febrile neutropenic patients.

    PubMed

    Johnson, P R; Yin, J A; Tooth, J A

    1990-12-01

    We have evaluated the use of high-dose intravenous ciprofloxacin as monotherapy in the empirical therapy of febrile episodes in neutropenic patients during the course of a randomized trial comparing ciprofloxacin with a standard combination regimen. Sixty-four episodes of fever were studied in a high risk population of 42 patients mostly undergoing intensive chemotherapy for leukaemia. Ciprofloxacin achieved clinical responses as follows: completely successful in 39%, partially successful in 20%, and unsuccessful in 41%. Infections were microbiologically documented in 37 (58%), with Gram-positive bacteria (of which 37% were coagulase negative staphylococci and 34% were streptococci) accounting for 81% of all organisms cultured. Responses in documented infections were as follows; completely successful in 32%, partially successful in 27%, and unsuccessful in 41%. One infection-related death occurred 30 h after starting ciprofloxacin, and a further three patients died before the resolution of neutropenia. The early death was caused by fulminant infection with a ciprofloxacin-resistant Pseudomonas aeruginosa. No other ciprofloxacin resistance was seen amongst eight Gram-negative isolates. There was no evidence of emerging ciprofloxacin resistance during the course of the study. Ciprofloxacin was associated with a low incidence of adverse events with skin rash (five cases) and nausea (one case) being reported as possibly or probably related to ciprofloxacin. We conclude that high-dose intravenous ciprofloxacin may be safely employed as monotherapy in the empirical treatment of febrile episodes in neutropenic patients. It has the additional advantages of twice daily administration, the availability of intravenous and oral presentations, and absence of cross-allergy in beta-lactam antibiotic hypersensitive patients. PMID:2292537

  10. Dosimetric investigation of high dose rate, gated IMRT

    SciTech Connect

    Lin, Teh; Chen Yan; Hossain, Murshed; Li, Jinsheng; Ma, C.-M.

    2008-11-15

    Increasing the dose rate offers time saving for IMRT delivery but the dosimetric accuracy is a concern, especially in the case of treating a moving target. The objective of this work is to determine the effect of dose rate associated with organ motion and gated treatment using step-and-shoot IMRT delivery. Both measurements and analytical simulation on clinical plans are performed to study the dosimetric differences between high dose rate and low dose rate gated IMRT step-and-shoot delivery. Various sites of IMRT plans for liver, lung, pancreas, and breast cancers were delivered to a custom-made motorized phantom, which simulated sinusoidal movement. Repeated measurements were taken for gated and nongated delivery with different gating settings and three dose rates, 100, 500, and 1000 MU/min using ion chambers and extended dose range films. For the study of the residual motion effect for individual segment dose and composite dose of IMRT plans, our measurements with 30%-60% phase gating and without gating for various dose rates were compared. A small but clinically acceptable difference in delivered dose was observed between 1000, 500, and 100 MU/min at 30%-60% phase gating. A simulation is presented, which can be used for predicting dose profiles for patient cases in the presence of motion and gating to confirm that IMRT step-and-shoot delivery with gating for 1000 MU/min are not much different from 500 MU/min. Based on the authors sample plan analyses, our preliminary results suggest that using 1000 MU/Min dose rate is dosimetrically accurate and efficient for IMRT treatment delivery with gating. Nonetheless, for the concern of patient care and safety, a patient specific QA should be performed as usual for IMRT plans for high dose rate deliveries.

  11. Assessments for High Dose Radionuclide Therapy Treatment Planning

    SciTech Connect

    Fisher, Darrell R.

    2003-10-01

    Advances in the biotechnology of cell-specific targeting of cancer, and the increased number of clinical trials involving treatment of cancer patients with radiolabeled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high-dose radionuclide therapy procedures. Optimized radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose-limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential time points using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organs tissues of concern, for the whole body, and sometimes for selected tumors. Patient-specific factors often require that dose estimates be customized for each patient. The Food and Drug Administration regulates the experimental use of investigational new drugs and requires reasonable calculation of radiation absorbed dose to the whole body and to critical organs using methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high-dose studies in the U.S. and elsewhere shows that 1) some studies are conducted with minimal dosimetry, 2) the marrow dose is difficult to establish and is subject to large uncertainties, and 3) despite the general availability of MIRD software, internal dosimetry methods are often inconsistent from one clinical center to another.

  12. Acidified sodium chlorite as an alternative to chlorine for elimination of Salmonella on alfalfa seeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The disadvantage associated with the use of chlorine for food processing and water treatment had been documented previously. This study was conducted to determine if acidified sodium chlorite (ASC) could be used to replace calcium hypochlorite [Ca(OCl)2] for disinfection of alfalfa seeds. Seeds co...

  13. EFFICACY OF SODIUM CHLORITE AS AN INHIBITOR OF ENZYMATIC BROWNING IN APPLE SLICES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sodium chlorite (SC) is an effective sanitizer for inhibiting microbial growth. This investigation was conducted to determine the efficacy of SC as a browning control agent for use on fresh-cut apple slices, applied alone, or in conjunction with organic acids. Additionally, the authors compared the ...

  14. Influence of drinking water treatments on chlorine dioxide consumption and chlorite/chlorate formation.

    PubMed

    Sorlini, Sabrina; Gialdini, Francesca; Biasibetti, Michela; Collivignarelli, Carlo

    2014-05-01

    Disinfection is the last treatment stage of a Drinking Water Treatment Plant (DWTP) and is carried out to maintain a residual concentration of disinfectant in the water distribution system. Chlorine dioxide (ClO2) is a widely used chemical employed for this purpose. The aim of this work was to evaluate the influence of several treatments on chlorine dioxide consumption and on chlorite and chlorate formation in the final oxidation/disinfection stage. A number of tests was performed at laboratory scale employing water samples collected from the DWTP of Cremona (Italy). The following processes were studied: oxidation with potassium permanganate, chlorine dioxide and sodium hypochlorite, coagulation/flocculation with ferric chloride and aluminum sulfate, filtration and adsorption onto activated carbon. The results showed that the chlorine dioxide demand is high if sodium hypochlorite or potassium permanganate are employed in pre-oxidation. On the other hand, chlorine dioxide leads to the highest production of chlorite and chlorate. The coagulation/flocculation process after pre-oxidation shows that chlorine dioxide demand decreases if potassium permanganate is employed as an oxidant, both with ferric chloride and aluminum sulfate. Therefore, the combination of these processes leads to a lower production of chlorite and chlorate. Aluminum sulfate is preferable in terms of the chlorine dioxide demand reduction and minimization of the chlorite and chlorate formation. Activated carbon is the most effective solution as it reduced the chlorine dioxide consumption by about 50% and the DBP formation by about 20-40%. PMID:24534637

  15. Elucidation of the mechanism of enzymatic browning inhibition by sodium chlorite

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sodium chlorite (SC) is a well known anti-microbial agent and its strong inhibitory effect on enzymatic browning of fresh-cut produce has recently been identified. We investigated the mechanisms of browning inhibition by SC using chlorogenic acid (CA) and PPO extracted from mushroom to emulate the b...

  16. SODIUM CHLORITE ADMINISTRATION IN LONG-EVANS RATS: REPRODUCTIVE AND ENDOCRINE EFFECTS

    EPA Science Inventory

    Long-Evans rats, 4-6 weeks of age, were given access to 0, 1, 10, or 100 ppm sodium chlorite in deionized water ad libitum as drinking water. Males were evaluated for sperm parameters and reproductive tract histopathology following the breeding. Females were exposed throughout ge...

  17. REACTIONS OF CHLORITE WITH ACTIVATED CARBON AND WITH VANILLIC ACID AND INDAN ADSORBED ON ACTIVATED CARBON

    EPA Science Inventory

    The reaction between chlorite (CO2(-1)) and vanillic acid, at pH 6.0 in the presence of granular activated carbon (GAC), yielded several reaction products identifiable by GC/MS; no products were found in the absence of GAC. Indan and ClO2 or ClO2(-1) reacted in aqueous solution a...

  18. Chlorite dismutases – a heme enzyme family for use in bioremediation and generation of molecular oxygen

    PubMed Central

    Hofbauer, Stefan; Schaffner, Irene; Furtmüller, Paul G; Obinger, Christian

    2014-01-01

    Chlorite is a serious environmental concern, as rising concentrations of this harmful anthropogenic compound have been detected in groundwater, drinking water, and soil. Chlorite dismutases (Clds) are therefore important molecules in bioremediation as Clds catalyze the degradation of chlorite to chloride and molecular oxygen. Clds are heme b-containing oxidoreductases present in numerous bacterial and archaeal phyla. This review presents the phylogeny of functional Clds and Cld-like proteins, and demonstrates the close relationship of this novel enzyme family to the recently discovered dye-decolorizing peroxidases. The available X-ray structures, biophysical and enzymatic properties, as well as a proposed reaction mechanism, are presented and critically discussed. Open questions about structure-function relationships are addressed, including the nature of the catalytically relevant redox and reaction intermediates and the mechanism of inactivation of Clds during turnover. Based on analysis of currently available data, chlorite dismutase from “Candidatus Nitrospira defluvii” is suggested as a model Cld for future application in biotechnology and bioremediation. Additionally, Clds can be used in various applications as local generators of molecular oxygen, a reactivity already exploited by microbes that must perform aerobic metabolic pathways in the absence of molecular oxygen. For biotechnologists in the field of chemical engineering and bioremediation, this review provides the biochemical and biophysical background of the Cld enzyme family as well as critically assesses Cld's technological potential. PMID:24519858

  19. Spectral characteristics of chlorites and Mg-serpentines using high- resolution reflectance spectroscopy

    USGS Publications Warehouse

    King, T.V.V.; Clark, R.N.

    1989-01-01

    The present laboratory study using high-resolution reflectance spectroscopy (0.25-2.7 ??m) focuses on two primary phyllosilicate groups, serpentines and chlorites. The results show that it is possible to spectrally distinguish between isochemical end-members of the Mg-rich serpentine group (chrysotile, antigorite, and lizardite) and to recognize spectral variations in chlorites as a function of Fe/Mg ratio (~8-38 wt% Fe). The position and relative strength of the 1.4-??m absorption feature in the trioctahedral chlorites appear to be correlated to the total iron content and/or the Mg/Si ratio and the loss on ignition values of the sample. Spectral differences in the 2.3-??m wavelength region can be attributed to differences in lattice environments and are characteristic for specific trioctahedral chlorites. The 1.4-??m feature in the isochemical Mg-rich serpentines (total iron content ~1.5-7.0 wt%) show marked spectral differences, apparently due to structural differences. -Authors

  20. ASSESSMENT OF MATERNAL TOXICITY, EMBRYOTOXICITY AND TERATOGENIC POTENTIAL OF SODIUM CHLORITE IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Groups of up to 13 pregnant rats were individually caged. Body weight, food and water consumption were recorded at days 1, 8, 15 and 22 of gestation and the dams were treated on days 8-15 with sodium chlorite, 0.1%, 0.5% or 2% in drinking water or by injection of 10, 20, or 50 mg...

  1. Chlorite reactivity and contribution to flow path modifications under conditions relevant for CO2 sequestration

    NASA Astrophysics Data System (ADS)

    Beckingham, L. E.; Yang, L.; Ajo Franklin, J. B.; Voltolini, M.; Banuelos, J. L.; Anovitz, L. M.; Bourg, I. C.; Steefel, C. I.

    2013-12-01

    Iron-bearing clay minerals, such as chlorite, have been identified as key reactants with CO2 in caprock and reservoir formations and have been frequently shown to coat pores and even govern connected microporosity in these formations. Some studies have linked the total amount of CO2 trapped as carbonate minerals to the abundance of chlorite, glauconite, and smectite. However, the reactivity of these minerals under the conditions and timescales relevant for geologic sequestration of CO2 is largely unknown. When these minerals occur along a fracture leakage pathway, dissolution and precipitation reactions may create self-sealing or self-enhancing leakage pathways. In this presentation, we describe experiments that probe the reactivity of chlorite and its potential to alter connected porosity and either enhance or seal fracture leakage pathways. Our experiments use a network of capillary tubes packed with chlorite to mimic the case where a CO2-acidified brine flows through a fracture and reacts with iron-bearing clays in the caprock matrix. Before and after reaction, the chlorite-filled capillaries are imaged using 3D X-ray synchrotron microtomography at three points along the column to track changes in the pore structure. During the experiment, effluent ion concentrations are tracked using ICP-MS to infer mineralogical changes. The packed capillaries are imaged periodically during the experiment using Raman Spectroscopy to interpret the evolution of minerals along the tube length. Alteration of nanoporosity is assessed through TEM imaging or SAXS. Our experiments reveal how the couplings between mass transport, weathering reactions, and pore structure alteration affect the geochemical evolution of fracture permeability.

  2. The Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

    PubMed Central

    Booth, Catherine; Tudor, Gregory; Tudor, Julie; Katz, Barry P; MacVittie, Thomas

    2012-01-01

    The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure. PMID:23091876

  3. Treatment of myasthenia gravis with high-dose intravenous immunoglobulin.

    PubMed

    Cosi, V; Lombardi, M; Piccolo, G; Erbetta, A

    1991-08-01

    We treated 37 patients affected by autoimmune generalized myasthenia gravis (MG) with high-dose intravenous gammaglobulin (HDIVIg), 400 mg/kg per day on 5 consecutive days. A one-degree improvement of Oosterhuis global clinical classification of myasthenic severity (OGCCMS), the disappearance of bulbar involvement or both were recorded 12 days after the beginning of the treatment in 70.3% of the patients and persisted up to 60 days in 58.7%. A two-degree improvement of OGCCMS was recorded in 54.1% of the patients and it was maintained up to 60 days in 37.8%. The percentage of improvement did not significantly differ between patients entering the treatment in a long-standing, drug-refractory stationary phase of the illness (n = 26) and patients who received HDIVIg in an acute phase of MG (n = 11). None of the patients experienced side effects. Our data indicates that HDIVIg is an interesting, virtually riskless therapeutic choice for MG patients, and allows the planning of a controlled trial versus plasma-exchange. PMID:1950455

  4. High-dose processing and application to Korean space foods

    NASA Astrophysics Data System (ADS)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-07-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods ( Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  5. High-Dose Resveratrol Supplementation in Obese Men

    PubMed Central

    Poulsen, Morten M.; Vestergaard, Poul F.; Clasen, Berthil F.; Radko, Yulia; Christensen, Lars P.; Stødkilde-Jørgensen, Hans; Møller, Niels; Jessen, Niels; Pedersen, Steen B.; Jørgensen, Jens Otto L.

    2013-01-01

    Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders. PMID:23193181

  6. Formation of vanadium silicide by high dose ion implantation

    NASA Astrophysics Data System (ADS)

    Salvi, V. P.; Narsale, A. M.; Vidwans, S. V.; Rangwala, A. A.; Guzman, L.; Dapor, M.; Giunta, G.; Calliari, L.; Marchetti, F.

    1987-10-01

    The vanadium silicide system has been found to be of increasing interest because one of the silicide phases viz. V 3Si with the A-15 structure is often accompanied by a high temperature superconductivity. We have studied the formation of vanadium silicide layers by high dose ion implantation. 30 keV 51V + ions were implanted at room temperature onto thermally evaporated a-Si films on thermally grown SiO 2 substrates. The samples were annealed in vacuum to study the possible evolution of V-Si phases. Both Seeman-Bohlin X-ray diffraction and Auger/sputter profiling techniques were used to analyse these samples. The observed Auger depth profile of the annealed samples shows a more uniform vanadium distribution as compared to the vanadium distribution in as-implanted samples, along with the changes in the Si L 2,3VV lineshape. The X-ray diffraction results show the formation of V 3Si, V 5Si 3 and VSi 2 phases. After annealing the sample in vacuum, a more ordered growth of V 3Si phase is found to be accompanied by an increase in VSi 2 phase. This has been related to the possible changes ocurring in the a-Si layers due to annealing of the sample.

  7. Wernicke's encephalopathy in a child with high dose thiamine therapy

    PubMed Central

    Park, So Won; Yi, Yoon Young; Han, Jung Woo; Kim, Heung Dong; Lee, Joon Soo

    2014-01-01

    Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. It has been reported in individuals with alcohol dependence, hyperemesis gravidarum, and prolonged parenteral nutrition without vitamin supplementation. Here we present the case of a 13-year-old male patient with neuroblastoma and a history of poor oral intake and nausea for 3 months. After admission, he showed gait disturbances, nystagmus, and excessive dizziness; his mental state, however, indicated he was alert, which did not fit the classical triad of Wernicke's encephalopathy. A diagnosis of Wernicke's encephalopathy was made only after brain magnetic resonance imaging and serum thiamine level analyses were performed. The patient's symptoms remained after 5 days of treatment with 100-mg thiamine once daily; thus, we increased the dosage to 500 mg 3 times daily, 1,500 mg per day. His symptoms then improved after 20 days of replacement therapy. This case report describes a pediatric patient who was promptly diagnosed with Wernicke's encephalopathy, despite only 2 suspicious symptoms, and who completely recovered after high doses of thiamine were given intravenously. PMID:25550705

  8. IIb trioctahedral chlorite from the Barberton greenstone belt: crystal structure and rock composition constraints with implications to geothermometry

    NASA Astrophysics Data System (ADS)

    Xie, Xiaogang; Byerly, Gary R.; Ferrell, Ray E., Jr.

    IIb trioctahedral chlorite in the Barberton greenstone belt (BGB) metavolcanic rocks was formed during pervasive greenschist metamorphism. The chem-ical composition of the chlorite is highly variable, with the Fe/(Fe+Mg) ratio ranging from 0.12 to 0.8 among 53 samples. The chemical variation of the chlorite results from the chemical diversity of the host rock, especially the MgO content of the rock, but major details of the variation pattern of the chlorite are due to the crystal structure of the chlorite. All major cation abundances in the chlorite are strongly correlated with each other. Sil-icon increases with Mg and decreases with Fe, while AlIV and AlVI decrease with Mg and increase with Fe2+. A complex exchange vector explains over 90% of the chlorite compositional variation: Mg4SiFe2+-3AlVI-1 AlIV-1, which has 3 parts Fe-Mg substitution coupled with one part tschermakite substitution. This ratio is required to maintain the charge and site balances and the dimensional fit between the tetrahedral and octahedral sheets. The subtle change in Al substitution in chlorite implies that AlVI is preferentially ordered in the M(4) site, and about 84% of the AlVI present is in the M(4) sites when they are nearly filled with AlVI. Based on 47 analyzed chlorite-bearing rock samples, chlorite (Chl) composition is strongly correlated with the MgO content of the host rock. Calculated correlation coefficients are +0.91 for SiO2Chl-MgORock, -0.87 for Al2O3Chl-MgORock, +0.89 for MgOChl-MgORock, and -0.85 for FeOChl-MgORock. Only weak correlations have been found between chlorite oxides and other oxides of rock (between same oxides in chlorite and rock: SiO2-0.67, Al2O3+0.59, FeO -0.41). However, MgOChl is saturated at about 36 wt% in rocks that have MgO above 22 wt%.The MgOChl is about 5 wt% when the host rock approaches 0 wt% of MgO. This implies that Mg substituting into the chlorite is approximately limited to 1.5-9.2 Mg atoms per formula unit and 1.0-3.2 AlIV. Chlorite

  9. Surface energy of talc and chlorite: Comparison between electronegativity calculation and immersion results.

    PubMed

    Douillard, Jean-Marc; Salles, Fabrice; Henry, Marc; Malandrini, Harold; Clauss, Frédéric

    2007-01-15

    The surface energies of talc and chlorite is computed using a simple model, which uses the calculation of the electrostatic energy of the crystal. It is necessary to calculate the atomic charges. We have chosen to follow Henry's model of determination of partial charges using scales of electronegativity and hardness. The results are in correct agreement with a determination of the surface energy obtained from an analysis of the heat of immersion data. Both results indicate that the surface energy of talc is lower than the surface energy of chlorite, in agreement with observed behavior of wettability. The influence of Al and Fe on this phenomenon is discussed. Surface energy of this type of solids seems to depend more strongly on the geometry of the crystal than on the type of atoms pointing out of the surface; i.e., the surface energy depends more on the physics of the system than on its chemistry. PMID:17081554

  10. Kinetics and mechanism of oxidation of nitrous acid by chlorite ion

    SciTech Connect

    Lengyel, I.; Gaspar, V.; Beck, M.T.

    1988-01-14

    Although the oxidation of nitrite by chlorite both stoichiometrically and kinetically is a fairly simple reaction when nitrite is in excess and the pH is above 4, it becomes exceedingly complex in acidic solution containing chlorite in excess. Cl/sub 2/O/sub 2/ appears to be a key intermediate, the transitory formation of which explains both the formation of ClO/sub 2/ and peculiar three-extrema E versus time curve. Assuming that the electrode process on the bright Pt electrode is HOCl + e/sup -/ + H/sup +/ = Cl/sub 2/ + H/sub 2/O, the reaction is an oligooscillatory one in which the concentration of HOCl exhibits three extrema at most.

  11. High dose intravenous immunoglobulin in autoimmune rheumatic disorders.

    PubMed

    Zeuner, R A; Euler, H H; Schroeder, J O

    1997-11-01

    Since the effectiveness of high dose intravenous immunoglobulin (IVIg) was first demonstrated in autoimmune thrombocytopenia, IVIg has been investigated in the treatment of various autoimmune rheumatic disorders. Controlled randomised studies have established the efficacy of IVIg in Kawasaki's syndrome, for which combined IVIg and aspirin (acetylsalicylic acid) now constitutes the standard treatment. Another controlled study has demonstrated the benefit of IVIg in dermatomyositis. IVIg treatment in juvenile rheumatoid arthritis has produced contradictory results. Uncontrolled studies and case reports on the application of IVIg in systemic lupus erythematosus, ANCA-associated vasculitides and adult rheumatoid arthritis generally describe short term positive effects. Various mechanisms are thought to underlie the effect of IVIg on autoimmune rheumatic diseases, such as: blockade of Fc receptors;immunomodulation via anti-idiotypic interactions;inhibition of complement-mediated tissue damage;modulation of cytokine expression by leucocytes and endothelial cells; andinhibition of superantigen-mediated T cell activation. IVIg is considered to be a low-risk form of treatment. Reported adverse effects include headache, aseptic meningitis and transient impairment of renal function. Haemolysis and anaphylactic reactions are rare. The effect profile of IVIg makes it a relevant, although still experimental, form of treatment in autoimmune rheumatic disorders, but its high cost renders it unsuitable as a first-line treatment. Because IVIg does not weaken patients' resistance to infection, it might serve as a therapeutic option in bridging clinical situations where immunosuppressive or cytotoxic approaches are contraindicated in patients with autoimmune disorders, such as intercurrent infection or in the period immediately before and after surgery. PMID:18020527

  12. High-dose neutron irradiation performance of dielectric mirrors

    SciTech Connect

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; Snead, Lance Lewis

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation-tolerance: alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of 1 and 4 dpa at 458 10K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa results in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to 1 dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failing at 4 dpa. Transmission electron microscopy (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects which increases size with irradiation dose. The typical size of each defect was 8 nm in 1 dpa and 42 nm in 4 dpa specimens. Buckling type delamination of the interface between the substrate and first layer was typically observed in both 1 and 4 dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high resolution scanning-TEM mode using energy dispersive spectroscopy. A significant interdiffusion between the film layers was observed in Al2O3/SiO2 mirror, though less evident in HfO2/SiO2 system. Lastly, the ultimate goal of this work is the provide insight into the radiation-induced failure mechanisms of these mirrors.

  13. High-dose neutron irradiation performance of dielectric mirrors

    DOE PAGESBeta

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; Snead, Lance Lewis

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation-tolerance: alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of 1 and 4 dpa at 458 10K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa results in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to 1 dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failing at 4 dpa. Transmission electron microscopymore » (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects which increases size with irradiation dose. The typical size of each defect was 8 nm in 1 dpa and 42 nm in 4 dpa specimens. Buckling type delamination of the interface between the substrate and first layer was typically observed in both 1 and 4 dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high resolution scanning-TEM mode using energy dispersive spectroscopy. A significant interdiffusion between the film layers was observed in Al2O3/SiO2 mirror, though less evident in HfO2/SiO2 system. Lastly, the ultimate goal of this work is the provide insight into the radiation-induced failure mechanisms of these mirrors.« less

  14. Molecular Mechanisms Linking High Dose Medroxyprogesterone with HIV-1 Risk

    PubMed Central

    Irvin, Susan C.; Herold, Betsy C.

    2015-01-01

    Background Epidemiological studies suggest that medroxyprogesterone acetate (MPA) may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms. Methods Human vaginal epithelial (VK2/E6E7), peripheral blood mononuclear (PBMC), and polarized endometrial (HEC-1-A) cells were treated with a range of concentrations of MPA (0.015-150 μg/ml) and the impact on gene expression, protein secretion, and HIV infection was evaluated. Results Treatment of VK2/E6E7 cells with high doses (>15μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively. Conclusion We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml) MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo. PMID:25798593

  15. An AFM study of the chlorite-fluid interface. [Atomic Force Microscopy

    SciTech Connect

    Vrdoljak, G.A.; Henderson, G.S.; Fawcett, J.J. . Dept. of Geology)

    1992-01-01

    Chlorite is a ubiquitous mineral in many geologic environments and plays an important role in elemental adsorption and retention in soils. Chlorite has a 2:1 layer structure consisting of two tetrahedral sheets with an octahedral sheet between them (talc-like layer). The 2:1 layer is charge balanced and hydrogen-bonded by an interlayer of MgOH[sub 6] octahedra (brucite-like layer). The nature of chlorite's structure, its ease of imaging, and perfect 001 cleavage, make this mineral an ideal substrate for use in elemental adsorption studies in solution, with the AFM. The 001 cleavage plane of a 2b polytype with composition (Mg[sub 4.4]Fe[sub 0.6]Al[sub 1.0])[(Si[sub 2.9]Al[sub 1.1])]O[sub 10](OH)[sub g] has been imaged in air, water, and oil by atomic force microscopy. Dissolution features are observed in water, showing sub-micron features dissolving in real-time. Atomic resolution of both the talc-like and brucite-like layers has been obtained in air. However, only the tetrahedral sheet of the talc-like layer has been imaged at atomic resolution in oil and water, which may indicate a structural instability of the brucite-like surface in solution. Measurements of the unit-cell dimensions (a and b) for the talc-like layer in the three different media indicate a structural expansion of the mineral surface in solution. The a unit cell dimension expands by 7.4 [+-] 0.1% when in water; conversely, the b dimension varies greatly when in oil ([minus]10% to +20%), relative to air. The effects of these solution media on the structure of chlorite are revealed by characterization with the AFM. This information should prove useful in future studies of adsorption onto layer silicates.

  16. Manipulating Conserved Heme Cavity Residues of Chlorite Dismutase: Effect on Structure, Redox Chemistry, and Reactivity

    PubMed Central

    2013-01-01

    Chlorite dismutases (Clds) are heme b containing oxidoreductases that convert chlorite to chloride and molecular oxygen. In order to elucidate the role of conserved heme cavity residues in the catalysis of this reaction comprehensive mutational and biochemical analyses of Cld from “Candidatus Nitrospira defluvii” (NdCld) were performed. Particularly, point mutations of the cavity-forming residues R173, K141, W145, W146, and E210 were performed. The effect of manipulation in 12 single and double mutants was probed by UV–vis spectroscopy, spectroelectrochemistry, pre-steady-state and steady-state kinetics, and X-ray crystallography. Resulting biochemical data are discussed with respect to the known crystal structure of wild-type NdCld and the variants R173A and R173K as well as the structures of R173E, W145V, W145F, and the R173Q/W146Y solved in this work. The findings allow a critical analysis of the role of these heme cavity residues in the reaction mechanism of chlorite degradation that is proposed to involve hypohalous acid as transient intermediate and formation of an O=O bond. The distal R173 is shown to be important (but not fully essential) for the reaction with chlorite, and, upon addition of cyanide, it acts as a proton acceptor in the formation of the resulting low-spin complex. The proximal H-bonding network including K141-E210-H160 keeps the enzyme in its ferric (E°′ = −113 mV) and mainly five-coordinated high-spin state and is very susceptible to perturbation. PMID:24364531

  17. Convection-Induced Fingering Fronts in the Chlorite-Trithionate Reaction.

    PubMed

    Liu, Yang; Zhou, Wenxiu; Zheng, Ting; Zhao, Yuemin; Gao, Qingyu; Pan, Changwei; Horváth, Attila K

    2016-04-28

    Based upon a former study, the chlorite-trithionate reaction can avoid the side reactions arising from the well-known alkaline decomposition of polythionates, making it a suitable candidate for investigating spatial front instabilities in a reaction-diffusion-convection system. In this work, the chlorite-trithionate reaction was investigated in a Hele-Shaw cell, in which fingering patterns were observed over a wide range of reactant concentrations. A significant density increment crossing the propagating front indicates that the fingering pattern is generated as a consequence of the buoyancy-driven instability due to the density changes of solute when the gap thickness is less than 4 mm. The velocity of the steepest descent in the propagating front depends almost linearly on the gap thickness but displays a saturation-like profile on the trithionate concentration as well as a maximum on the chlorite concentration. Numerical simulation using the Stokes-Brinkman Equation coupled to the reaction-diffusion processes, including hydrogen ion autocatalysis and consumption, reproduces the observed fingering fronts. PMID:27059304

  18. Nanoscale channels on ectomycorrhizal-colonized chlorite: Evidence for plant-driven fungal dissolution

    NASA Astrophysics Data System (ADS)

    Gazzè, Salvatore A.; Saccone, Loredana; Vala Ragnarsdottir, K.; Smits, Mark M.; Duran, Adele L.; Leake, Jonathan R.; Banwart, Steven A.; McMaster, Terence J.

    2012-09-01

    The roots of many trees in temperate and boreal forests are sheathed with ectomycorrhizal fungi (EMF) that extend into the soil, forming intimate contact with soil minerals, from which they absorb nutrient elements required by the plants and, in return, are supported by the organic carbon photosynthesized by the trees. While EMF are strongly implicated in mineral weathering, their effects on mineral surfaces at the nanoscale are less documented. In the present study, we investigated the effects of symbiotic EMF on the topography of a chlorite mineral using atomic force microscopy. A cleaning protocol was successfully applied to remove fungal hyphae without altering the underlying mineral structure and topography. Examination of the exposed chlorite surface showed the presence of primary channels, of the order of a micron in width and up to 50 nm in depth, the morphology of which strongly indicates a fungal-induced origin. Smaller secondary channels were observed extending from the primary channels and would appear to be involved in their enlargement. The presence of channels is the first nanoscale demonstration of the effects of fungal interaction, fuelled by plant photosynthate, on the topography of a chlorite mineral, and it provides clear evidence of the ability of EMF to enhance mineral dissolution.

  19. High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

    PubMed Central

    Jindani, Amina; Harrison, Thomas S.; Nunn, Andrew J.; Phillips, Patrick P.J.; Churchyard, Gavin J.; Charalambous, Salome; Hatherill, Mark; Geldenhuys, Hennie; McIlleron, Helen M.; Zvada, Simbarashe P.; Mungofa, Stanley; Shah, Nasir A.; Zizhou, Simukai; Magweta, Lloyd; Shepherd, James; Nyirenda, Sambayawo; van Dijk, Janneke H.; Clouting, Heather E.; Coleman, David; Bateson, Anna L.E.; McHugh, Timothy D.; Butcher, Philip D.; Mitchison, Denny A.

    2014-01-01

    BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and

  20. High-dose methotrexate: pharmacokinetics in children and young adults.

    PubMed

    Raude, E; Oellerich, M; Weinel, P; Freund, M; Schrappe, M; Riehm, H; Poliwoda, H

    1988-07-01

    Pharmacokinetics of methotrexate (MTX) was studied in 34 patients (age 1-25 years, median 12 years) predominantly with primary brain tumors and osteosarcoma, who received a total of 64 high-dose infusions (12 g/m2/4 h, maximum dose 20 g), followed by leucovorin rescue (COSS 82). Serum samples were collected over a period of at least 72 h after the end of infusion and MTX was measured by enzyme immunoassay (EMIT). The data were fitted to a biexponential equation using a nonlinear regression analysis. The concentration-time decay of MTX in serum observed in 29/34 patients receiving 4 x 15 mg/m2/d p.o. leucovorin up to 5 days was biphasic with mean half-lives (+/- SD) of 2.42 +/- 0.45 h for t1/2 alpha and 19.9 +/- 7.6 h for t1/2 beta. The steady-state volume of distribution (Vss) was 0.56 +/- 0.18 l/kg and the total body clearance (CL) 71 +/- 20 ml/min/m2 (mean +/- SD). Peak serum concentrations ranged from 674-1778 mumol/l (mean +/- SD, 1201 +/- 293 mumol/l). In 5/34 patients who received a prolonged leucovorin rescue due to a delayed MTX elimination t1/2 alpha was greater than 3.1 h. The data of this study suggest that patients with MTX serum concentrations of less than or equal to 6.3 mumol/l at 24 h, less than or equal to 0.77 mumol/l at 48 h, and less than or equal to 0.33 mumol/l at 72 h after the end of infusion, and a t1/2 alpha of less than or equal to 3.1 h (97.5th percentiles) are at low risk of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3209285

  1. Long-term in vivo carcinogenicity test of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan

    SciTech Connect

    Kurokawa, Y.; Takayama, S.; Konishi, Y.; Hiasa, Y.; Asahina, S.; Takahashi, M.; Maekawa, A.; Hayashi, Y.

    1986-11-01

    Long-term in vivo carcinogenicity tests of potassium bromate (KBrO/sub 3/), sodium hypochlorite (NaClO) and sodium chlorite (NaClO/sub 2/) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-weeks tests. The carcinogenic potential of KBrO/sub 3/ was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO/sub 3/ at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. No statistically significant differences were observed in the incidences of tumor formation between NaClO/sub 2/-treated and control groups of rats male mice, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls. The authors concluded that KBrO/sub 2/ was carcinogenic in rats of both sexes. NaClO was not carcinogenic in either rats and or mice under the conditions of the present studies. Although NaClO/sub 2/ was shown to be noncarcinogenic in rats, the results for mice were evaluated as inconclusive. Also the results of two-stage mouse skin carcinogenesis using KBrO/sub 3/, NaClO, and NaClO/sub 2/ are presented.

  2. How active site protonation state influences the reactivity and ligation of the heme in chlorite dismutase

    PubMed Central

    Streit, Bennett R.; Blanc, Béatrice; Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.; DuBois, Jennifer L.

    2010-01-01

    Chlorite dismutase catalyzes O2 release from chlorite with exquisite efficiency and specificity. The spectroscopic properties, ligand binding affinities, and steady state kinetics of chlorite dismutase from Dechloromonas aromatica were examined over pH 3–11.5 to gain insight into how the protonation state of the heme environment influences dioxygen formation. An acid/base transition was observed by UV/visible and resonance Raman spectroscopy with a pKa of 8.7, 2–3 pH units below analogous transitions observed in typical His-ligated peroxidases. This transition marks the conversion of a five coordinate high spin Fe(III) to a mixed high/low spin ferric-hydroxide, as confirmed by resonance Raman (rR) spectroscopy. The two Fe–OH stretching frequencies are quite low, consistent with a weak Fe–OH bond, despite the nearly neutral imidazole side chain of the proximal histidine ligand. The hydroxide is proposed to interact strongly with a distal H-bond donor, thereby weakening the Fe–OH bond. The rR spectra of Cld-CO as a function of pH reveal two forms of the complex, one in which there is minimal interaction of distal residues with the carbonyl oxygen and another, acidic form in which the oxygen is under the influence of positive charge. Recent crystallographic data reveal arginine 183 as the lone H-bond donating residue in the distal pocket. It is likely that this Arg is the strong, positively charged H-bond donor implicated by vibrational data to interact with exogenous axial heme ligands. The same Arg in its neutral (pKa ~ 6.5) form also appears to act as the active site base in binding reactions of protonated ligands, such as HCN, to ferric Cld. The steady state profile for the rate of chlorite decomposition is characterized by these same pKas. The 5 coordinate high spin acidic Cld is more active than the alkaline hydroxide-bound form. The acid form decomposes chlorite most efficiently when the distal Arg is protonated/cationic (maximum kcat = 2.0 (±0.6)

  3. Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of chlorite dismutase: a detoxifying enzyme producing molecular oxygen

    PubMed Central

    de Geus, Daniël C.; Thomassen, Ellen A. J.; van der Feltz, Clarisse L.; Abrahams, Jan Pieter

    2008-01-01

    Chlorite dismutase, a homotetrameric haem-based protein, is one of the key enzymes of (per)chlorate-reducing bacteria. It is highly active (>2 kU mg−1) in reducing the toxic compound chlorite to the innocuous chloride anion and molecular oxygen. Chlorite itself is produced as the intermediate product of (per)chlorate reduction. The chlorite dismutase gene in Azospira oryzae strain GR-1 employing degenerate primers has been identified and the active enzyme was subsequently overexpressed in Escherichia coli. Chlorite dismutase was purified, proven to be active and crystallized using sitting drops with PEG 2000 MME, KSCN and ammonium sulfate as precipitants. The crystals belonged to space group P21212 and were most likely to contain six subunits in the asymmetric unit. The refined unit-cell parameters were a = 164.46, b = 169.34, c = 60.79 Å. The crystals diffracted X-rays to 2.1 Å resolution on a synchrotron-radiation source and a three-wavelength MAD data set has been collected. Determination of the chlorite dismutase structure will provide insights into the active site of the enzyme, for which no structures are currently available. PMID:18678943

  4. Characterization of power transistors as high dose dosimeters

    NASA Astrophysics Data System (ADS)

    Fuochi, P. G.; Lavalle, M.; Corda, U.; Kovacs, A.; Peimel-Stuglik, Z.; Gombia, E.

    2009-02-01

    A bipolar transistor, previously investigated as a possible radiation dosimeter and tested under industrial irradiation conditions in high-activity gamma and high-energy, high-power electron beam facilities has been subjected to stability test in order to understand its behaviour and help to improve its performances. Charge carrier lifetime was measured for several sets of transistors which were then irradiated with various doses (3-60 kGy): seven sets with 60Co gamma rays and eight with a 10 MeV electron beam. After irradiation all the transistors were measured and each set was divided into three groups: one group was left untreated, the second group was heated at 100 °C for 30 minutes and the third group was heated at 150 °C for 30 minutes, for testing the stability of the lifetime. Our data showed that heat treatment quite successfully eliminates post-irradiation changes in the response. Response measurements of the irradiated transistors, heat-treated and untreated, were carried out at room temperature over several weeks after irradiation to establish post-irradiation stability and assess if these transistors could be used for recording dose history. Calibration curves in the range 3-60 kGy for the thermally treated and untreated devices are presented. Dependence of the response of the transistors on the temperature of the measurements in the range 20-50 °C is reported.

  5. High-dose-rate brachytherapy in uterine cervical carcinoma

    SciTech Connect

    Patel, Firuza D. . E-mail: patelfd@glide.net.in; Rai, Bhavana; Mallick, Indranil; Sharma, Suresh C.

    2005-05-01

    Purpose: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. Methods and Materials: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. Results: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for

  6. Mineralogy and geochemistry of laterites developed on chlorite schists in Tchollire region, North Cameroon

    NASA Astrophysics Data System (ADS)

    Banakeng, L. A.; Zame, P. Zo'o.; Tchameni, R.; Mamdem, L.; Bitom, D.

    2016-07-01

    Laterites developed from the weathering of chlorite schists have been studied in Tchollire region, North Cameroon. They include two profiles: a 5.5 m depth profile in Doudja site and a 12.3 m profile in Fimbe site. The chlorite schists have a lepidoblastic to lepidogranoblastic texture and are mainly composed of chlorite, muscovite, biotite, feldspars and quartz but that of Fimbe is marked by the presence of amphibole. It is felsic with a high SiO2 content (67%) and low Fe2O3 (5.8%) and MgO (2.4%) contents in Doudja site but has a lower content of SiO2 (46%) in the Fimbe site where it is mafic with higher contents in Fe2O3 (12.4%) and MgO (6.3%). The chlorite schists of Doudja show high contents in Zr, Sr, Ta, with moderate contents in Cr, V, U and Zn. That of Fimbe is particularly rich in Cr, V, Ni, Sr and Zn with a moderate Zr content. All chlorite schists have high barium contents (270-393 ppm) with LREE-enrichment. The soils are yellowish and, from bottom to top, are composed of a coarse saprolite, fine saprolite, loose clayey horizon and an organo mineral horizon. The main minerals are chlorite, muscovite, biotite, feldspars, quartz, smectites, vermiculite, kaolinite, hematite and goethite. In Doudja, SiO2 mainly decreases from the bottom to the top of the profile while, Al2O3 and Fe2O3 generally increase; in Fimbe, SiO2 and Al2O3 increase up the profile but Fe2O3 decreases; the general high Fe and corresponding decrease in Mg contents in the soils show that the smectite formed is nontronite. Chromium, V, Cu, Ba and Sr show high contents in the two studied profiles but Zr, U and Ta is higher in Doudja than in Fimbe. Copper generally has high contents in the loose clayey and organo mineral horizons. Nickel is higher in the Fimbe profile and probably issued from the Ni-rich mafic protolith. SiO2 has positive correlations with K2O, Zr, Li and Rb. Correlations of SiO2 with CaO, TiO2 and Cr are negative. Al2O3 and Fe2O3 have a positive correlation with Pb. Doudja

  7. Redox interactions between Cr(VI) and Fe(II) in bioreduced biotite and chlorite.

    PubMed

    Brookshaw, Diana R; Coker, Victoria S; Lloyd, Jonathan R; Vaughan, David J; Pattrick, Richard A D

    2014-10-01

    Contamination of the environment with Cr as chromate (Cr(VI)) from industrial activities is of significant concern as Cr(VI) is a known carcinogen, and is mobile in the subsurface. The capacity of Fe(II)-containing phyllosilicates including biotite and chlorite to alter the speciation, and thus the mobility, of redox-sensitive contaminants including Cr(VI) is of great interest since these minerals are common in soils and sediments. Here, the capacity of bacteria, ubiquitous in the surface and near-surface environment, to reduce Fe(III) in phyllosilicate minerals and, thus, alter their redox reactivity was investigated in two-step anaerobic batch experiments. The model Fe(III)-reducing bacterium Geobacter sulfurreducens was used to reduce Fe(III) in the minerals, leading to a significant transformation of structural Fe(III) to Fe(II) of 0.16 mmol/g (∼ 40%) in biotite and 0.15 mmol/g (∼ 20%) in chlorite. The unaltered minerals could not remove Cr(VI) from solution despite containing a larger excess of Fe(II) than would be required to reduce all the added Cr(VI), unless they were supplied in a very high concentration (a 1:10 solid to solution ratio). By contrast, even at very low concentrations, the addition of bioreduced biotite and chlorite caused removal of Cr(VI) from solution, and surface and near surface X-ray absorption spectroscopy confirmed that this immobilization was through reductive transformation to Cr(III). We provide empirical evidence that the amount of Fe(II) generated by microbial Fe(III) reduction is sufficient to reduce the Cr(VI) removed and, in the absence of reduction by the unaltered minerals, suggest that only the microbially reduced fraction of the iron in the minerals is redox-active against the Cr(VI). PMID:25196156

  8. Dimeric chlorite dismutase from the nitrogen-fixing cyanobacterium Cyanothece sp. PCC7425.

    PubMed

    Schaffner, Irene; Hofbauer, Stefan; Krutzler, Michael; Pirker, Katharina F; Bellei, Marzia; Stadlmayr, Gerhard; Mlynek, Georg; Djinovic-Carugo, Kristina; Battistuzzi, Gianantonio; Furtmüller, Paul G; Daims, Holger; Obinger, Christian

    2015-06-01

    It is demonstrated that cyanobacteria (both azotrophic and non-azotrophic) contain heme b oxidoreductases that can convert chlorite to chloride and molecular oxygen (incorrectly denominated chlorite 'dismutase', Cld). Beside the water-splitting manganese complex of photosystem II, this metalloenzyme is the second known enzyme that catalyses the formation of a covalent oxygen-oxygen bond. All cyanobacterial Clds have a truncated N-terminus and are dimeric (i.e. clade 2) proteins. As model protein, Cld from Cyanothece sp. PCC7425 (CCld) was recombinantly produced in Escherichia coli and shown to efficiently degrade chlorite with an activity optimum at pH 5.0 [kcat 1144 ± 23.8 s(-1), KM 162 ± 10.0 μM, catalytic efficiency (7.1 ± 0.6) × 10(6) M(-1) s(-1)]. The resting ferric high-spin axially symmetric heme enzyme has a standard reduction potential of the Fe(III)/Fe(II) couple of -126 ± 1.9 mV at pH 7.0. Cyanide mediates the formation of a low-spin complex with k(on)  = (1.6 ± 0.1) × 10(5) M(-1) s(-1) and k(off) = 1.4 ± 2.9 s(-1) (KD ∼ 8.6 μM). Both, thermal and chemical unfolding follows a non-two-state unfolding pathway with the first transition being related to the release of the prosthetic group. The obtained data are discussed with respect to known structure-function relationships of Clds. We ask for the physiological substrate and putative function of these O2 -producing proteins in (nitrogen-fixing) cyanobacteria. PMID:25732258

  9. Mechanism of and exquisite selectivity for O–O bond formation by the heme-dependent chlorite dismutase

    PubMed Central

    Lee, Amanda Q.; Streit, Bennett R.; Zdilla, Michael J.; Abu-Omar, Mahdi M.; DuBois, Jennifer L.

    2008-01-01

    Chlorite dismutase (Cld) is a heme b-dependent, O–O bond forming enzyme that transforms toxic chlorite (ClO2−) into innocuous chloride and molecular oxygen. The mechanism and specificity of the reaction with chlorite and alternate oxidants were investigated. Chlorite is the sole source of dioxygen as determined by oxygen-18 labeling studies. Based on ion chromatography and mass spectrometry results, Cld is highly specific for the dismutation of chlorite to chloride and dioxygen with no other side products. Cld does not use chlorite as an oxidant for oxygen atom transfer and halogenation reactions (using cosubstrates guaiacol, thioanisole, and monochlorodimedone, respectively). When peracetic acid or H2O2 was used as an alternative oxidant, oxidation and oxygen atom transfer but not halogenation reactions occurred. Monitoring the reaction of Cld with peracetic acid by rapid-mixing UV-visible spectroscopy, the formation of the high valent compound I intermediate, [(Por•+)FeIV = O], was observed [k1 = (1.28 ± 0.04) × 106 M−1 s−1]. Compound I readily decayed to form compound II in a manner that is independent of peracetic acid concentration (k2 = 170 ± 20 s−1). Both compound I and a compound II-associated tryptophanyl radical that resembles cytochrome c peroxidase (Ccp) compound I were observed by EPR under freeze-quench conditions. The data collectively suggest an O–O bond-forming mechanism involving generation of a compound I intermediate via oxygen atom transfer from chlorite, and subsequent recombination of the resulting hypochlorite and compound I. PMID:18840691

  10. Horizontally propagating three-dimensional chemo-hydrodynamic patterns in the chlorite-tetrathionate reaction

    NASA Astrophysics Data System (ADS)

    Pópity-Tóth, Éva; Horváth, Dezső; Tóth, Ágota

    2012-09-01

    Planar reaction fronts resulting from the coupling of exothermic autocatalytic reactions and transport processes can be deformed by convection in the presence of gravity field. We have experimentally investigated how buoyancy affects the spatiotemporal pattern formation at various solution thicknesses in three-dimensional medium. In the chlorite-tetrathionate reaction, a stable structure propagating horizontally with constant velocity and geometry develops when appropriately thick solutions are studied. Both the horizontal and the vertical projections of the resulting three-dimensional structures are quantitatively characterized: the smooth leading edge of the front is independent of the solution thickness and the structured trailing edge ends in a center cusp with a constant angle.

  11. Enhanced Interaction between Warfarin and High-Dose Ketoconazole: A Case Report

    PubMed Central

    Jackevicius, Cynthia A.; Ton, Mannhu N.

    2009-01-01

    This case describes the increased anticoagulation effect associated with the use of high-dose ketoconazole. A 59-year-old man treated with warfarin for aortic valve replacement was prescribed high-dose ketoconazole and hydrocortisone for the treatment of prostate cancer. Despite lowering the warfarin dosage by 35% during the start of high dose ketoconazole, an additional dose reduction was required subsequently when the INR rose from 2.62 to 3.82 within nine days. After a total dose reduction of 43%, the INR returned to therapeutic range within two weeks. The Naranjo probability scale revealed a probable adverse reaction of increased anticoagulant effect associated with high dose ketoconazole. Due to the inhibition of warfarin metabolism by ketoconazole, patients taking high dose ketoconazole concomitantly with warfarin may need their warfarin dosage reduced by more than is currently recommended, as well as receive more frequent INR monitoring to avoid over anticoagulation. PMID:20029646

  12. Clinical Characteristics of Veterans Prescribed High Doses of Opioid Medications for Chronic Non-Cancer Pain

    PubMed Central

    Morasco, Benjamin J.; Duckart, Jonathan P.; Carr, Thomas P.; Deyo, Richard A.; Dobscha, Steven K.

    2010-01-01

    Little is known about patients prescribed high doses of opioids to treat chronic non-cancer pain, though these patients may be at higher risk for medication-related complications. We describe the prevalence of high-dose opioid use and associated demographic and clinical characteristics among veterans treated in a VA regional healthcare network. Veterans with chronic non-cancer pain prescribed high doses of opioids (>=180 mg/day morphine equivalent; n=478) for 90+ consecutive days were compared to two groups with chronic pain: Traditional-dose (5–179 mg/day; n=500) or no opioid (n=500). High-dose opioid use occurred in 2.4% of all chronic pain patients and in 3.4% of all chronic pain patients prescribed opioids long-term. The average dose in the high-dose group was 324.9 (SD=285.1) mg/day. The only significant demographic difference among groups was race (p=0.03) with black veterans less likely to receive high doses. High-dose patients were more likely to have four or more pain diagnoses and the highest rates of medical, psychiatric, and substance use disorders. After controlling for demographic factors and VA facility, neuropathy, low back pain, and nicotine dependence diagnoses were associated with increased likelihood of high-dose prescriptions. High-dose patients frequently did not receive care consistent with treatment guidelines: there was frequent use of short-acting opioids, urine drug screens were administered to only 40.8% of patients in the prior year, and 32.0% received concurrent benzodiazepine prescriptions, which may increase risk for overdose and death. Further study is needed to identify better predictors of high-dose usage, as well as the efficacy and safety of such dosing. PMID:20801580

  13. Chlorite topography and dissolution of the interlayer studied with Atomic Force Microscopy

    SciTech Connect

    Gazze, Salvatore; Stack, Andrew G; Ragnarsdottir, K. Vala; McMaster, Terence

    2014-01-01

    Chlorite has a structure composed of a combination of two distinct layers, the tetrahedral15 octahedral-tetrahedral (TOT) and the interlayer (i.e. the octahedral layer between TOT layers). In this study, the morphology and dissolution of chlorite in pure water has been visualized using Atomic Force Microscopy. Upon cleavage, the TOT layer shows atomically flat terraces and steps, while the interlayer presents strips and voids. In pure water, dissolution channels and equilateral, mono-oriented triangular etch pits form in the interlayer and lead to progressively increased solubilisation. Dissolution channels are proposed to originate from structural defects, while a conceptual model is discussed to explain the presence of triangular etch pits. In this model, their formation is driven by the different reactivity of the two octahedral configurations along the etch pits. It is not currently known which of these is the most stable configuration, however we propose arguments that point towards a specific orientation. The conceptual model is supported by experimental data and is potentially applicable to all mineral structures constituted by continuous octahedral layers.

  14. Evaluation of experimental teat dip containing sodium chlorite and lactic acid by excised teat assay.

    PubMed

    Schmidt, A L; Oliver, S P; Fydenkevez, M E

    1984-12-01

    An experimental teat dip containing sodium chlorite and lactic acid, diluted in water, was evaluated by excised teat protocol. The teat dip was tested against 21 microorganisms. Included were: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Numerous strains were tested for strain differences. Environmental bacteria were included because of their increasing importance as a cause of bovine mastitis. All excised teats were dipped in a bacterial suspension containing about 1 X 10(8) cfu/ml. Negative control teats were not dipped in a germicidal compound. Positive controls were dipped in 1% iodophor. Effectiveness of the experimental teat dip was expressed as the percent reduction in mean log of bacteria recovered from dipped teats as compared to numbers recovered from control teats. The sodium chlorite - lactic acid dip caused a greater percent log reduction than iodophor for 14 of 21 strains tested. However, differences were generally slight. The experimental teat dip appeared effective against Gram-negative bacteria. Some differences in percent log reduction were observed between strains of the same species. Lowest effectiveness and greatest strain variation were observed with Staphylococcus aureus for both dips tested. PMID:6530497

  15. Dissimilatory perchlorate reduction linked to aerobic methane oxidation via chlorite dismutase

    NASA Astrophysics Data System (ADS)

    Oremland, R. S.; Baesman, S. M.; Miller, L. G.

    2013-12-01

    The presence of methane (CH4) in the atmosphere of Mars is controversial yet the evidence has aroused scientific interest, as CH4 could be a harbinger of extant or extinct microbial life. There are various oxidized compounds present on the surface of Mars that could serve as electron acceptors for the anaerobic oxidation of CH4, including perchlorate (ClO4-). We examined the role of perchlorate, chlorate (ClO3-) and chlorite (ClO2-) as oxidants linked to CH4 oxidation. Dissimilatory perchlorate reduction begins with reduction of ClO4- to ClO2- and ends with dismutation of chlorite to yield chloride (Cl-) and molecular oxygen (O2). We explored the potential for aerobic CH4 oxidizing bacteria to couple with oxygen derived from chlorite dismutation during dissimilatory perchlorate reduction. Methane (0.2 kPa) was completely removed within several days from the N2-flushed headspace above cell suspensions of methanotrophs (Methylobacter albus strain BG8) and perchlorate reducing bacteria (Dechloromonas agitata strain CKB) in the presence of 5 mM ClO2-. Similar rates of CH4 consumption were observed for these mixed cultures whether they were co-mingled or segregated under a common headspace, indicating that direct contact of cells was not required for methane consumption to occur. We also observed complete removal of 0.2 kPa CH4 in bottles containing dried soil (enriched in methanotrophs by CH4 additions over several weeks) and D. agitata CKB and in the presence of 10 mM ClO2-. This soil (seasonally exposed sediment) collected from the shoreline of a freshwater lake (Searsville Lake, CA) demonstrated endogenous CH4 uptake as well as perchlorate, chlorate and chlorite reduction/dismutation. However, these experiments required physical separation of soil from the aqueous bacterial culture to allow for the partitioning of O2 liberated from chlorite dismutation into the shared headspace. Although dissimilatory reduction of ClO4- and ClO3- could be inferred from the

  16. Preservation of anomalously high porosity in deeply buried sandstones by grain-coating chlorite: Examples from the Norwegian Continental Shelf

    SciTech Connect

    Ehrenberg, S.N. )

    1993-07-01

    Five Lower to Middle Jurassic sandstone reservoirs from the Norwegian sector provide examples of deep porosity preservation caused by grain-coating, authigenic chlorite. Wide porosity variations in clean sandstones correlate with an abundance of grain-coating chlorite and consequent inhibition of quarts cementation. Maximum porosities tend to decrease with increasing depth but generally are 10-15% higher than would be predicted from regional trends of mean porosity vs. depth. It is proposed in this paper that the high chlorite content of the porous zones reflects syndepositional concentration of Fe-rich marine clays analogous to minerals of the modern verdine facies. Fe-clay mineralization would have been localized where Fe-rich river water was discharged into the sea. The syndepositional clays were transformed during burial diagenesis into grain coatings of radially oriented chlorite crystals. Petrographic relationships indicate that these coatings grew mainly before the beginning of quartz cementation and feldspar grain dissolution (probably within the first 2 km of burial) but after grain contacts had become adjusted by mechanical compaction. The Norwegian examples demonstrate that a wide range of nearshore marine sand-body types is susceptible to chlorite mineralization. The distribution of anomalous porosity and the proportion of the net sand affected depend upon sedimentary facies architecture and the pattern of discharge of Fe-rich river water during sand deposition. This phenomenon can be critically important for hydrocarbon exploration because it can provide good reservoir quality at depths far below the [open quotes]economic basement[close quotes] originally defined on the basis of sandstones lacking chlorite coatings. 58 refs., 25 figs., 1 tab.

  17. An Alternative to the Use of High-Dose Estrogens for Postcoital Contraception.

    ERIC Educational Resources Information Center

    Schilling, Lee H.

    1979-01-01

    Research is reported on the use of ethinyl estradiol and norgestrel for contraception after intercourse. This treatment is offered as an alternative to high doses of estrogen and appears to be successful in preventing unwanted pregnancies. (JMF)

  18. High Doses of Fish Oil Might Help Healing After Heart Attack

    MedlinePlus

    ... Doses of Fish Oil Might Help Healing After Heart Attack Study found improved heart function, less scarring To ... 2, 2016 MONDAY, Aug. 1, 2016 (HealthDay News) -- Heart attack patients who took high doses of fish oil ...

  19. High-Dose Induced Thermoluminescence of Light-Colored Lithology in Chelyabinsk Meteorite

    NASA Astrophysics Data System (ADS)

    Weinstein, I. A.; Vokhmintsev, A. S.; Ishchenko, A. V.; Grokhovsky, V. I.

    2015-07-01

    This work presents the study results of high-dose irradiation effects on the laboratory TL parameters in Chelyabinsk LL5 chondrite fragments with light-colored lithology. Obtained data are analyzed in terms of the general order kinetic formalism.

  20. Dimeric chlorite dismutase from the nitrogen‐fixing cyanobacterium C yanothece sp. PCC7425

    PubMed Central

    Schaffner, Irene; Hofbauer, Stefan; Krutzler, Michael; Pirker, Katharina F.; Bellei, Marzia; Stadlmayr, Gerhard; Mlynek, Georg; Djinovic‐Carugo, Kristina; Battistuzzi, Gianantonio; Furtmüller, Paul G.; Daims, Holger

    2015-01-01

    Summary It is demonstrated that cyanobacteria (both azotrophic and non‐azotrophic) contain heme b oxidoreductases that can convert chlorite to chloride and molecular oxygen (incorrectly denominated chlorite ‘dismutase’, Cld). Beside the water‐splitting manganese complex of photosystem II, this metalloenzyme is the second known enzyme that catalyses the formation of a covalent oxygen–oxygen bond. All cyanobacterial Clds have a truncated N‐terminus and are dimeric (i.e. clade 2) proteins. As model protein, Cld from C yanothece sp. PCC7425 (CCld) was recombinantly produced in E scherichia coli and shown to efficiently degrade chlorite with an activity optimum at pH 5.0 [k cat 1144 ± 23.8 s−1, KM 162 ± 10.0 μM, catalytic efficiency (7.1 ± 0.6) × 106 M−1 s−1]. The resting ferric high‐spin axially symmetric heme enzyme has a standard reduction potential of the Fe(III)/Fe(II) couple of −126 ± 1.9 mV at pH 7.0. Cyanide mediates the formation of a low‐spin complex with k on = (1.6 ± 0.1) × 105 M−1 s−1 and k off = 1.4 ± 2.9 s−1 (KD ∼ 8.6 μM). Both, thermal and chemical unfolding follows a non‐two‐state unfolding pathway with the first transition being related to the release of the prosthetic group. The obtained data are discussed with respect to known structure–function relationships of Clds. We ask for the physiological substrate and putative function of these O2‐producing proteins in (nitrogen‐fixing) cyanobacteria. PMID:25732258

  1. Chemical and Steady-State Kinetic Analyses of a Heterologously Expressed Heme Dependent Chlorite Dismutase†

    PubMed Central

    Streit, Bennett R.; DuBois, Jennifer L.

    2013-01-01

    Chlorite dismutase carries out the heme-catalyzed decomposition of ClO2– to Cl– and O2, an unusual transformation with biotechnological and bioremediative applications. The enzyme has been successfully overexpressed for the first time in highly functional form in Escherichia coli and its steady state kinetics studied. The purified enzyme is abundant (55 mg/L cell culture), highly active (~4.7 × 103 μmol of ClO2– min–1 mg–1 subunit) and nearly stoichiometric in heme; further, it shares spectroscopic and physicochemical features with chlorite dismutases previously isolated from three organisms. A careful study of the enzyme's steady state kinetics has been carried out. ClO2– consumption and O2 release rates were measured, yielding comparable values of kcat (4.5 × 105 min–1), Km (~215 μM), and kcat/Km (3.5 × 107 M–1 s–1) via either method (4 °C, pH 6.8; all values referenced per heme-containing subunit). ClO2–:O2 stoichiometry exhibited a 1:1 relationship under all conditions measured. Though the value of kcat/Km indicates near diffusion control of the reaction, viscosogens had no effect on kcat/Km or Vmax. The product O2 did not inhibit the reaction at saturating [O2], but Cl– is a mixed inhibitor with relatively high values of KI (225 mM for enzyme and 95.6 mM for the enzyme–substrate complex), indicating a relatively low affinity of the heme iron for halogen ions. Chlorite irreversibly inactivates the enzyme after ~1.7 × 104 turnovers (per heme) and with a half-life of 0.39 min, resulting in bleaching of the heme chromophore. The inactivation KI (Kinact) of 166 μM is similar in magnitude to Km, consistent with a common Michaelis complex on the pathway to both reaction and inactivation. The one-electron peroxidase substrate guaiacol offers incomplete protection of the enzyme from inactivation. Mechanisms in keeping with the available data and the properties of other well-described heme enzymes are proposed. PMID:18422344

  2. Focal takotsubo cardiomyopathy with high-dose interleukin-2 therapy for malignant melanoma.

    PubMed

    Damodaran, Senthil; Mrozek, Ewa; Liebner, David; Kendra, Kari

    2014-12-01

    High-dose interleukin-2 (IL-2) is an available treatment option for patients with metastatic melanoma or renal cell carcinoma, and is associated with sustained complete and partial responses in a subset of patients. IL-2, however, is not devoid of toxicities, most of which involve the cardiovascular system and manifest as hypotension, arrhythmias, and cardiomyopathy. This report describes an unusual presentation of takotsubo cardiomyopathy in a postmenopausal woman receiving high-dose IL-2 for metastatic melanoma. PMID:25505207

  3. Early supradiaphragmatic Hodgkin's disease. High-dose gallium scanning obviates the need for staging laparotomy

    SciTech Connect

    Blackwell, E.A.; Joshua, D.E.; McLaughlin, A.F.; Green, D.; Kronenberg, H.; May, J.

    1986-08-15

    Experience with 16 sequential patients with Stage IA/IIA supradiaphragmatic Hodgkin's disease who had no evidence of intra-abdominal disease using high-dose gallium and computerized tomography scanning is reported. Subsequent staging laparotomy also was negative in all these patients and did not alter management decisions. It is suggested that high-dose, whole-body gallium scanning and other noninvasive staging procedures give reliable data for therapeutic decisions.

  4. Peripheral blood progenitor cell transplantation in multiple myeloma following high-dose melphalan-based therapy.

    PubMed

    Goldschmidt, H; Hegenbart, U; Wallmeier, M; Hohaus, S; Engenhart, R; Wannenmacher, M; Haas, R

    1998-01-01

    The objective of our study was to evaluate the efficacy and toxicity of a high-dose melphalan-based therapy with or without total body irradiation (TBI) followed by peripheral blood progenitor cell (PBPC) transplantation in patients with multiple myeloma. Between June 1992 and June 1996, 104 patients (71 male, 33 female) with a median age of 51 years (range 30-65 years) underwent transplantation at our center. PBPC were mobilized using high-dose chemotherapy followed by treatment with G-CSF. Fifty patients were treated with TBI+melphalan 140 mg/m2 while 54 patients received melphalan 200 mg/m2. Following PBPC autografting, the median time to attainment of platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l was 11 and 14 days, with no difference between the treatment groups. In the TBI group significantly longer periods of total parenteral nutrition were required due to the occurrence of severe mucositis. Two patients from the TBI group died of transplantation-related complications. Following high-dose treatment, remission state improved in 43 out of 102 patients. No statistically significant advantage in reaching complete or partial remission was observed with TBI+high-dose melphalan compared to the treatment with high-dose melphalan alone. The optimal high-dose treatment, with particular reference to the inclusion or omission of TBI, should be prospectively investigated. PMID:9304704

  5. Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan.

    PubMed Central

    Kurokawa, Y; Takayama, S; Konishi, Y; Hiasa, Y; Asahina, S; Takahashi, M; Maekawa, A; Hayashi, Y

    1986-01-01

    Long-term in vivo carcinogenicity tests of potassium bromate (KBrO3), sodium hypochlorite (NaClO), and sodium chlorite (NaClO2) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-week tests. Control animals were given distilled water. The carcinogenic potential of KBrO3 was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO3 at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. NaClO was administered to male and female rats, respectively, at doses of 1000 or 500 ppm and 2000 or 1000 ppm for 104 weeks. In mice, NaClO was given at doses of 1000 or 500 ppm to either sex for 103 weeks. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. NaClO2 was given to rats of both sexes at a dose of 600 or 300 ppm for 85 weeks. No statistically significant differences were observed in the incidences of tumor formation between NaClO2-treated and control groups of both sexes. NaClO2 was administered to mice at a concentration of 500 or 250 ppm for 85 weeks. In males, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls (p less than 0.05). However, these incidences in treated males were within the range of values of historical control data in our program. We concluded that KBrO3 was carcinogenic in rats of

  6. TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses

    PubMed Central

    Zheng, Xiao-Hui; Nie, Xin; Liu, Hai-Ying; Fang, Yi-Ming; Zhao, Yong; Xia, Li-Xin

    2016-01-01

    TMPyP4 is widely considered as a potential photosensitizer in photodynamic therapy and a G-quadruplex stabilizer for telomerase-based cancer therapeutics. However, its biological effects including a possible adverse-effect are poorly understood. In this study, whole genome RNA-seq analysis was used to explore the alteration in gene expression induced by TMPyP4. Unexpectedly, we find that 27.67% of changed genes were functionally related to cell adhesion. Experimental evidences from cell adhesion assay, scratch-wound and transwell assay indicate that TMPyP4 at conventional doses (≤0.5 μM) increases cell-matrix adhesion and promotes the migration of tumor cells. In contrast, a high dose of TMPyP4 (≥2 μM) inhibits cell proliferation and induces cell death. The unintended “side-effect” of TMPyP4 on promoting cell migration suggests that a relative high dose of TMPyP4 is preferred for therapeutic purpose. These findings contribute to better understanding of biological effects induced by TMPyP4 and provide a new insight into the complexity and implication for TMPyP4 based cancer therapy. PMID:27221067

  7. TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses.

    PubMed

    Zheng, Xiao-Hui; Nie, Xin; Liu, Hai-Ying; Fang, Yi-Ming; Zhao, Yong; Xia, Li-Xin

    2016-01-01

    TMPyP4 is widely considered as a potential photosensitizer in photodynamic therapy and a G-quadruplex stabilizer for telomerase-based cancer therapeutics. However, its biological effects including a possible adverse-effect are poorly understood. In this study, whole genome RNA-seq analysis was used to explore the alteration in gene expression induced by TMPyP4. Unexpectedly, we find that 27.67% of changed genes were functionally related to cell adhesion. Experimental evidences from cell adhesion assay, scratch-wound and transwell assay indicate that TMPyP4 at conventional doses (≤0.5 μM) increases cell-matrix adhesion and promotes the migration of tumor cells. In contrast, a high dose of TMPyP4 (≥2 μM) inhibits cell proliferation and induces cell death. The unintended "side-effect" of TMPyP4 on promoting cell migration suggests that a relative high dose of TMPyP4 is preferred for therapeutic purpose. These findings contribute to better understanding of biological effects induced by TMPyP4 and provide a new insight into the complexity and implication for TMPyP4 based cancer therapy. PMID:27221067

  8. Chlorite Dissolution Rates From 25 to 275 degrees and pH 3 to 10

    DOE Data Explorer

    Carroll, Susan

    2013-09-27

    We have calculated a chlorite dissolution rate equation at far from equilibrium conditions by combining new data (20 experiments at high temperature) with previously published data Smith et al. 2013 and Lowson et al. 2007. All rate data (from the 127 experiments) are tabulated in this data submission. More information on the calculation of the rate data can be found in our FY13 Annual support (Carroll LLNL, 2013) which has been submitted to the GDR. The rate equation fills a data gap in geothemal kinetic data base and can be used directly to estimate the impact of chemical alteration on all geothermal processes. It is especially important for understanding the role of chemical alteration in the weakening for shear zones in EGS systems.

  9. Bioavailability of 2,4-D sorbed to a chlorite-like complex.

    PubMed

    McGhee, I; Sannino, F; Gianfreda, L; Burns, R G

    1999-07-01

    An Al(OH)x-montmorillonite (chlorite) complex (AM18) was prepared and 2,4-dichlorophenoxyacetic acid (2,4-D) sorbed to saturation. After several washing cycles the 'strongly sorbed' 2,4-D was 507 micrograms g-1 AM18. The bioavailability of sorbed 2,4-D was assessed in a minimal salts medium with the AM18-2,4-D as the sole C and energy source. Over a 28-day period a Pseudomonas sp. degraded 23% more of the sorbed 2,4-D than could be accounted for by desorption from AM18 in the non-inoculated controls. Possible explanations for the increase in bioavailability are presented. PMID:10399845

  10. Enhancement of the nanofibrillation of wood cellulose through sequential periodate-chlorite oxidation.

    PubMed

    Liimatainen, Henrikki; Visanko, Miikka; Sirviö, Juho Antti; Hormi, Osmo E O; Niinimaki, Jouko

    2012-05-14

    Sequential regioselective periodate-chlorite oxidation was employed as a new and efficient pretreatment to enhance the nanofibrillation of hardwood cellulose pulp through homogenization. The oxidized celluloses with carboxyl contents ranging from 0.38 to 1.75 mmol/g could nanofibrillate to highly viscous and transparent gels with yields of 100-85% without clogging the homogenizer (one to four passes). On the basis of field-emission scanning electron microscopy images, the nanofibrils obtained were of typical widths of approximately 25 ± 6 nm. All of the nanofibrillar samples maintained their cellulose I crystalline structure according to wide-angle X-ray diffraction results, and the crystallinity index was approximately 40% for all samples. PMID:22512713

  11. Controlled clinical evaluations of chlorine dioxide, chlorite and chlorate in man.

    PubMed Central

    Lubbers, J R; Chauan, S; Bianchine, J R

    1982-01-01

    To assess the relative safety of chronically administered chlorine water disinfectants in man, a controlled study was undertaken. The clinical evaluation was conducted in the three phases common to investigational drug studies. Phase I, a rising dose tolerance investigation, examined the acute effects of progressively increasing single doses of chlorine disinfectants to normal healthy adult male volunteers. Phase II considered the impact on normal subjects of daily ingestion of the disinfectants at a concentration of 5 mg/l. for twelve consecutive weeks. Persons with a low level of glucose-6-phosphate dehydrogenase may be expected to be especially susceptible to oxidative stress; therefore, in Phase III, chlorite at a concentration of 5 mg/l. was administered daily for twelve consecutive weeks to a small group of potentially at-risk glucose-6-phosphate dehydrogenase-deficient subjects. Physiological impact was assessed by evaluation of a battery of qualitative and quantitative tests. The three phases of this controlled double-blind clinical evaluation of chlorine dioxide and its potential metabolites in human male volunteer subjects were completed uneventfully. There were no obvious undesirable clinical sequellae noted by any of the participating subjects or by the observing medical team. In several cases, statistically significant trends in certain biochemical or physiological parameters were associated with treatment; however, none of these trends was judged to have physiological consequence. One cannot rule out the possibility that, over a longer treatment period, these trends might indeed achieve proportions of clinical importance. However, by the absence of detrimental physiological responses within the limits of the study, the relative safety of oral ingestion of chlorine dioxide and its metabolites, chlorite and chlorate, was demonstrated. PMID:6961033

  12. Deformation microstructure of the chlorite dunite from the Åheim, Norway

    NASA Astrophysics Data System (ADS)

    Jung, S.; Yamamoto, T.; Ando, J. I.; Jung, H.

    2015-12-01

    The microstructure of the chlorite dunite samples from the Åheim, Norway was analyzed to understand the evolution of the microstructure through the Scandian Orogeny and the subsequent exhumation process. The lattice preferred orientation (LPO) of olivine and the slip systems of the dislocations in olivine are analyzed and compared to understand the relationship of the olivine fabrics and dislocation microstructures of olivine and their evolution during the orogenic event. To determine the LPO of olivine, an electron back-scattered diffraction (EBSD) system was used. For the olivine crystals with the subgrain boundaries, EBSD mapping along the olivine subgrain boundaries were performed to determine the dominant slip system of dislocations in subgrain walls. In addition, the thickness-fringe method was applied to weak-beam dark-field (WBDF) images of TEM to identify the Burgers vector and the slip system of dislocations in olivine. The Åheim chlorite dunites show porphyroclastic texture with subgrain boundaries. The sample with a large grain size showed A-type olivine LPO, which corresponds to the initial stage of deformation. On the other hand, the other sample with mostly recrystallized olivine grains showed the B-type of olivine LPO and it represents the secondary stage deformation in the water-rich condition during exhumation process. The EBSD mapping and TEM observation revealed that most olivine subgrain boundaries consist of the dislocations with (001)[100] slip systems. These subgrain boundaries might be resulted from the later stage deformation with a moderate water content in olivine or low strain deformation. TEM observation with the thickness-fringe method revealed that the free dislocations with (010)[100] slip system of olivine were dominant for both samples. Our data suggest that the subgrain boundaries and free dislocations in the olivines represent the later stage deformation associated with the exhumation process.

  13. Identification of spectrally similar materials using the USGS Tetracorder algorithm: The calcite-epidote-chlorite problem

    USGS Publications Warehouse

    Dalton, J.B.; Bove, D.J.; Mladinich, C.S.; Rockwell, B.W.

    2004-01-01

    A scheme to discriminate and identify materials having overlapping spectral absorption features has been developed and tested based on the U.S. Geological Survey (USGS) Tetracorder system. The scheme has been applied to remotely sensed imaging spectroscopy data acquired by the Airborne Visible and Infrared Imaging Spectrometer (AVIRIS) instrument. This approach was used to identify the minerals calcite, epidote, and chlorite in the upper Animas River watershed, Colorado. The study was motivated by the need to characterize the distribution of calcite in the watershed and assess its acid-neutralizing potential with regard to acidic mine drainage. Identification of these three minerals is difficult because their diagnostic spectral features are all centered at 2.3 ??m, and have similar shapes and widths. Previous studies overestimated calcite abundance as a result of these spectral overlaps. The use of a reference library containing synthetic mixtures of the three minerals in varying proportions was found to simplify the task of identifying these minerals when used in conjunction with a rule-based expert system. Some inaccuracies in the mineral distribution maps remain, however, due to the influence of a fourth spectral component, sericite, which exhibits spectral absorption features at 2.2 and 2.4 ??m that overlap the 2.3-??m absorption features of the other three minerals. Whereas the endmember minerals calcite, epidote, chlorite, and sericite can be identified by the method presented here, discrepancies occur in areas where all four occur together as intimate mixtures. It is expected that future work will be able to reduce these discrepancies by including reference mixtures containing sericite. ?? 2004 Elsevier Inc. All rights reserved.

  14. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH-DOSE

  15. Dual effectiveness of sodium chlorite for enzymatic browning inhibition and Escherichia coli inactivation on fresh-cut apples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated the dual effectiveness of sodium chlorite (SC) for browning inhibition and microbial inactivation on fresh-cut apples. The SC treatment exhibited a strong inhibition on browning reaction of fresh-cut Red Delicious apples during cold storage. Test results from examination of t...

  16. Effects of various pH conditions on authigenic chlorite and kaolinite surface characteristics using SEM and x-ray microanalysis

    SciTech Connect

    Dogan, A.U.; Leung, W.K.

    1987-05-01

    Authigenic chlorite and kaolinite are major diagenetic minerals in petroleum-bearing sandstone units. Authigenic chlorite in marine sandstone units of the Upper Cretaceous Parkman formation of Wyoming occurs as grain coatings which line pores. Chlorite plates developed on grain surfaces perpendicular to grain margins, with individual crystals being about 3 to 5 microns in diameter and 0.1 micron thick. Authigenic kaolinite occurs as stacked pseudohexagonal booklets that fill pores. Its crystal diameter is about 10 microns. Well-developed chlorite and kaolinite crystals coexist in many sandstone units. Some workers claim that chlorite is extremely sensitive to acid, and some claim that acidic conditions are required to form kaolinite, although fresh water need not be the only source of acidity. In the Parkman formation, chlorite is well preserved in pores. Therefore, it appears that the chlorite-bearing units may not have been subjected to acidic conditions after chlorite was formed. However, kaolinite in these units appears to have precipitated after chlorite formation. If this is so, then acidic conditions required to form kaolinite would have destroyed earlier formed chlorite. To test this problem, a laboratory experiment was designed to show effects of varying pH conditions on these crystals. Experiments were done under atmospheric conditions. Solutions were maintained with pH of 4, 6, 7, 8, and 10. Physical chemical changes on crystal surfaces were studied using scanning electron microscopy, x-ray microanalysis, and Shape Analyzer. Details of the precipitation mechanism and kinetics of equilibrium of these minerals will be discussed.

  17. Psychiatric side effects of acute high-dose corticosteroid therapy in neurological conditions.

    PubMed

    Lotan, Itay; Fireman, Liora; Benninger, Felix; Weizman, Abraham; Steiner, Israel

    2016-07-01

    It has been implied that high-dose corticosteroids (CSs) commonly cause psychiatric side effects. Here, we examined the rate and risk factors of psychiatric side effects during high-dose CS treatment in patients with neurological disorders. Patients treated with high-dose intravenous CSs for neurological disorders were evaluated for depression, mania, and psychosis using the Beck Depression Inventory, the Geriatric Depression Scale, the Young Mania Rating Scale, and the Brief Psychiatric Rating Scale before CS treatment, immediately after, and 1 month following treatment. Forty-nine consecutive patients were monitored. There was a reduction in the Beck Depression Inventory and Geriatric Depression Scale scores as well as in the Brief Psychiatric Rating Scale scores throughout the study period and a transitory increase in the Young Mania Rating Scale score immediately after CS administration. Thus, a tendency to develop transient mild euphoria during high-dose CS treatment exists, but is reversible at 1 month, whereas a reduction in depressive symptoms tended to persist. Overall, our data indicate that high-dose CS treatment for neurological diseases is relatively safe with respect to psychiatric complications. PMID:26938038

  18. High dose rate sources in remote afterloading brachytherapy: Implications for intracavitary and interstitial treatment of carcinoma

    SciTech Connect

    Syzek, E.J.; Bogardus, C.R. Jr. )

    1990-11-01

    Remote afterloading brachytherapy provides effective cancer treatment with zero personnel radiation exposure compared to conventional low dose rate systems requiring inpatient use of iridium, radium, or cesium sources. Clinical use of high dose rate brachytherapy is broadened to encompass curative treatment of cervical, endometrial, endobronchial, head and neck, esophageal, rectal, and prostatic carcinomas as well as palliation of intra-abdominal metastasis intraoperatively. Complications encountered with high dose rate sources will be compared to those of low dose rate systems commonly used in conjunction with external beam irradiation. Radiobiological effectiveness and economic benefits will be addressed to provide support for use of remote afterloading using high dose rate brachytherapy in palliative and curative treatment of selected carcinoma. 36 refs.

  19. Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation.

    PubMed

    Bang, Hyun Soon; Choi, Moo Hyun; Kim, Cha Soon; Choi, Seung Jin

    2016-06-01

    Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range. PMID:27006382

  20. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  1. Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation

    PubMed Central

    Bang, Hyun Soon; Choi, Moo Hyun; Kim, Cha Soon; Choi, Seung Jin

    2016-01-01

    Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range. PMID:27006382

  2. Nebuhaler or nebulizer for high dose bronchodilator therapy in chronic bronchitis: a comparison.

    PubMed

    Allen, M B; Pugh, J; Wilson, R S

    1988-10-01

    We have compared the clinical efficacy of high dose terbutaline sulphate (10 mg four times daily) delivered by either a Nebuhaler or jet nebulizer in 13 patients with chronic bronchitis in a 2-week, open, crossover study. Both treatment regimens improved run-in symptom scores but no significant changes were recorded in peak flow and spirometry. Side-effects were more common with the Nebuhaler and more patients preferred the nebulizer. However, the Nebuhaler is an alternative therapeutic option for delivery of high doses of bronchodilators in patients with chronic bronchitis. PMID:3076792

  3. Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

    PubMed

    Hannoun-Lévi, J-M; Peiffert, D

    2014-10-01

    Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations. PMID:25195117

  4. High-dose neuroleptics: uncontrolled clinical practice confirms controlled clinical trials.

    PubMed

    Bollini, P; Andreani, A; Colombo, F; Bellantuono, C; Beretta, P; Arduini, A; Galli, T; Tognoni, G

    1984-01-01

    The strategy of high-dose intramuscular haloperidol as routinely applied in a general hospital psychiatric ward to 74 successive patients, 33 of whom stayed only up to seven days, and a further 34 up to 15 days, led to a complete recovery in only six, and complete lack of change in 23. Adverse reactions were recorded in 42, severe enough to stop treatment in eight; there were three deaths. In view of this risk-benefit analysis, systematic application of this high dose strategy to get a more rapid turnover of patients is unjustified. PMID:6692073

  5. Efficacy of High-Dose Baclofen for Alcohol Use Disorder and Comorbid Bulimia: A Case Report.

    PubMed

    Weibel, Sébastien; Lalanne, Laurence; Riegert, Myriam; Bertschy, Gilles

    2015-01-01

    High-dose baclofen is a promising treatment for alcohol use disorder, with a specific action on craving. A more general action on craving in other addictive disorders has been suggested based on the hypothesis of a common neurobiological pathway in addictions. We report the case of a woman with both alcohol use disorder and bulimia nervosa. There was a positive response to high-dose baclofen on alcohol craving, but no response on food craving. The case illustrates that craving could be differentially responsive to anti-craving drugs. PMID:26457456

  6. Vitamin E ameliorates high dose trans-dehydrocrotonin-associated hepatic damage in mice.

    PubMed

    Rabelo, Alana Fontales Lima; Guedes, Marjorie Moreira; Tomé, Adriana da Rocha; Lima, Patricia Rodrigues; Maciel, Maria Aparecida; Lira, Silveria Regina de Sousa; Carvalho, Ana Carla da Silva; Santos, Flávia Almeida; Rao, Vietla Satyanarayana

    2010-04-01

    trans-Dehydrocrotonin (t-DCTN), the diterpenoid from Croton cajucara Bentham, exhibits hypoglycemic and hypolipidemic activities, but in high doses is associated with a discrete hepatotoxicity. In the search for measures to mitigate this, pretreatment with the antioxidants N-acetylcysteine and vitamin E has been examined. Mice that received a high dose t-DCTN (100 mg/kg) manifested hepatic damage, as evidenced by significant elevations in serum ALT and AST, and hepatic GSH, and histological alterations, which could be obliterated by pretreatment with vitamin E, but not with N-acetylcysteine, possibly by creating an effective antioxidant balance. PMID:20433064

  7. Scales of equilibrium and disequilibrium during cleavage formation in chlorite and biotite-grade phyllites, SE Vermont

    USGS Publications Warehouse

    McWilliams, C.K.; Wintsch, R.P.; Kunk, M.J.

    2007-01-01

    Detailed electron microprobe analyses of phyllosilicates in crenulated phyllites from south-eastern Vermont show that grain-scale zoning is common, and sympathetic zoning in adjacent minerals is nearly universal. We interpret this to reflect a pressure-solution mechanism for cleavage development, where precipitation from a very small fluid reservoir fractionated that fluid. Multiple analyses along single muscovite, biotite and chlorite grains (30-200 ??m in length) show zoning patterns indicating Tschermakitic substitutions in muscovite and both Tschermakitic and di/trioctahedral substitutions in biotite and chlorite. Using cross-cutting relationships and mineral chemistry it is shown that these patterns persist in cleavages produced at metamorphic conditions of chlorite-grade, chlorite-grade overprinted by biotite-grade and biotite-grade. Zoning patterns are comparable in all three settings, requiring a similar cleavage-forming mechanism independent of metamorphic grade. Moreover, the use of 40Ar/ 39Ar geochronology demonstrates this is true regardless of age. Furthermore, samples with chlorite-grade cleavages overprinted by biotite porphyroblasts suggest the closure temperatures for the diffusion of Al, Si, Mg and Fe ions are greater than the temperature of the biotite isograd (>???400 ??C). Parallel and smoothly fanning tie lines produced by coexisting muscovite-chlorite, and muscovite-biotite pairs on compositional diagrams demonstrate effectively instantaneous chemical equilibrium and probably indicate simultaneous crystallization. These results do not support theories suggesting cleavages form in fluid-dominated systems. If crenulation cleavages formed in systems in which the chemical potentials of all major components are fixed by an external reservoir, then the compositions of individual grains defining these cleavages would be uniform. On the contrary, the fine-scale chemical zoning observed probably reflects a grain-scale process consistent with a

  8. Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies

    PubMed Central

    Leyvraz, S; Herrmann, R; Guillou, L; Honegger, H P; Christinat, A; Fey, M F; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B

    2006-01-01

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m−2 (continuous infusion for 5 days), doxorubicin 30 mg m−2 day−1 × 3 (total dose 90 mg m−2), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1–6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33–63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade ⩾3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies. PMID:17031396

  9. Zn-Al-rich chlorite in interleaved phyllosilicate grains from the low-temperature metamorphic Ordovician terrane of Iglesiente, south-west Sardinia, Italy

    NASA Astrophysics Data System (ADS)

    Cruciani, Gabriele; Franceschelli, Marcello; Battaglia, Stefano; Pasci, Sandro; Puxeddu, Mariano

    2015-12-01

    Zn-Al chlorite with a ZnO content of 2-3 wt% has been found in the Monte Argentu Formation that belongs to the external zone of the Variscan Sardinian Belt in SW Sardinia. This chlorite occurs in metasiltite rocks characterized by the alternation of dark-coloured layers rich in Fe- and Ti-oxides and light-coloured layers rich in quartz and phyllosilicates. The Zn-Al chlorite is associated with K-white mica, pyrophyllite, and quartz. The most common interleavings consist of K-white mica + Zn-Al chlorite, K-white mica + pyrophyllite, K-white mica + Zn-Al chlorite + pyrophyllite, and Zn-Al chlorite + pyrophyllite. The X-ray patterns of the <2 μm fraction of the investigated samples are characterized by peaks for illite, pyrophyllite, chlorite and quartz. Metamorphic temperatures of 300°-400°C have been estimated on the basis of the pyrophyllite occurrence. Pressure estimated on the basis of K-white mica composition is in the 0.3-0.6 GPa range.

  10. A saponite and chlorite-rich clay assemblage in permian evaporite and red-bed strata, Palo Duro Basin, Texas Panhandle

    SciTech Connect

    Palmer, D.P.

    1987-01-01

    In this Department of Energy-funded project, the author describes lithology of core samples from two Department of Energy wells in Randall and Swisher Counties and determines clay mineralogy and X-ray diffraction response using 73 samples from the Randall County well and 40 samples from the Swisher County well. On the basis of his analyses, the author identifies the clay assemblage in the Palo Duro Basin evaporites as consisting of saponite, a magnesium-rich smectite; mixed-layer chlorite/smectite; chlorite/vermiculite; chlorite/swelling chlorite; vermiculite/swelling chlorite; chlorite, and illite. Chemical analyses reveal that the chemical composition of the mixed-layer clays is intermediate between normal aluminum-rich detrital clays and normal vermiculite and chlorite, magnesium clays of hydrothermal or metamorphic origin. The author postulates that rates and amounts of clay alteration are probably controlled by magnesium ion activity, brine salinity, brine pH, and sediment and clay residence time in the marine evaporite environment.

  11. EXAFS Study of Sr sorption to Illite, Goethite, Chlorite, and Mixed Sediment under Hyperalkaline Conditions.

    PubMed

    Fuller, Adam J; Shaw, Samuel; Peacock, Caroline L; Trivedi, Divyesh; Burke, Ian T

    2016-03-29

    Strontium is an important contaminant radionuclide at many former nuclear sites. This paper investigates the effect of changing pH and ionic strength on the sorption of Sr to a range of common soil minerals. Specifically it focuses on the sorption of Sr onto illite, chlorite, goethite, and a mixed sediment. The interplay between ionic strength and pH was determined by varying the background ionic strength of the system using both NaCl (for a constant pH) and NaOH (to also vary pH). Under conditions of moderate pH, Sr sorption decreased with increasing ionic strength, due to competition between the Na and Sr atoms for the outer-sphere complexes. However, where increasing ionic strength was accompanied by increasing pH, Sr sorption remained high. This suggested that Sr was sorbed to the minerals without competition from background Na ions. Extended X-ray absorption fine structure (EXAFS) spectra confirmed that at highly alkaline pH (>12.5) Sr was forming inner-sphere complexes on the surfaces of all minerals. This specific adsorption of the Sr (as SrOH(+)) explains why it was still adsorbed to the minerals under very high ionic strength conditions and was not out-competed by Na. PMID:26938867

  12. Long-lived oscillations in the chlorite-iodide-malonic acid reaction in batch

    SciTech Connect

    Noszticzius, Z.; Ouyang, Qi; McCormick, W.D.; Swinney, H.L.

    1992-05-20

    The title reaction is the subject of current interest because the first experimental Turing patterns were observed recently in this system. Here, the authors report the first observation of oscillations that are long lived (over 1 h) in this system in a batch reactor; even after cessation the oscillations can be restarted several times by adding ClO{sub 2} to the exhausted system. These low-frequency low-amplitude (LL) oscillations were detected with both platinum and iodide-selective electrodes in the chlorite-iodide-malonic acid (original CIMA) reaction and in the closely related chlorine dioxide-iodide-malonic acid (minimal CIMA) system. The LL oscillations follow after the already known high frequency oscillations, sometimes separated by a second induction period. LL oscillations can appear without any induction period if appropriate concentrations of chlorine dioxide, iodomalonic acid, and chloride (CIMA-Cl system) are established in a dilute sulfuric acid medium. In this case neither iodine, iodide, nor malonic acid is needed. Some suggestions are made regarding the mechanism of these newly discovered oscillations. 33 refs., 6 figs., 1 tab.

  13. 'In Vivo' Dosimetry in High Dose Rate Brachytherapy for Cervical Cancer Treatments

    SciTech Connect

    Gonzalez-Azcorra, S. A.; Ruiz-Trejo, C.; Buenfil, A. E.; Mota-Garcia, A.; Poitevin-Chacon, M. A.; Santamaria-Torruco, B. J.; Rodriguez-Ponce, M.; Herrera-Martinez, F. P.; Gamboa de Buen, I.

    2008-08-11

    In this prospective study, rectal dose was measured 'in vivo' using TLD-100 crystals (3x3x1 mm{sup 3}), and it has been compared to the prescribed dose. Measurements were performed in patients with cervical cancer classified in FIGO stages IB-IIIB and treated with high dose rate brachytherapy (HDR BT) at the Instituto Nacional de Cancerologia (INCan)

  14. Efficacy of high-dose methylprednisolone pulse therapy in the treatment of enterovirus 71 encephalitis.

    PubMed

    Zhang, Guangyou; Wang, Jiwen; Yao, Guo; Shi, Baohai

    2016-07-01

    To investigate the efficacy of high-dose methylprednisolone pulse therapy in the treatment of Enterovirus 71 (EV71) encephalitis. To determine whether high-dose methylprednisolone pulse therapy should be used, 80 cases of pediatric patients with EV71 encephalitis were randomly divided into steroid pulse therapy group and non-steroid pulse therapy group and their clinical information was compared using statistic analysis. There was no statistical difference in the duration of fever, duration of nervous system involvement, duration of hospital stay, blood pressure, and cure rates between the two groups (p>0.05). The heart rate, respiratory rate, white blood cell counts and blood glucose of the steroid pulse therapy group were significantly higher than those of the non-steroid pulse therapy group (p<0.05). High-dose steroid pulse therapy to treat EV71 encephalitis can't shorten the course or improve the prognosis of the disease. In contrast, it has side effects and might aggravate disease condition or interfere with disease diagnosis. Our study suggested that there is no beneficial effect to use high-dose steroid pulse therapy for the treatment of EV71 encephalitis. PMID:27592493

  15. Administration of high-dose interleukin-2 in a 2-year-old with metastatic melanoma.

    PubMed

    Bernhardt, M Brooke; Hicks, M John; Pappo, Alberto S

    2009-12-15

    Malignant melanoma is rare in pediatrics, and therapies for patients with disseminated disease have not been well studied. This report describes our experience with the use of high-dose interleukin 2 (aldesleukin, IL-2) in a 2-year-old child with metastatic melanoma and describes our approach for the administration of this agent to young patients. PMID:19731326

  16. High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

    PubMed

    Yang, Yang; Jing, Xiao-Peng; Zhang, Shou-Peng; Gu, Run-Xia; Tang, Fang-Xu; Wang, Xiu-Lian; Xiong, Yan; Qiu, Mei; Sun, Xu-Ying; Ke, Dan; Wang, Jian-Zhi; Liu, Rong

    2013-01-01

    Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit. PMID:23383172

  17. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

  18. Loudness perception affected by high doses of salicylate--a behavioral model of hyperacusis.

    PubMed

    Zhang, Chao; Flowers, Elizabeth; Li, Jun-Xu; Wang, Qiuju; Sun, Wei

    2014-09-01

    The major side-effects of high doses of salicylate include sensorial hearing loss and tinnitus. Although salicylate decreases cochlear output, it enhances the evoked potentials recorded from the central auditory system (CAS), suggesting an increase to sound sensitivity. However, the loudness change after salicylate administration has not yet been directly measured. In this study, we established an operant conditioning based behavioral task in rats and measured their loudness perception changes before and after high doses of salicylate injection (250 mg/kg, i.p.). We found that high doses of salicylate induced a significant increase to loudness response in 40% of the rats (out of 20 rats), suggesting a hyperacusis behavior. In another 40% of rats, a rapid increase of loudness response was detected, suggesting loudness recruitment. The reaction time of the rats was also measured during the loudness tests before and after salicylate exposure. The reaction time level functions are highly correlated to the loudness response functions. Our studies confirmed that increased sound sensitivity, which is commonly seen in patients with tinnitus and hyperacusis, can be induced by high doses of salicylate. This loudness change induced by salicylate may be related with hypersensitivity in the CAS. PMID:24882611

  19. Pregnancy outcomes following the administration of high doses of dexamethasone in early pregnancy

    PubMed Central

    Kayvan Jafari, Sabah; Nezafat Firizi, Maryam; Abbaspour, Ali Reza; Ghafoori Gharib, Fahime; Ghobadi, Yusef; Gholizadeh, Samira

    2016-01-01

    Objective In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. Methods Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and 17β-estradiol, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We also were measured fetal and placental growth parameters on GD 18.5. Results We found that high doses of DEX were associated with an increased abortion rate, enhancement of the immunosuppressive effect of the decidua, alterations in placental growth parameters, decreased progesterone and 17β-estradiol levels, and a reduced frequency of macrophages and uNK cells. Conclusion Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes. PMID:27104153

  20. Transient radiation effects following high dose I-131 therapy for differentiated thyroid cancer (DTC)

    SciTech Connect

    Khan, S.; Waxman, A.; Ramanna, L.

    1994-05-01

    There is limited information regarding the incidence of post-I-131 therapeutic side effects in pts. undergoing high-dose I-131 therapy for DTC. The purpose of the current study is to characterize side effects experienced by patients following 150 mCi.

  1. Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

    PubMed Central

    Zeiler, F. A.; Silvaggio, J.

    2015-01-01

    Background. Treatment of symptomatic delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is difficult. Recent studies suggest intravenous (IV) high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS) clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm. PMID:26457209

  2. High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans.

    PubMed

    Nguyen, M A; Staubach, P; Tamai, I; Langguth, P

    2015-02-20

    Naringin is considered the major causative ingredient of the inhibition of intestinal drug uptake by grapefruit juice. Moreover, it is contained in highly dosed nutraceuticals available on the market. A controlled, open, randomized, crossover study was performed in 10 healthy volunteers to investigate the effect of high-dose naringin on the bioavailability of talinolol, a substrate of intestinal organic anion-transporting polypeptide (OATP)-mediated uptake. Following 6-day supplementation with 3 capsules of 350 mg naringin daily, 100mg talinolol were administered orally with 3 capsules of the same dietary supplement (1050 mg naringin) on the seventh day. This test treatment was compared to 100mg talinolol only (control). The results showed that short-term high-dose naringin supplementation did not significantly affect talinolol pharmacokinetics. Geometric mean ratios of test versus control ranged between 0.90 and 0.98 for talinolol c(max), AUC(0-48 h), AUC(0-∞), t(1/2) and A(e(0-48 h)). The high dose may provoke inhibition of the efflux transporter P-glycoprotein (P-gp) which counteracts the uptake inhibition. As disintegration and dissolution processes are required for the solid dosage form, dissolved naringin may arrive at the site of interaction after talinolol is already absorbed. In conclusion, the effect of nutraceuticals on drug pharmacokinetics can deviate from that observed when administered as food component due to the different dose and dosage form. PMID:25486333

  3. Improving Positioning in High-Dose Radiotherapy for Prostate Cancer: Safety and Visibility of Frequently Used Gold Fiducial Markers

    SciTech Connect

    Fonteyne, Valerie; Ost, Piet; Villeirs, Geert; Oosterlinck, Willem; Impens, Aline; De Gersem, Werner; De Wagter, Carlos; De Meerleer, Gert

    2012-05-01

    Purpose: The use of gold fiducial markers (GFMs) for prostate positioning in high-dose radiotherapy is gaining interest. The purpose of this study was to compare five GFMs regarding feasibility of ultrasound-based implantation in the prostate and intraprostatic lesion (IPL); toxicity; visibility on transabdominal ultrasound (TU) and cone-beam CT (CBCT); reliability of automatic, soft tissue, and GFM-based CBCT patient positioning by comparing manual and automatic fusion CBCT. Methods and Materials: Twenty-five patients were included. Pain and toxicity were scored after implantation and high-dose radiotherapy. Fisher exact test was used to evaluate the correlation of patients' characteristics and prostatitis. Positioning was evaluated on TU and kilovoltage CBCT images. CBCT fusion was performed automatically (Elekta XVI technology, release 3.5.1 b27, based on grey values) and manually on soft tissue and GFMs. Pearson correlation statistics and Bland-Altman evaluation were used. Five GFMs were compared. Results: Twenty percent of the patients developed prostatitis despite antibiotic prophylaxis. Cigarette smoking was significantly correlated with prostatitis. The visualization of all GFMs on TU was disappointing. Consequently we cannot recommend the use of these GFMs for TU-based prostate positioning. For all GFMs, there was only fair to poor linear correlation between automatic and manual CBCT images, indicating that even when GFMs are used, an operator evaluation is imperative. However, when GFMs were analyzed individually, a moderate to very strong correlation between automatic and manual positioning was found for larger GFMs in all directions. Conclusion: The incidence of prostatitis in our series was high. Further research is imperative to define the ideal preparation protocol preimplantation and to select patients. Automatic fusion is more reliable with larger GFMs at the cost of more scatter. The stability of all GFMs was proven.

  4. Temperature micro-mapping and redox conditions of a chlorite zoning pattern in green-schist facies fault zone

    NASA Astrophysics Data System (ADS)

    Trincal, Vincent; Lanari, Pierre; Lacroix, Brice; Buatier, Martine D.; Charpentier, Delphine; Labaume, Pierre; Muñoz, Manuel

    2014-05-01

    Faults are major discontinuities driving fluid flows and playing a major role in precipitation of ore deposits. Mineral paragenesis and crystal chemistry depend on Temperature (T) condition, fluid composition but also on the redox environment of precipitation. The studied samples come from the Pic de Port Vieux thrust sheet, a minor thrust sheet associated to Gavarnie thrust fault zone (Central Pyrenees). The Pic de Port Vieux Thrust sheet comprises a 1-20 meter thick layer of Triassic red beds and mylonitized Cretaceous limestone. The thrust sheet is affected by faults and cleavage; the other important deformation product is a set of veins filled by quartz and chlorite. Microstructural and mineralogical investigations were performed based on the previous work of Grant (1992). The crystallization of chlorite is syn-tectonic and strongly controlled by the fluid circulation during the Gavarnie thrust sheet emplacement. Chlorite precipitated in extension veins, crack-seal shear veins or in open cavities. The chlorite filling the open cavities occurs as pseudo-uniaxial plates arranged in rosette-shaped aggregates. These aggregates appear to have developed as a result of radial growth of the chlorite platelets. According to point and microprobe X-ray images, these chlorites display oscillatory chemical zoning patterns with alternating iron rich and magnesium rich bands. The chlorite composition ranges from Fe rich pole (Si2.62Al1.38O10(Al1.47Fe1.87Mg2.61)6(OH)8) to Mg rich pole (Si2.68Al1.31O10(Al1.45Fe1.41Mg3.06)6(OH)8). In metamorphic rocks, zoning pattern or rimmed minerals results for varying P or T conditions and can be used to unravel the P-T history of the sample. In the present study, temperature maps are derived from standardized microprobe X-ray images using the program XMapTools (Lanari et al 2014). The (Fe3+/Fetot) value in chlorite was directly measured using μXANES spot analyses collected at the Fe-K edge. The results indicate a homogeneous temperature of

  5. Review of high-dose intravenous vitamin C as an anticancer agent.

    PubMed

    Wilson, Michelle K; Baguley, Bruce C; Wall, Clare; Jameson, Michael B; Findlay, Michael P

    2014-03-01

    In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial. PMID:24571058

  6. Redox Interactions of Tc(VII), U(VI), and Np(V) with Microbially Reduced Biotite and Chlorite.

    PubMed

    Brookshaw, Diana R; Pattrick, Richard A D; Bots, Pieter; Law, Gareth T W; Lloyd, Jonathan R; Mosselmans, J Fredrick W; Vaughan, David J; Dardenne, Kathy; Morris, Katherine

    2015-11-17

    Technetium, uranium, and neptunium are contaminants that cause concern at nuclear facilities due to their long half-life, environmental mobility, and radiotoxicity. Here we investigate the impact of microbial reduction of Fe(III) in biotite and chlorite and the role that this has in enhancing mineral reactivity toward soluble TcO4(-), UO2(2+), and NpO2(+). When reacted with unaltered biotite and chlorite, significant sorption of U(VI) occurred in low carbonate (0.2 mM) buffer, while U(VI), Tc(VII), and Np(V) showed low reactivity in high carbonate (30 mM) buffer. On reaction with the microbially reduced minerals, all radionuclides were removed from solution with U(VI) reactivity influenced by carbonate. Analysis by X-ray absorption spectroscopy (XAS) confirmed reductive precipitation to poorly soluble U(IV) in low carbonate conditions and both Tc(VII) and Np(V) in high carbonate buffer were also fully reduced to poorly soluble Tc(IV) and Np(IV) phases. U(VI) reduction was inhibited under high carbonate conditions. Furthermore, EXAFS analysis suggested that in the reaction products, Tc(IV) was associated with Fe, Np(IV) formed nanoparticulate NpO2, and U(IV) formed nanoparticulate UO2 in chlorite and was associated with silica in biotite. Overall, microbial reduction of the Fe(III) associated with biotite and chlorite primed the minerals for reductive scavenging of radionuclides: this has clear implications for the fate of radionuclides in the environment. PMID:26488884

  7. EFFECT OF EXOGENOUS GLUTATHIONE, GLUTATHIONE REDUCTASE, CHLORINE DIOXIDE, AND CHLORITE ON OSMOTIC FRAGILITY OF RAT BLOOD IN VITRO

    EPA Science Inventory

    Chlorine dioxide (ClO2), chlorite (ClO2(-1)), and chlorate (ClO3(-1)) in drinking water decreased blood glutathione and RBC osmotic fragility in vivo. The osmotic fragility and glutathione content were also studied in rat blood treated with ClO2, ClO2(-1), ClO3(-1) in vitro. RBC ...

  8. Timing and origin of zircon-bearing chlorite schists in the Ronda peridotites (Betic Cordilleras, Southern Spain)

    NASA Astrophysics Data System (ADS)

    Esteban, J. J.; Cuevas, J.; Tubía, J. M.; Liati, A.; Seward, D.; Gebauer, D.

    2007-11-01

    This paper reports the finding of zircon-bearing chlorite schists in the south-western part of the Sierra Bermeja, the largest massif of the Ronda peridotites (Alpujarride Complex, Betic Cordilleras, Spain). The chlorite schists contain unusually high amounts of zircon and monazite, never previously recorded in the granite dykes intruded into the peridotites nor in their country rocks. Structural, petrographic, geochemical and geochronological data suggest that late high temperature fluids/melts emanating from the crustally derived granite dykes locally altered the peridotites. The large, euhedral and U-rich zircons are very different to those of the granite dykes but probably formed from late high temperature fluids/melts. U-Pb SHRIMP data of these zircons yielded an age of 21.8 ± 0.5 Ma, leading to a precise age estimation for the emplacement of the granite dykes. In the course of later serpentinization processes chlorite schist formation took place during cooling at lower temperatures (289-322 °C). Fission-track zircon ages at 19.2 ± 1.1 Ma date this episode of cooling during exhumation of the peridotites.

  9. O2-evolving Chlorite Dismutase as a Tool to Study O2-Utilizing Enzymes†

    PubMed Central

    Dassama, Laura M. K.; Yosca, Timothy H.; Conner, Denise A.; Lee, Michael H.; Blanc, Béatrice; Streit, Bennett R.; Green, Michael T.; DuBois, Jennifer L.; Krebs, Carsten; Bollinger, J. Martin

    2012-01-01

    The direct interrogation of fleeting intermediates by rapid-mixing kinetic methods has significantly advanced our understanding of enzymes that utilize dioxygen. The gas’s modest aqueous solubility (< 2 mM at 1 atm) presents a technical challenge to this approach, because it limits the rate of formation and extent of accumulation of intermediates. This challenge can be overcome by use of the heme enzyme chlorite dismutase (Cld1) for the rapid, in situ generation of O2 at concentrations far exceeding 2 mM. This method was used to define the [O2] dependence of the reaction of the class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis, in which the enzyme’s MnIV/FeIII cofactor forms from a MnII/FeII complex and O2 via a MnIV/FeIV intermediate, at effective O2 concentrations as high as ~10 mM. With a more soluble receptor, myoglobin, an O2 adduct was accumulated to > 6 mM in < 15 ms. Finally, the C–H-bond-cleaving FeIV-oxo complex, J, in taurine:α-ketoglutarate dioxygenase and superoxo-Fe2III/III complex, G, in myo-inositol oxygenase, and the tyrosyl-radical-generating Fe2III/IV intermediate, X, in Escherichia coli RNR were all accumulated to yields more than twice those previously attained. This means of in situ O2 evolution permits a > 5 mM “pulse” of O2 to be generated in < 1 ms at the easily accessible [Cld] of 50 μM. It should therefore significantly extend the range of kinetic and spectroscopic experiments that can routinely be undertaken in the study of these enzymes and could also facilitate resolution of mechanistic pathways in cases of either sluggish or thermodynamically unfavorable O2-addition steps. PMID:22304240

  10. The effects of oil on As(V) adsorption on illite, kaolinite, montmorillonite and chlorite

    NASA Astrophysics Data System (ADS)

    Wainipee, Wimolporn; Cuadros, Javier; Sephton, Mark A.; Unsworth, Catherine; Gill, Martin G.; Strekopytov, Stanislav; Weiss, Dominik J.

    2013-11-01

    The effect of oil on As(V) adsorption on clay minerals has been investigated using batch experiments at low and high pH, NaCl concentration and oil contents. Four clay minerals were chosen because of their abundance in sediments and their different crystal chemistry: illite, kaolinite, montmorillonite, and chlorite. The values for pH were 4 and 8 and salt concentrations were 0.001 and 0.7 M NaCl to appreciate the effects of changing salinity, e.g. from fresh water to seawater conditions. For the coating experiments, a well-characterised oil was used to survey the main effects of complex organic mixtures on adsorption and oil to clay mineral (w/w) ratios were 0.0325 and 0.3250. As(V) adsorption increased with increasing NaCl concentration, suggesting that the mechanisms of As(V) adsorption are related to the formation of surface complexes in which Na+ ions act as bridges between the clay surface and the As(V) anions. Cation bridging is also indicated by zeta potential measurements which show that higher NaCl concentrations along with the presence of As(V) can cause the clay particles and adsorbed ions to have a more negative overall charge. Adsorption is lower at higher pH due to the reduced number of positively charged sites on the edge of clay mineral layers. Oil coating reduces As(V) adsorption by decreasing the available surface area of clay minerals, except in the case of oil-coated montmorillonite, where surface area following dispersion in water is increased. The main variables controlling As(V) adsorption are surface area and surface charge density, as confirmed by a simplified quantitative model. These findings advance our ability to predict the effects of complex pollution events in various freshwater and marine settings.

  11. Successful treatment of reactive airways dysfunction syndrome by high-dose vitamin D.

    PubMed

    Varney, Veronica A; Evans, Jane; Bansal, Amolak S

    2011-01-01

    Reactive airways dysfunction syndrome is a controversial and poorly understood condition produced by inhalational injury from gas, vapors, or fumes. The symptoms mimic asthma, but appear unresponsive to asthma treatments. If symptoms persist for more than 6 months, there is a risk that they can become chronic. For these cases, effective treatments are lacking and quality of life is poor. We describe the first use of high-dose vitamin D in a patient with this condition, who fulfilled the 1995 American College of Chest Physicians criteria for this syndrome. The patient we describe presented an extremely difficult management problem and was refractory to conventional treatments, but responded to high-dose oral vitamin D supplements. PMID:22034572

  12. CT of multiple sclerosis: reassessment of delayed scanning with high doses of contrast material

    SciTech Connect

    Spiegel, S.M.; Vinuela, F.; Fox, A.J.; Pelz, D.M.

    1985-09-01

    A prospective study involving 87 patients was carried out to evaluate the necessity for a high dose of contrast material in addition to delayed computed tomographic (CT) scanning for optimal detection of the lesions of multiple sclerosis in the brain. In patients with either clinically definite multiple sclerosis or laboratory-supported definite multiple sclerosis, CT scans were obtained with a uniform protocol. Lesions consistent with multiple sclerosis were demonstrated on the second scan in 54 patients. In 36 of these 54 patients, the high-dose delayed scan added information. These results are quite similar to those of a previous study from this institution using different patients, in whom the second scan was obtained immediately after the bolus injection of contrast material containing 40 g of organically bound iodine. The lack of real difference in the results of the two studies indicate that the increased dose, not just the delay in scanning, is necessary for a proper study.

  13. High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma

    PubMed Central

    Seo, Min-Seok; Kim, Ja-Kyung

    2015-01-01

    We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma. PMID:26256994

  14. Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

    PubMed Central

    Li, Chun-Xia; Patel, Sudeep; Wang, Danny JJ; Zhang, Xiaodong

    2014-01-01

    The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of isoflurane resulted in significant increase in the mean CBF of the global, cortical, subcortical regions and the regional CBF in all subcortical structures and most cortical structures (such as motor cortex, anterior cingulate cortex, but not media prefrontal cortex). In addition, the changes of regional CBF in the affected regions correlated linearly with increasing isoflurane concentrations. The study demonstrates region specific CBF abnormal increase in adult macaque monkeys under high dose (2%) isoflurane and suggests the brain functionality in corresponding structures may be affected and need to be taken consideration in either human or non-human primate neuroimaging studies. PMID:24890304

  15. Precipitate behavior in self-ion irradiated stainless steels at high doses

    NASA Astrophysics Data System (ADS)

    Jiao, Z.; Was, G. S.

    2014-06-01

    To study radiation-induced precipitation at high doses, solution annealed 304L SS and cold worked 316 SS were irradiated to 46 and 260 dpa at 380 °C using 5 MeV Fe++ and the radiation-induced precipitates were examined using atom probe tomography. Ni/Si-rich clusters were observed in all examined conditions. G-phase precipitates were observed in 316 SS at 46 dpa but only appeared in 304L SS at 260 dpa. Using the neutron irradiation to 46 dpa at 320 °C as a reference, the temperature shift for cold worked 316 SS appeared to be smaller than that of solution annealed 304L SS, probably due to the high density of dislocations, which served as defect sinks and mitigated the effect of high dose rate.

  16. Spatially resolved measurement of high doses in microbeam radiation therapy using samarium doped fluorophosphate glasses

    SciTech Connect

    Okada, Go; Morrell, Brian; Koughia, Cyril; Kasap, Safa; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean

    2011-09-19

    The measurement of spatially resolved high doses in microbeam radiation therapy has always been a challenging task, where a combination of high dose response and high spatial resolution (microns) is required for synchrotron radiation peaked around 50 keV. The x-ray induced Sm{sup 3+}{yields} Sm{sup 2+} valence conversion in Sm{sup 3+} doped fluorophosphates glasses has been tested for use in x-ray dosimetry for microbeam radiation therapy. The conversion efficiency depends almost linearly on the dose of irradiation up to {approx}5 Gy and saturates at doses exceeding {approx}80 Gy. The conversion shows strong correlation with x-ray induced absorbance of the glass which is related to the formation of phosphorus-oxygen hole centers. When irradiated through a microslit collimator, a good spatial resolution and high ''peak-to-valley'' contrast have been observed by means of confocal photoluminescence microscopy.

  17. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  18. Effect of high doses of gamma radiation on the functional characteristics of amniotic membrane

    NASA Astrophysics Data System (ADS)

    Singh, Rita; Purohit, Sumita; Chacharkar, M. P.

    2007-06-01

    The effect of different doses of gamma radiation viz. 25, 36 and 50 kGy on the chemical and functional characteristics of the amniotic membrane was studied. The change in the chemical structure of amniotic membranes at high doses of gamma irradiation was evaluated by means of Infrared (IR) Spectroscopy. The degradation of amnion on irradiation with gamma rays could produce a relative variation in IR absorption troughs. This kind of variation was absent in the samples irradiated to doses of 25, 36 and 50 kGy indicating no qualitative change in the material property of amnion. No significant differences in the water absorption capacity and water vapour transmission rate of amniotic membranes irradiated to different doses were observed. Impermeability of the amniotic membranes to different microorganisms was also not affected at high doses of gamma radiation. Gamma irradiation at doses of 25-50 kGy did not evoke undesirable changes in the functional properties of the amniotic membrane.

  19. Severe Refractory Immune Thrombocytopenia Successfully Treated with High-Dose Pulse Cyclophosphamide and Eltrombopag

    PubMed Central

    Anwer, Faiz; Yun, Seongseok; Nair, Anju; Ahmad, Yusuf; Krishnadashan, Ravitharan; Deeg, H. Joachim

    2015-01-01

    Severe refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D) immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag. PMID:26180646

  20. Severe Refractory Immune Thrombocytopenia Successfully Treated with High-Dose Pulse Cyclophosphamide and Eltrombopag.

    PubMed

    Anwer, Faiz; Yun, Seongseok; Nair, Anju; Ahmad, Yusuf; Krishnadashan, Ravitharan; Deeg, H Joachim

    2015-01-01

    Severe refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D) immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag. PMID:26180646

  1. Is Heparin Effective for the Controlled Delivery of High-Dose Bone Morphogenetic Protein-2?

    PubMed

    Kim, Ri Youn; Lee, Beomseok; Park, Si-Nae; Ko, Jae-Hyung; Kim, In Sook; Hwang, Soon Jung

    2016-05-01

    Sustained release of bone morphogenetic protein (BMP)-2 by heparin-contained biomaterials is advantageous for bone tissue regeneration using low-dose BMP-2. However, its effect with high-dose BMP-2 is still unclear and should be clarified considering the clinical use of a high dose of BMP-2 in spine and oral surgery. This study aimed to evaluate the efficacy of a heparin-conjugated collagen sponge (HCS) with high-dose BMP-2 delivery by investigating in vivo initial osteogenic regulation and bone healing over 12 weeks in comparison with that of an absorbable collagen sponge (ACS). The in vitro BMP-2 release profile in the HCS exhibited a lower burst followed by a sustained release of BMP-2, whereas that of the ACS showed an initial burst phase only. As a result of a lower burst, the HCS-BMP group showed higher expression of bone-forming/resorbing markers and enhanced activation of osteoclasts than the ACS-BMP group within the scaffold of defect after 7 days, which is presumed to be because of retention of relatively higher amounts of BMP-2. However, the surrounding calvariae were less resorbed in the HCS-BMP group, compared with the aggressive resorptive response in the ACS-BMP group. Microcomputed tomography and histology revealed that HCS-BMP guided more effective bone regeneration of central defect over time inducing minor ossification at the defect exterior, whereas ACS-BMP exhibited excessive ossification at the defect exterior. These results showed that HCS-mediated BMP-2 delivery at a high dose has advantages over ACS, including less early resorption of surrounding bone tissue and higher efficacy in compact bone regeneration over a longer period, highlighting a clinical feasibility of this technology. PMID:27098389

  2. Prescriptions of dialysate potassium concentration during short daily or long nocturnal (high dose) hemodialysis.

    PubMed

    Leypoldt, John K; Agar, Baris U; Bernardo, Angelito A; Culleton, Bruce F

    2016-04-01

    The prescription of dialysate potassium concentration during short daily and long nocturnal (high dose) hemodialysis (HD) is challenging due to limited clinical experience with such modalities. The aim here is to propose a quantitative approach for prescribing dialysate potassium concentrations during high-dose HD. Potassium kinetic parameters based on a pseudo one-compartment model from 547 patients participating in the HEMO Study were used for prediction purposes in this study. Patients were categorized based on the prescribed dialysate potassium concentration during thrice weekly HD as 1K (mean of 1.02 mEq/L, N = 60), 2K (2.01 mEq/L, N = 437), or 3K (3.01 mEq/L, N = 50). Dialysate potassium concentrations were then predicted for each patient during short daily and long nocturnal HD based on a pseudo one-compartment model to maintain the identical weekly dialytic potassium removal and predialysis serum potassium concentration as during thrice weekly HD. Predicted prescribed dialysate potassium concentrations for short daily HD were 0.18-0.45 mEq/L higher than during thrice weekly HD but were approximately 4 (3.72-4.26) mEq/L for all patients during long nocturnal HD. The intradialytic decrease in serum potassium concentration was predicted to be reduced by more than one-half during short daily HD and by approximately three-quarters during long nocturnal HD of that during thrice weekly HD. Prescribed dialysate potassium concentration during high-dose HD modalities can be quantitatively predicted using a pseudo one-compartment kinetic model. High-dose HD modalities may improve clinical outcomes by reducing intradialytic decreases in serum potassium. PMID:26179136

  3. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer*

    PubMed Central

    Pellizzon, Antônio Cássio Assis

    2016-01-01

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. PMID:27403021

  4. A dosimetric study on the Ir-192 high dose rate flexisource.

    PubMed

    Granero, D; Pérez-Calatayud, J; Casal, E; Ballester, F; Venselaar, J

    2006-12-01

    In this work, the dose rate distribution of a new Ir-192 high dose rate source (Flexisource used in the afterloading Flexitron system, Isodose Control, Veenendaal, The Netherlands) is studied by means of Monte Carlo techniques using the GEANT4 code. The dosimetric parameters of the Task Group No. 43 Report (TG43) formalism and two-dimensional rectangular look-up tables have been obtained. PMID:17278809

  5. A dosimetric study on the Ir-192 high dose rate Flexisource

    SciTech Connect

    Granero, D.; Perez-Calatayud, J.; Casal, E.; Ballester, F.; Venselaar, J.

    2006-12-15

    In this work, the dose rate distribution of a new Ir-192 high dose rate source (Flexisource used in the afterloading Flexitron system, Isodose Control, Veenendaal, The Netherlands) is studied by means of Monte Carlo techniques using the GEANT4 code. The dosimetric parameters of the Task Group No. 43 Report (TG43) formalism and two-dimensional rectangular look-up tables have been obtained.

  6. Enhanced lipid accumulation of photoautotrophic microalgae by high-dose CO2 mimics a heterotrophic characterization.

    PubMed

    Sun, Zhilan; Dou, Xiao; Wu, Jun; He, Bing; Wang, Yuancong; Chen, Yi-Feng

    2016-01-01

    Microalgae possess higher photosynthetic efficiency and accumulate more neutral lipids when supplied with high-dose CO2. However, the nature of lipid accumulation under conditions of elevated CO2 has not been fully elucidated so far. We now revealed that the enhanced lipid accumulation of Chlorella in high-dose CO2 was as efficient as under heterotrophic conditions and this may be attributed to the driving of enlarged carbon source. Both photoautotrophic and heterotrophic cultures were established by using Chlorella sorokiniana CS-1. A series of changes in the carbon fixation, lipid accumulation, energy conversion, and carbon-lipid conversion under high-dose CO2 (1-10%) treatment were characterized subsequently. The daily carbon fixation rate of C. sorokiniana LS-2 in 10% CO2 aeration was significantly increased compared with air CO2. Correspondingly, double oil content (28%) was observed in 10% CO2 aeration, close to 32.3% produced under heterotrophic conditions. In addition, with 10% CO2 aeration, the overall energy yield (Ψ) in Chlorella reached 12.4 from 7.3% (with air aeration) because of the enhanced daily carbon fixation rates. This treatment also improved the energetic lipid yield (Ylipid/Es) with 4.7-fold, tending to the heterotrophic parameters. More significantly, 2.2 times of carbon-lipid conversion efficiency (ηClipid/Ctotal, 42.4%) was observed in 10% CO2 aeration, towards to 53.7% in heterotrophic cultures, suggesting that more fixed carbon might flow into lipid synthesis under both 10% CO2 aeration and heterotrophic conditions. Taken together, all our evidence showed that 10% CO2 may push photoautotrophic Chlorella to display heterotrophic-like efficiency at least in lipid production. It might bring us an efficient model of lipid production based on microalgal cells with high-dose CO2, which is essential to sustain biodiesel production at large scales. PMID:26712624

  7. Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women.

    PubMed

    Ohtsu, T; Fujii, H; Wakita, H; Igarashi, T; Itoh, K; Imoto, S; Kohagura, M; Sasaki, Y

    1998-01-01

    The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P < 0.01). Liver dysfunction (n = 5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (< 10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view. PMID:9619751

  8. Effectiveness of once-daily high-dose ACTH for infantile spasms.

    PubMed

    Hodgeman, Ryan M; Kapur, Kush; Paris, Ann; Marti, Candice; Can, Afra; Kimia, Amir; Loddenkemper, Tobias; Bergin, Ann; Poduri, Annapurna; Libenson, Mark; Lamb, Nathan; Jafarpour, Saba; Harini, Chellamani

    2016-06-01

    There is insufficient evidence to recommend a specific protocol for treatment of infantile spasms (IS) and a lack of standardization among, and even within, institutions. Twice-daily dosing (for the first two weeks) of high-dose natural ACTH for IS is used by many centers and recommended by the National Infantile Spasms Consortium (NISC). Conversely, it is our practice to use once-daily dosing of high-dose natural ACTH for IS. In order to determine the effectiveness of our center's practice, we retrospectively reviewed 57 cases over the past four years at Boston Children's Hospital (BCH). We found that 70% of infants were spasm-free at 14days from ACTH initiation and 54% continued to be spasm-free at 3-month follow-up. Electroencephalogram showed resolution of hypsarrhythmia (when present on the pretreatment EEG) in all responders. Additionally, once-daily dosing of ACTH was well tolerated. We performed a meta-analysis to compare our results against the reports of published literature using twice-daily high-dose ACTH for treatment of IS. The meta-analysis revealed that our results were comparable to previously published outcomes using twice-daily ACTH administration for IS treatment. Our experience shows that once-daily dosing of ACTH is effective for treatment of IS. If larger prospective trials can confirm our findings, it would obviate the need for additional painful injections, simplify the schedule, and support a universal standardized protocol. PMID:27084976

  9. Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation

    SciTech Connect

    Speiser, B.L. ); Spratling, L.

    1993-03-15

    The purpose of the study was to describe a new clinical entity observed in follow-up bronchoscopies in patients who were treated with high dose rate and medium dose rate remote afterloading brachytherapy of the tracheobronchial tree. Patients were treated by protocol with medium dose rate, 47 patients receiving 1000 cGy at a 5 mm depth times three fractions, high dose rate 144 patients receiving 1000 cGy at a 10 mm depth for three fractions and high dose rate 151 patients receiving cGy at a 10 mm depth for three fractions followed by bronchoscopy. Incidence of this entity was 9% for the first group, 12% for the second, and 13% for the third group. Reactions were grade 1 consisting of mild inflammatory response with a partial whitish circumferential membrane in an asymptomatic patient; grade 2, thicker complete white circumferential membrane with cough and/or obstructive problems requiring intervention; grade 3, severe inflammatory response with marked membranous exudate and mild fibrotic reaction; and grade 4 a predominant fibrotic reaction with progressive stenosis. Variables associated with a slightly increased incidence of radiation bronchitis and stenosis included: large cell carcinoma histology, curative intent, prior laser photoresection, and/or concurrent external radiation. Survival was the strongest predictor of the reaction. Radiation bronchitis and stenosis is a new clinical entity that must be identified in bronchial brachytherapy patients and treated appropriately. 23 refs., 3 figs., 7 tabs.

  10. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    PubMed Central

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  11. Delayed activation of human microglial cells by high dose ionizing radiation.

    PubMed

    Chen, Hongxin; Chong, Zhao Zhong; De Toledo, Sonia M; Azzam, Edouard I; Elkabes, Stella; Souayah, Nizar

    2016-09-01

    Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation-induced degenerative outcomes. We therefore investigated the effects of γ-irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 γ rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of γ rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1α, IL-10 and TNFα. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of γ rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia. PMID:27265419

  12. Monitoring performance of the cameras under the high dose-rate gamma ray environments.

    PubMed

    Cho, Jai Wan; Choi, Young Soo; Jeong, Kyung Min

    2014-05-01

    CCD/CMOS cameras, loaded on a robot system, are generally used as the eye of the robot and monitoring unit. A major problem that arises when dealing with images provided by CCD/CMOS cameras under severe accident situations of a nuclear power plant is the presence of speckles owing to the high dose-rate gamma irradiation fields. To use a CCD/CMOS camera as a monitoring unit in a high radiation area, the legibility of the camera image in such intense gamma-radiation fields should therefore be defined. In this paper, the authors describe the monitoring index as a figure of merit of the camera's legibleness under a high dose-rate gamma ray irradiation environment. From a low dose-rate (10 Gy h) to a high dose-rate (200 Gy h) level, the legible performances of the cameras owing to the speckles are evaluated. The numbers of speckles generated by gamma ray irradiation in the camera image are calculated by an image processing technique. The legibility of the sensor indicator (thermo/hygrometer) owing to the number of speckles is also presented. PMID:24667385

  13. High-dose MVCT image guidance for stereotactic body radiation therapy

    SciTech Connect

    Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.; Chao, Edward; Lucas, Dan; Flynn, Ryan T.; Miften, Moyed

    2012-08-15

    Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a

  14. NEONATAL LOW- AND HIGH-DOSE EXPOSURE TO ESTRADIOL BENZOATE IN THE MALE RAT: I. EFFECTS ON THE PROSTATE GLAND

    EPA Science Inventory

    Neonatal Low- And High-Dose Exposure To Estradiol Benzoate In The Male Rat: 1. Effects On The Prostate Gland. Oliver Putz, Christian B. Schwartz, Steve Kim, Gerald A. LeBlanc Ralph L. Cooper, Gail S. Prins

    ABSTRACT
    Brief exposure of rats to high doses of natural estro...

  15. Preventing bovine mastitis by a postmilking teat disinfectant containing acidified sodium chlorite.

    PubMed

    Hillerton, J E; Cooper, J; Morelli, J

    2007-03-01

    A split-herd study was performed to determine if an acidified, sodium chlorite teat disinfectant, UDDERgold Platinum Germicidal Barrier Teat Dip (UG Pt, Ecolab Inc., Redmond, WA), was effective in preventing new intramammary infections (IMI) in lactating dairy cows compared with a licensed, iodophor teat disinfectant (Iosan, Novartis Animal Health, Ltd., Whittlesford, UK), and to show that the test product was tolerated equally well by teat skin. The study lasted 114 d and covered all weather conditions. The teats of 176 cows were dipped after each milking in UG Pt and the teats of 172 cows were dipped in Iosan, the positive-control product. Routine milk samples were taken from each quarter of every cow every 4 wk. Additional samples were taken from newly calved cows joining the trial and from cows with clinical signs of mastitis. Milk samples were cultured for the presence of bacteria and the cause of clinical mastitis. Each quarter was eligible for only 1 infection during the trial. The number of clinical cases was identical in each group (n = 13) and the number of subclinical infections was slightly lower in the UG Pt group than in the Iosan group (n = 27 and 31, respectively). These rates of infection suggest that the products did not differ in their ability to prevent a new IMI. At least 203 cows were assessed for skin integrity before the start of the trial and every 28 d throughout. The UG Pt teat dip had no adverse effects on teat condition. The prevalence of hyperkeratosis did not change with time for both groups (0.90 +/- 1.08 and 0.95 +/- 1.06 at wk 0 vs. 0.65 +/- 0.87 and 0.49 +/- 0.74 at wk 16 for fore and hind teats, respectively, for UG Pt and 1.02 +/- 1.25 and 1.16 +/- 1.11 at wk 0 vs. 0.51 +/- 0.71 and 0.45 +/- 0.65 at wk 16, respectively, for Iosan); no redness of the skin was observed in either group. Application of recommended statistical methods to demonstrate noninferiority was problematic. PMID:17297095

  16. Understanding the roles of strictly conserved tryptophan residues in O2 producing chlorite dismutases

    PubMed Central

    Blanc, Beatrice; Rodgers, Kenton R.

    2013-01-01

    The chlorite dismutases (Clds) degrade ClO2− to O2 and Cl− in perchlorate respiring bacteria, and they serve still poorly defined cellular roles in other diverse microbes. These proteins share 3 highly conserved Trp residues, W155, W156, and W227, on the proximal side of the heme. The Cld from Dechloromonas aromatica (DaCld) has been shown to form protein-based radicals in its reactions with ClO2− and peracetic acid. The roles of the conserved Trp residues in radical generation and in enzymatic function were assessed via spectroscopic and kinetic analysis of their Phe mutants. The W155F mutant was the most dramatically affected, appearing to lose the characteristic pentameric oligomerization state, secondary structure, and heme binding properties of the WT protein. The W156F mutant initially retains many features of the WT protein but over time acquires many of the features of W155F. Conversion to an inactive, heme-free form is accelerated by dilution, suggesting loss of the protein’s pentameric state. Hence, both W155 and W156 are important for heme binding and maintenance of the protein’s reactive pentameric structure. W227F by contrast retains many properties of the WT protein. Important differences are noted in the transient kinetic reactions with peracetic acid (PAA), where W227F appears to form an [Fe(IV)=O]-containing intermediate, which subsequently converts to an uncoupled [Fe(IV)=O + AA+.] system in a [PAA]-dependent manner. This is in contrast to the peroxidase-like formation of [Fe(IV)=O] coupled to a porphyrin π-cation radical in the WT protein, which decays in a [PAA]-independent manner. These observations and the lack of redox protection for the heme in any of the Trp mutants suggests a tendency for protein radical formation in DaCld that is independent of any of these conserved active site residues. PMID:23241559

  17. Chlorite dissolution rates under CO2 saturated conditions from 50 to 120 °C and 120 to 200 bar CO2

    NASA Astrophysics Data System (ADS)

    Black, Jay R.; Haese, Ralf R.

    2014-01-01

    Chlorite dissolution rates were measured in a series of batch reactor experiments testing the effect of pCO2, pH, chloride and bicarbonate concentrations and temperature. Chlorite is an important diagenetic mineral in sedimentary basins, often found cementing mineral grains and filling pore space in formations that may serve as reservoirs for storing carbon dioxide. Conflicting reports of whether chlorite acts as a barrier to reservoir rock reactivity or leads to enhanced porosity due to dissolution, after the injection of supercritical CO2 into a reservoir, makes studying the reactivity of chlorite in contact with CO2 saturated waters pertinent. Measured dissolution rates were initially rapid and decreased over time as the saturation state of solution relative to chlorite increased. Temperature had the strongest effect on dissolution rate, with an apparent activation energy of 16 ± 0.5 kJ mol-1 and rate constant of log k0 = -9.56 ± 0.07 mol m-2 s-1 assuming a rate law of the form: rate = k0exp(-EA/RT). The apparent activation energy is lower than previously accepted values, but is consistent with a study of chlorite dissolution using flow through techniques (Smith et al., 2013). Mineral dissolution rates are typically proton enhanced, but the lack of a significant pH effect or pCO2 effect on chlorite dissolution rate in this study suggests that the use of NaHCO3 to buffer the pH of CO2 saturated solutions led to an inhibition of mineral dissolution in competition with the expected pH effect. This is supported by the observed dissolution rate increasing dramatically (half a log unit) with the use of an organic acid buffer (KHpthalate) under CO2 free conditions. The effect of chloride (NaCl ∼5 to 50 g/L) was found not to affect the dissolution rate of chlorite. Various empirical rate laws are proposed and fit to the data and lead to the development of a surface complex model describing proton promoted dissolution and bicarbonate inhibition of chlorite

  18. High-dose Extended-Field Irradiation and High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Cervical Cancer With Positive Para-Aortic Lymph Nodes

    SciTech Connect

    Kim, Young Seok; Kim, Jong Hoon; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Choi, Eun Kyung

    2009-08-01

    Purpose: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. Methods and Materials: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). Results: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. Conclusion: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

  19. High-Dose Oral Ibuprofen in Treatment of Patent Ductus Arteriosus in Full-Term Neonates

    PubMed Central

    Pourarian, Shahnaz; Rezaie, Mehrdad; Amoozgar, Hamid; Shakiba, Ali-Mohammad; Edraki, Mohammad-Reza; Mehdizadegan, Nima

    2015-01-01

    Background: Patent ductus arteriosus (PDA) is an important risk for heart failure due to left to right shunt in term neonates. Objectives: In this study, we evaluated the effect of high dose ibuprofen in closure of PDA in term neonates. Patients and Methods: We used double dose ibuprofen (20 mg/kg, 10 mg/kg, and 10 mg/kg) for 3 - 30 day old term neonates with PDA who were admitted in the neonatal wards of Shiraz University of Medical Sciences. The results of this study were compared to the data of the previous study in our center which used the low dose of ibuprofen (10 mg/kg, 5 mg/kg, and 5 mg/kg). Results: 29 full term neonates received high-dose ibuprofen, in 18 neonates, PDA was closed after 4 days (62.1% versus 43.3% for the standard dose and 4.7% for the control group in the previous study) (P = 0.001). The results showed no significant correlation between the closure rate and gestational age, postnatal age, sex, and weight. In the 4th day of treatment, size of the pulmonic end of ductus arteriosus decreased from 2.09 mm to 0.77 mm compared to 1.68 mm to 0.81 mm in the standard dose of oral ibuprofen and 2.1 mm to 1.4 mm in the control group (P = 0.046). Conclusions: This study indicated that high-dose oral ibuprofen was more effective in closing or decreasing the size of PDA. PMID:26396694

  20. Severe complications of ulcerative colitis after high-dose prednisolone and azathioprine treatment.

    PubMed

    Matsuda, K; Watanabe, T; Abo, Y; Uchida, H; Kawamura, Y J; Masaki, T; Muto, T

    1999-06-01

    We report a rare case of ulcerative colitis (UC) associated with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections in multiple organs, and with compressive fracture from osteoporosis after the administration of high-dose prednisolone and azathioprine. A 25-year-old man had been treated with high-dose prednisolone for UC. He suddenly experienced severe lumbago, which prevented him from walking. Plain X-ray demonstrated compressive fractures of the thoracic and the lumbar vertebrae, which were thought to be due to osteoporosis as a side effect of the high-dose prednisolone. At this admission, in another hospital, he also had a bloody discharge from the rectum, and azathioprine was started; however, the patient's condition still did not show any improvement. The total doses of azathioprine and prednisolone he had received were 3150 mg and more than 15,000 mg, respectively. Considering the presence of the serious complications, surgical intervention was the treatment selected. Culture study revealed MRSA in the feces and nasal cavity, and P. aeruginosa in the feces and urine. Vancomycin hydrochloride and gentamicin were administered, and were effective, with a subsequent negative culture study. Subtotal colectomy with mucus fistula was performed. After the operation, culture studies remained negative. Major steroid side effects such as bone fracture and osteoporosis should be considered as an indication for surgery in UC patients. MRSA and P. aeruginosa are a menace, especially for UC immunosuppressed patients on steroid or immunosuppressive therapy. When these bacteria are detected, there should be prompt and adequate antimicrobial therapy against the organisms and the immunosuppressive therapy should be immediately discontinued. We conclude that surgical therapy should be considered in the earlier stage for patients with intractable UC, rather than continuing long-term administration of steroid or azathioprine, which may lead to

  1. Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

    PubMed Central

    Carter, Lawrence P.; Reissig, Chad J.; Johnson, Matthew W.; Klinedinst, Margaret A.; Griffiths, Roland R.

    2012-01-01

    BACKGROUND Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours. RESULTS Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse. PMID:22989498

  2. Comparison of Two High-Dose Magnesium Infusion Regimens in the Treatment of Status Asthmaticus

    PubMed Central

    Vaiyani, Danish

    2016-01-01

    OBJECTIVES: To determine the feasibility and safety of a simplified high-dose magnesium sulfate infusion (sHDMI) for the treatment of status asthmaticus. METHODS: We retrospectively compared 2 different high-dose magnesium sulfate infusion regimens, as adjunctive treatment in status asthmatics, using data that were preciously collected. The initial high-dose, prolonged magnesium infusion (HDMI) regimen consisted of a loading dose of 75 mg/kg (weight ≤ 30 kg) or 50 mg/kg (weight > 30 kg) over a period of 30 to 45 minutes followed by a continuous infusion of 40 mg/kg/hr for an additional 4 hours. This was compared to the sHDMI regimen that consisted of 50 mg/kg/hr for 5 hours. No loading dose was given to the patients in the sHDMI arm. Obese patients were dosed by using ideal body weight. Physiologic parameters (i.e., heart rate, blood pressure, respiratory rate, oxygen saturation) and serum magnesium (SrMg) concentrations were monitored during administration of magnesium sulfate. RESULTS: Nineteen patients receiving the initial HDMI regimen were compared with 10 patients who received the sHDMI regimen. There was no significant difference in SrMg concentrations or physiologic parameters between the 2 dose regimens. CONCLUSIONS: The HDMI and sHDMI regimens both produced SrMg concentrations that are associated with bronchodilation. The safety profile was also similar for the 2 regimens. The unambiguity of sHDMI has the potential to reduce medication errors that are associated with calculation of the loading dose, product preparation, and ultimate administration. PMID:27453701

  3. Patients treated with high-dose intravenous immunoglobulin show selective activation of regulatory T cells

    PubMed Central

    Tjon, A S W; Tha-In, T; Metselaar, H J; van Gent, R; van der Laan, L J W; Groothuismink, Z M A; te Boekhorst, P A W; van Hagen, P M; Kwekkeboom, J

    2013-01-01

    Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (Tregs) in humans in vivo. Blood was collected from IVIg-treated patients with immunodeficiency or autoimmune disease who were treated with low-dose (n = 12) or high-dose (n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4+CD25+forkhead box protein 3 (FoxP3+) Tregs and of conventional CD4+FoxP3− T-helper cells (Tconv) were measured. The suppressive capacity of Tregs purified from blood collected at the time-points indicated was determined in an ex-vivo assay. High-dose, but not low-dose, IVIg treatment enhanced the activation status of circulating Tregs, as shown by increased FoxP3 and human leucocyte antigen D-related (HLA-DR) expression, while numbers of circulating Tregs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified Tregs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of Tconv was not affected by IVIg. We conclude that high-dose IVIg treatment activates Tregs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders. PMID:23607448

  4. Single high-dose vs. fractionated radiotherapy: Effects on plant growth rates

    PubMed Central

    Guedea, Marc; Castel, Antoni; Arnalte, Marc; Mollera, Alex; Muñoz, Victor; Guedea, Ferran

    2013-01-01

    Aim To evaluate the differential effects of fractionated vs. high-dose radiotherapy on plant growth. Background Interest in hypofractionated radiotherapy has increased substantially in recent years as tumours (especially of the lung, prostate, and liver) can be irradiated with ever greater accuracy due to technological improvements. The effects of low-dose ionizing radiation on plant growth have been studied extensively, yet few studies have investigated the effect of high-dose, hypofractionated radiotherapy on plant growth development. Materials and methods A total of 150 plants from the genus Capsicum annuum were randomized to receive fractionated radiotherapy (5 doses of 10 Gy each), single high-dose (SHD) radiotherapy (single 50 Gy dose), or no radiotherapy (control group). Irradiation was delivered via linear accelerator and all samples were followed daily for 26 days to assess and compare daily growth. Results On day 26, plants in the control, fractionated, and SHD groups had grown to a mean height of 7.55 cm, 4.32 cm, and 2.94 cm, respectively. These differences in overall growth were highly significant (P = 0.005). The SHD group showed the least amount of growth. Conclusions SHD effectively stunts plant growth and development. Despite the evident differences between plant and animal cells, ionizing radiation is believed to work in a similar manner in all biological cells. These findings highlight the need to continue investigating the use of hypofractionated schemes in humans to improve cancer treatment outcomes. PMID:24416565

  5. The Effect of High Dose Radioiodine Therapy on Formation of Radiation Retinopathy During Thyroid Cancer Treatment

    PubMed Central

    Kaçar Güveli, Tülay; Özkan, Sezer; Öner Tamam, Müge; Uyanık, Ercan; Ediz, Nurcan; Mülazımoğlu, Mehmet; Özpaçacı, Tevfik

    2014-01-01

    Objective: Non-thyroidal complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Methods: Forty eyes of 20 patients (3 male, 17 female) who received 250-1000 mCi during 131I therapy and on ophthalmological follow up for a year after the last treatment were included in the study. Mean age of the study group was 50 years (range 25-70 years). In ophthalmologic examination, visual acuity was measured in order to determine visual loss. Intraocular pressure was measured in all the patients. Then lens examination was carried out with slit lamp biomicroscopy in order to investigate cataract or partial lens opacities. Fundus observation was carried out through the dilated pupil with slit lamp biomicroscopy using 90 D noncontact lens. Result: The best corrected visual aquity with Snellen chart was found as 1.0 in 36 eyes (90%) and between 0.6 and 0.9 (10%) in 4 eyes (10%). At the biomicroscopic fundus examination, retinal hemorrhage consistent with radiation retinopathy, microaneurysm, microinfarction, edema or exudation, vitreus hemorrhage, partial or total optical disc pallor indicating papillopathy in the optic disc were not observed in any of the eyes. Conclusion: This result indicates that there is not any significant correlation between repeated high-dose radioiodine therapy and radiation retinopathy in differentiated thyroid carcinomas. Even though there is not a significant restriction in use of higher doses of radioiodine therapy in differentiated thyroid carcinoma, more extensive studies are needed in order to obtain more accurate data on possible occurrence of retinopathy. PMID:25541931

  6. High-Dose Enalapril Treatment Reverses Myocardial Fibrosis in Experimental Uremic Cardiomyopathy

    PubMed Central

    Tyralla, Karin; Adamczak, Marcin; Benz, Kerstin; Campean, Valentina; Gross, Marie-Luise; Hilgers, Karl F.; Ritz, Eberhard; Amann, Kerstin

    2011-01-01

    Aims Patients with renal failure develop cardiovascular alterations which contribute to the higher rate of cardiac death. Blockade of the renin angiotensin system ameliorates the development of such changes. It is unclear, however, to what extent ACE-inhibitors can also reverse existing cardiovascular alterations. Therefore, we investigated the effect of high dose enalapril treatment on these alterations. Methods Male Sprague Dawley rats underwent subtotal nephrectomy (SNX, n = 34) or sham operation (sham, n = 39). Eight weeks after surgery, rats were sacrificed or allocated to treatment with either high-dose enalapril, combination of furosemide/dihydralazine or solvent for 4 weeks. Heart and aorta were evaluated using morphometry, stereological techniques and TaqMan PCR. Results After 8 and 12 weeks systolic blood pressure, albumin excretion, and left ventricular weight were significantly higher in untreated SNX compared to sham. Twelve weeks after SNX a significantly higher volume density of cardiac interstitial tissue (2.57±0.43% in SNX vs 1.50±0.43% in sham, p<0.05) and a significantly lower capillary length density (4532±355 mm/mm3 in SNX vs 5023±624 mm/mm3 in sham, p<0.05) were found. Treatment of SNX with enalapril from week 8–12 significantly improved myocardial fibrosis (1.63±0.25%, p<0.05), but not capillary reduction (3908±486 mm/mm3) or increased intercapillary distance. In contrast, alternative antihypertensive treatment showed no such effect. Significantly increased media thickness together with decreased vascular smooth muscles cell number and a disarray of elastic fibres were found in the aorta of SNX animals compared to sham. Both antihypertensive treatments failed to cause complete regression of these alterations. Conclusions The study indicates that high dose ACE-I treatment causes partial, but not complete, reversal of cardiovascular changes in SNX. PMID:21298056

  7. High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

    PubMed

    Cocorocchio, E; Peccatori, F; Vanazzi, A; Piperno, G; Calabrese, L; Botteri, E; Travaini, L; Preda, L; Martinelli, G

    2013-03-01

    High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL. PMID:22473680

  8. High-Dose Fluoride Impairs the Properties of Human Embryonic Stem Cells via JNK Signaling

    PubMed Central

    Fu, Xin; Xie, Fang-Nan; Dong, Ping; Li, Qiu-Chen; Yu, Guang-Yan; Xiao, Ran

    2016-01-01

    Fluoride is a ubiquitous natural substance that is often used in dental products to prevent dental caries. The biphasic actions of fluoride imply that excessive systemic exposure to fluoride can cause harmful effects on embryonic development in both animal models and humans. However, insufficient information is available on the effects of fluoride on human embryonic stem cells (hESCs), which is a novel in vitro humanized model for analyzing the embryotoxicities of chemical compounds. Therefore, we investigated the effects of sodium fluoride (NaF) on the proliferation, differentiation and viability of H9 hESCs. For the first time, we showed that 1 mM NaF did not significantly affect the proliferation of hESCs but did disturb the gene expression patterns of hESCs during embryoid body (EB) differentiation. Higher doses of NaF (2 mM and above) markedly decreased the viability and proliferation of hESCs. The mode and underlying mechanism of high-dose NaF-induced cell death were further investigated by assessing the sub-cellular morphology, mitochondrial membrane potential (MMP), caspase activities, cellular reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs). High-dose NaF caused the death of hESCs via apoptosis in a caspase-mediated but ROS-independent pathway, coupled with an increase in the phospho-c-Jun N-terminal kinase (p-JNK) levels. Pretreatment with a p-JNK-specific inhibitor (SP600125) could effectively protect hESCs from NaF-induced cell death in a concentration- and time-dependent manner. These findings suggest that NaF might interfere with early human embryogenesis by disturbing the specification of the three germ layers as well as osteogenic lineage commitment and that high-dose NaF could cause apoptosis through a JNK-dependent pathway in hESCs. PMID:26859149

  9. Conservative surgery for low rectal carcinoma after high-dose radiation. Functional and oncologic results.

    PubMed Central

    Rouanet, P; Fabre, J M; Dubois, J B; Dravet, F; Saint Aubert, B; Pradel, J; Ychou, M; Solassol, C; Pujol, H

    1995-01-01

    OBJECTIVE: Using a prospective, nonrandomized study, the authors evaluated the morbidity and functional and oncologic results of conservative surgery for cancer of the lower third of the rectum after high-dose radiation. SUMMARY BACKGROUND DATA: Colo-anal anastomosis has made sphincter conservation for low rectal carcinoma technically feasible. The limits to conservative surgery currently are oncologic rather than technical. Adjuvant radiotherapy has proven its benefit in terms of regional control, with a dose relationship. METHODS: Since June 1990, 27 patients with distal rectal adenocarcinoma were treated by preoperative radiotherapy (40 + 20 Gy delivered with three fields) and curative surgery. The mean distance from the anal verge was 47 mm (27-57 mm), and none of the tumors were fixed (15 T2, 12 T3). RESULTS: Mortality and morbidity were not increased by high-dose preoperative radiation. Twenty-one patients underwent conservative surgery (78%-17 total proctectomies and colo-anal anastomoses, 4 trans-anal resections). After colo-anal anastomosis, all patients with colonic pouch had good results; two patients had moderate results and one patient had poor results after straight colo-anal anastomosis. With a mean follow-up of 24 months, the authors noted 1 postoperative death, 2 disease-linked deaths, 1 controlled regional recurrence, 2 evolutive patients with pulmonary metastases, and 21 disease-free patients. CONCLUSIONS: These first results confirm the possibility of conservative surgery for low rectal carcinoma after high-dose radiation. A prospective, randomized trial could be induced to determine the real role of the 20 Gy boost on the sphincter-saving decision. PMID:7826163

  10. Comparison of low and high dose ionising radiation using topological analysis of gene coexpression networks

    PubMed Central

    2012-01-01

    Background The growing use of imaging procedures in medicine has raised concerns about exposure to low-dose ionising radiation (LDIR). While the disastrous effects of high dose ionising radiation (HDIR) is well documented, the detrimental effects of LDIR is not well understood and has been a topic of much debate. Since little is known about the effects of LDIR, various kinds of wet-lab and computational analyses are required to advance knowledge in this domain. In this paper we carry out an “upside-down pyramid” form of systems biology analysis of microarray data. We characterised the global genomic response following 10 cGy (low dose) and 100 cGy (high dose) doses of X-ray ionising radiation at four time points by analysing the topology of gene coexpression networks. This study includes a rich experimental design and state-of-the-art computational systems biology methods of analysis to study the differences in the transcriptional response of skin cells exposed to low and high doses of radiation. Results Using this method we found important genes that have been linked to immune response, cell survival and apoptosis. Furthermore, we also were able to identify genes such as BRCA1, ABCA1, TNFRSF1B, MLLT11 that have been associated with various types of cancers. We were also able to detect many genes known to be associated with various medical conditions. Conclusions Our method of applying network topological differences can aid in identifying the differences among similar (eg: radiation effect) yet very different biological conditions (eg: different dose and time) to generate testable hypotheses. This is the first study where a network level analysis was performed across two different radiation doses at various time points, thereby illustrating changes in the cellular response over time. PMID:22594378

  11. High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

    PubMed

    Pandit, A K; Kumar, P; Kumar, A; Chakravarty, K; Misra, S; Prasad, K

    2016-07-01

    Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings. PMID:26647879

  12. Brain Magnetic Resonance Imaging After High-Dose Chemotherapy and Radiotherapy for Childhood Brain Tumors

    SciTech Connect

    Spreafico, Filippo Gandola, Lorenza; Marchiano, Alfonso; Simonetti, Fabio; Poggi, Geraldina; Adduci, Anna; Clerici, Carlo Alfredo; Luksch, Roberto; Biassoni, Veronica; Meazza, Cristina; Catania, Serena; Terenziani, Monica; Musumeci, Renato; Fossati-Bellani, Franca; Massimino, Maura

    2008-03-15

    Purpose: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. Methods and Materials: We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. Results: Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T{sub 1}-weighted unevenly enhancing, and T{sub 2}-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74% {+-} 6% at 1 year and 57% {+-} 8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. Conclusion: Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-a-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.

  13. Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib.

    PubMed

    Olshen, Adam; Tang, Min; Cortes, Jorge; Gonen, Mithat; Hughes, Timothy; Branford, Susan; Quintás-Cardama, Alfonso; Michor, Franziska

    2014-11-01

    Treatment with the tyrosine kinase inhibitor imatinib is the standard of care for newly diagnosed patients with chronic myeloid leukemia. In recent years, several second-generation inhibitors - such as dasatinib and nilotinib - have become available: these promise to overcome some of the mutations associated with acquired resistance to imatinib. Despite eliciting similar clinical responses, the molecular effects of these agents on different subpopulations of leukemic cells remain incompletely understood. Furthermore, the consequences of using high-dose imatinib therapy have not been investigated in detail. Here we utilized clinical data from patients treated with dasatinib, nilotinib, or high-dose imatinib, together with a statistical data analysis and mathematical modeling approach, to investigate the molecular treatment response of leukemic cells to these agents. We found that these drugs elicit very similar responses if administered front-line. However, patients display significantly different kinetics when treated second-line, both in terms of differences between front-line and second-line treatment for the same drug, and among agents when used as second-line. We then utilized a mathematical framework describing the behavior of four differentiation levels of leukemic cells during therapy to predict the treatment response kinetics for the different cohorts of patients. The dynamics of BCR-ABL1 clearance observed in our study suggest that the use of standard or high-dose imatinib or a second-generation tyrosine kinase inhibitor such as nilotinib or dasatinib elicits similar responses when administered as front-line therapy for patients with chronic myeloid leukemia in chronic phase. PMID:25216683

  14. Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib

    PubMed Central

    Olshen, Adam; Tang, Min; Cortes, Jorge; Gonen, Mithat; Hughes, Timothy; Branford, Susan; Quintás-Cardama, Alfonso; Michor, Franziska

    2014-01-01

    Treatment with the tyrosine kinase inhibitor imatinib is the standard of care for newly diagnosed patients with chronic myeloid leukemia. In recent years, several second-generation inhibitors – such as dasatinib and nilotinib – have become available: these promise to overcome some of the mutations associated with acquired resistance to imatinib. Despite eliciting similar clinical responses, the molecular effects of these agents on different subpopulations of leukemic cells remain incompletely understood. Furthermore, the consequences of using high-dose imatinib therapy have not been investigated in detail. Here we utilized clinical data from patients treated with dasatinib, nilotinib, or high-dose imatinib, together with a statistical data analysis and mathematical modeling approach, to investigate the molecular treatment response of leukemic cells to these agents. We found that these drugs elicit very similar responses if administered front-line. However, patients display significantly different kinetics when treated second-line, both in terms of differences between front-line and second-line treatment for the same drug, and among agents when used as second-line. We then utilized a mathematical framework describing the behavior of four differentiation levels of leukemic cells during therapy to predict the treatment response kinetics for the different cohorts of patients. The dynamics of BCR-ABL1 clearance observed in our study suggest that the use of standard or high-dose imatinib or a second-generation tyrosine kinase inhibitor such as nilotinib or dasatinib elicits similar responses when administered as front-line therapy for patients with chronic myeloid leukemia in chronic phase. PMID:25216683

  15. High-dose reirradiation of head and neck cancer with curative intent

    SciTech Connect

    Stevens, K.R.; Britsch, A.; Moss, W.T.

    1994-07-01

    This study evaluates the response of new or recurrent head and neck cancers and the response of associated normal tissues to high dose reirradiation with curative intent. From 1964 to 1991, 15 patients with in-field new second head and neck cancers and 85 patients with recurrent head and neck cancers have had high-dose reirradiation that overlapped with previously irradiated volumes. Reirradiation was given only to patients with no more than apparent minimal clinical radiation effects from the first radiation course. The reirradiation consisted of external beam on in 82 patients, external beam plus intracavitary or interstitial implant irradiation in 14 patients, and interstitial implant irradiation only in four patients. The combined overlapping dose from both the initial and subsequent irradiation was 69-79 Gy in 14 patients, 90-99 Gy in 15 patients, 100-1999 Gy in 27 patients, and 120 Gy or greater in 44 patients. Four patients had areas of overlap that received greater than 180 Gy. The actuarial 5-year survival was 37% for patients with new second primary cancers and 17% for patients with recurrent cancers. Loco-regional tumor control was achieved in 60% of the patients with new tumors and in 27% of the patients with recurrent tumors. Nine of the 100 patients developed severe adverse normal tissue effects from the reirradiation. High-dose reirradiation of head and neck cancers can be successful curative treatment in a significant proportion of patients. It is associated with substantial but acceptable risks in properly selected patients. 46 refs., 8 tabs.

  16. Effects of high dose intraperitoneal cytosine arabinoside on the radiation tolerance of the rat spinal cord

    SciTech Connect

    Menten, J.; Landuyt, W.; van der Kogel, A.J.; Ang, K.K.; van der Schueren, E.

    1989-07-01

    The effect of intraperitoneal high dose (9 g/kg) cytosine arabinoside (Ara-C) on the early delayed radiation response of the rat cervical spinal cord has been studied. When given 2 hrs before irradiation, systemically administered Ara-C significantly reduces the isoeffect doses for the induction of paralysis due to white matter necrosis by a factor of approximately 1.2 for both a single irradiation treatment and for a two fraction irradiation with 24 hr interval. No effect on the latency time to develop paralysis was recorded.

  17. Measurement of dosimetric parameters for the Alpha-Omega high-dose-rate Iridium-192 source

    SciTech Connect

    Muller-Runkel, R. . E-mail: renate.muller@ssfhs.org

    2005-09-30

    Thermoluminescent (TLD) measurements of dose-rate constant, anisotropy function, and radial dose function are reported for the Alpha-Omega high dose rate (HDR) Iridium-192 ({sup 192}Ir) source, which has been available since 1998 for use in the MicroSelectron HDR afterloader manufactured by the Nucletron Corporation. Measurement results are compared with published or available Monte Carlo calculations for both sources. They are found in good agreement, and, within experimental accuracy, no difference is seen in the dosimetric parameters of both sources.

  18. In vivo TLD dose measurements in catheter-based high-dose-rate brachytherapy.

    PubMed

    Adlienė, Diana; Jakštas, Karolis; Urbonavičius, Benas Gabrielis

    2015-07-01

    Routine in vivo dosimetry is well established in external beam radiotherapy; however, it is restricted mainly to detection of gross errors in high-dose-rate (HDR) brachytherapy due to complicated measurements in the field of steep dose gradients in the vicinity of radioactive source and high uncertainties. The results of in vivo dose measurements using TLD 100 mini rods and TLD 'pin worms' in catheter-based HDR brachytherapy are provided in this paper alongside with their comparison with corresponding dose values obtained using calculation algorithm of the treatment planning system. Possibility to perform independent verification of treatment delivery in HDR brachytherapy using TLDs is discussed. PMID:25809111

  19. Cation disorder determined by MAS {sup 27}Al NMR in high dose neutron irradiated spinel

    SciTech Connect

    Cooper, E.A.; Sickafus, K.E.; Hughes, C.D.; Earl, W.L.; Hollenberg, G.W.; Garner, F.A.; Bradt, R.C.

    1995-12-31

    Spinel (MgAl{sub 2}O{sub 4}) single crystals which had been neutron irradiated to high doses (53-250 dpa) were examined using {sup 27}Al magic angle spinning (MAS) nuclear magnetic resonance (NMR). The sensitivity of this procedure to a specific cation (Al) residing in different crystallographic environments allowed one to determine the distribution of the Al between the two cation sites in the spinel structure. The samples were irradiated at two different temperatures (400 and 750{degrees}C) and various doses. These results indicate that the Al was nearly fully disordered over the two lattice sites after irradiation.

  20. Persistent DNA Damage after High Dose In Vivo Gamma Exposure of Minipig Skin

    PubMed Central

    Ahmed, Emad A.; Agay, Diane; Schrock, Gerrit; Drouet, Michel; Meineke, Viktor; Scherthan, Harry

    2012-01-01

    Background Exposure to high doses of ionizing radiation (IR) can lead to localized radiation injury of the skin and exposed cells suffer dsDNA breaks that may elicit cell death or stochastic changes. Little is known about the DNA damage response after high-dose exposure of the skin. Here, we investigate the cellular and DNA damage response in acutely irradiated minipig skin. Methods and Findings IR-induced DNA damage, repair and cellular survival were studied in 15 cm2 of minipig skin exposed in vivo to ∼50 Co-60 γ rays. Skin biopsies of control and 4 h up to 96 days post exposure were investigated for radiation-induced foci (RIF) formation using γ-H2AX, 53BP1, and active ATM-p immunofluorescence. High-dose IR induced massive γ-H2AX phosphorylation and high 53BP1 RIF numbers 4 h, 20 h after IR. As time progressed RIF numbers dropped to a low of <1% of keratinocytes at 28–70 days. The latter contained large RIFs that included ATM-p, indicating the accumulation of complex DNA damage. At 96 days most of the cells with RIFs had disappeared. The frequency of active-caspase-3-positive apoptotic cells was 17-fold increased 3 days after IR and remained >3-fold elevated at all subsequent time points. Replicating basal cells (Ki67+) were reduced 3 days post IR followed by increased proliferation and recovery of epidermal cellularity after 28 days. Conclusions Acute high dose irradiation of minipig epidermis impaired stem cell replication and induced elevated apoptosis from 3 days onward. DNA repair cleared the high numbers of DBSs in skin cells, while RIFs that persisted in <1% cells marked complex and potentially lethal DNA damage up to several weeks after exposure. An elevated frequency of keratinocytes with persistent RIFs may thus serve as indicator of previous acute radiation exposure, which may be useful in the follow up of nuclear or radiological accident scenarios. PMID:22761813

  1. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    PubMed Central

    2012-01-01

    Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels. In

  2. Novel application of high-dose rate brachytherapy for severe, recalcitrant palmoplantar pustulosis.

    PubMed

    Timerman, D; Devlin, P M; Nambudiri, V E; Wright, N A; Vleugels, R A; Clark, R A; Kupper, T S; Merola, J F; Patel, M

    2016-07-01

    Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain, often limiting daily activities. We present the case of a 36-year-old man with severe PPP who had treatment failure with multiple medical therapies but showed marked improvement with high-dose rate brachytherapy. Brachytherapy has the advantage of providing a conformal dose distribution over complex curved surfaces, such as the foot and ankle. Our observations suggest that brachytherapy may be a well-tolerated treatment option for patients with severe, refractory PPP. PMID:26848819

  3. Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer

    PubMed Central

    Petsuksiri, J; Chansilpa, Y; Hoskin, P J

    2014-01-01

    Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy and brachytherapy alone. Recently, high-dose-rate brachytherapy has been used instead of low-dose-rate brachytherapy. Image-guided brachytherapy enables sufficient coverage of tumour and reduction of dose to the organs at risk, thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90–100% and 70–90%, respectively). PMID:24807067

  4. Interstitial injection in silicon after high-dose, low-energy arsenic implantation and annealing

    SciTech Connect

    Tsamis, C.; Skarlatos, D.; BenAssayag, G.; Claverie, A.; Lerch, W.; Valamontes, V.

    2005-11-14

    In this work, we investigate the interstitial injection into the silicon lattice due to high-dose, low-energy arsenic implantation. The approach consists in monitoring the diffusion of the arsenic profile as well as of the boron profile in buried {delta}-doped layers, when amounts of the as-implanted arsenic profile are removed by low-temperature wet silicon etching. The experimental results indicate that the contribution of the implantation damage to the transient enhanced diffusion of boron, and thus the interstitial injection, is not the main one. On the contrary, interstitial generation due to arsenic clustering seems to be more important for the present conditions.

  5. Germicidal activity of a chlorous acid-chlorine dioxide teat dip and a sodium chlorite teat dip during experimental challenge with Staphylococcus aureus and Streptococcus agalactiae.

    PubMed

    Boddie, R L; Nickerson, S C; Adkinson, R W

    1998-08-01

    Three postmilking teat dips were tested for efficacy against Staphylococcus aureus and Streptococcus agalactiae in two separate studies using experimental challenge procedures that were recommended by the National Mastitis Council. The first study evaluated a barrier teat dip product containing chlorous acid-chlorine dioxide as the germicidal agent, and the second study evaluated a sodium chlorite product with a barrier component as well as a sodium chlorite product without a barrier component. The chlorous acid-chlorine dioxide teat dip reduced new intramammary infections (IMI) caused by Staph. aureus by 91.5% and reduced new IMI caused by Strep. agalactiae by 71.7%. The barrier dip containing sodium chlorite reduced new IMI caused by Staph. aureus and Strep. agalactiae by 41.0 and 0%, respectively. The nonbarrier dip containing sodium chlorite reduced new IMI caused by Staph. aureus by 65.6% and reduced new IMI caused by Strep. agalactiae by 39.1%. Teat skin and teat end conditions were evaluated before and after the second study; no deleterious effects among dipped quarters compared with control quarters were noted for the two sodium chlorite products. PMID:9749396

  6. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation.

    PubMed

    Sanders, J E; Hawley, J; Levy, W; Gooley, T; Buckner, C D; Deeg, H J; Doney, K; Storb, R; Sullivan, K; Witherspoon, R; Appelbaum, F R

    1996-04-01

    Patients successfully treated with a marrow transplant often have concerns about fertility and pregnancy. This study was performed to determine pregnancy outcome among patients who had received high-dose chemotherapy alone or with total-body irradiation (TBI) and marrow transplantation for aplastic anemia or hematologic malignancy. Records of 1,326 postpubertal and 196 prepubertal patients currently more than 12 years of age after marrow transplant in Seattle from August 1971 to January 1992 were reviewed to determine the patients with normal gonadal function and pregnancies. Among 708 postpubertal women, 110 recovered normal ovarian function and 32 became pregnant. In addition, nine formerly prepubertal girls with normal gonadal function became pregnant. Among 618 postpubertal men, 157 recovered testicular function and partners of 33 became pregnant. An additional two formerly prepubertal men had partners who became pregnant. Forty-one female patients and partners of 35 male patients had 146 pregnancies after transplant. All 76 patients responded to a questionnaire requesting pregnancy history, outcome, infant birth weight, and congenital anomalies information for all clinically recognized pregnancies. There were 115 live births among 146 (79%) pregnancies. Spontaneous abortion terminated four of 56 (7%) pregnancies for 28 female cyclophosphamide (CY) recipients and six of 16 (37%) pregnancies for 13 TBI recipients (P = .02). Partners of 28 male CY recipients had four of 62 (6.4%) pregnancies terminate with spontaneous abortion, but there were no spontaneous abortions among eight pregnancies of five TBI recipients' partners. Preterm delivery occurred for eight of 44 (18%) and five of eight (63%) live births for 24 CY and eight TBI female recipients (P = .01). This 25% incidence among all female patient pregnancies is higher than the expected incidence of 8% to 10% (P = .0001). The 13 preterm deliveries resulted in 10 low birth weight ([LBW] 1.8 to 2.24 kg) and

  7. The dissolution of biotite and chlorite at 25°C in the near-neutral pH region

    NASA Astrophysics Data System (ADS)

    Malmström, Maria; Banwart, Steven; Lewenhagen, Jeanette; Duro, Lara; Bruno, Jordi

    1996-02-01

    We studied the dissolution of biotite and chlorite in laboratory systems with flow-through and batch reactors. The initial dissolution of biotite in the near-neutral pH region, under N 2(g) atmosphere is highly non-stoichiometric. A slow linear release of iron during a period of weeks indicates a surface-chemical-reaction-controlled mechanism of release for iron. The release of potassium is much faster than that of iron. A parabolic dependence of accumulated release with time suggests a diffusion-controlled mechanism of potassium release. The rates of magnesium, aluminium and silicon release are between those for potassium and iron and approach that of iron with time. There is no significant influence of (bi)carbonate or pH on biotite dissolution rate or stoichiometry in the pH region 7 < pH < 8.5. The release rates of elements from chlorite are close to stoichiometric and similar to the iron release rate from biotite. In closed batch reactors at near-basic pH the composition of test solutions in contact with biotite is apparently controlled by gibbsite (Al), kaolinite (Si) and Fe(III)-(hydr)oxide. We estimated a turn-over time (10 1-10 2 yr) for molecular oxygen and a time scale (10 months) to develop characteristic Fe(II) concentrations for a granitic groundwater.

  8. Single Molecule Investigation of Glycine-Chlorite Interaction by Cross-Correlated Scanning Probe Microscopy and Quantum Mechanics Simulations.

    PubMed

    Moro, Daniele; Ulian, Gianfranco; Valdrè, Giovanni

    2015-04-21

    In this work, we studied the interaction of glycine with the (001) surface of chlorite mineral at a single molecule level by cross-correlating scanning probe microscopy (SPM) and ab initio quantum mechanics (QM) investigations. Chlorite mineral is particularly interesting and peculiar for the interaction with organic molecules because it presents an alternated stacking of brucite-like (hydrophobic) and talc-like (hydrophilic) layers of different polarities. Brucite-like is positive, whereas talc-like is negative. The experimental atomic force microscopy (AFM) observations show that glycine is stably and selectively adsorbed on the brucite-like layer, organized in monolayers with different patterns. The sizes of single molecules of glycine measured by AFM are in agreement with those calculated by QM. Glycine molecules were found to align both at the edges and on the terraces of the brucitic surface. QM simulations confirmed the AFM observations that glycine molecule is adsorbed with high adsorption energy preferentially with its plane parallel to the (001) brucite-like surface. QM also provided the geometry conformation of the molecule and the bonding scheme between glycine and brucite surface. This kind of data can be very helpful both to biotechnological applications of this substrate and to depict some important processes that might have been occurred in prebiotic environments. PMID:25830864

  9. DC conductivity, cationic exchange capacity, and specific surface area related to chemical composition of pore lining chlorites.

    PubMed

    Henn, François; Durand, Claudine; Cerepi, Adrian; Brosse, Etienne; Giuntini, J C

    2007-07-15

    Low resistivity in argillaceous sandstone reservoirs may be attributed either to the effect of microporosity, or to specific effects due to intrinsic clays' conducting properties or to other conducting minerals. In order to distinguish these effects, cation exchange capacity, specific surface areas, and dc conductivity of various pore lining chlorite-bearing sandstones from different hydrocarbon reservoir measurements are investigated. Cation exchange capacity and specific surface area are measured on whole rocks as well as on size-separated fractions. Both sets of values are low, in agreement with the structural and textural observations. The conductivity of these chlorites, measured in air conditions and after dehydration, is investigated by means of complex impedance spectroscopy on size-separated fractions as a function of temperature and compared to that of reference clays. The results show a large influence of moisture, applied electric field frequency, and temperature on the electrical properties. The magnitude of the dehydrated clays' conductivity is such that its influence on the conductivity of argillaceous sandstone is lower than that related to the presence of water or brine by several orders of magnitude. The dc conductivity and the related activation energy of the dehydrated samples appear to be related to the chemical composition of the clays. More specifically, a clear correlation occurs with the electrical charges of the clay network, that is to say with the location, i.e., tetrahedral or octahedral sites, of the substituting trivalent elements. PMID:17433348

  10. Succession of Permian and Mesozoic metasomatic events in the eastern Pyrenees with emphasis on the Trimouns talc-chlorite deposit

    NASA Astrophysics Data System (ADS)

    Boutin, Alexandre; de Saint Blanquat, Michel; Poujol, Marc; Boulvais, Philippe; de Parseval, Philippe; Rouleau, Caroline; Robert, Jean-François

    2016-04-01

    Recent studies proposing pre-orogenic mantle exhumation models have helped renew the interest of the geosciences community in the Pyrenees, which should be now interpreted as a hyper-extended passive margin before the convergence between Iberia and Eurasia occurred. Unresolved questions of the Pyrenean geology, as well as the understanding of the formation of hyper-extended passive margins, are how the crust was thinned, and when, where and how the crustal breakoff occurred. The study of the Variscan and pre-Variscan Pyrenean basement is thus critical to document and understand this Cretaceous crustal thinning. In order to specify the timing of Mesozoic metasomatism and the associated deformation in the pre-Mesozoic basement of the Pyrenees, we carried out a U-Th-Pb laser ablation ICP-MS study on a large panel of REE and titanium-rich minerals (titanite and rutile) from talc-chlorite ores from the eastern Pyrenees, with a special emphasis on the Trimouns deposit, the world's largest talc quarry. Our results suggest that the Trimouns talc formation was restricted to the upper Aptian-Cenomanian time, while the talc and chlorite formation in the eastern Pyrenees occurred during several distinct Permian, Jurassic and Cretaceous episodes. These results give strong constraints on the tectonic setting of the Pyrenean domain during the transition between the Variscan and Alpine orogenic cycles, and particularly on when and how the upper crust was thinned before the crustal breakoff and the final mantle exhumation.

  11. The Use of Very High-Doses of Baclofen for the Treatment of Alcohol-Dependence: A Case Series

    PubMed Central

    de Beaurepaire, Renaud

    2014-01-01

    Baclofen, particularly high-dose baclofen, has recently emerged as a treatment of major interest for alcohol-dependence. However, baclofen has many potentially dangerous side effects, and the maximal dose of baclofen that may be used is a matter of discussion. Here, the author analyses the medical charts of the last 100 patients seen in his clinic, 17 of whom have been taking a very high dose of baclofen, which is to say, more than 300 mg/day. The analysis of the charts shows that the very high-doses baclofen were justified in almost all the cases. Side effects are analyzed. PMID:25346700

  12. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

    PubMed Central

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L.; Potthoff, Sebastian A.; Kelm, Malte; Schurgers, Leon J.; Westenfeld, Ralf

    2015-01-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  13. Targeting Pin1 Protects Mouse Cardiomyocytes from High-Dose Alcohol-Induced Apoptosis

    PubMed Central

    Wang, Yuehong; Li, Zizhuo; Zhang, Yu; Yang, Wei; Sun, Jiantao; Shan, Lina; Li, Weimin

    2016-01-01

    Long-term heavy alcohol consumption is considered to be one of the main causes of left ventricular dysfunction in alcoholic cardiomyopathy (ACM). As previously suggested, high-dose alcohol induces oxidation stress and apoptosis of cardiomyocytes. However, the underlying mechanisms are yet to be elucidated. In this study, we found that high-dose alcohol treatment stimulated expression and activity of Pin1 in mouse primary cardiomyocytes. While siRNA-mediated knockdown of Pin1 suppressed alcohol-induced mouse cardiomyocyte apoptosis, overexpression of Pin1 further upregulated the numbers of apoptotic mouse cardiomyocytes. We further demonstrated that Pin1 promotes mitochondria oxidative stress and loss of mitochondrial membrane potential but suppresses endothelial nitric oxide synthase (eNOS) expression in the presence of alcohol. Taken together, our results revealed a pivotal role of Pin1 in regulation of alcohol-induced mouse cardiomyocytes apoptosis by promoting reactive oxygen species (ROS) accumulation and repressing eNOS expression, which could be potential therapeutic targets for ACM. PMID:26697133

  14. Not too little, not too much-just right! (Better ways to give high dose melphalan).

    PubMed

    Shaw, P J; Nath, C E; Lazarus, H M

    2014-12-01

    Of the 13 286 autologous haematopoietic cell transplant procedures reported in the US in 2010-2012 for plasma cell disorders, 10 557 used single agent, high-dose melphalan. Despite 30 years of clinical and pharmacokinetic (PK) experience with high-dose melphalan, and its continuing central role as cytoreductive therapy for large numbers of patients with myeloma, the pharmacodynamics and pharmacogenomics of melphalan are still in their infancy. The addition of protectant agents such as amifostine and palifermin allows dose escalation to 280 mg/m(2), but at these doses it is cardiac, rather than gut, toxicity that is dose-limiting. Although combination with additional alkylating agents is feasible, the additional TRM may not be justified when so many post-consolidation therapies are available for myeloma patients. Current research should optimise the delivery of this single-agent chemotherapy. This includes the use of newer formulations and real-time PKs. These strategies may allow a safe and effective platform for adding synergistic novel therapies and provide a window of lymphodepletion for the addition of immunotherapies. PMID:25133893

  15. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma.

    PubMed

    Kaufman, G P; Gertz, M A; Dispenzieri, A; Lacy, M Q; Buadi, F K; Dingli, D; Hayman, S R; Kapoor, P; Lust, J A; Russell, S; Go, R S; Hwa, Y L; Kyle, R A; Rajkumar, S V; Kumar, S K

    2016-03-01

    Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence in situ hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years. PMID:26487275

  16. High-dose continuous infusion plus pulse interleukin-2 and famotidine in melanoma.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, W Chris; Vinogradov, Mikhail; Khan, Nawazish; Jackson, Shawn

    2004-12-01

    High-dose, continuous infusion interleukin-2 (IL-2) regimens generate greater Lymphokine Activated Killer cell (LAK) cytotoxicity in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 then subsequently pulsed with IL-2 have increased cytotoxicity against cancer cells. Famotidine may enhance the lysis of tumors by cytotoxic lymphocytes. Fourteen patients with melanoma were treated with famotidine 20 mg intravenously twice per day and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes for 1 dose (12 patients) or daily for 3 doses (2 patients). Most common toxicities were fever, nausea/emesis, hypophosphatemia, hypomagnesemia, and rigors. Nine partial responses (64% response rate; 95% Confidence Interval: 39%-84%) have been seen. Median survival has not been reached at greater than 10 months. Two patients responding to therapy showed an increase in detectable CD 56(+) cells in serial subcutaneous or lymph node biopsies, while 1 patient undergoing progression of disease had no such infiltrate. High-dose, 72-hour continuous infusion plus pulse interleukin-2 with famotidine has activity in melanoma. CD 56(+) cells may play a role in responding patients. PMID:15665626

  17. High-dose continuous infusion plus pulse interleukin-2 and famotidine in metastatic kidney cancer.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, Chris; Vinogradov, Mikhail; Quan, Francine; Khan, Nawazish

    2005-02-01

    High-dose continuous infusion interleukin-2 (IL-2) regimens generate a higher degree of lymphokine activated killer cell (LAK) cytotoxicity when tested against tumor cells in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 have increased cytotoxicity against cancer cells when they are subsequently pulsed with additional IL-2. Famotidine may enhance LAK cytolytic ability. Six patients with kidney cancer have been treated with a combination of famotidine 20 mg intravenous bid and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes. The most common metastatic sites were the lung, lymph node, and bone. Median number of cycles received = 5 (range, 3-8). The most common toxicities were fever, rigors, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and metabolic acidosis. There were no treatment-related deaths, and no patients required intensive care admission. Two partial responses (33% response rate) have been seen. Median survival has not been reached at greater than 8 months. The combination of high-dose continuous infusion plus pulse IL-2 and famotidine is active in metastatic kidney cancer. An accrual of additional patients is needed to better assess the response rate. PMID:15778577

  18. High-dose rifaximin treatment alleviates global symptoms of irritable bowel syndrome

    PubMed Central

    Jolley, John

    2011-01-01

    Background: To evaluate the efficacy of rifaximin for reduction of gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). Methods: Medical records were identified for consecutive patients diagnosed with IBS according to Rome III criteria, who had abnormal lactulose breath test results and had received rifaximin 1200 mg/day for 10 days. The efficacy of rifaximin for reducing gastrointestinal symptoms and for eradicating small intestinal bacterial overgrowth was ascertained in these patients. In addition, these endpoints were examined in patients who were initially unresponsive to rifaximin 1200 mg/day and received subsequent rifaximin 2400 mg/day. Results: Patients who received rifaximin 1200 mg/day (n = 162) experienced a mean improvement of 52% in global IBS symptoms at the end of rifaximin treatment. Similarly, initially unresponsive patients who received additional rifaximin 2400 mg/day (n = 81) experienced a 53% mean improvement in global IBS symptoms. Forty-nine percent of patients who received initial rifaximin and 47% of patients who received high-dose rifaximin achieved ≥50% global symptom improvement during at least one follow-up visit. Normalization of lactulose breath test results was only apparent in some patients who received high-dose rifaximin. Rifaximin was well tolerated. Conclusion: Rifaximin 1200 mg/day for 10 days reduced gastrointestinal symptoms in patients with IBS. Patients with incomplete symptom resolution may respond to increased doses of rifaximin. PMID:21694871

  19. High-dose Daptomycin Therapy for Staphylococcal Endocarditis and When to Apply It

    PubMed Central

    Smith, Jordan R.; Claeys, Kimberly; Barber, Katie E.; Rybak, Michael J.

    2014-01-01

    Infective endocarditis (IE) continues to present a large burden to the healthcare system. Staphylococcus aureus, the leading pathogen associated with the disease, has always proven difficult to treat. Increasing numbers of S. aureus isolates are demonstrating reduced susceptibility to vancomycin, and therapeutic options are limited. Daptomycin is frequently employed when vancomycin therapy proves unsuccessful or when vancomycin MIC values rise above 1 mg/L. Currently, daptomycin is FDA-approved at a dose of 6 mg/kg/day for the treatment of S. aureus bacteremia and associated right-sided endocarditis. However, numerous in vitro and clinical studies suggest that daptomycin doses up to 12 mg/kg/day may provide improved efficacy and resistance prevention. Additionally, high-dose daptomycin has demonstrated excellent safety. Together, these data suggest a role for high-dose daptomycin in staphylococcal IE patients who are severely ill, previously failed therapy with vancomycin, or possess a S. aureus isolate with an elevated vancomycin MIC. PMID:25165017

  20. [Cytosine-arabinoside in high doses in refractory acute granulocytic leukemia. Apropos of 17 cases].

    PubMed

    Jouet, J P; Simon, M; Fenaux, P; Pollet, J P; Bauters, F

    1985-01-01

    A total of 17 patients, 6 female and 11 male (age range 13 to 56 years), received high dose Ara-C for treatment of refractory acute myelogenous leukemia. Ara-C was given at 3 g/m2 twice daily for 6 days as a 1 infusion. 1 patient (with induced acute leukemia) was treated directly, two after failure of a chemotherapy schedule containing the usual dose Ara-C, 12 for first relapse and 2 for subsequent relapse. Maximum follow up is 16 months. Beside hematological toxicity, systemic tolerance was good with no neurological of cutaneous effects. Despite preventive corticoid eyewash, ocular complications occurred in 6 cases, mild and resolvable in 5 of them. The immediate results were as follows: 3 deaths during induction (18%); 6 failures (35%); 8 complete remissions (CR) (47%). After primary chemo-resistance (two cases) failure was always noted. In 3 cases, after less than 12 infusions had been given, 2 failures and 1 very short CR were noted. In 2 patients, when doxorubicin was added to Ara-C, we observed 1 death during induction and 1 failure. Of the patients achieving CR 8 were treated by periodic courses with high dose Ara-C and 4 of them relapsed. The longest failure free duration was 11 months. Median survival duration of the 17 patients is 5 months. PMID:3862072

  1. High-Dose Hook Effect in 17-Hydroxyprogesterone Assay in a Patient with 21-Hydroxylase Deficiency.

    PubMed

    Parlak, Mesut; Ellidağ, Hamit Yaşar; Türkkahraman, Doğa

    2015-12-01

    Congenital adrenal hyperplasia (CAH) describes a group of disorders characterized by enzyme defects in adrenal steroidogenesis. 21-hydroxylase deficiency (21-OHD) is the most commonly encountered form. The analysis of steroids in pediatric cases requires high-sensitivity assays. A 14-year-old Syrian girl was referred for evaluation of short stature, amenorrhea, and hirsutism. On physical examination, breast development was Tanner stage 1. She had a phallic clitoris with a single urogenital orifice. Laboratory findings revealed primary adrenal deficiency with high androgen levels and low levels of 17-hydroxyprogesterone (17-OHP), (<0.05 ng/mL) and estrogen. This unexpected result led to suspicion of a high-dose hook effect. The measurement was repeated after 1/10 dilution of serum, and a high level of 17-OHP (115.4 ng/mL) was detected with the same test-enzyme-linked immunosorbent assay (ELISA). Simple virilizing form of CAH (21-OHD) was suspected and confirmed with genetic analysis. After initiation of glucocorticoid therapy, breast development was noted along with a decrease in testosterone level and an increase in estrogen level. To our knowledge, this is the first case report of hook effect for 17-OHP immunoassay in a patient with 21-OHD. High-dose hook effect should be suspected in patients with CAH when the test results are incompatible with one another. Additionally, this case demonstrates that a high testosterone level can block aromatase activity and consequently also estrogen production and breast development. PMID:26777045

  2. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

    PubMed Central

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2013-01-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered at PND90. Mechanisms underlying this “resistance” were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. PMID:21190217

  3. High dose chemotherapy with stem cell support in the treatment of testicular cancer

    PubMed Central

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-01-01

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  4. Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma

    SciTech Connect

    Holoye, P.Y.; Libnoch, J.A.; Anderson, T.; Cox, J.D.; Byhardt, R.W.; Hoffmann, R.G.

    1985-04-01

    The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals.

  5. Economic and social effects of high-dose buprenorphine substitution therapy. Six-month results.

    PubMed

    Lavignasse, Pierre; Lowenstein, William; Batel, Philippe; Constant, Marie-Véronique; Jourdain, Jean-Jacques; Kopp, Pierre; Reynaud-Maurupt, Catherine; Riff, Bertrand; Videau, Benjamin; Mucchielli, Alain

    2002-05-01

    The purpose of this study was to analyze the impact of high-dose buprenorphine substitution therapy in opiate-dependent patients in terms of use of psychoactive substances, associated risks, social integration, and the social cost generated by the use of these substances. This was a longitudinal quantitative survey carried out in 1083 patients who were evaluated at three times: at the beginning of substitution therapy (D0), at 6 months and then at 12 months follow up (M6, M12). Data were collected with an anonymous self-administered questionnaire, completed in the presence of an investigating physician. Results demonstrated that patients treated with high-dose buprenorphine for 6 months, consumed fewer psychoactive drugs (heroin, cocaine, benzodiazepines) and had fewer associated risks. Additionally, several criteria involved in social integration showed improvement; morbidity and mortality decreased after the first 6 months of substitution therapy. These improvements were followed by a reduction in the social cost of drug use generated by the group of patients considered. These initial results require confirmation in the final analysis of the study taking into account the 12-month follow up. PMID:12218879

  6. Reproductive toxicity in rats with crystal nephropathy following high doses of oral melamine or cyanuric acid.

    PubMed

    Stine, Cynthia B; Reimschuessel, Renate; Keltner, Zachary; Nochetto, Cristina B; Black, Thomas; Olejnik, Nicholas; Scott, Michael; Bandele, Omari; Nemser, Sarah M; Tkachenko, Andriy; Evans, Eric R; Crosby, Tina C; Ceric, Olgica; Ferguson, Martine; Yakes, Betsy J; Sprando, Robert

    2014-06-01

    The industrial chemical melamine was used in 2007 and 2008 to raise the apparent protein content in pet feed and watered down milk, respectively. Because humans may be exposed to melamine via several different routes into the human diet as well as deliberate contamination, this study was designed to characterize the effect of high dose melamine or cyanuric acid oral exposure on the pregnant animal and developing fetus, including placental transfer. Clear rectangular crystals formed following a single triazine exposure which is a different morphology from the golden spherulites caused by combined exposure or the calculi formed when melamine combines with endogenous uric acid. Crystal nephropathy, regardless of cause, induces renal failure which in turn has reproductive sequelae. Specifically, melamine alone-treated dams had increased numbers of early and late fetal deaths compared to controls or cyanuric acid-treated dams. As melamine was found in the amniotic fluid, this study confirms transfer of melamine from mammalian mother to fetus and our study provides evidence that cyanuric acid also appears in the amniotic fluid if mothers are exposed to high doses. PMID:24582682

  7. High dose chemotherapy with stem cell support in the treatment of testicular cancer.

    PubMed

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-12-26

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  8. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  9. [High-dose chemotherapy and residual tumor resection in male germ cell tumors].

    PubMed

    Lorch, A; Albers, P; Winter, C; Beyer, J

    2011-09-01

    As a consequence of the unsatisfactory results of conventional dose salvage regimens, in particular for patients with poor prognostic features at the time of relapse or in patients with refractory disease, high-dose chemotherapy (HDCT) was introduced into clinical practice in the late 1980s. The combination of carboplatin and etoposide (CE) still remains the backbone of most high-dose regimens. Multiple modifications with more dose escalations or addition of further drugs have been explored, most often with increased toxicity. With improved expertise in supportive care and the use of peripheral blood stem cells, hematopoetic recovery has been significantly shortened and the initial high treatment-related mortality reduced from more than 10% to about 3%. Since the incorporation of HDCT, even patients with unfavorable prognostic features or patients with second or subsequent relapses can achieve long-term remission. Following HDCT residual tumor resection plays a major role in achieving these long-term results. The proportion of vital residual tumor after HDCT is much higher than in patients after conventional chemotherapy. The role of HDCT remains controversial particularly as a first-line treatment and less so in the first salvage setting. As these patients are rare HDCT and residual tumor resection should only be be provided by high-volume centers with sufficient expertise in performing these complex procedures. PMID:21845425

  10. The use of small fraction numbers in high dose-rate gynaecological afterloading: some radiobiological considerations.

    PubMed

    Dale, R G

    1990-04-01

    Using commonly assumed alpha/beta ratios for tumours and late-reacting tissues, the linear-quadratic (LQ) model has been used to compare low dose-rate (LDR) gynaecological treatment with high dose-rate (HDR) techniques given in small fraction numbers. Even in the absence of relatively favourable tissue recovery constants (mu values) it is shown that, provided a modest extra amount of geometrical sparing of critical tissues is available (by means of spacing or shielding), HDR treatment in a small number of fractions may be used in place of an LDR regime without loss of therapeutic ratio. This general result, although not universally true, does indicate that HDR treatment delivered in a small number of fractions may be more feasible than is sometimes thought. These findings do not contradict currently accepted radiobiological philosophy, which cautions against the use of small numbers of high-dose fractions. Primarily they serve to emphasize the importance of the recommendations of the ICRU (1985), which stress the need to consider the complete time-dose pattern of radiation delivery to all the critical tissues in an intracavitary treatment. PMID:2346867

  11. Posterior Reversible Encephalopathy Syndrome due to High Dose Corticosteroids for an MS Relapse.

    PubMed

    Morrow, Sarah A; Rana, Robina; Lee, Donald; Paul, Terri; Mahon, Jeffrey L

    2015-01-01

    Increased blood pressure is a known adverse effect associated with corticosteroids but little is published regarding the risk with the high doses used in multiple sclerosis (MS). A 53-year-old female with known relapsing remitting MS presented with a new brainstem relapse. Standard of care treatment for an acute MS relapse, 1250 mg of oral prednisone for 5 days, was initiated. She developed an occipital headache and dizziness and felt generally unwell. These symptoms persisted after treatment was complete. On presentation to medical attention, her blood pressure was 199/110 mmHg, although she had no history of hypertension. MRI changes were consistent with posterior reversible encephalopathy syndrome (PRES), demonstrating abnormal T2 signal in both thalami, the posterior occipital and posterior parietal white matter with mild sulcal effacement. As her pressure normalized with medication, her symptoms resolved and the MRI changes improved. No secondary cause of hypertension was found. This is the first reported case of PRES secondary to high dose corticosteroid use for an MS relapse without a history of hypertension and with no other secondary cause of hypertension identified. This rare complication should be considered in MS patients presenting with a headache or other neurological symptoms during treatment for a relapse. PMID:26101676

  12. High-Dose Radioiodine Outpatient Treatment: An Initial Experience in Thailand

    PubMed Central

    Nantajit, Danupon; Saengsuda, Sureerat; NaNakorn, Pattama; Saengsuda, Yuthana

    2015-01-01

    Objective(s): The aim of this study was to determine whether high-dose radioactive iodine (Na131I) outpatient treatment of patients with thyroid carcinoma is a pragmatically safe approach, particularly for the safety of caregivers. Methods: A total of 79 patients completed the radiation-safety questionnaires prior to receiving high-dose radioactive iodine treatment. The questionnaire studied the subjects’ willingness to be treated as outpatients, along with the radiation safety status of their caregivers and family members. In patients, who were selected to be treated as outpatients, both internal and external radiation exposures of their primary caregivers were measured, using thyroid uptake system and electronic dosimeter, respectively. Results: Overall, 62 out of 79 patients were willing to be treated as outpatients; however, only 44 cases were eligible for the treatment. The primary reason was that the patients did not use exclusive, separated bathrooms. The caregivers of 10 subjects, treated as outpatients, received an average radiation dose of 138.1 microsievert (mSv), which was almost entirely from external exposure; the internal radiation exposures were mostly at negligible values. Therefore, radiation exposure to caregivers was significantly below the public exposure limit (1 mSv) and the recommended limit for caregivers (5 mSv). Conclusion: A safe 131I outpatient treatment in patients with thyroid carcinoma could be achieved by selective screening and providing instructions for patients and their caregivers.

  13. Physiological and psychological effects of a high dose of alcohol in young men and women.

    PubMed

    Vinader-Caerols, Concepción; Monleón, Santiago; Parra, Andrés

    2014-01-01

    The objective of this study was to evaluate the effects of a high dose of alcohol on physiological and psychological parameters in young men and women with a previous history of alcohol consumption. Systolic and diastolic blood pressure, heart rate, state anxiety, attention, time estimation and manual dexterity were registered before (phase 1) and after (phase 2) intake of alcohol (38.4 g) or a non-alcoholic beverage. Trait anxiety was registered in phase 2 only. The results showed that acute consumption of a high dose of alcohol: i) improves attention in men (although the performance of alcohol consumers was not better than that of non-consumers); ii) blocks the systolic blood pressure habituation phenomenon (observed in controls) in women; and iii) blocks the improvement in manual dexterity (associated with experience in non-consumers) in both sexes. On the other hand, male consumers had a lower heart rate than non-consumers, independently of the phase, while female consumers had a higher state anxiety and performed worse in attention than controls, also independently of the phase. These results help to understand the extent of performance impairment of different tasks produced by risk alcohol consumption in young men and women. PMID:25314039

  14. The Effect of High Dose Methylprednisolone on Experimental Ovarian Torsion/Reperfusion Injury in Rats.

    PubMed

    Osmanağaoğlu, M A; Kesim, M; Yuluğ, E; Menteşe, A; Karahan, C S

    2012-01-01

    Purpose: Aim of the study was to evaluate the effects of high dose methylprednisolone on experimental ovarian torsion-detorsion injury in rats. Materials and Methods: Twenty-two Sprague-Dawley rats were randomly divided into three groups. Group 1 (ischemia group, 8 rats) were subjected to left adnexal torsion for 2 h but received no treatment. Group 2 (methylprednisolone group, 8 rats) were subjected to left adnexal torsion for 2 h and received methylprednisolone (30 mg/kg, administered intraperitoneally) at the end of a 2-hour ischemic period followed by 24-hour reperfusion. Group 3 (control group, 6 rats) underwent a sham operation with no adnexal torsion and no treatment. Results: Serum malondialdehyde (MDA), ischemia-modified albumin (IMA), total oxidant status (TOS) and tissue MDA levels were increased in Group 1 rats; total antioxidant status (TAS) levels and oxidative stress index (OSI) were significantly decreased compared with rats in Groups 2 and 3 (p < 0.05). MDA, IMA, TOS and tissue MDA levels were lower and TAS levels and OSI were higher in Group 3 compared to Group 2. Ovarian damage scores in Group 1 were significantly higher compared with Groups 2 and 3 (p < 0.05). Conclusion: This study demonstrated that high dose methylprednisolone reduces ovarian ischemia/reperfusion injury. PMID:25253907

  15. High Dose Ilaprazole/Amoxicillin as First-Line Regimen for Helicobacter pylori Infection in Korea

    PubMed Central

    Graham, David Y.

    2016-01-01

    Objective. The eradication rate of Helicobacter pylori (H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicating H. pylori in Korea. Methods. This was an open-labeled study of H. pylori infected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4–6 weeks to confirm H. pylori status through a urea breath test. Results. The cure rate of H. pylori was 79.3% (23 of 29) (95% confidence interval: 61.6–90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable. Conclusion. A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicating H. pylori in Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance. PMID:27413365

  16. Effect of a high dose of vitamin D on a rabbit model of atherosclerosis.

    PubMed

    Malek, H A; Shata, A

    2014-01-01

    Multifactorial factors have been involved in atherosclerosis. An association has been shown between osteoporosis and carotid atherosclerosis. This work evaluates the effect of vitamin D on regression of atherosclerosis. Forty-eight male rabbits were divided into: Group Ia: [Standard diet + saline for 4 weeks]; Group I b: [Standard diet + a high dose of vitamin D3 daily for 4 weeks]; Group IIa: [Cholesterol–enriched diet for 4 weeks]; Group IIb: [Cholesterol–enriched diet + a single high dose of vit D3, daily for 4 weeks. At the end of 4 weeks, the rabbits were sacrificed for assay in serum lipid profile, C reactive protein (CRP), vitamin D3 metabolite, calcium, soluble adhesion molecules (sVCAM and sICAM) and nitrite (NO) and malondialdehyde (MDA) released from isolated aortic rings. Results showed that vitamin D produced a significant reduction in the sera of lipid profile, CRP, and adhesion molecules, associated with a non-significant change in serum calcium and a significant increase in the body level of vitamin D3. Addition of vitamin D to the incubated aortic rings of the atherosclerotic rabbits resulted in a significant increase in NO and decrease in MDA release. It could be concluded that vitamin D has anti-atherosclerotic effects, and may exert these effects by inhibiting lipid peroxidation and stimulation of nitric oxide, resulting in attenuation of the inflammatory atherosclerotic process. PMID:25004831

  17. Systemic effects of local treatment with high doses of potent corticosteroids in psoriatics.

    PubMed

    Nilsson, J E; Gip, L J

    1979-01-01

    The risk of systemic effects of high doses of potent topical corticosteroids was evaluated in 6 psoriatics with lesions on more than 50% of the body surface. Before the examinations the patients had been treated for 3-4 months with 35-65 g fluorinated corticosteroids daily. General clinical examination, plasma cortisol determinations, and tetracosactrin tests were carried out. One patient showed clinical signs of Cushing's syndrome including diabetes mellitus, another had a slight Cushingoid appearance. The plasma cortisol levels were depressed in 5 of the 6 patients on the first post-treatment day. A subnormal plasmacortisol response to tetracosactrin stimulation was noted in 3 of the patients. In these cases the potent corticosteroid therapy was discontinued. One month later a follow-up was performed, which showed a clinical and laboratory normalization except for the tetracosactrin test in one case. The study emphasizes the risk of serious systemic effects of the absorbed corticosteroids, if high doses are used for long periods. PMID:87083

  18. Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation

    PubMed Central

    Pamplin, Jeremy; Studer, Lynette; Hughes, Rhome L.; King, Booker T.; Graybill, John C.; Chung, Kevin K.

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  19. Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation.

    PubMed

    Buehner, Michelle; Pamplin, Jeremy; Studer, Lynette; Hughes, Rhome L; King, Booker T; Graybill, John C; Chung, Kevin K

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  20. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

    PubMed Central

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-01-01

    Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h

  1. High-dose immunosuppression and hematopoietic stem cell transplantation in autoimmune disease: clinical review.

    PubMed

    Openshaw, Harry; Nash, Richard A; McSweeney, Peter A

    2002-01-01

    Since 1996, a number of investigators have carried out phase I-II studies of high-dose immunosuppression with autologous hematopoietic stem cell transplantation (HSCT) in autoimmune diseases. Most of this activity has been in studies of multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA). Supported by animal models of antigen-induced autoimmunity, the rationale of HSCT is to time-shift the clinical autoimmunity to an earlier period, restoring self-tolerance. Even with the considerable experience of more than 200 transplantations since 1996, it is difficult to judge the optimal approach. This difficulty is in part because of the multiplicity of centers and protocols and the variability in patient eligibility and assessment, the extent of T-cell depletion, and the intensity of the preparatory regimens used. Other than that found in RA, treatment-related mortality has been higher than expected: 17% in SSc (with an additional 10% mortality from progressive disease), 13% in SLE, 13% in JIA, and 8% in MS. Protocol changes to improve safety have been instituted. These changes include the avoidance of high-dose rabbit antithymocyte serum in patients who received T-cell-depleted grafts, use of corticosteroids with granulocyte colony-stimulating factor during stem cell mobilization and as prophylaxis for the engraftment syndrome in MS, lung radiation shielding in SSc, and multiple precautions against the macrophage activation syndrome in JIA. Responses to primary and secondary endpoints have been seen, and there is a consensus among investigators and regulatory bodies that the time has come for randomized phase II-III studies. Each disease presents distinct difficulties: in MS, restriction of eligibility to patients with active inflammatory disease; in SSc, formulation of cardiopulmonary eligibility criteria to decrease risk; in SLE, judgment of whether HSCT adds any

  2. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

    PubMed Central

    Chader, Driss; Cohen-Aubart, Fleur; Haroche, Julien; Fadlallah, Jehane; Claër, Laetitia; Musset, Lucile; Gorochov, Guy; Amoura, Zahir; Miyara, Makoto

    2015-01-01

    Background/Purpose A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE. Methods We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score. Results Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2. Conclusion IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE. PMID:26629828

  3. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria

    PubMed Central

    2014-01-01

    Introduction The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses. Methods We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated. Results Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure. Conclusions TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria. PMID:24887101

  4. 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

  5. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    SciTech Connect

    Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

    2015-10-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  6. High-dose regions versus likelihood of cure after prostate brachytherapy

    SciTech Connect

    Wallner, Kent . E-mail: kent.wallner@med.va.gov; Merrick, Gregory; Sutlief, Steven; True, Laurence; Butler, Wayne

    2005-05-01

    Purpose: To analyze the effect of high-dose regions on biochemical cancer control rates after prostate brachytherapy. Methods and Materials: Patients with 1997 American Joint Committee on Cancer clinical Stage T1c-T2a prostate carcinoma (Gleason grade 5-6, prostate-specific antigen level 4-10 ng/mL) were randomized to implantation with {sup 125}I (144 Gy) vs. {sup 103}Pd (125 Gy, National Institute of Standards and Technology 1999). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. Of the 313 patients entered in the protocol, 270 were included in this analysis. The {sup 125}I source strength ranged from 0.4 to 0.89 mCi (median, 0.55 mCi), and the {sup 103}Pd source strength ranged from 1.3 to 1.6 mCi (median, 1.5 mCi). CT was performed within 4 h after implantation. The dosimetric parameters analyzed included the percentage of the postimplant prostate volume covered by the 100%, 150%, 200%, and 300% prescription dose (V{sub 100}, V{sub 150}, V{sub 200}, and V{sub 300}, respectively). The median time to the last follow-up for patients without failure was 2.7 years. Freedom from biochemical failure was defined as a serum prostate-specific antigen level of {<=}0.5 ng/mL at last follow-up. Patients were censored at last follow-up if their serum prostate-specific antigen level was still decreasing. Results: The mean V{sub 100}, V{sub 150}, V{sub 200}, and V{sub 300} value was 90% ({+-}8%), 63% ({+-}14), 35% ({+-}13%), and 14% ({+-}7%), respectively. Patients with a V{sub 100} of {>=}90% had a 3-year freedom from biochemical failure rate of 96% vs. 87% for those with a V{sub 100} of <90% (p = 0.0029). Overall, patients with more high-dose regions had a greater chance of biochemical control. However, when only patients with a V{sub 100} of {>=}90% were analyzed, no relationship was found between higher dose regions and the likelihood of cancer control. This lack of effect on biochemical control was apparent for both

  7. Interstitial high-dose-rate brachytherapy in locally advanced and recurrent vulvar cancer

    PubMed Central

    Białas, Brygida; Fijałkowski, Marek; Wojcieszek, Piotr; Szlag, Marta; Cholewka, Agnieszka; Ślęczka, Maciej; Kołosza, Zofia

    2016-01-01

    Purpose The aim of the study was to report our experience with high-dose-rate interstitial brachytherapy (HDR-ISBT) in locally advanced and recurrent vulvar cancer. Material and methods Between 2004 and 2014, fourteen women with locally advanced or recurrent vulvar cancer were treated using HDR-ISBT in our Centre. High-dose-rate interstitial brachytherapy was performed as a separate treatment or in combination with external beam radiotherapy (EBRT) (given prior to brachytherapy). Results Patients were divided into: group I (n = 6) with locally advanced tumors, stages III-IVA after an incisional biopsy only, and group II (n = 8) with recurrent vulvar cancer after previous radical surgery. In group I, median follow up was 12 months (range 7-18 months); 1-year overall survival (OS) was 83%. Transient arrest of cancer growth or tumor regression was noticed in all patients but 4/6 developed relapse. Median time to failure was 6.3 months (range 3-11 months). The 1-year progression-free survival (PFS) was 33%. In group II, median follow up was 28 months (range 13-90 months). The 1-year and 3-year OS was 100% and 80%, respectively. The arrest of cancer growth or tumor regression was achieved in all patients. In 4/8 patients neither clinical nor histological symptoms of relapse were observed but 4/8 women experienced relapse. Median time to failure was 31 months (range 13-76 months). The 1-year and 3-year PFS was 100% and 62.5%, respectively. Two patients (14.3%) in group II had severe late toxicity (G3). Conclusions High-dose-rate interstitial brachytherapy is a well-tolerated treatment option in selected patients with advanced or recurrent vulvar cancer. It is a safe and effective treatment modality for advanced and recurrent vulvar cancer, yielding good local control with acceptable late treatment related side effects. In our study, patients with recurrent vulvar cancer had better results in HDR-ISBT treatment, probably because of the smaller tumor volume. This

  8. Bladder–Rectum Spacer Balloon in High-Dose-Rate Brachytherapy in Cervix Carcinoma

    SciTech Connect

    Rai, Bhavana; Patel, Firuza D.; Chakraborty, Santam; Sharma, Suresh C.; Kapoor, Rakesh; Aprem, Abi Santhosh

    2013-04-01

    Purpose: To compare bladder and rectum doses with the use of a bladder–rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions. Methods and Materials: This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm{sup 3}, 1-cm{sup 3}, 2-cm{sup 3}, 5-cm{sup 3}, and 10-cm{sup 3} volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test. Results: A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, 5 cm{sup 3}, and 10 cm{sup 3} and ICRU bladder point. Statistically significant dose reductions to 0.1-cm{sup 3}, 1-cm{sup 3}, and 2-cm{sup 3} volumes for rectum were observed with the BRSB. No significant differences in 5-cm{sup 3} and 10-cm{sup 3} volumes and ICRU rectum point were observed. Conclusion: A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of

  9. Effectiveness of acidified sodium chlorite and other sanitizers to control Escherichia coli O157:H7 on tomato surfaces.

    PubMed

    Inatsu, Yasuhiro; Kitagawa, Tomoko; Bari, Md Latiful; Nei, Daisuke; Juneja, Vijay; Kawamoto, Shinichi

    2010-06-01

    The use of a suitable sanitizer can reduce the risk of produce-related foodborne illnesses. We evaluated the effectiveness of several sanitizers to reduce inoculated Escherichia coli O157:H7 on the surface of cherry tomatoes (Solanum lycopersicum var. cerasiform). Depending on the method of inoculation (dipping/spotting), each of 80 g (eight tomatoes) of inoculated cherry tomatoes was washed in 400 mL of sanitizer solutions or 400 mL distilled water for 5 minutes. The effectiveness of sanitizers on spot-inoculated E. coli O157:H7 on tomato surfaces was found higher than on dip-inoculated tomatoes. Washing with water or chlorine water (0.1 g/L as free chlorine) could reduce 1.3 log CFU/g of E. coli O157:H7 in dip-inoculated (6.8 log CFU/g) tomatoes. Washing with lactic acid (LA) solution (1.0 g/L), phytic acid solution (1.0 g/L), calcinated seashells (oyster/sakhalin surf clam), and 1.0 g/L chitosan in 0.5 g/L LA (Chito) did not exhibit a significant higher effectiveness than that of water wash alone (1.0 log CFU/g). Acidified sodium chlorite (ASC) solution prepared from 0.5 g/L of sodium chlorite and 1.0 g/L LA or phytic acid reduced 3.5 log CFU/g of E. coli O157:H7 in dip-inoculated tomato surfaces. ASC (0.5 g/L of sodium chlorite and 1.0 g/L of LA) wash followed by a second wash with LA exhibited an additional sanitary effectiveness compared to a single wash with ASC. However, washing with ASC followed by a second wash with Chito exhibited an additional 1.0 log CFU/g reduction compared to a secondary wash with water. No significant difference of color, taste, and texture was observed among the washed cherry tomatoes. PMID:20113205

  10. Effect of high dose corticosteroids alone or combined with other drugs on survival in septic shock.

    PubMed

    Almqvist, P M; Ekström, B; Kuenzig, M; Haglund, U; Schwartz, S I

    1985-01-01

    The effect of high dose corticosteroids on survival has been studied in a limited number of canine septic shock models which are reviewed in this presentation. Following injection of live bacteria neither methylprednisolone, nor gentamicin but a combination improved survival. Methylprednisolone increased survival following a slow but not a bolus infusion of endotoxin. In a recent study the effects of short term treatment with methylprednisolone, naloxone and ibuprofen were studied in endotoxin shock. All control animals died within 36 hours. Five of 9 dogs receiving the combination methylprednisolone, naloxone and ibuprofen were permanent survivors. The combined treatment with methylprednisolone and ibuprofen also increased survival. Dogs treated with methylprednisolone alone did not differ significantly from controls. It is concluded that methylprednisolone alone has no significant effect on survival in septic shock, but seems to be an important therapeutic factor to achieve increased survival. PMID:3867205

  11. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy

    PubMed Central

    Yang, Ying-Chieh; Chiang, Chi-Shiun

    2016-01-01

    Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer. PMID:27446811

  12. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

    PubMed Central

    2012-01-01

    Background High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. Methods This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. Results The AUC0-10 hr and Cmax values increased nonlinearly between100 mg and 1500 mg. The slope of the AUC0-10 hr vs dose, as well as the Cmax vs dose, plots are steepest at the lowest thiamine doses. Conclusion Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process. Trial Registration ClinicalTrials.gov: NCT00981877 PMID:22305197

  13. Fluorescent screen for high-dose-rate (HDR) brachytherapy quality assurance

    SciTech Connect

    Lightstone, A.W. . E-mail: Alex.Lightstone@sw.ca

    2005-09-30

    This article describes apparatus for quickly checking the positioning and dwell times of a high-dose-rate (HDR) afterloader as part of daily quality assurance (QA). A groove was milled into an aluminum plate to align an HDR applicator, and fluorescent screens were placed on either side of the groove. Lines were drawn at the fluorescent screen corresponding to distances to which the radioactive source should travel in our daily QA treatment protocol. By dimming the room lights, the fluorescence from the source was seen with a closed-circuit video camera, and the positioning accuracy and dwell time of the source could be efficiently verified. Not only is this an excellent QA tool, but it also provides good training for radiation therapists and other HDR professionals.

  14. [Proton Pump Inhibitor and High-dose Methotrexate: Two Cases Reports].

    PubMed

    Evrard, Julien; Farnier, Elodie; Carcel, Corine; Lachenal, Florence; Vial, Thierry; Pont, Emmanuelle

    2015-01-01

    Methotrexate (MTX) is a cytotoxic agent prescribed at high dose in treatment of malignancy. Association of MTX to proton pump inhibitor (PPI) is not recommended if doses are more than 20 mg per weeks and only to take into account for smaller doses. Review relate some cases of delayed elimination of methotrexate in patients taking PPI, which increase risk of toxic event. However, currently there is no status quo on interaction between PPI and MTX according to available data. We report two clinical cases illustrating one more time a toxic event to MTX in presence of PPI. In absence of risk/benefit ratio set correctly, an assessment of appropriateness of PPI prescription before MTX therapy can limit an iatrogenic risk. PMID:26242498

  15. Recurrent myelitis in common variable immunodeficiency successfully managed with high-dose subcutaneous immunoglobulin

    PubMed Central

    Danieli, Maria Giovanna; Pettinari, Lucia; Marinangeli, Lucia; Logullo, Francesco

    2012-01-01

    Acute myelitis is an aetiologically heterogeneous inflammatory disorder of the spinal cord. We report on a 71-year-old woman with a recurrent cervical and thoracic myelitis who presented with a new relapse of the disease. Neuromyelitis optica was ruled out such as other possible causes of acute and/or recurrent myelopathy. Serum immunoglobulin levels and specific antibody responses were consistent with the diagnosis of common variable immunodeficiency (CVID). She was treated with high-dose methylprednisolone and intravenous immunoglobulin. As a remission-maintaining drug, we decided to treat her with subcutaneous immunoglobulin (CSL Behring) at 0.2 g/kg/week at doses higher than usually employed in replacement therapy in CVID. At 3-year follow-up, the response to treatment was good. No relapses occurred. Our case suggests the effectiveness and safety of subcutaneous immunoglobulin in maintaining remission and in sparing prednisone in a woman with recurrent myelitis associated with CVID. PMID:22878981

  16. Primary central nervous system lymphoma: implication of high-dose chemotherapy followed by auto-SCT

    PubMed Central

    Reddy, N; Savani, BN

    2016-01-01

    Primary central nervous system lymphoma is a rare and distinct subtype of non-Hodgkin's lymphoma that is sensitive to radiation and chemotherapy. Decisions regarding the initial therapeutic approach are influenced by age and risk of therapy-related neurotoxicity. Despite several albeit small phase II studies, and the acknowledged need for larger prospective trials, there is supporting evidence to consider auto-SCT following induction chemotherapy in patients with good performance status. The international extranodal lymphoma study group is conducting a randomized phase II study comparing consolidative radiation therapy to high-dose therapy. Novel therapeutic options including early aggressive approach with upfront auto-SCT and strategies to prevent relapse following transplantation is an area of focus. PMID:22002486

  17. Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk

    PubMed Central

    Kumar, Vinod; Garg, Rakesh; Bharati, Sachidanand Jee; Gupta, Nishkarsh; Bhatanagar, Sushma; Mishra, Seema; Balhara, Yatan Pal Singh

    2015-01-01

    Chronic phantom limb pain (PLP) is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants) and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation). Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction. PMID:25709194

  18. High-dose-rate prostate brachytherapy inverse planning on dose-volume criteria by simulated annealing

    NASA Astrophysics Data System (ADS)

    Deist, T. M.; Gorissen, B. L.

    2016-02-01

    High-dose-rate brachytherapy is a tumor treatment method where a highly radioactive source is brought in close proximity to the tumor. In this paper we develop a simulated annealing algorithm to optimize the dwell times at preselected dwell positions to maximize tumor coverage under dose-volume constraints on the organs at risk. Compared to existing algorithms, our algorithm has advantages in terms of speed and objective value and does not require an expensive general purpose solver. Its success mainly depends on exploiting the efficiency of matrix multiplication and a careful selection of the neighboring states. In this paper we outline its details and make an in-depth comparison with existing methods using real patient data.

  19. Recurrent myelitis in common variable immunodeficiency successfully managed with high-dose subcutaneous immunoglobulin.

    PubMed

    Danieli, Maria Giovanna; Pettinari, Lucia; Marinangeli, Lucia; Logullo, Francesco

    2012-01-01

    Acute myelitis is an aetiologically heterogeneous inflammatory disorder of the spinal cord. We report on a 71-year-old woman with a recurrent cervical and thoracic myelitis who presented with a new relapse of the disease. Neuromyelitis optica was ruled out such as other possible causes of acute and/or recurrent myelopathy. Serum immunoglobulin levels and specific antibody responses were consistent with the diagnosis of common variable immunodeficiency (CVID). She was treated with high-dose methylprednisolone and intravenous immunoglobulin. As a remission-maintaining drug, we decided to treat her with subcutaneous immunoglobulin (CSL Behring) at 0.2 g/kg/week at doses higher than usually employed in replacement therapy in CVID. At 3-year follow-up, the response to treatment was good. No relapses occurred. Our case suggests the effectiveness and safety of subcutaneous immunoglobulin in maintaining remission and in sparing prednisone in a woman with recurrent myelitis associated with CVID. PMID:22878981

  20. High-dose-rate prostate brachytherapy inverse planning on dose-volume criteria by simulated annealing.

    PubMed

    Deist, T M; Gorissen, B L

    2016-02-01

    High-dose-rate brachytherapy is a tumor treatment method where a highly radioactive source is brought in close proximity to the tumor. In this paper we develop a simulated annealing algorithm to optimize the dwell times at preselected dwell positions to maximize tumor coverage under dose-volume constraints on the organs at risk. Compared to existing algorithms, our algorithm has advantages in terms of speed and objective value and does not require an expensive general purpose solver. Its success mainly depends on exploiting the efficiency of matrix multiplication and a careful selection of the neighboring states. In this paper we outline its details and make an in-depth comparison with existing methods using real patient data. PMID:26760757

  1. Steady-state, high-dose neutron generation and concentration apparatus and method for deuterium atoms

    SciTech Connect

    Uhm, H.S.; Lee, W.M.

    1991-01-01

    A steady-state source of neutrons is produced within an electrically grounded and temperature controlled chamber confining tritium or deuterium plasma at a predetermined density to effect implantation of ions in the surface of a palladium target rod coated with diffusion barrier material and immersed in such plasma. The rod is enriched with a high concentration of deuterium atoms after a prolonged plasma ion implantation. Collision of the deuterium atoms in the target by impinging ions of the plasma initiates fusion reactions causing emission of neutrons during negative voltage pulses applied to the rod through a high power modulator. The neutrons are so generated at a relatively high dose rate under optimized process conditions.

  2. Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk.

    PubMed

    Kumar, Vinod; Garg, Rakesh; Bharati, Sachidanand Jee; Gupta, Nishkarsh; Bhatanagar, Sushma; Mishra, Seema; Balhara, Yatan Pal Singh

    2015-01-01

    Chronic phantom limb pain (PLP) is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants) and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation). Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction. PMID:25709194

  3. [Successful anesthetic management of a patient with giant pheochromocytoma using high-dose landiolol hydrochloride].

    PubMed

    Kitano, Manabu; Komasawa, Nobuyasu; Sawai, Toshiyuki; Minami, Toshiaki

    2014-08-01

    We report successful anesthetic management of a patient with pheochromocytoma using high-dose landiolol hydrochloride. A 55-year-old man was scheduled to undergo resection of giant pheochromocytoma. Epidural anesthesia was not performed due to anticoagulant therapy for lower limb thrombus. Tracheal intubation was performed with the Pentax-AWS Airwayscope. Preoperative screening revealed urine adrenaline 2.567.0 microg x day(-1) urine noradrenaline 1,734.0 microg x day(-1), and a tumor diameter of 96 x 60 mm. Catecholamine surge was controlled with 50 microg x kg(-1) x min(-1) continuous infusion of landiolol hydrochloride and IV bolus phentolamine. On tumor resection, although systemic blood pressure increased to 294 mmHg and was unresponsive to repeated phentolamine administration, the heart rate remained at 70-105 beats x min(-1) and there were no significant ST changes. PMID:25199327

  4. [Changes in the rat liver after exposure to high doses of bromex].

    PubMed

    Krustev, L; Kaloianova-Simeonova, F

    1982-01-01

    Experiments were carried out with male albino rats treated with the phosphorous-organic compound--bromex. The pesticide was perorally administered to one of the experimental groups--a single dose of 1/2 LD50. The same quantity bromex was administered to the other experimental group after a previous 20-day treatment with the same preparation but with a dose of 1/20 LD50. The changes, not particularly well manifested, progressing the organelles of the liver cells were followed up. The changes were established (in mitochondria, endoplasmatic reticulum, lysozoymes and some other organelles) to be better manifested in the group under a single effect of bromex. In this case they are interpreted as manifestation of one initial alterative process. In the group with the 20-day low doses, followed up by one high dose, the changes were gradual, lighter and considered a manifestation of a sort of adaptation or a form of subcellular liver regeneration. PMID:7178067

  5. Transient hyperammonemia related to chemotherapy with continuous infusion of high-dose 5-fluorouracil.

    PubMed

    Liaw, C C; Liaw, S J; Wang, C H; Chiu, M C; Huang, J S

    1993-06-01

    Hyperammonemic encephalopathy has been reported in patients receiving chemotherapy (CT). It is characterized by abrupt alteration in mental status with markedly elevated plasma ammonium levels in the absence of obvious liver disease. This paper reports seven patients who developed transient hyperammonemia during chemotherapy. The regimens all included continuous infusion of high-dose 5-fluorouracil (5-FU). The onset of hyperammonemic encephalopathy was 1.5-4 days after the start of CT. Five cases had infection and six had prerenal azotemia at the time of hyperammonemia. After management, plasma ammonium levels all returned to the normal range within 2 days. Except for one persistent coma, status of consciousness cleared completely. The true mechanism of transient hyperammonemia is unclear. The excess production of ammonium due to metabolites of 5-FU added to precipitating factors such as infection, hypovolemia or constipation may be the explanation for transient hyperammonemia in our study. PMID:8358058

  6. High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia.

    PubMed Central

    Rohatiner, A. Z.; Bassan, R.; Battista, R.; Barnett, M. J.; Gregory, W.; Lim, J.; Amess, J.; Oza, A.; Barbui, T.; Horton, M.

    1990-01-01

    In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables. PMID:2206954

  7. High-dose-rate (HDR) brachytherapy for the treatment of benign obstructive endobronchial granulation tissue

    SciTech Connect

    Madu, Chika N. . E-mail: chikam@xrt.upenn.edu; Machuzak, Michael S.; Sterman, Daniel H.; Musani, Ali; Ahya, Vivek; McDonough, James; Metz, James M.

    2006-12-01

    Background: Severe airway obstruction can occur in the setting of benign granulation tissue forming at bronchial anastomotic sites after lung transplantation in up to 20% of patients. Many of these benign lesions respond to stent placement, laser ablation, or balloon bronchoplasty. However, in certain cases, proliferation of granulation tissue may persist despite all therapeutic attempts. This study describes a series of refractory patients treated with high-dose-rate (HDR) brachytherapy for benign proliferation of granulation tissue, causing airway compromise. Methods and Materials: Between April 2002 and June 2005, 5 patients with significant airway compromise from recurrent granulation tissue were treated with HDR brachytherapy. All patients had previously failed to maintain a patent airway despite multiple bronchoscopic interventions. Treatment was delivered using an HDR brachytherapy afterloader with {sup 192}Ir. Dose prescription was to a depth of 1 cm. All patients were treated weekly, with total doses ranging from 10 Gy to 21 Gy in two to three fractions. Results: The median follow-up was 12 months. All patients experienced a reduction in therapeutic bronchoscopic procedures after HDR brachytherapy compared with the pretreatment period. With the exception of possible radiation-induced bronchitis in 1 patient, there were no other treatment related complications. At the time of this report, 2 patients have died and the other 3 are alive with marked symptomatic improvement and reduced bronchoscopic procedures. Conclusion: High-dose-rate brachytherapy is an effective treatment for benign proliferation of granulation tissue causing airway obstruction. The early response to therapy is encouraging and further follow-up is necessary to determine long-term durability and late effects.

  8. Assessment of simulated high-dose partial-body irradiation by PCC-R assay

    PubMed Central

    Romero, Ivonne; García, Omar; Lamadrid, Ana I.; Gregoire, Eric; González, Jorge E.; Morales, Wilfredo; Martin, Cécile; Barquinero, Joan-Francesc; Voisin, Philippe

    2013-01-01

    The estimation of the dose and the irradiated fraction of the body is important information in the primary medical response in case of a radiological accident. The PCC-R assay has been developed for high-dose estimations, but little attention has been given to its applicability for partial-body irradiations. In the present work we estimated the doses and the percentage of the irradiated fraction in simulated partial-body radiation exposures at high doses using the PCC-R assay. Peripheral whole blood of three healthy donors was exposed to doses from 0–20 Gy, with 60Co gamma radiation. To simulate partial body irradiations, irradiated and non-irradiated blood was mixed to obtain proportions of irradiated blood from 10–90%. Lymphocyte cultures were treated with Colcemid and Calyculin-A before harvest. Conventional and triage scores were performed for each dose, proportion of irradiated blood and donor. The Papworth's u test was used to evaluate the PCC-R distribution per cell. A dose-response relationship was fitted according to the maximum likelihood method using the frequencies of PCC-R obtained from 100% irradiated blood. The dose to the partially irradiated blood was estimated using the Contaminated Poisson method. A new D0 value of 10.9 Gy was calculated and used to estimate the initial fraction of irradiated cells. The results presented here indicate that by PCC-R it is possible to distinguish between simulated partial- and whole-body irradiations by the u-test, and to accurately estimate the dose from 10–20 Gy, and the initial fraction of irradiated cells in the interval from 10–90%. PMID:23596200

  9. Effects of high-dose selegiline on morphine reinforcement and precipitated withdrawal in dependent rats.

    PubMed

    Grasing, K; He, S

    2005-02-01

    Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects. Several lines of evidence suggest that treatment with selegiline at doses that exceed levels required for inhibition of MAO can produce distinct pharmacologic effects. The purpose of this study was to evaluate the effects of chronic treatment with high-dose selegiline on extinction responding, cue-induced reinstatement, morphine reinforcement and naloxone-precipitated withdrawal. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of 3.2 mg/kg per injection of morphine under a progressive ratio schedule. Daily treatment with saline or 6.4 mg/kg per day of selegiline was then administered over extinction, reinstatement and re-acquisition of morphine self-administration. To enhance or diminish the potential for psychostimulant effects, selegiline was administered either immediately prior to (pre-session) or 1 h following (post-session) extinction, reinstatement and self-administration sessions. Pre-session selegiline decreased the number of ratios completed on days 2, 3 and 4 of extinction, and decreased morphine self-administration during all four re-acquisition sessions. When administered at the same dose level, post-session selegiline decreased responding on the fourth extinction session, and was ineffective in modifying re-acquisition of self-administration. Selegiline administered by either schedule did not modify cue-induced reinstatement. Daily treatment with 6.4 mg/kg per day of selegiline did not modify self-administration of food under a progressive ratio schedule. Acute treatment with single, 6.4 mg/kg doses of selegiline attenuated naloxone-induced increases in ptosis and global withdrawal score, but did not modify any other sign of withdrawal or global withdrawal score calculated without ratings of ptosis. In conclusion, high-dose selegiline can attenuate extinction responding

  10. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Chang, Jee Suk; Wang, Michael L.C.; Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun; Song, Si Young; Seong, Jinsil

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  11. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock

    PubMed Central

    Zabet, Mohadeseh Hosseini; Mohammadi, Mostafa; Ramezani, Masoud; Khalili, Hossein

    2016-01-01

    Objective: Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock. Methods: Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes. Findings: During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009). Conclusion: High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies. PMID:27162802

  12. Nalbuphine Sedation in a Patient with Long Term, High Dose Chemotherapeutically Controlled Psychosis

    PubMed Central

    Kelly, Maureen; Howell, Robert M.

    1985-01-01

    Consideration of which pharmacologic agent to use when a patient requires sedation prior to an oral surgery procedure entails a number of factors, including past medical history, current medications and dose level, duration of administration, pharmacologic interactions, and the dental needs of the patient. The case described in this report illustrates the importance of consideration of these factors in a patient who required sedation prior to oral surgery while taking 800 mg chlorpromazine, 300 mg amantadine hydrochloride, and 900 mg of cimetidine daily. The possible pharmacologic interactions which could occur from concomitantly administering either diazepam or a narcotic in the presence of these agents are numerous and significant. The choice of sedative agent was further complicated by the fact that the patient was prescribed chlorpromazine and amantadine in doses which far exceeded the usual therapeutic levels and had been maintained for an extended period of time, over 8 months. Consequently, any adverse reactions that may have resulted when sedating a patient taking chlorapromazine and amantadine hydrochloride in lower doses for a shorter duration would be more likely to occur with greater speed and severity in a patient receiving such high-dose, long-term therapy. Also, unusual reactions which have not been reported with usual therapeutic dose levels might also occur since these high doses approach toxic levels for some patients. Additionally, a sedative agent had to be used which would not interfere with the antipsychotic effects of chlorpromazine since the patient's psychiatric condition required maintenance of these unusually high therapeutic levels. The following case report gives the rationale and outcome of utilizing nalbuphine for obtunding pain and producing sedation during an oral surgery procedure under such complex therapeutic conditions. PMID:3866505

  13. Nalbuphine sedation in a patient with long-term, high-dose chemotherapeutically controlled psychosis.

    PubMed

    Kelly, M; Howell, R M

    1985-01-01

    Consideration of which pharmacologic agent to use when a patient requires sedation prior to an oral surgery procedure entails a number of factors, including past medical history, current medications and dose level, duration of administration, pharmacologic interactions, and the dental needs of the patient. The case described in this report illustrates the importance of consideration of these factors in a patient who required sedation prior to oral surgery while taking 800 mg chlorpromazine, 300 mg amantadine hydrochloride, and 900 mg of cimetidine daily. The possible pharmacologic interactions which could occur from concomitantly administering either diazepam or a narcotic in the presence of these agents are numerous and significant. The choice of sedative agent was further complicated by the fact that the patient was prescribed chlorpromazine and amantadine in doses which far exceeded the usual therapeutic levels and had been maintained for an extended period of time, over 8 months. Consequently, any adverse reactions that may have resulted when sedating a patient taking chlorapromazine and amantadine hydrochloride in lower doses for a shorter duration would be more likely to occur with greater speed and severity in a patient receiving such high-dose, long-term therapy. Also, unusual reactions which have not been reported with usual therapeutic dose levels might also occur since these high doses approach toxic levels for some patients. Additionally, a sedative agent had to be used which would not interfere with the antipsychotic effects of chlorpromazine since the patient's psychiatric condition required maintenance of these unusually high therapeutic levels. The following case report gives the rationale and outcome of utilizing nalbuphine for obtunding pain and producing sedation during an oral surgery procedure under such complex therapeutic conditions. PMID:3866505

  14. Magnetic Resonance Lymphography-Guided Selective High-Dose Lymph Node Irradiation in Prostate Cancer

    SciTech Connect

    Meijer, Hanneke J.M.; Debats, Oscar A.; Kunze-Busch, Martina; Kollenburg, Peter van; Leer, Jan Willem; Witjes, J. Alfred; Kaanders, Johannes H.A.M.; Barentsz, Jelle O.; Lin, Emile N.J.Th. van

    2012-01-01

    Purpose: To demonstrate the feasibility of magnetic resonance lymphography (MRL) -guided delineation of a boost volume and an elective target volume for pelvic lymph node irradiation in patients with prostate cancer. The feasibility of irradiating these volumes with a high-dose boost to the MRL-positive lymph nodes in conjunction with irradiation of the prostate using intensity-modulated radiotherapy (IMRT) was also investigated. Methods and Materials: In 4 prostate cancer patients with a high risk of lymph node involvement but no enlarged lymph nodes on CT and/or MRI, MRL detected pathological lymph nodes in the pelvis. These lymph nodes were identified and delineated on a radiotherapy planning CT to create a boost volume. Based on the location of the MRL-positive lymph nodes, the standard elective pelvic target volume was individualized. An IMRT plan with a simultaneous integrated boost (SIB) was created with dose prescriptions of 42 Gy to the pelvic target volume, a boost to 60 Gy to the MRL-positive lymph nodes, and 72 Gy to the prostate. Results: All MRL-positive lymph nodes could be identified on the planning CT. This information could be used to delineate a boost volume and to individualize the pelvic target volume for elective irradiation. IMRT planning delivered highly acceptable radiotherapy plans with regard to the prescribed dose levels and the dose to the organs at risk (OARs). Conclusion: MRL can be used to select patients with limited lymph node involvement for pelvic radiotherapy. MRL-guided delineation of a boost volume and an elective pelvic target volume for selective high-dose lymph node irradiation with IMRT is feasible. Whether this approach will result in improved outcome for these patients needs to be investigated in further clinical studies.

  15. High-Dose-Rate Endobronchial Brachytherapy for Recurrent Airway Obstruction From Hyperplastic Granulation Tissue

    SciTech Connect

    Tendulkar, Rahul D. Fleming, Peter A.; Reddy, Chandana A.; Gildea, Thomas R.; Machuzak, Michael; Mehta, Atul C.

    2008-03-01

    Purpose: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions. Methods and Materials: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV{sub 1}), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB. Results: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV{sub 1} improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula. Conclusion: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively.

  16. Safety of high-dose doripenem in adult patients with cystic fibrosis

    PubMed Central

    Strawbridge, Seth; Nailor, Michael D.

    2016-01-01

    Background: High doses of β-lactam antibiotics have been advocated for acute pulmonary exacerbations caused by Pseudomonas aeruginosa in patients with cystic fibrosis (CF) secondary to high minimum inhibitory concentrations (MIC) of the infecting organisms. Some β-lactam antibiotics have increased elimination in CF patients. This case series examines the safety of high-dose doripenem (HDD), 2 g intravenously every 8 hours, which is 4 times the labeled dose, in CF patients. Methods: This was a retrospective, single site, chart review of all CF patients given HDD during a 3-year period. Adverse events were prospectively defined using labeled definitions within the package insert and the medical literature. A standard case report form was used to collect demographic details, antibiotic lengths of therapy and adverse events. Results: A total of 17 patients (9 males), with a median age of 24 years, contributed 43 unique visits and 382 HDD exposure days. Mean duration of inpatient doripenem use was 8.9 days. Concurrent antibiotics were common, with a median number of additional antibiotics per admission of three. The median number of adverse effects documented was two. The most common adverse event was anemia, which was identified in 41 of 43 visits, but was present on admission in 31 instances. One patient developed leukopenia for 1 day, but returned to normal without dose adjustment. There were three instances of Clostridium difficile infection. One patient was documented to have an allergic reaction that led to discontinuation, but was ultimately rechallenged without adverse effect. Other common adverse events were gastrointestinal in origin. No other possible adverse effects led to discontinuation of the drug. Conclusions: In adult patients with CF, HDD in combination with other antibiotics did not lead to adverse effects necessitating discontinuation. HDD should be considered in this selected patient population, particularly when high MIC organisms are identified

  17. High-Dose Conformal Radiotherapy for Patients With Stage III Non-Small-Cell Lung Carcinoma

    SciTech Connect

    Nakayama, Hidetsugu; Satoh, Hiroaki; Kurishima, Koichi; Ishikawa, Hiroichi; Tokuuye, Koichi

    2010-11-01

    Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

  18. External beam radiation therapy followed by high-dose-rate brachytherapy for inoperable superficial esophageal carcinoma

    SciTech Connect

    Pasquier, David . E-mail: d-pasquier@o-lambret.fr; Mirabel, Xavier; Adenis, Antoine; Rezvoy, Nicolas; Hecquet, Genevieve; Fournier, Charles; Coche-Dequeant, Bernard; Prevost, Bernard; Castelain, Bernard; Lartigau, Eric

    2006-08-01

    Purpose: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer. Patients and Methods: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy ({+-}4.83) and 8.82 Gy ({+-}3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications. Results: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%). Conclusion: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.

  19. Effect of high dose vitamin C on Epstein-Barr viral infection

    PubMed Central

    Mikirova, Nina A.; Hunninghake, Ronald

    2014-01-01

    Background Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection. Material/Methods The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection. Results Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels. Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease. In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D. Conclusions The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro. PMID:24793092

  20. High-Dose-Rate 192Ir Brachytherapy Dose Verification: A Phantom Study

    PubMed Central

    Nikoofar, Alireza; Hoseinpour, Zohreh; Rabi Mahdavi, Seied; Hasanzadeh, Hadi; Rezaei Tavirani, Mostafa

    2015-01-01

    Background: The high-dose-rate (HDR) brachytherapy might be an effective tool for palliation of dysphagia. Because of some concerns about adverse effects due to absorbed radiation dose, it is important to estimate absorbed dose in risky organs during this treatment. Objectives: This study aimed to measure the absorbed dose in the parotid, thyroid, and submandibular gland, eye, trachea, spinal cord, and manubrium of sternum in brachytherapy in an anthropomorphic phantom. Materials and Methods: To measure radiation dose, eye, parotid, thyroid, and submandibular gland, spine, and sternum, an anthropomorphic phantom was considered with applicators to set thermoluminescence dosimeters (TLDs). A specific target volume of about 23 cm3 in the upper thoracic esophagus was considered as target, and phantom planned computed tomography (CT) for HDR brachytherapy, then with a micro-Selectron HDR (192Ir) remote after-loading unit. Results: Absorbed doses were measured with calibrated TLDs and were expressed in centi-Gray (cGy). In regions far from target (≥ 16 cm) such as submandibular, parotid and thyroid glands, mean measured dose ranged from 1.65 to 5.5 cGy. In closer regions (≤ 16 cm), the absorbed dose might be as high as 113 cGy. Conclusions: Our study showed similar depth and surface doses; in closer regions, the surface and depth doses differed significantly due to the role of primary radiation that had imposed a high-dose gradient and difference between the plan and measurement, which was more severe because of simplifications in tissue inhomogeneity, considered in TPS relative to phantom. PMID:26413250

  1. Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects.

    PubMed

    Lee, Jonghyun; Lee, Hyung K; Kim, Chan Y; Hong, Young J; Choe, Chul M; You, Tae W; Seong, Gong J

    2005-06-01

    The aim of the present study was to determine the effect of purified high-dose anthocyanoside oligomer administration on nocturnal visual function and clinical symptoms in low-to-moderate myopia subjects. The study was a randomized, double-blind, placebo-controlled trial and involved sixty subjects with asthenopia and refractive errors between -1.00 and -8.00 diopters in both eyes. Thirty subjects were administered a purified high-dose anthocyanoside oligomer (100 mg tablet comprising 85 % anthocyanoside oligomer), and thirty were given a placebo in tablet form twice daily for 4 weeks. Prior to the treatment, the placebo and anthocyanoside groups were similar in terms of age and contrast sensitivity. Before and after treatment, subjects completed a questionnaire to determine their clinical symptoms and were also assessed for nocturnal visual function using contrast sensitivity testing. Questionnaire data analysis showed that, following treatment, twenty-two (73.3 %) anthocyanoside subjects showed improved symptoms, whereas only one placebo subject showed an improvement (Fisher's exact test, P<0.0001). Contrast sensitivity levels according to each cycle per degree significantly improved in the anthocyanoside group and remained stable in the placebo group. The mean contrast sensitivity change in the anthocyanoside group was 2.41 (SD) 1.91, compared with -0.66 (SD) 2.66 dB for the placebo group (unpaired Student's t test, P<0.0001). At all cycle per degree levels, contrast sensitivity changes in the anthocyanoside group were better than in the placebo group (unpaired Student's t test, P<0.05). The present data show that the administration of anthocyanoside oligomer appears to improve subjective symptoms and objective contrast sensitivity in myopia subjects with asthenopia. PMID:16022759

  2. High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization

    SciTech Connect

    Hurkmans, Coen W. . E-mail: coen.hurkmans@cze.nl; Meijer, Gert J.; Vliet-Vroegindeweij, Corine van; Cassee, Jorien

    2006-11-01

    Purpose: Recently a Phase III randomized trial has started comparing a boost of 16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young women. Our main aim was to develop an efficient simultaneously integrated boost (SIB) technique for the high-dose arm of the trial. Methods and Materials: Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A tangential field intensity-modulated radiotherapy technique added to a sequentially planned 3-field boost (SEQ) was compared with a simultaneously planned technique (SIB) using inverse optimization. Normalized total dose (NTD)-corrected dose volume histogram parameters were calculated and compared. Results: The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and 2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost receiving more than 95% of the prescribed dose was 97% or more for both techniques. Also, the mean lung dose and mean heart dose did not differ much between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a significantly more conformal irradiation of the PTV-boost. The volume of the PTV-breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost dose could be reduced considerably using the SIB as compared with the SEQ from 129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). Conclusions: A high-dose simultaneously integrated breast boost technique has been developed. The unwanted excessive dose to the breast was significantly reduced.

  3. Dosimetric Effects of Air Pockets Around High-Dose Rate Brachytherapy Vaginal Cylinders

    SciTech Connect

    Richardson, Susan; Palaniswaamy, Geethpriya; Grigsby, Perry W.

    2010-09-01

    Purpose: Most physicians use a single-channel vaginal cylinder for postoperative endometrial cancer brachytherapy. Recent published data have identified air pockets between the vaginal cylinders and the vaginal mucosa. The purpose of this research was to evaluate the incidence, size, and dosimetric effects of these air pockets. Methods and Materials: 25 patients receiving postoperative vaginal cuff brachytherapy with a high-dose rate vaginal cylinders were enrolled in this prospective data collection study. Patients were treated with 6 fractions of 200 to 400 cGy per fraction prescribed at 5 mm depth. Computed tomography simulation for brachytherapy treatment planning was performed for each fraction. The quantity, volume, and dosimetric impact of the air pockets surrounding the cylinder were quantified. Results: In 25 patients, a total of 90 air pockets were present in 150 procedures (60%). Five patients had no air pockets present during any of their treatments. The average number of air pockets per patient was 3.6, with the average total air pocket volume being 0.34 cm{sup 3} (range, 0.01-1.32 cm{sup 3}). The average dose reduction to the vaginal mucosa at the air pocket was 27% (range, 9-58%). Ten patients had no air pockets on their first fraction but air pockets occurred in subsequent fractions. Conclusion: Air pockets between high-dose rate vaginal cylinder applicators and the vaginal mucosa are present in the majority of fractions of therapy, and their presence varies from patient to patient and fraction to fraction. The existence of air pockets results in reduced radiation dose to the vaginal mucosa.

  4. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin.

    PubMed

    Lundvig, Ditte M S; Pennings, Sebastiaan W C; Brouwer, Katrien M; Mtaya-Mlangwa, Matilda; Mugonzibwa, Emeria; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-08-15

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between epidermal keratinocytes and dermal fibroblasts are essential. We previously demonstrated that curcumin increased reactive oxygen species (ROS) formation and apoptosis in dermal fibroblasts, which could be prevented by pre-induction of the cytoprotective enzyme heme oxygenase (HO)-1. To better understand the effects of curcumin on wound repair, we now assessed the effects of high doses of curcumin on the survival of HaCaT keratinocytes and the role of the HO system. We exposed HaCaT keratinocytes to curcumin in the presence or absence of the HO-1 inducers heme (FePP) and cobalt protoporphyrin (CoPP). We then assessed cell survival, ROS formation, and caspase activation. Curcumin induced caspase-dependent apoptosis in HaCaT keratinocytes via a ROS-dependent mechanism. Both FePP and CoPP induced HO-1 expression, but only FePP protected against curcumin-induced ROS formation and caspase-mediated apoptosis. In the presence of curcumin, FePP but not CoPP induced the expression of the iron scavenger ferritin. Together, our data show that the induction of ferritin, but not HO, protects HaCaT keratinocytes against cytotoxic doses of curcumin. The differential response of fibroblasts and keratinocytes to high curcumin doses may provide the basis for improving curcumin-based wound healing therapies. PMID:26071936

  5. [Effect of high dose pergolide mesilate on restless legs syndrome associated with Parkinson disease].

    PubMed

    Imamura, Akiko; Tsuboi, Yoshio; Tanaka, Miki; Obata, Toyoshi; Yamada, Tatsuo

    2007-04-01

    Restless legs syndrome (RLS) is one of the common nocturnal disturbance seen in Parkinson's disease (PD) patients. The prevalence of RLS with PD is greater than that of general populations; however, etiology of RLS in patients with PD is still controversial. We report a 63-year-old man with PD, who was admitted to our hospital with uncontrollable unpleasant feeling in both legs leading to sleep disturbance. At age 59, he experienced numbness and nocturnal myoclonus in his right foot. One year later, he developed resting tremor and bradykinesia in his right hand, and was diagnosed as PD. Levodopa was initiated with favorable response for his resting tremor and bradykinesia, however, his dysesthesia of the legs spread to both side and associated with an urge to move which occurs at rest and was ameliorated by walking. On admission, his parkinsonism was well controlled by 400 mg/ day of levodopa/benserazide. Polysomnography (PSG) revealed periodic limb movements in sleep (PLMS). Secondary RLS such as drug-induced, iron deficiency and uraemia, was excluded in this patient. Because levodopa did not improve his RLS, additional symptomatic RLS treatment was initiated. Oral dosage with 150 microg pergolide did not have any effect on his RLS symptoms. An increase up to 750 microg pergolide led to a marked reduction of symptoms. Repeated PSG showed significant reduction of PLMS and improved sleep efficacy. Usually, low dose of dopamine agonist is enough to treat RLS occurred in general populations. However, moderate to high dose of dopamine agonists were needed for our patient with RLS, indicating that pharmacological responses might be different between RLS in general and that associated with PD. It is important to consider that PD-related RLS can be treated with high dose dopamine agonist to obtain favorable management of nocturnal disturbances. PMID:17511286

  6. Mechanical Performance of Ferritic Martensitic Steels for High Dose Applications in Advanced Nuclear Reactors

    NASA Astrophysics Data System (ADS)

    Anderoglu, Osman; Byun, Thak Sang; Toloczko, Mychailo; Maloy, Stuart A.

    2013-01-01

    Ferritic/martensitic (F/M) steels are considered for core applications and pressure vessels in Generation IV reactors as well as first walls and blankets for fusion reactors. There are significant scientific data on testing and industrial experience in making this class of alloys worldwide. This experience makes F/M steels an attractive candidate. In this article, tensile behavior, fracture toughness and impact property, and creep behavior of the F/M steels under neutron irradiations to high doses with a focus on high Cr content (8 to 12) are reviewed. Tensile properties are very sensitive to irradiation temperature. Increase in yield and tensile strength (hardening) is accompanied with a loss of ductility and starts at very low doses under irradiation. The degradation of mechanical properties is most pronounced at <0.3 T M ( T M is melting temperature) and up to 10 dpa (displacement per atom). Ferritic/martensitic steels exhibit a high fracture toughness after irradiation at all temperatures even below 673 K (400 °C), except when tested at room temperature after irradiations below 673 K (400 °C), which shows a significant reduction in fracture toughness. Creep studies showed that for the range of expected stresses in a reactor environment, the stress exponent is expected to be approximately one and the steady state creep rate in the absence of swelling is usually better than austenitic stainless steels both in terms of the creep rate and the temperature sensitivity of creep. In short, F/M steels show excellent promise for high dose applications in nuclear reactors.

  7. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

    PubMed Central

    Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

    2013-01-01

    Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

  8. Safety and T Cell Modulating Effects of High Dose Vitamin D3 Supplementation in Multiple Sclerosis

    PubMed Central

    Smolders, Joost; Peelen, Evelyn; Thewissen, Mariëlle; Cohen Tervaert, Jan Willem; Menheere, Paul; Hupperts, Raymond; Damoiseaux, Jan

    2010-01-01

    Background A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures. Methodology/Principal Findings Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31–175) at week 0 to 380 nmol/L (151–535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P = 0.143). An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P = 0.021). Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P = 0.035). Conclusion/Significance Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials. Trial Registration Clinicaltrials.gov NCT00940719 PMID:21179201

  9. Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

    SciTech Connect

    Able, Charles M.; Bright, Megan; Frizzell, Bart

    2013-03-01

    Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles with 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.

  10. High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone.

    PubMed

    Allolio, B; Oremus, M; Reincke, M; Schaeffer, H J; Winkelmann, W; Heck, G; Schulte, H M

    1995-12-01

    High concentrations of unbound cortisol in late pregnancy have been explained by the antiglucocorticoid activity of high progesterone levels. To further test this hypothesis we studied the effect of high-dose progesterone on baseline and corticotrophin-releasing hormone (CRH)-induced hormone secretion in humans. In a double-blind crossover study eight healthy male volunteers received either progesterone (0.714 mg.kg-1.h-1 for 60 min followed by a dose of 0.45 mg.kg-1.h-1 over a total infusion time of 315 min) or vehicle as a continuous intravenous infusion. At 210 min a CRH test (0.1 microgram/kg body weight as bolus iv) was performed. Within 30 min after the start of progesterone administration the serum progesterone level increased to 454 +/- 31 nmol/l and remained in the range of third trimester pregnancy concentrations throughout the infusion period. During vehicle infusion the progesterone level remained in the normal range for healthy males and demonstrated a small but significant increase after CRH (1.52 +/- 0.23 vs 0.74 +/- 0.14 mmol/l; p < 0.01). However, baseline and CRH-stimulated serum cortisol and plasma adrenocorticotrophic hormone remained unaffected by high-dose progesterone. Moreover, unbound salivary cortisol also was not affected by progesterone, suggesting that there is no significant competition for transcortin binding sites. In conclusion, no antiglucorticoid activity was found after short-term administration of progesterone in males. These findings cast doubts on the concept that the alterations of the pituitary-adrenal axis in late pregnancy are induced by the antiglucocorticoid activity of high progesterone concentrations. PMID:8548055

  11. High doses of pseudoephedrine hydrochloride accelerate onset of CNS oxygen toxicity seizures in unanesthetized rats.

    PubMed

    Pilla, R; Held, H E; Landon, C S; Dean, J B

    2013-08-29

    Pseudoephedrine (PSE) salts (hydrochloride and sulfate) are commonly used as nasal and paranasal decongestants by scuba divers. Anecdotal reports from the Divers Alert Network suggest that taking PSE prior to diving while breathing pure O₂ increases the risk for CNS oxygen toxicity (CNS-OT), which manifests as seizures. We hypothesized that high doses of PSE reduce the latency time to seizure (LS) in unanesthetized rats breathing 5 atmospheres absolute (ATA) of hyperbaric oxygen. Sixty-three male rats were implanted with radio-transmitters that recorded electroencephalogram activity and body temperature. After ≥7-day recovery, and 2 h before "diving", each rat was administered either saline solution (control) or PSE hydrochloride intragastrically at the following doses (mg PSE/kg): 0, 40, 80, 100, 120, 160, and 320. Rats breathed pure O₂ and were dived to 5ATA until the onset of behavioral seizures coincident with neurological seizures. LS was the time elapsed between reaching 5ATA and exhibiting seizures. We observed a significant dose-dependent decrease in the LS at doses of 100-320 mg/kg, whereas no significant differences in LS from control value were observed at doses ≤80 mg/kg. Our findings showed that high doses of PSE accelerate the onset of CNS-OT seizures in unanesthetized rats breathing 5ATA of poikilocapnic hyperoxia. Extrapolating our findings to humans, we conclude that the recommended daily dose of PSE should not be abused prior to diving with oxygen-enriched gas mixes or pure O₂. PMID:23624060

  12. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    PubMed Central

    Moral, Angel; Moreno, Victoria; Girón, Francisco; El-Qutob, David; Moure, José D; Alcántara, Manuel; Padial, Antonia; Oehling, Alberto G; Millán, Carmen; de la Torre, Fernando

    2016-01-01

    Background Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. Patients and methods A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. Results The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). Conclusion In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. PMID:27418842

  13. Prevention of high-dose-rate brachytherapy accidents. ICRP Publication 97.

    PubMed

    Valentin, J

    2005-01-01

    High-dose-rate brachytherapy is a rapidly growing technique (HDR) that has been replacing low-dose-rate (LDR) procedures over the last few years in both industrialised and developing countries. It is estimated that about 500,000 procedures (administration of treatment) are performed by HDR units annually. LDR equipment has been discontinued by many manufacturers over the last few years, leaving HDR brachytherapy as the major alternative. HDR brachytherapy techniques deliver a very high dose, of the order of 1.6-5.0 Gy/min, so mistakes can lead to under- or overdosage with the potential for clinical adverse effects. More than 500 HDR accidents (including one death) have been reported along the entire chain of procedures from source packing to delivery of dose. Human error has been the prime cause of radiation events. In the present report, the International Commission on Radiological Protection concludes that many accidents could have been prevented if staff had had functional monitoring equipment and paid attention to the results. Since iridium has relatively short half-life, the HDR sources need to be replaced approximately every 4 months. Over 10,000 HDR sources are transported annually, with the resultant potential for accidents; therefore, appropriate procedures and regulations must be observed. A number of specific recommendations on procedures and equipment are given in this report. The need for an emergency plan and for practising emergency procedures is stressed. The possibility of loss or theft of sources must be kept in mind. A collaborating team of specifically trained personnel following quality assurance (QA) procedures is necessary to prevent accidents. Maintenance is indispensable component of QA; external audits of procedures re-enforce good and safe practice, and identify potential causes of accidents. QA should include peer review of cases. Accidents and incidents should be reported and the lessons learned should be shared with other users to

  14. Chlorite dismutases, DyPs, and EfeB: 3 microbial heme enzyme families comprise the CDE structural superfamily

    PubMed Central

    Goblirsch, Brandon; Kurker, Richard C.; Streit, Bennett R.; Wilmot, Carrie M.; DuBois, Jennifer L.

    2011-01-01

    Heme proteins are extremely diverse, widespread, and versatile biocatalysts, sensors, and molecular transporters. The chlorite dismutase family of hemoproteins received its name due to the ability of the first-isolated members to detoxify anthropogenic ClO2−, a function believed to have evolved only in the last few decades. Family members have since been found in fifteen bacterial and archaeal genera, suggesting ancient roots. A structure- and sequence-based examination of the family is presented, in which key sequence and structural motifs are identified and possible functions for family proteins are proposed. Newly identified structural homologies moreover demonstrate clear connections to two other large, ancient, and functionally mysterious protein families. We propose calling them collectively the CDE superfamily of heme proteins. PMID:21354424

  15. Reverse osmosis membrane composition, structure and performance modification by bisulphite, iron(III), bromide and chlorite exposure.

    PubMed

    Ferrer, O; Gibert, O; Cortina, J L

    2016-10-15

    Reverse osmosis (RO) membrane exposure to bisulphite, chlorite, bromide and iron(III) was assessed in terms of membrane composition, structure and performance. Membrane composition was determined by Rutherford backscattering spectrometry (RBS) and membrane performance was assessed by water and chloride permeation, using a modified version of the solution-diffusion model. Iron(III) dosage in presence of bisulphite led to an autooxidation of the latter, probably generating free radicals which damaged the membrane. It comprised a significant raise in chloride passage (chloride permeation coefficient increased 5.3-5.1 fold compared to the virgin membrane under the conditions studied) rapidly. No major differences in terms of water permeability and membrane composition were observed. Nevertheless, an increase in the size of the network pores, and a raise in the fraction of aggregate pores of the polyamide (PA) layer were identified, but no amide bond cleavage was observed. These structural changes were therefore, in accordance with the transport properties observed. PMID:27470468

  16. Authigenic chlorite as a controlling factor in the exploration of Turonian/Coniacian turbidites in the Santos Basin

    SciTech Connect

    Porsche, E.; Lopes de Freitas, E.

    1996-08-01

    Upper Turonian/Coniacian and Campanian turbidites are major targets for petroleum exploration in the Santos Basin, southeastern Brazil. They occur between 140 and 1000 m of present water depth, are buried at about 4500 m, and reach thickness of up to 60 m. The main reservoir facies is composed of unstratified, fine to very fine grained, poorly sorted sandstones, which framework is compositionally immature, including a high proportion of feldspars and volcanic rock fragments. Early coating of grains by authigenic chlorite inhibited pressure solution and quartz cementation in the reservoir. This diagenetic characteristic allowed important preservation of primary porosity (>20%) in the reservoir; nevertheless its permeability never exceeds 30 ml. The study of sedimentary facies and related depositional processes has been conducted to predict the distribution of petroleum-bearing turbidites throughout the Santos Basin; this comprises a major challenge for the petroleum exploration in this important Brazilian exploration frontier.

  17. Multiple hydrothermal and metamorphic events in the Kidd Creek volcanogenic massive sulphide deposit, Timmins, Ontario: evidence from tourmalines and chlorites

    USGS Publications Warehouse

    Slack, J.F.; Coad, P.R.

    1989-01-01

    The tourmalines and chlorites record a series of multiple hydrothermal and metamorphic events. Paragenetic studies suggest that tourmaline was deposited during several discrete stages of mineralization, as evidence by brecciation and cross-cutting relationships. Most of the tourmalines have two concentric growth zones defined by different colours (green, brown, blue, yellow). Some tourmalines also display pale discordant rims that cross-cut and embay the inner growth zones and polycrystalline, multiple-extinction domains. Late sulphide veinlets (chalcopyrite, pyrrhotite) transect the inner growth zones and pale discordant rims of many crystals. The concentric growth zones are interpreted as primary features developed by the main ore-forming hydrothermal system, whereas the discordant rims, polycrystalline domains, and cross-cutting sulphide veinlets reflect post-ore metamorphic processes. Variations in mineral proportions and mineral chemistry within the deposit mainly depend on fluctuations in temperature, pH, water/rock ratios, and amounts of entrained seawater. -from Authors

  18. Phyllosilicate weathering pathways in chlorite-talc bearing soil parent materials, D.R. Congo: early findings.

    NASA Astrophysics Data System (ADS)

    Dumon, Mathijs; Oostermeyer, Fran; Timmermans, Els; De Meulemeester, Aschwin; Mees, Florias; Van Driessche, Isabel; Erens, Hans; Bazirake Mujinya, Basile; Van Ranst, Eric

    2015-04-01

    The study of the formation and transformation of clay minerals is of the upmost importance to understand soil formation and to adjust land-use management to the land surface conditions. These clay minerals determine to a large extent the soil physical and chemical properties. It is commonly observed that over time the mineralogy of any parent material is transformed to a simple assemblage composed mostly of Al and Fe oxides and low-activity clays, e.g. kaolinite. This is especially obvious in the humid tropics, which have been protected from glacial erosion, allowing deep, highly weathered soils to form. Despite the abundant presence of kaolinite in these soils, its formation pathways are still under debate: either neoformation by dissolution-crystallisation reactions or solid-state transformation of 2:1 phyllosilicates. To elucidate this, weathering sequences in a unique 40 m core taken below a termite mound, reaching a talc-chlorite bearing substrate in the Lubumbashi area, Katanga, DR Congo are being investigated in detail using a.o. quantitative X-ray diffraction analysis, chemical characterization, micromorphology and µXRF-scanning with the main objective to improve the understanding of the formation pathways of kaolinite subgroup minerals in humid tropical environments. Based on an initial characterization of the core, two zones of interest were selected for more detailed analysis, for which the early findings will be presented. The first zone extends from ca. 9 m to 11 m below the surface is dominated by kaolinite but shows early traces of primary talc and micas. The second zone extends from 34 to 36 m below the surface and contains large amounts of chlorite, with smaller amounts of talc, micas and kaolinite.

  19. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease.

    PubMed

    Yuen, A R; Rosenberg, S A; Hoppe, R T; Halpern, J D; Horning, S J

    1997-02-01

    Sixty patients with Hodgkin's disease, refractory to or at first recurrence after chemotherapy, received cytoreductive therapy followed by high-dose etoposide, cyclophosphamide and either total body irradiation or carmustine and autografting (median follow-up, 3.6 years; range, 1.1 to 7.5 years). A matched conventional salvage group of 103 patients was selected from patients treated at Stanford University Medical Center between January 1976 and January 1989 (median follow-up, 10.3 years; range, 3.0 to 15.7 years). Overall survival (OS), event-free survival (EFS), and freedom from progression (FFP) at 4 years follow-up favored patients who received high-dose therapy compared with conventional salvage treatment (OS: 54% v 47%, P = .25; EFS: 53% v 27%, P < .01; FFP: 62% v 32%, P < .01). In Cox regression analysis, response to cytoreductive or salvage therapy and B symptoms at relapse were the most important predictors of OS. The use of high-dose therapy at relapse, a longer duration of remission, and favorable response to cytoreductive or salvage therapy were most predictive of superior FFP and EFS. These data from a single institution comparing conventional and high-dose therapy in matched patients demonstrate an advantage for high-dose therapy and autografting in the sustained control of Hodgkin's disease. As with primary therapy, it is difficult to demonstrate a statistically significant survival advantage, despite an apparently superior cure rate. However, patients failing induction therapy or relapsing within 1 year benefited significantly from high-dose therapy by all outcome measures (OS, EFS, FFP). As the transplant-related mortality rates decline in Hodgkin's disease, it is predicted that cure rates and late effects will become ultimate determinants of the success of high-dose therapy and autografting. PMID:9028312

  20. Assessment of sodium hypochlorite and acidified sodium chlorite as antimicrobial agents to inhibit growth of Escherichia coli O157:H7 and natural microflora on shredded carrots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influence of cold tap water, sodium hypochlorite (200 ppm) and acidified sodium chlorite (100, 250, 500 and 1000 ppm) washes on survival and growth of Escherichia coli O157:H7 inoculated onto shredded carrots was determined after treatment and 7 and 14 days of storage. Growth of total mesophilic...

  1. EVALUATION OF THE IMMUNOMODULATORY EFFECTS OF THE DISINFECTION BYPRODUCT, SODIUM CHLORITE, IN FEMALE B6C3F1 MICE: A DRINKING WATER STUDY

    EPA Science Inventory

    Evaluation of the Immunomodulatory Effects of the Disinfection By-product, Sodium chlorite, in Female B6C3f1 mice: A Drinking Water Study.

    Niel A. Karrow, Tal, L. Guo, J. Ann McCay, Greg W. Johnson, Ronnetta D. Brown, Debrorah L. Musgrove, Dori R. Germolec, Robert W. Lueb...

  2. Combination of sodium chlorite and calcium propionate reduces enzymatic browning and microbial population of fresh-cut ‘Granny Smith’ apples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tissue browning and microbial growth are the main concerns associated with fresh-cut apples. In this study, effects of sodium chlorite (SC) and calcium propionate (CP), individually and combined, on quality and microbial population of apple slices were investigated. ‘Granny Smith’ apple slices, dipp...

  3. Combined effects of sodium chlorite dip treatment and chitosan coatings on the quality of fresh-cut d’Anjou pears

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study evaluated the effects of sodium chlorite (SC) alone and its sequential treatment with edible coatings on browning inhibition and quality maintenance of fresh-cut d’Anjou pears. Edible coatings were prepared from chitosan (CH) and its water soluble derivative: carboxymethyl chitosan (CMCH...

  4. Effectiveness of Home Exercise on Pain, Function, and Strength of Manual Wheelchair Users With Spinal Cord Injury: A High-Dose Shoulder Program With Telerehabilitation

    PubMed Central

    Van Straaten, Meegan; Cloud, Beth A.; Morrow, Melissa M.; Ludewig, Paula M.; Zhao, Kristin D.

    2014-01-01

    Objective To test the effectiveness of a high-dose home exercise/telerehabilitation program for manual wheelchair users who have a spinal cord injury (SCI) and determine whether the intervention would reduce pain and increase function, as we hypothesized. Design A pre-post trial with outcomes measured at 3 time points: baseline, postintervention (12wk), and follow-up (24+ weeks). Setting Subjects performed an exercise program at their homes using telerehabilitation for therapist monitoring of technique and exercise advancement. Baseline and postintervention data were collected at a motion analysis laboratory in a tertiary medical center. Participants A convenience sample of manual wheelchair users (N = 16, 3 women; average age, 41y; average time in a wheelchair, 16y) with shoulder pain (average pain duration, 9y) and mechanical impingement signs on physical examination. Interventions A 12-week home exercise program of rotator cuff and scapular stabilization exercises was given to each participant. The program included a high dose of 3 sets of 30 repetitions, 3 times weekly, and regular physical therapist supervision via videoconferencing. Main Outcome Measures Primary outcomes of pain and function were measured with the Wheelchair User's Shoulder Pain Index (WUSPI), Disabilities of Arm, Shoulder, and Hand (DASH) Index, and Shoulder Rating Questionnaire (SRQ). Secondary outcomes of strength were measured with isometric strength tests of scapulothoracic and glenohumeral muscles, and a static fatigue test of the lower trapezius. Results Pain was reduced and function improved after the intervention. There was a significant main effect for pain and function between the 3 time points based on the Friedman signed-ranked test, WUSPI (χ22 = 5.10, P = .014), DASH Index (χ22 = 5.41, P = .012), and SRQ (χ22 = 23.71, P ≤.001). Wilcoxon signed-rank tests demonstrated that isometric strength measurements of the serratus anterior and scapular retractors increased after the

  5. A systematic review of pediatric clinical trials of high dose vitamin D

    PubMed Central

    Nama, Nassr; Menon, Kusum; Iliriani, Klevis; Pojsupap, Supichaya; Sampson, Margaret; O’Hearn, Katie; Zhou, Linghong (Linda); McIntyre, Lauralyn; Fergusson, Dean

    2016-01-01

    Background. Due to inadequate UV exposure, intake of small quantities of vitamin D is recommended to prevent musculoskeletal disease. Both basic science and observational literature strongly suggest that higher doses may benefit specific populations and have non-musculoskeletal roles. Evaluating the evidence surrounding high dose supplementation can be challenging given a relatively large and growing body of clinical trial evidence spanning time, geography, populations and dosing regimens. Study objectives were to identify and summarize the clinical trial literature, recognize areas with high quality evidence, and develop a resource database that makes the literature more immediately accessible to end users. Methods. Medline (1946 to January 2015), Embase (1974 to January 2015), and Cochrane databases (January 2015), were searched for trials. All pediatric (0–18 years) trials administering doses higher than 400 IU (<1 year) or 600 IU (≥1 year) were included. Data was extracted independently by two of the authors. An online searchable database of trials was developed containing relevant extracted information (http://www.cheori.org/en/pedvitaminddatabaseOverview). Sensitivity and utility were assessed by comparing the trials in the database with those from systematic reviews of vitamin D supplementation including children. Results. A total of 2,579 candidate papers were identified, yielding 169 trials having one or more arms meeting eligibility criteria. The publication rate has increased significantly from 1 per year (1970–1979) to 14 per year (2010–2015). Although 84% of the total trials focused on healthy children or known high risk populations (e.g., renal, prematurity), this proportion has declined in recent years due to the rise in trials evaluating populations and outcomes not directly related to the musculoskeletal actions of vitamin D (27% in 2010s). Beyond healthy children, the only pediatric populations with more than 50 participants from low risk

  6. Oxygen isotope fractionation between chlorite and water from 170 to 350 C: A preliminary assessment based on partial exchange and fluid/rock experiments

    SciTech Connect

    Cole, D.R.; Ripley, E.M.

    1999-02-01

    Oxygen isotope fractionations in laboratory systems have been determined between chlorite and water at 170--350 C. In one series of experiments, the Northrop-Clayton partial exchange method was used where three (sometimes four) isotopically different waters were reacted with chlorite. The percents of exchange determined for the four times from shortest to longest are 4.4, 6.5, 8.0, and 11.9. The fractionations calculated from the Northrop and Clayton method are in modest agreement for the four run durations: 0.13, 0.26, {minus}0.46, and {minus}0.55 per mil. Errors associated with each of these fractionations are quite large (e.g. {+-}1.2 per mil for the longest run). The value determined for the longest run of {approximately}20 weeks is the most reliable of the group and compares very closely with a value of {approximately}{minus}0.7 per mil estimated by Wenner and Taylor based on natural chlorides. Good agreement is also observed with the estimates, {minus}1.2 and {minus}1.3% calculated at 350 C for chlorite compositions with [({Sigma}Fe)/{Sigma}Fe + Mg] = 0.313 and 0.444, respectively, from equations given by Savin and Lee based on their empirical bond-type method. Additional fractionation data have been estimated from hydrothermal granite-fluid experiments where chlorite formed from biotite. Detailed thin section, scanning electron microscope (SEM), x-ray diffraction (XRD), and electron microprobe analyses demonstrate that biotite is altered exclusively to chlorite in 13 granite-fluid experiments conducted at the following conditions: T = 170--300 C, P = vapor saturation - 200 b, salinity = H{sub 2}O, 0.1 and 1 m NaCl, fluid/biotite mass ratios = 3--44, run durations = 122--772 h. The amount of chlorite, quantified through point counting and XRD, increased with increasing temperature, salinity, and time. The isotope compositions of chlorite were calculated from mass balance and compared to the final measured {delta}{sup 18}O of the fluids. The 10{sup 3}ln {alpha

  7. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

    PubMed Central

    Naderer, O; Nafziger, A N; Bertino, J S

    1997-01-01

    The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers. PMID:9371351

  8. Trends in Any and High-Dose Opioid Analgesic Receipt Among Aging Patients With and Without HIV

    PubMed Central

    Gordon, Kirsha; Edelman, E. Jennifer; Kerns, Robert D.; Crystal, Stephen; Dziura, James D.; Fiellin, Lynn E.; Gordon, Adam J.; Goulet, Joseph L.; Justice, Amy C.; Fiellin, David A.

    2016-01-01

    Harms of opioid analgesics, especially high-dose therapy among individuals with comorbidities and older age, are increasingly recognized. However, trends in opioid receipt among HIV-infected patients are not well characterized. We examined trends, from 1999 to 2010, in any and high-dose (≥120 mg/day) opioid receipt among patients with and without HIV, by age strata, controlling for demographic and clinical correlates. Of 127,216 patients, 64 % received at least one opioid prescription. Opioid receipt increased substantially among HIV-infected and uninfected patients over the study; high-dose therapy was more prevalent among HIV-infected patients. Trends in high-dose receipt stratified by three age groups revealed an increasing trend in each age strata, higher among HIV-infected patients. Correlates of any opioid receipt included HIV, PTSD and major depression. Correlates of high-dose receipt included HIV, PTSD, major depression and drug use disorders. These findings suggest a need for appropriate balance of risks and benefits, especially as these populations age. PMID:26384973

  9. In vivo measurements for high dose rate brachytherapy with optically stimulated luminescent dosimeters

    SciTech Connect

    Sharma, Renu; Jursinic, Paul A.

    2013-07-15

    Purpose: To show the feasibility of clinical implementation of OSLDs for high dose-rate (HDR) in vivo dosimetry for gynecological and breast patients. To discuss how the OSLDs were characterized for an Ir-192 source, taking into account low gamma energy and high dose gradients. To describe differences caused by the dose calculation formalism of treatment planning systems.Methods: OSLD irradiations were made using the GammaMedplus iX Ir-192 HDR, Varian Medical Systems, Milpitas, CA. BrachyVision versions 8.9 and 10.0, Varian Medical Systems, Milpitas, CA, were used for calculations. Version 8.9 used the TG-43 algorithm and version 10.0 used the Acuros algorithm. The OSLDs (InLight Nanodots) were characterized for Ir-192. Various phantoms were created to assess calculated and measured doses and the angular dependence and self-absorption of the Nanodots. Following successful phantom measurements, patient measurements for gynecological patients and breast cancer patients were made and compared to calculated doses.Results: The OSLD sensitivity to Ir-192 compared to 6 MV is between 1.10 and 1.25, is unique to each detector, and changes with accumulated dose. The measured doses were compared to those predicted by the treatment planning system and found to be in agreement for the gynecological patients to within measurement uncertainty. The range of differences between the measured and Acuros calculated doses was -10%-14%. For the breast patients, there was a discrepancy of -4.4% to +6.5% between the measured and calculated doses at the skin surface when the Acuros algorithm was used. These differences were within experimental uncertainty due to (random) error in the location of the detector with respect to the treatment catheter.Conclusions: OSLDs can be successfully used for HDR in vivo dosimetry. However, for the measurements to be meaningful one must account for the angular dependence, volume-averaging, and the greater sensitivity to Ir-192 gamma rays than to 6 MV x

  10. Administration of high-dose continuous infusion interleukin-2 to patients age 70 or over.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, Chris; Quan, Francine; Vinogradov, Mikhail; Walker, Paul

    2005-02-01

    High-dose bolus or continuous infusion interleukin-2-based therapy can cause capillary leak syndrome. Significant cardiovascular/hemodynamic events, including myocardial infarction, hypotension, pulmonary edema, and cardiac arrhythmia, have been described with such therapy. Concern over the toxicity of highdose interleukin-2 (IL-2) therapy has led to some clinicians excluding patients 70 years of age or over. We have treated 15 patients 70 years of age or over having an Eastern Conference Oncology Group (ECOG) performance status of 0 or 1, with therapy based on continuous infusion IL-2 18 MIU/sq m/24 hours for 72 hours. All patients underwent a pretreatment evaluation of cardiac status with a low-level stress or adenosine stress test. Cycles were typically repeated every 3 weeks for 4 cycles, then every 3-4 weeks thereafter. Patients were treated by oncology nurses in either the stem cell transplant (intermediate unit) or the oncology inpatient unit. Patient characteristics were: median age, 72 years (range, 70-83 years); tumor types: melanoma (10), kidney cancer (5); most common sites of disease: lung (11), lymph nodes (6), subcutaneous (3), liver (2); prior therapy included: none (8), outpatient IL-2 (5), other immunotherapy (4). Median number of cycles received: 3 (1-10). Most common toxicities were: fever, rigors, nausea, emesis, hypophosphatemia, and hypomagnesemia. Three patients required the use of dopamine for blood pressure support. Two patients declined further therapy. There were no treatment-related deaths. No patients required endotracheal intubation or transfer to an intensive care unit. One complete and 8 partial responses (60% response rate) have been seen. Responding sites include the lung, lymph node, intact kidney primary, and liver. Median survival has not been reached at over 14 months (range 3+-26+ months). Patients who are 70 years of age and older with an ECOG performance status of 0 or 1 are able to tolerate high-dose continuous infusion IL

  11. Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

    SciTech Connect

    Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

    2012-08-01

    Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade {>=}3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade {>=}3 toxicity at V12 = 3.78 cm{sup 3} (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm{sup 3} (RR 13, P=.0013), V20 = 0.11 cm{sup 3} (RR 6, P=0.01), and V22 = 0.0 cm{sup 3} (RR 13, P=.0013). The median split for D2.5 cm{sup 3} (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm{sup 3}. One hundred percent (n = 7) of grade {>=}4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade {>=}3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation

  12. Effect of high-dose irradiation on quality characteristics of ready-to-eat chicken breast

    NASA Astrophysics Data System (ADS)

    Yun, Hyejeong; Haeng Lee, Kyung; Jung Lee, Hyun; Woon Lee, Ju; Uk Ahn, Dong; Jo, Cheorun

    2012-08-01

    High-dose (higher than 30 kGy) irradiation has been used to sterilize specific-purposed foods for safe and long-term storage. The objective of this study was to investigate the effect of high-dose irradiation on the quality characteristics of ready-to-eat chicken breast in comparison with those of the low-dose irradiation. Ready-to-eat chicken breast was manufactured, vacuum-packaged, and irradiated at 0, 5, and 40 kGy. The populations of total aerobic bacteria were 4.75 and 2.26 Log CFU/g in the samples irradiated at 0 and 5 kGy, respectively. However, no viable cells were detected in the samples irradiated at 40 kGy. On day 10, bacteria were not detected in the samples irradiated at 40 kGy but the number of bacteria in the samples irradiated at 5 kGy was increased. The pH at day 0 was higher in the samples irradiated at 40 kGy than those at 0 and 5 kGy. The 2-thiobarbituric acid reactive substance (TBARS) values of the samples were not significantly different on day 0. However, on day 10, the TBARS value was significantly higher in the samples irradiated at 40 kGy than those at 0 and 5 kGy. There was no difference in the sensory scores of the samples, except for off-flavor, which was stronger in samples irradiated at 5 and 40 kGy than control. However, no difference in off-flavor between the irradiated ones was observed. After 10 days of storage, only the samples irradiated at 40 kGy showed higher off-flavor score. SPME-GC-MS analysis revealed that 5 kGy of irradiation produced 2-methylbutanal and 3-methylbutanal, which were not present in the control, whereas 40 kGy of irradiation produced hexane, heptane, pentanal, dimethly disulfide, heptanal, and nonanal, which were not detected in the control or the samples irradiated at 5 kGy. However, the amount of compounds such as allyl sulfide and diallyl disulfide decreased significantly in the samples irradiated at 5 kGy and 40 kGy.

  13. Effect of High Dose of Steroid on Plateletcount in Acute Stage of Dengue Fever with Thrombocytopenia

    PubMed Central

    Shashidhara, K.C.; Murthy, K.A. Sudharshan; Gowdappa, H. Basavana; Bhograj, Abhijith

    2013-01-01

    Background: Dengue infection is the most rapidly spreading mosquito-borne viral disease in the world and an estimated 50 million dengue infections reported annually. The pathogenesis of Thrombocytopenia in dengue fever (DF) is not clearly understood. Increased peripheral destruction of antibody coated platelets and acute bone marrow suppression were strongly suspected as the possible mechanism. This often leads to life threatening dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Steroids are used in the treatment of Idiopathic thrombocytopenic purpura to increase the platelet count which is mediated by auto antibodies .This hypothesis would support the use of steroids in dengue fever. Aim and Objectives: The objective of this study was to test whether an intravenous high dose dexamethasone was efficacious in increasing the platelet count in acute stage of dengue fever with thrombocytopenia. Methods: During the study period between June 2010 - 2011 in JSS Hospital Mysore, 127 patients were screened for dengue fever with thrombocytopenia (<50000/cumm) and 61patients were randomly allocated, 30 to the study group and 31 to the control group, in an open labeled study. The study group received intravenous dexamethasone 8mg initially followed by 4 mg every 8 h thereafter for 4 days and IV fluids whenever required. The control Group received only IV fluids and antipyretics whenever it was indicated. The daily measurement of platelet count was carried out in all patients from the day of enrolment to the fourth day of post treatment. Results: The baseline data (age, sex, and the mean duration of the illness, Hb%, haematocrit, and platelets) were similar in both the groups. The analysis of variance (ANOVA) statistics showed a significant linear association of the mean platelet counts with the days in either group. The mean platelet counts increased steadily in both the groups from days 1 to 4: day1 (0.687), day2 (0.34), day3 (0.530) and day4 (0.844). There was

  14. Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

    SciTech Connect

    Lilleby, Wolfgang; Tafjord, Gunnar; Raabe, Nils K.

    2012-07-01

    Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgen deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal

  15. Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer

    SciTech Connect

    Hepel, Jaroslaw T.; Syed, A.M. Nisar . E-mail: bvigil@memnet.org; Puthawala, Ajmel; Sharma, Anil; Frankel, Paul

    2005-08-01

    Background: A significant portion of head-and-neck cancer patients will develop persistent or recurrent disease after definitive treatment. Radiation therapy is often used as definitive therapy or as an adjunct to surgery. Recurrent cancer of the head and neck in the previously irradiated field is, thus, a common occurrence and poses a therapeutic challenge. Some studies have evaluated low-dose-rate (LDR) brachytherapy as a therapeutic option, including a large case series with long-term follow-up by our own institution. High-dose-rate (HDR) brachytherapy offers therapeutic advantages over LDR brachytherapy. This study evaluates the local control and outcomes of patients with previously irradiated recurrent head-and-neck cancer treated with HDR interstitial brachytherapy. Methods and Materials: Between 1997 and 2002, 30 patients who received prior radiation therapy for primary tumors of the head and neck were treated for biopsy-proven recurrent disease. All patients received previous radiation as definitive therapy alone or as adjunct to surgery. All patients were inoperable, refused surgery, or had gross residual disease after salvage surgery for their recurrent disease. Thirty-six sites on the 30 patients were implanted by application of high-dose-rate interstitial brachytherapy techniques with mean tumor dose of 34 Gy (18-48 Gy) in twice daily fractions of 300 to 400cGy per fraction. Results: At a minimum follow-up of 12 months, local tumor control was achieved in 69% of implanted sites. Disease-specific survival at 1 and 2 years was 54% and 45%, respectively. Overall survival at 1 and 2 years was 56% and 37%, respectively. Grade 3/4 late complications occurred in 16% of the patients. No fatal complications occurred. Conclusion: HDR brachytherapy can play an important role in the salvage treatment of previously irradiated recurrent head-and-neck cancer. This study shows that comparable results are obtained by HDR brachytherapy with fewer late complications than

  16. High Dose Simvastatin Exhibits Enhanced Lipid Lowering Effects Relative to Simvastatin/Ezetimibe Combination Therapy

    PubMed Central

    Settergren, Magnus; D'Alexandri, Fabio Luiz; Haeggström, Jesper Z.; Fiehn, Oliver; Hyötyläinen, Tuulia; Pedersen, Theresa L.; Newman, John W.; Orešič, Matej; Pernow, John; Wheelock, Craig E.

    2014-01-01

    Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in LDL-C. Thirty-nine patients were treated with either 80mg simvastatin (n=20) or 10mg simvastatin plus 10mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable LDL-C reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (e.g., eicosanoids, endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. Following statistical analysis and orthogonal projections to latent structures (OPLS) multivariate modeling, no changes were observed in lipid mediator levels, while global structural lipids were reduced in response to both mono- (R2Y=0.74, Q2=0.66, CV-ANOVA p=7.0×10-8) and combination therapy (R2Y=0.67, Q2=0.54, CV-ANOVA p=2.6×10−5). OPLS modeling identified a subset of 12 lipids that classified the two treatment groups after 6 weeks (R2Y=0.65, Q2=0.61, CV-ANOVA p=5.4×10−8). Decreases in the lipid species PC(15:0/18:2) and HexCer(d18:1/24:0) were the strongest discriminators of LDL-C reductions for both treatment groups (q<0.00005), while PE(36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease. PMID:25516625

  17. Developing A Directional High-Dose Rate (d-HDR) Brachytherapy Source

    NASA Astrophysics Data System (ADS)

    Heredia, Athena Yvonne

    Conventional sources used in brachytherapy provide nearly isotropic or radially symmetric dose distributions. Optimizations of dose distributions have been limited to varied dwell times at specified locations within a given treatment volume, or manipulations in source position for seed implantation techniques. In years past, intensity modulated brachytherapy (IMBT) has been used to reduce the amount of radiation to surrounding sensitive structures in select intracavitary cases by adding space or partial shields. Previous work done by Lin et al., at the University of Wisconsin-Madison, has shown potential improvements in conformality for brachytherapy treatments using a directionally shielded low dose rate (LDR) source for treatments in breast and prostate. Directional brachytherapy sources irradiate approximately half of the radial angles around the source, and adequately shield a quarter of the radial angles on the opposite side, with sharp gradient zones between the treated half and shielded quarter. With internally shielded sources, the radiation can be preferentially emitted in such a way as to reduce toxicities in surrounding critical organs. The objective of this work is to present findings obtained in the development of a new directional high dose rate (d-HDR) source. To this goal, 103Pd (Z = 46) is reintroduced as a potential radionuclide for use in HDR brachytherapy. 103Pd has a low average photon energy (21 keV) and relatively short half -life (17 days), which is why it has historically been used in low dose rate applications and implantation techniques. Pd-103 has a carrier-free specific activity of 75000 Ci/g. Using cyclotron produced 103Pd, near carrier-free specific activities can be achieved, providing suitability for high dose rate applications. The evolution of the d-HDR source using Monte Carlo simulations is presented, along with dosimetric parameters used to fully characterize the source. In addition, a discussion on how to obtain elemental

  18. Single high dose gentamicin for perioperative prophylaxis in orthopedic surgery: Evaluation of nephrotoxicity

    PubMed Central

    Dubrovskaya, Yanina; Tejada, Rainer; Bosco, Joseph; Stachel, Anna; Chen, Donald; Feng, Melinda; Rosenberg, Andrew; Phillips, Michael

    2015-01-01

    Background: Recent studies described an increase in acute kidney injury when high dose gentamicin was included in perioperative prophylaxis for orthopedic surgeries. To this effect, we compared the rate of nephrotoxicity for selected orthopedic surgeries where gentamicin was included (Gentamicin Group) to those where it was not included (Control Group) for perioperative prophylaxis and evaluated risk factors for nephrotoxicity. Methods: Spine, hip and knee surgeries performed between April 2011 and December 2013 were reviewed retrospectively. Gentamicin was given to eligible patients based on age, weight and Creatinine Clearance. Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria. Results: Among selected surgeries (N = 1590 in Gentamicin Group: hip = 926, spine = 600, knee = 64; N = 2587 in Control Group: hip = 980, spine = 902, knee = 705), patients’ body weight, serum creatinine, comorbidities and surgery duration were similar in Gentamicin Group and Control Group. Gentamicin median dose was 4.5 mg/kg of dosing weight. Nephrotoxicity rate was 2.5% in Gentamicin Group and 1.8% in Control Group, p = 0.17. Most cases of nephrotoxicity were Risk category by RIFLE criteria (67% in Gentamicin Group and 72% in Control Group, p = 0.49). In logistic regression, risk factors for nephrotoxicity were hospital stay >1 day prior to surgery (odds ratio = 8.1; 95% confidence interval = 2.25–28.97, p = 0.001), knee or hip surgery (odds ratio = 4.7; 95% confidence interval = 2.9–9.48, p = 0.0005) and diabetes (odds ratio = 1.95; 95% confidence interval = 1.13–3.35, p = 0.016). Receipt of gentamicin was not an independent predictor of nephrotoxicity (odds ratio = 1.5; 95% confidence interval = 0.97–2.35, p = 0.07). Conclusion: In this cohort, rate of nephrotoxicity was similar between Gentamicin Group and Control Group. Single

  19. Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome

    PubMed Central

    Saharkhiz, Nasrin; Akbari Sene, Azadeh; Salehpour, Saghar; Tamimi, Maryam; Vasheghani Farahani, Masoumeh; Sheibani, Kourosh

    2014-01-01

    Background: The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. Case: High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Conclusion: Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy. PMID:25469130

  20. Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia

    NASA Astrophysics Data System (ADS)

    Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.

    2015-05-01

    The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.

  1. Effects of long term inhaled high dose beclomethasone dipropionate on adrenal function.

    PubMed Central

    Smith, M J; Hodson, M E

    1983-01-01

    Studies of adrenal function were performed on 54 asthmatic patients who were taking long term high doses of inhaled beclomethasone dipropionate ranging from 500 to 2000 micrograms/day for between six and 60 months. Of the 43 patients taking up to 1500 micrograms/day, 39 (91%) had normal basal plasma cortisol concentrations and normal short tetracosactrin responses and 24 hour urinary free cortisol excretion was within the normal range in eight of nine patients tested. Some evidence of adrenal suppression was found in patients taking 2000 micrograms/day, with basal plasma cortisol below the normal range in four out of 11 patients and 24 hour urinary free cortisol excretion below the normal range in five out of six patients tested. Only one of the 11 patients taking 2000 micrograms/day had a short tetracosactrin response below the normal range: the mean rise in plasma cortisol was, however, significantly lower in this group than in those taking 1000 micrograms/day (328 (SE 30) and 506 (34) nmol/l respectively) (p less than 0.01). Patients taking more than 1500 micrograms/day of inhaled beclomethasone may require systemic corticosteroids during prolonged stress. PMID:6684806

  2. Thermal annealing recovery of fracture toughness in HT9 steel after irradiation to high doses

    NASA Astrophysics Data System (ADS)

    Byun, Thak Sang; Baek, Jong-Hyuk; Anderoglu, Osman; Maloy, Stuart A.; Toloczko, Mychailo B.

    2014-06-01

    The HT9 ferritic/martensitic steel with a nominal chemistry of Fe(bal.)12%Cr1%MoVW has been used as a primary core material for fast fission reactors such as FFTF because of its high resistance to radiation-induced swelling and embrittlement. Both static and dynamic fracture test results have shown that the HT9 steel can become brittle when it is exposed to high dose irradiation at a relatively low temperature (<430 °C). This article aims at a comprehensive discussion on the thermal annealing recovery of fracture toughness in the HT9 steel after irradiation up to 3148 dpa at 378504 °C. A specimen reuse technique has been established and applied to this study: the fracture specimens were tested Charpy specimens or broken halves of Charpy bars (13 × 3 × 4 mm). The post-anneal fracture test results indicated that much of the radiation-induced damage can be recovered by a simple thermal annealing schedule: the fracture toughness was incompletely recovered by 550 °C annealing, while nearly complete or complete recovery occurred after 650 °C annealing. This indicates that thermal annealing is a feasible damage mitigation technique for the reactor components made of HT9 steel. The partial recovery is probably due to the non-removable microstructural damages such as void or gas bubble formation, elemental segregation and precipitation.

  3. Effect of carbon on whole-biofilm metabolic response to high doses of streptomycin

    PubMed Central

    Jackson, Lindsay M. D.; Kroukamp, Otini; Wolfaardt, Gideon M.

    2015-01-01

    Biofilms typically exist as complex communities comprising multiple species with the ability to adapt to a variety of harsh conditions. In clinical settings, antibiotic treatments based on planktonic susceptibility tests are often ineffective against biofilm infections. Using a CO2 evolution measurement system we delineated the real-time metabolic response in continuous flow biofilms to streptomycin doses much greater than their planktonic susceptibilities. Stable biofilms from a multispecies culture (containing mainly Pseudomonas aeruginosa and Stenotrophomonas maltophilia), Gram-negative environmental isolates, and biofilms formed by pure culture P. aeruginosa strains PAO1 and PAO1 ΔMexXY (minimum planktonic inhibitory concentrations between 1.5 and 3.5 mg/l), were exposed in separate experiments to 4000 mg/l streptomycin for 4 h after which growth medium resumed. In complex medium, early steady state multispecies biofilms were susceptible to streptomycin exposure, inferred by a cessation of CO2 production. However, multispecies biofilms survived high dose exposures when there was extra carbon in the antibiotic medium, or when they were grown in defined citrate medium. The environmental isolates and PAO1 biofilms showed similar metabolic profiles in response to streptomycin; ceasing CO2 production after initial exposure, with CO2 levels dropping toward baseline levels prior to recovery back to steady state levels, while subsequent antibiotic exposure elicited increased CO2 output. Monitoring biofilm metabolic response in real-time allowed exploration of conditions resulting in vulnerability after antibiotic exposure compared to the resistance displayed following subsequent exposures. PMID:26441887

  4. Histopathological changes in rat liver after a single high dose of aluminium.

    PubMed

    Bogdanović, Milka; Janeva, Ana Begić; Bulat, Petar

    2008-06-01

    Aluminium (Al) exposure may affect the liver of experimental animals. This investigation aimed at evaluating morphological changes in rat liver after a single high dose of Al (as metallic powder suspension). A total of forty female Wistar rats were divided in one exposed and one control group, 20 rats each. The exposed rats received 0.5 mL of sterile physiological suspension of fine Al powder in the concentration of 100 mg mL-1 intraperitoneally (50 mg Al per rat). After 7 weeks all animals were killed (by exsanguination from the abdominal aorta in ether anaesthesia). Liver aluminium was analysed using electrothermal atomic absorption spectrometry. For light microscopy the liver tissue was stained with hematoxylin and eosin, and for histochemical analysis with aurin threecarbocsillic acid (aluminon). Liver Al level was markedly higher in the exposed (37.1 microg g-1) than in control rats (0.71 microg g-1). The exposed rats showed crystalloid Al inclusions in the capsular, subcapsular, and portal liver tissue. The basic liver structure remained intact. Slightly multiplied bile ductuli were found in 16 of 20 exposed and in 8 of 20 control rats. Three exposed rats had mycrovesicular steatosis. The peritoneum and Glisson's capsule showed strong macrophage infiltration and a foreign-body-like reaction with multiple giant macrophages containing Al crystalloid inclusions. Although this reaction was a defense against the metal, some Al passed this barrier and entered the liver tissue, exerting toxic effects in bile ductuli and hepatocytes. PMID:18573746

  5. Selenium metabolites in urine of cancer patients receiving L-selenomethionine at high doses

    SciTech Connect

    Kuehnelt, Doris; Juresa, Dijana; Francesconi, Kevin A. . E-mail: kevin.francesconi@uni-graz.at; Fakih, Marwan; Reid, Mary E.

    2007-04-15

    We investigated, with quantitative HPLC/mass spectrometry, the selenium metabolites in urine from five cancer patients receiving high doses of L-selenomethionine over an extended period (2 x 4000 {mu}g Se/day for 7 days, then 4000 {mu}g Se/day for 21 days) as an adjunct to their normal cancer chemotherapy. Urine samples were collected at day 0 (all 5 patients), and at 2-3 additional collection times ranging from 1 to 33 days. The background selenium concentrations ranged from 12 to 55 {mu}g Se/L and increased to 870 to 4420 {mu}g Se/L for the five patients during the study. All five patients had appreciable levels of selenosugars in their background urine sample, and the concentrations increased dramatically after selenium intake. Trimethylselenonium ion (TMSe), on the other hand, was generally present as only a trace metabolite in background urine, and, although the concentration of TMSe increased following selenium exposure, it became a less significant proportion relative to selenosugars. These data refute the currently accepted role of TMSe as the preferred excretion metabolite when selenium exposure is high.

  6. Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans.

    PubMed

    Johnson, Matthew W; MacLean, Katherine A; Caspers, Michael J; Prisinzano, Thomas E; Griffiths, Roland R

    2016-04-01

    Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A. PMID:26880225

  7. Three Patients Needing High Doses of Valproic Acid to Get Therapeutic Concentrations

    PubMed Central

    Jackson, James; McCollum, Betsy; Ognibene, Judy; Diaz, Francisco J.; de Leon, Jose

    2015-01-01

    Valproic acid (VPA) can autoinduce its own metabolism. Cases requiring VPA doses >4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases, have never been published. Case 1 received VPA for seizures and schizophrenia and had >50 VPA concentrations in 4 years. A high dose of 5,250 mg/day of VPA concentrate was prescribed for years but this dose led to an intoxication when switched to the enterocoated divalproex sodium formulation, requiring a normal dose of 2000 mg/day. VPA metabolic capacity was significantly higher (t = −9.6; df = 6.3, p < 0.001) during the VPA concentrate therapy, possibly due to autoinduction in that formulation. Case 2 had VPA for schizoaffective psychosis with 10 VPA concentrations during an 8-week admission. To maintain a VPA level ≥50 μg/mL, VPA doses increased from 1500 to 4000 mg/day. Case 3 had tuberous sclerosis and epilepsy and was followed up for >4 years with 137 VPA concentrations. To maintain VPA concentrations ≥50 μg/mL, VPA doses increased from 3,375 to 10,500 mg/day. In Cases 2 and 3, the duration of admission and the VPA dose were strongly correlated (r around 0.90; p < 0.001) with almost no change after controlling for VPA concentrations, indicating progressive autoinduction that increased with time. PMID:26000191

  8. A New Model of Biodosimetry to Integrate Low and High Doses

    PubMed Central

    Pujol, Mònica; Barquinero, Joan-Francesc; Puig, Pedro; Puig, Roser; Caballín, María Rosa; Barrios, Leonardo

    2014-01-01

    Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy, the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberration-among-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation. PMID:25461738

  9. Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone pulse therapy.

    PubMed

    Nagayama, Y; Izumi, M; Kiriyama, T; Yokoyama, N; Morita, S; Kakezono, F; Ohtakara, S; Morimoto, I; Okamoto, S; Nagataki, S

    1987-12-01

    This preliminary study was undertaken to investigate the efficacy of high-dose iv methylprednisolone pulse therapy in 5 patients with Graves' ophthalmopathy. One gram of methylprednisolone sodium succinate was given iv daily for 3 successive days. The 3-day infusion was repeated 3 to 7 times at intervals of 1 week; total duration of pulse therapy was 3 to 7 weeks. The clinical improvement of eye involvements by pulse therapy was assessed immediately after the last pulse therapy. The clinical assessment of the effect of pulse therapy for Graves' ophthalmopathy showed a good response in 3 patients, a fair response in one, and no response in one. However, in one patient, who was judged to show no response, complete improvement of the enlarged extraocular muscle was observed on orbital computed tomography. Moreover, two patients, who have been followed without any other therapies, showed no relapse of eye involvements for 32 and 10 months, respectively. Although it is impossible to determine whether pulse therapy is more effective than other immunosuppressive therapies, the results of this preliminary study suggest that pulse therapy may be a good immunosuppressive therapy for Graves' ophthalmopathy too. Controlled studies are desired. PMID:3321820

  10. Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

    PubMed

    Hassan, M; Oberg, G; Björkholm, M; Wallin, I; Lindgren, M

    1993-01-01

    The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used. PMID:8269597

  11. Plasma pharmacokinetics of high-dose oral busulfan in children and adults undergoing bone marrow transplantation.

    PubMed

    Bostrom, Bruce; Enockson, Karen; Johnson, Amy; Bruns, Alyssa; Blazar, Bruce

    2003-01-01

    We have analyzed the plasma pharmacokinetics of busulfan in 272 patients receiving high-dose oral busulfan and intravenous cyclophosphamide in conjunction with allogeneic or autologous bone marrow transplantation. The patients ranged in age from 2 months to 59 yr (mean 10, median 12 yr) and had the following diagnoses: thalassemia or sickle cell anemia (n = 74); leukemia or myelodysplasia (n = 112); inborn errors of metabolism (n = 41) or immunodeficiency (n = 45). Plasma specimens were collected following the first dose for each patient which ranged from 1 to 4 mg/kg (mean +/- SD, 1.21 +/- 0.41, median 1.15). Busulfan was quantitated using ultraviolet absorbance detection after derivatization and HPLC separation. Pharmacokinetic parameters were derived by modeling the raw data to fit first-order single compartment kinetics. The kinetic parameters showed wide interpatient variability independent of age and diagnosis. There was a statistically significant correlation of age with the following parameters: area under the curve (AUC); maximal concentration; minimum concentration; clearance; volume of distribution and absorption half-time. The coefficients of determination (i.e. correlation coefficient squared) were low ranging from 0.04 to 0.12 implying only a small part (i.e. 4-12%) of the variance was explained by age. Although busulfan pharmacokinetics are age-related most of the variability is not explained by age or diagnosis. PMID:12603688

  12. Survival of tumor cells after proton irradiation with ultra-high dose rates

    PubMed Central

    2011-01-01

    Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly. PMID:22008289

  13. Postoperative vaginal irradiation with high dose rate afterloading technique in endometrial carcinoma stage I

    SciTech Connect

    Sorbe, B.G.; Smeds, A.C. )

    1990-02-01

    A high dose rate ({sup 60}Co) afterloading technique was used for postoperative prophylactic vaginal irradiation in a series of 404 women with endometrial carcinoma Stage I. The total recurrence rate was 3.7% with 0.7% vaginal deposits. The crude 5-year survival rate for the complete series was 91.8% compared to 13.3% for those with recurrences. Depth of myometrial infiltration (greater than 1/3 of the uterine wall) and nuclear grade were the most important prognostic factors. Clinically significant late radiation reactions (bladder and/or rectum) were recorded in 6.9%. Dose per fraction and the size of the target volume were highly significantly related to the occurrence of both early and late radiation reactions. Vaginal shortening is closely related to the dose per fraction, length of the reference isodose, and the applicator diameter. The shape of the vaginal applicator versus the isodoses and the importance of the source train geometry and relative activity for dose gradient inhomogeneities within the target volume are discussed. Cumulative radiation effect (CRE) and linear-quadratic (LQ) calculations have been performed and related to tissue reactions within the target volume and in the risk organs. An alpha-beta quotient of 8.8 for vaginal shrinkage effect and 2.0 for late rectal complications are suggested on the basis of calculations using a maximum likelihood method for quantal radiation data.

  14. Determination of the tissue inhomogeneity correction in high dose rate Brachytherapy for Iridium-192 source

    PubMed Central

    Ravikumar, Barlanka; Lakshminarayana, S.

    2012-01-01

    In Brachytherapy treatment planning, the effects of tissue heterogeneities are commonly neglected due to lack of accurate, general and fast three-dimensional (3D) dose-computational algorithms. In performing dose calculations, it is assumed that the tumor and surrounding tissues constitute a uniform, homogeneous medium equivalent to water. In the recent past, three-dimensional computed tomography (3D-CT) based treatment planning for Brachytherapy applications has been popularly adopted. However, most of the current commercially available planning systems do not provide the heterogeneity corrections for Brachytherapy dosimetry. In the present study, we have measured and quantified the impact of inhomogeneity caused by different tissues with a 0.015 cc ion chamber. Measurements were carried out in wax phantom which was employed to measure the heterogeneity. Iridium-192 (192Ir) source from high dose rate (HDR) Brachytherapy machine was used as the radiation source. The reduction of dose due to tissue inhomogeneity was measured as the ratio of dose measured with different types of inhomogeneity (bone, spleen, liver, muscle and lung) to dose measured with homogeneous medium for different distances. It was observed that different tissues attenuate differently, with bone tissue showing maximum attenuation value and lung tissue resulting minimum value and rest of the tissues giving values lying in between those of bone and lung. It was also found that inhomogeneity at short distance is considerably more than that at larger distances. PMID:22363109

  15. Thermal annealing recovery of fracture toughness in HT9 steel after irradation to high doses

    SciTech Connect

    Byun, Thak Sang; Baek, Jong-Hyuk; Anderoglu, Osman; Maloy, Stuart A.; Toloczko, Mychailo B.

    2013-08-03

    The HT9 ferritic/martensitic steel with a nominal chemistry of Fe(bal.)–12%Cr–1%MoVW has been used as a primary core material for fast fission reactors such as FFTF because of its high resistance to radiationinduced swelling and embrittlement. Both static and dynamic fracture test results have shown that the HT9 steel can become brittle when it is exposed to high dose irradiation at a relatively low temperature 430 °C). This article aims at a comprehensive discussion on the thermal annealing recovery of fracture toughness in the HT9 steel after irradiation up to 3–148 dpa at 378–504 °C. A specimen reuse technique has been established and applied to this study: the fracture specimens were tested Charpy specimens or broken halves of Charpy bars (13 3 4 mm). The post-anneal fracture test results indicated that much of the radiation-induced damage can be recovered by a simple thermal annealing schedule: the fracture toughness was incompletely recovered by 550 °C annealing, while nearly complete or complete recovery occurred after 650 °C annealing. This indicates that thermal annealing is a feasible damage mitigation technique for the reactor components made of HT9 steel. The partial recovery is probably due to the non-removable microstructural damages such as void or gas bubble formation, elemental segregation and precipitation.

  16. A Convenient Method for Measuring Blood Ascorbate Concentrations in Patients Receiving High-Dose Intravenous Ascorbate

    PubMed Central

    Ma, Yan; Sullivan, Garrett G; Schrick, Elizabeth; Choi, In-Young; He, Zhuoya; Lierman, JoAnn; Lee, Phil; Drisko, Jeanne A; Chen, Qi

    2013-01-01

    Objective A simple method of using fingerstick blood glucose monitors (FSBG) to estimate blood ascorbate values after high-dose intravenous (IV) ascorbate infusion is evaluated as a substitution for HPLC measurement. Methods In 33 participants, readings from FSBG were taken before and after IV ascorbate infusions at various time points, with the post-infusion FSBG readings subtracted by the baseline glucose readings. The results of the subtractions (AAFSBG) were correlated with ascorbate concentrations detected by HPLC (AAHPLC). Results A linear regression was found between ascorbate concentrations detected by the fingersitck method (AAFSBG) and by HPLC (AAHPLC). The linear correlations were identical in healthy subjects, diabetic subjects and cancer patients. ANOVA analysis obtained an AAFSBG/AAHPLC ratio of 0.90, with 90% confidence interval of (0.69, 1.20). The corrections of AAFSBG improved similarity to AAHPLC, but did not significantly differ from the un-corrected values. Conclusion The FSBG method can be used as an approximate estimation of high blood ascorbate concentration after IV ascorbate (>50 mg/dL, or 2.8 mM) without correction. However this measurement is not accurate in detecting lower or baseline blood ascorbate. It is also important to highlight that in regard to glucose monitoring, FSBG readings will be erroneously elevated following intravenous ascorbate use and insulin should not be administered to patients based on these readings. PMID:23885992

  17. High Dose Intraveneous Vitamin C and Chikungunya Fever: A Case Report

    PubMed Central

    Gonzalez, Michael J.; Miranda-Massari, Jorge R.; Berdiel, Miguel J.; Duconge, Jorge; Rodríguez-López, Joshua L.; Hunninghake, Ron; Cobas-Rosario, Vicente J.

    2015-01-01

    The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, left knee pain and fever. The symptoms started on a Saturday in September 2014 in middle of the night. The patient was treated with high doses of intravenous vitamin C over two days. The symptoms resolved after the infusions without any side effects. Based on the positive outcome in this case, we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections. PMID:25705076

  18. Novel Use of the Contura for High Dose Rate Cranial Brachytherapy

    SciTech Connect

    Scanderbeg, Daniel J.; Alksne, John F.; Lawson, Joshua D.; Murphy, Kevin T.

    2011-01-01

    A popular choice for treatment of recurrent gliomas was cranial brachytherapy using the GliaSite Radiation Therapy System. However, this device was taken off the market in late 2008, thus leaving a treatment void. This case study presents our experience treating a cranial lesion for the first time using a Contura multilumen, high-dose-rate (HDR) brachytherapy balloon applicator. The patient was a 47-year-old male who was diagnosed with a recurrent right frontal anaplastic oligodendroglioma. Previous radiosurgery made him a good candidate for brachytherapy. An intracavitary HDR balloon brachytherapy device (Contura) was placed in the resection cavity and treated with a single fraction of 20 Gy. The implant, treatment, and removal of the device were all completed without incident. Dosimetry of the device was excellent because the dose conformed very well to the target. V90, V100, V150, and V200 were 98.9%, 95.7%, 27.2, and 8.8 cc, respectively. This patient was treated successfully using the Contura multilumen balloon. Contura was originally designed for deployment in a postlumpectomy breast for treatment by accelerated partial breast irradiation. Being an intracavitary balloon device, its similarity to the GliaSite system makes it a viable replacement candidate. Multiple lumens in the device also make it possible to shape the dose delivered to the target, something not possible before with the GliaSite applicator.

  19. Integration of High Dose Boron Implants--Modification of Device Parametrics through Implant Temperature Control

    SciTech Connect

    Schmeide, Matthias; Ameen, M. S.; Kondratenko, Serguei; Krimbacher, Bernhard; Reece, Ronald N.

    2011-01-07

    In the present study, we have extended a previously reported 250 nm logic p-S/D implant (7 keV B 4.5x10{sup 15} cm{sup -2}) process matching exercise [5] to include wafer temperature, and demonstrate that matching can be obtained by increasing the temperature of the wafer during implant. We found that the high dose rate delivered by the single wafer implanter caused the formation of a clear amorphous layer, which upon subsequent annealing altered the diffusion, activation, and clustering properties of the boron. Furthermore, increasing the temperature of the wafer during the implant was sufficient to suppress amorphization, allowing profiles and device parameters to become matched. Figure 5 shows a representative set of curves indicating the cluster phenomena observed for the lower temperature, high flux single wafer implanter, and the influence of wafer temperature on the profiles. The results indicate the strong primary effect of dose rate in determining final electrical properties of devices, and successful implementation of damage engineering using wafer temperature control.

  20. Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'.

    PubMed

    Salter, Bill J; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

    2011-04-01

    Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min(-1)) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach. PMID:21364260

  1. Increased thermal pain sensitivity in animals exposed to chronic high dose Vicodin but not pure hydrocodone.

    PubMed

    O'Connell, Thomas F; Carpenter, Patrick S; Caballero, Nadia; Putnam, Andrew J; Steere, Joshua T; Matz, Gregory J; Foecking, Eileen M

    2014-01-01

    Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one of the most prescribed drugs on the market today. Opioids have demonstrated the ability to paradoxically cause increased pain sensitivity to users in a phenomena called opioid-induced hyperalgesia (OIH). While selected opioids have been shown to produce OIH symptoms in an animal model, hydrocodone and the combination drug Vicodin have yet to be studied. The purpose of this study was to explore the effect of exposure to chronic high dose Vicodin or its components on the sensitivity to both thermal and mechanical pain. Animals were randomly divided into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and administered the drug daily for 120 days. Rats were subsequently tested for thermal and mechanical sensitivity. The rats in the Vicodin group displayed a significant decrease in withdrawal time to thermal pain. The rats receiving acetaminophen, hydrocodone, and vehicle showed no statistically significant hypersensitivity in thermal testing. None of the groups demonstrated statistically significant hypersensitivity to mechanical testing. The data suggests Vicodin produces signs of OIH in a rodent model. However, increased pain sensitivity was only noted in the thermal pathway and the hypersensitivity was only seen with the opioid combination drug, not the opioid alone. The results of this study both support the results of previous rodent opioid studies while generating further questions about the specific properties of Vicodin that contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic pain necessitates further research looking into this paradoxical pain response. PMID:25054394

  2. Adherence to Vaginal Dilation Following High Dose Rate Brachytherapy for Endometrial Cancer

    SciTech Connect

    Friedman, Lois C.; Abdallah, Rita; Schluchter, Mark; Panneerselvam, Ashok; Kunos, Charles A.

    2011-07-01

    Purpose: We report demographic, clinical, and psychosocial factors associated with adherence to vaginal dilation and describe the sexual and marital or nonmarital dyadic functioning of women following high dose rate (HDR) brachytherapy for endometrial cancer. Methods and Materials: We retrospectively evaluated women aged 18 years or older in whom early-stage endometrial (IAgr3-IIB) cancers were treated by HDR intravaginal brachytherapy within the past 3.5 years. Women with or without a sexual partner were eligible. Patients completed questionnaires by mail or by telephone assessing demographic and clinical variables, adherence to vaginal dilation, dyadic satisfaction, sexual functioning, and health beliefs. Results: Seventy-eight of 89 (88%) eligible women with early-stage endometrial cancer treated with HDR brachytherapy completed questionnaires. Only 33% of patients were adherers, based on reporting having used a dilator more than two times per week in the first month following radiation. Nonadherers who reported a perceived change in vaginal dimension following radiation reported that their vaginas were subjectively smaller after brachytherapy (p = 0.013). Adherers reported more worry about their sex lives or lack thereof than nonadherers (p = 0.047). Patients reported considerable sexual dysfunction following completion of HDR brachytherapy. Conclusions: Adherence to recommendations for vaginal dilator use following HDR brachytherapy for endometrial cancer is poor. Interventions designed to educate women about dilator use benefit may increase adherence. Although sexual functioning was compromised, it is likely that this existed before having cancer for many women in our study.

  3. Dietary intake of high-dose biotin inhibits spermatogenesis in young rats.

    PubMed

    Sawamura, Hiromi; Ikeda, Chieko; Shimada, Ryoko; Yoshii, Yui; Watanabe, Toshiaki

    2015-02-01

    To characterize a new function of the water-soluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats. PMID:25039897

  4. Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours

    PubMed Central

    De Giorgi, U; Rosti, G; Slavin, S; Yaniv, I; Harousseau, J L; Ladenstein, R; Demirer, T; Dini, G

    2005-01-01

    We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1–20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31–173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients. PMID:16106248

  5. High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration

    PubMed Central

    Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung

    2016-01-01

    Purpose Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. Methods In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. Results The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Conclusions Increasing the dose of bevacizumab in refractory PED may be a possible treatment option. PMID:27478353

  6. Towards enabling ultrasound guidance in cervical cancer high-dose-rate brachytherapy

    NASA Astrophysics Data System (ADS)

    Wong, Adrian; Sojoudia, Samira; Gaudet, Marc; Yap, Wan Wan; Chang, Silvia D.; Abolmaesumi, Purang; Aquino-Parsons, Christina; Moradi, Mehdi

    2014-03-01

    MRI and Computed Tomography (CT) are used in image-based solutions for guiding High Dose Rate (HDR) brachytherapy treatment of cervical cancer. MRI is costly and CT exposes the patients to ionizing radiation. Ultrasound, on the other hand, is affordable and safe. The long-term goal of our work is to enable the use of multiparametric ultrasound imaging in image-guided HDR for cervical cancer. In this paper, we report the development of enabling technology for ultrasound guidance and tissue typing. We report a system to obtain the 3D freehand transabdominal ultrasound RF signals and B-mode images of the uterus, and a method for registration of ultrasound to MRI. MRI and 3D ultrasound images of the female pelvis were registered by contouring the uterus in the two modalities, creating a surface model, followed by rigid and B-spline deformable registration. The resulting transformation was used to map the location of the tumor from the T2-weighted MRI to ultrasound images and to determine cancerous and normal areas in ultrasound. B-mode images show a contrast for cancer vs. normal tissue. Our study shows the potential and the challenges of ultrasound imaging in guiding cervical cancer treatments.

  7. Acute effect of high dose (48 mg) of piretanide in advanced renal insufficiency.

    PubMed Central

    Hadj Aissa, A; Pozet, N; Labeeuw, M; Pellet, M; Traeger, J

    1981-01-01

    1 The acute effects of a high dose of piretanide, a new potent diuretic were studied in eight patients with severely impaired renal function (GFR between 0.09 and 0.17 ml s-1 1.73 m-2). 2 After hydration and following two control periods, a single dose of 48 mg piretanide was ingested. Thereafter, urine was collected every 30 min for 2 h and every hour for the next 4 h. Urinary fluid losses were replaced orally (100 ml of water ever hour) and intravenously (isotonic saline + glucose infusion). 3 The following measurements were made: urine flow rate, clearances of inulin, PAH, urea, creatinine, uric acid, osmolar and free water clearances, excretion rates of sodium, chloride, potassium, calcium, phosphate, bicarbonate, ammonium, titratable acidity and urine pH. 4 Piretanide (48 mg) appeared to be effective in advanced renal insufficiency, producing a significant increase in urine flow rate, in sodium, chloride, potassium and calcium excretion and in Cosm. 5 There was no significant change in GFR, as measured by inulin clearance, or in the other measured parameters. PMID:7213511

  8. [5-fluorouracil, high dose folinic acid and mitomycin C in the treatment of advanced digestive cancers].

    PubMed

    Seitz, J F; Diaw, A; Giovannini, M; Perrier, H; Gouvernet, J

    1994-02-01

    Thirty five patients presenting with advanced unresectable digestive tract cancers were treated with high-dose folinic acid (200 mg/m2/d, i.v. bolus) followed by 5-fluorouracil (400 mg/m2 i.v. bolus) on day 2 of uneven courses (day 2, day 58, day 114...). There were 20 colorectal cancers, nine gastric cancers, two oesophageal cancers, two cholangiocarcinomas, one islet cell pancreatic carcinoma and one adenocarcinoma of unknown origin. An objective response was noted in 11/27 evaluable patients (40.7 +/- 19%): four complete and seven partial responses including three of the seven patients who previously failed to respond to 5FU-containing regimen, and eight of the 20 patients who received no prior chemotherapy. Objective responses were encountered in three of the five gastric cancers, five of the 17 colorectal cancers, one oesophageal cancer, one islet cell pancreatic carcinoma and one cholangiocarcinoma. The median duration of response was 6 months and overall median survival was 12 months (range: 1-48). There was one toxic death (non reversible medullar aplasia after the 1st course). This study confirms that this combination is an active regimen both for patients previously resistant to 5FU or untreated patients. It warrants further evaluation (perhaps with continuous 5FU infusions). PMID:7894119

  9. Serial observations after high dose talc slurry in the rabbit model for pleurodesis.

    PubMed

    Xie, C; Teixeira, L R; Wang, N; McGovern, J P; Light, R W

    1998-01-01

    The mechanisms leading to a pleurodesis after the intrapleural injection of a sclerosing agent are not completely understood. The purpose of the present study was to make serial observations over 28 days on the pleural fluid findings and the gross and microscopic changes in the pleura after talc slurry administered intrapleurally at a high dose. Sixty-six rabbits received 400 mg/kg talc slurry. Ten to 12 rabbits were sacrificed 1, 2, 4, 7, 14, and 28 days after the intrapleural injection. At sacrifice the pleural fluid was measured and analyzed, and the pleural surfaces were studied grossly and microscopically. The intrapleural injection of 400 mg/kg talc slurry resulted in an acute exudative pleural effusion that persisted for 4 days. There was a progressive increase in the gross and microscopic fibrosis over the 28 days. Talc was present at the time of sacrifice in all animals. At 28 days there was a clinically significant pleurodesis in all rabbits; pleurodesis was not observed before this time. From this study we conclude that the intrapleural injection of 400 mg/kg talc slurry leads to an acute exudative pleural effusion and clinically significant pleurodesis that is present on day 28 but not day 14. It appears that the production of a pleurodesis requires higher doses of talc in rabbits without a chest tube than in humans with a chest tube. PMID:9685526

  10. The effect of high dose oral manganese exposure on copper, iron and zinc levels in rats.

    PubMed

    Mercadante, Courtney J; Herrera, Carolina; Pettiglio, Michael A; Foster, Melanie L; Johnson, Laura C; Dorman, David C; Bartnikas, Thomas B

    2016-06-01

    Manganese is an essential dietary nutrient and trace element with important roles in mammalian development, metabolism, and antioxidant defense. In healthy individuals, gastrointestinal absorption and hepatobiliary excretion are tightly regulated to maintain systemic manganese concentrations at physiologic levels. Interactions of manganese with other essential metals following high dose ingestion are incompletely understood. We previously reported that gavage manganese exposure in rats resulted in higher tissue manganese concentrations when compared with equivalent dietary or drinking water manganese exposures. In this study, we performed follow-up evaluations to determine whether oral manganese exposure perturbs iron, copper, or zinc tissue concentrations. Rats were exposed to a control diet with 10 ppm manganese or dietary, drinking water, or gavage exposure to approximately 11.1 mg manganese/kg body weight/day for 7 or 61 exposure days. While manganese exposure affected levels of all metals, particularly in the frontal cortex and liver, copper levels were most prominently affected. This result suggests an under-appreciated effect of manganese exposure on copper homeostasis which may contribute to our understanding of the pathophysiology of manganese toxicity. PMID:26988220

  11. Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy

    SciTech Connect

    Schaake-Koning, C.S.; Schuster-Uitterhoeve, L.; Hart, G.; Gonzalez, D.G.

    1983-07-01

    A retrospective study was made of the results of high dose radiotherapy (greater than or equal to 50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971-April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with >65 Gy, the two year local control was 35%. If treated with <65 Gy the one year local control was less than or equal to 40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was <100 cm/sup 2/, the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis was found.

  12. High Dose Rate Brachytherapy as a Treatment Option in Endobronchial Tumors

    PubMed Central

    Hosni, Ali; Rink, Alexandra; Czarnecka, Kasia; McPartlin, Andrew; Patterson, Susan; Saibishkumar, Elantholiparameswaran

    2016-01-01

    Purpose. To report our experience with high dose rate endobronchial brachytherapy (HDR-EBBT) and to assess its efficacy and tolerability with possibility of its use in selected cases with curative intent. Method. Retrospective review of patients with endobronchial tumors treated at our institution in 2007–2013 with HDR-EBBT. Subjective response and treatment related toxicity were extracted from patients' records. Clinical response was evaluated by chest CT +/− bronchoscopy 2-3 months after treatment. Local control (LC) and overall survival (OS) were analyzed. Results. Overall 23 patients were identified. Ten patients were treated with curative intent, in 8 of them HDR-EBBT was combined with external beam radiotherapy. Short term palliation was as follows: dyspnea (13/15), cough (12/14), and hemoptysis (3/3). Seventeen patients were evaluated, of whom 9 (53%) showed complete response. Four patients developed local failure (only 1 of them treated with curative intent) and were salvaged with HDR-EBBT (n = 1), chemotherapy (n = 2), and laser (n = 1). Among patients treated with curative intent, the 2-year LC and OS were 89% and 67%, respectively, and 2 out of 4 deaths were cancer-related. Late toxicity included bronchial stenosis (n = 1). Only 1 patient had fatal hemoptysis and postmortem examination indicated local recurrence. Conclusion. HDR-EBBT is promising treatment with tolerable complication if used in properly selected patients. PMID:27493804

  13. Radiation tolerant nanocrystalline ZrN films under high dose heavy-ion irradiations

    SciTech Connect

    Jiao, L.; Wang, H.; Yu, K. Y.; Chen, D.; Jacob, C.; Shao, L.; Zhang, X.

    2015-04-14

    ZrN, a refractory ceramic material, finds many potential applications in advanced nuclear reactors. However, the grain size dependent radiation response in nanocrystalline (nc) ZrN under high dose heavy ion irradiation has not yet been studied to date. Here, we compare the radiation response of nc-ZrN films (with a respective average grain size of ∼9 and 31 nm) to Fe{sup 2+} ion irradiations up to a damage level of 10 displacements-per-atom (dpa). The ZrN film with the average grain size of 9 nm shows prominently enhanced radiation tolerance as evidenced by suppressed grain growth, alleviated radiation softening, as well as reduced variation in electrical resistivity. In contrast, ZrN with the larger average grain size of 31 nm shows prominent radiation softening and resistivity increase, attributed to the high density of defect cluster formed inside the grains. The influence of grain boundaries on enhanced irradiation tolerance in nc-ZrN is discussed.

  14. Impact of Surface Curvature on Dose Delivery in Intraoperative High-Dose-Rate Brachytherapy

    SciTech Connect

    Oh, Moonseong Wang Zhou; Malhotra, Harish K.; Jaggernauth, Wainwright; Podgorsak, Matthew B.

    2009-04-01

    In intraoperative high-dose-rate (IOHDR) brachytherapy, a 2-dimensional (2D) geometry is typically used for treatment planning. The assumption of planar geometry may cause serious errors in dose delivery for target surfaces that are, in reality, curved. A study to evaluate the magnitude of these errors in clinical practice was undertaken. Cylindrical phantoms with 6 radii (range: 1.35-12.5 cm) were used to simulate curved treatment geometries. Treatment plans were developed for various planar geometries and were delivered to the cylindrical phantoms using catheters inserted into Freiburg applicators of varying dimension. Dose distributions were measured using radiographic film. In comparison to the treatment plan (for a planar geometry), the doses delivered to prescription points were higher on the concave side of the geometry, up to 15% for the phantom with the smallest radius. On the convex side of the applicator, delivered doses were up to 10% lower for small treated areas ({<=} 5 catheters) but, interestingly, the dose error was negligible for large treated areas (>5 catheters). Our measurements have shown inaccuracy in dose delivery when the original planar treatment plan is delivered with a curved applicator. Dose delivery errors arising from the use of planar treatment plans with curved applicators may be significant.

  15. Treatment of Irradiated Mice with High-Dose Ascorbic Acid Reduced Lethality

    PubMed Central

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure. PMID:25651298

  16. SU-E-T-244: Motion Control Challenges in High Dose Rate Brachytherapy

    SciTech Connect

    Hyvarinen, M; Leventouri, T; Pella, S; Dumitru, N

    2014-06-01

    Purpose: High dose rate (HDR) brachytherapy dose distribution is highly localized and has a very sharp fall-off. Thus the one of the most important part of the treatment is the localization and immobilization of the applicator from the implantation to the setup verification to the treatment delivery. The smallest motions of the patient can induce a small rotation, tilt, or translational movement of the applicator that can convert into miss of a significant part of the tumor or to over irradiating a nearby critical organ.The purpose of this study is to revise most of the HDR types of treatments with their applicators and their localization challenges. Since every millimeter of misplacement counts the study will look into the necessity of increasing the immobilization for several types of applicators. Methods: The study took over 136 plans generated by the treatment planning system (TPS) looking into the applicator placement in regard to the organs at risk (OR) and simulated the three possible displacements at the hottest dose point on the critical organ for several accessories to evaluate the variation of the delivered dose at the point due to the displacement. Results: Many of the present immobilization devices produced for external radiotherapy can be used to improve the localization of HDR applicators during transportation of the patient and during treatment. Conclusion: This study data indicates that an improvement of the immobilization devices for HDR is absolutely necessary. Better applicator fixation devices are required too. Developing new immobilization devices for all the applicators is recommended.

  17. High-dose interleukin 2-induced myocarditis: can myocardial damage reversibility be assessed by cardiac MRI?

    PubMed

    Chow, Shien; Cove-Smith, Laura; Schmitt, Matthias; Hawkins, Robert

    2014-06-01

    High-dose interleukin 2 (HD-IL2) is one of the therapeutic options for patients with metastatic renal cell carcinoma. In well-selected patients with favorable clinical and pathologic features, it offers impressive response and potential long-term remission. It also has a place for treatment for metastatic malignant melanoma and in adoptive cell therapy. However, it is known for its intensive course and toxicities. Myocarditis is one of the known complications of this treatment and can pose a diagnostic challenge to treating oncologists because of its nonspecific and similar presentation to acute coronary syndrome (ACS). We report 3 short cases of HD-IL2-related myocarditis, which were either missed or misdiagnosed as ACS using conventional assessment but subsequently accurately diagnosed by cardiac magnetic resonant imaging (CMR). We discussed the clinical presentation of these cases and demonstrated the diagnostic advantage of CMR compared with standard investigations including its superior capability to assess myocardial reversibility, which has important short-term and long-term implications. The use of CMR also avoided unnecessary invasive intervention such as coronary angiogram in all 3 patients. These example cases call for effort to conduct prospective research to assess and confirm the utility of CMR, thus informing a more effective management pathway for immune-related myocarditis in HD-IL2 and other cancer immunotherapy. PMID:24810642

  18. Effect of carbon on whole-biofilm metabolic response to high doses of streptomycin.

    PubMed

    Jackson, Lindsay M D; Kroukamp, Otini; Wolfaardt, Gideon M

    2015-01-01

    Biofilms typically exist as complex communities comprising multiple species with the ability to adapt to a variety of harsh conditions. In clinical settings, antibiotic treatments based on planktonic susceptibility tests are often ineffective against biofilm infections. Using a CO2 evolution measurement system we delineated the real-time metabolic response in continuous flow biofilms to streptomycin doses much greater than their planktonic susceptibilities. Stable biofilms from a multispecies culture (containing mainly Pseudomonas aeruginosa and Stenotrophomonas maltophilia), Gram-negative environmental isolates, and biofilms formed by pure culture P. aeruginosa strains PAO1 and PAO1 ΔMexXY (minimum planktonic inhibitory concentrations between 1.5 and 3.5 mg/l), were exposed in separate experiments to 4000 mg/l streptomycin for 4 h after which growth medium resumed. In complex medium, early steady state multispecies biofilms were susceptible to streptomycin exposure, inferred by a cessation of CO2 production. However, multispecies biofilms survived high dose exposures when there was extra carbon in the antibiotic medium, or when they were grown in defined citrate medium. The environmental isolates and PAO1 biofilms showed similar metabolic profiles in response to streptomycin; ceasing CO2 production after initial exposure, with CO2 levels dropping toward baseline levels prior to recovery back to steady state levels, while subsequent antibiotic exposure elicited increased CO2 output. Monitoring biofilm metabolic response in real-time allowed exploration of conditions resulting in vulnerability after antibiotic exposure compared to the resistance displayed following subsequent exposures. PMID:26441887

  19. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation

    SciTech Connect

    Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.

    1982-04-01

    Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

  20. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation

    SciTech Connect

    Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.

    1982-04-01

    Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given either as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to to 4 X 10/sup 8/ cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single-dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis.In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after in vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

  1. High-dose-rate vaginal brachytherapy with chemotherapy for surgically staged localized uterine serous carcinoma

    PubMed Central

    Higgins, Susan A.; Ratner, Elena; De Leon, Maria C.; Mani, Sheida; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Rutherford, Thomas; Schwartz, Peter E.

    2015-01-01

    Purpose To evaluate our institutional experience combining carboplatin-paclitaxel (C/T) chemotherapy with high-dose-rate (HDR) intra-vaginal brachytherapy (IVB) following comprehensive surgical staging in localized uterine serous carcinoma (USC). Material and methods Institutional chart review identified 56 patients with FIGO 2009 stage I-II USC treated between 2000-2010. Patients underwent total hysterectomy, bilateral salpingo-oopherectomy, and comprehensive surgical staging including pelvic and para-aortic lymph node dissection, omentectomy, and peritoneal cytology. Chemotherapy was 6 cycles of C/T, and the IVB dose was 14 Gy in 2 fractions, prescribed to 0.5 cm from the cylinder surface. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS) and overall survival (OS). Results The median follow-up time was 49 months (range: 9-145). The 5-yr RFS and OS were 85% and 93%, respectively. In all cases of recurrence (n = 8), the first site of failure was extra-pelvic. There were no isolated vaginal recurrences, however, there was one vaginal apex recurrence recorded at 19 months in a patient with simultaneous lung metastases. Thus, the 2-year vaginal RFS was 98%. Conclusions Excellent vaginal/pelvic control rates were observed. Further study of HDR brachytherapy dose and fractionation in combination with chemotherapy is worthwhile. PMID:25829935

  2. Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

    NASA Astrophysics Data System (ADS)

    Gay, H. A.; Allison, R. R.; Downie, G. H.; Mota, H. C.; Austerlitz, C.; Jenkins, T.; Sibata, C. H.

    2007-06-01

    A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

  3. Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation.

    PubMed

    Creton, Stuart; Saghir, Shakil A; Bartels, Michael J; Billington, Richard; Bus, James S; Davies, Will; Dent, Matthew P; Hawksworth, Gabrielle M; Parry, Simon; Travis, Kim Z

    2012-03-01

    Toxicokinetic (TK) information can substantially enhance the value of the data generated from toxicity testing, and is an integral part of pharmaceutical safety assessment. It is less widely used in the chemical, agrochemical and consumer products industries, but recognition of its value is growing, as reflected by increased reference to the use of TK information in new and draft OECD test guidelines. To help promote increased consideration of the important role TK can play in chemical risk assessment, we have gathered practical examples from the peer-reviewed literature, as well as in-house industry data, that highlight opportunities for the use of TK in the selection of dose levels. Use of TK can help to ensure studies are designed to be of most relevance to assessing potential risk in humans, and avoid the use of excessively high doses that could result in unnecessary suffering in experimental animals. Greater emphasis on the potential contribution of TK in guiding study design and interpretation should be incorporated in regulatory data requirements and associated guidance. PMID:22198561

  4. High doses of gamma radiation suppress allergic effect induced by food lectin

    NASA Astrophysics Data System (ADS)

    Vaz, Antônio F. M.; Souza, Marthyna P.; Vieira, Leucio D.; Aguiar, Jaciana S.; Silva, Teresinha G.; Medeiros, Paloma L.; Melo, Ana M. M. A.; Silva-Lucca, Rosemeire A.; Santana, Lucimeire A.; Oliva, Maria L. V.; Perez, Katia R.; Cuccovia, Iolanda M.; Coelho, Luana C. B. B.; Correia, Maria T. S.

    2013-04-01

    One of the most promising areas for the development of functional foods lies in the development of effective methods to reduce or eliminate food allergenicity, but few reports have summarized information concerning the progress made with food irradiation. In this study, we investigated the relationship between allergenicity and molecular structure of a food allergen after gamma irradiation and evaluate the profile of the allergic response to irradiated allergens. Cramoll, a lectin isolated from a bean and used as a food allergen, was irradiated and the possible structural changes were accompanied by spectrofluorimetry, circular dichroism and microcalorimetry. Subsequently, sensitized animals subjected to intragastric administration of non-irradiated and irradiated Cramoll were treated for 7 days. Then, body weight, leukocytes, cytokine profiles and histological parameters were also determined. Cramoll showed complete inhibition of intrinsic activity after high radiation doses. Changes in fluorescence and CD spectra with a simultaneous collapse of the tertiary structure followed by a pronounced decrease of native secondary structure were observed after irradiation. After oral challenge, sensitized mice demonstrate an association between Cramoll intake, body weight loss, eosinophilia, lymphocytic infiltrate in the gut and Eotaxin secretion. Irradiation significantly reduces, according to the dose, the effects observed by non-irradiated food allergens. We confirm that high-dose radiation may render protein food allergens innocuous by irreversibly compromising their molecular structure.

  5. Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate.

    PubMed

    Ahmad, A; Kahler, S G; Kishnani, P S; Artigas-Lopez, M; Pappu, A S; Steiner, R; Millington, D S; Van Hove, J L

    1999-12-01

    A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. Head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. Biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg(-1)/day(-1)), aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3(1/2) years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor. PMID:10588840

  6. Glycerol Monolaurate Microbicide Protection against Repeat High-Dose SIV Vaginal Challenge

    PubMed Central

    Haase, Ashley T.; Rakasz, Eva; Schultz-Darken, Nancy; Nephew, Karla; Weisgrau, Kimberly L.; Reilly, Cavan S.; Li, Qingsheng; Southern, Peter J.; Rothenberger, Meghan; Peterson, Marnie L.; Schlievert, Patrick M.

    2015-01-01

    Measures to prevent sexual mucosal transmission are critically needed, particularly to prevent transmission to young women at high risk in the microepidemics in South Africa that disproportionally contribute to the continued pandemic. To that end, microbicides containing anti-retroviral (ARV) agents have been shown to prevent transmission, but with efficacy limited both by adherence and pre-existing innate immune and inflammatory conditions in the female reproductive tract (FRT). Glycerol monolaurate (GML) has been proposed as a microbicide component to enhance efficacy by blocking these transmission-facilitating innate immune response to vaginal exposure. We show here in an especially rigorous test of protection in the SIV-rhesus macaque model of HIV-1 transmission to women, that GML used daily and before vaginal challenge protects against repeat high doses of SIV by criteria that include virological and immunological assays to detect occult infection. We also provide evidence for indirect mechanisms of action in GML-mediated protection. Developing a sustained formulation for GML delivery could contribute an independent, complementary protective component to an ARV-containing microbicide. PMID:26057743

  7. The role of spinal nitric oxide and glutamate in nociceptive behaviour evoked by high-dose intrathecal morphine in rats.

    PubMed

    Watanabe, Chizuko; Sakurada, Tsukasa; Okuda, Kazuhiro; Sakurada, Chikai; Ando, Ryuichiro; Sakurada, Shinobu

    2003-12-01

    Injection of high-dose of morphine into the spinal lumbar intrathecal (i.t.) space of rats elicits a nociceptive behavioural syndrome characterized by periodic bouts of spontaneous agitation and severe vocalization. The induced behavioural response such as vocalization and agitation was observed dose-dependently by i.t. administration of morphine (125-500 nmol). Pretreatment with naloxone (s.c. and i.t.), an opioid receptor antagonist, failed to reverse the morphine-induced behavioural response. The excitatory effect of morphine was inhibited dose-dependently by pretreatment with 3-((+)2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist and MK-801, a non-competitive NMDA receptor antagonist. The non-selective nitric oxide (NO) synthase inhibitor N(G)-nitro L-arginine methyl ester (L-NAME) inhibited dose-dependently the behavioural response to high-dose i.t. morphine (500 nmol), whereas D-NAME was without affecting the response to high-dose i.t. morphine. In the present study, we measured NO metabolites (nitrite/nitrate) in the extracellular fluid of rat dorsal spinal cord using in vivo microdialysis. The i.t. injection of morphine (500 nmol) evoked significant increases in NO metabolites and glutamate from the spinal cord. Not only NO metabolites but also glutamate released by high-dose morphine were reduced significantly by pretreatment with L-NAME (400 nmol). Pretreatment with CPP and MK-801 showed a significant reduction of the NO metabolites and glutamate levels elevated by high-dose i.t. morphine. These results suggest that the excitatory action of high-dose i.t. morphine may be mediated by an NMDA-NO cascade in the spinal cord. PMID:14659510

  8. SU-E-T-315: The Change of Optically Stimulated Luminescent Dosimeters (OSLDs) Sensitivity by Accumulated Dose and High Dose

    SciTech Connect

    Han, S; Jung, H; Kim, M; Ji, Y; Kim, K; Choi, S; Park, S; Yoo, H; Yi, C

    2014-06-01

    Purpose: The objective of this study is to evaluate radiation sensitivity of optical stimulated luminance dosimeters (OSLDs) by accumulated dose and high dose. Methods: This study was carried out in Co-60 unit (Theratron 780, AECL, and Canada) and used InLight MicroStar reader (Landauer, Inc., Glenwood, IL) for reading. We annealed for 30 min using optical annealing system which contained fluorescent lamps (Osram lumilux, 24 W, 280 ∼780 nm). To evaluate change of OSLDs sensitivity by repeated irradiation, the dosimeters were repeatedly irradiated with 1 Gy. And whenever a repeated irradiation, we evaluated OSLDs sensitivity. To evaluate OSLDs sensitivity after accumulated dose with 5 Gy, We irradiated dose accumulatively (from 1 Gy to 5 Gy) without annealing. And OSLDs was also irradiated with 15, 20, 30 Gy to certify change of OSLDs sensitivity after high dose irradiation. After annealing them, they were irradiated with 1Gy, repeatedly. Results: The OSLDs sensitivity increased up to 3% during irradiating seven times and decreased continuously above 8 times. That dropped by about 0.35 Gy per an irradiation. Finally, after 30 times irradiation, OSLDs sensitivity decreased by about 7%. For accumulated dose from 1 Gy to 5 Gy, OSLDs sensitivity about 1 Gy increased until 4.4% after second times accumulated dose compared with before that. OSLDs sensitivity about 1 Gy decreased by 1.6% in five times irradiation. When OSLDs were irradiated ten times with 1Gy after irradiating high dose (10, 15, 20 Gy), OSLDs sensitivity decreased until 6%, 9%, 12% compared with it before high dose irradiation, respectively. Conclusion: This study certified OSLDs sensitivity by accumulated dose and high dose. When irradiated with 1Gy, repeatedly, OSLDs sensitivity decreased linearly and the reduction rate of OSLDs sensitivity after high dose irradiation had dependence on irradiated dose.

  9. Combination of sodium chlorite and calcium propionate reduces enzymatic browning and microbial population of fresh-cut "Granny Smith" apples.

    PubMed

    Guan, Wenqiang; Fan, Xuetong

    2010-03-01

    Tissue browning and microbial growth are the main concerns associated with fresh-cut apples. In this study, effects of sodium chlorite (SC) and calcium propionate (CP), individually and combined, on quality and microbial population of apple slices were investigated. "Granny Smith" apple slices, dipped for 5 min in CP solutions at 0%, 0.5%, 1%, and 2% (w/v) either alone or in combination with 0.05% (w/v) SC, were stored at 3 and 10 degrees C for up to 14 d. Color, firmness, and microflora population were measured at 1, 7, and 14 d of storage. Results showed that CP alone had no significant effect on the browning of cut apples. Even though SC significantly inhibited tissue browning initially, the apple slices turned brown during storage at 10 degrees C. The combination of CP and SC was able to inhibit apple browning during storage. Samples treated with the combination of SC with CP did not show any detectable yeast and mold growth during the entire storage period at 3 degrees C. At 10 degrees C, yeast and mold count increased on apple slices during storage while CP reduced the increase. However, high concentrations of CP reduced the efficacy of SC in inactivating E. coli inoculated on apples. Overall, our results suggested that combination of SC with 0.5% and 1% CP could be used to inhibit tissue browning and maintain firmness while reducing microbial population. Practical Application: Apple slices, which contain antioxidants and other nutrient components, have emerged as popular snacks in food service establishments, school lunch programs, and for family consumption. However, the further growth of the industry is limited by product quality deterioration caused by tissue browning, short shelf-life due to microbial growth, and possible contamination with human pathogens during processing. Therefore, this study was conducted to develop treatments to reduce microbial population and tissue browning of "Granny Smith" apple slices. Results showed that an antimicrobial

  10. Monte Carlo Dosimetry of the 60Co BEBIG High Dose Rate for Brachytherapy

    PubMed Central

    Campos, Luciana Tourinho; de Almeida, Carlos Eduardo Veloso

    2015-01-01

    Introduction The use of high-dose-rate brachytherapy is currently a widespread practice worldwide. The most common isotope source is 192Ir, but 60Co is also becoming available for HDR. One of main advantages of 60Co compared to 192Ir is the economic and practical benefit because of its longer half-live, which is 5.27 years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading brachytherapy machine (MultiSource®); it has the option to use either the 60Co or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co source (model Co0.A86), which is referred to as the new BEBIG 60Co HDR source and is a modified version of the 60Co source (model GK60M21), which is also from BEBIG. Objective and Methods The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate the required treatment-planning parameters. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, which is a part of EGS++ that allows calculating the radial dose function around the source. The spectrum to simulate 60Co was composed of two photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used; the contribution of the electrons to the dose is negligible because of the full absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon cross-section library was used in subsequent simulations, and the

  11. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern.

    PubMed

    Borot de Battisti, M; Maenhout, M; Denis de Senneville, B; Hautvast, G; Binnekamp, D; Lagendijk, J J W; van Vulpen, M; Moerland, M A

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm(3)to 23.3 cm(3)) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions. PMID:26378657

  12. High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

    SciTech Connect

    Kaprealian, Tania; Weinberg, Vivian; Speight, Joycelyn L.; Gottschalk, Alexander R.; Roach, Mack; Shinohara, Katsuto; Hsu, I.-Chow

    2012-01-01

    Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy Multiplication-Sign 3 fractions (patient group 1) and 950 cGy Multiplication-Sign 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy Multiplication-Sign 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy Multiplication-Sign 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score {>=}7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

  13. High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.

    PubMed

    Shim, Hee Jin; Lee, Eun-Mi; Nguyen, Long Duy; Shim, Jaekyung; Song, Young-Han

    2014-01-01

    Ionizing radiation (IR) treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs) generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis. PMID:24551207

  14. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

    SciTech Connect

    Shwetha, Bondel; Ravikumar, Manickam; Supe, Sanjay S.; Sathiyan, Saminathan; Lokesh, Vishwanath; Keshava, Subbarao L.

    2012-04-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  15. High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma.

    PubMed

    Aurer, Igor; Nemet, Damir; Mitrović, Zdravko; Dujmović, Dino; Bašić-Kinda, Sandra; Radman, Ivo; Sertić, Dubravka; Šantek, Fedor; Kralik, Marko; Dotlić, Snježana; Mazić, Sanja; Labar, Boris

    2016-06-01

    Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options. PMID:27103009

  16. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

    NASA Astrophysics Data System (ADS)

    Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

  17. Clinical results and pharmacokinetics of high-dose cytosine arabinoside (HD ARA-C).

    PubMed

    Breithaupt, H; Pralle, H; Eckhardt, T; von Hattingberg, M; Schick, J; Löffler, H

    1982-10-01

    Four patients with acute nonlymphoblastic leukemia and one malignant teratoma refractory to conventional chemotherapy were treated with high doses of cytosine arabinoside (HD ARA-C). They received up to 12 cycles of 1.8 to 3 g/m2 every 12 hours applied by 2-hour infusions. A total of 55 HD ARA-C infusions was performed. All leukemic patients responded. A complete clearance of blasts from the bone marrow was observed in two patients following 8-12 cycles of 3 g/m2. However, relapses occurred after three and seven weeks, in one case with resistance to HD ARA-C. The patient with malignant teratoma did not respond. No severe toxicity emerged even after repeated applications. Adverse reactions included moderate nausea and vomiting (4 patients), diarrhea (2 patients), hepatic dysfunction (1 patient), bone pain (1 patient), blurred vision (1 patient), conjunctivitis (1 patient), and exanthema with partial epidermiolysis (1 patient). Granulocytopenia occurring between 3-8 days after having started the therapy, subsided within 4-25 days. Plasma levels of ARA-C and the metabolite uracil arabinoside (ARA-U) were monitored. At steady state plasma concentrations of ARA-C were 32-97 microM (8-24 micrograms/ml). ARA-C disappeared from the plasma mono- or biphasic with a terminal half-life (t50%) of 7.8-12.6 minutes. The total clearance (Cl) of ARA-C varied between 1.7 and 2.9 liters/kg . h, and the distribution volume (Vss) between 0.44 and 0.86 liters/kg. Cerebrospinal fluid (CSF) levels of ARA-C reached 10-15% of steady state concentrations in plasma. PMID:7104969

  18. High-dose-rate interstitial brachytherapy for female peri-urethral cancer

    PubMed Central

    Gandhi, Ajeet Kumar; Bhatla, Neerja; Kumar, Sunesh; Rath, Goura Kisor

    2016-01-01

    Purpose Peri-urethral cancer (PUC) in females is a rare malignancy. Surgery is not usually contemplated due to associated morbidity. Radiation therapy (RT) can be employed in the form of interstitial brachytherapy (IBT) alone for early lesions, and external beam radiation therapy (EBRT) with or without IBT for advanced lesions. We report our first experience in the literature to evaluate the role of high-dose-rate (HDR) IBT in female PUC. Material and methods Between 2008 and 2013, 10 female patients with PUC (5 primary and 5 recurrent) were treated with HDR-IBT with or without EBRT at our center. Size of the lesion ranged from 1.5 cm to 5.0 cm. A 2-3 plane free-hand implant was performed using plastic catheters. The prescribed dose of HDR-IBT was 42 Gy in 14 fractions for brachytherapy alone (5 patients), and 18-21 Gy for the boost along with EBRT (5 patients). Patients were followed up regularly for assessment of disease control and toxicity. Results At a median follow up of 25 months, six patients were disease free at their last follow up. Four patients developed recurrence: 2 at inguinal nodes, 1 at local site, and 1 at both local as well as inguinal nodes. Moist desquamation was the commonest acute toxicity observed in all 5 patients treated with IBT alone, which healed within 4 weeks’ time. Overall, grade II delayed complication rate was 30%. Conclusions Though small sample size, the results of our study have shown that HDR-IBT provides good loco-regional control with acceptable toxicity for female PUC. PMID:26985196

  19. Interaction of 2-Gy Equivalent Dose and Margin Status in Perioperative High-Dose-Rate Brachytherapy

    SciTech Connect

    Martinez-Monge, Rafael; Cambeiro, Mauricio; Moreno, Marta; Gaztanaga, Miren; San Julian, Mikel; Alcalde, Juan; Jurado, Matias

    2011-03-15

    Purpose: To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods: Patients (n = 312) enrolled in several PHDRB prospective Phase I-II studies conducted at the Clinica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results: No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions: Two-gray equivalent doses {>=}70 Gy may compensate the effect of close margins {>=}1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose-margin interaction is observed in patients treated at lower Eq2Gy doses {<=}50 Gy with PHDRB alone.

  20. Dosimetric characterizations of GZP6 60Co high dose rate brachytherapy sources: application of superimposition method

    PubMed Central

    Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Mowlavi, Ali Asghar; Meigooni, Ali Soleimani

    2012-01-01

    Background Dosimetric characteristics of a high dose rate (HDR) GZP6 Co-60 brachytherapy source have been evaluated following American Association of Physicists in MedicineTask Group 43U1 (AAPM TG-43U1) recommendations for their clinical applications. Materials and methods MCNP-4C and MCNPX Monte Carlo codes were utilized to calculate dose rate constant, two dimensional (2D) dose distribution, radial dose function and 2D anisotropy function of the source. These parameters of this source are compared with the available data for Ralstron 60Co and microSelectron192Ir sources. Besides, a superimposition method was developed to extend the obtained results for the GZP6 source No. 3 to other GZP6 sources. Results The simulated value for dose rate constant for GZP6 source was 1.104±0.03 cGyh-1U-1. The graphical and tabulated radial dose function and 2D anisotropy function of this source are presented here. The results of these investigations show that the dosimetric parameters of GZP6 source are comparable to those for the Ralstron source. While dose rate constant for the two 60Co sources are similar to that for the microSelectron192Ir source, there are differences between radial dose function and anisotropy functions. Radial dose function of the 192Ir source is less steep than both 60Co source models. In addition, the 60Co sources are showing more isotropic dose distribution than the 192Ir source. Conclusions The superimposition method is applicable to produce dose distributions for other source arrangements from the dose distribution of a single source. The calculated dosimetric quantities of this new source can be introduced as input data to the GZP6 treatment planning system (TPS) and to validate the performance of the TPS. PMID:23077455

  1. Genetic compensation of high dose radiation-induced damage in an anhydrobiotic insect

    NASA Astrophysics Data System (ADS)

    Gusev, Oleg; Nakahara, Yuichi; Sakashita, Tetsuya; Kikawada, Takahiro; Okuda, Takashi

    Anhydrobiotic larvae of African chironomid Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. The tolerance against various extreme environments exhibited by that insect might be due to being almost completely desiccated replacing water with trehalose, a state where little or no chemical reactions occur. From 2005 dried larvae of this insect are being used in a number of space experiments, both inside and outside of ISS as a model organism for estimation the limits of higher organisms' resistance to space environment stresses and long-term storage of the alive anhydrobiotic organisms during continues spaceflight. We have shown previously that both hydrated and dried larvae of Polypedilum vanderplanki have very higher tolerance against both highand low-linear energy transfer (LET), surviving after 7000Gy irradiation. It was suggested that the larvae would have effective DNA-reparation system in addition to artificial protection provided by glass-stage without water. In the present study we conducted analysis of stress-related gene expression in the larvae after 70-2000 Gy irradiations. Both DNA damage level and activity of DNA-reparation, anti-apoptotic and protein-damage related genes were analyzed. Direct visualization of DNA damage in the larvae fat body cells using Comet Assay showed that fragmented by radiation DNA is re-arranged within 76-98 hours after exposure. We found that massive overexpression of hsp and anti-oxidant genes occur in larvae entering anhydrobiosis , and provides refolding of proteins after rehydration. In the irradiated larvae overexpression of DNA-reparation enzymes anti-apoptotic genes was confirmed, suggesting that survival after high-dose irradiation is a result of combination of highly effective blocking of entering the apoptosis after severe DNA damage and DNA reparation.

  2. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    SciTech Connect

    Demanes, D. Jeffrey; Martinez, Alvaro A.; Ghilezan, Michel; Hill, Dennis R.; Schour, Lionel; Brandt, David; Gustafson, Gary

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  3. In vivo real-time dosimetric verification in high dose rate prostate brachytherapy

    SciTech Connect

    Seymour, Erin L.; Downes, Simon J.; Fogarty, Gerald B.; Izard, Michael A.; Metcalfe, Peter

    2011-08-15

    Purpose: To evaluate the performance of a diode array in the routine verification of planned dose to points inside the rectum from prostate high dose rate (HDR) brachytherapy using a real-time planning system. Methods: A dosimetric study involving 28 patients was undertaken where measured doses received during treatment were compared to those calculated by the treatment planning system (TPS). After the ultrasound imaging required for treatment planning had been recorded, the ultrasound probe was replaced with a geometric replica that contained an 8 mm diameter cylindrical cavity in which a PTW diode array type 9112 was placed. The replica probe was then positioned inside the rectum with the individual diode positions determined using fluoroscopy. Dose was then recorded during the patients' treatment and compared to associated coordinates in the planning system. Results: Factors influencing diode response and experimental uncertainty were initially investigated to estimate the overall uncertainty involved in dose measurements, which was determined to be {+-}10%. Data was acquired for 28 patients' first fractions, 11 patients' second fractions, and 13 patients' third fractions with collection dependent upon circumstances. Deviations between the diode measurements and predicted values ranged from -42% to +35% with 71% of measurements experiencing less than a 10% deviation from the predicted values. If the {+-}10% measurement uncertainty was combined with a tolerated dose discrepancy of {+-}10% then over 95% of the diode results exhibited agreement with the calculated data to within {+-}20%. It must also be noted that when large dose discrepancies were apparent they did not necessarily occur for all five diodes in the one measurement. Conclusions: This technique provided a method that could be utilized to detect gross errors in dose delivery of a real-time prostate HDR plan. Limitations in the detection system used must be well understood if meaningful results are to

  4. Tensile stress corrosion cracking of type 304 stainless steel irradiated to very high dose

    SciTech Connect

    Chung, H. M.; Ruther, W. E.; Strain, R. V.; Shack, W. J.

    2001-09-01

    Certain safety-related core internal structural components of light water reactors, usually fabricated from Type 304 or 316 austenitic stainless steels (SSs), accumulate very high levels of irradiation damage (20--100 displacement per atom or dpa) by the end of life. The data bases and mechanistic understanding of, the degradation of such highly irradiated components, however, are not well established. A key question is the nature of irradiation-assisted intergranular cracking at very high dose, i.e., is it purely mechanical failure or is it stress-commotion cracking? In this work, hot-cell tests and microstructural characterization were performed on Type 304 SS from the hexagonal fuel can of the decommissioned EBR-11 reactor after irradiation to {approximately}50 dpa at {approximately}370 C. Slow-strain-rate tensile tests were conducted at 289 C in air and in water at several levels of electrochemical potential (ECP), and microstructural characteristics were analyzed by scanning and transmission electron microcopies. The material deformed significantly by twinning and exhibited surprisingly high ductility in air, but was susceptible to severe intergranular stress corrosion cracking (IGSCC) at high ECP. Low levels of dissolved O and ECP were effective in suppressing the susceptibility of the heavily irradiated material to IGSCC, indicating that the stress corrosion process associated with irradiation-induced grain-boundary Cr depletion, rather than purely mechanical separation of grain boundaries, plays the dominant role. However, although IGSCC was suppressed, the material was susceptible to dislocation channeling at low ECP, and this susceptibility led to poor work-hardening capability and low ductility.

  5. Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

    SciTech Connect

    Mehta, Niraj H.; Kamrava, Mitchell; Wang, Pin-Chieh; Steinberg, Michael; Demanes, Jeffrey

    2013-07-15

    Purpose: To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Methods and Materials: Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). Results: A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). Conclusions: A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

  6. High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma

    PubMed Central

    Ambady, Prakash; Abdelaziz, Ahmed; Sarai, Guneet; Bonekamp, David; Blakeley, Jaishri; Grossman, Stuart A.; Ye, Xiaobu

    2014-01-01

    Objective: To evaluate the efficacy of rituximab (R) when added to high-dose methotrexate (HD-MTX) in patients with newly diagnosed immunocompetent primary CNS lymphomas (PCNSLs). Methods: Immunocompetent adults with newly diagnosed PCNSL treated at The Johns Hopkins Hospital between 1995 and 2012 were investigated. From 1995 to 2008, patients received HD-MTX monotherapy (8 g/m2 initially every 2 weeks and after complete response [CR] monthly to complete 12 months of therapy). From 2008 to 2012, patients received the same HD-MTX with rituximab (375 mg/m2) with each HD-MTX treatment. CR rates and median overall and progression-free survival were analyzed for each patient cohort in this single-institution, retrospective study. Results: A total of 81 patients were identified: 54 received HD-MTX (median age 66 years) while 27 received HD-MTX/R (median age 65 years). CR rates were 36% in the HD-MTX cohort and 73% in the HD-MTX/R cohort (p = 0.0145). Median progression-free survival was 4.5 months in the HD-MTX cohort and 26.7 months in the HD-MTX/R cohort (p = 0.003). Median overall survival was 16.3 months in the HD-MTX cohort and has not yet been reached in the HD-MTX/R cohort (p = 0.01). Conclusions: The addition of rituximab to HD-MTX appears to improve CR rates as well as overall and progression-free survival in patients with newly diagnosed PCNSL. Comparisons of long-term survival in the 2 cohorts await further maturation of the data. Classification of evidence: This study provides Class III evidence that in immunocompetent patients with PCNSL, HD-MTX plus rituximab compared with HD-MTX alone improves CR and overall survival rates. PMID:24928128

  7. Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements

    PubMed Central

    Whitaker, May

    2016-01-01

    Purpose Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. Material and methods This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. Results The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. Conclusions The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected. PMID:27504129

  8. Effects of topical pimecrolimus 1% on high-dose ultraviolet B-irradiated epidermal Langerhans cells.

    PubMed

    Yin, ZhiQiang; Xu, JiaLi; Zhang, ZhiHong; Luo, Dan

    2012-12-01

    Some studies reported no changes in the number of epidermal Langerhans cells (LC) that were observed in mice treated with pimecrolimus, and low-dose stimulated solar radiation (once)-induced changers in LC are minimally affected by pimecrolimus. This study is to investigate the effects of topical pimecrolimus 1% on high-dose ultraviolet B (UVB)-irradiated epidermal LC. Forty human foreskin tissues were randomly divided into 4 groups of 10 tissues each: Group A, control; Group B, pimecrolimus 1% (once)-only; Group C, 180 mJ/cm(2) UVB (once)-only; Group D, UVB+pimecrolimus. Each tissue was cut into 4 pieces corresponding to 4 time points. All the tissues were cultured at 37 °C. After being treated, the tissues were collected respectively and processed for immunohistochemical staining and immunofluorescence staining. For UVB-only group, epidermal CD1a(+) LC number at 18h decreased from 39.6 ± 8.30 to 22.3 ± 2.26/5 high magnification, compared to CD1a(+) LC number at 0 h (P<0.01). The CD1a(+) LC number of UVB-only group was significantly less than other groups at 18 h, 24h and 48 h (P<0.05, respectively). Similar results were obtained with immunofluorescence staining for CD 1a and immunohistochemical staining for Langerin. The numbers of epidermal HLA-DR(+) LC had no significant differences among all groups at different time points. Our study found a single 180 mJ/cm(2) UVB irradiation significantly reduced epidermal LC numbers at 18 h, 24h and 48 h, however, topical pimecrolimus could reverse these changes. UVB plus pimecrolimus treatment did not affect human LC maturation. PMID:23079131

  9. High-dose ionizing radiation-induced hematotoxicity and metastasis in mice model.

    PubMed

    Shin, Jang Woo; Son, Jin Young; Raghavendran, Hanumantha Rao Balaji; Chung, Weon Kyu; Kim, Hyeong Geug; Park, Hye Jung; Jang, Seong Soon; Son, Chang Gue

    2011-12-01

    Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been investigated using mice model having real-time condition of leucopenia. C57BL/6 mice were pre-exposed to a X-irradiation dose of 6 Gy on previous days 2, 5, 7, 10. Complete hematological parameters including lymphocyte subpopulation in blood and lung tissues were analyzed. Additionally, a group of mice including a non-irradiated group were inoculated with B16F10 cells (3 × 10(5)/200 μl) via tail vein at the same day, and lung metastasized colonies were compared among groups at day 14 of post-inoculation. We observed that (i) total leucocytes and platelet were gradually depleted by day 10; (ii) lung tissue showed gradual infiltration of leucocytes including neutrophils and lymphocytes; (iii) pulmonary colonies were maximum and minimum on day 5 and 10 respectively; (iv) lymphocyte subpopulation analysis showed most number of natural killer (NK) cells in lung tissues on day 10; (v) gene expression of platelet/endothelial cell adhesion molecule (PECAM) in lung tissues peaked on day 5. To sum-up the study, severity of leucopenia did not influence the incidence of metastasis but blood platelets and microenvironment alteration of targeting tissue may be responsible factors for lung metastasis in our experimental model. PMID:21769700

  10. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

    PubMed Central

    Garcia, Maristela Magnavita Oliveira; Varela, Carolina Garcez; Silva, Patricia Fontes; Lima, Paulo Roberto Passos; Góes, Paulo Meira; Rodrigues, Marilia Galeffi; Silva, Maria de Lourdes Lima Souza e; Ladeia, Ana Marice Teixeira; Guimarães, Armênio Costa; Correia, Luis Claudio Lemos

    2016-01-01

    Background The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms. PMID:27142792

  11. Interfraction patient motion and implant displacement in prostate high dose rate brachytherapy

    SciTech Connect

    Fox, C. D.; Kron, T.; Leahy, M.; Duchesne, G.; Williams, S.; Tai, K. H.; Haworth, A.; Herschtal, A.; Foroudi, F.

    2011-11-15

    Purpose: To quantify movement of prostate cancer patients undergoing treatment, using an in-house developed motion sensor in order to determine a relationship between patient movement and high dose rate (HDR) brachytherapy implant displacement. Methods: An electronic motion sensor was developed based on a three axis accelerometer. HDR brachytherapy treatment for prostate is delivered at this institution in two fractions 24 h apart and 22 patients were monitored for movement over the interval between fractions. The motion sensors functioned as inclinometers, monitoring inclination of both thighs, and the inclination and roll of the abdomen. The implanted HDR brachytherapy catheter set was assessed for displacement relative to fiducial markers in the prostate. Angle measurements and angle differences over a 2 s time base were binned, and the standard deviations of the resulting frequency distributions used as a metric for patient motion in each monitored axis. These parameters were correlated to measured catheter displacement using regression modeling. Results: The mean implant displacement was 12.6 mm in the caudal direction. A mean of 19.95 h data was recorded for the patient cohort. Patients generally moved through a limited range of angles with a mean of the exception of two patients who spent in excess of 2 h lying on their side. When tested for a relationship between movement in any of the four monitored axes and the implant displacement, none was significant. Conclusions: It is not likely that patient movement influences HDR prostate implant displacement. There may be benefits to patient comfort if nursing protocols were relaxed to allow patients greater freedom to move while the implant is in situ.

  12. Single fraction multimodal image guided focal salvage high-dose-rate brachytherapy for recurrent prostate cancer

    PubMed Central

    Rischke, Hans-Christian; Meyer, Philipp Tobias; Knobe, Sven; Volgeova-Neher, Natalja; Kollefrath, Michael; Jilg, Cordula Annette; Grosu, Anca Ligia; Baltas, Dimos; Kroenig, Malte

    2016-01-01

    Purpose We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. Material and methods We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging – transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. Results Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. Conclusions Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials. PMID:27504134

  13. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss.

    PubMed

    Swift, Joshua M; Swift, Sibyl N; Smith, Joan T; Kiang, Juliann G; Allen, Matthew R

    2015-12-01

    The present study investigated the detrimental effects of non-lethal, high-dose (whole body) γ-irradiation on bone, and the impact that radiation combined with skin trauma (i.e. combined injury) has on long-term skeletal tissue health. Recovery of bone after an acute dose of radiation (RI; 8 Gy), skin wounding (15-20% of total body skin surface), or combined injury (RI+Wound; CI) was determined 3, 7, 30, and 120 days post-irradiation in female B6D2F1 mice and compared to non-irradiated mice (SHAM) at each time-point. CI mice demonstrated long-term (day 120) elevations in serum TRAP 5b (osteoclast number) and sclerostin (bone formation inhibitor), and suppression of osteocalcin levels through 30 days as compared to SHAM (p<0.05). Radiation-induced reductions in distal femur trabecular bone volume fraction and trabecular number through 120 days post-exposure were significantly greater than non-irradiated mice (p<0.05) and were exacerbated in CI mice by day 30 (p<0.05). Negative alterations in trabecular bone microarchitecture were coupled with extended reductions in cancellous bone formation rate in both RI and CI mice as compared to Sham (p<0.05). Increased osteoclast surface in CI animals was observed for 3 days after irradiation and remained elevated through 120 days (p<0.01). These results demonstrate a long-term, exacerbated response of bone to radiation when coupled with non-lethal wound trauma. Changes in cancellous bone after combined trauma were derived from extended reductions in osteoblast-driven bone formation and increases in osteoclast activity. PMID:26335157

  14. Obstructive urination problems after high-dose-rate brachytherapy boost treatment for prostate cancer are avoidable

    PubMed Central

    Kragelj, Borut

    2016-01-01

    Background Aiming at improving treatment individualization in patients with prostate cancer treated with combination of external beam radiotherapy and high-dose-rate brachytherapy to boost the dose to prostate (HDRB-B), the objective was to evaluate factors that have potential impact on obstructive urination problems (OUP) after HDRB-B. Patients and methods In the follow-up study 88 patients consecutively treated with HDRB-B at the Institute of Oncology Ljubljana in the period 2006-2011 were included. The observed outcome was deterioration of OUP (DOUP) during the follow-up period longer than 1 year. Univariate and multivariate relationship analysis between DOUP and potential risk factors (treatment factors, patients’ characteristics) was carried out by using binary logistic regression. ROC curve was constructed on predicted values and the area under the curve (AUC) calculated to assess the performance of the multivariate model. Results Analysis was carried out on 71 patients who completed 3 years of follow-up. DOUP was noted in 13/71 (18.3%) of them. The results of multivariate analysis showed statistically significant relationship between DOUP and anti-coagulation treatment (OR 4.86, 95% C.I. limits: 1.21-19.61, p = 0.026). Also minimal dose received by 90% of the urethra volume was close to statistical significance (OR = 1.23; 95% C.I. limits: 0.98-1.07, p = 0.099). The value of AUC was 0.755. Conclusions The study emphasized the relationship between DOUP and anticoagulation treatment, and suggested the multivariate model with fair predictive performance. This model potentially enables a reduction of DOUP after HDRB-B. It supports the belief that further research should be focused on urethral sphincter as a critical structure for OUP. PMID:27069455

  15. Dosimetric perturbations of a lead shield for surface and interstitial high-dose-rate brachytherapy.

    PubMed

    Candela-Juan, Cristian; Granero, Domingo; Vijande, Javier; Ballester, Facundo; Perez-Calatayud, Jose; Rivard, Mark J

    2014-06-01

    In surface and interstitial high-dose-rate brachytherapy with either (60)Co, (192)Ir, or (169)Yb sources, some radiosensitive organs near the surface may be exposed to high absorbed doses. This may be reduced by covering the implants with a lead shield on the body surface, which results in dosimetric perturbations. Monte Carlo simulations in Geant4 were performed for the three radionuclides placed at a single dwell position. Four different shield thicknesses (0, 3, 6, and 10 mm) and three different source depths (0, 5, and 10 mm) in water were considered, with the lead shield placed at the phantom surface. Backscatter dose enhancement and transmission data were obtained for the lead shields. Results were corrected to account for a realistic clinical case with multiple dwell positions. The range of the high backscatter dose enhancement in water is 3 mm for (60)Co and 1 mm for both (192)Ir and (169)Yb. Transmission data for (60)Co and (192)Ir are smaller than those reported by Papagiannis et al (2008 Med. Phys. 35 4898-4906) for brachytherapy facility shielding; for (169)Yb, the difference is negligible. In conclusion, the backscatter overdose produced by the lead shield can be avoided by just adding a few millimetres of bolus. Transmission data provided in this work as a function of lead thickness can be used to estimate healthy organ equivalent dose saving. Use of a lead shield is justified. PMID:24705066

  16. High-Dose-Rate Intraoperative Radiation Therapy for Recurrent Head-and-Neck Cancer

    SciTech Connect

    Perry, David J.; Chan, Kelvin; Wolden, Suzanne; Zelefsky, Michael J.; Chiu, Johnny; Cohen, Gilad; Zaider, Marco; Kraus, Dennis; Shah, Jatin; Lee, Nancy

    2010-03-15

    Purpose: To report the use of high-dose-rate intraoperative radiation therapy (HDR-IORT) for recurrent head-and-neck cancer (HNC) at a single institution. Methods and Materials: Between July 1998 and February 2007, 34 patients with recurrent HNC received 38 HDR-IORT treatments using a Harrison-Anderson-Mick applicator with Iridium-192. A single fraction (median, 15 Gy; range, 10-20 Gy) was delivered intraoperatively after surgical resection to the region considered at risk for close or positive margins. In all patients, the target region was previously treated with external beam radiation therapy (median dose, 63 Gy; range, 24-74 Gy). The 1- and 2-year estimates for in-field local progression-free survival (LPFS), locoregional progression-free survival (LRPFS), distant metastases-free survival (DMFS), and overall survival (OS) were calculated. Results: With a median follow-up for surviving patients of 23 months (range, 6-54 months), 8 patients (24%) are alive and without evidence of disease. The 1- and 2-year LPFS rates are 66% and 56%, respectively, with 13 (34%) in-field recurrences. The 1- and 2-year DMFS rates are 81% and 62%, respectively, with 10 patients (29%) developing distant failure. The 1- and 2-year OS rates are 73% and 55%, respectively, with a median time to OS of 24 months. Severe complications included cellulitis (5 patients), fistula or wound complications (3 patients), osteoradionecrosis (1 patient), and radiation-induced trigeminal neuralgia (1 patient). Conclusions: HDR-IORT has shown encouraging local control outcomes in patients with recurrent HNC with acceptable rates of treatment-related morbidity. Longer follow-up with a larger cohort of patients is needed to fully assess the benefit of this procedure.

  17. Impact of violated high-dose refuge assumptions on evolution of Bt resistance.

    PubMed

    Campagne, Pascal; Smouse, Peter E; Pasquet, Rémy; Silvain, Jean-François; Le Ru, Bruno; Van den Berg, Johnnie

    2016-04-01

    Transgenic crops expressing Bacillus thuringiensis (Bt) toxins have been widely and successfully deployed for the control of target pests, while allowing a substantial reduction in insecticide use. The evolution of resistance (a heritable decrease in susceptibility to Bt toxins) can pose a threat to sustained control of target pests, but a high-dose refuge (HDR) management strategy has been key to delaying countervailing evolution of Bt resistance. The HDR strategy relies on the mating frequency between susceptible and resistant individuals, so either partial dominance of resistant alleles or nonrandom mating in the pest population itself could elevate the pace of resistance evolution. Using classic Wright-Fisher genetic models, we investigated the impact of deviations from standard refuge model assumptions on resistance evolution in the pest populations. We show that when Bt selection is strong, even deviations from random mating and/or strictly recessive resistance that are below the threshold of detection can yield dramatic increases in the pace of resistance evolution. Resistance evolution is hastened whenever the order of magnitude of model violations exceeds the initial frequency of resistant alleles. We also show that the existence of a fitness cost for resistant individuals on the refuge crop cannot easily overcome the effect of violated HDR assumptions. We propose a parametrically explicit framework that enables both comparison of various field situations and model inference. Using this model, we propose novel empiric estimators of the pace of resistance evolution (and time to loss of control), whose simple calculation relies on the observed change in resistance allele frequency. PMID:27099624

  18. Endocrine function following high dose proton therapy for tumors of the upper clivus

    SciTech Connect

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  19. Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies.

    PubMed

    Sime, Fekade Bruck; Roberts, Michael S; Tiong, Ing Soo; Gardner, Julia H; Lehman, Sheila; Peake, Sandra L; Hahn, Uwe; Warner, Morgyn S; Roberts, Jason A

    2015-09-01

    While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic/pharmacodynamic target attainment from a 2-g intravenous (i.v.) every 8 h (q8h) cefepime regimen in febrile neutropenic patients with hematological malignancies. Cefepime plasma concentrations were measured in the 3rd, 6th, and 9th dosing intervals at 60% of the interval and/or trough point. The selected pharmacokinetic/pharmacodynamic targets were the proportion of the dosing interval (60% and 100%) for which the free drug concentration remains above the MIC (fT>MIC). Target attainment was assessed in reference to the MIC of isolated organisms if available or empirical breakpoints if not. The percentage of fT>MIC was also estimated by log-linear regression analysis. All patients achieved >60% fT>MIC in the 3rd and 6th dosing intervals. A 100% fT>MIC was not attained in 6/12, 4/10, and 4/9 patients in the 3rd, 6th, and 9th dose intervals, respectively, or in 14/31 (45%) of the dosing intervals investigated. On the other hand, 29/31 (94%) of trough concentrations were at or above 4 mg/liter. In conclusion, for patients with normal renal function, a high-dose 2-g i.v. q8h cefepime regimen appears to provide appropriate exposure if the MIC of the organism is ≤4 mg/liter but may fail to cover less susceptible organisms. PMID:26124158

  20. Formation of CoSi sub 2 in SIMOX wafers by high dose Co implantation

    SciTech Connect

    Sjoreen, T.P. Kernforschungsanlage Juelich GmbH . Inst. fuer Schicht- und Ionentechnik); Jebasinski, R.; Schmidt, K.; Mantl, S. . Inst. fuer Schicht- und Ionentechnik); Holzbrecher, H.; Speier, W. . Zentralabteilung fuer Chemische Analysen)

    1991-01-01

    SIMOX wafers have been implanted with high doses of Co and annealed at high temperatures in order to study the formation of buried single-crystal CoSi{sub 2} layers in this material. For this study SIMOX wafers of (100) oriented Si were implanted at 100--200 keV with doses of 1.2 {minus} 2.0 {times} 10{sup 17} Co{sup +}/cm{sup 2}, and annealed in rapid thermal processor or tube furnace. As-implanted and annealed samples were analyzed by Rutherford backscattering/channeling spectroscopy (RBS), cross-sectional transmission electron microscopy (XTEM), secondary ion mass spectroscopy, and the Van der Pauw technique. The best buried CoSi{sub 2} layers were obtained at an implantation energy of 100 keV and by subsequent RTA. RBS minimum yields of {approximately}6% were obtained for the buried layer, this is the same as that reported for bulk (100) Si. The measured resistivity of 15 {mu}{Omega}-cm and XTEM confirmed the continuity of the layer. Buried CoSi{sub 2} layers were successfully produced up to an implantation energy of 180 keV. However, as the energy was increased the quality of the CoSi{sub 2} layer degraded, with minimum yields increasing to 24% at 180 keV, and with a corresponding degradation in the minimum yields in the top Si layer. At 200 keV a buried epitaxial layer was not produced. The degradation of crystal quality with ion implantation energy and the failure to produce a buried layer at 200 keV are discussed. 11 refs., 4 figs.

  1. Voluntarily exposure to a single, high dose of probiotic Escherichia coli results in prolonged colonisation.

    PubMed

    Wassenaar, T M; Beimfohr, C; Geske, T; Zimmermann, K

    2014-12-01

    The ability of probiotic Escherichia coli to colonise the human gut was determined in a volunteer study following national (German) regulations. Five persons voluntarily took a single, high dose of Symbioflor®2, which contains 6 different probiotic E. coli genotypes, to assess tolerance of the product, after which presence of E. coli in their faeces was tested for a follow-up period of 30 weeks. Intake of the product did not result in severe side effect in any of the individuals, though mild side effects were observed. Stool analysis showed that the probiotic E. coli had colonised all five persons for a period of 10 to 30 weeks (mean: 18.7 weeks, median: 25.7 weeks). In two individuals there was evidence of competition between host E. coli and probiotic E. coli, while in two others total E. coli levels increased persistently with at least a factor of 10 as a result of the received dose. In one individual, who had lacked detectable levels of faecal E. coli at the start of the post-authorisation safety study, long-term colonisation was established, first by probiotic E. coli exclusively, which were later replaced by host E. coli strains. In four out of five individuals, total E. coli faecal counts were higher on average than at the start of the experiment, while in none total levels exceeded 5×107 cfu/g. When the specific genotypes of the 6 probiotic E. coli were analysed, it was found that one and the same common genotype was responsible for prolonged colonisation in all five individuals. PMID:24985025

  2. High doses of salicylate causes prepulse facilitation of onset-gap induced acoustic startle response.

    PubMed

    Sun, Wei; Doolittle, Lauren; Flowers, Elizabeth; Zhang, Chao; Wang, Qiuju

    2014-01-01

    Prepulse inhibition of acoustic startle reflex (PPI), a well-established method for evaluating sensorimotor gating function, has been used to detect tinnitus in animal models. Reduced gap induced PPI (gap-PPI) was considered as a sign of tinnitus. The silent gap used in the test contains both onset and offset signals. Tinnitus may affect these cues differently. In this experiment, we studied the effects of a high dose of salicylate (250 mg/kg, i.p.), an inducer of reversible tinnitus and sensorineural hearing loss, on gap-PPI induced by three different gaps: an onset-gap with 0.1 ms onset and 25 ms offset time, an offset-gap with 25 ms onset and 0.1 ms offset time, and an onset-offset-gap with 0.1 ms onset and offset time. We found that the onset-gaps induced smaller inhibitions than the offset-gaps before salicylate treatment. The offset-gap induced PPI was significantly reduced 1-3h after salicylate treatment. However, the onset-gap caused a facilitation of startle response. These results suggest that salicylate induced reduction of gap-PPI was not only caused by the decrease of offset-gap induced PPI, but also by the facilitation induced by the onset-gap. Since the onset-gap induced PPI is caused by neural offset response, our results suggest that salicylate may cause a facilitation of neural response to an offset acoustical signal. Treatment of vigabatrin (60 mg/kg/day, 14 days), which elevates the GABA level in the brain, blocked the offset-gap induced PPI and onset-gap induced facilitation caused by salicylate. These results suggest that enhancing GABAergic activities can alleviate salicylate induced tinnitus. PMID:24149068

  3. Treatment of Recurrent Bronchial Carcinoma: The Role of High-Dose-Rate Endoluminal Brachytherapy

    SciTech Connect

    Hauswald, Henrik; Stoiber, Eva; Rochet, Nathalie; Lindel, Katja; Grehn, Christian; Becker, Heinrich D.; Debus, Juergen; Harms, Wolfgang

    2010-06-01

    Purpose: This study's aim was to assess outcome and toxicity of high-dose-rate endoluminal brachytherapy (HDREB) for recurrent bronchial carcinoma. Methods and Materials: From 1987 to 2005, 41 patients were treated with HDREB for symptomatic recurrent bronchial carcinoma. All patients had previously undergone external beam radiotherapy (EBRT) with a median dose of 56 Gy (range, 30-70 Gy). The median HDREB dose applied was 15 Gy (range, 5-29 Gy). The median time interval between primary EBRT and reirradiation was 9 months (range, 2-54 months). Results: After a median follow-up of 6.7 months, the 6-, 12-, and 24-month overall survival rates were 58%, 18%, and 7%, respectively. The median overall survival time was 6.7 months. Local remission was achieved in 73% of patients (n = 30). A total of 24% of patients (n = 10) showed no response or progressive disease within 8 weeks after treatment. In 1 patient, treatment response was not documented. The 6-, 12-, and 24-month local control rates were 38%, 17%, and 3%, respectively. The median local progression-free survival time was 4 months (range, 1-23 months). Prognostic factors were a total dose of >=15 Gy of HDREB (p = 0.029) and a Karnofsky performance score of >=80% (p = 0.0012). The cause of death was locoregional progression in 27% of patients (n = 11), distant metastases in 24% of patients (n = 10), fatal hemorrhage in 15% of patients (n = 6), and other causes in 29% of patients (n = 12). None of the patients with locally controlled disease showed grade 3 or 4 late effects. Conclusions: Palliative treatment of symptomatic, locally recurrent bronchial carcinoma with HDREB can effectively relieve symptoms in the majority of patients while causing only few complications. Still, time to progression is short.

  4. Cardiovascular Safety Profile and Clinical Experience With High-Dose Domperidone Therapy for Nausea and Vomiting

    PubMed Central

    Ortiz, Arleen; Cooper, Chad J.; Alvarez, Alicia; Gomez, Yvette; Sarosiek, Irene

    2015-01-01

    Abstract: Introduction: Domperidone is a dopamine receptor antagonist with peripheral prokinetic and central antiemetic properties. Prolongation of the QTc interval with chronic use of oral domperidone in standard doses has been reported in the literature. Our goal was to investigate cardiac toxicity in patients receiving 2-fold greater doses than in previous reports. Methods: A retrospective chart review was conducted of patients with nausea (N) and vomiting (V) receiving domperidone from 2009 to 2013 under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, clinical outcomes, cardiac symptoms and electrocardiogram tracings were reviewed. Prolonged QTc was verified if >470 milliseconds in females (F) and >450 milliseconds in males (M). Results: A total of 64 patients, 44 female (37% Hispanic, 60% white, 3% African American), were taking domperidone for diabetic gastroparesis 45%; idiopathic gastroparesis 36%; chronic N&V 8%; dumping syndrome 5%; cyclic vomiting 5% and conditioned vomiting 1%. Mean duration of therapy was 8 months (range, 3 months to 4 years). Doses ranged from 40 to 120 mg/d with 90% receiving 80 to 120 mg compared with the standard dose of 40 mg. Of note, 73% of subjects benefited from treatment with reduced nausea and vomiting. Thirty-seven patients had follow-up electrocardiograms available, and they showed that the mean QTc at baseline was 424 milliseconds ± 28.4 (SD) compared with 435 milliseconds ± 27.2 (SD) at follow-up (not significant). Ten of these patients had prolonged QTc at F/U ranging from 453 to 509 milliseconds, without any cardiovascular complaints. There was no relationship between prolonged QTc and daily dose of domperidone, body mass index or age. Conclusions: Our data indicate that at very high dosing, the prokinetic/antiemetic agent domperidone has a low risk of adverse cardiovascular events while exhibiting good clinical efficacy. PMID:25828198

  5. High-dose diazepam facilitates core cooling during cold saline infusion in healthy volunteers.

    PubMed

    Hostler, David; Northington, William E; Callaway, Clifton W

    2009-08-01

    Studies have suggested that inducing mild hypothermia improves neurologic outcomes after traumatic brain injury, major stroke, cardiac arrest, or exertional heat illness. While infusion of cold normal saline is a simple and inexpensive method for reducing core temperature, human cold-defense mechanisms potentially make this route stressful or ineffective. We hypothesized that intravenous administration of diazepam during a rapid infusion of 30 mL.kg-1 of cold (4 degrees C) 0.9% saline to healthy subjects would be more comfortable and reduce core body temperature more than the administration of cold saline alone. Fifteen subjects received rapidly infused cold (4 degrees C) 0.9% saline. Subjects were randomly assigned to receive, intravenously, 20 mg diazepam (HIGH), 10 mg diazepam (LOW), or placebo (CON). Main outcomes were core temperature, skin temperature, and oxygen consumption. Data for the main outcomes were analyzed with generalized estimating equations to identify differences in group, time, or a group x time interaction. Core temperature decreased in all groups (CON, 1.0 +/- 0.2 degrees C; LOW, 1.4 +/- 0.2 degrees C; HIGH, 1.5 +/- 0.2 degrees C), while skin temperature was unchanged. Mean (95% CI) oxygen consumption was 315.3 (253.8, 376.9) mL.kg-1.min-1 in the CON group, 317.9 (275.5, 360.3) in the LOW group, and 226.1 (216.4, 235.9) in the HIGH group. Significant time and group x time interaction was observed for core temperature and oxygen consumption (p < 0.001). Administration of high-dose diazepam resulted in decreased oxygen consumption during cold saline infusion, suggesting that 20 mg of intravenous diazepam may reduce the shivering threshold without compromising respiratory or cardiovascular function. PMID:19767791

  6. High dose intravitreal foscarnet in the treatment of cytomegalovirus retinitis in AIDS.

    PubMed Central

    Diaz-Llopis, M; España, E; Muñoz, G; Navea, A; Chipont, E; Cano, J; Menezo, J L; Romero, F J

    1994-01-01

    The efficacy and tolerance of high dose intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS was studied. Foscarnet in a dose of 2400 micrograms was injected directly into the vitreous of 11 patients (15 eyes). Five patients had active retinitis (eight eyes, 53.3%), and received a 3 week induction therapy of six injections as the first step. Six patients had initial inactive retinitis (seven eyes, 46.7%), and received only maintenance therapy which consisted of a weekly injection. The main indications for intravitreal therapy were: myelosuppression, kidney toxicity, catheter related sepsis, or refusal of intravenous therapy. The patients were followed for a mean period of 16 weeks (range 8-28 weeks) and received a total of 304 injections. Vitreous foscarnet levels were measured by high performance liquid chromatography. After a 3 week course of induction therapy, complete resolution of the active retinitis was seen in 62.5% (5/8 cases), while 37.5% (3/8 cases) had partial resolution. No cases failed to respond or progress. The rate of relapse on maintenance therapy was 33% (five of 15 eyes) by 20 weeks, and two of these eyes did not respond to reinduction and progressed in involvement of the macula or optic nerve. Neither important local complications nor intraocular drug toxicity were observed. Vitreous foscarnet levels in two different patients were 896 mumol/l and 74.9 mumol/l at 22 3/4 hours and 42 1/2 hours after the injection. Intravitreal foscarnet appears to be a safe, effective, and useful alternative in patients with intolerance to intravenous and viral therapy. PMID:8123619

  7. Calibration of 192Ir high dose rate brachytherapy source using different calibration procedures

    PubMed Central

    Bondel, Shwetha; Ravikumar, Manickham; Supe, Sanjay Sudhakar; Reddy, Buchuppudi Rekha

    2013-01-01

    Aim To calibrate Ir-192 high dose rate (HDR) brachytherapy source using different calibration methods and to determine the accuracy and suitability of each method for routine calibrations. Background The source calibration is an essential part of the quality assurance programme for dosimetry of brachytherapy sources. The clinical use of brachytherapy source requires an independent measurement of the air kerma strength according to the recommendations of medical physics societies. Materials and methods The Ir-192 HDR brachytherapy source from Gammamed plus machine (Varian Medical Systems, Palo Alto, CA) was calibrated using three different procedures, one using the well-type ionization chamber, second by the in-air calibration method and third using solid water phantoms. The reference air kerma rate (RAKR) of the source was determined using Deutsche Gesellschaft fur Medizinische Physik (DGMP) recommendations. Results The RAKR determined using different calibration methods are in good agreement with the manufacturer stated value. The mean percentage variations of 0.21, −0.94, −0.62 and 0.58 in RAKR values with respect to the manufacturer quoted values were observed with the well-type chamber, in-air calibration, cylindrical phantom and slab phantom measurements, respectively. Conclusion Measurements with a well-type chamber are relatively simple to perform. For in-air measurements, the indigenously designed calibration jig provides an accurate positioning of the source and chamber with minimum scatter contribution. The slab phantom system has an advantage that no additional phantom and chamber are required other than those used for external beam therapy dosimetry. All the methods of calibration discussed in this study are effective to be used for routine calibration purposes. PMID:24944818

  8. Dose characterization in the near-source region for two high dose rate brachytherapy sources.

    PubMed

    Wang, Ruqing; Li, X Allen

    2002-08-01

    High dose rate (HDR) 192Ir sources are currently used in intravascular brachytherapy (IVB) for the peripheral arterial system. This poses a demand on evaluating accurate dose parameters in the near-source region for such sources. The purpose of this work is to calculate the dose parameters for the old VariSource HDR 192Ir source and the new microSelectron HDR 192Ir source, using Monte Carlo electron and photon transport simulation. The two-dimensional (2D) dose rate distributions and the air kerma strengths for the two HDR sources were calculated by EGSnrc and EGS4 Monte Carlo codes. Based on these data, the dose parameters proposed in the AAPM TG-60 protocol were derived. The dose rate constants obtained are 13.119+/-0.028 cGy h(-1) U(-1) for the old VariSource source, and 22.751+/-0.031 cGy h(-1) U(-1) for the new microSelectron source at the reference point (r0 = 2 mm, theta = pi/2). The 2D dose rate distributions, the radial dose functions, and the anisotropy functions presented for the two sources cover radial distances ranging from 0.5 to 10 mm. In the near-source region on the transverse plane, the dose effects of the charged particle nonequilibrium and the beta-particle dose contribution were studied. It is found that at radial distances ranging from 0.5 to 2 mm, these effects increase the calculated dose rates by up to 29% for the old VariSource source, and by up to 12% for the new microSelectron source, which, in turn, change values of the radial dose function and the anisotropy function. The present dose parameters, which account for the charged particle nonequilibrium and the beta particle contribution, may be used for accurate IVB dose calculation. PMID:12201413

  9. High dose rates obtained outside ISS in June 2015 during SEP event

    NASA Astrophysics Data System (ADS)

    Dachev, T. P.; Tomov, B. T.; Matviichuk, Yu. N.; Dimitrov, Pl. G.; Bankov, N. G.

    2016-06-01

    The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7 MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000 μGy h-1, while the inner radiation belt maximum dose was at the level of 2200 μGy h-1. If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84 mGy after 6.5 h, which is similar to the average absorbed dose inside ISS for 15 days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA.

  10. High Dose-Rate Versus Low Dose-Rate Brachytherapy for Lip Cancer

    SciTech Connect

    Ghadjar, Pirus; Bojaxhiu, Beat; Simcock, Mathew; Terribilini, Dario; Isaak, Bernhard; Gut, Philipp; Wolfensberger, Patrick; Broemme, Jens O.; Geretschlaeger, Andreas; Behrensmeier, Frank; Pica, Alessia; Aebersold, Daniel M.

    2012-07-15

    Purpose: To analyze the outcome after low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy for lip cancer. Methods and Materials: One hundred and three patients with newly diagnosed squamous cell carcinoma of the lip were treated between March 1985 and June 2009 either by HDR (n = 33) or LDR brachytherapy (n = 70). Sixty-eight patients received brachytherapy alone, and 35 received tumor excision followed by brachytherapy because of positive resection margins. Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events 3.0. Results: Median follow-up was 3.1 years (range, 0.3-23 years). Clinical and pathological variables did not differ significantly between groups. At 5 years, local recurrence-free survival, regional recurrence-free survival, and overall survival rates were 93%, 90%, and 77%. There was no significant difference for these endpoints when HDR was compared with LDR brachytherapy. Forty-two of 103 patients (41%) experienced acute Grade 2 and 57 of 103 patients (55%) experienced acute Grade 3 toxicity. Late Grade 1 toxicity was experienced by 34 of 103 patients (33%), and 5 of 103 patients (5%) experienced late Grade 2 toxicity; no Grade 3 late toxicity was observed. Acute and late toxicity rates were not significantly different between HDR and LDR brachytherapy. Conclusions: As treatment for lip cancer, HDR and LDR brachytherapy have comparable locoregional control and acute and late toxicity rates. HDR brachytherapy for lip cancer seems to be an effective treatment with acceptable toxicity.

  11. High dose rates obtained outside ISS in June 2015 during SEP event.

    PubMed

    Dachev, T P; Tomov, B T; Matviichuk, Yu N; Dimitrov, Pl G; Bankov, N G

    2016-06-01

    The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000µGyh(-1), while the inner radiation belt maximum dose was at the level of 2200µGyh(-1). If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84mGy after 6.5h, which is similar to the average absorbed dose inside ISS for 15days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA. PMID:27345205

  12. High dose rates obtained outside ISS in June 2015 during SEP event

    NASA Astrophysics Data System (ADS)

    Dachev, T. P.; Tomov, B. T.; Matviichuk, Yu. N.; Dimitrov, Pl. G.; Bankov, N. G.

    2016-06-01

    The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7 MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000 μGy h-1, while the inner radiation belt maximum dose was at the level of 2200 μGy h-1. If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84 mGy after 6.5 h, which is similar to the average absorbed dose inside ISS for 15 days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA.

  13. Safety of treatment with high-dose daptomycin in 102 patients with infective endocarditis.

    PubMed

    Durante-Mangoni, Emanuele; Andini, Roberto; Parrella, Antonio; Mattucci, Irene; Cavezza, Giusi; Senese, Alessandra; Trojaniello, Claudia; Caprioli, Roberta; Diana, Maria Veronica; Utili, Riccardo

    2016-07-01

    Daptomycin is commonly used at doses >6 mg/kg/day for various indications, including infective endocarditis (IE). A systematic assessment of skeletal muscle, renal, haematological, hepatic and pulmonary toxicity of high-dose daptomycin (HDD) in IE is lacking. A total of 102 IE patients treated with HDD were included in this non-comparative, observational, single-centre cohort study conducted from 2007 to 2014. The incidence, timing, severity and evolution of adverse events (AEs) were assessed. Patients had a median age of 61.5 years and a high prevalence of co-morbidities. Staphylococci were cultured in 87.2% of cases (62.2% meticillin-resistant). The median daptomycin dose was 8.2 mg/kg/day for a median of 20 days (range, 1-60 days). HDD was withdrawn due to AEs in 12 patients (11.8%). On-treatment death occurred in 4 cases (3.9%, none HDD-related). Muscle toxicity occurred in 15 patients in a median of 15 days after HDD starts, which was largely mild and reversible with ongoing HDD use. Mild renal toxicity was observed in 9 patients (8.8%) after a median of 12 days of HDD (RIFLE-Risk in 8, Injury in 1). A rise of peripheral blood eosinophils occurred in 16 patients (15.7%). There were three cases of eosinophilic interstitial pneumonia. Four patients (3.9%) had mild allergic or idiosyncratic reactions. No other hepatic or haematological AEs were observed. Our current experience with 102 patients suggests that HDD is safe in significantly ill IE patients with multiple co-morbidities. Muscle toxicity was clinically negligible. Most importantly, there was no significant renal toxicity. Eosinophils should be carefully monitored. PMID:27259674

  14. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.; Kasap, S. O.

    2014-02-01

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm3+) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm3+-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm3+-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm2+ to Sm3+ reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm2+ to Sm3+ reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  15. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    SciTech Connect

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C. Kasap, S. O.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.

    2014-02-14

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm{sup 3+}) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm{sup 3+}-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm{sup 3+}-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm{sup 2+} to Sm{sup 3+} reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm{sup 2+} to Sm{sup 3+} reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  16. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups.

    PubMed

    Luskin, Marlise R; Lee, Ju-Whei; Fernandez, Hugo F; Abdel-Wahab, Omar; Bennett, John M; Ketterling, Rhett P; Lazarus, Hillard M; Levine, Ross L; Litzow, Mark R; Paietta, Elisabeth M; Patel, Jay P; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Sun, Zhuoxin; Luger, Selina M

    2016-03-24

    The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m(2)) improved overall survival in adults <60 years old with acute myeloid leukemia (AML); however, at initial analysis, the benefit was restricted to younger patients (<50 years) and patients without unfavorable cytogenetics or aFLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m(2)), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P= .001). Younger patients (<50 years) benefited from HD daunorubicin (HR, 0.66;P= .002), as did patients with favorable and intermediate cytogenetics (HR, 0.51;P= .03 and HR, 0.68;P= .01, respectively). Patients with unfavorable cytogenetics were shown to benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66;P= .04). Patients withFLT3-ITD (24%),DNMT3A(24%), andNPM1(26%) mutant AML all benefited from HD daunorubicin (HR, 0.61,P= .009; HR, 0.62,P= .02; and HR, 0.50,P= .002; respectively). HD benefit was seen in the subgroup of older patients (50-60 years) with theFLT3-ITD orNPM1mutation. Additionally, the presence of anNPM1mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction. PMID:26755712

  17. High doses of dietary zinc induce cytokines, chemokines, and apoptosis in reproductive tissues during regression.

    PubMed

    Sundaresan, N R; Anish, D; Sastry, K V H; Saxena, V K; Nagarajan, K; Subramani, J; Leo, M D M; Shit, N; Mohan, J; Saxena, M; Ahmed, K A

    2008-06-01

    In chickens, high levels of dietary zinc cause molting, and the reproductive system undergoes complete remodeling concomitant to feather replacement. In the present study, the expression profiles of cytokines and chemokines were investigated in the ovary and oviduct of control hens and of hens induced to molt by zinc feeding. The zinc-induced feed-intake suppression, the changes in corticosterone levels, the immune cell populations in the reproductive tract, and the apoptosis of reproductive tissues were analyzed. The expression of mRNAs for interleukin-6 (IL-6), interferon-gamma (IFN-gamma), the avian ortholog of mammalian IL-8 (chCXCLi2), and a chicken MIP-1beta-like chemokine (chCCLi2) in the ovary and of mRNAs for IL-1beta, IL-6, IFN-gamma, transforming growth factor-beta2, chCXCLi2, and chCCLi2 in the oviduct were upregulated significantly during zinc-induced molting. A simultaneous feed-intake reduction was observed with higher expression of cytokines and chemokines. The results of the present investigation also suggested that the upregulation of corticosterone was closely associated with the increased expression of cytokines and chemokines. An increase in apoptosis within reproductive tissue during tissue regression was also noted. We had previously observed the upregulation of these cytokines expression in an earlier study (molting by feed withdrawal). However, the pattern and the level of expression were different among these two methods. These findings indicate that cytokines might be a common mediator of tissue regression during molting induced by diverse methods, although the pattern of induction is different. Thus, a high dose of dietary zinc seems to induce reproductive regression via the upregulation of cytokines and chemokines, the suppression of feed intake, and the increase in serum corticosterone, resulting finally in the apoptosis of reproductive tissues. PMID:18351392

  18. Safety of high-dose intravenous immunoglobulin in systemic autoimmune diseases.

    PubMed

    Tufan, Fatih; Kamali, Sevil; Erer, Burak; Gul, Ahmet; Inanc, Murat; Ocal, Lale; Konice, Meral; Aral, Orhan

    2007-11-01

    It is reported that the usage of high-dose intravenous immunoglobulin (HD-IVIG) in systemic autoimmune diseases is associated with various adverse events in a wide range of severity. We aimed to investigate the frequency and profile of adverse events in a group of patients with diffuse connective tissue diseases and Wegener's granulomatosis (WG) who were administrated HD-IVIG for different indications. We recorded the data of 38 patients (25 females and 13 males) aged 38 +/- 15 (12-75) years who were followed up with the diagnosis of systemic autoimmune diseases between 1994 and 2006 according to a predefined protocol. Patients with active disease were treated with HD-IVIG and standard immunosuppressives concomitantly. We evaluated the occurrence of allergy, acute renal failure, thromboembolic events, neutropenia, hemolytic anemia, aseptic meningitis, and vasculitis during infusion therapy of HD-IVIG and in the following 3 weeks. We commenced a total of 130 infusions of HD-IVIG. Patients were administrated 1-12 (3.4 +/- 2.6) infusions of HD-IVIG as needed. Indications for HD-IVIG were unresponsiveness or partial response to standard treatment, severe infections along with disease activity, and severe thrombocytopenia in the preoperative period in 97, 23, and 5% of patients, respectively. Minor adverse events were seen in two patients during HD-IVIG infusions. One patient with WG developed rapidly progressive renal failure during severe disease flare between HD-IVIG infusions. Another patient with WG developed recurrence of deep-vein thrombosis during severe disease flare 3 months after HD-IVIG. Both events were attributed to severe disease activity. Adverse events like allergy, acute renal failure, thromboembolic events, hematological problems, aseptic meningitis, and vasculitis are reported in different frequencies (1-81%) in patients who were administered HD-IVIG for systemic autoimmune diseases. HD-IVIG is considered a safe treatment in selected patients

  19. [Clinical and biochemical alterations in rats treated with high doses of vitamin A].

    PubMed

    Alarcón-Corredor, O M; Alfonso, R

    2007-09-01

    In the present work the effect of intramuscular administration of 30.000, 50.000 and 100.000 IU of vitamin A palmitate daily for seven days, respectively, on the liver enzyme activity in 45 white male Wistar rats, aged 12 weeks and weighing 180-200 g, have been studied. The group control was integrated by 15 healthy rats with similar characteristics (strain, gender, age and weight) to treated animals. Food and water consumption and body weights were recorded at the end of the experimental period. Rats were observed for clinical signs of toxicity. At the end of the study, rats were sacrificed under ether anesthesia. Liver samples were taken for the determination of enzyme activity. Administration of excess of vitamin A produced a significant (p < 0.05) increase in the content of liver vitamin A, determined diverse and variable clinical signs (such as, anorexia, loss of body weight, alopecia, conjunctivitis, external and internal hemorrhages, skin abnormalities and death) and increased (p < 0.05) the activity of the following enzymes: alanine aminotransferase, aspartate aminotransferase, acid maltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase and alkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylase, alpha-amylase, cholinesterase and arginase decreased (p < 0.05) as compared with untreated controls. These changes depend on the doses given of vitamin A. In conclusion, our results provide evidence that short-term administration of high doses of vitamin A determined diverse and variable clinical signs and produces a marked alteration of activity of liver enzymes. PMID:18271400

  20. 3D-printed surface mould applicator for high-dose-rate brachytherapy

    NASA Astrophysics Data System (ADS)

    Schumacher, Mark; Lasso, Andras; Cumming, Ian; Rankin, Adam; Falkson, Conrad B.; Schreiner, L. John; Joshi, Chandra; Fichtinger, Gabor

    2015-03-01

    In contemporary high-dose-rate brachytherapy treatment of superficial tumors, catheters are placed in a wax mould. The creation of current wax models is a difficult and time consuming proces.The irradiation plan can only be computed post-construction and requires a second CT scan. In case no satisfactory dose plan can be created, the mould is discarded and the process is repeated. The objective of this work was to develop an automated method to replace suboptimal wax moulding. We developed a method to design and manufacture moulds that guarantee to yield satisfactory dosimetry. A 3D-printed mould with channels for the catheters designed from the patient's CT and mounted on a patient-specific thermoplastic mesh mask. The mould planner was implemented as an open-source module in the 3D Slicer platform. Series of test moulds were created to accommodate standard brachytherapy catheters of 1.70mm diameter. A calibration object was used to conclude that tunnels with a diameter of 2.25mm, minimum 12mm radius of curvature, and 1.0mm open channel gave the best fit for this printer/catheter combination. Moulds were created from the CT scan of thermoplastic mesh masks of actual patients. The patient-specific moulds have been visually verified to fit on the thermoplastic meshes. The masks were visually shown to fit onto the thermoplastic meshes, next the resulting dosimetry will have to be compared with treatment plans and dosimetry achieved with conventional wax moulds in order to validate our 3D printed moulds.

  1. Adequacy of High-Dose Cefepime Regimen in Febrile Neutropenic Patients with Hematological Malignancies

    PubMed Central

    Roberts, Michael S.; Tiong, Ing Soo; Gardner, Julia H.; Lehman, Sheila; Peake, Sandra L.; Hahn, Uwe; Warner, Morgyn S.; Roberts, Jason A.

    2015-01-01

    While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic/pharmacodynamic target attainment from a 2-g intravenous (i.v.) every 8 h (q8h) cefepime regimen in febrile neutropenic patients with hematological malignancies. Cefepime plasma concentrations were measured in the 3rd, 6th, and 9th dosing intervals at 60% of the interval and/or trough point. The selected pharmacokinetic/pharmacodynamic targets were the proportion of the dosing interval (60% and 100%) for which the free drug concentration remains above the MIC (fT>MIC). Target attainment was assessed in reference to the MIC of isolated organisms if available or empirical breakpoints if not. The percentage of fT>MIC was also estimated by log-linear regression analysis. All patients achieved >60% fT>MIC in the 3rd and 6th dosing intervals. A 100% fT>MIC was not attained in 6/12, 4/10, and 4/9 patients in the 3rd, 6th, and 9th dose intervals, respectively, or in 14/31 (45%) of the dosing intervals investigated. On the other hand, 29/31 (94%) of trough concentrations were at or above 4 mg/liter. In conclusion, for patients with normal renal function, a high-dose 2-g i.v. q8h cefepime regimen appears to provide appropriate exposure if the MIC of the organism is ≤4 mg/liter but may fail to cover less susceptible organisms. PMID:26124158

  2. High Dose-Rate Intracavitary Brachytherapy for Cervical Carcinomas With Lower Vaginal Infiltration

    SciTech Connect

    Kazumoto, Tomoko Kato, Shingo; Tabushi, Katsuyoshi; Kutsutani-Nakamura, Yuzuru; Mizuno, Hideyuki; Takahashi, Michiko; Shiromizu, Kenji; Saito, Yoshihiro

    2007-11-15

    Purpose: This report presents the clinical applications of an automated treatment-planning program of high-dose-rate intracavitary brachytherapy (HDR-ICBT) for advanced uterine cervical cancer infiltrating the parametrium and the lower vagina. Methods and Materials: We adopted HDR-ICBT under optimized dose distribution for 22 cervical cancer patients with tumor infiltration of the lower half of the vagina. All patients had squamous cell carcinoma with International Federation of Gyne