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Sample records for high-dose stabilized chlorite

  1. Stability of nanosized oxides in ferrite under extremely high dose self ion irradiations

    NASA Astrophysics Data System (ADS)

    Aydogan, E.; Almirall, N.; Odette, G. R.; Maloy, S. A.; Anderoglu, O.; Shao, L.; Gigax, J. G.; Price, L.; Chen, D.; Chen, T.; Garner, F. A.; Wu, Y.; Wells, P.; Lewandowski, J. J.; Hoelzer, D. T.

    2017-04-01

    A nanostructured ferritic alloy (NFA), 14YWT, was produced in the form of thin walled tubing. The stability of the nano-oxides (NOs) was determined under 3.5 MeV Fe+2 irradiations up to a dose of ∼585 dpa at 450 °C. Transmission electron microscopy (TEM) and atom probe tomography (APT) show that severe ion irradiation results in a ∼25% reduction in size between the unirradiated and irradiated case at 270 dpa while no further reduction within the experimental error was seen at higher doses. Conversely, number density increased by ∼30% after irradiation. This 'inverse coarsening' can be rationalized by the competition between radiation driven ballistic dissolution and diffusional NO reformation. No significant changes in the composition of the matrix or NOs were observed after irradiation. Modeling the experimental results also indicated a dissolution of the particles.

  2. Stability of nanosized oxides in ferrite under extremely high dose self ion irradiations

    DOE PAGES

    Aydogan, E.; Almirall, N.; Odette, G. R.; ...

    2017-01-10

    We produced a nanostructured ferritic alloy (NFA), 14YWT, in the form of thin walled tubing. The stability of the nano-oxides (NOs) was determined under 3.5 MeV Fe+2 irradiations up to a dose of ~585 dpa at 450 °C. Transmission electron microscopy (TEM) and atom probe tomography (APT) show that severe ion irradiation results in a ~25% reduction in size between the unirradiated and irradiated case at 270 dpa while no further reduction within the experimental error was seen at higher doses. Conversely, number density increased by ~30% after irradiation. Moreover, this ‘inverse coarsening’ can be rationalized by the competition betweenmore » radiation driven ballistic dissolution and diffusional NO reformation. There were no significant changes in the composition of the matrix or NOs observed after irradiation. Modeling the experimental results also indicated a dissolution of the particles.« less

  3. Stability of nanosized oxides in ferrite under extremely high dose self ion irradiations

    DOE PAGES

    Aydogan, E.; Almirall, N.; Odette, G. R.; ...

    2017-01-10

    We produced a nanostructured ferritic alloy (NFA), 14YWT, in the form of thin walled tubing. The stability of the nano-oxides (NOs) was determined under 3.5 MeV Fe+2 irradiations up to a dose of ~585 dpa at 450 °C. Transmission electron microscopy (TEM) and atom probe tomography (APT) show that severe ion irradiation results in a ~25% reduction in size between the unirradiated and irradiated case at 270 dpa while no further reduction within the experimental error was seen at higher doses. Conversely, number density increased by ~30% after irradiation. Moreover, this ‘inverse coarsening’ can be rationalized by the competition betweenmore » radiation driven ballistic dissolution and diffusional NO reformation. There were no significant changes in the composition of the matrix or NOs observed after irradiation. Modeling the experimental results also indicated a dissolution of the particles.« less

  4. Stability of high-dose insulin in normal saline bags for treatment of calcium channel blocker and beta blocker overdose.

    PubMed

    Laskey, Dayne; Vadlapatla, Rajesh; Hart, Katherine

    2016-11-01

    High-dose insulin has become a first-line therapy for treating severe calcium channel blocker and beta blocker toxicity. Insulin infusions used to treat other conditions (e.g., diabetic ketoacidosis) may be used, but this may lead to pulmonary compromise due to fluid volume overload. An obvious solution would be to use a more concentrated insulin infusion; however, data describing the stability of insulin in polyvinyl chloride bags at concentrations >1 unit/mL are not readily available. To determine the stability of insulin at 16 units/mL in 0.9% saline solution. Eight-hundred units of regular insulin (8 mL from a stock vial containing 100 units/mL) were added to 42 mL of 0.9% saline solution in a polyvinyl chloride bag to make a final concentration of 16 units/mL. Two bags were stored at 4 °C (refrigerated) and two at 25 °C (room temperature). Samples were withdrawn and tested for insulin concentration periodically over 14 days. Concentrated regular insulin in a polyvinyl chloride bag remained within 90% of equilibrium concentration at all time points, indicating the 16 units/mL concentration was sufficiently stable both refrigerated and at room temperature for 14 days. Administration of high-dose insulin can cause fluid volume overload when using traditional insulin formulations. The 16 units/mL concentration allows for the treatment of a patient with severe calcium channel blocker or beta blocker toxicity for a reasonable period of time without administering excessive fluid. Insulin at a concentration of 16 units/mL is stable for 14 days, the maximum timeframe currently allowed under US Pharmacopeia rules for compounding of sterile preparations. This stability data will allow institutions to issue beyond-use dating for intravenous fluids containing concentrated insulin and used for treating beta blocker and calcium channel blocker toxicity.

  5. Chlorite (sodium salt)

    Integrated Risk Information System (IRIS)

    EPA / 635 / R - 00 / 007 TOXICOLOGICAL REVIEW OF CHLORINE DIOXIDE AND CHLORITE ( CAS Nos . 10049 - 04 - 4 and 7758 - 19 - 2 ) In Support of Summary Information on the ( IRIS ) Integrated Risk Information System September 2000 U.S . Environmental Protection Agency Washington , DC DISCLAIMER This docu

  6. New generation of nuclear fuels: Stability of different stearates under high doses gamma irradiation in the manufacturing process

    NASA Astrophysics Data System (ADS)

    Lebeau, D.; Esnouf, S.; Gracia, J.; Audubert, F.; Ferry, M.

    2017-07-01

    In the future reactors, the pellets radioactivity will increase due to the modification of the plutonium concentration. The stability of the organic additive used as lubricating/deagglomerating agent has thus to be evaluated. Up to now, zinc stearate is employed, but new additives are tested in this study and compared to zinc stearate. In a first part of this paper, the order of magnitude of the dose deposited in the stearates has been estimated. Afterward, three different stearates have been irradiated, using gamma-rays at doses as high as 2000 kGy. Two atmospheres of irradiation were tested, i.e. inert atmosphere and air. Samples were characterized using the following analytical tools: mass spectrometry, thermogravimetry and infrared spectroscopy. The objective is the evaluation of the ageing of these materials. In the nuclear fuel pellets manufacturing context, the candidate which could replace zinc stearate, if this one is too degraded to fulfill its role of lubricant in the pellets of the future manufacturing, has been determined.

  7. Production and stability of chlorine dioxide in organic acid solutions as affected by pH, type of acid, and concentration of sodium chlorite, and its effectiveness in inactivating Bacillus cereus spores.

    PubMed

    Kim, Hoikyung; Kang, Youngjee; Beuchat, Larry R; Ryu, Jee-Hoon

    2008-12-01

    We studied the production and stability of chlorine dioxide (ClO(2)) in organic acid solutions and its effectiveness in killing Bacillus cereus spores. Sodium chlorite (5000, 10,000, or 50,000 microg/ml) was added to 5% acetic, citric, or lactic acid solution, adjusted to pH 3.0, 4.0, 5.0, or 6.0, and held at 21 degrees C for up to 14 days. The amount of ClO(2) produced was higher as the concentration of sodium chlorite was increased and as the pH of the acid solutions was decreased. However, the stability in production of ClO(2) was enhanced by increasing the pH of the organic acid solutions. To evaluate the lethal activity of ClO(2) produced in various acid solutions as affected by acidulant and pH, suspensions of B. cereus spores were treated at 21 degrees C for 1, 3, 5, or 10 min in hydrochloric acid or organic acid solutions (pH 3.0, 4.0, 5.0, or 6.0) containing ClO(2) at concentrations of 100, 50, or 25 microg/ml. Populations of viable spores treated with ClO(2) at concentrations of 100 or 50 microg/ml in organic acid solutions decreased more rapidly than populations treated with the same concentrations of ClO(2) in HCl. Rates of inactivation tended to increase with higher pH of ClO(2) solutions. Results show that ClO(2) formed in organic acid solutions has higher stability and is more lethal to B. cereus spores than ClO(2) formed at the same concentration in HCl solution. This finding emphasizes the benefits of using organic acid solutions to prepare ClO(2) intended for use as an antimicrobial.

  8. Studies of carcinogenicity of sodium chlorite in B6C3F1 mice.

    PubMed Central

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

    1987-01-01

    The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentrations 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. PMID:3447900

  9. 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 is...

  10. 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...

  11. 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...

  12. 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...

  13. 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

  14. Mechanism of reaction of chlorite with mammalian heme peroxidases.

    PubMed

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

    2014-06-01

    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.

  15. 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 from...

  16. High-dose neutron detector project update

    SciTech Connect

    Menlove, Howard Olsen; Henzlova, Daniela

    2016-08-10

    These are the slides for a progress review meeting by the sponsor. This is an update on the high-dose neutron detector project. In summary, improvements in both boron coating and signal amplification have been achieved; improved boron coating materials and procedures have increased efficiency by ~ 30-40% without the corresponding increase in the detector plate area; low dead-time via thin cell design (~ 4 mm gas gaps) and fast amplifiers; prototype PDT 8” pod has been received and testing is in progress; significant improvements in efficiency and stability have been verified; use commercial PDT 10B design and fabrication to obtain a faster path from the research to practical high-dose neutron detector.

  17. 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

  18. Correlation of Chlorite Frictional Strength with Composition

    NASA Astrophysics Data System (ADS)

    Moore, D. E.; Lockner, D. A.

    2015-12-01

    Chlorite is a common phyllosilicate mineral in crustal fault zones, and it is generally considered to contribute to fault-zone weakening. However, very little is known about its frictional properties, in part because of the difficulty in obtaining suitable material for study. Synthetic gouges (<90 μm grain size) have been prepared from four chlorite-rich separates whose compositions range between 18.3 and 33.6 wt% MgO, 1.3-21.6 wt% FeO (total Fe content), and 25.0-33.0 wt% SiO2 (electron microprobe analysis). Magnesium contents vary directly with Si and inversely with Fe. Frictional strengths were measured in the temperature range 25-300°C and shearing rates between 0.00115 and 1.15 μm/s, with fluid pressure and effective normal stress held constant at 60 and 100 MPa, respectively. The chlorites are velocity strengthening at all tested conditions, promoting stable slip. No obvious trends in strength relative to either temperature or velocity were discernible for a given chlorite. In contrast, the frictional strength at any given set of physical conditions is a function of chlorite composition, the most Fe-rich chlorite being the strongest (coefficient of friction, μ in the range 0.26-0.36) and the most Mg- and Si-rich sample the weakest (μ = 0.16-0.22). This is one of the first reports of a compositional influence on the frictional properties of a mineral. The results confirm that chlorite will contribute to strength reduction in fault gouge, but the Mg-rich chlorites associated with ultramafic rocks will be more effective weakening agents than the relatively high-Fe chlorites more typical of quartzofeldspathic crustal rocks.

  19. A case of sodium chlorite toxicity managed with concurrent renal replacement therapy and red cell exchange.

    PubMed

    Romanovsky, Adam; Djogovic, Dennis; Chin, Dat

    2013-03-01

    Sodium chlorite is a powerful oxidizing agent with multiple commercial applications. We report the presentation and management of a single case of human toxicity of sodium chlorite. A 65-year-old man presented to hospital after accidentally ingesting a small amount of a sodium chlorite solution. His principal manifestations were mild methemoglobinemia, severe oxidative hemolysis, disseminated intravascular coagulation, and anuric acute kidney injury. He was managed with intermittent hemodialysis, followed by continuous venovenous hemofiltration for management of acute kidney injury and in an effort to remove free plasma chlorite. Concurrently, he underwent two red cell exchanges, as well as a plasma exchange, to reduce the burden of red cells affected by chlorite. These interventions resulted in the cessation of hemolysis with stabilization of serum hemoglobin and platelets. The patient survived and subsequently recovered normal renal function. This is only the second case of sodium chlorite intoxication reported in the medical literature and the first to report the use of renal replacement therapy in combination with red cell exchange in its management.

  20. 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.

  1. Toxicological effects of chlorite in the mouse.

    PubMed Central

    Moore, G S; Calabrese, E J

    1982-01-01

    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 glucose-6-phosphate dehydrogenase activity for both strains. Chlorite exposure of pregnant A/J mice resulted in a significant decrease in the weight of pups at weaning and a lower average birth to weaning growth rate. Mice exposed to as much as 100 ppm sodium chlorite (NaClO2) in their drinking water for up to 120 days failed to demonstrate any histopathological changes in kidney structure. PMID:7151765

  2. Pedogenic chlorites in podzolic soils with different intensities of hydromorphism: Origin, properties, and conditions of their formation

    NASA Astrophysics Data System (ADS)

    Tolpeshta, I. I.; Sokolova, T. A.; Bonifacio, E.; Falcone, G.

    2010-07-01

    Minerals of the pedogenic chlorite group were studied in the clay fractions isolated from the mineral horizons of podzolic and gleyic peat-podzolic soils. In the AE and E horizons of the podzolic soil, pedogenic chlorites are thought to develop from vermiculite, whereas in the E horizon of the gleyic peat-podzolic soil, they can be formed from smectite minerals. For estimating the degree of chloritization (the degree of filling of the interlayer space of 2: 1 minerals with Al hydroxides), a numerical criterion was is proposed. The difference between the values of this criterion before and after the treatment of the preparations with NH4F indicated that the degree of chloritization in the pedogenic chlorites decreases in the following sequence: the E horizon of the podzolic soil > the AE horizon of the podzolic soil > the E horizon of the gleyic peat-podzolic soil. Another numerical criterion was proposed to estimate the degree of polymerization of Al-hydroxy complexes in pedogenic chlorites. This criterion was based on the thermal stability of soil chlorites and represented the temperature at which an increase in the intensity of the 1.0-nm peak after heating the K-saturated preparations exceeds 50% of its initial value. According to this criterion, the degree of polymerization of the Al-hydroxy interlayers in pedogenic chlorites decreases in the following sequence: the E horizon of the podzolic soil > the E horizon of the gleyic peat-podzolic soil ≥ the AE horizon of the podzolic soil. The distinct interrelation between the soil properties and the degrees of chloritization and polymerization of the Al-hydroxy interlayers attests to the modern origin of the pedogenic chlorites.

  3. 21 CFR 173.325 - Acidified sodium chlorite solutions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Acidified sodium chlorite solutions. 173.325... HUMAN CONSUMPTION Specific Usage Additives § 173.325 Acidified sodium chlorite solutions. Acidified sodium chlorite solutions may be safely used in accordance with the following prescribed conditions: (a...

  4. 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

  5. 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.

  6. High dose insulin in toxic cardiogenic shock.

    PubMed

    Holger, Joel S; Engebretsen, Kristin M; Marini, John J

    2009-04-01

    To report the successful use of high dose insulin (HDI) in previously unreported insulin dosing ranges in a patient with severe myocardial toxicity due to an amitriptyline and citalopram overdose. A 65-year-old female presented in respiratory arrest, which was followed by bradycardic pulseless electrical activity after ingesting multiple medications. After a prolonged resuscitation, the patient was maintained only on infusions of norepinephrine (40 mcg/min), vasopressin (4 units/h), insulin (80 units/h), and sodium bicarbonate. Due to a deteriorating clinical condition and limited prognosis, the insulin infusion was titrated incrementally upwards to 600 units/h (6 units/kg/h) over a 5 h time period while simultaneously completely weaning off both vasopressors. She developed brisk pulses and warm extremities, and her cardiac output nearly tripled. After 2 days of stabilization the insulin was slowly tapered, and the patient recovered. HDI as a single cardiovascular agent significantly improved clinical and cardiovascular parameters after the failure of vasopressor therapy in severe cardiovascular toxicity. Higher doses of insulin than previously recommended may be needed in toxic poisonings when severe myocardial depression is present.

  7. Fluzone High-Dose Seasonal Influenza Vaccine

    MedlinePlus

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine/Variant Pandemic Other Fluzone High-Dose Seasonal Influenza Vaccine Questions & Answers Language: English (US) Español ...

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

    PubMed Central

    Goblirsch, Brandon R.; Streit, Bennett R.; DuBois, Jennifer L.

    2010-01-01

    Chlorite dismutase (Cld) is a heme enzyme capable of rapidly and selectively decomposing chlorite (ClO2−) to Cl− and O2. The ability of Cld to promote O2 formation from ClO2− is unusual. Heme enzymes generally utilize ClO2− 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 (NO2−) 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 ClO2− within the distal pocket generates hypochlorite (ClO−) and a compound I intermediate. The sterically restrictive distal pocket probably facilitates the rapid rebound of ClO− with compound I forming the Cl− and O2 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 O2 may have a preferential direction for exiting the active site. PMID:20386942

  9. 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.

  10. [Hopes of high dose-rate radiotherapy].

    PubMed

    Fouillade, Charles; Favaudon, Vincent; Vozenin, Marie-Catherine; Romeo, Paul-Henri; Bourhis, Jean; Verrelle, Pierre; Devauchelle, Patrick; Patriarca, Annalisa; Heinrich, Sophie; Mazal, Alejandro; Dutreix, Marie

    2017-04-01

    In this review, we present the synthesis of the newly acquired knowledge concerning high dose-rate irradiations and the hopes that these new radiotherapy modalities give rise to. The results were presented at a recent symposium on the subject. Copyright © 2017. Published by Elsevier Masson SAS.

  11. 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.

  12. 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

  13. 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.

  14. High dose Nutrizym 22 in cystic fibrosis.

    PubMed

    Shah, A; Dinwiddie, R; Madge, S; Prescott, P; Hudson, G

    1993-09-01

    New high dose pancreatic enzyme preparations could be potentially helpful to cystic fibrosis (CF) patients. The purpose of this study was to compare the efficacy of the new high dose pancreatic enzyme preparation, Nutrizym 22 with the standard preparation Nutrizym GR. Twenty-five CF children (aged 7-16 years) entered the study and 22 completed it; 3 did not, due to non-compliance. All were taking Nutrizym GR for at least 2 weeks before entering the study. A randomised double blind, crossover method using standard Nutrizym GR or double strength Nutrizym 22 capsules was carried out over two consecutive 14-day periods. Crossover analyses of variance showed no statistically significant differences in actual weight gain, appetite, abdominal pain, stool consistency or faecal fat during the prestudy and study periods. It is concluded that half the capsule numbers of the high strength preparation are just as effective as the standard capsule dosage.

  15. 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.

  16. 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.

  17. Pregnancy under high-dose buprenorphine.

    PubMed

    Simmat-Durand, Laurence; Lejeune, Claude; Gourarier, Laurent

    2009-02-01

    This study was first conducted to compare the consequences of the use of methadone and high-dose buprenorphine in pregnancy in France and secondly to describe the heterogeneity of women under high-dose buprenorphine. This paper focuses on the second point only. From October 1998 to September 1999, data on pregnancy, delivery outcomes and neonatal parameters were collected for 251 addicted women on methadone or high-dose buprenorphine (HDB) substitution followed in 35 hospitals and clinics in continental France. Then the data of 159 women who had been taking HDB during pregnancy and had delivered 160 live infants were analyzed. Most of these women were treated as outpatients by general practitioners. 43% of them belong to what we considered a "hidden population" of drug users: most of them were native French citizens, who lived with the future fathers in their own homes, had at least some secondary education, and were usually not followed in specialized centers for drug addicts. Almost all the women smoked every day during their pregnancies; 20% used heroin during the last 4 weeks preceding delivery; 16% admitted having injected HDB at least once. Notably, neither the severity nor the duration of the neonatal abstinence syndrome (NAS) seemed to be related to the daily doses of the substitution agent. Half of the newborns were treated for NAS, mainly with morphine hydrochloride. Although two different populations of women were clearly identified, 64 with no social disadvantage and 95 socially disadvantaged, there was no difference between the groups as for the severity of NAS which was only related to the mothers' compliance with a programme of treatment against addiction.

  18. [Teratogenicity study of sodium chlorite in rats by oral administration].

    PubMed

    Sakemi, K; Usami, M; Kurebayashi, H; Ohno, Y

    1999-01-01

    The teratogenicity of sodium chlorite (NaClO2) was assessed in Wistar rats (Crj: Wistar). Sodium chlorite dissolved in distilled water was given to pregnant Wistar rats by gavage once a day from day 6 through 15 of pregnancy at doses of 0, 25, 50 and 100 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy, and their fetuses were examined for malformations. Sodium chlorite caused decreased food consumption, anemia, sedation, hematuria, and death in the pregnant rats at 100 mg/kg, but no fetal effects, such as malformations or growth retardation, were observed even at 100 mg/kg. It was concluded that sodium chlorite has no teratogenicity in rats when administered orally. The no-observed-adverse-effect level was 50 mg/kg/day for pregnant rats and 100 mg/kg/day or more for rat fetuses.

  19. 21 CFR 173.325 - Acidified sodium chlorite solutions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN CONSUMPTION Specific Usage Additives § 173.325 Acidified sodium chlorite solutions. Acidified...., College Park, MD 20740, or may be examined at the Center for Food Safety and Applied Nutrition's...

  20. Immune reactivity after high-dose irradiation

    SciTech Connect

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-03-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient.

  1. High-dose fenretinide in oral leukoplakia.

    PubMed

    William, William N; Lee, J Jack; Lippman, Scott M; Martin, Jack W; Chakravarti, Nitin; Tran, Hai T; Sabichi, Anita L; Kim, Edward S; Feng, Lei; Lotan, Reuben; Papadimitrakopoulou, Vassiliki A

    2009-01-01

    We previously showed that low-dose fenretinide (200 mg/d) had limited activity in retinoid-resistant oral leukoplakia (34% response rate) possibly because serum drug levels were insufficient to induce retinoid receptor-independent apoptosis. Therefore, we designed the single-arm phase II trial reported here to investigate whether higher-dose fenretinide would improve leukoplakia response over that of our previous study. Leukoplakia patients received fenretinide (900 mg/m(2) twice daily) in four 3-week cycles (1 week on drug followed by 2 weeks off). At week 12, clinical responses were determined and blood samples were collected for serum drug level assessments. A planned interim futility analysis led to early trial closure after the initial 15 (of 25 planned) patients because only 3 (20%) had a partial response (stopping rule: high-dose fenretinide inhibited the growth of head and neck cancer cells more and oral leukoplakia cells less than did lower doses of fenretinide. This result is consistent with our clinical finding that high-dose fenretinide did not improve on the historical response rate of lower-dose fenretinide in our previous oral leukoplakia trial.

  2. “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

  3. Development of an automated on-line electrochemical chlorite ion sensor.

    PubMed

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

    2012-05-30

    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.

  4. 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.

  5. EPR/Homotaurine: A possible dosimetry system for high doses

    NASA Astrophysics Data System (ADS)

    Maghraby, A.; Salama, E.; Mansour, A.

    2011-12-01

    An EPR investigation of radiation induced radicals in Homotaurine revealed that there are two types of radicals produced after exposure to gamma radiation (60Co). EPR spectra were recorded and analyzed; also the microwave power saturation curves for both radicals were studied. The effect of change in modulation amplitude on peak-to-peak signal height and line width was investigated; this is in addition to the evaluation of energy dependence parameters compared to soft tissue and alanine dosimeters. Response of Homotaurine to different radiation doses (0.5 kGy-50 kGy) was studied and found to follow a linear relationship. Radiation induced radicals in Homotaurine persisted and showed a noticeable stability over 30 days following irradiation. It was found that Homotaurine possesses good dosimetric properties using EPR spectroscopy in high doses and is characterized by its simple spectrum.

  6. 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.

  7. Cervix cancer brachytherapy: high dose rate.

    PubMed

    Miglierini, P; Malhaire, J-P; Goasduff, G; Miranda, O; Pradier, O

    2014-10-01

    Cervical cancer, although less common in industrialized countries, is the fourth most common cancer affecting women worldwide and the fourth leading cause of cancer death. In developing countries, these cancers are often discovered at a later stage in the form of locally advanced tumour with a poor prognosis. Depending on the stage of the disease, treatment is mainly based on a chemoradiotherapy followed by uterovaginal brachytherapy ending by a potential remaining tumour surgery or in principle for some teams. The role of irradiation is crucial to ensure a better local control. It has been shown that the more the delivered dose is important, the better the local results are. In order to preserve the maximum of organs at risk and to allow this dose escalation, brachytherapy (intracavitary and/or interstitial) has been progressively introduced. Its evolution and its progressive improvement have led to the development of high dose rate brachytherapy, the advantages of which are especially based on the possibility of outpatient treatment while maintaining the effectiveness of other brachytherapy forms (i.e., low dose rate or pulsed dose rate). Numerous innovations have also been completed in the field of imaging, leading to a progress in treatment planning systems by switching from two-dimensional form to a three-dimensional one. Image-guided brachytherapy allows more precise target volume delineation as well as an optimized dosimetry permitting a better coverage of target volumes.

  8. Identification of chlorite and serpentine in cosmetic or pharmaceutical talc.

    PubMed Central

    Blount, A M; Vassiliou, A H

    1983-01-01

    Chlorite is the most common accessory mineral group found in high purity talc ore used in cosmetic or pharmaceutical consumer talcum products. X-ray diffraction and wet chemical analytical data obtained on geologic samples representing commercial talc ore deposits of high purity and on processed samples representing talc found in consumer talcum products indicate that clinochlore and penninite are the two chlorite minerals most commonly found in all talc samples irrespective of origin or source, but sheridanite is also found in some samples representing talc deposits that are associated with serpentinite rocks. The chlorite minerals exhibit certain well-defined X-ray diffraction characteristics which differentiate them from each other as well as from those of serpentine minerals, including the hazardous chrysotile asbestos. PMID:6641661

  9. High dose rate brachytherapy for oral cancer

    PubMed Central

    YamazakI, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. PMID:23179377

  10. 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

  11. High-dose fluoroscopy: the administrator's responsibilities.

    PubMed

    Archer, Benjamin R

    2002-01-01

    During the past 15 years, developments in x-ray technologies have substantially improved the ability of practitioners to treat patients using fluoroscopically guided interventional techniques. Many of these procedures require a greater use of fluoroscopy and serial imaging (cine). This has increased the potential for radiation-induced dermatitis, epilation and severe radiation-induced burns to patients. Radiology administrators must realize that these high-dose procedures increase the risk for radiation injury and radiation-induced cancer in personnel as well as in patients. This article discusses particular clinical cases and describes positive, pro-active steps that practitioners and administrators can take to help prevent such injuries in their facilities. Unfortunately, with the exception of radiologists, a large proportion of physicians who use fluoroscopy have effectively no training or credentials in management of radiation or the biological effects associated with its use. In 1994, an FDA advisory warned that training of physicians for modern-day use of the fluoroscope was for the most part insufficient and needed to be expanded. Many prominent medical organizations such as the American College of Cardiology (14) and the American Heart Association (15) have published strongly worded position papers agreeing that there is an urgent need for such training. The consensus is that "rubber-stamp" privileges (16,17) to perform fluoroscopic procedures should no longer be granted. At present, the JCAHO is considering the implementation of a statement regarding JCAHO standards and privileges for practitioners to use fluoroscopic x-ray equipment. Whether or not the JCAHO becomes involved, it is becoming increasingly clear that all practitioners who use fluoroscopic radiation should be required to complete focused training in radiation physics, radiation biology and radiation safety. Training should include the pertinent aspects of radiation management in the clinical

  12. 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.

  13. 21 CFR 173.325 - Acidified sodium chlorite solutions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... solution of sodium chlorite (CAS Reg. No. 7758-19-2) with any generally recognized as safe (GRAS) acid. (b... accordance with current industry practice in the processing of red meat, red meat parts, and organs as a component of a spray or in the processing of red meat parts and organs as a component of a dip. Applied as...

  14. Mössbauer study of some Argentinian chlorites

    NASA Astrophysics Data System (ADS)

    Gregori, Daniel A.; Mercader, R. C.

    1994-12-01

    Three chlorite samples obtained from mining areas in Mendoza, Argentina, have been studied by wet chemical analysis, X-ray diffraction and57Fe Mössbauer spectroscopy. The total Fe contents and the Fe2+/Fe3+ atomic ratio are used to characterize the samples and are discussed in connection to the likely genesis of the minerals.

  15. 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 good...

  16. A true chemical clock: Serially coupled chlorite iodide oscillators

    NASA Astrophysics Data System (ADS)

    Long, David A.; Chodroff, Leah; O'Neal, Tim M.; Hemkin, Sheryl

    2007-10-01

    A set of serially coupled flow reactors are modeled which contain chlorite-iodide oscillators. By independently varying the reactor flow rates it is possible to produce oscillatory systems with differing periods where the ratio of the period of oscillation between reactors is always an integer value. This system was thoroughly examined and utilized to produce a 'true' chemical clock whose three reactors oscillate with a frequency of minutes, hours, and days.

  17. Chlorite-Oxidized Amylose as an Adjuvant for Interferon Production

    PubMed Central

    Levy, Hilton B.; Duenwald, Jeff; Buckler, Charles E.

    1973-01-01

    Chlorite-oxidized amylose (COAM), when given intraperitoneally to mice and to cats, increased the titer of serum interferon subsequently induced by polyinosinic·polycytidylic acid (In·Cn). Increases ranged from 6- to 100-fold. Maximal effect was observed when COAM was given 3 h prior to In·Cn. COAM given intravenously prior to Newcastle disease virus also significantly increased serum interferon titers. PMID:4713694

  18. Measurement of chlorite dismutase activities in perchlorate respiring bacteria.

    PubMed

    Xu, Jianlin; Logan, Bruce E

    2003-08-01

    Chlorite dismutase (CD) catalyzes the disproportionation of chlorite to chloride (ClO(2)(-)-->Cl(-)+O(2)) and is present in bacteria capable of cell respiration using perchlorate or chlorate. The activity of this enzyme has previously been measured by monitoring oxygen evolution using a Clark-type dissolved oxygen (DO) probe. We demonstrate here, using two other methods to measure CD activity (a chloride-specific electrode and ion chromatography (IC)) via chloride production, that the DO probe method underestimates dismutation rates. Of the three methods, the chloride probe was the easiest to use and did not require extensive sample handling or post-experimental analysis. Using the chloride electrode method, we determined whole cell rate constants (V(max)=64 U/mg DW, K(m)=0.17 mM) for the chlorate-grown suspensions of Dechlorosoma sp. strain KJ. We compared the CD activities of strain KJ at a fixed chlorite concentration (0.6 mM) to four other perchlorate respiring bacteria (PRB), and to one non-PRB (Pseudomonas aeruginosa). Chlorate-grown cultures of the five PRB strains had CD activities ranging from 25 to 50 U/mg of cell dry weight (DW), while aerobically grown cultures of the PRB had much lower CD activities (0.5-4 U/mg DW). To our knowledge, this is the first systematic comparison of the different methods to measure CD activities, and the first comparison of CD activities of different PRBs.

  19. Concerted dismutation of chlorite ion: water-soluble iron-porphyrins as first generation model complexes for chlorite dismutase.

    PubMed

    Zdilla, Michael J; Lee, Amanda Q; Abu-Omar, Mahdi M

    2009-03-02

    Three iron-5,10,15,20-tetraarylporphyrins (Fe(Por-Ar4), Ar = 2,3,5,6-tetrafluro-N,N,N-trimethylanilinium (1), N,N,N-trimethylanilinium (2), and p-sulfonatophenyl (3)) have been investigated as catalysts for the dismutation of chlorite (ClO2-). Degradation of ClO2- by these catalysts occurs by two concurrent pathways. One leads to formation of chlorate (ClO3-) and chloride (Cl-), which is determined to be catalyzed by O=FeIV(Por) (Compound II) based on stopped-flow absorption spectroscopy, competition with 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonicacid), 18O-labeling studies, and kinetics. The second pathway is a concerted dismutation of chlorite to dioxygen (O2) and chloride. On the basis of isotope labeling studies using a residual gas analyzer, the mechanism is determined to be formation of O=FeIV(Por)*+ (Compound I) from oxygen atom transfer, and subsequent rebound with the resulting hypochlorite ion (ClO-) to give dioxygen and chloride. While the chlorate production pathway is dominant for catalysts 2 and 3, the O2-producing pathway is significant for catalyst 1. In addition to chlorite dismutation, complex 1 catalyzes hypochlorite disproportionation to chloride and dioxygen quantitatively.

  20. 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

  1. Purpura and dermal thinning associated with high dose inhaled corticosteroids.

    PubMed Central

    Capewell, S; Reynolds, S; Shuttleworth, D; Edwards, C; Finlay, A Y

    1990-01-01

    OBJECTIVE--To assess the effect of high dose inhaled corticosteroids on skin. DESIGN--Cross sectional study of patients receiving treatment for chest diseases. SETTING--Outpatient chest clinic in a teaching hospital. PATIENTS--68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES--Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS--Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION--Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids. PMID:2372620

  2. Stochastic dynamics of the chlorite-iodide reaction

    NASA Astrophysics Data System (ADS)

    Sagués, F.; Ramírez-Piscina, L.; Sancho, J. M.

    1990-04-01

    A recently proposed theoretical framework appropriate to the study of the stochastic behavior of several chemical systems is used to analyze the irreproducibility of the observed reaction times in the chlorite-iodide clock reaction. Noise terms are incorporated through the kinetic constants and their intensity is further correlated with the inverse of the stirring rate. Analytical and simulation results are obtained for the first moments of the reaction time distribution. These results are compared with recent experimental data obtained by Nagypál and Epstein.

  3. Sodium chlorite as an efficient oxidant and hydroxy ion pump in osmium-catalyzed asymmetric dihydroxylation.

    PubMed

    Junttila, Mikko H; Hormi, Osmo E O

    2004-07-09

    Sodium chlorite is an efficient stoichiometric oxidant in Sharpless asymmetric dihydroxylation. One sodium chlorite provides the reaction with the stoichiometric number of electrons and hydroxide ions needed to dihydroxylate two olefins without the consumption of any additional base. 100% conversion in sodium chlorite asymmetric dihydroxylation of styrene was achieved twice as fast as in the established Sharpless K(3)[Fe(CN)(6)] dihydroxylation. Even internal olefins were dihydroxylated fast with sodium chlorite without hydrolysis aids. Eight olefins were dihydroxylated to corresponding vicinal diols with yields and ees as good as those reported in the literature for other similar processes.

  4. Relevance of high-dose chemotherapy in solid tumours.

    PubMed

    Nieboer, P; de Vries, E G E; Mulder, N H; van der Graaf, W T A

    2005-05-01

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.

  5. Key Technologies for Ultra High Dose CMOS Applications

    SciTech Connect

    Jeon, Y.; Koo, I.; Singh, V.; Oh, J.; Jin, S.; Lee, J.; Rouh, K.; Ju, M.; Jeon, S.; Ku, J.; Lee, S. B.; Lee, S. W.; Ok, M. T.; Butterbaugh, J.; Lee, A.; Kim, K.; Lee, S. W.; Ju, K. J.; Park, J. W.

    2008-11-03

    The trend towards shrinking advanced microelectronic Logic and DRAM devices will require ultra high dose implantation. One ultra high dose application in DRAM, being rapidly adopted in production is Dual Poly Gate (DPG). Three main challenges existed for the adoption of this high dose dual poly gate (DPG) doping applications: monitoring of high dose implantation, photoresist stripping and maintaining high throughput. In this paper we present how these challenges have been addressed. VSEA's plasma doping (PLAD) tool offers several unique advantages for DPG applications. When compared to conventional or molecular beam line implanters or other immersion techniques, PLAD delivers 3 to 7 times higher throughput (compared to traditional ion implanter) without dopant penetration through the thin doped polysilicon layer into the gate oxide. It also improves P{sup +} poly silicon DPG device properties at superior throughput. In this work we demonstrate how hot spray photoresist strip processing eliminates the need for multiple-tools required for wet+ash+wet process. In addition to PLAD's patented in-situ dose control metrology we also demonstrate an ex-situ high dose implantation metrology using spectroscopic ellipsometer (SE) and spectroscopic reflectometer (SR). The technique shows good correlation (R{sup 2}{approx}0.99) between implant dose and damaged layer thickness.

  6. Kinetics of chlorite dismutase in a perchlorate degrading reactor sludge.

    PubMed

    Nadaraja, Anupama Vijaya; Veetil, Prajeesh Gangadharan Puthiya; Vidyadharan, Athira; Bhaskaran, Krishnakumar

    2013-01-01

    Kinetics of chlorite dismutase (CD), the terminal enzyme involved in the perchlorate (ClO4(-)) reduction pathway, in a ClO4(-)-degrading bioreactor are reported in this study. Enzyme activity was determined from dissolved oxygen released during disproportionation of chlorite (ClO2(-)). CD activity was in the range 29.8-36.4 U/mg dry weight sludge, and kinetic constants Vmax and K(m) of the enzyme were 37.83 U/mg dry weight and 0.28 mM, respectively. Among reactor operational conditions, enzyme activity was observed at pH 4.0-9.0, with an optimum at pH 6.0. Redox potential in the range -50 to +120mV and NaCl up to 3.5 g/L had no significant effect on CD activity. However, co-occurring pollutants such as ammonium at 10 ppm, nitrite at 50 ppm and EDTA at 100 microM reduced CD activity substantially. The present study highlights ideal bioreactor conditions to avoid ClO2(-) toxicity, while indicating the buffering potential of a mixed microbial system against inhibiting factors to maintain stable CD activity in bioreactors.

  7. A novel, simple and sensitive resonance scattering spectral method for the determination of chlorite in water by means of rhodamine B.

    PubMed

    Kang, Cai-yan; Jiang, Zhi-liang; Xi, Dan-li; He, Xing-cun

    2006-01-01

    A new resonance scattering method was proposed for the determination of chlorite, basing on the resonance scattering effect of rhodamine dye. In HCl-sodium acetate buffer solution, chlorite oxidizes I- into I2 and the reaction of I2 and excess I- results in I3- It is respectively combined with rhodamine dyes, including rhodamine B (RhB), butyl rhodamine B (b-RhB), rhodamine G (RhG) and rhodamine S (RhS), to form association complex particles, which exhibit stronger resonance scattering (RS) effect at 400 nm. The chlorite concentration of ClO2- in the range of 0.00726-0.218 microg/ml, 0.0102-0.292 microg/ml, 0.00726 0.145 microg/ml and 0.0290 0.174 microg/ml is respectively linear to the RS intensity of association complex particle systems at 400 nm for the RhB, b-RhB, RhG and RhS. The detection limits of the four systems were respectively 0.00436, 0.00652, 0.00580 and 0.01450 microg/ml ClO2-. In the four systems, the RhB system possesses good stability and high sensitivity. It has been applied to the analysis of chlorite in wastewater with satisfactory results.

  8. 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

  9. Pharmacokinetics of high-dose metoclopramide in cancer patients.

    PubMed

    McGovern, E M; Grevel, J; Bryson, S M

    1986-01-01

    The introduction of new cytotoxic drug regimens has been associated with an increase in the incidence and severity of adverse effects. This in turn has highlighted the need for more effective adjuvant therapy. The use of metoclopramide for the prophylaxis of nausea and vomiting, in high intravenous doses (50 to 1000 mg), has become established since 1981. As a lipid-soluble drug, metoclopramide has a large volume of distribution. The reported mean values after high doses range between 2.8 and 4.6 L/kg. The mean values for total body clearance and terminal half-life range from 0.31 to 0.69 L/kg/h and from 4.5 to 8.8 hours, respectively. The values of these pharmacokinetic parameters are essentially similar to those obtained after conventional doses (less than 50mg). Pharmacokinetic parameters appear unaffected by age, although no high-dose study has been conducted in children. Bodyweight is apparently correlated with clearance. An influence of renal function indices on terminal half-life and clearance has been shown, which is rather surprising since renal clearance accounts for only 20% of the total clearance. No thorough investigations exist which examine the influence of hepatic disease, cancer type and cytotoxic drug regimen on the disposition of metoclopramide. A relationship between dose (or concentration) and therapeutic or adverse effects of metoclopramide is outlined. The therapeutic benefit of high doses (up to 14 mg/kg) may be dependent on age, and on the combination of cytotoxic drugs. The advantages of high doses of metoclopramide are most apparent when the drug is used as protection against the adverse effects of high doses of cisplatin (greater than 60 mg/m2). Despite considerable pharmacokinetic variability, intravenous administration of high doses of metoclopramide is relatively safe due to its large therapeutic index.

  10. Interstratification and other reaction microstructures in the chlorite-berthierine series

    NASA Astrophysics Data System (ADS)

    Xu, H.; Veblen, David R.

    1996-08-01

    Transmission electron microscopy (TEM) results show there is a series of periodically and nonperiodically interstratified structures composed of berthierine and chlorite layers in low-temperature “chlorite” that is one of the alteration products of granulite-facies Archean ironstone from the eastern border of the Beartooth Mountains, Montana. An antiphase domain structure suggests that the interstratified structures are intermediate transformation products formed by reaction from berthierine (serpentine structure) to chlorite. Periodically interstratified structures consisting of chlorite (C) and serpentine-like (S) (or berthierine) layers include (CS), (CCS), (CCCS), (CCCCS), and (CCCCCCS). The layer sequences in interstratified chlorite-berthierine are indicative of the reaction mechanisms that produce the interstratified structures (e.g., crystallization from solution or solid-state transformation). The reaction from berthierine to chlorite is crystallographically much like a cell-preserved phase transformation, even though it is highly reconstructive. Berthierine can be considered a polymorph of the Fe-rich chlorite mineral chamosite, with berthierine as the los-temperature phase. Interstratification and integrowths in the chlorite-berthierine series may be common phenomena in low-temperature layer silicates resembling chlorite. Although such relations are difficult to recognize from chemical analyses or powder X-ray diffraction patterns, they can be observed readily with TEM method.

  11. Acidified sodium chlorite antimicrobial treatment of broiler carcasses.

    PubMed

    Kemp, G K; Aldrich, M L; Waldroup, A L

    2000-08-01

    An acidified sodium chlorite (ASC) solution was investigated for its antimicrobial effects on broiler carcasses processed under conditions similar to those used in U.S. commercial poultry facilities. Of particular interest was the ability of the ASC solution to reduce natural bioburden in a prechill procedure. A number of parameters such as pretreatment washing of carcasses with water (no wash versus water wash), ASC concentration (500, 850, and 1,200 ppm), method of application (spray versus dip), and method of acid activation (phosphoric acid versus citric acid) were explored to evaluate disinfection conditions. ASC dip solutions (18.9 liters) were freshly prepared for groups of five prechill eviscerated carcasses per treatment (n = 10 carcasses). ASC treatment was shown to be an effective method for significantly reducing naturally occurring microbial contamination on carcasses. Reductions following immersion dipping were demonstrated at all disinfectant concentrations for total aerobes (82.9 to 90.7%), Escherichia coli (99.4 to 99.6%), and total coliforms (86.1 to 98.5%). Additionally, testing showed that ASC solutions maintained stable pH and minimal chlorite ion concentration deviations throughout each treatment. The results of the parameter evaluations indicated that maximal antimicrobial activity was achieved in carcasses that were prewashed and then exposed to a 5-s dip in a solution containing phosphoric acid- or citric acid-activated ASC. At 1,200 ppm ASC, a mild but transitory whitening of the skin was noted on dipped carcasses. The results support the methods currently approved by the U.S. Department of Agriculture for the use of ASC solutions as a prechill antimicrobial intervention in U.S. poultry processing plants.

  12. Comparative study on the effects of chlorite oxygen reaction product TCDO (tetrachlorodecaoxygen) and sodium chlorite solution (NaClO2) with equimolar chlorite content on bone marrow and peripheral blood of BDIX rats.

    PubMed

    Kempf, S R; Blaszkiewitz, K; Reim, M; Ivankovic, S

    1993-01-01

    The effects of the chlorite-oxygen reaction product TCDO (tetrachlorodecaoxygen, active ingredient of the systemic application form of WF 10) were investigated on bone marrow and peripheral blood of BDIX rats in comparison to a sodium chlorite solution with a chlorite content identical to that of WF 10. Despite difficulties in determining the chemical differences between TCDO and a sodium chlorite solution, their differing effects on cells, tissue and organism were striking. The following characteristics have been observed: Stimulation of the bone marrow, evidenced by the pronounced increase in mature granulocytes, pronormo- and normoblasts, or increased cell proliferation rate, determined by means of the BrdUrd method, was achieved only with WF 10 (TCDO). Stimulation of the bone marrow led in turn to increased numbers of leucocytes and monocytes in the peripheral blood. In addition, WF 10 induced the production of large granular lymphocytes (LGLs), referred to as natural killer cells (NK-cells). In contrast, NaClO2 solution suppressed bone marrow function, exhibiting a toxic effect when given on a long-term basis. At the same time the number of mature granulocytes as well as pronormo- and normoblasts decreased, while the presence of LGLs was not observed. The results showed that TCDO is a potent stimulator of the bone marrow function and an effective modulator of the entire immune system. The toxic effect of chlorite, derived from the TCDO matrix, is not noticeable, being completely compensated by the favourable effects of TCDO.

  13. 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.

  14. Dosimetric characteristics of jasper samples for high dose dosimetry.

    PubMed

    Teixeira, Maria Inês; Caldas, Linda V E

    2012-07-01

    Different colored jasper samples from Brazilian mines were powdered and mixed with teflon (composites jasper-teflonTM). This paper describes a preliminary study of a thermoluminescent method (TL) to verify the possibility of their use as high dose dosimeters or irradiation indicators in industrial areas. The jasper samples were exposed to different radiation doses, using the gamma-cell 220 system (60Co) of IPEN. The TL emission curves of samples presented two peaks at 130 °C and 190 °C. Calibration curves were obtained for the jasper samples between 50 Gy and 20 kGy. All five types of jasper samples showed their usefulness as irradiation indicators and as high-dose dosimeters.

  15. 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.

  16. 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

  17. High-dose allergen exposure leads to tolerance.

    PubMed

    Woodfolk, Judith A

    2005-02-01

    Reports of decreased sensitization to cat allergen (Fel d 1) among individuals living with a cat or subjects exposed to high-dose cat allergen may be explained by the development of a form of high-dose tolerance resulting from natural exposure to an inhalant allergen. Although the epidemiological data regarding the relationship between exposure and sensitization to Fel d 1 are conflicting, the ability for high-dose Fel d 1 to induce a characteristic nonallergic immune response with a distinctive serum antibody profile has been established. Definition of this modified T-helper (Th)2 response to cat allergen, coupled with the renewed interest in regulatory T cells within the immunology field, has provided an avenue for exploring the mechanism by which IgE antibody-mediated responses are controlled. There is mounting evidence to suggest that the modified Th2 response is a variation of the allergic response and that the modified Th2-allergic axis is influenced by allergen dose and genetics. This article discusses putative immune mechanisms of tolerance within the context of an allergen-specific system. The relevance of high-dose allergen exposure and alternate factors such as endotoxin to the development of tolerance is considered. Fel d 1 exhibits unique molecular and immunological characteristics that may contribute to its tolerogenic properties. Major T-cell epitopes of Fel d 1 that preferentially induce regulatory factors have been defined. Furthermore, high-titer IgE antibody responses associated with atopic dermatitis are characterized by a defect in the T-cell repertoire that is specific to these epitopes. Identification of Fel d 1 epitopes that induce interleukin-10 may provide new targets for treatment.

  18. Retinal risks of high-dose ornithine supplements: a review.

    PubMed

    Hayasaka, Seiji; Kodama, Tatsuo; Ohira, Akihiro

    2011-09-01

    We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH(3) detoxification in the hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 μmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 μmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Blood ornithine levels below 250 μmol/l do not produce retinal alteration. We concluded that short-term, low-dose or transient high-dose ornithine intake is safe for the retina; its nutritional usefulness and effect on NH(3) detoxification are supported by many researchers, but the effect may be limited; and long-term, high-dose ornithine intake may be risky for the retina. Patients with GA should avoid taking ornithine; amino acid supplementation should be administered carefully for patients with the HHH syndrome, relatives of patients with GA (heterozygotes) and subjects with RPE lesions; and blood ornithine levels and retinal conditions should be evaluated in individuals taking long-term, high-dose ornithine.

  19. Preventing and Managing Toxicities of High-Dose Methotrexate.

    PubMed

    Howard, Scott C; McCormick, John; Pui, Ching-Hon; Buddington, Randall K; Harvey, R Donald

    2016-12-01

    : High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m(2), is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated.

  20. 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.

  1. 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

  2. Investigation of U(VI) adsorption in quartz-chlorite mineral mixtures.

    PubMed

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

    2014-07-15

    A batch and cryogenic laser-induced time-resolved luminescence spectroscopy investigation of U(VI) adsorbed on quartz-chlorite mixtures with variable mass ratios have been performed under field-relevant uranium concentrations (5×10(-7) M and 5×10(-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 possibly caused by surface modifications stemming from chlorite dissolution; The largest deviation occurred when the mass fractions of the two minerals were equal. U(VI) adsorbed on quartz and chlorite displayed characteristic individual luminescence 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 luminescence intensity decreased in a nonlinear manner as the adsorbed U(VI) concentration increased with increasing chlorite mass fraction-likely due to ill-defined luminescence quenching by both structural Fe/Cr in chlorite, and trace amounts of solubilized and reprecipitated 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 with approximate linear correlations, offering a method to estimate of U(VI) concentration distribution between the mineral components with luminescence spectroscopy.

  3. 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.

  4. 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

  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. 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.

  7. Tolerability of high doses of lercanidipine versus high doses of other dihydropyridines in daily clinical practice: the TOLERANCE Study.

    PubMed

    Barrios, Vivencio; Escobar, Carlos; de la Figuera, Mariano; Llisterri, Jose Luis; Honorato, Jesus; Segura, Julián; Calderón, Alberto

    2008-01-01

    The TOLERANCE study was aimed to compare the tolerability of high doses of lercanidipine (20 mg) with that of other frequently used dihydropyridines (amlodipine 10 mg/nifedipine GITS 60 mg) in the treatment of essential hypertension in daily clinical practice. It was an observational, transversal, multicentre study performed in a Primary Care Setting. A total of 650 evaluable patients with essential hypertension and age > or = 18 years were included. They had been treated with high doses of lercanidipine (n= 446) or amlodipine/nifedipine GITS (n= 204) during at least 1 month and previously with low doses (10 mg, 5 mg, and 30 mg, respectively) of the same drugs. The main objective was to compare the rates of vasodilation-related adverse events between both groups. Rates of signs and symptoms related to vasodilation were significantly higher (P < 0.001) in the amlodipine/nifedipine GITS group (76.8%, CI 95%[70.7; 82.9]) than in lercanidipine group (60.8%, [56.1;65.5]). Blood pressure control (< 140/90 mmHg or <130/80 for diabetics) and type of concomitant antihypertensive medications were similar in both groups. Treatment compliance was good (around 93%) and fairly comparable in both groups. Most adverse events with lercanidipine were mild (74.5% vs. 64% in amlodipine/nifedipine GITS group, P= 0.035) whereas severe adverse event rates did not differ significantly between groups (2.8% vs. 3.6%). In conclusion, treatment with lercanidipine at high doses is associated with a lower rate of adverse events related to vasodilation compared to high doses of amlodipine or nifedipine GITS in clinical practice.

  8. Reaction pathways of NO oxidation by sodium chlorite powder.

    PubMed

    Byun, Youngchul; Ko, Kyoung Bo; Cho, Moohyun; Namkung, Won; Lee, Kiman; Shin, Dong Nam; Koh, Dong Jun

    2009-07-01

    NO oxidation is an important prerequisite step to assist selective catalytic reduction at low temperatures (< 250 degrees C). If sodium chlorite powder (NaClO2(s)) can oxidize NO to NO2, the injection of NaClO2(s) can be simply adapted to NO oxidation. Therefore, we explored the reaction pathways of NO oxidation by NaClO2(s). Known concentrations of NO and NO2 in N2 balance were injected into packed-bed reactor containing NaClO2(s) at 130 degreesC. NaClO2(s) oxidized NO to NO2 which reacts again with NaClO2(s) to produce OClO. Comparison of experimental data with simulation results demonstrates that each NO2 molecule removed by the reaction with NaClO2(s) generated one OClO molecule, which also oxidized NO to NO2 with the production of ClNO and ClNO2. Using these results, we conclude that the oxidation of NO by NaClO2(s) occurred by two pathways. One is through the direct reaction of NO with NaClO(s). The other is through both the reaction of NO with OlCO produced by the reaction of NO2 with NaClO2(s) and the reaction of NO with ClO produced by the reaction of NO with OClO.

  9. 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.

  10. High-dose, conventionally fractionated thoracic reirradiation for lung tumors.

    PubMed

    Griffioen, Gwendolyn H M J; Dahele, Max; de Haan, Patricia F; van de Ven, Peter M; Slotman, Ben J; Senan, Suresh

    2014-03-01

    Loco-regional recurrences and second primary lung tumors are not uncommon after high-dose thoracic radiotherapy. The availability of improved radiotherapy techniques increases options for reirradiation. We describe a single-institutional experience with high-dose conventional thoracic reirradiation for both loco-regional recurrences and new primary tumors. Retrospective chart review of patients undergoing reirradiation between February 2004 and February 2013. Of 24 patients identified, 54% had a loco-regional recurrence, and 46% a new primary tumor. The majority (63%) had stage III NSCLC at both initial and second treatment; median interval between treatments was 51 months (5-189), median follow-up after reirradiation was 19.3 months (95% CI: 2.8-35.9). Median overall survival (OS) after reirradiation was 13.5 months, with 1-year survival 51%. Median event-free survival (EFS) was 8.4 months. Median time between reirradiation and local progression (n=8) or distant progression (n=8) was 6.7 and 11.8 months, respectively. Three patients died with possible grade 5 bleeding. Other toxicities were uncommon. Planning target volume (PTV) at reirradiation was the most important prognostic factor; PTV <300 versus ≥300cc was significantly associated with median OS (17.4 vs 8.2 months, p=0.03) and EFS (14.1 vs 5.5 months, p=0.03). Magnitude of overlap between the initial and subsequent PTVs, and between dose distributions, did not influence survival. Thoracic reirradiation with high dose conventional radiotherapy appears to deliver a meaningful survival benefit in low volume new primary or recurrent lung cancer. Further studies are needed to confirm these findings, and to establish reliable normal tissue tolerance doses for reirradiation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. [Neurological disturbances in patient who ingested high doses of simvastatin].

    PubMed

    Schetz, Daria; Sein Anand, Jacek

    2014-01-01

    We presented a case of 54-year old man, with dyslipidemia who, during his work, was exposed to prolonged electromagnetic radiation. Because of his concerns about the development of atherosclerosis, higher doses of simvastatin than recommended by the doctor, were used by him. After five weeks of such therapy the central nervous system symptoms such as: memory loss, cognitive disorders, sleeplessness, nervousness were presented. It is probable that the mentioned above symptoms were caused by high doses of drug took by the patient, and increased in blood-brain barrier permeability caused by electromagnetic radiation which lasted for about eight years.

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

    PubMed

    He, Qiang; Luo, Yaguang; Chen, Pei

    2008-10-15

    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 effect of SC on polyphenol oxidase (PPO) and its substrate, chlorogenic acid (CA), as it relates to the mechanisms of browning inhibition by SC. Results indicate that the browning reaction of CA (1.0mM) catalyzed by PPO (33U/mL) was significantly inhibited by 1.0mM SC at pH 4.6. Two PPO isoforms were identified by native polyacrylamide gel electrophoresis, and both were inactivated by SC (3.0mM). This suggests that SC serves as a PPO inhibitor to prevent enzymatic browning. Furthermore, the effect of SC on the stability of CA in both acidic (pH 4.5) and basic conditions (pH 8.3) was studied by UV-Vis scan and LC-MS analysis. The results showed that at the presence of SC (3.0mM), CA (0.1mM) degraded to quinic acid and caffeic acid as well as other intermediates. Hence, the anti-browning property of SC can be attributed to the two modes of action: the inactivation of polyphenol oxidase directly and the oxidative degradation of phenolic substrates. Published by Elsevier Ltd.

  13. Determination of chlorite in drinking water by differential pulse voltammetry on graphite.

    PubMed

    Pezzatini, Giovanni; Midili, Ilaria; Toti, Gabriele; Loglio, Francesca; Innocenti, Massimo

    2004-10-01

    The chlorite ion is an unavoidable by-product of the disinfection of drinking water by means of chlorine dioxide. The maximum concentration values of chlorite accepted in many countries' regulations range from 0.2 to 1.0 mg L(-1). A simple, inexpensive and quickly set up voltammetric procedure for the on-site determination of chlorite in drinking water networks is described. This procedure is suitable for the whole range of applications in drinking water plants. A useful cell for on-field analysis has been developed. Surface morphology and behaviour of carbon-based working electrodes have been investigated by voltammetry and atomic force microscopy (AFM). Actual samples of different types of water networks have been analysed for chlorite concentration.

  14. [Determination of sodium chlorite in processed herring roe by ion chromatography with a conductivity detector].

    PubMed

    Kawasaki, Yoko; Kubota, Hiroki; Yomota, Chikako; Tanamoto, Kenichi

    2005-08-01

    An analytical method for residual sodium chlorite in several kinds of processed herring roe treated with sodium chlorite was studied. Sodium chlorite was extracted with 9 mmol/L sodium carbonate. After centrifugation, the supernatant was filtered through a 0.2 microm nylon filter. The filtrate was deproteinized by ultrafiltration and chloride ion was removed with an On-Guard Ag cartridge column. The eluate was subjected to conductivity detector-ion chromatography. Recoveries of sodium chlorite from herring roe spiked at the level of 5 mg/kg were 88 +/- 3.7% (n = 5, CV 4.2%). The method had a quantitation limit of 5 mg/kg for processed herring roes.

  15. High-dose desvenlafaxine in outpatients with major depressive disorder.

    PubMed

    Ferguson, James M; Tourian, Karen A; Rosas, Gregory R

    2012-09-01

    This study investigated the safety and efficacy of long-term treatment with high-dose desvenlafaxine (administered as desvenlafaxine succinate) in major depressive disorder (MDD). In this multicenter, open-label study, adult outpatients with MDD aged 18-75 were treated with flexible doses of desvenlafaxine (200-400 mg/d) for ≤ 1 year. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs), patient discontinuations due to adverse events, electrocardiograms, vital signs, and laboratory determinations. The primary efficacy measure was mean change from baseline in the 17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score. The mean daily desvenlafaxine dose range over the duration of the trial was 267-356 mg (after titration). The most frequent TEAEs in the safety population (n = 104) were nausea (52%) and headache (41%), dizziness (31%), insomnia (29%), and dry mouth (27%). All TEAEs were mild or moderate in severity. Thirty-four (33%) patients discontinued from the study because of TEAEs; nausea (12%) and dizziness (9%) were the most frequently cited reasons. The mean change in HAM-D(17) total score for the intent-to-treat population (n = 99) was -9.9 at the last on-therapy visit in the last-observation-carried-forward analysis and -14.0 at month 12 in the observed cases analysis. Conclusion High-dose desvenlafaxine (200-400 mg/d) was generally safe and effective in the long-term treatment of MDD.

  16. Comparative pharmacokinetics of low- and high-dose ticarcillin.

    PubMed Central

    Guglielmo, B J; Flaherty, J F; Batman, R; Barriere, S L; Gambertoglio, J G

    1986-01-01

    Certain antipseudomonal penicillins, such as mezlocillin, exhibit a nonlinear pharmacokinetic disposition with increasing doses. We evaluated the effect of a single low dose (50 mg/kg) compared with a high dose (80 mg/kg) on the pharmacokinetics of ticarcillin in a crossover trial of eight healthy volunteers. No significant alteration in plasma clearance (130.1 +/- 36.5 versus 120.5 +/- 38.0 ml/min), nonrenal clearance (36.5 +/- 8.4 versus 33.4 +/- 18.5 ml/min), or volume of distribution at steady state (12.8 +/- 3.5 versus 12.3 +/- 4.5 liters) was observed between the low- and high-dose regimens, respectively. The elimination half-life remained unchanged between the two doses (67.9 +/- 14.3 versus 68.0 +/- 12.2 min). Unlike other newer antipseudomonal penicillins, ticarcillin did not display dose-dependent pharmacokinetic behavior with the range of doses used in the clinical setting. PMID:3777901

  17. 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.

  18. Formation of titanium silicides by high dose ion implantation

    NASA Astrophysics Data System (ADS)

    Salvi, V. P.; Vidwans, S. V.; Rangwala, A. A.; Arora, B. M.; Kuldeep; Jain, Animesh K.

    1987-09-01

    We have investigated titanium silicide formation using high dose (˜ 2 × 10 21 ions/m 2) ion implantation of 30 keV, 48Ti + ions a room temperature into two different types of Si substrates: (a) n-type <111> single crystals and (b) amorphous Si films (˜ 200 nm thick) vacuum deposited onto a thermally grown SiO 2 layer. XRD and RBS techniques were employed to characterize various silicide phases and their depth distribution in as-implanted as well as in annealed samples. We find that a mixture of TiSi, TiSi 2 and Ti 5Si 4 silicides is formed by high dose implantation. Out of these, TiSi; was found to be the dominant phase. The composition of these silicide layers is practically uniform with depth and remains unaltered on heat treatment up to 750° C. The electrical properties of silicide layers have also been investigated using sheet resistance measurements. The resistivity of as-implanted layers is rather high ( ˜ 10 μΩ m), but drops sharply by nearly a factor of 20 after a post-implantation anneal above 800° C. The resistivity of silicide layers thus obtained compare well with silicides prepared by other techniques.

  19. 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.

  20. 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.

  1. 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.

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

    PubMed

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

    2013-05-20

    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.

  3. 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

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

    PubMed

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

    2013-05-22

    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.

  5. 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

  6. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma.

    PubMed

    Anderson, Peter M; Wiseman, Gregory A; Erlandson, Linda; Rodriguez, Vilmarie; Trotz, Barbara; Dubansky, Stephen A; Albritton, Karen

    2005-10-01

    Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

  7. Pharmacokinetics of high-dose intravenous melatonin in humans.

    PubMed

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette M; Fenger, Andreas Q; Petersen, Marian C; Rosenberg, Jacob; Gögenur, Ismail

    2016-03-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5-326,175.0) pg/mL and 1,251,500.0 (864,375.0-1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0- ∞ , 8,997,633.0 (6,071,696.2-11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6-105,779,612.0) pg · min/mL. High-dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.

  8. 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.

  9. 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

  10. Kinetics and mechanism of styrene epoxidation by chlorite: role of chlorine dioxide.

    PubMed

    Leigh, Jessica K; Rajput, Jonathan; Richardson, David E

    2014-07-07

    An investigation of the kinetics and mechanism for epoxidation of styrene and para-substituted styrenes by chlorite at 25 °C in the pH range of 5-6 is described. The proposed mechanism in water and water/acetonitrile includes seven oxidation states of chlorine (-I, 0, I, II, III, IV, and V) to account for the observed kinetics and product distributions. The model provides an unusually detailed quantitative mechanism for the complex reactions that occur in mixtures of chlorine species and organic substrates, particularly when the strong oxidant chlorite is employed. Kinetic control of the reaction is achieved by the addition of chlorine dioxide to the reaction mixture, thereby eliminating a substantial induction period observed when chlorite is used alone. The epoxidation agent is identified as chlorine dioxide, which is continually formed by the reaction of chlorite with hypochlorous acid that results from ClO produced by the epoxidation reaction. The overall stoichiometry is the result of two competing chain reactions in which the reactive intermediate ClO reacts with either chlorine dioxide or chlorite ion to produce hypochlorous acid and chlorate or chloride, respectively. At high chlorite ion concentrations, HOCl is rapidly eliminated by reaction with chlorite, minimizing side reactions between HOCl and Cl2 with the starting material. Epoxide selectivity (>90% under optimal conditions) is accurately predicted by the kinetic model. The model rate constant for direct reaction of styrene with ClO2(aq) to produce epoxide is (1.16 ± 0.07) × 10(-2) M(-1) s(-1) for 60:40 water/acetonitrile with 0.20 M acetate buffer. Rate constants for para substituted styrenes (R = -SO3(-), -OMe, -Me, -Cl, -H, and -NO2) with ClO2 were determined. The results support the radical addition/elimination mechanism originally proposed by Kolar and Lindgren to account for the formation of styrene oxide in the reaction of styrene with chlorine dioxide.

  11. High-Dose Vitamin D Failed to Curb Heart Disease in Study

    MedlinePlus

    ... medlineplus.gov/news/fullstory_164472.html High-Dose Vitamin D Failed to Curb Heart Disease in Study ... 5, 2017 (HealthDay News) -- Taking high doses of vitamin D once a month won't lower your ...

  12. High Doses of Vitamin D Fail to Cut Cancer Risk, Study Finds

    MedlinePlus

    ... gov/news/fullstory_164325.html High Doses of Vitamin D Fail to Cut Cancer Risk, Study Finds ... March 28, 2017 (HealthDay News) -- High doses of vitamin D supplements may not lower older women's risk ...

  13. Novel radiochromic dosimeters based on Calcein dye for high dose applications

    NASA Astrophysics Data System (ADS)

    Aldweri, Feras M.; Rabaeh, Khalid A.; Al-Ahmad, Kefaia N.

    2017-10-01

    New compositions of radio-chromic solutions and polyvinyl alcohol (PVA) films containing different concentrations of Calcein dye have been introduced as high dose dosimeter. The dosimeters were irradiated with gamma rays from 60C o source at doses from 5 to 30 kGy for film and from 0.25 to 1 kGy for solution. UV/vis spectrophotometry was used to investigate the absorbance (optical density) of unirradiated and irradiated films and solutions in terms of absorbance at 493 nm for film and 496 nm for solution. The effects of scan temperature, relative humidity and stability of the response of films and solutions after irradiation were investigated. The results show that these films could be used as dosimeter in industrial radiation processing. The useful dose range of developed Calcein-PVA film and solution dosimeters is in the range of 5-20 kGy and 0.25-1 kGy respectively

  14. [Anaphylactic shock during the use of high doses of aprotinin in cardiac surgery].

    PubMed

    Cottineau, C; Moreau, X; Drouet, M; De Brux, J L; Brenet, O; Delhumeau, A

    1993-01-01

    A 77-year-old man was admitted for mitral valve replacement, 46 days after a failed conservative mitral surgery where he received high-dose aprotinin. Twenty minutes after induction of anaesthesia, 250 UPh E of aprotinin were infused intravenously; before the end of this infusion, bronchospasm, systemic hypotension and generalized rash were noted. Immediate treatment included intravenous adrenaline and methylprednisolone; cardiovascular stability was restored after 10 minutes. Immediate histamine liberation was confirmed by the analysis of the time course of the clinical events, a previous contact and positive skin tests. Aprotinin has the antigenic molecular structure of natural proteins. Since 1987, it is used in cardiac surgery to reduce postoperative blood loss: to prevent serious allergic reactions to aprotinin, it is necessary, in patients known to have had previous aprotinin therapy, to perform skin testing with diluted aprotinin before infusion.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Very high dose phenobarbital for refractory status epilepticus.

    PubMed

    Tiamkao, Somsak; Mayurasakorn, Nattakarn; Suko, Panit; Jitpimolmard, Suthipun; Arunpongpaisal, Suwanna; Phuttharak, Warinthorn; Auevitchayapat, Narong; Vannaprasaht, Suda; Tiamkao, Siriporn; Phunikhom, Kutcharin; Chaiyakum, Aporanee; Saengsuwan, Jiamjit

    2007-12-01

    Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to first, second and third-line therapy. The RSE is associated with high morbidity and mortality. Treatment guidelines of RSE give a spectrum of options, such as, continuous intravenous (i.v.) midazolam (MDL), or continuous i.v. propofol (PRO) as alternatives to phenobarbital (PB) or continuous i.v. pentobarbital (PTB). To study the efficacy of very-high-dose phenobarbital (VHDPB) for treatment RSE. Retrospective study The authors collected and analyzed data from adult patients who were diagnosed with RSE. The authors present 10 patients with RSE who were treated with VHDPB. All of them were generalized convulsive status epilepticus (GCSE). Ages ranged from 16-86 years old (mean.: 43 years). PB dosage ranged 40-140 mg/kg/day (mean: 70 mg/kg/day). The duration of status epilepticus (SE) varied widely, ranged 1-44 days (mean: 7 days). PB level ranged 35.29-218.34 ug/mL (mean 88.1 ug/mL). RSE was controlled by VHDPB 70%, 30% were not controlled. VHDPB were considered as alternative treatment for RSE.

  20. Mummification of the infarcted myocardium by high dose corticosteroids.

    PubMed

    Kloner, R A; Fishbein, M C; Lew, H; Maroko, P R; Braunwald, E

    1978-01-01

    There is evidence that glucocorticoids reduce infarct size but their use in myocardial infarction remains controversial because of their potential adverse effects on healing of the infarct. To investigate the healing process, rats received either four parenteral doses of 50 mg/kg of methylprednisolone (MP) or saline 5 min, 3,6 and 24 hr after coronary occlusion and their hearts were examined by light and electron microscopy 48 hr and seven days after occlusion. At 48 hr, in five untreated rats, only 12 +/- 7% of injured myocytes showed the persistence of striations and a relatively intact sarcolemma despite loss of nuclei and hence appeared "mummified" whereas in six MP-treated rats 72 +/- 8% of myocytes exhibited this appearance (P less than 0.001). In treated rats there were fewer phagocytes than in controls. At seven days, in seven MP-rats, mummified cells were still more prominent than in five untreated rats and there were fewer phagocytes and less collagen. In conclusion, high dose of MP delays the inflammatory process and retards the disintegration of necrotic myocytes, resulting in impaired healing.

  1. High-dose naltrexone therapy for cocaine-alcohol dependence.

    PubMed

    Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard

    2009-01-01

    This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.

  2. 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.

  3. High-dose radiation sensor with wireless optical detection

    NASA Astrophysics Data System (ADS)

    Knapkiewicz, Paweł; Augustyniak, Izabela; Sareło, Katarzyna; Gorecka-Drzazga, Anna; Dziuban, Jan

    2017-05-01

    We present a miniature silicon-glass MEMS sensor for measurement of high doses of ionizing radiation (above 10 kGy) using a novel wireless optical detection method. The radiation sensor is a miniaturized version of the so-called hydrogen dosimeter. An amount of high-density polyethylene, located inside the MEMS sensor, degrades under ionizing radiation, releasing gaseous hydrogen. The increasing pressure deflects the thin silicon membrane. The sensor’s destructive and proportional modes of work are also proposed. In the destructive mode, sensors provide in situ information on excessive and discrete levels of radiation. The optical detection method is based on an optical head consisting of a moving membrane and a silicon screen with a matrix of micro-holes. Laser light is reflected from the membrane and scattered when the membrane is deflected, in the process illuminating the holes on the silicon screen. The number of illuminated holes is a function of the degree of membrane deflection; the transformation of the holes to the deflection allows for the calculation of pressure and eventually the dose of ionizing radiation.

  4. 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

  5. Theoretically required urinary flow during high-dose methotrexate infusion.

    PubMed

    Sasaki, K; Tanaka, J; Fujimoto, T

    1984-01-01

    The renal excretion of methotrexate (MTX) and its major metabolite 7-hydroxymethotrexate (7-OH-MTX) was analysed in 12 children with malignancies during 52 courses of high-dose methotrexate (H-D-MTX) infusion at dosages ranging from 0.7 to 8.4 g/m2. The peak concentrations of both MTX and 7-OH-MTX exceeded the aqueous solubilities of these compounds at low pH (less than or equal to 6.0). The cumulative MTX excretion in urine was 75%-98% of the administered amount of MTX, and the cumulative 7-OH-MTX excretion in the urine was 3%-15%. The theoretically required urinary flow (TRUF) was estimated as the minimum urine volume needed for complete resolution of MTX and its metabolites in urine. TRUF during MTX infusion from 0 to 6 h and from 6 to 12 h was correlated with the dosage of MTX, and these values were 0.1-1.8 ml/min/m2 at pH 7.0, 0.5-11.1 ml/min/m2 at pH 6.0, and 1.9-42.2 ml/min/m2 at pH 5.0 with dosages of 0.7 to 8.4 g/m2. The value of the theoretically required urinary flow is important to ensure adequate hydration and the optimum alkalinization schedule for massive MTX infusion.

  6. Shelf-stable food through high dose irradiation

    NASA Astrophysics Data System (ADS)

    Plaček, V.; Svobodová, V.; Bartoníček, B.; Rosmus, J.; Čamra, M.

    2004-09-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75°C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30°C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Řež 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO x-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

  7. Effects of high-dose isoflavones on rat uterus.

    PubMed

    Carbonel, Adriana Aparecida Ferraz; Simões, Ricardo Santos; Santos, Regiane Helena Barros Rabelo; Baracat, Maria Cândida Pinheiro; Simões, Manuel de Jesus; Baracat, Edmund Chada; Soares Júnior, José Maria

    2011-01-01

    To evaluate the effects of high-dose isoflavones on the uterus of castrated adult rats. Adult, ovariectomized virgin rats (n = 40) were treated by gavage during 30 consecutive days with vehicle (propylene glycol, group GCtrl) or different doses of genistein: 42 (group GES42), 125 (GES125), or 250 (GES250) µg/g body weight per day. Animals were killed, weighed, vaginal and uterine samples were taken for cytologic evaluation, and serum levels of 17 β-estradiol and progesterone were determined. The middle third of the uterine horns was dissected, fixed in 10% formaldehyde and processed for paraffin inclusion; 5-µm thick sections were obtained and stained with HE for further histological study under light microscopy. The endometrial morphology and area, number and area of glands, and number of eosinophils in the lamina propria were analyzed. ANOVA and the Tukey-Kramer test were used for statistical analyses. Uterine weight, endometrial glandular area, and number of glands and eosinophils were all higher in GES250 > G125 than in the other groups (GES250 > GES125 > GES42 = GCtrl; p < 0.05). Morphological data showed signs of endometrial proliferation upon treatment with genistein, especially in animals in GES125 and GES250 compared to other groups. In all animals in GES250, signs of uterine squamous metaplasia were observed. A short treatment period with high daily doses of isoflavones can promote endometrial squamous metaplasia in ovariectomized rats.

  8. Survival After Shock Requiring High-Dose Vasopressor Therapy

    PubMed Central

    Lanspa, Michael J.; Jones, Jason P.; Kuttler, Kathryn G.; Li, Yao; Carlson, Rick; Miller, Russell R.; Hirshberg, Eliotte L.; Grissom, Colin K.; Morris, Alan H.

    2013-01-01

    Background: Some patients with hypotensive shock do not respond to usual doses of vasopressor therapy. Very little is known about outcomes after high-dose vasopressor therapy (HDV). We sought to characterize survival among patients with shock requiring HDV. We also evaluated the possible utility of stress-dose corticosteroid therapy in these patients. Methods: We conducted a retrospective study of patients with shock requiring HDV in the ICUs of five hospitals from 2005 through 2010. We defined HDV as receipt at any point of ≥ 1 μg/kg/min of norepinephrine equivalent (calculated by summing norepinephrine-equivalent infusion rates of all vasopressors). We report survival 90 days after hospital admission. We evaluated receipt of stress-dose corticosteroids, cause of shock, receipt of CPR, and withdrawal or withholding of life support therapy. Results: We identified 443 patients meeting inclusion criteria. Seventy-six (17%) survived. Survival was similar (20%) among the 241 patients with septic shock. Among the 367 nonsurvivors, 254 (69%) experienced withholding/withdrawal of care, and 115 (31%) underwent CPR. Stress-dose corticosteroid therapy was associated with increased survival (P = .01). Conclusions: One in six patients with shock survived to 90 days after HDV. The majority of nonsurvivors died after withdrawal or withholding of life support therapy. A minority of patients underwent CPR. Additionally, stress-dose corticosteroid therapy appears reasonable in patients with shock requiring HDV. PMID:22911566

  9. Effect of acid-chlorite delignification on cellulose degree of polymerization.

    PubMed

    Hubbell, Christopher A; Ragauskas, Arthur J

    2010-10-01

    Two types of pure cellulose, Avicel PH-101 and Whatman filter paper, were treated with an acid-chlorite delignification procedure in the presence of varying amounts of incorporated lignin, and the molecular weight distributions and degrees of polymerization (DP) of derivatized cellulose were determined by gel permeation chromatography (GPC). Avicel samples with 0% added lignin showed a DP reduction of nearly 5% during acid-chlorite delignification, compared to a 1% drop in DP with 30% added lignin. Lignin-free filter paper samples showed a DP reduction of nearly 35% after hollocellulose delignification. This drop in DP was reduced to less than 12% for samples which contained 30% lignin. Thus, the presence of lignin in biomass samples minimized the DP reduction of cellulose due to acid catalyzed cleavage during acid-chlorite delignification.

  10. Direct chemical method for preparing 2,3-epoxyamides using sodium chlorite.

    PubMed

    Fuentes, Lilia; Osorio, Urbano; Quintero, Leticia; Höpfl, Herbert; Vázquez-Cabrera, Nixache; Sartillo-Piscil, Fernando

    2012-07-06

    A direct method for preparing 2,3-epoxyamides from tertiary allylamines via a tandem C-H oxidation/double bond epoxidation using sodium chlorite is reported. Apparently, the reaction course consists of two steps: (i) allylic oxidation of the starting allylamine to corresponding unsaturated allylamide with sodium chlorite followed by (ii) epoxidation of the allylamide to the 2,3-epoxyamide mediated by hypochlorite ion, which is formed in situ by reduction of sodium chlorite. The reaction conditions tolerate the presence of free hydroxyl groups and typical functional groups such as TBS, aryl, alkyl, allyl, acetyl, and benzyl groups; however, when an activated aromatic ring (e.g., sesamol) is present in the substrate, the use of a scavenger is necessary.

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

    PubMed

    Loh, John Ming Ren; Shafi, Humaira

    2014-11-24

    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. 2014 BMJ Publishing Group Ltd.

  12. Kikuchi-Fujimoto disease presenting after consumption of ‘Miracle Mineral Solution’ (sodium chlorite)

    PubMed Central

    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

  13. Impact of high dose vitamin C on platelet function

    PubMed Central

    Mohammed, Bassem M; Sanford, Kimberly W; Fisher, Bernard J; Martin, Erika J; Contaifer Jr, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S; Chalfant, Charles E; Brophy, Donald F; Fowler III, Alpha A; Natarajan, Ramesh

    2017-01-01

    AIM To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of VitC used here correspond to plasma VitC levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography (TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate (ATP) secretion in response to collagen or adenosine diphosphate (ADP); and flow cytometry, for changes in expression of CD-31, CD41a, CD62p and CD63. In addition, PLT intracellular VitC content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time (PT), partial thrombplastin time (PTT), functional fibrinogen] and Lipidomics analysis (UPLC ESI-MS/MS). RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L (Lo VitC) and 15.7 mmol/L (Hi VitC, P < 0.05). VitC supplementation did not significantly change PT and PTT values, or functional fibrinogen levels over the 8 d exposure period (P > 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle (P < 0.05). There was also a fall of 20 mm in maximum amplitude associated with the Hi VitC compared to

  14. Modulation of the proteolytic cascade systems by high dose corticosteroids.

    PubMed

    Aasen, A O; Ruud, T E; Pillgram-Larsen, J; Röise, O; Stadaas, J

    1985-01-01

    The effects of high-dose corticosteroids (HDC) on activities within the proteolytic cascade systems were studied in vitro and in vivo using chromogenic peptide substrate assays. In in vitro experiments 20 mg methylprednisolone sodium succinate (Solu-Medrol) per ml plasma significantly inhibited activation of plasma prekallikrein, prothrombin and plasminogen and reduced functional plasma kallikrein inhibition, antithrombin and antiplasmin activities. The effects of HDC on activities within these proteolytic cascade systems were further evaluated in experimental acute pancreatitis in pigs. Acute pancreatitis was induced by injection of Na-taurocholate into the pancreatic duct. Seven test animals received methylprednisolone sodium succinate 30 mg per kg intravenously for 30 minutes before the induction of pancreatitis as pretreatment. Eight animals remained untreated. Trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and mean arterial pressure (MAP) were monitored regularly before and during a 6 hour observation period. During untreated pancreatitis a reduction of PKK levels of about 40% were found, paralleled by an increased KK activity and a reduction of KKI capacity. Several of the animals experienced high TRY activities. The mortality rate was 63% (5 out of 8 animals). In the pretreated groups, all animals survived the observation period. CO and MAP were significantly less reduced than the untreated group at 6 hours. HDC was also found to reduce significantly plasma kallikrein activities in the peritoneal exudate compared with untreated animals. No changes in TRY activities were found in pretreated animals. Furthermore, plasma prekallikrein and functional plasma kallikrein inhibition values in the exudate were elevated significantly in HDC treated animals compared with untreated animals.

  15. Tolerance of the Brachial Plexus to High-Dose Reirradiation.

    PubMed

    Chen, Allen M; Yoshizaki, Taeko; Velez, Maria A; Mikaeilian, Argin G; Hsu, Sophia; Cao, Minsong

    2017-05-01

    To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus-related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). The development of brachial plexus-related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Continuous spinal anesthesia with high dose of local anesthetics.

    PubMed

    Imbelloni, Luiz Eduardo; Neto, Savino Gasparini; Ganem, Eliana Marisa

    2010-01-01

    Better control of the level, intensity, and duration of spinal analgesia represents the greatest advantages of continuous spinal anesthesia. With the advent of intermediate catheters (over-the-needle catheter) and its low incidence of headaches and neurological symptoms, the technique has been gaining credibility. The objective of this paper is to report the possible safety of the new catheter with a large dose of hyperbaric 0.5% bupivacaine with 1.6% glucose associated with hyperbaric 2% lidocaine with 1.6% glucose. Male patient, 78 years old, 85 kg, 168 cm, physical status ASA III, with hypertension, coronary artery disease, and chronic renal failure. The patient was candidate for surgery for huge bilateral inguinal and umbilical hernias, being submitted to preoperative pneumoperitoneum for one week to stretch abdominal cavity. After venoclysis with an 18G catheter, he was monitored with cardioscope, non-invasive blood pressure, and pulse oximetry; he was sedated with 1 mg of midazolam and 100 μg of fentanyl intravenously, and placed in left lateral decubitus. He underwent continuous spinal anesthesia by a median puncture in L₃-L₄ with a set with a 27G cut-bevel needle and 22G catheter. The total dose of anesthetic used was 25mg of 0.5% bupivacaine (hyperbaric, with 1.6% glucose), 160 mg of 2% lidocaine (hyperbaric, with 1.6% glucose), and morphine (100 μg). The patient was followed-up until the 30th postoperative day without neurological complaints. Recently, the poor distribution of the local anesthetic through the microcatheter was attributed as the cause of cauda equina syndrome. This case report showed that, with the administration of high doses of hyperbaric anesthetics through the new catheter, poor distribution or risk of cauda equina syndrome were not observed. Copyright © 2010 Elsevier Editora Ltda. All rights reserved.

  17. Painful peripheral neuropathy after treatment with high-dose ifosfamide.

    PubMed

    Frisk, P; Stålberg, E; Strömberg, B; Jakobson A

    2001-10-01

    Ifosfamide is successfully employed in the treatment of bone and soft tissue sarcomas in children and young adults. Used at high doses (HDI) the drug may cause severe multiorgan toxicity. Peripheral neuropathy is a less well-known side effect that may limit its use. We describe a 16-year-old girl with a Ewing sarcoma who was given post-operative treatment with HDI (15 mg/m(2) infused over 5 days). After the second course she experienced paresthesias in both feet. After the third course she developed signs of severe toxicity in the CNS, kidneys, heart, and severe pain in her feet. Neurologic and neurophysiologic investigations, including neurographic studies of motor and sensory nerves, EMG, and thermotest, were performed in the acute phase and after 6 and 21 months, respectively. Renal and cardiac function was also assessed. She developed generalized weakness of the arms and legs and an extremely painful hyperesthesia of the soles. The symptoms improved gradually during follow-up but remained to some extent even after more than 2 years. Serial neurophysiologic investigations indicated classical signs of axonal neuropathy, which tended to improve during follow-up. After 18 months the glomerular filtration rate and the effective renal plasma flow were 30 and 12% of normal, respectively, while other organ functions had returned to baseline. Symptoms of peripheral neuropathy after HDI may herald severe multiorgan toxicity, if continued. Early administration of anesthetics through the intrathecal route should be considered in case of ifosfamide-induced painful peripheral neuropathy. Copyright 2001 Wiley-Liss, Inc.

  18. High-dose neutron irradiation performance of dielectric mirrors

    DOE PAGES

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

    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 I and 4 displacements per atom (dpa) at 458 ± 10 K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa result in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to I dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failingmore » at 4 dpa. Transmission electron microscopy (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects, which increase in size with irradiation dose. The typical size of each defect was approximate to 8 nm in 1-dpa specimens 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. Lastly, a significant interdiffusion between the film layers was observed in the Al2O3/SiO2 mirror, although it was less evident in the HfO2/SiO2 system. The ultimate goal of this work is to provide insight into the radiation-induced failure mechanisms of these mirrors.« less

  19. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk.

    PubMed

    Irvin, Susan C; Herold, Betsy C

    2015-01-01

    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. 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. Treatment of VK2/E6E7 cells with high doses (>15 μg/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. 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.

  20. 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.

  1. 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

  2. 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

  3. Dosimetry modeling for focal high-dose-rate prostate brachytherapy.

    PubMed

    Mason, Josh; Al-Qaisieh, Bashar; Bownes, Peter; Thwaites, David; Henry, Ann

    2014-01-01

    The dosimetry of focal high-dose-rate prostate brachytherapy was assessed. Dose volume histogram parameters, robustness to source position errors, and Monte Carlo (MC) simulations were compared for whole-gland (WG), hemi-gland (HEMI), and ultra-focal (UF) treatment plans. Tumor volumes were delineated based on MRI and template biopsy results for 9 patients. WG, HEMI, and UF plans were produced assuming 19 Gy single fraction monotherapy treatments. For UF plans, a 6-mm margin was applied to the visible tumor to create a focal-planning target volume (F-PTV). Systematic source position shifts of 1-4 mm were applied to assess plan robustness. The dosimetric impact of steel catheters was assessed using MC simulation. Mean D90 and V100 were 20.4 Gy and 97.9% for prostate in WG plans, 22.2 Gy and 98.1% for hemi-prostate in HEMI plans, and 23.0 Gy and 98.2% for F-PTV in UF plans. Mean urethra D10 was 20.3, 19.7, and 9.2 Gy in WG, HEMI, and UF plans, respectively. Mean rectal D2cc was 12.5, 9.8, and 4.6 Gy in WG, HEMI, and UF plans, respectively. Focal treatment plans were sensitive to source position errors-2 mm systematic shifts reduced mean prostate D90 by 0.7%, hemi-prostate D90 by 2.6%, and F-PTV D90 by 8.3% in WG, HEMI, and UF plans, respectively. MC simulation results were similar for all plan types with most dose volume histogram parameters reduced by <2%. HEMI and UF treatments can achieve higher D90 values compared with WG treatments with reduced organ at risk dose. Focal treatments are more sensitive to systematic source position errors than WG treatments. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  4. Cauda equina tolerance to high-dose fractionated irradiation

    SciTech Connect

    Pieters, Richard S.; Niemierko, Andrzej; Fullerton, Barbara C.; Munzenrider, John E. . E-mail: jmunzenrider@partners.org

    2006-01-01

    Purpose: To report late neurologic toxicity rates and clinical outcomes for patients treated with high dose fractionated radiation therapy using three-dimensional treatment planning and combined proton and photon beams to portions of the cauda equina (L2-coccyx). Methods and Materials: Medical records of 53 patients treated to fields encompassing the cauda equina were reviewed for the onset of neurologic symptoms in the absence of local failure. All doses were normalized to equivalent dose delivered in 2-Gy fractions. Median cauda dose was 65.8 cobalt Gray equivalents (CGE) (range, 31.9-85.1). Median follow-up was 87 months (range, 14-217 months). Results: Nineteen patients experienced local recurrences, and 13 others had neurologic toxicity. A total of 54% (i.e., 7/13) of the toxicities occurred 5 years or more after treatment. Median caudal dose was 73.7 CGE in the group with neurologic toxicity, and 55.6 CGE in those without. On multivariate actuarial analysis, cauda dose and gender were statistically significant for neurotoxicity at p = 0.002 and p = 0.017, respectively. The estimated tolerance doses 5 years from treatment, TD 5/5 and TD 50/5, were 55 CGE and 72 CGE, respectively, for males and 67 CGE and 84 CGE for females. The tolerance doses were about 8 CGE lower when estimated at 10 years from treatment. Disease-free survival rates at 5 and 10 years were 66% and 53%, respectively. Conclusions: This study suggests that the probability of neurotoxicity is a relatively steep function of dose to cauda equina (slope {gamma}{sub 5} = approximately 3). The cauda equina tolerance is greater for females than males by about 11 CGE (at 2 CGE per fraction). Extended follow-up is necessary to accurately assess neurologic damage and then differentiate that phenomenon from local recurrence; the traditional 5-year assessment has limited meaning in this population. Local control remains an issue for these patients, even with the radical doses used.

  5. 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 I and 4 displacements per atom (dpa) at 458 ± 10 K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa result in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to I 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 increase in size with irradiation dose. The typical size of each defect was approximate to 8 nm in 1-dpa specimens 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. Lastly, a significant interdiffusion between the film layers was observed in the Al2O3/SiO2 mirror, although it was less evident in the HfO2/SiO2 system. The ultimate goal of this work is to provide insight into the radiation-induced failure mechanisms of these mirrors.

  6. Interference of chlorate and chlorite with nitrate reduction in resting cells of Paracoccus denitrificans.

    PubMed

    Kucera, Igor

    2006-12-01

    When grown anaerobically on a succinate+nitrate (SN) medium, Paracoccus denitrificans forms the membrane-bound, cytoplasmically oriented, chlorate-reducing nitrate reductase Nar, while the periplasmic enzyme Nap is expressed during aerobic growth on butyrate+oxygen (BO) medium. Preincubation of SN cells with chlorate produced a concentration-dependent decrease in nitrate utilization, which could be ascribed to Nar inactivation. Toluenization rendered Nar less sensitive to chlorate, but more sensitive to chlorite, suggesting that the latter compound may be the true inactivator. The Nap enzyme of BO cells was inactivated by both chlorate and chlorite at concentrations that were at least two orders of magnitude lower than those shown to affect Nar. Partial purification of Nap resulted in insensitivity to chlorate and diminished sensitivity to chlorite. Azide was specific for SN cells in protecting nitrate reductase against chlorate attack, the protective effect of nitrate being more pronounced in BO cells. The results are discussed in terms of different metabolic activation of chlorine oxoanions in both types of cells, and limited permeation of chlorite across the cell membrane.

  7. 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

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

    PubMed

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

    2014-04-01

    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. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. A simple method for epoxidation of olefins using sodium chlorite as an oxidant without a catalyst.

    PubMed

    Geng, Xue-Li; Wang, Zhi; Li, Xiao-Qiang; Zhang, Chi

    2005-11-11

    [Reaction: see text]. Sodium chlorite has been demonstrated to be capable of epoxidizing a variety of olefins at 55-65 degrees C (oil bath). Chlorine dioxide is believed to be the pivotal epoxidizing agent in the reaction on the basis of the mechanistic studies.

  10. Efficacy of chlorine and acidified sodium chlorite on microbial population and quality changes of spinach leaves.

    PubMed

    Nei, Daisuke; Choi, Ji-Weon; Bari, Md Latiful; Kawasaki, Susumu; Kawamoto, Shinichi; Inatsu, Yasuhiro

    2009-06-01

    Efficacy of washing with distilled water, chlorine solution, and acidified sodium chlorite (ASC) solution on populations of microorganisms on spinach leaves was evaluated. Washing with chlorine (100 mg/L) and ASC (sodium chlorite, 15 mg/L; citric acid, 200 mg/L) resulted in significant population reduction (1.1-1.9 log CFU/g) of aerobic microflora, coliform, and Escherichia coli O157:H7 (p < 0.05). There was no remarkable difference in decontamination efficacy between chlorine and ASC solution. In recent years, several sodium chlorite chemicals have been commercially available, and no difference in decontamination efficacy among the chemicals was observed when same concentration of sodium chlorite and citric acid were used. In addition, the reduction of E. coli O157:H7 population was influenced depending on the inoculation method and type of washing. It has been seen that dip-inoculated spinach leaves showed lower reduction than that of spot-inoculated spinach. After washing, populations of aerobic microflora, coliform, and E. coli O157:H7 were increased during storage at 10 degrees C, and washing condition before storage did not affect the subsequent increases in microbial population. Color of spinach leaves washed with ASC solution was not different from the color of those washed with water or chlorine solution, and washing with ASC solution was concluded to has no effect on appearance of spinach leaves.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. Higher acid-chlorite reactivity of cell corner middle lamella lignin in black spruce

    Treesearch

    Umesh P. Agarwal

    2007-01-01

    To determine if there was a delignification behavior difference between secondary wall (S2) and middle lamella (cell corner or CC) lignin, black spruce cross-sections were acid-chlorite delignified and the tissue was evaluated in-situ by Raman imaging. Lignin concentration in S2 and CC was determined in numerous latewood cell areas in the two hour delignified cross...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  14. 40 CFR 180.1070 - Sodium chlorite; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD... chlorite is exempted from the requirement of a tolerance for residues when used in accordance with good agricultural practice as a seed-soak treatment in the growing of the raw agricultural commodities...

  15. 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

  16. 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%.

  17. Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis.

    PubMed

    Peyro Saint Paul, Laure; Debruyne, Danièle; Bernard, Delphine; Mock, Donald M; Defer, Gilles L

    2016-01-01

    Multiple sclerosis (MS) is a chronic, potentially highly disabling neurological disorder. No disease-modifying treatments are approved in the progressive and not active forms of the disease. High doses of biotin were tested in an open-label pilot study involving 23 patients with progressive MS and reported positive results. A randomized, double-blind, placebo-controlled trial in 154 progressive MS patients confirmed the beneficial effect of MD1003 (high-dose biotin) on reversing or stabilizing disability progression, with a good safety profile. It is proposed that MD1003 in progressive MS 1) increases energy production in demyelinated axons and/or 2) enhances myelin synthesis in oligodendrocytes. Biotin is highly bioavailable; absorption and excretion are rapid. The major route of elimination is urinary excretion. A high oral dose of biotin seems generally well tolerated but a few important safety concerns were identified: 1) teratogenicity in one species and 2) interference with some biotin-based laboratory immunoassays. The animal toxicity data are limited at such high doses. Further preclinical studies would be useful to address the mechanism of action of MD1003. Assessment of clinical benefit duration in responders will be also very important to set. Results of randomized, placebo-controlled trial are reassuring and provide hope for the treatment of progressive MS.

  18. 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.

  19. Assessment of maternal toxicity, embryotoxicity and teratogenic potential of sodium chlorite in Sprague-Dawley rats.

    PubMed Central

    Couri, D; Miller, C H; Bull, R J; Delphia, J M; Ammar, E M

    1982-01-01

    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/kg IP or by gavaging with 200 mg/kg. To prevent ingestion of stillborn pups some dams were sacrificed at day 22. Other dams were allowed to deliver at term. Fetuses were weighed, measured and examined for soft tissue and skeletal malformations. Sodium chlorite, 20 or 50 mg/kg daily IP or gavaging with 200 mg/kg, caused vaginal and urethral bleeding. Doses of 10, 20 or 50 mg/kg daily IP caused 0, 50 and 100% mortality of dams, respectively. No deaths were caused by sodium chlorite in the drinking water, but the dams' body weight, water and food consumption decreased during all treatments except 0.1% in the drinking water. Blood smears from the dams injected IP or drinking 2% sodium chlorite showed irregular, bizarre and ruptured erythrocytes. Injection of 10 or 20 mg/kg or drinking 2% resulted in decreased litter size and increased stillbirths and resorption sites. Drinking 0.1% or 0.5% sodium chlorite did not produce any significant embryotoxicity. With all treatments, no significant gross soft tissue or skeletal malformations were observed. Postnatal growth of the pups was not affected by any treatment of the dams during the gestation period. PMID:7151764

  20. Sense and nonsense of high-dose cytarabine for acute myeloid leukemia.

    PubMed

    Löwenberg, Bob

    2013-01-03

    High-dose cytarabine applied during remission induction or as consolidation after attainment of a complete remission has become an established element in the treatment of adults with acute myeloid leukemia. Recent evidence has challenged the need for these exceptionally high-dose levels of cytarabine. In this review, we present a reappraisal of the usefulness of high-dose cytarabine for acute myeloid leukemia treatment.

  1. 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

  2. Anti-emetic effect of high-dose metoclopramide vs alizapride--a randomised crossover study.

    PubMed Central

    Seng, K T; Tiong, C E; Hiang, T C

    1994-01-01

    A randomised double-blind crossover study was undertaken to compare the anti-emetic efficacy of alizapride against high dose metoclopramide. A total of 32 patients on cisplatin were randomised to receive either high dose metoclopramide (7 mg kg-1 day-1) or alizapride (5 mg kg-1 day-1). Anti-emetic responses in terms of control of vomiting episodes were similar in both regimens (59%). However, patients showed a statistically significant preference for high dose metoclopramide (P = 0.02). Side effects of both regimens were minimal. We conclude that alizapride is not superior to high dose metoclopramide in controlling cisplatin induced vomiting. PMID:7826833

  3. Phase stability and microstructures of high entropy alloys ion irradiated to high doses

    NASA Astrophysics Data System (ADS)

    Xia, Songqin; Gao, Michael C.; Yang, Tengfei; Liaw, Peter K.; Zhang, Yong

    2016-11-01

    The microstructures of AlxCoCrFeNi (x = 0.1, 0.75 and 1.5 in molar ratio) high entropy alloys (HEAs) irradiated at room temperature with 3 MeV Au ions at the highest fluence of 105, 91, and 81 displacement per atom, respectively, were studied. Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analyses show that the initial microstructures and phase composition of all three alloys are retained after ion irradiation and no phase decomposition is observed. Furthermore, it is demonstrated that the disordered face-centered cubic (FCC) and disordered body-centered cubic (BCC) phases show much less defect cluster formation and structural damage than the NiAl-type ordered B2 phase. This effect is explained by higher entropy of mixing, higher defect formation/migration energies, substantially lower thermal conductivity, and higher atomic level stress in the disordered phases.

  4. Contribution of long-term hydrothermal experiments for understanding the smectite-to-chlorite conversion in geological environments

    NASA Astrophysics Data System (ADS)

    Mosser-Ruck, Régine; Pignatelli, Isabella; Bourdelle, Franck; Abdelmoula, Mustapha; Barres, Odile; Guillaume, Damien; Charpentier, Delphine; Rousset, Davy; Cathelineau, Michel; Michau, Nicolas

    2016-11-01

    The smectite-to-chlorite conversion is investigated through long-duration experiments (up to 9 years) conducted at 300 °C. The starting products were the Wyoming bentonite MX80 (79 % smectite), metallic iron and magnetite in contact with a Na-Ca chloride solution. The predominant minerals in the run products were an iron-rich chlorite (chamosite like) and interstratified clays interpreted to be chlorite/smectite and/or corrensite/smectite, accompanied by euhedral crystals of quartz, albite and zeolite. The formation of pure corrensite was not observed in the long-duration experiments. The conversion of smectite into chlorite over time appears to take place in several steps and through several successive mechanisms: a solid-state transformation, significant dissolution of the smectite and direct precipitation from the solution, which is over-saturated with respect to chlorite, allowing the formation of a chamosite-like mineral. The reaction mechanisms are confirmed by X-ray patterns and data obtained on the experimental solutions (pH, contents of Si, Mg, Na and Ca). Because of the availability of some nutrients in the solution, total dissolution of the starting smectite does not lead to 100 % crystallization of chlorite but to a mixture of two dominant clays: chamosite and interstratified chlorite/smectite and/or corrensite/smectite poor in smectite. The role of Fe/(Fe + Mg) in the experimental medium is highlighted by chemical data obtained on newly formed clay particles alongside previously published data. The newly formed iron-rich chlorite has the same composition as that predicted by the geothermometer for diagenetic to low-grade metamorphic conditions, and the quartz + Fe-chlorite + albite experimental assemblage in the 9-year experiment is close to that fixed by water-rock equilibrium.

  5. The importance of the location of sodium chlorite application in a multipollutant flue gas cleaning system.

    PubMed

    Krzyzynska, Renata; Hutson, Nick D

    2012-06-01

    In this study, removing sulfur dioxide (SO2), nitrogen oxides (NO(x)), and mercury (Hg) from simulated flue gas was investigated in two laboratory-sized bubbling reactors that simulated an oxidizing reactor (where the NO and Hg(0) oxidation reactions are expected to occur) and a wet limestone scrubber, respectively. A sodium chlorite solution was used as the oxidizing agent. The sodium chlorite solution was an effective additive that enhanced the NO(x), Hg, and SO2 capture from the flue gas. Furthermore, it was discovered that the location of the sodium chlorite application (before, in, or after the wet scrubber) greatly influences which pollutants are removed and the amount removed. This effect is related to the chemical conditions (pH, absence/presence of particular gases) that are present at different positions throughout the flue gas cleaning system profile. The research results indicated that there is a potential to achieve nearly zero SO2, NO(x), and Hg emissions (complete SO2, NO, and Hg removals and -90% of NO(x) absorption from initial values of 1500 ppmv of SO2, 200 ppmv of NO(x), and 206 microg/m3 of Hg(0)) from the flue gas when sodium chlorite was applied before the wet limestone scrubber. However applying the oxidizer after the wet limestone scrubber was the most effective configuration for Hg and NO(x) control for extremely low chlorite concentrations (below 0.002 M) and therefore appears to be the best configuration for Hg control or as an additional step in NO(x) recleaning (after other NO(x) control facilities). The multipollutant scrubber, into which the chlorite was injected simultaneously with the calcium carbonate slurry, appeared to be the least expensive solution (when consider only capital cost), but exhibited the lowest NO(x) absorption at -50%. The bench-scale test results presented can be used to develop performance predictions for a full- or pilot-scale multipollutant flue gas cleaning system equipped with wet flue gas desulfurization

  6. High-dose cyclophosphamide and adriamycin with DTIC maintenance for metastatic soft tissue sarcomas.

    PubMed

    Clamon, G; Sinkey, C; Jochimsen, P

    1983-08-01

    Intensive chemotherapy with high-dose cyclophosphamide and adriamycin with DTIC maintenance was given to 12 patients with metastatic soft tissue sarcomas. A partial response rate of 25% was seen; this is no better than can be achieved with single-agent therapy. Because of substantial toxicity without improved efficacy, the trial of high dose therapy was halted.

  7. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    PubMed

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  8. Induced liver injury after high-dose methylprednisolone in a patient with multiple sclerosis.

    PubMed

    Oliveira, Ana Torres; Lopes, Sandra; Cipriano, Maria Augusta; Sofia, Carlos

    2015-07-21

    A 33-year-old woman with multiple sclerosis, medicated with high doses of methylprednisolone, cyclophosphamide and glatiramer acetate, was referred to our department due to acute liver injury. The laboratory investigation was normal except for weakly positive antinuclear antibodies. Cyclophosphamide and glatiramer acetate were suspended, and intravenous immunoglobulin with maintenance of high doses of methylprednisolone was initiated. The patient developed another episode of acute hepatitis so the immunoglobulin was stopped. After that, she had three more episodes of elevation of liver enzymes with no hepatic insufficiency while medicated only with high doses of methylprednisolone. At this time, liver biopsy showed focal centrilobubar hepatocyte necrosis with minimal interface hepatitis. After the high doses of methylprednisolone were suspended, the patient remained asymptomatic, with normal hepatic enzymes. This case emphasises that, although rare, induced liver injury after high doses of methylprednisolone can occur. 2015 BMJ Publishing Group Ltd.

  9. Barium chlorite hydrate, Ba(ClO2)2.3.5H2O.

    PubMed

    Smolentsev, Anton I; Naumov, Dmitry Yu

    2005-05-01

    The structure of barium chlorite hydrate, Ba(ClO2)2.3.5H2O, has been determined by single-crystal X-ray analysis at 150 K. The structure is monoclinic, space group C2/c, with Z = 8. It contains layers of Ba2+ cations coordinated by ClO2- anions and water molecules. There are also solvate water molecules involved only in hydrogen bonding of the layers. Three solvate water O atoms are on sites of twofold symmetry, while all other atoms are in general positions. The full coordination environment of the Ba2+ cation consists of ten O atoms belonging to six chlorites and three water molecules, forming a bicapped square antiprism.

  10. Microscopic distribution of trace elements in minerals (chlorites, sulfides, sulfates) in submarine hydrothermal systems

    SciTech Connect

    Janecky, D.R.; Benjamin, T.M.; Rogers, P.S.Z.; Bayhurst, G.K.; Haymon, R.M.

    1989-01-01

    We have analyzed trace elements in two types of hydrothermal precipitates using the Los Alamos Nuclear Microprobe. Chlorites and epidotes in basalt were analyzed from the Samail Ophiolite of Oman. Sulfide and sulfate minerals were analyzed from samples of active chimney walls from 21/degree/N. East Pacific Rise. These samples are ideal for our study because of the extensive background information available on processes and component characteristics. Initial results indicate significant differences in mobile trace elements between chlorites associated with and those distinctly separate from major stockwork flow zones, consistent with greater water-rock reaction within stockworks. Trace element concentrations across chimney walls also exhibit distinctive patterns which can be correlated with mineral/chemical zonation and possible also with variations in elemental source. 9 refs., 2 figs., 1 tab.

  11. Effect of sodium chloride, chlorite, and perchlorate on the hypochlorite-induced peroxidation of phospholipid liposomes.

    PubMed

    Panasenko, O M; Arnhold, J; Sergienko, V I

    1997-01-01

    The abilities of sodium hypochlorite (NaClO), chlorite (NaClO2), chlorate (NaClO3), and perchlorate (NaClO4) to initiate lipid peroxidation (LP) in liposomes formed from unsaturated phosphatidylcholine were compared. It was shown that only NaClO induced an intensive accumulation of LP products (thiobarbituric acid-reactive substances and diene conjugates) in the liposomes as a result of their co-incubation. The other oxochlorates produced no similar effects and did not affect the hypochlorite-induced LP. This indicates that the observed hypochlorite-induced LP does not result from the presence of chlorite, chlorate, or perchlorate anion admixtures in the medium.

  12. Occurrence of bromate, chlorite and chlorate in drinking waters disinfected with hypochlorite reagents. Tracing their origins.

    PubMed

    Garcia-Villanova, Rafael J; Oliveira Dantas Leite, M Vilani; Hernández Hierro, J Miguel; de Castro Alfageme, Santiago; García Hernández, Cristina

    2010-05-15

    Bromate was first reported as a disinfection by-product from ozonated waters, but more recently it has been reported also as a result of treatment using hypochlorite solutions worldwide. The aim of this study was to study the scope of this phenomenon in the drinking waters (n=509) of Castilla y León, Spain, and in the hypochlorite disinfectant reagents. Two thirds of the treated waters monitored were found to have bromate concentrations higher than 1 microg/l, and of them a median value of 8 microg/l and a maximum of 49 microg/l. These concentrations are higher than those reported so far, however, a great variability can be found. Median values for chlorite were of 5 microg/l, and of 119 microg/l for chlorate. Only 7 out of 40 hypochlorite feedstock solutions were negative for bromate, the rest showing a median of 1022 mg/l; and 4 out of 14 calcium hypochlorite pellets were also negative, the rest with a median of 240 mg/kg. Although bromate is cited as potentially added to water from calcium hypochlorite pellets, no reference is found in scientific literature regarding its real content. Chlorite (median 2646 mg/l) and chlorate (median 20,462 mg/l) and chlorite (median 695 mg/kg) and chlorate (median 9516 mg/kg) were also monitored, respectively, in sodium hypochlorite solutions and calcium hypochlorite pellets. The levels of chlorite and chlorate in water are considered satisfactory, but not those of bromate, undoubtedly owing to the high content of bromide in the raw brines employed by the chlor-alkali manufacturers. Depending on the manufacturer, the bromate concentrations in the treated waters may be very heterogeneous owing to the lack of specification for this contaminant in the disinfectant reagents -the European Norms EN 900 and 901 do not mention it.

  13. 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.

  14. 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

  15. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS

    PubMed Central

    Hutton, George J.; Racke, Michael K.; Popat, Uday; Devine, Steven M.; Steinmiller, Kaitlyn C.; Griffith, Linda M.; Muraro, Paolo A.; Openshaw, Harry; Sayre, Peter H.; Stuve, Olaf; Arnold, Douglas L.; Wener, Mark H.; Georges, George E.; Wundes, Annette; Kraft, George H.; Bowen, James D.

    2017-01-01

    Objective: To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT). Methods: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0–5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE). Results: Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12–72). EFS was 69.2% (90% confidence interval [CI] 50.2–82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%–97.2%), 86.9% (90% CI 69.5%–94.7%), and 86.3% (90% CI 68.1%–94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of −0.5 (interquartile range −1.5 to 0.0; p = 0.001) among participants who survived and completed the study. Conclusion: HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years. ClinicalTrials.gov identifier: NCT00288626. Classification of evidence: This study provides Class IV evidence that participants with RRMS experienced sustained remissions with toxicities as expected from HDIT/HCT. PMID:28148635

  16. Evaluation of chlorite and chlorate genotoxicity using plant bioassays and in vitro DNA damage tests.

    PubMed

    Feretti, D; Zerbini, I; Ceretti, E; Villarini, M; Zani, C; Moretti, M; Fatigoni, C; Orizio, G; Donato, F; Monarca, S

    2008-09-01

    In the last few years chlorine dioxide has been increasingly used for disinfecting drinking water in many countries. Although it does not react with humic substances, chlorine dioxide added to water is reduced primarily to chlorite and chlorate ions, compounds that are under investigation for their potential adverse effects on human health. The aim of this research was to study the genotoxicity of chlorite and chlorate and their mixtures. The end-points included two plant tests (chromosomal aberration test in Allium cepa and micronucleus assay in Tradescantia, carried out at different times of exposure) and two genotoxicity tests in human HepG2 cells (comet assay and cytokinesis-blocked micronucleus test). Preliminary toxicity tests were carried out for both plant and HepG2 assays. The results showed that chlorite and chlorate are able to induce chromosomal damage to plant systems, particularly chromosomal aberrations in A. cepa root tip cells, even at concentrations lower than the limit established by Italian normative law and WHO guidelines. In HepG2 cells increased DNA damage was only observed for chlorate at the lowest concentration. No increase in micronuclei frequency was detected in any of the samples tested in human HepG2 cells.

  17. Production of bio-sugar and bioethanol from coffee residue (CR) by acid-chlorite pretreatment.

    PubMed

    Kim, Ho Myeong; Choi, Yong-Soo; Lee, Dae-Seok; Kim, Yong-Hwan; Bae, Hyeun-Jong

    2017-07-01

    Nowadays, coffee residue (CR) after roasting is recognized as one of the most useful resources in the world for producing the biofuel and bio-materials. In this study, we evaluated the potential of bio-sugar and bioethanol production from acid-chlorite treated CR. Notably, CR treated three times with acid-chlorite after organic solvent extraction (OSE-3), showed the high monosaccharide content, and the efficient sugar conversion yield compared to the other pretreatment conditions. The OSE-3 (6% substrate loading, w/v) can produce bio-sugar (0.568g/g OSE-3). Also, simultaneous saccharification and fermentation (SSF) produced ethanol (0.266g/g OSE-3), and showed an ethanol conversion yield of 73.8% after a 72-h reaction period. These results suggest that acid-chlorite pretreatment can improve the bio-sugar and bioethanol production of CR by removing the phenolic and brown compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Validation of thiosulfate for neutralization of acidified sodium chlorite in microbiological testing.

    PubMed

    Kemp, G K; Schneider, K R

    2000-12-01

    At low pH, acidified sodium chlorite (ASC) has antimicrobial activity against a variety of foodborne contaminants. To evaluate the antimicrobial efficacy of ASC at specific time points posttreatment, it is necessary to halt the action of the disinfectant by removing residual chlorite or by increasing the pH. In this study, thiosulfate was investigated at varying concentrations for its effect on microbial survival and was investigated at a concentration of 0.1% in the presence of ASC for its effect on the antimicrobial and chemical activity of the test solution. Additionally, sodium thiosulfate was tested in two buffering systems, buffered peptone water (BPW) and Butterfield's phopshate buffer (BPB), for its ability to inactivate ASC chemistry. The results of this study show that, at a concentration of 0.1%, sodium thiosulfate has no deleterious effect on Escherichia coli survival and is effective in halting the antimicrobial action of ASC by eliminating the production of residual chlorite. The BPW alone and BPB in combination with thiosulfate were found to be effective inactivators of ASC chemistry.

  19. Environmental genomics reveals a functional chlorite dismutase in the nitrite-oxidizing bacterium 'Candidatus Nitrospira defluvii'.

    PubMed

    Maixner, Frank; Wagner, Michael; Lücker, Sebastian; Pelletier, Eric; Schmitz-Esser, Stephan; Hace, Karin; Spieck, Eva; Konrat, Robert; Le Paslier, Denis; Daims, Holger

    2008-11-01

    Nitrite-oxidizing bacteria of the genus Nitrospira are ubiquitous in natural ecosystems and also in wastewater treatment plants. Nitrospira are members of a distinct phylum, not closely related to other nitrifiers, and no genomic sequences from this genus have been available so far. Here we applied an environmental genomics approach to sequence and assemble a 137 kbp-long genome fragment of 'Candidatus Nitrospira defluvii', which had been enriched from activated sludge and belongs to Nitrospira sublineage I without isolated representatives. The annotation of this contig, which carried the 16S rRNA gene of N. defluvii, offered first insight into the genome of Nitrospira. Surprisingly, we found a gene similar to genes encoding chlorite dismutase (CLD), an enzyme degrading chlorite (ClO(2)(-)) to Cl(-) and O(2). To date, CLDs with high catalytic activity have been found only in perchlorate- and chlorate-reducing bacteria but not in nitrifiers. Heterologous expression in E. coli followed by enzymatic tests confirmed that this gene of Nitrospira encodes a highly active CLD, which is also expressed in situ by Nitrospira, indicating that this nitrite oxidizer might be involved in the bioremediation of perchlorate and chlorite. Phylogenetic analyses showed that CLD and related proteins are widely distributed among the Bacteria and Archaea, and indicated that this enzyme family appeared relatively early in evolution, has been subject to functional diversification and might play yet unknown roles in microbial metabolism.

  20. Temporal and spatial organization of chemical and hydrodynamic processes. The system Pb(2+)-chlorite-thiourea.

    PubMed

    Udovichenko, Vladimir V; Strizhak, Peter E; Toth, Agata; Horwath, Dezso; Ning, Steven; Maselko, Jerzy

    2008-05-22

    Precise spatio-temporal organization of chemical, hydrodynamic, and mechanical processes is typical for biological systems where particular chemical reactions have to accrue in precisely assignment place and time. It is rarely studied and observed in chemical systems. We report unusual precipitation pattern formation of PbSO(4) in chemical media (Pb(2+)-Chlorite-Thiourea System). We have found that there is a region in a plane of initial concentrations of chlorite ions and thiourea where precipitation of lead sulfate appears in a form of ring if a pellet of lead nitrate is placed into the system. The whole process may be divided into three stages: movement of first circular front of lead containing solution, formation of a ringlike pattern of lead sulfate, and finally, propagation of this pattern resulting in a formation of ring with final inside diameter. Our experiments indicate that the following values are reproducible and quantify the PbSO(4) ring evolution: induction time, radius of the ring birth, speed of ring propagation toward the center, and final inside radius of the ring. Numerical solution of kinetic equations allowed us to give a qualitative explanation for the phenomenon observed. Formation and evolution of the PbSO(4) rings are caused by interplay of concentration gradients in the system and chemical reactions that occur in excitable chlorite-thiourea system. Chemical reactions and hydrodynamic processes form a complex causal network that made morphogenesis of this unusual pattern possible.

  1. Use of layer silicate for protein crystallization: effects of Micromica and chlorite powders in hanging drops.

    PubMed

    Takehara, Masahide; Ino, Keita; Takakusagi, Yoichi; Oshikane, Hiroyuki; Nureki, Osamu; Ebina, Takeo; Mizukami, Fujio; Sakaguchi, Kengo

    2008-02-15

    Two kinds of layer silicate powder, Micromica and chlorite, were used to aid protein crystallization by the addition to hanging drops. Using appropriate crystallization buffers, Micromica powder facilitated crystal growth speed for most proteins tested in this study. Furthermore, the addition of Micromica powder to hanging drops allowed the successful crystallization of lysozyme, catalase, concanavalin A, and trypsin even at low protein concentrations and under buffer conditions that otherwise would not generate protein crystals. Except for threonine synthase and apoferritin, the presence of chlorite delayed crystallization but induced the formation of large crystals. X-ray analysis of thaumatin crystals generated by our novel procedure gave better quality data than did that of crystals obtained by a conventional hanging drop method. Our results suggest that the speed of crystal growth and the quality of the corresponding X-ray data may be inversely related, at least for the formation of thaumatin crystals. The effect of Micromica and chlorite powders and the application of layer silicate powder for protein crystallization are discussed.

  2. 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.

  3. Efficacy of acidified sodium chlorite treatments in reducing Escherichia coli O157:H7 on Chinese cabbage.

    PubMed

    Inatsu, Yasuhiro; Bari, Md Latiful; Kawasaki, Susumu; Isshiki, Kenji; Kawamoto, Shinichi

    2005-02-01

    Efficacy of acidified sodium chlorite for reducing the population of Escherichia coli O157:H7 pathogens on Chinese cabbage leaves was evaluated. Washing leaves with distilled water could reduce the population of E. coli O157:H7 by approximately 1.0 log CFU/g, whereas treating with acidified chlorite solution could reduce the population by 3.0 log CFU/g without changing the leaf color. A similar level of reduction was achieved by washing with sodium chlorite solution containing various organic acids. However, acidified sodium chlorite in combination with a mild heat treatment reduced the population by approximately 4.0 log CFU/g without affecting the color, but it softened the leaves. Moreover, the efficacy of the washing treatment was similar at low (4 degrees C) and room (25 degrees C) temperatures, indicating that acidified sodium chloride solution could be useful as a sanitizer for surface washing of fresh produce.

  4. Determinants of Quality of Life in High-Dose Benzodiazepine Misusers

    PubMed Central

    Tamburin, Stefano; Federico, Angela; Faccini, Marco; Casari, Rebecca; Morbioli, Laura; Sartore, Valentina; Mirijello, Antonio; Addolorato, Giovanni; Lugoboni, Fabio

    2017-01-01

    Benzodiazepines (BZDs) are among the most widely prescribed drugs in developed countries, but they have a high potential for tolerance, dependence and misuse. High-dose BZD misuse represents an emerging addiction phenomenon, but data on quality of life (QoL) in high-dose BZD misusers are scant. This study aimed to explore QoL in high-dose BZD misuse. We recruited 267 high-dose BZD misusers, compared the QoL scores in those who took BZD only to poly-drug misusers, and explored the role of demographic and clinical covariates through multivariable analysis. Our data confirmed worse QoL in high-dose BZD misusers and showed that (a) QoL scores were not negatively influenced by the misuse of alcohol or other drugs, or by coexisting psychiatric disorders; (b) demographic variables turned out to be the most significant predictors of QoL scores; (c) BZD intake significantly and negatively influenced QoL. Physical and psychological dimensions of QoL are significantly lower in high-dose BZD misusers with no significant effect of comorbidities. Our data suggest that the main reason for poor QoL in these patients is high-dose BZD intake per se. QoL should be considered among outcome measures in these patients. PMID:28054975

  5. 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Variation in long-term antipsychotic polypharmacy and high-dose prescribing across physicians and hospitals.

    PubMed

    Latimer, Eric A; Naidu, Adonia; Moodie, Erica E M; Clark, Robin E; Malla, Ashok K; Tamblyn, Robyn; Wynant, Willy

    2014-10-01

    This study had two aims: to measure the prevalence of long-term prescribing of high doses of antipsychotics and antipsychotic polypharmacy in a large Canadian province and to estimate the relative contributions of patient-, physician-, and hospital-level factors. Government hospital discharge, physician, and pharmaceutical claims data were linked to identify individuals with schizophrenia who in 2004 had antipsychotics available to them for at least 11 months. Individuals on a high dose throughout that period, as well as individuals on multiple concurrent antipsychotics (polypharmacy), were identified. Logistic and generalized linear mixed models using patient-, physician-, and hospital-level predictors were estimated. Among the 12,150 individuals identified, 11.9% were on a high dose and 10.4% on antipsychotic polypharmacy continually, with 3.7% in both groups. After adjustment for potential confounders, analyses showed that systematic propensity for physicians to prescribe high doses accounted for 10.9% of the remaining unexplained variance, and physicians as a group who prescribed high doses across a hospital or psychiatry department accounted for 3.0%. For antipsychotic polypharmacy the corresponding percentages were 9.7% and 6.2%. Even after adjustment, the variation in high-dose prescribing and antipsychotic polypharmacy remained substantial. Long-term high-dose and antipsychotic polypharmacy prescribing appeared partly driven by some physicians' and some hospitals' propensities to prescribe in this way independently of patient characteristics. Given the weight of the evidence against high-dose prescribing and antipsychotic polypharmacy, measures addressed to physicians and hospitals most likely to prescribe high doses, antipsychotic polypharmacy, or both should be considered.

  7. 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)

  8. Two-generation reproduction and developmental neurotoxicity study with sodium chlorite in the rat.

    PubMed

    Gill, M W; Swanson, M S; Murphy, S R; Bailey, G P

    2000-01-01

    The potential for sodium chlorite to produce reproductive toxicity, developmental neurotoxicity and alterations in hematology and thyroid hormones was evaluated in Sprague-Dawley rats administered sodium chlorite in the drinking water continuously for two generations. The F(0) generation animals (30 of each gender per group) and F(1) generation animals (25 of each gender per group) selected to rear the F(2) generation were allowed free access to drinking water containing 0, 35, 70 or 300 ppm sodium chlorite for a 10-week prebreed period, through mating for males and through mating, gestation and lactation for females. These drinking water concentrations corresponded to sodium chlorite doses of approximately 4, 8 and 30 mg kg(-1) day(-1) for males and 5, 10 and 39 mg kg(-1) day(-1) for females, respectively. Evaluations included standard reproductive and postnatal indices, sperm morphology and motility, estrous cyclicity, a functional observational battery, motor activity, auditory startle, swim maze, hematology, serum thyroid hormone analyses and histopathology of reproductive and nervous system tissues. Sodium chlorite resulted in a decrease in water consumption in all groups and a decrease in food consumption and body weights in the 70 and 300 ppm groups. There was no evidence of reproductive toxicity. Pup body weight was decreased in the 300 ppm group and small delays were observed in the time to preputial separation and vaginal opening. Mild anemia and mild methemoglobinemia were observed for animals in the 300 ppm group. Thyroid hormone levels were not affected by treatment. Changes to the nervous system were limited to small decreases in amplitude of auditory startle response for postnatal day (PND) 25 pups in the 70 and 300 ppm groups and a small decrease in absolute brain weight for PND 11 pups in the 300 ppm group. These effects were considered to be of questionable neurotoxicological significance. Based on the results of this study, the no

  9. Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer

    DTIC Science & Technology

    2015-02-01

    AWARD NUMBER: W81XWH-14-1-0014 TITLE: Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer PRINCIPAL INVESTIGATOR: Peter Maxim...TITLE AND SUBTITLE ery High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0014 5c...1 Contract number: W81XWH-14-1-0014 Title: Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer Principal Investigator: Peter G

  10. [Development of a perforated peptic ulcer in a child during high dose prednisolone treatment].

    PubMed

    Moll Harboe, Kirstine; Midtgaard, Helle; Wewer, Vibeke; Cortes, Dina

    2012-09-24

    Since perforated peptic ulcer is uncommon in children proton pump inhibitor prophylaxis is not routinely recommended when children are treated with high dose steroids. We describe a case of perforated ulcer in a six-year-old patient with nephrotic syndrome treated with high dose prednisolone. Initially, ulcer was not suspected due to uncharacteristic symptoms. The child developed peritoneal signs and surgery revealed a perforated peptic ulcer in the stomach. We recommend treatment with proton pump inhibitors if children, who are treated with high dose steroids develop abdominal symptoms, which can be caused by an ulcus.

  11. "Half-half" blisters in bullous pemphigoid successfully treated with adjuvant high-dose intravenous immunoglobulin.

    PubMed

    Pacheco, David; Lopes, Leonor; Soares-Almeida, Luis; Marques, Manuel Sacramento; Filipe, Paulo

    2012-09-01

    Bullous pemphigoid is a rare, autoimmune blistering disease. Its clinical presentation is tense blisters that may arise on normal-appearing or erythematous skin. Bullous pemphigoid refractory to systemic corticosteroids in combination with immunosuppressants such as azathioprine and mycophenolate mofetil may benefit from adjuvant high-dose intravenous immunoglobulin (IVIg). We describe a particular case with an unusual clinical presentation unresponsive to systemic corticosteroids plus azathioprine, in which the addition of high-dose IVIg was successful. The combined therapy of systemic corticosteroids and azathioprine plus high-dose IVIg can be an option in refractory cases due to its efficiency and tolerability.

  12. High dose of ascorbic acid induces cell death in mesothelioma cells.

    PubMed

    Takemura, Yukitoshi; Satoh, Motohiko; Satoh, Kiyotoshi; Hamada, Hironobu; Sekido, Yoshitaka; Kubota, Shunichiro

    2010-04-02

    Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

  13. [Exposure to organic halogen compounds in drinking water of 9 Italian regions: exposure to chlorites, chlorates, thrihalomethanes, trichloroethylene and tetrachloroethylene].

    PubMed

    Fantuzzi, G; Aggazzotti, G; Righi, E; Predieri, G; Giacobazzi, P; Kanitz, S; Barbone, F; Sansebastiano, G; Ricci, C; Leoni, V; Fabiani, L; Triassi, M

    2007-01-01

    This study investigated the exposure to organohalogens compounds in drinking water from 9 Italian towns (Udine, Genova, Parma, Modena, Siena, Roma, L'Aquila, Napoli and Catania). Overall, 1199 samples collected from 72 waterworks were analyzed. THMs, trichloroethylene and tetrachloroethylene were evaluated using the head-space gas chromatographic technique (detection limit of 0.01 microg/l; chlorite and chlorate analysis was performed by ion chromatography (detection limit of 20 microg/l). THMs were evidenced in 925 samples (77%) (median value: 1.12 micro/l; range: 0.01-54 mciro/l) and 7 were higher than the THMs Italian limit of 30 microg/l. Chlorite and chlorate levels were higher than the detection limit in 45% for chlorite and in 34% for chlorate samples; median values were 221 microg/l and 76 microg/l, respectively. Chlorite values were higher than the chlorite Italian limit (700 microg/l) in 35 samples (8.7%). Trichloroethylene and tetrachloroethylene were measured in 29% and 44% of the investigated samples and showed values lower than the Italian limit (highest levels of 6 microg/l and 9 microg/l, respectively). The low levels detected of THMs, trichloroethylene and tetrachloroethylene have no potentials effects on human health, whereas, the levels of chlorite and chlorates should be further evaluated and their potential effects for the populations using these drinking waters, better understood.

  14. High-Dose Flu Shot May Help Nursing Home Residents Avoid Hospital

    MedlinePlus

    ... medlineplus.gov/news/fullstory_167348.html High-Dose Flu Shot May Help Nursing Home Residents Avoid Hospital ... July 21, 2017 (HealthDay News) -- Nobody wants the flu, but it can prove deadly for frail residents ...

  15. High-dose monoclonal antibodies via the subcutaneous route: challenges and technical solutions, an industry perspective.

    PubMed

    Narasimhan, Chakravarthy; Mach, Henryk; Shameem, Mohammed

    2012-07-01

    This review summarizes the various challenges in product development involved in subcutaneous administration of high-dose monoclonal antibodies and attempts to provide an industry perspective of some of the available technologies and potential avenues to overcome these challenges.

  16. 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)

  17. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

    DTIC Science & Technology

    2008-06-01

    computed tomography –based high dose rate brachytherapy of prostate cancer, Journal of Applied Clinical Medical Physics, Vol. 8, No. 4, Fall 2007...Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy PRINCIPAL INVESTIGATOR: Jean Pouliot, Ph.D. I-Chow Hsu, M.D...response, including the time for reviewing instructions, searching existing data sources , gathering and maintaining the data needed, and completing and

  18. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy. Addendum

    DTIC Science & Technology

    2009-06-01

    Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy PRINCIPAL INVESTIGATOR: Jean Pouliot, Ph.D. I-Chow Hsu...data sources , gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this...NUMBER Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy 5b. GRANT NUMBER W81XWH-04-1-0262

  19. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

    DTIC Science & Technology

    2010-06-01

    Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy PRINCIPAL INVESTIGATOR: Jean Pouliot, Ph.D. I-Chow Hsu...data sources , gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this...Intraprostatic lesions with Inverse-Planned 5a. CONTRACT NUMBER W81XWH-04-1-0262 High Dose Rate Brachytherapy 5b. GRANT NUMBER

  20. High-dose fractionated radiation therapy for select patients with brain metastases

    SciTech Connect

    Pezner, R.D.; Lipsett, J.A.; Archambeau, J.O.; Fine, R.M.; Moss, W.T.

    1981-08-01

    Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites. The risk of radiotherapy side effects in the brain is discussed.

  1. [The risk-benefit of high doses of botulinum toxin injections for muscle spasticity ].

    PubMed

    Rousseaux, M; Daveluy, W

    2007-01-01

    To bring general elements of reflection on the use of the high doses of botulinum toxin in spastic children and adults. Review of the literature on the high doses and the benefit-risk associated with botulinum toxin injections. The medical literature exclusively relates to the use of the high doses in children and adolescents. Comparative work with conventional doses suggests a relative interest, but with a risk of increased side effects. Several articles report on treatments with high and even very high doses in series of patient, with a documented effectiveness. But their justification remains partial and the study of the possible side effects is limited. Reflections are brought to contribute to the debate on the use of high doses, taking into account the local physiological effect of botulinum toxin, the risk of regional and general diffusion, the need for a progressive strategy, the variability of effects, the cost of the treatment and the need for obtaining an informed consent of the patient and of significant others. The use of high doses of botulinum toxin increases progressively, but must remain very careful.

  2. High-dose immunoglobulin infusion for thrombotic thrombocytopenic purpura refractory to plasma exchange and steroid therapy.

    PubMed

    Park, Seh Jong; Kim, Seok Jin; Seo, Hee Yun; Jang, Moon Ju; Oh, Doyeun; Kim, Byung Soo; Kim, Jun Suk

    2008-09-01

    The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

  3. 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

  4. 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

  5. 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. © 2015 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  6. 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

  7. On topotaxy and compaction during antigorite and chlorite dehydration: an experimental and natural study

    NASA Astrophysics Data System (ADS)

    Padrón-Navarta, José Alberto; Tommasi, Andréa; Garrido, Carlos J.; Mainprice, David

    2015-04-01

    Dehydration reactions result in minerals' replacement and a transient fluid-filled porosity. These reactions involve interface-coupled dissolution-precipitation and might therefore lead to fixed crystallographic orientation relations between reactant (protolith) and product phases (i.e. topotaxy). We investigate these two phenomena in the dehydration of a foliated antigorite (atg) serpentinite by comparing the crystallographic preferred orientation (CPO) developed by olivine (ol), orthopyroxene (opx) and chlorite (chl) during high-pressure antigorite and chlorite dehydration in piston-cylinder experiments and in natural samples recording the dehydration of antigorite (Cerro del Almirez, Betic Cordillera, Spain). Experiments were performed under undrained conditions resulting in fluid-filled porosity and in strong CPO of the prograde minerals, controlled by the pre-existing antigorite CPO in the reactant foliated serpentinite. The orientation of a ol,opx and is parallel to from the protolith. The Cerro del Almirez samples show similar, locally well-developed topotactic relations between orthopyroxene, chlorite and antigorite, but the product CPOs are weaker and more complex at the thin section scale. In contrast to the experiments, olivine from natural samples shows a weak correlation between b ol and the former . We relate the strengthening of local topotactic relations and the weakening of the inherited CPO at a larger scale in natural samples to compaction and associated fluid migration. Microstructural features that might be related to compaction in the natural samples include: (1) smooth bending of the former foliation, (2) gradual crystallographic misorientation (up to 16°) of prismatic orthopyroxene due to buckling by dislocation creep, (3) inversion of enstatite to low clinoenstatite (P21/c) along lamellae and (4) brittle fracturing of prismatic orthopyroxene enclosed by plastically deformed chlorite. The coexistence of orthopyroxene buckling and

  8. Stochastic behavior and stirring rate effects in the chlorite-iodide reaction

    NASA Astrophysics Data System (ADS)

    Nagypál, István; Epstein, Irving R.

    1988-12-01

    The autocatalytic reaction between chlorite and iodide ions in a closed system is a clock reaction, showing a sudden appearance of brown I2 followed by a rapid disappearance of the color. Under certain conditions, the reaction time displays a striking irreproducibility. This stochastic behavior is studied potentiometrically and spectrophotometrically as a function of initial [I- ], stirring rate and solution volume. The results imply that the irreproducibility is an inherent feature of the reaction generated by fluctuations in the solution after it is ``well mixed.'' The key contributors to the stochasticity are local concentration inhomogeneities resulting from imperfect stirring and the ``supercatalytic'' reaction kinetics. A qualitative explanation is given that incorporates these aspects.

  9. Evaluation of the immunomodulatory effects of the disinfection by-product, sodium chlorite, in female B6C3F1 mice: a drinking water study.

    PubMed

    Karrow, N A; Guo, T L; McCay, J A; Johnson, G W; Brown, R D; Musgrove, D L; Germolec, D R; Luebke, R W; White, K L

    2001-08-01

    Sodium chlorite is an inorganic by-product of chlorine dioxide formed during the chlorination of drinking water. Relatively little is known about the adverse health effects of exposure to sodium chlorite in drinking water. In this study, we evaluated sodium chlorite's immunomodulatory properties using female B6C3F1 mice and a panel of immune assays that were designed to evaluate potential changes in innate and acquired cellular and humoral immune responses. Female B6C3F1 mice were exposed to sodium chlorite in their drinking water (0, 0.1, 1, 5, 15, and 30 mg/L) for 28 days, and then evaluated for immunomodulation. Overall, minimal toxicological and immunological changes were observed after exposure to sodium chlorite. Increases in the percentages of blood reticulocytes, and the relative spleen weights were both observed at different sodium chlorite treatment levels; however, these increases were not dose-dependent. An increasing trend in the number of spleen antibody-forming cells was observed over the range of sodium chlorite concentrations. This increase was not, however, significant at any individual treatment level, and was not reflected by changes in serum IgM levels. A significant increase (26%) in the total number of splenic CD8+ cells was observed in mice treated with 30 mg/L of sodium chlorite, but not at the other concentrations. Splenic mixed leukocyte response and peritoneal macrophage activity were unaffected by sodium chlorite. Lastly, exposure to sodium chlorite did not affect natural killer cell activity, although a decrease in augmented natural killer cell activity (42%) was observed at the lowest sodium chlorite treatment level. These results suggest that sodium chlorite, within the range 0.1-30 mg/L, produces minimal immunotoxicity in mice.

  10. The clinical and microbiological effects of a novel acidified sodium chlorite mouthrinse on oral bacterial mucosal infections.

    PubMed

    Fernandes-Naglik, L; Downes, J; Shirlaw, P; Wilson, R; Challacombe, S J; Kemp, G K; Wade, W G

    2001-09-01

    Acidified sodium chlorite mouthrinses have been shown to have equivalent anti-plaque activity to those containing chlorhexidine, the current 'gold standard'. In this study, sodium chlorite mouthrinses (ASC) acidified with either malic or gluconic acids were compared to each other and with a chlorhexidine rinse and sterile water for their effect on salivary bacterial counts. Sixteen subjects participated in the study, which had a cross-over Latin square design. In a second study, a sodium chlorite/gluconic acid rinse was compared with chlorhexidine for its clinical and microbiological effects in 36 patients with oral mucosal infections. The sodium chlorite rinses acidified with malic and gluconic acids and the chlorhexidine rinse caused significant reductions in salivary bacterial counts up to 7 h after a single rinse compared with water. There were no significant differences between the three active treatments. In the mucosal infection study, there was a significant reduction in erythema in the chlorhexidine group compared with the ASC group. Patients who received the ASC rinse reported significantly less discomfort following treatment than those receiving the chlorhexidine rinse. Staphylococcus aureus counts were significantly reduced in the group who received the sodium chlorite rinse. There were no other significant differences between the treatments. ASC appears to be an effective alternative to chlorhexidine mouthrinse.

  11. Magnesium isotopic behavior during the formation of chlorite-rich hydrothermal sediment in the middle Okinawa Trough

    NASA Astrophysics Data System (ADS)

    Shao, H.; Yang, S.; Teng, F. Z.; Cai, D.; Humphris, S. E.

    2016-12-01

    Chlorite is a common alteration product during water-rock reactions in seafloor hydrothermal systems. This chlorite is commonly characterized by high concentrations of magnesium. However, the source of the Mg and its behavior during hydrothermal alteration have yet to be clarified. Mg isotopes have been used in recent years to investigate a variety of geological processes, including low temperature weathering and metamorphism processes, and Mg cycling in sediments. In this study, we investigate the source of Mg and its behavior in chlorite-rich sediments collected during IODP Expedition 331 from the active hydrothermal Iheya North Knoll field in the middle Okinawa Trough — an intra-continental rift in continental crust. This area is characterized by hemipelagic muds with interbedded thick layers of felsic pumiceous volcanic material. Based on mineralogical, geochemical, and isotopic data, we have previously suggested that the chlorite-rich sediments resulted from hydrothermal alteration of the pumiceous layers at temperatures of 220-300°C. Prior to Mg isotope analysis, all selected samples were pretreated with 1N HCl in order to remove carbonates and other unstable minerals, and measurements were made on both the residues (mainly chlorite) and leachates, as well as on bulk samples. The residues are expected to show higher δ26Mg than the leachates reflecting the Mg isotopic signature of the pumiceous material precursor and provide insight into the behavior of Mg isotopes during the high-temperature hydrothermal processes.

  12. Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia.

    PubMed

    Burns, C Patrick; Halabi, Susan; Clamon, Gerald; Kaplan, Ellen; Hohl, Raymond J; Atkins, James N; Schwartz, Michael A; Wagner, Brett A; Paskett, Electra

    2004-07-15

    The authors undertook a multiinstitutional Phase II cooperative group study to examine the potential of oral fish oil fatty acid supplements administered at high doses to slow weight loss and to improve quality of life in patients with malignancy-related cachexia. Patients with advanced malignancy and weight loss > or = 2% of body weight in the preceding month took concentrated, high-dose omega-3 fatty acid capsules (7.5 g eicosapentaenoic acid plus docosahexaenoic acid for a 70 kg individual) that were supplied by the National Institutes of Health. Forty-three patients with moderate or severe malnutrition were enrolled. The median time receiving treatment was 1.2 months. For the 36 patients who took at least 1 capsule and did not have edema, there was a weight change ranging from -6.2 kg to +3.5 kg and an overall median weight loss of 0.8 kg. Twenty-four patients had weight stabilization (a gain of < or = 5% or a loss of < 5%), 6 patients gained > 5% of their body weight, and 6 patients lost > or = 5% of their body weight. There was marked variability in the tolerability of the capsules, and many patients had gastrointestinal side effects. There was a correlation between time receiving treatment and weight gain for the 22 patients who were able to tolerate the capsules for at least 1 month. Quality-of-life scores were superior for patients who gained weight. A majority of patients did not gain weight, and in that sense, the results of the study were unfavorable. However, a small but definite subset of patients had weight stabilization or weight gain. This suggests that omega-3 fatty acids have potential utility at the study doses, which were more than twice the doses used in published Phase III studies. Copyright 2004 American Cancer Society.

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

    PubMed

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

    2015-10-01

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

  14. 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.

  15. Reactions of aquacobalamin and cob(II)alamin with chlorite and chlorine dioxide.

    PubMed

    Dereven'kov, Ilia A; Shpagilev, Nikita I; Valkai, László; Salnikov, Denis S; Horváth, Attila K; Makarov, Sergei V

    2017-06-01

    Reactions of aquacobalamin (H2O-Cbl(III)) and its one-electron reduced form (cob(II)alamin, Cbl(II)) with chlorite (ClO2(-)) and chlorine dioxide (ClO 2(•) ) were studied by conventional and stopped-flow UV-Vis spectroscopies and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). ClO2(-) does not react with H2O-Cbl(III), but oxidizes Cbl(II) to H2O-Cbl(III) as a major product and corrin-modified species as minor products. The proposed mechanism of chlorite reduction involves formation of OCl(-) that modifies the corrin ring during the course of reaction with Cbl(II). H2O-Cbl(III) undergoes relatively slow destruction by ClO 2(•) via transient formation of oxygenated species, whereas reaction between Cbl(II) and ClO 2(•) proceeds extremely rapidly and leads to the oxidation of the Co(II)-center.

  16. Determination of chlorate and chlorite and mutagenicity of seafood treated with aqueous chlorine dioxide.

    PubMed

    Kim, J; Marshall, M R; Du, W X; Otwell, W S; Wei, C I

    1999-09-01

    The use of chlorine dioxide (ClO(2)) as a potential substitute for aqueous chlorine to improve the quality of seafood products has not been approved by regulatory agencies due to health concerns related to the production of chlorite (ClO(2)(-)) and chlorate (ClO(3)(-)) as well as possible mutagenic/carcinogenic reaction products. Cubes of Atlantic salmon (Salmo salar) and red grouper (Epinephelus morio) were treated with 20 or 200 ppm aqueous chlorine or ClO(2) solutions for 5 min, and extracts of the treated fish cubes and test solutions were checked for mutagenicity using the Ames Salmonella/microsome assay. No mutagenic activity was detected in the treated fish samples or test solutions with ClO(2). Only the sample treated with 200 ppm chlorine showed weak mutagenic activity toward S. typhimurium TA 100. No chlorite residue was detected in sea scallops, mahi-mahi, or shrimp treated with ClO(2) at 3.9-34.9 ppm. However, low levels of chlorate residues were detected in some of the treated samples. In most cases, the increase in chlorate in treated seafood was time- and dose-related.

  17. 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

  18. Uranyl-chlorite sorption/desorption: Evaluation of different U(VI) sequestration processes

    NASA Astrophysics Data System (ADS)

    Singer, David M.; Maher, Kate; Brown, Gordon E., Jr.

    2009-10-01

    Sequestration of soluble uranium(VI) in the form of uranyl UO22+ by clay minerals such as chlorite is potentially a major sink for U in U-contaminated environments. We have used batch sorption/desorption experiments combined with U L III-edge X-ray absorption near-edge structure (XANES) spectroscopy, extended X-ray absorption fine structure (EXAFS) spectroscopy, scanning and transmission electron microscopy, synchrotron-based microdiffraction, and surface complexation modeling to investigate the dominant sorption process(es) governing uranyl uptake by chlorite. Uranium(VI) sorption is independent of ionic strength, suggesting dominantly inner-sphere sorption, which was supported by selective chemical extraction results. The maximum sorption loadings were 0.28 μmol U g -1 chlorite (at pH 4) and 6.3 μmol U g -1 chlorite (at pH 6.5 and 10). Uranium(VI) uptake as a function of solution composition followed the trends (at pH 6.5): CO 3-Ca-free system >CO 3-Ca-bearing system >CO 3-bearing system; (at pH 10): CO 3-Ca-bearing system >CO 3-Ca-free system ≈CO 3-bearing system. Desorption experiments based on selective chemical extractions indicated that (1) there is little or no weakly bound U(VI) or U(VI)-bearing precipitates, (2) 60-80% of U(VI) inner-sphere sorption complexes are desorbed following a 0.1 M HCl step over 1 week, and (3) 100% desorption of adsorbed U(VI) is accomplished by a 1.0 M HCl step over 1 week. Fits of the EXAFS spectra of the short-term sorption samples indicate that UO22+ forms inner-sphere sorption complexes with carbonate (when present) at [Fe(O,OH) 6] octahedral sites in a bidentate, edge-sharing manner. EXAFS-derived structural parameters were used to constrain the type(s) of U(VI)-bearing surface species and were combined with observed batch sorption trends as input for a diffuse double-layer surface complexation model (SCM). This model successfully predicts U(VI) sorption over a range of U(VI) concentrations, pH values, and solution

  19. [Maintenance treatment with high-dose buprenorphine: are the recommendations being followed?].

    PubMed

    Seyer, D; Dif, C; Balthazard, G; Sciortino, V

    1998-01-01

    Since February 1996, high-dose buprenorphine has been approved for use in the treatment of opioid dependence. In addition, recommendations concerning indications, patient selection, prescribing information and patient delivery have been addressed to doctors and pharmacists. Between its date of approval for use and late 1996, the medical service of French National Health Insurance followed 149 illicit drug users who received high-dose buprenorphine. They all lived in the Vosges 'département' and were affiliated with French Social Security Health Insurance. In general, the recommendations (consultation with a specialist, psychosocial follow-up and dosage schedules) were not followed by prescribing physicians. Concomitant prescriptions with psychotropic drugs, mainly benzodiazepines, were frequently encountered. This raises considerable concern since there have been recent reports of lethal intoxications with high-dose buprenorphine.

  20. High dose of tigecycline for extremely resistant Gram-negative pneumonia: yes, we can

    PubMed Central

    2014-01-01

    Few antimicrobials are currently active to treat infections caused by extremely resistant Gram-negative bacilli (ERGNB), which represent a serious global public health concern. Tigecycline, which covers the majority of these ERGNB (with the exception of Pseudomonas aeruginosa), is not currently approved for hospital-acquired pneumonia, and several meta-analyses have suggested an increased risk of death in patients receiving this antibiotic. Other studies suggest that the use of high-dose tigecycline may represent an alternative in daily practice. De Pascale and colleagues report that the clinical cure rate in patients with ventilator-associated pneumonia is significantly higher with a high dose of tigecycline than with the conventional dose, although mortality was unaffected. This high dose is safe; no patients required discontinuation or dose reduction. PMID:25043402

  1. Influence of early high-dose steroid treatment on Bell's palsy evolution.

    PubMed

    Lagalla, G; Logullo, F; Di Bella, P; Provinciali, L; Ceravolo, M G

    2002-09-01

    The objective of this double-blind, randomized, placebo-controlled study was to test the efficacy of high-dose prednisone, administered as early as possible, in modifying the natural progression of Bell's palsy. Sixty-two consecutive patients, enrolled within 72 hours of facial palsy onset, were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy (group A) or polyvitaminic therapy alone (group B). Clinical grading of facial muscle strength and length of absence from work were evaluated. An early worsening of facial muscle strength was observed in controls, leading to the divergence in the trends of the grading scores in the two groups; this result was not confirmed in the long-term follow-up. Treated patients returned to work earlier than controls. In conclusion, early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell's palsy.

  2. Bone metastasis in breast cancer is treated by high-dose tamoxifen.

    PubMed

    Stathopoulos, George P; Trafalis, Dimitrios; Kaparelou, Maria

    2016-01-01

    Bone metastases in breast cancer are quite common, and some patients may have no other site of metastasis. An effective treatment is often endocrine agents administration (tamoxifen or antiaromatases), given mainly to postmenopausal women. Radiation treatment is also effective, although difficult to perform in cases of extensive skeletal disease. Chemotherapy does not help. The purpose of this study was to investigate the effectiveness of high-dose tamoxifen in female patients with breast cancer and bone metastasis. 28 patients with breast cancer were treated with high-dose tamoxifen. All of them had been pretreated with hormonal therapy including low-dose tamoxifen. The results were extremely positive with clinical amelioration and also disappearance of osteolysis in some patients. Twenty six out of 28 patients responded to the treatment, the criteria being mainly pain reduction and body mobilization (an amelioration which lasted 8 months-4 years). Tamoxifen is efficient when readministered at high dose to breast cancer patient with bone metastasis.

  3. Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer

    PubMed Central

    Schöttle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Siobal, Maike; Florin, Alexandra; Rokitta, Dennis; Hinze, Yvonne; Dietlein, Felix; Plenker, Dennis; König, Katharina; Albus, Kerstin; Heuckmann, Johannes M.; Rauh, Daniel; Franz, Thomas; Neumaier, Bernd; Fuhr, Uwe; Heukamp, Lukas C.; Ullrich, Roland T.

    2015-01-01

    Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy. PMID:26540572

  4. Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer.

    PubMed

    Schöttle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Siobal, Maike; Florin, Alexandra; Rokitta, Dennis; Hinze, Yvonne; Dietlein, Felix; Plenker, Dennis; König, Katharina; Albus, Kerstin; Heuckmann, Johannes M; Rauh, Daniel; Franz, Thomas; Neumaier, Bernd; Fuhr, Uwe; Heukamp, Lukas C; Ullrich, Roland T

    2015-11-17

    Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy.

  5. Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment.

    PubMed

    Fernandez-Bañares, Fernando; Piqueras, Marta; Guagnozzi, Danila; Robles, Virginia; Ruiz-Cerulla, Alexandra; Casanova, María José; Gisbert, Javier P; Busquets, David; Arguedas, Yolanda; Pérez-Aisa, Angeles; Fernández-Salazar, Luis; Lucendo, Alfredo J

    2017-09-01

    Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  6. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy

    PubMed Central

    Wang, Chunyu; Fu, Xiaolong; Cai, Xuwei; Wu, Xianghua; Hu, Xichun; Fan, Min; Xiang, Jiaqing; Zhang, Yawei; Chen, Haiquan; Jiang, Guoliang; Zhao, Kuaile

    2016-01-01

    Nimotuzumab (h-R3) is a humanized monoclonal antibody that is safe to use against epidermal growth factor receptor (EGFR). However, the available information is insufficient about the dose effect of monoclonal antibody against epidermal growth factor receptor for the treatment of esophageal squamous cell carcinoma (ESCC). We retrospectively recruited 66 patients with ESCC who were treated with h-R3 and chemoradiotherapy/radiotherapy. Patients who received more than 1,200 mg of h-R3 were classified as the high-dose group, and the remaining patients were classified as the low-dose group. The endpoint for efficacy was the overall survival. Differences in survival between the groups were analyzed using the log-rank test. The Cox proportional hazards model was used in multivariate analysis to identify independent prognostic factors. The low-dose and high-dose groups comprised 55 and eleven patients, respectively. The median follow-up time in the final analysis was 46 months. The high-dose group showed no increased incidence of toxicities compared to the low-dose group. The 1-, 2-, and 5-year overall survival rates in the low-dose and high-dose groups were 66.9%, 50.0%, 31.5% and 90.0%, 80.0%, 66.7%, respectively (P=0.04). Multivariate analyses showed that the high-dose group had better survival than the low-dose group (hazard ratio 0.28, 95% confidence interval 0.09–0.94, P=0.039). Taken together, high-dose h-R3 showed limited toxicity and improved survival in patients with ESCC. PMID:26766917

  7. 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

  8. [High-dose daidzein affects growth and development of reproductive organs in male rats].

    PubMed

    Jiang, Chun-Xia; Pan, Lian-Jun; Feng, Yao; Xia, Xin-Yi; Huang, Yu-Feng

    2008-04-01

    To explore the effect of the phytoestrogen daidzein on the growth and development of the testis and epididymis in male SD rats. Thirty 10-week old (early adult) and 30 4-week old (pubertal) male SD rats were included in the study, each age group equally divided into 5 subgroups: normal control, positive control, low-dose, medium-dose and high-dose. The normal and positive control groups were given 1 ml distilled water and the same amount of distilled water containing diethylstilbestrol (DES) at the dose of 0.1 mg/kg, and the low-, medium- and high-dose groups administered daidzein in the dose of 2mg/kg, 20 mg/ kg and 100 mg/kg, respectively, all by gavage for 90 days. Observations were made on the changes in body weight and testicular and epididymal indexes, as well as on the structural changes of the testis and epididymis by H&E staining. The early adult rats showed no significant differences in body weight and testicular and epididymal indexes between the claiclzein groups and the control (P > 0.05), nor did the pubertal rats in epididymal index (P > 0.05). The testicular index differed significantly between the high-dose group (3.21 +/- 0.07) and the normal control (3.71 +/- 0.45) (P < 0.05). The body weight reduced markedly in the high-dose group (P < 0.05), but with no significant differences between the normal control and the other two dose groups (P > 0.05). No obvious changes were observed in epididymal morphology in all the daidzein groups of the early adult and pubertal rats, but high-dose daidzein resulted in smaller testes and impaired spermatogenesis. The phytoestrogen daidzein, administered in a high dose, could delay the growth and development of the testis and induce structural changes of testicular tissues in pubertal SD rats.

  9. 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

  10. 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.

  11. 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.

  12. High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study.

    PubMed

    Aguin, Tina; Akins, Robert A; Sobel, Jack D

    2014-05-01

    The purpose of this study was to explore the benefit of high-dose intravaginal metronidazole as a maintenance therapy in reducing recurrence rates of bacterial vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV were treated with metronidazole 750 mg suppository intravaginally daily for 7 days. Those in remission by Amsel criteria received metronidazole 750 mg twice weekly for 3 months with further follow-up for 3 months. High-dose metronidazole intravaginally was associated with rare clinical recurrence during the period of use. After cessation of suppression therapy, recurrence was high.

  13. Mucormycoses: serious complication of high-dose corticosteroid therapy for traumatic optic neuropathy.

    PubMed

    Dojcinovic, I; Richter, M

    2008-04-01

    Mucormycosis is harmless to a healthy person, but can cause opportunistic infections in immunocompromised patients, and once it has invaded internal organs is frequently fatal. Traumatic optic neuropathy is a rare complication of maxillofacial trauma. Management is controversial, and there are no treatment guidelines in the literature. The main methods of treatment of this condition employed today are high-dose corticosteroids and surgical optic nerve decompression, either alone or in combination. In this case, the patient was in good health, but received high-dose corticosteroids for 2 weeks, which temporarily diminished immune response and permitted the development of mucormycosis.

  14. Progressive muscle weakness after high-dose steroids in two children with CIDP.

    PubMed

    Rostasy, Kevin M; Diepold, Katharina; Buckard, Johannes; Brockmann, Knut; Wilken, Bernd; Hanefeld, Folker

    2003-09-01

    Corticosteroids and intravenous immunoglobulins belong to the first line of treatment in chronic inflammatory demyelinating polyneuropathy. In patients with a progressive course, plasma exchange and immunomodulatory drugs are added to the regimen. To reduce the side effects of long-term oral prednisolone, high-dose pulsatile intravenous methylprednisolone treatment has been advocated. We report two children with chronic inflammatory demyelinating polyneuropathy who, after high-dose intravenous pulsatile methylprednisolone, experienced a significant clinical deterioration with profound loss of muscle strength. Both patients improved after changing treatment to immunoglobulins in one and cyclosporine combined with immunoglobulins and oral prednisolone in the other.

  15. High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study.

    PubMed

    Irazuzta, Jose E; Paredes, Fatima; Pavlicich, Viviana; Domínguez, Sara L

    2016-02-01

    To assess the efficacy of a high-dose prolonged magnesium sulfate infusion in patients with severe, noninfectious-mediated asthma. Prospective, randomized, open-label study. Twenty-nine-bed pediatric emergency department located in a children's hospital in Asuncion, Paraguay. All patients of 6-16 years old who failed to improve after 2 hours of standard therapy for asthma. Subjects were randomized to receive magnesium sulfate, 50 mg/kg over 1 hour (bolus) or high-dose prolonged magnesium sulfate infusion of 50 mg/kg/hr for 4 hours (max, 8.000 mg/4 hr). Patients were monitored for cardiorespiratory complications. Asthma severity was assessed via asthma scores and peak expiratory flow rates at 0-2-6 hours. The primary outcome was discharge to home at 24 hours. An analysis of the hospital length of stay and costs was a secondary outcome. Thirty-eight patients were enrolled, 19 in each group. The groups were of similar ages, past medical history of asthma, asthma score, and peak expiratory flow rate. There was a significant difference in the patients discharged at 24 hours: 47% in high-dose prolonged magnesium sulfate infusion (9/19) versus 10% (2/21) in the bolus group (p = 0.032) with an absolute risk reduction 37% (95% CI, 10-63) and a number needed to treat of 2.7 (95% CI, 1.6-9.5) to facilitate a discharge at or before 24 hours. The length of stay was shorter in the high-dose prolonged magnesium sulfate infusion group (mean ± SD in hr: high-dose prolonged magnesium sulfate infusion, 34.13 ± 19.54; bolus, 48.05 ± 18.72; p = 0.013; 95% CI, 1.3-26.5). The cost per patient in the high-dose prolonged magnesium sulfate infusion group was one third lower than the bolus group (mean ± SD: high-dose prolonged magnesium sulfate infusion, $603.16 ± 338.47; bolus, $834.37 ± 306.73; p < 0.016). There were no interventions or discontinuations of magnesium sulfate due to adverse events. The early utilization of high-dose prolonged magnesium sulfate infusion (50 mg/kg/hr/4

  16. High-dose intravenous IgG treatment and renal function.

    PubMed

    Schifferli, J; Leski, M; Favre, H; Imbach, P; Nydegger, U; Davies, K

    1991-02-23

    In an open trial of high dose intravenous IgG (IVIG) treatment in nephrotic patients with glomerulonephritis, the first six patients so far studied showed a transient rise in plasma creatinine. This increase was not associated with any symptoms and the urinary deposit remained unchanged. Two other patients with pre-existing renal impairment but without nephrotic syndrome had a transient and reversible rise in plasma creatinine immediately after IVIG. These observations suggest that high-dose IVIG infusion can produce short-lived disturbances in renal function in patients with kidney diseases.

  17. 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.

  18. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report.

    PubMed

    Herrlinger, Ulrich; Küker, Wilhelm; Uhl, Martin; Blaicher, Hans-Peter; Karnath, Hans-Otto; Kanz, Lothar; Bamberg, Michael; Weller, Michael

    2005-06-01

    The NOA-03 trial explored high-dose methotrexate alone in 37 patients with primary central nervous system lymphoma. The overall median survival was 25 months. After 4 years, the rate of leukoencephalopathy in patients surviving more than 12 months was 58% with and 10% without whole-brain radiotherapy given at relapse (p = 0.11). Attention deficits were found in all six tested patients, and memory deficits in four patients. Two patients had normal, three had moderately restricted, and one had markedly restricted quality of life. Thus, high-dose methotrexate with deferred radiotherapy had only moderate efficacy and was associated with significant neurotoxicity in long-term surviving patients.

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

    PubMed

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

    2006-11-20

    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) x 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 > or =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.

  20. Chlorite dissolution kinetics at pH 3–10 and temperature to 275°C

    DOE PAGES

    Smith, Megan M.; Carroll, Susan A.

    2015-12-02

    Sheet silicates and clays are ubiquitous in geothermal environments. Their dissolution is of interest because this process contributes to scaling reactions along fluid pathways and alteration of fracture surfaces which could affect reservoir permeability. Here, in order to better predict the geochemical impacts on long-term performance of engineered geothermal systems, we have measured chlorite dissolution and developed a generalized kinetic rate law applicable over an expanded range of solution pH and temperature. Chlorite, (Mg,Al,Fe)12(Si,Al)8O20(OH)16, commonly occurs in many geothermal host rocks as either a primary mineral or alteration product.

  1. Kinetics and mechanisms of chlorine dioxide and chlorite oxidations of cysteine and glutathione.

    PubMed

    Ison, Ana; Odeh, Ihab N; Margerum, Dale W

    2006-10-16

    Chlorine dioxide oxidation of cysteine (CSH) is investigated under pseudo-first-order conditions (with excess CSH) in buffered aqueous solutions, p[H+] 2.7-9.5 at 25.0 degrees C. The rates of chlorine dioxide decay are first order in both ClO2 and CSH concentrations and increase rapidly as the pH increases. The proposed mechanism is an electron transfer from CS- to ClO2 (1.03 x 10(8) M(-1) s(-1)) with a subsequent rapid reaction of the CS* radical and a second ClO2 to form a cysteinyl-ClO2 adduct (CSOClO). This highly reactive adduct decays via two pathways. In acidic solutions, it hydrolyzes to give CSO(2)H (sulfinic acid) and HOCl, which in turn rapidly react to form CSO3H (cysteic acid) and Cl-. As the pH increases, the (CSOClO) adduct reacts with CS- by a second pathway to form cystine (CSSC) and chlorite ion (ClO2-). The reaction stoichiometry changes from 6 ClO2:5 CSH at low pH to 2 ClO2:10 CSH at high pH. The ClO2 oxidation of glutathione anion (GS-) is also rapid with a second-order rate constant of 1.40 x 10(8) M(-1) s(-1). The reaction of ClO2 with CSSC is 7 orders of magnitude slower than the corresponding reaction with cysteinyl anion (CS-) at pH 6.7. Chlorite ion reacts with CSH; however, at p[H+] 6.7, the observed rate of this reaction is slower than the ClO2/CSH reaction by 6 orders of magnitude. Chlorite ion oxidizes CSH while being reduced to HOCl, which in turn reacts rapidly with CSH to form Cl-. The reaction products are CSSC and CSO3H with a pH-dependent distribution similar to the ClO2/CSH system.

  2. 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

  3. 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

  4. High Dose Zinc Supplementation Induces Hippocampal Zinc Deficiency and Memory Impairment with Inhibition of BDNF Signaling

    PubMed Central

    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

  5. High-dose vs low-dose oxytocin for labor augmentation: a systematic review.

    PubMed

    Wei, Shu-Qin; Luo, Zhong-Cheng; Qi, Hui-Ping; Xu, Hairong; Fraser, William D

    2010-10-01

    The objective of this systematic review was to estimate the efficacy and safety of high-dose vs low-dose oxytocin for labor augmentation on the risk of cesarean section and on indicators of maternal and neonatal morbidity. We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for randomized clinical trials published until January 2010. Ten randomized clinical trials, including 5423 women, met the inclusion criteria. High-dose oxytocin was associated with a moderate decrease in the risk of cesarean section (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.97), a small increase in spontaneous vaginal delivery (RR, 1.07; 95% CI, 1.02-1.12), and a decrease in labor duration (mean difference: -1.54 hours, 95% CI, -2.44 to -0.64). While hyperstimulation was increased with high-dose oxytocin (RR, 1.91; 95% CI, 1.49-2.45), there was no evidence of an increase in maternal or neonatal morbidity. We conclude that high-dose oxytocin for labor augmentation is associated with a decrease in cesarean section and shortened labor. Copyright © 2010 Mosby, Inc. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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,...

  7. [Relationship between plasma concentrations of valproic acid and hepatotoxicity in patients receiving high doses].

    PubMed

    Ghozzi, H; Hakim, A; Sahnoun, Z; Ben Mahmoud, L; Atheymen, R; Hammami, S; Zeghal, K

    2011-01-01

    Valproic acid (VPA) is an anticonvulsivant drug widely prescribed in the treatment of many forms of generalized epilepsy. In literature, the incidence of liver damage induced by AVP is 0.01%. It is potentialized by the combination therapy (phenobarbital, carbamazepine). Severe hepatotoxicity is rare and appears to be independent of dose and to cause a high mortality. The aim of our study was to evaluate the relationship between plasma concentrations of AVP and the occurrence of side effects especially hepatotoxicity in patients receiving high doses of AVP. In this period, 425 plasmatic AVP monitoring were carried out in our laboratory. From 128 patients treated by high doses of AVP, only 73 were included in this study. Our work showed that adverse effects in epileptics under high doses of AVP was related to the association of the AVP with other antiepileptic in particular carbamazépine, phenobarbital and benzodiazepines rather than supra-therapeutic plasmatic concentrations of AVP. The association of AVP to major antiepileptics (carbamazépine and or phenobarbital) does not seem to generate an increase in the plasmatic concentration of AVP, which was not associated with a greater risque of adverse effects. Consequently, clinical signs of liver toxicity may be present in AVP concentrations generally considered in the therapeutic range especially when used in high doses and or combined with antiepileptic drugs like phenobarbital or carbamazepine. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  8. Enhancement of isodense subdural hematoma on delayed-high-dose contrast computed tomography

    SciTech Connect

    Miller, D.L.; Hinck, V.C.

    1983-02-01

    A case is presented in which bilateral, isodense subdural hematomas, not readily apparent on immediate rapid-high-dose computed tomography, became enhanced and clearly visible on delayed scans. If difficulty is encountered in interpreting the immediate scan of a patient suspected of having isodense subdural hematoma, further scans after a one-hour delay may resolve the dilemma.

  9. [High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].

    PubMed

    Selle, Frédéric; Gligorov, Joseph; Soares, Daniele G; Lotz, Jean-Pierre

    2016-10-01

    The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses.

  10. High-dose re-irradiation following radical radiotherapy for non-small-cell lung cancer.

    PubMed

    De Ruysscher, Dirk; Faivre-Finn, Corinne; Le Pechoux, Cecile; Peeters, Stéphanie; Belderbos, José

    2014-12-01

    As the prognosis of lung cancer patients improves, more patients are at risk of developing local recurrence or a new primary tumour in previously irradiated areas. Technological advances in radiotherapy and imaging have made treatment of patients with high-dose re-irradiation possible, with the aim of long-term disease-free survival and even cure. However, high-dose re-irradiation with overlapping volumes of previously irradiated tissues is not without risks. Late, irreversible, and potentially serious normal tissue damage may occur because of injury to surrounding thoracic structures and organs at risk. In this Review, we aimed to report the efficacy and toxic effects of high-dose re-irradiation for locoregional recurrent non-small-cell lung cancer. Our findings indicate that high-dose re-irradiation might be beneficial in selected patients; however, patients and physicians should be aware of the scarcity of high-quality data when considering this treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-03-01

    In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. 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. 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. Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes.

  12. 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

  13. Effects of high-dose ethanol intoxication and hangover on cognitive flexibility.

    PubMed

    Wolff, Nicole; Gussek, Philipp; Stock, Ann-Kathrin; Beste, Christian

    2016-10-27

    The effects of high-dose ethanol intoxication on cognitive flexibility processes are not well understood, and processes related to hangover after intoxication have remained even more elusive. Similarly, it is unknown in how far the complexity of cognitive flexibility processes is affected by intoxication and hangover effects. We performed a neurophysiological study applying high density electroencephalography (EEG) recording to analyze event-related potentials (ERPs) and perform source localization in a task switching paradigm which varied the complexity of task switching by means of memory demands. The results show that high-dose ethanol intoxication only affects task switching (i.e. cognitive flexibility processes) when memory processes are required to control task switching mechanisms, suggesting that even high doses of ethanol compromise cognitive processes when they are highly demanding. The EEG and source localization data show that these effects unfold by modulating response selection processes in the anterior cingulate cortex. Perceptual and attentional selection processes as well as working memory processes were only unspecifically modulated. In all subprocesses examined, there were no differences between the sober and hangover states, thus suggesting a fast recovery of cognitive flexibility after high-dose ethanol intoxication. We assume that the gamma-aminobutyric acid (GABAergic) system accounts for the observed effects, while they can hardly be explained by the dopaminergic system. © 2016 Society for the Study of Addiction.

  14. 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.

  15. Reversible myoclonus, asterixis, and tremor associated with high dose trimethoprim-sulfamethoxazole: a case report

    PubMed Central

    Foo, Dominic

    2016-01-01

    Case Diagnosis Reversible myoclonus, tremor, and asterixis induced by high dose trimethoprim-sulfamethoxazole. Case Description The patient was a 66-year-old male with T9 AIS1 C quadriplegia secondary to spinal cord compression by a tumor due to large B cell lymphoma. Subsequent to tumor resection and chemotherapy, the patient was discovered to have Pneumocystis jiroveci pneumonia (PJP). Once started on high dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy (15.6 mg/kg/day of trimethoprim) for the treatment of PJP, he displayed bilateral upper extremity myoclonic jerks at rest, asterixis, and postural tremor. Symptoms resolved once TMP-SMX therapy was discontinued. Discussion Myoclonus, asterixis, and tremor have been linked to high dose TMP-SMX therapy as a toxic side effect. Our patient's symptoms did improve with levetiracetam therapy, but did not fully resolve until TMP-SMX was discontinued. Conclusions This is thought to be the first reported case of reversible myoclonus, tremor, and asterixis induced by high dose TMP-SMX in the spinal cord injury population. Early recognition of TMP-SMX induced complications were of key importance as they negatively impacted the rehabilitation process. We also recommend consideration of symptomatic treatment with levetiracetam for the duration of required TMP-SMX therapy as it appeared to mitigate the severity of our patient's movement disorders. PMID:26111222

  16. '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)

  17. Treatment failure of a single high dose of ivermectin for Mansonella perstans filariasis.

    PubMed

    Van den Enden, E; Van Gompel, A; Van der Stuyft, P; Vervoort, T; Van den Ende, J

    1993-01-01

    Infections with Mansonella perstans are common in certain parts of Africa and South America. There is no standard treatment at present. We evaluated the effect of a single high dose of ivermectin (600 micrograms/kg) on microfilaraemia in 7 consecutive patients. No decrease in microfilarial counts could be demonstrated after a follow-up period of 7-56 d.

  18. 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.

  19. 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.

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

    PubMed

    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 (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

  1. 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

  2. The financial impact of increasing home-based high dose haemodialysis and peritoneal dialysis.

    PubMed

    Liu, Frank Xiaoqing; Treharne, Catrin; Culleton, Bruce; Crowe, Lydia; Arici, Murat

    2014-10-02

    Evidence suggests that high dose haemodialysis (HD) may be associated with better health outcomes and even cost savings (if conducted at home) versus conventional in-centre HD (ICHD). Home-based regimens such as peritoneal dialysis (PD) are also associated with significant cost reductions and are more convenient for patients. However, the financial impact of increasing the use of high dose HD at home with an increased tariff is uncertain. A budget impact analysis was performed to investigate the financial impact of increasing the proportion of patients receiving home-based dialysis modalities from the perspective of the England National Health Service (NHS) payer. A Markov model was constructed to investigate the 5 year budget impact of increasing the proportion of dialysis patients receiving home-based dialysis, including both high dose HD at home and PD, under the current reimbursement tariff and a hypothetically increased tariff for home HD (£575/week). Five scenarios were compared with the current England dialysis modality distribution (prevalent patients, 14.1% PD, 82.0% ICHD, 3.9% conventional home HD; incident patients, 22.9% PD, 77.1% ICHD) with all increases coming from the ICHD population. Under the current tariff of £456/week, increasing the proportion of dialysis patients receiving high dose HD at home resulted in a saving of £19.6 million. Conducting high dose HD at home under a hypothetical tariff of £575/week was associated with a budget increase (£19.9 million). The costs of high dose HD at home were totally offset by increasing the usage of PD to 20-25%, generating savings of £40.0 million - £94.5 million over 5 years under the increased tariff. Conversely, having all patients treated in-centre resulted in a £172.6 million increase in dialysis costs over 5 years. This analysis shows that performing high dose HD at home could allow the UK healthcare system to capture the clinical and humanistic benefits associated with this therapy while

  3. High-dose barbiturates for refractory intracranial hypertension in children with severe traumatic brain injury.

    PubMed

    Mellion, Sarah A; Bennett, Kimberly Statler; Ellsworth, German L; Moore, Kevin; Riva-Cambrin, Jay; Metzger, Ryan R; Bratton, Susan L

    2013-03-01

    To evaluate high-dose barbiturates as a second-tier therapy for pediatric refractory intracranial hypertension complicating severe traumatic brain injury. This is a retrospective cohort study of children with refractory intracranial hypertension treated with high-dose barbiturates. A single center level I pediatric trauma from 2001 to 2010. Thirty-six children with refractory intracranial hypertension defined as intracranial pressure greater than 20 mm Hg despite standard management treated with high-dose barbiturates after severe traumatic brain injury. High-dose barbiturates were administered for refractory intracranial hypertension for a minimum duration of 6 hours and monitored by continuous electroencephalography. Exposure was control of refractory intracranial hypertension defined as > 20 mm Hg within 6 hours after starting barbiturates. Pediatric cerebral performance category scores at hospital discharge and at 3 months (or longer) follow-up were the primary outcomes. Ten of 36 patients (28%) had control of refractory intracranial hypertension. Neither demographic nor injury characteristics were associated with refractory intracranial hypertension control. Children who responded received barbiturates significantly later after injury (76 vs. 29 median hours). Overall, 14 children died, 13 without control of intracranial pressure. Survival was more common in those who responded compared with those who did not respond to high-dose barbiturates, although this did not reach statistical significance (relative risk of death 0.2; 95% confidence interval; [0.03-1.3]). Of the 22 survivors, 19 had an acceptable survival (pediatric cerebral performance category less than 3) at 3 months or longer after injury; however, only three returned to normal function. Among survivors, control of refractory intracranial hypertension was associated with significantly better pediatric cerebral performance category scores and over two-fold likelihood of acceptable long-term outcome

  4. High Dose versus Low Dose Intravenous Pantoprazole in Bleeding Peptic Ulcer: A Randomized Clinical Trial

    PubMed Central

    Masjedizadeh, Abdol Rahim; Hajiani, Eskandar; Alavinejad, Pezhman; Hashemi, Seyed Jalal; Shayesteh, Ali Akbar; Jamshidian, Noordin

    2014-01-01

    BACKGROUND The appropriate dose of proton pump inhibitors for treatment of patients with upper (GI) bleeding remains controversial. This study compares high-dose versus low-dose intravenous proton pump inhibitor (PPI) infusion for prevention of GI bleeding complications. METHODS A total of 166 patients with bleeding peptic ulcers underwent therapeutic endoscopy using concomitant therapy by argon plasma coagulation (APC) and diluted epinephrine injection. Patients were randomly divided into two groups: high-dose pantoprazole (80 mg bolus, 8 mg per hour) and low-dose pantoprazole (40 mg bolus, 4 mg per hour) infused for three days. Initial outcomes were rebleeding, need for surgery, hemoglobin drop more than two units, and hospitalization for more than five days. Secondary outcome included mortality rate. RESULTS Overall, 166 patients (83 patients per group) enrolled in the study. The average age of patients in the high-dose group was 59.5±15.6 years and 52.3±13.3 years in the low-dose group (p=0.58). Males comprised 69.7% of patients. In the high-dose group, the mean number of units of transfused blood was 3.3±1.71 and in the low-dose group, it was 2.82±1.73 (p=0.50). There were 36 (43.37%) patients in the high-dose group and 40 (48.19%) in the low-dose group who were hospitalized for more than 5 days (p=0.53). Rebleeding was observed in 27 (32.53%) patients in the high-dose group and in 21 (25.30%) in the low-dose group (p=0.30). There were no significant differences observed in drop in hemoglobin of more than two units (p=0.15), mortality (p=0.99) and surgery (p=0.75) between the two groups. CONCLUSION For controlling peptic ulcer bleeding, there is no difference between high dose and low dose pantoprazole infusion. PMID:25093061

  5. The interaction of sodium chlorite with phospholipids and glutathione: a comparison of effects in vitro, in mammalian and in microbial cells.

    PubMed

    Ingram, Paul R; Homer, Natalie Z M; Smith, Rachel A; Pitt, Andrew R; Wilson, Clive G; Olejnik, Orest; Spickett, Corinne M

    2003-02-01

    In this study the interaction of the preservative sodium chlorite with unsaturated lipids and glutathione was investigated, in comparison with peroxides, sodium hypochlorite, and benzalkonium chloride. The aim was to determine whether the action of sodium chlorite could involve membrane lipid damage or antioxidant depletion, and how this related to toxicity in both mammalian and microbial cells. The treatment of phospholipids with chlorite yielded low levels of hydroperoxides, but sodium chlorite oxidized the thiol-containing antioxidant glutathione to its disulfide form very readily in vitro, with a 1:4 oxidant:GSH stoichiometry. In cultured cells, sodium chlorite also caused a substantial depletion of intracellular glutathione, whereas lipid oxidation was not very prominent. Sodium chlorite had a lower toxicity to ocular mammalian cells than benzalkonium chloride, which could be responsible for the different effects of long-term application in the eye. The fungal cells, which were most resistant to sodium chlorite, maintained higher percentage levels of intracellular glutathione during treatment than the mammalian cells. The results show that sodium chlorite can cause oxidative stress in cells, and suggest that cell damage is more likely to be due to interaction with thiol compounds than with cell membrane lipids. The study also provides important information about the differential resistance of ocular cells and microbes to various preservatives and oxidants.

  6. Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice.

    PubMed

    Campbell, Elizabeth J; Vissers, Margreet C M; Wohlrab, Christina; Hicks, Kevin O; Strother, R Matthew; Bozonet, Stephanie M; Robinson, Bridget A; Dachs, Gabi U

    2016-10-01

    Despite recent evidence for an anti-tumour role for high-dose ascorbate, potential mechanisms of action are still unclear. At mM concentrations that are achieved with high-dose intravenous administration, autoxidation of ascorbate can generate cytotoxic levels of H2O2. Ascorbate is also a required co-factor for the hydroxylases that suppress the transcription factor hypoxia-inducible factor (HIF-1). HIF-1 supports an aggressive tumour phenotype and is associated with poor prognosis, and previous studies have shown that optimizing intracellular ascorbate levels down-regulates HIF-1 activation. In this study we have simultaneously measured ascorbate concentrations and the HIF-1 pathway activity in tumour tissue following high dose ascorbate administration, and have studied tumour growth and physiology. Gulo(-/-) mice, a model of the human ascorbate dependency condition, were implanted with syngeneic Lewis lung tumours, 1g/kg ascorbate was administered into the peritoneum, and ascorbate concentrations were monitored in plasma, liver and tumours. Ascorbate levels peaked within 30min, and although plasma and liver ascorbate returned to baseline within 16h, tumour levels remained elevated for 48h, possibly reflecting increased stability in the hypoxic tumour environment. The expression of HIF-1 and its target proteins was down-regulated with tumour ascorbate uptake. Elevated tumour ascorbate levels could be maintained with daily administration, and HIF-1 and vascular endothelial growth factor protein levels were reduced in these conditions. Increased tumour ascorbate was associated with slowed tumour growth, reduced tumour microvessel density and decreased hypoxia. Alternate day administration of ascorbate resulted in lower tumour levels and did not consistently decrease HIF-1 pathway activity. Levels of sodium-dependent vitamin C transporters 1 and 2 were not clearly associated with ascorbate accumulation by murine tumour cells in vitro or in vivo. Our results support

  7. Influence of polyvinylpyrrolidone, microcrystalline cellulose and colloidal silicon dioxide on technological characteristics of a high-dose Petiveria alliacea tablet.

    PubMed

    García-Pérez, Martha-Estrella; Lemus-Rodríguez, Zoe; Hung-Arbelo, Mario; Vistel-Vigo, Marlen

    2017-08-03

    Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub used by its immunomodulatory, anticancerogenic and anti-inflammatory properties. This study determined the influence of polyvinylpyrrolidone (PVP), colloidal silicon dioxide (CSD) and microcrystalline cellulose (MC) on the technological characteristic of a high-dose P. alliacea tablet prepared by the wet granulation method. The botanical and pharmacognostic analysis of the plant material was firstly performed, followed by a 2(3) factorial design considering three factors at two levels: (a) the binder (PVP) incorporated in formulation at 10% and 15% (w/w); (b) the compacting agent (CSD) added at 10% and 15% (w/w) and; (c) the diluent (MC) included at 7.33% and 12.46% (w/w). The analysis of pharmaceutical performance and the accelerated and long-term stability of the best prototype were also completed. The binder, compacting agent and the interaction binder/diluent had a significant impact on breaking force of high-dose P. alliacea tablet. The optimum formula was found to contain 15% (w/w) of CSD, 7.33% (w/w) of MC and 10% (w/w) of PVP. At these conditions, the tablet shows a breaking force of 77.96 N, a friability of 0.39%, a total phenol content of 1.30 mg/tablet and a maximum disintegration time of 6 min. The use of adequate amounts of PVP, MC and CSD as per the factorial design allowed the preparation of a tablet suitable for administration, despite the inappropriate flow and compressibility properties of the P. alliacea powder.

  8. 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.

  9. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

    PubMed Central

    Shah, Jan Muhammad; Qureshi, Toufique Ahmed; Shah, Tahmina; Shah, Qurban Ali; Arain, Muhammad Asif; Bhutto, Zohaib Ahmed; Saeed, Muhammad; Siyal, Farman Ali

    2016-01-01

    Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex) with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w.) and high doses (40 and 60 mg) of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and bilirubin on all timings, and increased (p<0.05) the serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate-pyruvate transaminase (SGPT) levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg) significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01) increased at all timing points. Creatinine values were altered (p<0.01, <0.05) in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05) for 72 h and 60 mg persisted same effect (p<0.01) up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05) at all timings. The bilirubin indexes also (p<0.05) elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin. PMID:27847425

  10. High-dose anti-histamine use and risk factors in children with urticaria

    PubMed Central

    Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

    2016-01-01

    Aim The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. Material and Methods The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. Results The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p<0.0001). There was no difference between the two groups in terms of blood eosinophil and basophil counts, and serum total IgE levels (p>0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=−0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03–1.15]) and basopenia (OR: 6.77; CI 95%: [2.01–22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. Conclusion The requirement of high-dose H1-antihistamines was higher with children’s increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines. PMID:28123332

  11. 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. © 2014 Wiley Publishing Asia Pty Ltd.

  12. Challenging the clinical relevance of folinic acid over rescue after high dose methotrexate (HDMTX).

    PubMed

    Cohen, Ian J

    2013-11-01

    The use of adequate folinic acid rescue (in clinically relevant doses) after high dose methotrexate will prevent neurotoxicity without reducing treatment results. A literature search was performed to test the hypothesis that no evidence for the existence of folinic acid over-rescue of high-dose methotrexate (MTX) in clinically relevant situations exists (evidence that too much folinic acid reduced cure rate). Examples of folinic acid over-rescue after lower doses of MTX were found and has been cited as evidence of over rescue of high dose MTX. Mega doses of folinic acid, used when toxic levels of MTX occurred, also could neutralize the MTX effect. Data were found to support the contention that higher levels of MTX require disproportionally higher folinic acid doses for rescue. Careful examination of the available studies after HDMTX yielded more convincing alternative explanations for reduction in cure rate than over rescue. Little convincing evidence for the existence of over rescue after HDMTX was found. The rescue of high-dose MTX with an appropriate dose of folinic acid that can prevent toxicity, especially neurotoxicity, was not shown to reduce the therapeutic effect. No evidence was found that higher doses of folinic acid after high dose MTX reduces the therapeutic effect. Acceptance of the hypothesis can prevent harm being caused (especially brain damage) by reversing the trend of dose reduction in FA rescue. The recognition that the use of higher folinic acid doses is safe, can prevent neurotoxicity, and does not reduce prognosis has important implications for the development of effective non toxic treatment protocols. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Effects of low and high doses of fosinopril on the structure and function of resistance arteries.

    PubMed

    Rizzoni, D; Castellano, M; Porteri, E; Bettoni, G; Muiesan, M L; Cinelli, A; Rosei, E A

    1995-07-01

    It has been suggested that angiotensin-converting enzyme inhibitors may induce a significant regression of cardiovascular hypertrophy not only through blood pressure reduction but also as a possible consequence of growth factor inhibition. The aim of this study was to evaluate the effects of the angiotensin-converting enzyme inhibitor fosinopril, given either at a hypotensive high dose or a nonhypotensive low dose, on structural and functional alterations of mesenteric resistance arteries and on cardiac mass in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats. Fosinopril was administered in the drinking water from 6 to 12 weeks of age. Rats were killed at 12 weeks, and the ratio of heart weight to body weight was measured. Mesenteric arterioles were dissected and mounted on a micromyograph (Mulvany's technique). Vascular morphology (media-lumen ratio, media thickness) and endothelial function (response to acetylcholine) were then assessed. During the 6 weeks of treatment, systolic pressure in SHR treated with high-dose fosinopril was significantly lower compared with that in untreated SHR, whereas no difference was observed with low-dose fosinopril. In SHR treated with both high-dose and low-dose fosinopril, a statistically significant reduction of vascular structural alterations, in terms of both media-lumen ratio and media thickness, was observed. The ratio of heart weight to body weight was reduced only in SHR treated with high-dose fosinopril. An improvement in the endothelium-dependent relaxation to acetylcholine was observed in SHR treated with high-dose fosinopril compared with untreated SHR, whereas in SHR treated with low-dose fosinopril no improvement in endothelial function was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Tolerance to 3,4-Methylenedioxymethamphetamine (MDMA) in Rats Exposed to Single High-Dose Binges

    PubMed Central

    Baumann, Michael H.; Clark, Robert D.; Franken, Frederick H.; Rutter, John J.; Rothman, Richard B.

    2008-01-01

    3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) stimulates the transporter-mediated release of monoamines, including serotonin (5-HT). High-dose exposure to MDMA causes persistent 5-HT deficits (e.g., depletion of brain 5-HT) in animals, yet the functional and clinical relevance of such deficits are poorly defined. Here we examine functional consequences of MDMA-induced 5-HT depletions in rats. Male rats received binges of 3 ip injections of MDMA or saline, one injection every 2 h; MDMA was given at a threshold pharmacological dose (1.5 mg/kg × 3, low dose) or at a 5-fold higher amount (7.5 mg/kg × 3, high dose). One week later, jugular catheters and intracerebral guide cannulae were implanted. Two weeks after binges, rats received acute iv challenge injections of 1 and 3 mg/kg MDMA. Neuroendocrine effects evoked by iv MDMA (prolactin and corticosterone secretion) were assessed via serial blood sampling, while neurochemical effects (5-HT and dopamine release) were assessed via microdialysis in brain. MDMA binges elevated core temperatures only in the high-dose group, with these same rats exhibiting ~50% loss of forebrain 5-HT two weeks later. Prior exposure to MDMA did not alter baseline plasma hormones or dialysate monoamines, and effects of iv MDMA were similar in saline and low-dose groups. By contrast, rats pretreated with high-dose MDMA displayed significant reductions in evoked hormone secretion and 5-HT release when challenged with iv MDMA. As tolerance developed only in rats exposed to high-dose binges, hyperthermia and 5-HT depletion are implicated in this phenomenon. Our results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation. PMID:18313226

  15. Low and high dose UVB regulation of transcription factor NF-E2-related factor 2.

    PubMed

    Kannan, Sankaranarayanan; Jaiswal, Anil K

    2006-09-01

    Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant response element (ARE)-mediated expression and coordinated induction of chemoprotective proteins in response to chemical stress. In this report, we investigated Nrf2 response to low and high dose UVB irradiation. Low dose (7.5 J/m(2)) UVB exposure of mouse hepatoma, mouse keratinocyte, and human skin fibroblast cells led to the nuclear accumulation of Nrf2 and up-regulation of ARE-mediated gene expression. On the contrary, and intriguingly, high dose (20 J/m(2)) UVB exposure of cells led to the nuclear exclusion of Nrf2 and down-regulation of chemoprotective gene expression with possible implications in UVB carcinogenesis. We investigated the mechanism by which high dose UVB induced the nuclear exclusion of Nrf2. Prior treatment with nuclear export inhibitor, leptomycin B, abrogated the UVB-induced nuclear exclusion of Nrf2, indicating that the decrease of Nrf2 in the nucleus was due to the nuclear export of Nrf2. High dose UVB increased the phosphorylation of Nrf2Y568 which stimulated the nuclear export of Nrf2. Mutation of Nrf2Y568 to phenylalanine and src kinase inhibitor PP2 abrogated/reduced the UVB-induced phosphorylation of Nrf2Y568 and nuclear exclusion of Nrf2. Transfection with src family member Fyn small interfering RNA resulted in the nuclear accumulation of Nrf2 and an increase in the expression and UVB induction of ARE-mediated gene expression. UVB exposure also induced the nuclear localization of Fyn. These results suggest that high dose UVB induced the activation/nuclear localization of Fyn which led to increased phosphorylation of Nrf2Y568 and enhanced nuclear export of Nrf2. This resulted in nuclear exclusion of Nrf2 and down-regulation of ARE-mediated chemoprotective gene expression.

  16. High Dose Vitamin B1 Reduces Proliferation in Cancer Cell Lines Analogous to Dichloroacetate

    PubMed Central

    Hanberry, Bradley S.; Berger, Ryan; Zastre, Jason A.

    2014-01-01

    Purpose The dichotomous effect of thiamine supplementation on cancer cell growth is characterized by growth stimulation at low doses and growth suppression at high doses. Unfortunately, how thiamine reduces cancer cell proliferation is currently unknown. Recent focuses on metabolic targets for cancer therapy have exploited the altered regulation of the thiamine-dependent enzyme pyruvate dehydrogenase (PDH). Cancer cells inactivate PDH through phosphorylation by overexpression of pyruvate dehydrogenase kinases (PDKs). Inhibition of PDKs by dichloracetate (DCA) exhibits a growth suppressive effect in many cancers. Recently it has been shown that the thiamine co-enzyme, thiamine pyrophosphate reduces PDK mediated phosphorylation of PDH. Therefore, the objective of this study was to determine if high dose thiamine supplementation reduces cell proliferation through a DCA like mechanism. Methods Cytotoxicity of thiamine and DCA were assessed in SK-N-BE and Panc-1 cancer cell lines. Comparative effects of high dose thiamine and DCA on PDH phosphorylation were measured by Western blot. The metabolic impact of PDH reactivation was determined by glucose and lactate assays. Changes in the mitochondrial membrane potential, ROS production, and caspase-3 activation were assessed to characterize the mechanism of action. Results Thiamine exhibited a lower IC50 value in both cell lines compared to DCA. Both thiamine and DCA reduced the extent of PDH phosphorylation, reduced glucose consumption, lactate production, and mitochondrial membrane potential. High dose thiamine and DCA did not increase ROS but increased caspase-3 activity. Conclusion Our findings suggest that high dose thiamine reduces cancer cell proliferation by a mechanism similar to that described for dichloroacetate. PMID:24452394

  17. 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.

  18. 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.

  19. Enhanced bactericidal action of acidified sodium chlorite caused by the saturation of reactants.

    PubMed

    Kim, N H; Park, T H; Rhee, M S

    2014-06-01

    Factors affecting the antibacterial action of acidified sodium chlorite (ASC), a widely used disinfectant, have not been determined. This study investigated the significant factors suggesting efficient production method to maximize bactericidal action of ASC. The effects of (i) preparation procedures (total three methods); (ii) initial concentrations of reactants: sodium chlorite (SC) and citric acid (CTA) (up to maximum solubility of each reactant) and (iii) final pH values (3·0 and 2·5) to the bactericidal action of ASC were investigated with a fixed final concentration of SC (10 ppm) using various foodborne pathogens (Escherichia coli O157:H7, Listeria monocytogenes, Salmonella Typhimurium and Staphylococcus aureus). The antimicrobial compounds produced and the bactericidal effects depended on the preparation procedure and the initial concentrations of the reactants. The ASC prepared by premixing highly concentrated reactants (in particular > 40%) followed by dilution (dilution after reaction, DAR) was more effective in inactivating foodborne pathogens, and it produced higher antimicrobial compound (Cl(2) and ClO(2)) yields than the other procedures. A 5-min treatment with ASC, produced using the other procedures, resulted in a reduction of < 3·5 log CFU ml(-1) (Gram positive = 0·18-0·78; Gram negative = 0·03-3·49 log CFU ml(-1)), whereas ASC produced with the DAR procedure using the saturated reactants completely inactivated all of the test pathogens within 5 min without recovery (initial concentration = 6·94-7·08 log CFU ml(-1)). The ASC production with the DAR procedure using the saturated reactants maximizes both the antimicrobial compound yields and bactericidal effects of the ASC solutions. This study will contribute to increase the efficiency of ASC treatments for disinfections reducing the effective SC concentrations for industrial use. © 2014 The Society for Applied Microbiology.

  20. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Effects of postchill application of acidified sodium chlorite to control Campylobacter spp. and Escherichia coli on commercial broiler carcasses.

    PubMed

    Oyarzabal, Omar A; Hawk, Christopher; Bilgili, Sacit F; Warf, C Cayce; Kemp, G Kere

    2004-10-01

    Experiments were performed to assess the reduction of Campylobacter spp. and Escherichia coli in commercial broiler carcasses by postchill dip applications of acidified sodium chlorite. Carcass rinses were collected before the inside-outside-bird washer (IOBW), post-IOBW, postchill, and after the postchill application of acidified sodium chlorite. Prevalence and counts of Campylobacter spp. and E. coli were determined. The mean values for Campylobacter spp. and E. coli counts differed significantly at sampling sites. The IOBW reduced the bacterial counts significantly in only one experiment. The chiller reduced Campylobacter counts significantly in both experiments but failed to significantly reduce the counts of E. coli in one experiment. No major reduction in the prevalence after enrichment for Campylobacter spp. was detected post-IOBW or postchill. However, a significant reduction in Campylobacter spp. and in E. coli counts and Campylobacter spp. prevalence was seen after the postchill application of acidified sodium chlorite. These results demonstrate that the antimicrobial effect of acidified sodium chlorite applied postchill may be used to significantly reduce Campylobacter spp. and E. coli in commercial broiler carcasses. Postchill systems may eventually be used in different applications, such as mist, spray, or bath, which could be applied closer to the final stages in processing.

  3. Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin.

    PubMed

    Reinl, Erin L; Goodwin, Zane A; Raghuraman, Nandini; Lee, Grace Y; Jo, Erin Y; Gezahegn, Beakal M; Pillai, Meghan K; Cahill, Alison G; de Guzman Strong, Cristina; England, Sarah K

    2017-08-01

    Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ(2) tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value < .05 was considered statistically significant. The high-dose-requiring women had greater rates of obesity and diabetes and were more likely to have undergone labor induction and required prostaglandins. High-dose-requiring women were more likely to undergo cesarean delivery for first-stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P

  4. Clinical effect of preoperative high-dose atorvastatin against no-reflow after PCI

    PubMed Central

    Liu, Wenbo; Zou, Zhipeng; Jiang, Haipeng; Li, Qiang; Guo, Fangming; Wang, Zhen; Zhu, Hongguang

    2017-01-01

    The aim of the present study was to evaluate the use of preoperative high-dose atorvastatin to prevent the no-reflow phenomenon after percutaneous coronary intervention (PCI). A total of 138 patients with ST-segment elevation myocardial infarction, admitted from March 2014 to January 2015, were enrolled and randomly divided into 3 groups of 46 individuals each. The groups included a control group in which patients were not treated with atorvastatin before PCI; a conventional-dose atorvastatin treatment group in which patients received a single dose of 20 mg at bedtime one day prior to PCI; and a high-dose atorvastatin treatment group in which patients were treated with 40 mg divided in two doses the day before PCI. The treatment effects were assessed by re-examining the echocardiography, high-sensitivity C-reactive protein and brain natriuretic peptide (BNP) levels after the PCI. The follow-up examinations included determinations of ultrasound imaging indicators and the contact with patients was maintained for a whole year. The CTFC (frame), pro-BNP, CK-MB peak and WMSI levels of the patients in the high-dose treatment group were significantly lower than those in the conventional dose or the control group. Trombolysis in myocardial infarction ≤2 and myocardial blush grade ≤1 levels were significantly lower than those in the conventional dose group (P=0.01) or those in the control group (P=0.01), although the echocardiographic indicators of the three groups were not significantly different (P<0.05). Nevertheless, it was found that there were significantly fewer adverse cardiovascular events in the high-dose group (P<0.05 in both cases). During the follow-up period, thromboembolism and restenosis were most infrequent in the high-dose atorvastatin group. Based on our findings the oral administration of high-dose atorvastatin before bedtime, one day before the procedure, can effectively prevent no-reflow cases, reduce adverse events and improve the long

  5. When is high-dose intravenous iron repletion needed? Assessing new treatment options

    PubMed Central

    Gozzard, David

    2011-01-01

    High doses of intravenous iron have a role in the treatment of a number of clinical situations associated with iron deficiency, iron deficiency anemia, and blood loss. In the presence of functioning erythropoiesis, iron supplementation alone may be adequate to replenish iron stores and restore blood loss. Where hormone replacement with an erythropoiesis-stimulating agent is required, iron adequacy will optimize treatment. Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. The literature indicates that high doses of iron are required, with levels of 1500 mg in nondialysis-dependent chronic kidney disease and up to 3600 mg in inflammatory bowel disease. New formulations of intravenous iron have recently been introduced that allow clinicians to administer high doses of iron in a single administration. Ferumoxytol is available in the US, has a maximum dose of 510 mg iron in a single administration, but is limited to use in chronic kidney disease. Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indications. The latest introduction is iron isomaltoside 1000. Again, a test dose is not required, and it can be delivered rapidly as an infusion (in an hour), allowing even higher doses of iron to be administered in a single infusion, ie, 20 mg/kg body weight with no ceiling. This will allow clinicians to

  6. High-dose insulin: a consecutive case series in toxin-induced cardiogenic shock.

    PubMed

    Holger, Joel S; Stellpflug, Samuel J; Cole, Jon B; Harris, Carson R; Engebretsen, Kristin M

    2011-08-01

    Cardiovascular medication overdoses can be difficult to treat. Various treatment modalities are currently recommended. To describe patient outcomes and adverse events of high-dose insulin therapy in consecutive overdose patients in cardiogenic shock after implementation of a high-dose insulin protocol (1-10 U/kg/h, while avoiding or tapering off vasopressors). This is an observational consecutive case series of patients identified from a registry. Data were collected by retrospective chart review of patients treated by our toxicology service with this protocol from February 2007 until March 2010. Twelve patients were treated with high-dose insulin. The mean age was 36.5 years (SD 11.7). Seven patients had pre-existing vasopressor therapy, and all were tapered off vasopressors while on insulin. Two patients experienced pulseless electrical activity cardiac arrest prior to high-dose insulin therapy. Intravenous fat emulsion was given to two patients. The mean maximum insulin infusion rate was 8.35 U/kg/h (mean = 8.35, SD 6.34). The mean duration of insulin infusion was 23.5 h (SD 19.7). The mean duration of glucose infusion post-insulin was 25.2 h (SD 17.7). The primary toxins were β-blocker in five, calcium channel blocker in two, combined β-blocker/calcium channel blocker in two, tricyclic antidepressant in one, and polydrug in 2. CLINICAL OUTCOMES: Eleven of 12 patients survived. One patient expired 9 h into insulin therapy from cardiac arrest shortly after the insulin was stopped and a vasopressor re-initiated (protocol deviation). Six patients experienced a total of 19 hypoglycemic events. Hypokalemia (defined as < 3.0 mEq/L) developed in eight patients. ADVERSE SEQUELAE: Necrotic digits occurred in one patient with known clotting disorder after receiving high-dose norepinephrine and INR reversal with fresh frozen plasma prior to insulin therapy. One patient was discharged with mild anoxic injury thought due to pulseless electrical activity arrest prior to

  7. High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis.

    PubMed

    Gopal, Ajay K; Gooley, Theodore A; Maloney, David G; Petersdorf, Stephen H; Eary, Janet F; Rajendran, Joseph G; Bush, Sharon A; Durack, Lawrence D; Golden, Jane; Martin, Paul J; Matthews, Dana C; Appelbaum, Frederick R; Bernstein, Irwin D; Press, Oliver W

    2003-10-01

    We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P =.03) and elevated international prognostic score (41% versus 19%, P =.02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P =.02; adjusted HR, 0.3, P =.004) and progression-free survival (PFS) (unadjusted HR =.6 [95% C.I., 0.3-1.0], P =.06; adjusted HR, 0.5, P =.03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be.076 at 8 years in the HD-RIT group and.086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL.

  8. High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

    PubMed Central

    Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Smith, Dori A.; Yancey, Linda J.; Crump, Michael; Stadtmauer, Edward A.; Biron, Pierre; Crown, John P.; Schmid, Peter; Lotz, Jean-Pierre; Rosti, Giovanni; Bregni, Marco; Demirer, Taner

    2011-01-01

    Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

  9. Vitamin D insufficiency underlies unexpected hypocalcemia following high dose glucocorticoid therapy.

    PubMed

    Kinoshita, Yuka; Masuoka, Kazuhiro; Miyakoshi, Shigesaburo; Taniguchi, Shuichi; Takeuchi, Yasuhiro

    2008-01-01

    Vitamin D insufficiency is a reemerging and common health problem for skeletal system. Pharmacological application of glucocorticoid inhibits intestinal calcium absorption and stimulates tubular calcium excretion, thus induces severely negative calcium balance. We report a patient presenting symptomatic hypocalcemia following high dose glucocorticoid administration. After a pulse-therapy with methylprednisolone, hypocalcemia with muscle cramp developed in association with hypercalciuria and secondary hyperparathyroidism in the absence of hypomagnesemia. Circulating level of 1,25-dihydroxyvitamin D was in a reference range, while that of 25-hydroxyvitamin D was insufficient. Treatment with alfacalcidol of 1 mug/day promptly improved serum calcium level within a couple of weeks. Vitamin D insufficiency could be a serious problem in patients with high dose glucocorticoid therapy.

  10. HIGH-DOSE BIOTIN TREATMENT FOR SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS MAY INTERFERE WITH THYROID ASSAYS

    PubMed Central

    Minkovsky, Alissa; Lee, Mark N.; Dowlatshahi, Mitra; Angell, Trevor E.; Mahrokhian, Lilian S.; Petrides, Athena K.; Melanson, Stacy E.F.; Marqusee, Ellen; Woodmansee, Whitney W.

    2016-01-01

    Objective To review cases and increase awareness in clinicians treating patients who may be taking biotin. Methods We describe the presentation and workup of a woman with secondary progressive multiple sclerosis on high dose biotin with laboratory studies suggestive of thyrotoxicosis. Results Plasma samples showed laboratory evidence of elevated thyroid hormone levels with elevated free thyroxine >7.8 ng/dl (reference interval (RI) 0.9-1.7 ng/dl) and decreased thyroid stimulating hormone <0.02 uIU/ml (RI 0.50-5.70 uIU/ml). Laboratory values normalized when biotin was withheld prior to repeat testing. Conclusions Our case report demonstrates that ingestion of high dose biotin in multiple sclerosis patients can cause interference with laboratory assessment of thyroid function. This interference causes laboratory values suggestive of thyrotoxicosis and can lead to unnecessary evaluation. Clinicians should be aware of the risk of laboratory interference in this patient demographic. PMID:27917400

  11. HIGH-DOSE BIOTIN TREATMENT FOR SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS MAY INTERFERE WITH THYROID ASSAYS.

    PubMed

    Minkovsky, Alissa; Lee, Mark N; Dowlatshahi, Mitra; Angell, Trevor E; Mahrokhian, Lilian S; Petrides, Athena K; Melanson, Stacy E F; Marqusee, Ellen; Woodmansee, Whitney W

    2016-01-01

    To review cases and increase awareness in clinicians treating patients who may be taking biotin. We describe the presentation and workup of a woman with secondary progressive multiple sclerosis on high dose biotin with laboratory studies suggestive of thyrotoxicosis. Plasma samples showed laboratory evidence of elevated thyroid hormone levels with elevated free thyroxine >7.8 ng/dl (reference interval (RI) 0.9-1.7 ng/dl) and decreased thyroid stimulating hormone <0.02 uIU/ml (RI 0.50-5.70 uIU/ml). Laboratory values normalized when biotin was withheld prior to repeat testing. Our case report demonstrates that ingestion of high dose biotin in multiple sclerosis patients can cause interference with laboratory assessment of thyroid function. This interference causes laboratory values suggestive of thyrotoxicosis and can lead to unnecessary evaluation. Clinicians should be aware of the risk of laboratory interference in this patient demographic.

  12. 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.

  13. High-dose MR in the evaluation of brain metastases: Will increased detection decrease costs?

    SciTech Connect

    Black, W.C. |

    1994-06-01

    Brain metastases occur in about 25% of patients with cancer and are often diagnosed within the first year after the diagnosis of the primary tumor. The treatment of patients with brain metastases usually depends on whether they are solitary or multiple. Surgical resection has been shown to prolong survival by 6 months and improve the quality of life in patients with solitary brain metastases. However, surgery is not usually considered appropriate for patients with multiple brain metastases. A phase III multicenter trial in this issue demonstrates that the sensitivity of magnetic resonance (MR) in the detection of brain metastases can be increased by increasing the dose of contrast. In this trial comparing high-dose (0.3 mmol/kg) with standard-dose (0.1 mmol/kg) gadolinium, 50% more lesions were detected on the high-dose examinations. 15 refs., 1 tab.

  14. High dose eicosapentaenoic acid ethyl ester: effects on lipids and neutrophil leukotriene production in normal volunteers.

    PubMed Central

    Hawthorne, A B; Filipowicz, B L; Edwards, T J; Hawkey, C J

    1990-01-01

    1. A 93% pure ethyl ester of eicosapentaenoic acid was investigated for tolerability and biochemical effects on neutrophil leukotriene synthesis and plasma lipoproteins when given in high dose. Six healthy volunteers received 6 g eicosapentaenoic acid ethyl ester daily for 6 weeks, followed by a 4 week wash-out and then 18 g daily for 6 weeks. 2. There was inhibition of neutrophil leukotriene B4 and 5-hydroxyeicosatetraenoic acid synthesis, with no significant differences between low and high dose. 3. There was a dose dependent increase in leukotriene B5 and 5-hydroxyeicosatetraenoic acid acid synthesis. 4. Plasma triglycerides were reduced maximally on 6 g daily, with no greater suppression at 18 g daily. 5. Plasma cholesterol was only suppressed significantly at 18 g daily. 6. The 6 g daily dose was well tolerated but the 18 g daily dose produced diarrhoea and steatorrhoea. PMID:2169832

  15. The ASTEROID trial: coronary plaque regression with high-dose statin therapy.

    PubMed

    Chhatriwalla, Adnan K; Nicholls, Stephen J; Nissen, Steven E

    2006-11-01

    A Study To Evaluate the effect of Rosuvastatin On Intravascular ultrasound-Derived coronary atheroma burden (ASTEROID) investigated the impact of high-dose rosuvastatin therapy on the rate of atheroma progression in patients with coronary artery disease. Serial intravascular ultrasound (IVUS) was performed in 349 patients at baseline and following 24 months of therapy with rosuvastatin 40 mg/day. Rosuvastatin therapy lowered low-density lipoprotein cholesterol to 60.8 mg/dl and raised high-density lipoprotein cholesterol by 14.7%. This was associated with a significant reduction in all IVUS measures of atheroma burden. These results suggest that intensive modification of lipid levels with high-dose statin therapy can promote atheroma regression. Further studies will be required to determine whether this benefit is associated with a reduction in clinical events.

  16. High-dose radiation-induced meningiomas following acute lymphoblastic leukemia in children.

    PubMed

    Salvati, M; Cervoni, L; Artico, M

    1996-05-01

    The authors review three personal cases of patients who developed cerebral meningiomas following high-dose radiotherapy for acute lymphoblastic leukemia. Two patients were female and one male. Their ages when the leukemia appeared were between 11 and 15 years. All patients were treated with a course of prophylactic irradiation to the neuraxis for a total dose of 24 Gy. After an average interval of 10.4 years, all three patients presented a meningioma; histologically, one was meningothelial and two were fibrous. All three meningiomas presented atypical features. At follow-up 1, 4, and 4 years respectively after surgery, none of these patients presents neurological deficits or neuroradiological signs of recurrence. Forty-nine cases of high-dose radiation-induced meningioma are also reviewed.

  17. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery.

    PubMed

    Kirkpatrick, John P; Meyer, Jeffrey J; Marks, Lawrence B

    2008-10-01

    The linear-quadratic (LQ) model is widely used to model the effect of total dose and dose per fraction in conventionally fractionated radiotherapy. Much of the data used to generate the model are obtained in vitro at doses well below those used in radiosurgery. Clinically, the LQ model often underestimates tumor control observed at radiosurgical doses. The underlying mechanisms implied by the LQ model do not reflect the vascular and stromal damage produced at the high doses per fraction encountered in radiosurgery and ignore the impact of radioresistant subpopulations of cells. The appropriate modeling of both tumor control and normal tissue toxicity in radiosurgery requires the application of emerging understanding of molecular-, cellular-, and tissue-level effects of high-dose/fraction-ionizing radiation and the role of cancer stem cells.

  18. Fulminant myocarditis owing to high-dose interleukin-2 therapy for metastatic melanoma

    PubMed Central

    Thavendiranathan, P; Verhaert, D; Kendra, K L; Raman, S V

    2011-01-01

    High-dose interleukin-2 (IL-2) therapy may cause acute myocarditis characterised by diffuse myocardial involvement and occasionally fulminant heart failure. Cardiac MRI (CMRI) provides a comprehensive assessment of myocardial function, inflammation and injury in a single examination and has shown value in the diagnosis of myocarditis. We report a case of a 54-year-old male with metastatic melanoma who developed acute severe myocarditis with fulminant heart failure after high-dose IL-2 therapy. CMRI using a combination of T2 weighted imaging and T1 weighted late post-gadolinium enhancement techniques played a key role in establishing the diagnosis. To our knowledge we present the first case report of the combined use of T1 and T2 weighted CMRI techniques to diagnose IL-2 induced myocarditis. PMID:21511746

  19. High dose of prokinetics for refractory hiccups after chemotherapy or the return to a simple drug

    PubMed Central

    Uña, Esther; Alonso, Pilar

    2013-01-01

    Hiccups in patients with cancer might be difficult to treat, impacting negatively on the quality of life. Many therapies are available, but they are usually started empirically, and often they are unsuccessful. We report a case of a man with metastatic colon cancer who after the first cycle of chemotherapy developed persistent hiccups refractory to neuroleptics and low dose of metoclopramide. After searching for the potential cause, a high dose of prokinetics was initiated in the hospital and his symptoms disappeared. This case shows how searching for potential causes helps start the right treatment immediately, and therefore it is relevant for the prompt relief from this bothersome symptom. So far, no cases reporting high doses of prokinetics to treat persistent hiccups after chemotherapy have been published. This option should be taken into account when developing hiccups and gastro-oesophageal reflux after chemotherapy, especially if low doses of prokinetics have already been tried. PMID:24169870

  20. Effect of high-dose intravenous eletriptan on coronary artery diameter.

    PubMed

    Goldstein, J A; Massey, K D; Kirby, S; Gibson, M; Hettiarachchi, J; Rankin, A J; Jackson, N C

    2004-07-01

    The goal of this study was to evaluate the coronary vasoconstrictive effects of high doses of eletriptan compared with a standard dose of sumatriptan. Patients with no clinically significant coronary artery disease were randomized to receive high-dose intravenous eletriptan (n = 24) vs a standard dose of sumatriptan (n = 18; 6 mg subcutaneously) vs placebo (n = 18). Serial angiograms were obtained. The primary non-inferiority analysis found equivalence between the mean maximum change in left anterior descending coronary artery diameter for eletriptan, -22%[95% confidence interval (CI) -26, -19], and sumatriptan, -19% (95% CI -22, -16). The change due to placebo was -16% (95% CI -20, -12). No individual cases of clinically significant vasoconstriction were observed. The results confirm that eletriptan has a broad cardiovascular safety margin, with plasma concentrations comparable to three to five times the Cmax of an oral 80-mg dose associated with modest vasoconstriction equivalent to standard therapeutic doses of sumatriptan.

  1. Advances in the vaccination of the elderly against influenza: role of a high-dose vaccine.

    PubMed

    Sullivan, Seth J; Jacobson, Robert; Poland, Gregory A

    2010-10-01

    On 23 December 2009, the US FDA approved Fluzone® High Dose, a high-dose formulation of the trivalent inactivated influenza vaccine, for prevention of influenza in people 65 years of age and older. As it was approved via an accelerated process designed to allow expeditious availability of safe and effective products with promise to treat or prevent serious or life-threatening diseases, the manufacturer is required to conduct further studies to demonstrate effectiveness. Although these studies are underway, a recently completed randomized, controlled trial demonstrated that this vaccine, containing four-times more hemagglutinin than standard-dose inactivated influenza vaccines, can produce an enhanced immunologic response in subjects of 65 years of age and older, while maintaining a favorable safety profile. This article introduces the vaccine, presents currently available safety and immunogenicity data, discusses current recommendations for use, and proposes what we can expect in the coming years.

  2. [High-dose magnesium sulfate in the treatment of aconite poisoning].

    PubMed

    Clara, A; Rauch, S; Überbacher, C A; Felgenhauer, N; Drüge, G

    2015-05-01

    This article reports the case of a 62-year-old male patient who ingested the roots of Monkshood (Aconitum napellus) and white hellebore (Veratrum album) dissolved in alcohol with a suicidal intention and suffered cardiotoxic and neurotoxic symptoms. After contacting the Poison Information Centre ventricular arrhythmia was treated with high-dose magnesium sulphate as the only antiarrhythmic agent and subsequently a stable sinus rhythm could be established after approximately 3 h. Aconitum napellus is considered the most poisonous plant in Europe and it is found in gardens, the Alps and the Highlands. Poisoning is mainly caused by the alkaloid aconite that leads to persistent opening and activation of voltage-dependent sodium channels resulting in severe cardiac and neurological toxicity. As no specific antidote is known so far, poisoning is associated with a high mortality. The therapy with high-dose magnesium sulphate is based on in vitro and animal experiments as well as limited clinical case reports.

  3. 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.

  4. 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.

  5. [A case of primary erythromelalgia successfully treated with high-dose intravenous immunoglobulin therapy].

    PubMed

    Kuroda, Takeshi; Sugimoto, Azusa; Ishigaki, Seiichirou; Murakami, Hidetomo; Kawamura, Mitsuru

    2014-02-01

    Erythromelalgia is a rare condition characterized by constant or paroxysmal burning pain, erythema, and the elevation of skin temperature in the extremities. Recently, the impairment of C-fiber function due to autoimmune system involvement is considered as the primary cause of erythromelalgia. However, a successful treatment has yet not been established. We report a case of a 39-year-old woman with primary erythromelalgia accompanied by high cerebrospinal fluid protein concentration and axonal neuropathy. She received various antiepileptic and anti-inflammatory drugs, but failed to improve. She finally underwent high-dose intravenous immunoglobulin therapy, which dramatically improved her symptoms and normalized cerebrospinal fluid protein concentration. This result demonstrates the effectiveness of high-dose intravenous immunoglobulin therapy for the treatment of primary erythromelalgia and the possibility of autoimmune system involvement.

  6. A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy.

    PubMed

    Rivard, Mark J; Melhus, Christopher S; Zinkin, Heather D; Stapleford, Liza J; Evans, Krista E; Wazer, David E; Odlozilíková, Anna

    2005-09-01

    While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.

  7. Outcomes of Patients with Alcohol Withdrawal Syndrome Treated with High-Dose Sedatives and Deferred Intubation.

    PubMed

    Stewart, Robert; Perez, Ricardo; Musial, Bogdan; Lukens, Carrie; Adjepong, Yaw Amoateng; Manthous, Constantine A

    2016-02-01

    High doses of sedating drugs are often used to manage critically ill patients with alcohol withdrawal syndrome. To describe outcomes and risks for pneumonia and endotracheal intubation in patients with alcohol withdrawal syndrome treated with high-dose intravenous sedatives and deferred endotracheal intubation. Observational cohort study of consecutive patients treated in the intensive care unit (ICU) of a university-affiliated, community hospital for alcohol withdrawal syndrome, where patients were not routinely intubated to receive high-dose or continuously infused sedating medications. We studied 188 patients hospitalized with alcohol withdrawal syndrome from 2008 through 2012 at one medical center. The mean age (SD) of the subjects was 50.8 ± 9.0 years and their mean ICU admission APACHE (Acute Physiology and Chronic Health Evaluation) II score was 6.2 ± 3.4. Thirty subjects (16%) developed pneumonia, and 38 (20.2%) required intubation. All of the 188 patients received lorazepam (median total dose, 42.5 mg), and 170 of 188 received midazolam, all but 2 by continuous intravenous infusion (median total dose, 527 mg; all administered in ICU); 19 received propofol (median total dose, 6,000 mg); and 19 received dexmedetomidine (median total dose, 1,075 mg). Intubated patients received substantially more benzodiazepine (median total dose, 761 mg of lorazepam equivalent vs. 229 mg for subjects in the nonintubated group; P < 0.0001). Endotracheal intubation was associated with pneumonia and higher acuity of illness (APACHE II score, >10). Intubated patients had a longer duration of hospital stay (median, 15 d vs. 6 d; P ≤ 0.0001). One patient did not survive hospitalization. In this single-center, observational study, where endotracheal intubation was deferred until aspiration or cardiopulmonary decompensation, treatment of alcohol withdrawal syndrome with high-dose, continuously infused sedating medications was not associated with excess morbidity

  8. Changes in choroidal thickness after systemic administration of high-dose corticosteroids: a pilot study.

    PubMed

    Han, Jeong Mo; Hwang, Jeong-Min; Kim, Ji Soo; Park, Kyu Hyung; Woo, Se Joon

    2014-01-21

    To characterize the effects of corticosteroids on choroidal thickness, we measured the choroid thickness in patients treated systemically with a high-dose corticosteroid. A prospective, pilot study was conducted on 20 patients who required high-dose corticosteroid pulse therapy (>500 mg/d). Choroidal thickness was measured at baseline, 1 day, 1 week, and 1 month after corticosteroid administration. Blood pressure was measured four times a day for the first 5 days of steroid treatment. This study ultimately included 35 eyes from 18 patients. Each patient was treated with high-dose corticosteroid therapy at a concentration of 19.5 ± 4.1 mg per kg body weight for 5.2 ± 1.1 days. Mean subfoveal choroidal thickness at baseline was 259.8 μm (range, 86.4-394.7 μm). Choroidal thickness showed no significant change at 1 day, 1 week, or 1 month after corticosteroid administration (P = 0.197). Mean systolic blood pressure increased by 13 mmHg (P = 0.008), but diastolic pressure did not change (P = 0.117). One patient (5.6%) who had presented with pigment epithelial detatchment (PED) and thick choroid (381.1 μm) developed bilateral focal subretinal fluid during the study and showed central serous chorioretinopathy (CSC) with a 13.1% increase in subfoveal choroidal thickness. No consistent changes in choroidal thickness were observed after systemic high-dose corticosteroid treatment, but one patient with PED and thick choroid showed an increase in choroidal thickening as well as features of CSC. Thus, steroid-induced CSC may be an idiosyncratic response in selected vulnerable individuals rather than a dose-dependent effect.

  9. Acute high dose lithium-induced exacerbation of obsessive compulsive symptoms.

    PubMed

    Umesh, Shreekantiah; Sinha, Vinod Kumar

    2014-05-01

    Obsessive compulsive disorder (OCD) is a chronic neuropsychiatric disorder whose pathophysiology is linked to serotonergic dysfunction. More recently, the role of glutamate has also been posited. Lithium is used as an adjunctive for the treatment of OCD which is found to enhance serotonergic transmission. We present a case of OCD who was on stable dose of sertraline developed exacerbation of obsessive compulsive symptoms with acute high dose of lithium but improved after dose reduction.

  10. Acute High Dose Lithium-Induced Exacerbation of Obsessive Compulsive Symptoms

    PubMed Central

    Umesh, Shreekantiah; Sinha, Vinod Kumar

    2014-01-01

    Obsessive compulsive disorder (OCD) is a chronic neuropsychiatric disorder whose pathophysiology is linked to serotonergic dysfunction. More recently, the role of glutamate has also been posited. Lithium is used as an adjunctive for the treatment of OCD which is found to enhance serotonergic transmission. We present a case of OCD who was on stable dose of sertraline developed exacerbation of obsessive compulsive symptoms with acute high dose of lithium but improved after dose reduction. PMID:25253935

  11. Necrosis and Apoptosis in Hepatocellular Carcinoma Following Low-Dose Versus High-Dose Preoperative Chemoembolization

    SciTech Connect

    Lu Wei Li Yanhao He Xiaofeng; Zhao Jianbo; Chen Yong; Mei Quelin

    2008-11-15

    Our purpose was to study necrosis and apoptosis of hepatocellular carcinoma (HCC) cells after preoperative transcatheter arterial chemoembolization (TACE) with use of low-dose and high-dose anticancer drugs in HCCs. Fifty-four patients with advanced but surgically resectable HCC were studied. Thirty-four patients who elected to undergo preoperative superselective TACE were randomized to low- and high-dose TACE. Patients in group A (n = 16) received low-dose anticancer drugs: 2 mg mitomycin C (MMC), 10 mg epirubicin (EPI), and 100 mg carboplatin (CBP). Patients in group B (n = 18) were given high doses of anticancer drugs (10 mg MMC, 40 mg EPI, and 300 mg CBP). Hepatic resection was subsequently performed. Group C comprised 20 patients who underwent resection without TACE. In all patients the necrosis rates and apoptosis index of tumor cells were evaluated by pathologic examinations and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay. There was no significant difference between group A and group B in tumor response (p > 0.05) after TACE. Necrosis rates in groups A, B, and C were 88.4 {+-} 11.1%, 87.1 {+-} 12.5%, and 7.3 {+-} 3.5%, respectively. There was no significant difference between group A and group B (p > 0.05), while statistical difference was found between group A and group C (p < 0.001) and between group B and group C (p < 0.001). Apoptosis indexes in the three groups were 11.0 {+-} 4.0%, 10.7 {+-} 3.9%, and 5.6 {+-} 2.6%, respectively. Statistical difference exhibited between group A and group C (p < 0.001) and group B versus group C (p < 0.001). No significant difference was observed between group A and group B (p > 0.05). In conclusion, superselective TACE with low- and high-dose chemotherapeutic agents induced similar degrees of cellular apoptosis and necrosis.

  12. 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.

  13. Ultrastructural changes in the parenchymal liver cells of rats treated with high doses of rifampicin.

    PubMed Central

    Piriou, A.; Maissiat, R.; Jacqueson, A.; Warnet, J. M.; Claude, J. R.

    1987-01-01

    Ultrastructural study of hepatic parenchyma was carried out in female Wistar rats after they had received high doses (400 mg X kg-1) of rifampicin for 1, 2, 4, 6 and 8 days. Morphological changes in the endoplasmic reticulum, Golgi apparatus and mitochondria were observed as early as day 1 of intoxication. These changes corroborate the biochemical data available regarding RFP-induced fatty liver. Images Fig. 1 Fig. 2 Fig. 3 & 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:3580280

  14. On line high dose static position monitoring by ionization chamber detector for industrial gamma irradiators.

    PubMed

    Rodrigues, Ary A; Vieira, Jose M; Hamada, Margarida M

    2010-01-01

    A 1 cm(3) cylindrical ionization chamber was developed to measure high doses on line during the sample irradiation in static position, in a (60)Co industrial plant. The developed ionization chamber showed to be suitable for use as a dosimeter on line. A good linearity of the detector was found between the dose and the accumulated charge, independently of the different dose rates caused by absorbing materials.

  15. Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose.

    PubMed

    Hill, Catherine L; March, Lynette M; Aitken, Dawn; Lester, Susan E; Battersby, Ruth; Hynes, Kristen; Fedorova, Tanya; Proudman, Susanna M; James, Michael; Cleland, Leslie G; Jones, Graeme

    2016-01-01

    To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis (OA). A randomised, double-blind, multicentre trial enrolled 202 patients with knee OA and regular knee pain. They were randomised 1:1 to high-dose fish oil (4.5 g omega-3 fatty acids) 15 mL/day or (2) low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 mL/day. The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score. Although there was improvement in both groups, the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group, whereas between-group differences at 1 year did not reach statistical significance. There was no difference between the two groups in cartilage volume loss at 2 years. For other secondary endpoints, there was no difference between the two groups at 2 years. In people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation. Australian New Zealand Clinical Trials Registry (ACTRN 12607000415404). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Effects of high-dose phytoestrogens on circulating cellular microparticles and coagulation function in postmenopausal women.

    PubMed

    Cheng, Wern-Cherng; Lo, Shyi-Chyi; Tsai, Keh-Sung; Tu, Shih-Te; Wu, Jin-Shan; Chang, Ching-I; Chen, Chi-Ling; Shaw, Ning-Sing; Peng, Hui-Yu; Wang, Shu-Yi; Wu, Chih-Hsing; Jan, I-Shaw; Hsu, Ssu-Chun; Liu, Chao-Wei; Lee, Li-Na; Tai, Tong-Yuan

    2015-08-01

    Estrogen in hormone replacement therapy causes homeostatic changes. However, little is known regarding the safety of high-dose phytoestrogen on coagulation and hematological parameters in healthy postmenopausal women. This study evaluated the effects of high-dose soy isoflavone (300 mg/day) on blood pressure, hematological parameters, and coagulation functions including circulating microparticles in healthy postmenopausal women. The original study is a 2-year prospective, double-blind, placebo-controlled study. In total, 431 postmenopausal women (from 3 medical centers) were randomly assigned to receive either high-dose isoflavone or placebo for 2 years. At baseline, 6 months, 1 year, and 2 years after treatment, blood pressure, body weight, liver function tests, hematological parameters, and lipid profiles were measured. The 1(st) year blood specimens of 85 cases of 144 eligible participants (from one of the three centers) were analyzed as D-dimer, von Willebrand factor antigen, factor VII, plasminogen activator inhibitor type 1, and circulating cellular microparticles, including the measurement of monocyte, platelet, and endothelial microparticles. In the isoflavone group, after 1 year, the changes in liver function tests, hematological parameters, and coagulation tests were not different from those of the control. Triglyceride levels were significantly lower after 6 months of isoflavone treatment than the placebo group, but the difference did not persist after 1 year. Endothelial microparticles increased steadily in both groups during the 1-year period but the trend was not affected by treatment. The results of the present study indicate that high-dose isoflavone treatment (300 mg/day) does not cause hematological abnormalities or activate coagulation factors. Copyright © 2013. Published by Elsevier B.V.

  17. Implementation and Evaluation 
of a High-Dose Cytarabine Neurologic Assessment Tool.

    PubMed

    Szoch, Stephanie; Snow Kaiser, Karen

    2015-06-01

    Patients receiving high-dose cytarabine as part of their chemotherapy regimen have a chance of experiencing neurotoxicities. Prompt identification of signs and symptoms can greatly reduce the chance of patients sustaining permanent neurologic damage. This article describes the development and successful implementation of an evidence-based, standardized neurologic assessment and documentation tool that was evaluated using a clinical utility questionnaire and an adherence audit.

  18. Hyperglycemia related to high-dose glucocorticoid use in noncritically ill patients

    PubMed Central

    2013-01-01

    Background Glucocorticoids commonly cause drug-induced diabetes. This association is well recognized but available evidence does not answer clinically relevant issues in subjects without diabetes. Methods Thirty-five individuals without diabetes with a recent diagnosis of acute lymphoblastic leukemia or non-Hodgkin’s lymphoma on high-dose glucocorticoid therapy were studied. Close systematic monitoring of fasting and postprandial glycemia and fasting insulin determinations, HOMA-insulin resistance and HOMA β-cell function were performed. The primary objective was to define the incidence of secondary diabetes in patients treated with high-dose glucocorticoids. Secondary objectives were to specify the intensity, the moment it appears and the evolution of hyperglycemia, in addition to the risk factors, mechanisms and impact of continuous and cyclical glucocorticoids on the development of hyperglycemia. Results Mean age of patients was 38.4 ± 18.7 years. The incidence of diabetes was 40.6% and was found after the first week; half the time it occurred between the second and fourth. Two-thirds spontaneously normalized by eight weeks. Continuous glucocorticoid administration had a higher incidence of fasting hyperglycemia (P = 0.003). Mean peak insulin levels were significantly higher in cases of diabetes. Conclusions High-dose prednisone for 2 to 3 months produced an elevated incidence of diabetes, usually with mild hyperglycemia occurring between the second and fourth week, normalizing spontaneously in all cases. Hyperglycemia was more frequent with continuous doses and occurred in cases with increased insulin resistance. The clinical and therapeutic characteristics of our participants, who were otherwise healthy, could represent the clinical setting of many patients with illness from other medical areas that might require high doses of GC for six to twelve weeks. PMID:23557386

  19. Screening for adult attention deficit/hyperactivity disorder in high-dose benzodiazepine dependent patients.

    PubMed

    Tamburin, Stefano; Federico, Angela; Morbioli, Laura; Faccini, Marco; Casari, Rebecca; Zamboni, Lorenzo; Briguglio, Giuseppe; Lugoboni, Fabio

    2017-09-01

    Adult attention-deficit/hyperactivity disorder (ADHD) is frequent in patients with substance use disorders (SUD), but information on its prevalence in high-dose benzodiazepine (BZD) dependence is lacking. We estimated the prevalence of adult ADHD in a group of treatment-seeking high-dose BZD dependent patients according to a valid screening tool, and explored the demographic and clinical characteristics of patients that screened positive for ADHD (ADHD+) in comparison to those that screened negative (ADHD-). We prospectively recruited 167 consecutive patients with high-dose BZD dependence and screened them for adult ADHD with the World Health Organization Adult ADHD Self-Report Scale version 1.1 (ASRS-v1.1) Symptom Checklist Part A. We compared demographic and clinical characteristics in ADHD+ and ADHD- groups. Fifty-three patients (31.7% of the sample) were positive to adult ADHD screening. ADHD+ patients showed a significantly larger prevalence of poly-drug abuse than ADHD- ones. BZD formulation and active principle significantly differed between the two groups. The other clinical variables, including psychiatric comorbidity, as well as the demographic ones, did not differ in ADHD+ versus ADHD- comparison. Adult ADHD may be common in treatment-seeking high-dose BZD dependent patients according to ASRS-v1.1 Symptom Checklist Part A. Screening for ADHD in this type of SUD with this questionnaire is quick and may offer useful information for prognosis and treatment. (Am J Addict 2017;26:610-614). © 2017 American Academy of Addiction Psychiatry.

  20. 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

  1. Effects of long term low- and high-dose sodium arsenite exposure in human transitional cells

    PubMed Central

    He, Jianming; Wang, Feng; Luo, Fen; Chen, Xuedan; Liang, Xi; Jiang, Wenbin; Huang, Zhizhong; Lei, Jiafan; Shan, Fabo; Xu, Xueqing

    2017-01-01

    Epidemiological studies have revealed the association between increased risk of bladder cancer and chronic arsenic exposure. Here, we explored biological effects of arsenic in T24. Microarray analysis was applied to analyze mRNA in T24 following 0, 2 or 5 μM sodium arsenite (As) exposure for 72 hours. Long term (up to 140 days) low-dose (200 nM) and high-dose (1,000 nM) As decreased E-cadherin protein level through different mechanisms because the mRNA levels of E-cadherin increased following low-dose As exposure but decreased following high-dose As exposure. Long term As increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Low-dose As exposure resulted in a change in the morphology of T24 cells from an epithelial to a mesenchymal-like appearance. Knockdown of E-cadherin increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Cell proliferation and growth of T24 with or without As exposure for 100 days were assayed using EdU and WST, respectively. Low-dose As exposure increased cell proliferation and growth while high-dose As exposure decreased both. Long term As activated p53 on account of increasing protein levels of p53, p-p53 (Ser15), and mRNA levels of p21. These demonstrate that arsenic exposure exerts multiple effects. Long term low- or high-dose arsenic induces epithelial-mesenchymal transition, likely via downregulation of E-cadherin, activates p53, and differently affects cell proliferation/growth. PMID:28337271

  2. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients.

    PubMed

    Albacker, Turki; Carvalho, George; Schricker, Thomas; Lachapelle, Kevin

    2008-07-01

    Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that is implicated in the pathogenesis of several postoperative complications. Studies have shown that proinflammatory cytokines are increased by acute hyperglycemia. Recent evidence suggests that insulin has antiinflammatory properties. Therefore, we hypothesized that high-dose insulin therapy would attenuate the systemic inflammatory response to cardiopulmonary bypass and surgery in coronary artery bypass patients while maintaining normoglycemia. A total of 52 patients who presented for elective coronary artery bypass were randomized to receive intraoperative intravenous insulin infusion, titrated to maintain blood glucose concentrations less than 180 mg/dL (group I, n = 25), or receive intraoperative fixed high dose of intravenous insulin infusion (5 mU/kg/min) with dextrose 20% infused separately to maintain a blood glucose level between 70 and 110 mg/dL (group II, n = 27). Blood samples were collected at different time points to determine tumor necrosis factor alpha (TNFalpha), interleukin 6 and 8 (IL6 and IL8), and complement factor 3 and 4 (C3 and C4). Patients in both groups had similar preoperative characteristics. Patients in the high-dose insulin group had higher blood insulin concentrations and tighter blood glucose control. There were lower levels of IL6 (150 pg/dL vs 245 pg/dL, p = 0.03), IL-8 (49 pg/dL vs 74 pg/dL, p = 0.05), and TNFalpha (2.2 pg/dL vs 3.0 pg/dL, p = 0.04) in group II in the early postoperative period. High-dose insulin therapy blunts the early postoperative surge in inflammatory response to CPB as reflected by decreased levels of IL6, IL8, and TNFalpha.

  3. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

    DTIC Science & Technology

    2011-06-01

    requirements depending on rectal and bladder doses. The class solution in inverse planned HDR prostate brachythe - rapy for dose escalation of a DIL...High-dose-rate brachyther- apy without external beam irradiation for locally advanced prostate cancer. Radiother Oncol 2006; 80: 62-68. 7. Galalae RM... prostate brachytherapy for dose escalation of DIL defined by combined MRI/MRSI. Radiother Oncol 2008; 88: 148-155. 16. Pouliot J, Kim Y, Lessard E et al

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

    PubMed

    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.

  5. 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.

  6. 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.

  7. 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

  8. Maculopapular skin rashes associated with high-dose chemotherapy: prevalence and risk factors.

    PubMed

    Wright, Lynette G

    2006-11-27

    To determine the prevalence of and risk factors for maculopapular skin rashes associated with high-dose chemotherapy. Observational pilot study. A bone marrow transplant hematology-oncology unit in a private city hospital. Data were collected on 14 patients who developed maculopapular rashes out of 127 patients who received high-dose chemotherapy (purposive sampling). Observation of the distribution and nature of skin rashes in relation to chemotherapy, disease, adjuvant medications, and white blood cell counts. Diseases, chemotherapy protocols and doses, adjuvant medications, and blood counts. Skin reactions ranged from mild, scattered macular or maculopapular rashes to severe rashes. Patients newly diagnosed with acute myelogenous leukemia (AML) who received induction protocols containing cytarabine had the most rashes, affecting 6 of 11 patients (55%). No rashes were observed on patients treated with the protocol that included high-dose corticosteroids. Patients rarely had recurrence of the rash with further courses of chemotherapy. Cytarabine doses higher than 700 mg/m2 may be a cause of maculopapular skin rashes. Patients most at risk were those newly diagnosed with AML who received induction therapy. Corticosteroids may prevent the development of skin rashes. No useful nursing strategy exists to prevent, lessen the intensity of, or shorten the course of a delayed hypersensitivity rash. Knowing which patients are most at risk is useful to enable close monitoring and patient and staff education.

  9. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids

    PubMed Central

    Gorlin, Andrew W; Rosenfeld, David M; Maloney, Jillian; Wie, Christopher S; McGarvey, Johnathan; Trentman, Terrence L

    2016-01-01

    The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted. PMID:27703394

  10. Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

    PubMed

    da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

    2015-10-01

    The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline.

  11. Polybutadiene and Styrene-Butadiene rubbers for high-dose dosimetry

    SciTech Connect

    Oliveira, Lucas N.; Vieira, Silvio L.; Schimidt, Fernando; Antonio, Patricia L.; Caldas, Linda V.E.

    2015-07-01

    Polybutadiene and Styrene-Butadiene are synthetical rubbers used widely for pneumatic tires manufacturing. In this research, the dosimeter characteristics of those rubbers were studied for application in high-dose dosimetry. The rubber samples were irradiated with doses of 10 Gy up to 10 kGy, using a {sup 60}Co Gamma Cell-220 system (dose rate of 1.089 kGy/h) and their readings were taken on a Fourier Transform Infrared Spectroscopy-FTIR system (model Frontier/Perkin Elmer). The ratios of two absorbance peaks were taken for each kind of rubber spectrum, Polybutadiene (1306/1130 cm{sup -1}) and Styrene-Butadiene (1449/1306 cm{sup -1}). The ratio calculated was used as the response to the irradiation, and is not uniform across the sample. From the results, it can be concluded for both rubbers: a) the dose-response curves may be useful for high-dose dosimetry (greater than 250 Gy); b) their response for reproducibility presented standard deviations lower than 2.5%; c) the relative sensitivity was higher for Styrene-Butadiene (1.86 kGy{sup -1}) than for Polybutadiene (1.81 kGy{sup -1}), d) for doses of 10 kGy to 200 kGy, there was no variation in the dosimetric response. Both types of rubber samples showed usefulness as high-dose dosimeters. (authors)

  12. A fatal outcome in a patient with glioblastoma multiforme after receiving high-dose methotrexate.

    PubMed

    Price, Samantha; Harless, William; Rikhye, Somi; Altaha, Ramin

    2008-03-01

    The most common adult primary brain tumor is glioblastoma multiforme (GBM). Current treatment is surgical resection, adjuvant radiation and chemotherapy, which can extend the median survival 20-36 weeks (Mansky et al. Central nervous system tumors. In Abraham J, Allegra CJ, Gulley J, eds. Bethesda Handbook of clinical oncology, 2nd edn. Philadelphia, Pennsylvania: Lippincott Williams and Wilkins, 2000: 440-2; Knox S. Intracranial tumors. In Pillot G, Chantler M, Magiera H, Peles S, et al., eds. The Washington Manual Hematology and Oncology Subspecialty Consult. Philadelphia, Pennsylvania: Lippincott Williams and Wilkins, 2004: 204-6.). But treatment efficacy is limited, mandating the exploration of more effective treatments. We report on a patient with GBM treated as per a clinical protocol with high-dose methotrexate (12 g/m(2)), who expired within hours after the initiation of treatment secondary to transtentorial herniation. Although it is not completely clear what caused the patient's herniation, we think that high-dose methotrexate therapy may have played a crucial role. We suggest that high-dose methotrexate should be used cautiously in patients with GBM.

  13. The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients.

    PubMed

    Awadzi, K; Attah, S K; Addy, E T; Opoku, N O; Quartey, B T

    1999-01-01

    Ivermectin, at the standard dose of 150 micrograms/kg bodyweight, does not kill the adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilarial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by an equivalent, single, high dose. One hundred men participated in a double-blind placebo-controlled trial and received increasing doses of ivermectin from 150 micrograms/kg to 1600 micrograms/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 micrograms/kg were not significantly more effective than 150 micrograms/kg. Moreover, they did not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, at comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that repeated high-dose regimens are unlikely to be more effective than a similar number of 150 micrograms/kg doses. This deficiency of ivermectin requires that the search for macrofilaricides remains a top priority.

  14. Effect of high-dose vocal fold injection of cidofovir and bevacizumab in a porcine model.

    PubMed

    Ahmed, Mostafa M; Connor, Matthew P; Palazzolo, Mitzi; Thompson, Michelle E; Lospinoso, Josh; O'Connor, Peter; Howard, N Scott; Maturo, Stephen C

    2017-03-01

    Perform a follow-up study to investigate the histologic impact of high-dose intralaryngeal cidofovir injections in porcine vocal cords, either alone or in combination with bevacizumab, and compared to saline controls. This was an in vivo study involving 24 pigs with blinded pathologist review of specimens. Six groups were created, with four subjects in each group. Each subject received 10 or 20 mg of either cidofovir or bevacizumab alone, or in combination, injected into the right vocal cord. The left vocal fold was used as a saline control. Three separate injections were made at 2-week intervals. Larynges were harvested at 8 and 12 weeks, stained with hematoxylin and eosin and trichrome stain, and reviewed for histologic changes by two blinded pathologists. Minimal inflammation, edema, and atypia were noted with all treatments. Increased glandular inflammation was noted with 10 mg bevacizumab (P < 0.05), which decreased when combined with 10 mg cidofovir (P < 0.05). No lamina propria or muscle fibrosis was observed. Drug duration had no statistically significant histologic impact. High-dose cidofovir and bevacizumab do not induce detrimental vocal fold changes. Combination cidofovir and bevacizumab do not cause vocal fold scarring. Further work is needed to assess systemic concentration with this high-dose combination in humans. N/A. Laryngoscope, 127:671-675, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  15. High dose anakinra for treatment of severe neonatal Kawasaki disease: a case report

    PubMed Central

    2014-01-01

    We report an 11-week-old female who presented with Kawasaki disease (KD) complicated by macrophage activation syndrome (MAS). The infant presented to the hospital with persistent fever, cough, diarrhea, and emesis, among other symptoms. Her condition quickly began to decompensate, and she developed classic features (conjunctivitis, rash, cracked lips, distal extremity edema) prompting a diagnosis of acute KD. The patient was treated with standard therapy for KD including three doses of intravenous immunoglobulin (IVIG), aspirin, and high dose glucocorticoids with no change in her condition. Due to a high suspicion for MAS, high dose anakinra therapy was initiated resulting in dramatic clinical improvements. She also received one dose of infliximab for concern for coronary artery changes, and over the course of several months, anakinra and high dose glucocorticoids were tapered. Nearly complete reversal of echocardiogram changes were observed after 8 months, and the infant is now off all immunosuppressive therapy. In this case report, we briefly review the importance of early recognition of MAS in pediatric patient populations with rheumatic diseases, and we suggest early initiation of anakinra therapy as a rapid and effective treatment option. PMID:25045337

  16. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids.

    PubMed

    Gorlin, Andrew W; Rosenfeld, David M; Maloney, Jillian; Wie, Christopher S; McGarvey, Johnathan; Trentman, Terrence L

    2016-01-01

    The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted.

  17. High-dose oral acyclovir in acute herpes zoster ophthalmicus: the end of the corticosteroid era.

    PubMed

    Herbort, C P; Buechi, E R; Piguet, B; Zografos, L; Fitting, P

    1991-01-01

    Systemic acyclovir (ACV), a new potent anti-herpes drug, was shown to reduce effectively the morbidity in the acute phase of herpes zoster ophthalmicus (AHZO). Using high dose oral ACV (5 X 800 mg/day) our aim in this study was: (1) to compare disease profiles in the ACV-treated group and in a group of zoster patients having had no ACV, analysed retrospectively; (2) to establish if high-dose ACV was able to prevent severe long term complications of AHZO; and (3) to determine the present role of corticosteroids in AHZO. From 1984 to 1988, 48 patients with AHZO of less than 3 days' duration were included. All patients received at least 7 days of oral ACV (5 X 800 mg/d) associated with topical ACV. Steroids were not given unless severe uveitis occurred. Follow-up was 2 years in 43 patients and 1 year in all 48 patients. Main conclusions from our study are: 1. Ocular involvement occurred in 67% of ACV-treated cases, a rate comparable to our retrospective group (59%) and to the literature (71%). However the rate of severe long term complications was minimal (4%) when compared to our non-treated retrospective group (21%). 2. Steroid treatment was not necessary in any of the ACV-treated patients. 3. ACV was well tolerated and did not have to be discontinued in any of the patients. High dose ACV and avoidance of steroids seems to eliminate the severe complications of AHZO.

  18. 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.

  19. 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

  20. High dose cyclophosphamide performs better than monthly dose cyclophosphamide in quality of life measures.

    PubMed

    Dussán, K B; Magder, L; Brodsky, R A; Jones, R J; Petri, M

    2008-12-01

    In spite of current therapies, the overall health status of patients with SLE is poor. High-dose cyclophosphamide (50 mg/kg for 4 days) with or without stem-cell rescue has been introduced as a new therapy for severe SLE, including renal and central nervous system (CNS)-SLE. Long-term durable responses have been found to be 40%. A randomised clinical trial was completed comparing high-dose cyclophosphamide with monthly intravenous cyclophosphamide (750 mg/m squared bovine serum albumin) in patients with SLE who need cyclophosphamide for the first time. The primary outcome of the trial was complete clinical response. In this report, we compare the treatment groups with respect to quality of life. The patients in this study had a mean age of 35.3 +/- 10.1 years, were of Caucasian (35%), African-American (51%), Hispanic (8%) and Asian (6%) people, and 88% were women. The organ leading to treatment was renal lupus in 29%, CNS-lupus in 45% and other organs in 26%. Quality of life was measured at each visit using the Medical Outcome Study Short-Form 36 (SF-36). At 6 months, the patients in the high-dose cyclophosphamide trial arm had significantly greater improvement than patients in the monthly intravenous cyclophosphamide arm (P = 0.026; P = 0.0082, respectively) in the categories of general health and social functioning. At 18 months, the improvement in the role-physical score was significantly greater in the high-dose cyclophosphamide trial arm than in the monthly-dose cyclophosphamide arm (P = 0.025). At the end of the two and a half-year study, there were no significant differences between the groups with respect to changes in SF-36. By pooling the groups, at 30 months, there was a statistically significant (P < 0.05) improvement over baseline in 6 of the 8 SF-36 domains. This study shows earlier improvement in SF-36 measures at 6 months in the high-dose cyclophosphamide group but equal improvement in both arms at two and one and a half years. Eventual improvements

  1. High-dose versus low-dose oxytocin for augmentation of delayed labour.

    PubMed

    Kenyon, Sara; Tokumasu, Hironobu; Dowswell, Therese; Pledge, Debbie; Mori, Rintaro

    2013-07-13

    A major cause of failure to achieve spontaneous vaginal birth is delay in labour due to presumed inefficient uterine action. Oxytocin is given to increase contractions and high-dose regimens may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. To compare starting dose and increment dose of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high-dose regimens of oxytocin improves labour outcomes and to examine the effect on both maternal/neonatal outcomes and women's birth experiences. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. We included all randomised and quasi-randomised controlled trials for women in delayed labour requiring augmentation by oxytocin comparing high-dose regimens (defined as starting dose and increment of equal to or more than 4 mU per minute) with low-dose regimens (defined as starting dose and an increment of less than 4 mU per minute). Increase interval: between 15 and 40 minutes. The separation of low- and high-dose regimens is based on an arbitrary decision. Four review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. We included four studies involving 644 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in the rate of caesarean section (risk ratio (RR) 0.62; 95% CI 0.44 to 0.86 four trials, 644 women) and an increase in the rate of spontaneous vaginal birth in the high-dose group (RR 1.35; 95% CI 1.13 to 1.62, three trials, 444 women), although for both

  2. 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

  3. The bactericidal effects of an acidified sodium chlorite-containing oral moisturizing gel: a pilot study.

    PubMed

    Kuroyama, Iwao; Osato, Shigeo; Ogawa, Takahiro

    2013-12-01

    The aim of this study was to examine the bactericidal effects and bactericidal time of an acidified sodium chlorite compound gel (ASC-Gel) on bacteria isolated from the peri-implant sulci of 10 patients who received implants 3-27 years previously, and the depth of each peri-implant sulcus was 5 mm or less. Porphyromonas gingivalis (ATCC33277) was used as the control bacterium. Five ASC-Gel preparations were created by adding 3.3%, 5.0%, 7.0%, 9.0%, and 11.0% citric acid (CA) (condition a, b, c, d, and e, respectively) into an oral moisturizing gel containing sodium chlorite. The concentrations of chlorine dioxide (ClO2) generated in ASC-Gel under conditions (a) to (e) were 12.1, 14.1, 17.2, 21.2, and 39.3 ppm, respectively. We examined the bactericidal effects of the 5 ASC-Gel preparations at volumes of 0.5, 1.0, and 2.0 mL, and measured the bactericidal time when 2.0 mL of ASC-Gel was used under condition (e). The bactericidal effects of ASC-Gel became significantly greater with increased concentrations of CA and ClO2 and with increased usage (0.5-2.0 mL) of the gel. All bacteria were killed by using 2.0 mL of ASC-Gel under condition (e). ASC-Gel also needed between 45 and 90 minutes to kill all microbes under condition (e). Within the limits of the present investigation, these results suggest that ASC-Gel is useful as a chemical disinfectant against bacteria in the peri-implant sulcus. Further studies are also required to protect teeth, the surface of hydroxyapatite-coated implants, and the surrounding soft tissues from effects of chemical dissolution such as acid erosion due to the low pH of ASC-Gel.

  4. Massive reduction of tumour load and normalisation of hyperprolactinaemia after high dose cabergoline in metastasised prolactinoma causing thoracic syringomyelia

    PubMed Central

    van Uum, S H M; van Alfen, N; Wesseling, P; van Lindert, E; Pieters, G; Nooijen, P; Hermus, A

    2004-01-01

    On administration of high dose cabergoline, 0.5 mg twice a day orally, the plasma prolactin levels decreased within one month and then normalised within 26 months. Tumour load reduced considerably but unfortunately, her signs and symptoms did not improve. This case illustrates that a high dose dopamine agonist might be an important therapeutic option in patients with a metastasised prolactinoma. PMID:15377706

  5. 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...

  6. 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...

  7. Neoarchean high-pressure margarite-phengitic muscovite-chlorite corona mantled corundum in quartz-free high-Mg, Al phlogopite-chlorite schists from the Bundelkhand craton, north central India

    NASA Astrophysics Data System (ADS)

    Saha, L.; Pant, N. C.; Pati, J. K.; Upadhyay, D.; Berndt, J.; Bhattacharya, A.; Satynarayanan, M.

    2011-04-01

    In quartz-free Fe, Na-poor and high-Mg, Al schists from the Bundelkhand craton in north central India, corundum porphyroblasts in finely interleaved phlogopite-chlorite aggregates with rare clinozoisite are mantled by fine-grained (<3 μm) intergrowths of outer collars (>200 μm wide) of phengitic-muscovite and chlorite (phlogopite + corundum + H2O → phengitic-muscovite + chlorite), and <100 μm wide inner collars of margarite-muscovite (corundum + clinozoisite + phengitic muscovite → margarite + muscovite + H2O). Wide-beam electron probe microanalyses indicate Mg in the bi-layered corona increases from corundum outwards, with a complementary decrease in Al and K. Si and Ca increase and then decrease to matrix values. The sharp chemical gradients across the highly structured bi-layered corona are inferred to suggest that the corona-forming reactions were promoted by local grain-boundary-controlled thermodynamic instability as opposed to element transport by advective diffusion. The P-T convergence of KMASH reactions and NCKMASH pseudosection phase relations computed using micro-domain compositions indicate the chlorite-phengitic muscovite outer collar formed at 18-20 kbar and ca. 630°C. The NCKMASH margarite-muscovite inner collar yielded lower metamorphic P-T conditions of 11 ± 3 kbar, ca. 630°C. U-Th-Pb chemical dating of metamorphic monazite and LA-ICPMS U-Pb isotope dating of re-equilibrated zircon yield ca. 2.78 Ga ages, which are interpreted to date corona formation and Neoarchean high-P metamorphism in the Bundelkhand craton, hitherto unknown in the Indian Precambrian. (220)

  8. The efficacy of high-dose penicillin for community-acquired pneumonia diagnosed by pneumococcal urine antigen test.

    PubMed

    Oka, Hideaki; Ueda, Atsuhisa; Watanuki, Yuji; Tsukiji, Jun; Kuroda, Hideyo; Akashi, Syunsuke; Hirai, Yoshihiro; Fuyuki, Toshiharu; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2009-04-01

    We analyzed the efficacy of both the Streptococcus pneumoniae urine antigen test as a quick diagnostic tool and the administration of high-dose penicillin in response to a positive S. pneumoniae urine antigen test. We conducted a retrospective analysis of 48 cases of pneumococcal pneumonia, in which the patients were treated with high-dose penicillin. All the cases were diagnosed by a positive urine antigen test. Treatment with high-dose penicillin was effective in 43 of the 48 patients. This treatment was also effective in 12 of 16 culture-confirmed cases with low susceptibility to penicillin. Eleven patients who were positive for the S. pneumoniae urine antigen test but culture-negative showed clinical improvement with high-dose penicillin. Pneumonia caused by S. pneumoniae appeared to be treated safely and effectively with high-dose penicillin based on positive results of the urine antigen test, as penicillin resistance was unlikely to be a problem.

  9. Algal toxicity of the alternative disinfectants performic acid (PFA), peracetic acid (PAA), chlorine dioxide (ClO2) and their by-products hydrogen peroxide (H2O2) and chlorite (ClO2(-)).

    PubMed

    Chhetri, Ravi Kumar; Baun, Anders; Andersen, Henrik Rasmus

    2016-12-01

    Environmental effect evaluation of disinfection of combined sewer overflow events with alternative chemical disinfectants requires that the environmental toxicity of the disinfectants and the main by-products of their use are known. Many disinfectants degrade quickly in water which should be included in the evaluation of both their toxicity as determined in standardized tests and their possible negative effect in the water environment. Here we evaluated according to the standardized ISO 8692 test the toxicity towards the green microalgae, Pseudokirchneriella subcapitata, of three disinfectants: performic acid (PFA), peracetic acid (PAA) and chlorine dioxide (ClO2) as well as two by-products of their use: hydrogen peroxide (H2O2) and chlorite. All of the five chemicals investigated showed clear toxicity to the algae with well-defined dose response curves. The EC50 values ranged from 0.16 to 2.9mg/L based on nominal concentrations leading to the labeling of the chemicals as either toxic or very toxic. The five investigated chemicals decreased in toxicity in the order chlorine dioxide, performic acid, peracetic acid, chlorite and hydrogen peroxide. The stability of the chemicals increased in the same order as the toxicity decrease. This indicates that even though ClO2 has the highest environmental hazard potential, it may still be suitable as an alternative disinfectant due to its rapid degradation in water.

  10. Immature pea seeds: effect of storage under modified atmosphere packaging and sanitation with acidified sodium chlorite.

    PubMed

    Collado, Elena; Venzke Klug, Tâmmila; Martínez-Sánchez, Ascensión; Artés-Hernandez, Francisco; Aguayo, Encarna; Artés, Francisco; Fernández, Juan A; Gómez, Perla A

    2017-10-01

    Appropriate sanitation is a priority for extending the shelf life and promoting the consumption of immature pea seeds, as processing accelerates quality deterioration and microbial growth. The combined effect of disinfection with acidified sodium chlorite (ASC) or sodium hypochlorite (SH) and packaging under a passive modified atmosphere (MAP) at 1 or 4 °C on quality was analysed. After 14 days, greenness and vitamin C had decreased, especially in the SH-disinfected samples. Total phenols and antioxidant capacity were not affected by disinfection. Proteins levels fell by around 27%, regardless of the sanitizer and storage temperature. Compared with the initial microbial load, samples stored at 1 °C showed an increase of 1 log CFU g(-1) in psychrophiles when treated with SH, whereas no increase of note occurred with ASC. In general, microbial counts were always below 3 log CFU g(-1) for all the treatments. Immature pea seeds could be stored for 14 days at 1-4 °C under MAP with only minor quality changes. Disinfection with ASC resulted in better sensory quality, higher content of vitamin C and lower psychrophile counts. More research is needed to analyse the effect of these treatments on other quality parameters. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  11. Prewashing with acidified sodium chlorite reduces pathogenic bacteria in lightly fermented Chinese cabbage.

    PubMed

    Inatsu, Yasuhiro; Maeda, Yutaka; Bari, M L; Kawasaki, Susumu; Kawamoto, Shinichi

    2005-05-01

    Efficacy of prewashing with acidified sodium chlorite (ASC) for the sanitation of lightly fermented Chinese cabbage was evaluated. The population of the natural microflora on the cabbage leaves was reduced about 2.0 log CFU/g just after washing with ASC, a significant reduction compared with the control distilled water wash (P < or = 0.05). In the control experiment, viable aerobic bacteria increased gradually when incubated at 10 degrees C; however, ASC-washed cabbage maintained a lower microbial concentration. The treatment of Chinese cabbage with ASC reduced the population of artificially inoculated Escherichia coli O157:H7, Salmonella Enteritidis, Staphylococcus aureus, and Listeria monocytogenes by 2.4 log CFU/g. The sanitation efficacy of ASC was 1.6 log CFU/g higher than that of distilled water washing. The viable cell counts of all pathogenic bacteria tested remained constant during 8 days of storage at 10 degrees C for both washing treatments, with the exception of L. monocytogenes, whose viable cell counts increased gradually with time for both treatments. No significant differences in color, odor, taste, and texture in raw leaves were observed after the ASC wash compared with after the distilled water wash. These results indicate that prewashing with ASC could control bacterial growth in lightly fermented Chinese cabbage without changing the product quality.

  12. Effect of acidified sodium chlorite treatment on chicken carcases processed in South Australia.

    PubMed

    Sexton, Margaret; Raven, Geoff; Holds, Geoff; Pointon, Andrew; Kiermeier, Andreas; Sumner, John

    2007-04-10

    A trial on the effectiveness of acidified sodium chlorite (ASC) on Salmonella and Campylobacter was undertaken on chicken carcases after they exited the screw chiller of a commercial premises in Adelaide, Australia. On untreated carcases mean log10 total viable count (25 degrees C) was 2.78/cm2 compared with 1.23/cm2 on treated carcases. Prevalence of E. coli, Salmonella and Campylobacter was 100%, 90% and 100% respectively, on untreated carcases and 13%, 10% and 23% respectively, on treated carcases. The distributions of E. coli, Salmonella and Campylobacter (mean log10 of positive samples) from untreated carcases were 1.55, -1.80 and 1.59/cm2 respectively, and -0.64, -1.85 and -2.21/cm2 respectively, on treated carcases. On untreated carcases S. Sofia and S. Infantis were isolated from 73% and 37% of carcases, respectively; only S. Sofia was isolated from treated carcases. The significant reductions in both prevalence and concentration demonstrated in the present trial indicate that ASC is a risk management option immediately available to the poultry industry.

  13. Acidified sodium chlorite optimisation assessment to improve quality of fresh-cut tatsoi baby leaves.

    PubMed

    Tomás-Callejas, Alejandro; López-Velasco, Gabriela; Artés, Francisco; Artés-Hernández, Francisco

    2012-03-15

    The fresh-cut industry commonly uses sodium hypochlorite (NaClO) for disinfection. However, there are certain problems related to its use, and acidified sodium chlorite (ASC) could be an alternative sanitiser to replace it. There is limited research evaluating the effect of ASC on the overall quality of fresh-cut produce, especially sensory quality. In this study the decontamination efficacy and quality attribute effects of ASC on fresh-cut tatsoi after application and during storage were investigated. Tatsoi baby leaves were minimally processed at 8 °C and stored under passive modified atmosphere packaging for up to 11 days at 5 and 10 °C. Low to moderate doses of ASC (100-500 mg L⁻¹) showed an initial antimicrobial efficacy on natural microflora and Escherichia coli as effective as that of NaClO. Regarding contact time, ASC was effective in reducting the E. coli population during the first 30 s of washing, and an increase in contact time did not improve the antimicrobial effect. Sensory quality attributes were well kept for up to 11 days at 5 °C but for only 5 days at the abusive temperature of 10 °C. ASC provides an alternative sanitising technique to NaClO for maintaining the quality and safety of fresh-cut tatsoi baby leaves for up to 11 days at 5 °C. Copyright © 2011 Society of Chemical Industry.

  14. Kinetics of the Inactivation of Vibrio parahaemolyticus in Weakly Acidic Sodium Chlorite Solution.

    PubMed

    Takahashi, Kazuhiro; Tanaka, Reiji; Fukuzaki, Satoshi

    2017-01-01

     The kinetics of the inactivation of Vibrio parahaemolyticus in sodium chlorite (NaClO2) solution was studied in the weakly acidic pH range of 4.0 to 6.5 and at various temperatures. The logarithmic reduction of the survival ratio depended on the concentration-time product, and all the inactivation curves showed a linear reduction phase. The first-order inactivation rate constant (k) increased by approximately twice for every 0.44 unit fall in pH. During the inactivation experiments, no formation of chlorine dioxide occurred. These data indicated that undissociated HClO2 was the active species governing the inactivation of V. parahaemolyticus. It was also shown that the use of weakly acidic NaClO2 solutions containing high concentrations of ionized ClO2(-) gave slower kinetics of the inactivation, whereas it could achieve the significant reduction of viable cells of more than 4-log. The k value showed an Arrhenius-type temperature dependence in the temperature range of 5 to 40℃. The apparent activation energy for the inactivation of V. parahaemolyticus was estimated to be 43.5 kJ/mol. The k value increased by approximately 1.8 times for every 10℃ rise in temperature.

  15. Acid--chlorite pretreatment and liquefaction of cornstalk in hot-compressed water for bio-oil production.

    PubMed

    Liu, Hua-Min; Feng, Bing; Sun, Run-Cang

    2011-10-12

    In this study, cornstalk was pretreated by an acid-chlorite delignification procedure to enhance the conversion of cornstalk to bio-oil in hot-compressed water liquefaction. The effects of the pretreatment conditions on the compositional and structural changes of the cornstalk and bio-oil yield were investigated. It was found that acid-chlorite pretreatment changed the main components and physical structures of cornstalk and effectively enhanced the bio-oil yield. Shorter residence time favored production of the total bio-oil products, whereas longer time led to cracking of the products. A high water loading was found to be favorable for high yields of total bio-oil and water-soluble oil. GC-MS analysis showed that the water-soluble oil and heavy oil were the complicated products of C(5-10) and C(8-11) organic compounds.

  16. 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

  17. Chlorite dissolution kinetics at pH 3–10 and temperature to 275°C

    SciTech Connect

    Smith, Megan M.; Carroll, Susan A.

    2015-12-02

    Sheet silicates and clays are ubiquitous in geothermal environments. Their dissolution is of interest because this process contributes to scaling reactions along fluid pathways and alteration of fracture surfaces which could affect reservoir permeability. Here, in order to better predict the geochemical impacts on long-term performance of engineered geothermal systems, we have measured chlorite dissolution and developed a generalized kinetic rate law applicable over an expanded range of solution pH and temperature. Chlorite, (Mg,Al,Fe)12(Si,Al)8O20(OH)16, commonly occurs in many geothermal host rocks as either a primary mineral or alteration product.

  18. High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

    PubMed

    Meyer, Markus; Bell, Stephen P; Chen, Zengyi; Nyotowidjojo, Iwan; Lachapelle, Richard R; Christian, Timothy F; Gibson, Pamela C; Keating, Friederike F; Dauerman, Harold L; LeWinter, Martin M

    2013-11-01

    We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.

  19. 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.

  20. Heart failure in hypophosphatemic rickets: complications from high-dose phosphate therapy.

    PubMed

    Sun, Grace E Ching; Suer, Ozan; Carpenter, Thomas O; Tan, Carmela D; Li-Ng, Melissa

    2013-01-01

    To report a rare case of hypophosphatemic rickets (HR) leading to extensive cardiac complications. We present the clinical course and autopsy findings of a patient with HR, treated with chronic phosphate-only therapy as a child, who subsequently developed tertiary hyperparathyroidism leading to extensive cardiac calcifications and complications. We also review the literature on the pathophysiology of calcifications from HR. A 34-year-old man was diagnosed with HR at 4 years of age after presenting with growth delay and leg bowing. Family history was negative for the disease. He was initiated on high-dose phosphate therapy (2-6 g of elemental phosphorus/day) with sporadic calcitriol use between 4-18 years of age. For 6 years he received phosphate-only therapy. Subsequently, he developed nephrocalcinosis, heart valve calcifications, severe calcific coronary artery disease, heart block, and congestive heart failure. At a young age, he required an aortic valve replacement and a biventricular pacemaker that was subsequently upgraded to an implantable cardioverter defibrillator. Autopsy showed extensive endocardial, myocardial, and coronary artery calcifications. Cardiac calcification is a known sequela of tertiary hyperparathyroidism when it occurs in patients with renal failure, but it is rarely seen in HR due to high phosphate therapy. Phosphate alone should never be used to treat HR; high doses, even with calcitriol, should be avoided. It is important to be cognizant of high-dose phosphate effects and to consider parathyroidectomy for autonomous function, if needed. This case emphasizes the importance of appropriate therapy, monitoring, and management of patients with HR.

  1. High-dose immunosuppressant alters the immunological status of New Zealand white rabbits following skin transplantation.

    PubMed

    Cheng, Peilun; Zhong, Liming; Jiang, Zesheng; Wang, Yan; Pan, Mingxin; Gao, Y I

    2015-09-01

    The aim of this study was to investigate the effect of an immunosuppressant on the immunological status of New Zealand white rabbits after skin grafting, and to evaluate a method for monitoring the immunological status of subjects with skin transplants. The rabbits were randomly divided into allograft rejection, autograft tolerance, nontransplant, allograft low-dose immunosuppressant and allograft high-dose immunosuppressant groups. The rabbits in the low- and high-dose immunosuppressant groups were treated with cyclosporine A intravenously 8 h prior to skin transplantation and once daily following transplantation at doses of 2 and 25 mg/kg, respectively. At 12 days after skin transplantation, the spleens of donor (female) rabbits and recipient (male) rabbits were harvested for the preparation of single-cell suspensions. The splenocytes from recipient and donor rabbits were labeled with 0.3 or 6 µM carboxy fluorescein diacetate succinimidyl ester, respectively, and a mixed cell suspension was prepared. The final preparation was intravenously injected into recipient New Zealand white rabbits. The ratio of the two fluorescently labeled cell populations in the peripheral blood was measured using flow cytometry at 1, 2, 4 and 8 h after the injection, and the cell death rate was calculated. Histological analysis was also performed on samples collected at the time of splenectomy. The cell death rates of the allograft rejection and low-dose immunosuppressant groups reached their highest levels 8 h after the injection of spleen cell suspension. Allogeneic spleen cells from donor male rabbits were almost completely removed within 8 h of injection. The cell death rate increased slowly in the nontransplant, autograft and high-dose immunosuppressant groups without specificity. This study provides a specific method for the in vivo monitoring of the immunological status of patients after skin grafting. This method can quickly and accurately detect the immunological status of

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

    PubMed

    Ray, Monika; Yunis, Reem; Chen, Xiucui; Rocke, David M

    2012-05-17

    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. 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. 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.

  3. High-dose cyclophosphamide therapy associated with diffuse alveolar hemorrhage after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Mo, Xiao-Dong; Xu, Lan-Ping; Liu, Dai-Hong; Zhang, Xiao-Hui; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Yu; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2013-01-01

    The occurrence of diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. There are few reports that have examined the correlation between pre-HSCT chemotherapeutic exposure and DAH. We examine the role of pre-HSCT chemotherapeutic exposure, conditioning regimens, pre-HSCT comorbidities and transplant-related complications in the development of DAH after allo-HSCT and evaluate the effect of the high-dose corticosteroid strategy on DAH. A retrospective nested case-control study was designed. Cases with DAH and controls matched for year of allo-HSCT and length of follow-up were identified from a cohort of 597 patients who underwent allo-HSCT between 2006 and 2011 for acute leukemia. Twenty-two patients suffered from DAH; the mean age at the time of presentation was 30.4 years (±12.9) and the mean time to presentation was 7.8 months (±8.1) post-HSCT. The pre-HSCT cyclophosphamide exposure and the cumulative cyclophosphamide dose were significantly higher among the DAH cases compared with the controls, and the cumulative cyclophosphamide dose of ≥5 g/m(2) was independently associated with DAH (OR = 3.4, p = 0.030). High-dose corticosteroid treatment did not significantly improve survival. From these results we can identify patients who are at a higher risk of developing DAH after allo-HSCT, and we found that high-dose corticosteroid therapy may not alter the poor outcome associated with this syndrome. Copyright © 2012 S. Karger AG, Basel.

  4. 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

  5. Safety and Efficacy of Intermittent Intravenous Administration of High-Dose Micafungin

    PubMed Central

    Neofytos, Dionysis; Huang, Yao-Ting; Cheng, Kimberly; Cohen, Nina; Perales, Miguel-Angel; Barker, Juliet; Giralt, Sergio; Jakubowski, Ann; Papanicolaou, Genovefa

    2015-01-01

    Background. The use of mold-active azoles for antifungal prophylaxis after allogeneic stem cell transplantation (SCT) is hindered by adverse events and drug–drug interactions. Higher doses of echinocandins administered intermittently may be an alternative in this setting. Methods. This was a single-center, observational 5-year study to characterize the safety and efficacy of intermittent administration of high-dose intravenous micafungin (≥5 doses of ≥300 mg micafungin 2–3 times weekly) in patients with acute leukemia and allogeneic SCT recipients. Results. A total of 104 patients (84 allogeneic SCT recipients and 20 patients with leukemia) received intermittent high-dose intravenous micafungin, 83 (79.8%) as prophylaxis. Large variability in the micafungin dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg micafungin 3 times weekly. Liver function tests decreased from baseline to end of treatment (EOT; P < .001). Patients with normal baseline liver function (n = 55 [52%]) maintained similar enzyme levels throughout the study. For patients with abnormal baseline liver function (n = 49 [47%]), liver function tests significantly improved from baseline to EOT (P ≤ .005). Duration and/or micafungin dosing algorithms were not associated with liver toxicity at EOT. There were no significant changes in renal function, and infusion-related reactions or deaths were not observed. Five of 83 (6.0%) patients in the prophylaxis group developed a breakthrough fungal infection. Conclusions. In this largest cohort of patients to date, intermittent administration of high-dose micafungin was well tolerated, without any associated liver or renal function abnormalities, and may be considered an alternative antifungal prophylactic strategy. Prospective studies are needed to further validate these findings. PMID:26567284

  6. Prior Methamphetamine Self-Administration Attenuates Serotonergic Deficits Induced by Subsequent High-Dose Methamphetamine Administrations

    PubMed Central

    McFadden, Lisa M.; Hunt, Madison M.; Vieira-Brock, Paula L.; Muehle, Janice; Nielsen, Shannon; Allen, Scott C.; Hanson, Glen R.; Fleckenstein, Annette E.

    2012-01-01

    Background Pre-clinical studies indicate that high-dose, non-contingent methamphetamine (METH) administration both rapidly and persistently decreases serotonergic neuronal function. Despite research indicating the hippocampus plays an important role in METH abuse and is affected by METH use, effects of METH self-administration on hippocampal serotonergic neurons are not well understood, and were thus an important focus of the current study. Because humans often administer METH in a binge-like pattern, effects of prior METH self-administration on a subsequent “binge-like” METH treatment were also examined. Methods Rats were treated as described above, and sacrificed 1 or 8 d after self-administration or 1 h or 7 d after the final binge METH or saline exposure. Hippocampal serotonin (5-hydroxytryptamine; 5HT) content and transporter (SERT) function were assessed. Results METH self-administration per se had no persistent effect on hippocampal 5HT content or SERT function. However, this treatment attenuated the persistent, but not acute, hippocampal serotonergic deficits caused by a subsequent repeated, high-dose, non-continent METH treatment administered 1 d the last self-administration session. No attenuation in persistent deficits were seen when the high-dose administration of METH occurred 15 d after the last self-administration session. Conclusions The present findings demonstrate that METH self-administration alters serotonergic neurons so as to engender “tolerance” to the persistent serotonergic deficits caused by a subsequent METH exposure. However, this “tolerance” does not persist. These data provide a foundation to investigate complex questions including how the response of serotonergic neurons to METH may contribute to contingent-related disorders such as dependence and relapse. PMID:22647900

  7. High-dose chemoradiotherapy (HDC) in the Ewing family of tumors (EFT).

    PubMed

    Burdach, S; Jürgens, H

    2002-02-01

    EFT is defined by the expression of ews/ets fusion genes. The type of the fusion transcript impacts on the clinical biology. EFT requires risk adapted treatment. A risk-adapted treatment is determined by tumor localisation, tumor stage and volume. For metastatic and relapsed disease the pattern of spread and the time of relapse are the determinants of risk stratification. Staging of Ewing tumors has been considerably improved by magnetic resonance imaging and modern isotope scanning techniques. However, the determination of the extent of the metastatic spread in particular number of involved bones remains an unresolved issue. The prognosis for high-risk Ewing tumors has been improved by multimodal and high-dose radio/chemotherapy (HDC). The concepts for high-dose therapy in Ewing tumors are based on dose response and dose intensity relationships. In single agent HDC most experience exists with Melphalan. Several chemotherapeutic agents have been used in combination HDC with or without TBI such as Adriamycin, BCNU, Busulphan, Carboplatin, Cyclophosphamide, Etoposide, Melphalan, Thiotepa Procarbazin and Vincristine. To date, superiority of any high-dose chemotherapy regimen has not been established. However, the clinical biology, the pattern of spread and the time of relapse determine the prognosis of patient who are eligible for HDC. In particular, patients with multifocal bone or bone marrow metastases have a poorer prognosis than patients with lung metastases. In addition, patients with a relapse within 24 months have a poorer prognosis than patients with a relapse later than 24 months after diagnosis. This review will analyze the results of single- and multi-agent chemotherapy with respect to agent combination, dose and risk stratum of patient population. Future therapeutic modalities for the treatment of EFT might encompass immunotherapeutic and genetic strategies including allogeneic stem cell transplantation.

  8. Vitamin E Reversed Apoptosis of Cardiomyocytes Induced by Exposure to High Dose Formaldehyde During Mice Pregnancy.

    PubMed

    Wu, Dongyuan; Jiang, Zhirong; Gong, Bing; Dou, Yue; Song, Mingxuan; Song, Xiaoxia; Tian, Yu

    2017-09-30

    In this study, we investigated the protection effect of Vitamin E (Vit E) on formaldehyde (FA) exposure during pregnancy induced apoptosis of cardiomyocytes, and used an HL-1 cell line to confirmed the findings in vivo.Pregnant mice received different doses of FA (0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 0.1 μg Vit E, or 1.5 mg/kg + 0.1 μg Vit E). TUNEL staining was used to reveal the apoptosis in cardiomyocytes, and SOD, MDA, GSH, Livin, and Caspase-3 in cardiomyocytes were detected by ELISA, RT-PCR, and Western blot. For in vitro study, HL-1 cells were treated with vehicle, 5 μmol/L FA, 25 μmol/L FA, 50 μmol/L FA, 10 mg/L Vit. E, and 50 μmol/L FA+ 10 mg/L Vit E, respectively. CCK-8 assay and flow cytometry were used to evaluate cell vitality and apoptosis. A high dose of FA exposure led to cytotoxicity in both pregnant mice and offspring, as TUNEL staining revealed a significant apoptosis of cardiomyocytes, and the alternation in SOD, GSH, MDA, Livin, and Caspase-3 was found in cardiomyocytes. 0.1 μg Vit. E could reverse high doses of FA exposure induced apoptosis of cardiomyocytes in both pregnant mice and offspring. The in vitro study revealed that FA exposure induced a decrease of cell viability and increased cell apoptosis, as well as oxidative stress in HL-1 cells with alternation in SOD, GSH, MDA, Livin, and Caspase-3.This study revealed a high dose of FA induced oxidative stress and apoptosis of cardiomyocytes in both pregnant mice and offspring, and Vit E supplement during pregnancy reversed the systemic and myocardial toxicity of FA.

  9. High-dose subchronic imipramine treatment: effects on anxiety-like (conflict) behavior in rats.

    PubMed

    Commissaris, R L; Hill, T J

    In the management of both anxiety and depression, agents such as imipramine (IMI) are noted for their 3-5 week delay to onset of clinical effect. A similar delay to onset has been reported for the anxiolytic-like (i.e., anticonflict) effect of chronic IMI treatment (2.5 mg/kg, BID for 5 weeks) in the Conditioned Suppression of Drinking (CSD) conflict paradigm; similar effects have been reported with other antidepressants and in other conflict procedures. In contrast, in the Forced Swim Test (FST) model of depression, antidepressant-like effects are reported immediately following subchronic treatment with relatively high doses of these agents (e.g., 30 mg/kg IMI, 3 times in 24 hr). The present study examined the effects of this high-dose, subchronic treatment with IMI on CSD conflict behavior. Conflict-trained female Sprague Dawley rats were divided into three groups with comparable pretreatment baselines for shocks received. Treatments (0, 15, and 30 mg/kg IMI) were administered intraperitoneally (IP) at 23, 5, and 1 hr prior to CSD conflict testing on day 1; CSD conflict behavior was then monitored daily (Mon-Fri) for 5 weeks following treatment. IMI treatment (30 and, to a lesser extent, 15 mg/kg) significantly reduced shocks received (punished responding) and water intake (unpunished responding) on day 1; although water intake was also slightly reduced in both IMI treatment groups for the remainder of test week 1, there was no difference in shocks received between the various treatments for this period. Subjects receiving 30 mg/kg IMI (but not those receiving 15 mg/kg IMI or vehicle) accepted significantly more shocks than controls on weeks 2-4 (maximal increase at week 3) and returned to pretreatment baseline levels by week 5. Thus, subchronic high-dose treatment with IMI (and perhaps other antidepressants) produces anxiolytic-like effects which are delayed in nature and persist for several weeks after treatment.

  10. High doses of biotin in chronic progressive multiple sclerosis: a pilot study.

    PubMed

    Sedel, Frédéric; Papeix, Caroline; Bellanger, Agnès; Touitou, Valérie; Lebrun-Frenay, Christine; Galanaud, Damien; Gout, Olivier; Lyon-Caen, Olivier; Tourbah, Ayman

    2015-03-01

    No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  11. High doses of atorvastatin and simvastatin induce key enzymes involved in VLDL production.

    PubMed

    Roglans, Núria; Verd, Joan C; Peris, Cristina; Alegret, Marta; Vázquez, Manuel; Adzet, Tomás; Díaz, Cristina; Hernández, Gonzalo; Laguna, Juan C; Sánchez, Rosa M

    2002-05-01

    Treatments with high doses of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors may induce the expression of sterol regulatory element binding protein (SREBP)-target genes, causing different effects from those attributed to the reduction of hepatic cholesterol content. The aim of this study was to investigate the effects of high doses of statins on the key enzymes involved in VLDL production in normolipidemic rats. To examine whether the effects caused by statin treatment are a consequence of HMG-CoA reductase inhibition, we tested the effect of atorvastatin on these enzymes in mevalonate-fed rats. Atorvastatin and simvastatin enhanced not only HMG-CoA reductase but also the expression of the SREBP-2 gene itself. As a result of the overexpression of SREBP-2 caused by the statin treatment, genes regulated basically by SREBP-1, as FA synthase and acetyl-coenzyme A carboxylase, were also induced and their mRNA levels increased. DAG acyltransferase and microsomal TG transfer protein mRNA levels as well as phosphatidate phosphohydrolase activity were increased by both statins. Simvastatin raised liver cholesterol content, ACAT mRNA levels, and CTP:phosphocholine cytidylyltransferase activity, whereas it reduced liver DAG and phospholipid content. Mevalonate feeding reversed all changes induced by the atorvastatin treatment. These results show that treatment with high doses of statins induces key enzymes controlling rat liver lipid synthesis and VLDL assembly, probably as a result of SREBP-2 overexpression. Despite the induction of the key enzymes involved in VLDL production, both statins markedly reduced plasma TG levels, suggesting that different mechanisms may be involved in the hypotriglyceridemic effect of statins at high or low doses.

  12. 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

  13. High dose rate brachytherapy in early stage squamous-cell carcinoma of the lip.

    PubMed

    Mut, Alejandro; Guinot, José Luis; Arribas, Leoncio; Díez-Presa, Lorena; Tortajada, María Isabel; Santos, Miguel Ángel; Samper, Josefa; Santamaría, Paula; Vendrell, Juan Bosco

    2016-01-01

    To analyze the results obtained after treatment of early stage (T1-T2) squamous cell carcinoma of the lip with high dose rate brachytherapy and evaluate the efficacy of this treatment in both local and regional control. Retrospective analysis of the treatments performed at our department from March 1999 to March 2013 with high dose rate brachytherapy with rigid needles. We included 68 patients, 63 men and 5 women; 37 patients (54.4%) presented a T1 tumour, less than or equal to 2cm, while the other 31 (45.6%) were classified as T2. Median total dose was 45Gy, with a median dose per fraction of 5Gy x 9 fractions twice a day for 5 days. With a mean follow-up of 56.4 months, local control was 96.9%. Stratifying by tumour size, local control of T1 cases was 100%, while T2 achieved 93.2% (2 local recurrences). Regional control at 5 years was 93.8% for T1, and 80.8% for T2. In 11 cases with elective cervical treatment, no regional failure happened. As for toxicity, no patient presented soft tissue, or bone, necrosis. All patients achieved good or excellent cosmetic and functional results. High dose rate brachytherapy allows effective, safe treatments for squamous cell carcinoma of the lip, with good aesthetic and functional results. It can be considered a valid alternative for surgery in early stage tumours. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  14. 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.

  15. Intravenous lipid emulsion and high-dose insulin as adjunctive therapy for propranolol toxicity in a pediatric patient.

    PubMed

    Thompson, Amanda M; Franco Palacios, Carlos R; Henriksen, Maria N

    2016-06-15

    The concurrent use of intravenous lipid emulsion (ILE) and high-dose insulin (HDI) for the management and treatment of propranolol toxicity in a pediatric patient is described. A seven-month-old infant (weight, 6.1 kg) was admitted to a hospital emergency department with lethargy and bradycardia after an unintentional overdose of propranolol suspension, which had been prescribed several days previously for treatment of a scalp hemangioma. Notable physical examination and laboratory findings were as follows: blood pressure, 121/84 mm Hg (normal range, 90 ± 30/60 ± 10 mm Hg); heart rate, 62 beats/min (normal range, 100-150 beats/min); respiratory rate, 24 breaths/min (normal range, 25-35 breaths/min); oxygen saturation, 100% on room air; and rectal temperature, 35.7 °C (normal range, 36.6-38.0 °C). The patient was lethargic. Treatment included i.v. fluid boluses of 0.9% sodium chloride injection and i.v. boluses and continuous infusions of HDI, dextrose, and ILE. After the completion of these treatments, hemodynamic stability was regained. The case is believed to be the first reported case in which a pediatric patient less than one year of age regained hemodynamic stability after administration of ILE and HDI rescue therapy. Monitoring blood glucose frequently with HDI is essential to avoid hypoglycemia. The rationale for using ILE and HDI for reversal of drug toxicities is discussed. A symptomatic pediatric patient with acute propranolol toxicity exhibited clinical improvement with the administration of ILE in conjunction with HDI. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  16. High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS)

    PubMed Central

    Nash, Richard A.; Hutton, George J.; Racke, Michael K.; Popat, Uday; Devine, Steven M.; Griffith, Linda M.; Muraro, Paolo A.; Openshaw, Harry; Sayre, Peter H.; Stüve, Olaf; Arnold, Douglas L.; Spychala, Meagan E.; McConville, Kaitlyn C.; Harris, Kristina M.; Phippard, Deborah; Georges, George E.; Wundes, Annette; Kraft, George H.; Bowen, James D.

    2016-01-01

    IMPORTANCE Most patients with relapsing-remitting (RR) multiple sclerosis (MS) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, in contrast, induce sustained remissions in early MS. OBJECTIVE To evaluate the safety, efficacy, and durability of MS disease stabilization through 3 years after HDIT/HCT. DESIGN, SETTING, AND PARTICIPANTS Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) is an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling. Participants are evaluated through 5 years after HCT. This report is a prespecified, 3-year interim analysis of the trial. Thirty-six patients with RRMS from referral centers were screened; 25 were enrolled. INTERVENTIONS Autologous peripheral blood stem cell grafts were CD34+ selected; the participants then received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before autologous HCT. MAIN OUTCOMES AND MEASURES The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes: (1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging. Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS Grafts were collected from 25 patients, and 24 of these individuals received HDIT/HCT. The median follow-up period was 186 weeks (interquartile range, 176–250) weeks). Overall event-free survival was 78.4% (90% CI, 60.1%–89.0%) at 3 years. Progression-free survival and clinical relapse

  17. 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

  18. Application of jade samples for high-dose dosimetry using the EPR technique.

    PubMed

    Teixeira, Maria Inês; Melo, Adeilson P; Ferraz, Gilberto M; Caldas, Linda V E

    2010-01-01

    The dosimeter characteristics of jade samples were studied for application in high-dose dosimetry. Jade is the common denomination of two silicates: jadeite and actinolite. The EPR spectra of different jade samples were obtained after irradiation with absorbed doses of 100 Gy up to 20 kGy. The jade samples present signals that increase with the absorbed dose (g-factors around 2.00); they can be attributed to electron centers. The EPR spectra obtained for the USA jade samples and their main dosimetric properties as reproducibility, calibration curves and energy dependence were investigated.

  19. Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

    PubMed

    Pallavee, P; Samal, Sunita; Samal, Rupal

    2013-01-01

    The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

  20. [High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia].

    PubMed

    Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

    2005-03-01

    A 12 year-old girl was treated with prophylatic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylatic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed.

  1. Can anisodamine be a potential substitute for high-dose atropine in cases of organophosphate poisoning?

    PubMed

    Wang, W; Chen, Q-F; Ruan, H-L; Chen, K; Chen, B; Wen, J-M

    2014-11-01

    A case of organophosphate (OP) poisoning was admitted to the emergency room. The patient accepted treatment with pralidoxime (PAM), atropine, and supporting therapy. It was observed that even after 22 h after treatment, 960 mg of atropine was not enough for the patient to be atropinized. However, a 160-mg follow-up treatment of anisodamine was quite enough for atropinization after 4 h. As a case report, more studies are required before any definite conclusion can be reached regarding the use of anisodamine as a potential substitute for high-dose atropine in cases of OP poisoning.

  2. High-Dose Chemotherapy and Autologous Stem Cell Transplant in Older Patients with Lymphoma

    PubMed Central

    Lahoud, Oscar B.; Sauter, Craig S.; Hamlin, Paul A.

    2017-01-01

    High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HDT/ASCT) can improve survival in patients with lymphoma. Limited experience is available on the safety and efficacy of HDT/ASCT in elderly patients. In this article, we review the published data on the role of HDT/ASCT in management of lymphoma in older patients. Based on available data, evaluation of comorbidities, functional status, and comprehensive geriatric assessment (CGA) will help identify those who can benefit most from this intervention. Prospective clinical trials focusing on HDT/ASCT in older patients with lymphoma are needed to establish optimal management protocols in this select population. PMID:26201264

  3. 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

  4. Spurious thyroid cancer metastasis: saliva contamination artifact in high dose iodine-131 metastases survey

    SciTech Connect

    Park, H.M.; Tarver, R.D.; Schauwecker, D.S.; Burt, R.

    1986-05-01

    The use of high dose /sup 131/I for workup of thyroid cancer patients increases the chance of contamination artifact which may mimic metastases. Two elderly male patients with follicular carcinoma of the thyroid had salivary contamination artifacts on metastatic survey scans. These patients received a 1 and 10 mCi dose of /sup 131/I, respectively. The artifacts were recognized only retrospectively when follow-up scans were obtained and compared. The characteristics of contamination artifacts and several methods to confirm these are discussed.

  5. High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience.

    PubMed

    Bosly, A; Haioun, C; Gisselbrecht, C; Reyes, F; Coiffier, B

    2001-07-01

    Autologous stem-cell transplantation (ASCT) has permitted to deliver high-dose therapy (HDT). In aggressive lymphomas, the GELA group conducted prospective and retrospective studies comparing HDT + ASCT to conventional sequential chemotherapy. In relapsing patients and in partial remission, retrospective studies showed a survival advantage for HDT + ASCT over sequential chemotherapy. In complete response, advantage for HDT + ASCT was demonstrated in a prospective trial only for patients with high intermediate or high risk in the IPI score. The attainment of a maximal reduction of the tumoral mass before going HDT is very important either in first line or in relapsing patients.

  6. Adverse effects of high doses of intravenous alpha lipoic Acid on liver mitochondria.

    PubMed

    Vigil, Michael; Berkson, Burton M; Garcia, Ana Patricia

    2014-01-01

    Alpha lipoic acid (ALA, thioctic acid), among other actions, is an essential coenzyme in the conversion of pyruvate to acetyl co-enzyme A. Therefore, it is necessary for the production of energy for aerobic organisms. Scientists have found that it can be used medically to help regenerate liver tissue, reverse the complications of diabetes mellitus, slow or stop the growth of cancer cells, and chelate heavy metals, among other actions. In this article, the authors describe the cellular mitochondrial damage from excessively high doses of this beneficial agent.

  7. 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

  8. Hypersensitivity Reaction to High-Dose Methotrexate and Successful Rechallenge in a Pediatric Patient with Osteosarcoma

    PubMed Central

    Scott, Jeffrey R.; Ward, Deborah A.; Crews, Kristine R.; Panetta, John C.; Navid, Fariba

    2014-01-01

    Hypersensitivity reactions to methotrexate are rare, but have been reported. Methotrexate has shown activity against many malignancies, and omission of methotrexate therapy may increase the risk of cancer-related death in some patients. Therefore, rechallenging patients with methotrexate following hypersensitivity may be beneficial. We report a case of a child with metastatic osteosarcoma who experienced a hypersensitivity reaction to high-dose methotrexate and was successfully rechallenged with methotrexate using a 6-hour infusion. Using this regimen, adequate peak methotrexate plasma concentrations were achieved and no further hypersensitivity reactions were noted. PMID:23955991

  9. Hypersensitivity reaction to high-dose methotrexate and successful rechallenge in a pediatric patient with osteosarcoma.

    PubMed

    Scott, Jeffrey R; Ward, Deborah A; Crews, Kristine R; Panetta, John C; Navid, Fariba

    2014-02-01

    Hypersensitivity reactions to methotrexate are rare, but have been reported. Methotrexate has shown activity against many malignancies, and omission of methotrexate therapy may increase the risk of cancer-related death in some patients. Therefore, rechallenging patients with methotrexate following hypersensitivity may be beneficial. We report a case of a child with metastatic osteosarcoma who experienced a hypersensitivity reaction to high-dose methotrexate and was successfully rechallenged with methotrexate using a 6-hour infusion. Using this regimen, adequate peak methotrexate plasma concentrations were achieved and no further hypersensitivity reactions were noted.

  10. [G6PD phenotype and red blood cell sensitivity to the oxidising action of chlorites in drinking water].

    PubMed

    Contu, A; Bajorek, M; Carlini, M; Meloni, P; Cocco, P; Schintu, M

    2005-01-01

    Chlorine dioxide is widely used to replace sodium hypochlorite in the disinfection of surface waters for human consumption, in order to avoid or reduce the formation of organohalogenated compounds with mutagenic and carcinogenic activity. However, chlorine dioxide may lead to the formation of by-products, such as chlorites and chlorates, that have an oxidative effect on the blood corpuscled fraction. In this investigation, blood crasis was assessed in relation to the G6PD phenotype and the consumption of tap water, disinfected with chlorine dioxide, or bottled mineral water from non-disinfected underground sources. The results show that the effect of oxidative stress resulting from the uptake of chlorites with drinking water is not additive to the effect due to G6PD deficiency. The observed change in haematological parameters, including those related to the G6PD polymorphism, is always within the normal range. However, it is still possible that more relevant changes would follow exposure to chlorites concentrations greater than that observed in the present study.

  11. Three autocatalysts and self-inhibition in a single reaction: a detailed mechanism of the chlorite-tetrathionate reaction.

    PubMed

    Horváth, Attila K; Nagypál, István; Epstein, Irving R

    2006-11-27

    The chlorite-tetrathionate reaction has been studied spectrophotometrically in the pH range of 4.65-5.35 at T = 25.0 +/- 0.2 degrees C with an ionic strength of 0.5 M, adjusted with sodium acetate as a buffer component. The reaction is unique in that it demonstrates autocatalysis with respect to the hydrogen and chloride ion products and the key intermediate, HOCl. The thermodynamically most-favorable stoichiometry, 2S(4)O(6)2- + 7ClO2- + 6H2O --> 8SO(4)2- + 7Cl- + 12H+, is not found. Under our experimental conditions, chlorine dioxide, the chlorate ion, or both are detected in appreciable amounts among the products. Initial rate studies reveal that the formation of chlorine dioxide varies in an unusual way, with the chlorite ion acting as a self-inhibitor. The reaction is supercatalytic (i.e., second order with respect to autocatalyst H+). The autocatalytic behavior with respect to Cl- comes from chloride catalysis of the chlorite-hypochlorous acid and hypochlorous acid-tetrathionate subsystems. A detailed kinetic study and a model that explains this unusual kinetic behavior are presented.

  12. Drug-induced liver injury associated with high-dose ceftriaxone: a retrospective cohort study adjusted for the propensity score.

    PubMed

    Nakaharai, Kazuhiko; Sakamoto, Yohei; Yaita, Kenichiro; Yoshimura, Yukihiro; Igarashi, Shun; Tachikawa, Natsuo

    2016-08-01

    Ceftriaxone has been recognized as a well-tolerated drug; however, in some instances, liver dysfunction occurs after using high-dose ceftriaxone. We aimed to assess the incidence of liver injury due to high-dose ceftriaxone and to determine whether there is a dose-dependent risk of liver injury with this drug. We conducted a retrospective cohort study of hospitalized adult patients treated with ceftriaxone at a tertiary care hospital from January 2012 to October 2013. We collected demographic and clinical data by reviewing their medical records. The incidence of liver injury based on biochemical criteria, defined as a primary outcome, was compared between patients treated with high-dose ceftriaxone (4 g/day) and those treated with a normal dose of ceftriaxone (2 g/day) for ≥5 consecutive days. A propensity score for the use of high-dose ceftriaxone was calculated from five factors. We identified 37 patients treated with high-dose ceftriaxone and 434 patients treated with a normal dose of ceftriaxone. Among these 471 patients, 15 patients (3.2 %) experienced liver injury, of whom six patients (6/37, 16.2 %) had received high-dose ceftriaxone and nine patients (9/434, 2.1 %) had received normal doses of ceftriaxone. In the multivariate analysis adjusted for the propensity score, high-dose ceftriaxone was independently associated with liver injury (odds ratio, 7.23; 95 % confidence interval, 2.01-26.0). The present study revealed that high-dose ceftriaxone was associated with a significantly higher incidence of liver injury compared with the normal-dose regimen. Therefore, clinicians should carefully observe for signs of liver injury after high-dose ceftriaxone use.

  13. Synergistic anti-Parkinsonism activity of high doses of B vitamins in a chronic cellular model.

    PubMed

    Jia, Haiqun; Liu, Zhongbo; Li, Xin; Feng, Zhihui; Hao, Jiejie; Li, Xuesen; Shen, Weili; Zhang, Hongyu; Liu, Jiankang

    2010-04-01

    We propose that elevation of mitochondrial enzyme cofactors may prevent or ameliorate neurodegenerative diseases by improving mitochondrial function. In the present study, we investigated the effects of high doses of B vitamins, the precursors of mitochondrial enzyme cofactors, on mitochondrial dysfunction, oxidative stress, and Parkinsonism in a 4-week long rotenone treatment-induced cellular model of Parkinson's disease (PD). Pretreatment with B vitamins (also 4 weeks) prevented rotenone-induced: (1) mitochondrial dysfunction, including reduced mitochondrial membrane potential and activities of complex I; (2) oxidative stress, including increase in reactive oxygen species, oxidative DNA damage and protein oxidation, and (3) Parkinsonism parameters, including accumulation of alpha-synuclein and poly-ubiquitin. The optimum doses were found around 2.5- and 5-fold of that in normal MEM medium. The 4-week pretreatment was chosen based on time-dependent experiments that pretreatments longer than 2 weeks resulted in a decrease in oxidants, an increase in oxygen consumption, and up-regulation of complex I activity and PGC-1alpha expression. Individual B vitamins at the same doses did not show a similar effect suggesting that these B vitamins work synergistically. These results suggest that administration of high doses of B vitamins sufficient to elevate mitochondrial enzyme cofactors may be effective in preventing PD by reducing oxidative stress and improving mitochondrial function.

  14. Pharmacopeial methodologies for determining aerodynamic mass distributions of ultra-high dose inhaler medicines.

    PubMed

    Wong, William; Crapper, John; Chan, Hak-Kim; Traini, Daniela; Young, Paul M

    2010-03-11

    Three different impactor methodologies, the Andersen cascade impactor (ACI), next-generation impactor (NGI) and multistage-liquid impinger (MSLI) were studied to determine their performance when testing ultra-high dose dry powder formulations. Cumulative doses of spray-dried mannitol (Aridol) were delivered to each impactor at a flow rate of 60Lmin(-1) (up to a max dose of 800mg delivering 20 sequential 40mg capsules). In general, total drug collected in both the ACI and NGI falls below the range 85-115% of label claim criteria recommended by the United States of America Food and Drug Administration (FDA) at nominal mannitol doses exceeding 20mg and 200mg, respectively. In comparison analysis of the MSLI data, over a 5-800mg cumulative dosing range, indicated that the percentage of nominal dose recovered from the MSLI was within the +/-15% limits set in this study. Furthermore all samples, apart from the 5mg and 10mg analysis were within 5% of the nominal cumulative dose. While the MSLI is not routinely used for regulatory submission, the use of this impinger when studying ultra-high dose formulations should be considered as a complementary and comparative source of aerosol deposition data.

  15. An ultra-high dose of electron radiation response of Germanium Flat Fiber and TLD-100

    NASA Astrophysics Data System (ADS)

    Alawiah, A.; Amin, Y. M.; Abdul-Rashid, H. A.; Abdullah, W. S. Wan; Maah, M. J.; Bradley, D. A.

    2017-01-01

    The thermoluminescence (TL) response of Germanium Flat Fiber (GFF) and TLD-100 irradiated with 2.5 MeV electrons for the doses up to 1 MGy were studied and compared. The aim was to evaluate the TL supralinearity response at an ultra-high dose (UHD) range and to investigate the change in kinetic parameters of the glow peaks, as the doses increases up to 1 MGy. It is found that the critical dose limit (CDL) of GFF is 5 times higher as compared to TLD-100. CDL is determined by the dose at the maximum supralinearity, f(D)max. It is also found that annealing the TLD-100 and GFF with temperature more than 400 °C is required to reset it back to its original condition, following radiation doses up to 1 MGy. It is also noticed the strange behavior of Peak 4 (TLD-100), which tends to be invisible at the lower dose (<10 kGy) and starts to be appeared at the critical dose limit of 10 kGy. This result might be an important clue to understand the behavior of TLD-100 at extremely high dose range. For both samples, it is observed that the TL intensity is not saturated within the UHD range studied.

  16. 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

  17. High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer

    PubMed Central

    Motohara, Takeshi; Saito, Fumitaka; Takaishi, Kiyomi; Fukumatsu, Yukitoshi; Tohya, Toshimitsu; Shibata, Saburo; Mimori, Hiroyuki; Tashiro, Hironori; Katabuchi, Hidetaka

    2015-01-01

    Objective The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. Methods This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. Results In the UFT group, 103 patients (63.6%) received UFT for ≥90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). Conclusion High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease. PMID:25686399

  18. Use of high-dose chemotherapy in front-line therapy of childhood malignant glioma.

    PubMed

    Massimino, Maura; Biassoni, Veronica

    2006-05-01

    Brain tumors are the second most common cancer in pediatric patients and the main cause from death of malignant tumors in this age group. High-grade or malignant glioma, among which anaplastic astrocytomas and glioblastoma are the most prevalent histotypes, represent 10% of pediatric brain tumors and, taken as a whole, are the second most frequent malignant histotype after medulloblastoma. Apart from complete excision followed by full-dose local radiotherapy, chemotherapy appears to provide some benefit to the final outcome. Different trials have explored the role of high-dose chemotherapy that, theoretically, could give an advantage to these patients by overcoming the blood-brain barrier, cell chemoresistance and inducing a wider number of responses. However, it is still doubtful if more responses translate into better outcome and it is not fully understood which patients can experience a true benefit from this treatment strategy. New protocols under evaluation include new agents with specific biological targets, multiple cycles of high-dose chemotherapy, and vaccination, as an immunotherapeutic approach.

  19. 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.

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

    PubMed

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

    2015-08-18

    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.

  1. High dose folic acid supplementation in women with epilepsy: are we sure it is safe?

    PubMed

    Asadi-Pooya, Ali A

    2015-04-01

    Most experts agree that folic acid supplementation is a key preconception intervention, particularly in women with epilepsy who take anti-epileptic drugs (AEDs). Primary prevention of neural tube defect through folic acid supplementation results in reduction of risk in an otherwise healthy population. The current folic acid supplementation recommendation is that all women of childbearing potential be supplemented with at least 0.4 mg of folic acid daily prior to conception and during pregnancy. It is recommended that all women with epilepsy and of childbearing potential be supplemented with folic acid daily prior to conception and during pregnancy. However, considering the potential significant drug-drug interactions between high doses of folic acid and some AEDs in patients with epilepsy and also with the emerging evidence from animal studies that high levels of folic acid throughout gestation may have adverse effects on fetal brain development, it is not suggested to advocate high dose folic acid supplementation in women with epilepsy until more information is available about its appropriate, safe and optimal dosing.

  2. A real-time image-guided intraoperative high-dose-rate brachytherapy system.

    PubMed

    Li, Shidong; Frassica, Deborah; DeWeese, Theodore; Lee, Ding-Jen; Geng, Jason; Nag, Subir

    2003-01-01

    To develop a real-time, image-guided intraoperative high-dose-rate brachytherapy system. The surface applicator, a catheter array on a 1-mm-thick soft and semitransparent silicone rubber sheet, was directly sutured on the surgical bed. A three-dimensional video camera was then used to instantly capture images of the catheters and the surgical surface. Tracing the catheters on the images allowed us to automatically determine the dwell source positions. Dwell times in the dwell positions were optimized to minimize the dose variation and deviation from the treatment prescription. A dose-texture plot was created to quantify the dose distribution. Treatment planning time was reduced from hours to a few minutes. Phantom tests have shown that the new source localization is accurate with sigma<1.5 mm. All hot spots and cold spots had been eliminated after the dwell-time optimization. This real-time, image-guided planning system can provide optimal image-guided intraoperative high-dose-rate brachytherapy with geometric and dosimetric improvements and a short planning time.

  3. High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis

    PubMed Central

    Tirouvanziam, Rabindra; Conrad, Carol K.; Bottiglieri, Teodoro; Herzenberg, Leonore A.; Moss, Richard B.; Herzenberg, Leonard A.

    2006-01-01

    Neutrophilic airway inflammation is a hallmark of cystic fibrosis (CF). As high oxidant producers, airway neutrophils contribute largely to the systemic redox imbalance seen in CF. In turn, this chronic and profound imbalance can impact circulating neutrophils before their migration into airways. Indeed, in 18 CF patients with stable disease, blood neutrophils were readily deficient in the pivotal antioxidant glutathione (P = 0.003, compared with 9 healthy controls). In a phase 1 study, this deficiency was improved (P = 0.025) by the glutathione prodrug N-acetylcysteine, given orally in high doses (0.6 to 1.0 g three times daily, for 4 weeks). This treatment was safe and markedly decreased sputum elastase activity (P = 0.006), the strongest predictor of CF pulmonary function. Consistently, neutrophil burden in CF airways was decreased upon treatment (P = 0.003), as was the number of airway neutrophils actively releasing elastase-rich granules (P = 0.005), as measured by flow cytometry. Pulmonary function measures were not improved, as expected with short-term treatment. After excluding data from subjects without baseline airway inflammation, positive treatment effects were more pronounced and included decreased sputum IL-8 levels (P = 0.032). Thus, high-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF. PMID:16537378

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

    PubMed

    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

    2011-08-01

    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.

  5. High-dose zoledronic acid narrows the periodontal space in rats.

    PubMed

    Okamoto, Y; Hirota, M; Monden, Y; Murata, S; Koyama, C; Mitsudo, K; Iwai, T; Ishikawa, Y; Tohnai, I

    2013-05-01

    The aim of this experiment was to evaluate the histological effects of zoledronic acid on the periodontal space in rats. 40 male Wistar rats were divided into three zoledronic acid groups and a control group. Zoledronic acid was injected subcutaneously at doses of 10, 50, or 500 μg/kg once a week for 3 weeks. The rats were killed 1 or 9 weeks after the last injection. Histological examination of the periodontal space around the incisor tooth revealed that zoledronic acid did not inhibit tooth development. In the rats killed 1 week after treatment discontinuation, the periodontal space gradually narrowed in response to increasing zoledronic acid doses, and the changes were statistically significant according to ANOVA but not according to ANOVA with post hoc tests. The changes persisted in the high-dose zoledronic acid group despite zoledronic acid discontinuation, with significant differences identified by ANOVA and ANOVA with post hoc tests. Therefore, although zoledronic acid had an insignificant effect on tooth development, it had a significant effect on the periodontal space when high doses were administered. The results of this experiment may provide useful information for future investigations on the role of zoledronic acid in the osteonecrosis of the jaw. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. 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

  7. 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

  8. High-Dose Risperidone Induced Latent Syndrome of Inappropriate Antidiuretic Hormone Secretion With Seizure Presentation.

    PubMed

    Lee, Yen-Feng; Tsai, Chia-Kuang; Liang, Chih-Sung

    2015-01-01

    We report a case of a patient with schizophrenia treated with high-dose risperidone, who developed syndrome of inappropriate antidiuretic hormone secretion (SIADH) with the only early symptom of tonic-clonic seizures. A 40-year-old woman with schizophrenia was treated with risperidone 2 mg/d. After the dosage was titrated to 6 mg/d, she experienced generalized seizure attacks. Laboratory screening revealed that the serum sodium level was 106 mmol/L, the urine sodium concentration was 41.2 mmol/L, and the urine osmolality was 371 mOsm/kg H2O. A diagnosis of SIADH was made, and risperidone was stopped. After infusion of hypertonic saline, the serum sodium returned to normal levels, and seizures did not recur. In this patient, SIADH advanced in a latent manner because the first and only symptom of SIADH was seizure attack. High-dose risperidone treatment is the most probable cause, and the mechanisms may be related to risperidone's high affinity for the 5-hydroxytryptamine 2A and dopamine 2 receptors. Patients with schizophrenia can display atypical features of medical illnesses. Routine physical and laboratory examinations may prevent silent disease progression.

  9. High-dose chemotherapy with peripheral blood stem cell rescue in blastoid natural killer cell lymphoma.

    PubMed

    Mukai, H Y; Kojima, H; Suzukawa, K; Hori, M; Komeno, T; Hasegawa, Y; Ninomiya, H; Mori, N; Nagasawa, T

    1999-02-01

    A 25-year-old man was referred because of skin rash, lymphadenopathy and anemia. Laboratory examinations revealed severe anemia (Hb, 4.8 g/dl) and elevated levels of GOT, GPT, LDH and soluble interleukin-2 receptor. Work-up studies disclosed the involvement of lymphoma cells in lymph nodes, skin, bilateral kidneys and bone marrow. Lymph node biopsy revealed diffuse proliferation of medium- to large-sized lymphoblastic cells. Bone marrow aspiration showed massive infiltration of large blastic cells with no cytoplasmic granules. The lymphoma cells in bone marrow and lymph node showed surface CD3-, cytoplasmic CD3epsilon+, CD4+, CD8-, CD56+, CD57-, CD16- and CD43 (MT-1)+ phenotype. Analyses of T cell receptor beta and gamma genes showed germ line configurations. EBER-1 was not detectable in the lymphoma cells. He was diagnosed as having blastoid natural killer (NK) cell lymphoma. In spite of several courses of combination chemotherapy, the lymphoma was progressive. He was then treated with high-dose chemotherapy and peripheral blood stem cell rescue, achieving remission which has now lasted for more than 12 months. We consider that blastoid NK cell lymphoma is an extremely aggressive subtype of CD56-positive lymphomas, and high-dose chemotherapy with peripheral blood stem cell rescue should be included for the choice of the treatment.

  10. High dose pulsatile dexamethasone therapy in children with opsoclonus-myoclonus syndrome.

    PubMed

    Rostásy, K; Wilken, B; Baumann, M; Müller-Deile, K; Bieber, I; Gärtner, J; Möller, P; Angelini, P; Hero, B

    2006-10-01

    Opsoclonus-myoclonus syndrome (OMS) is a rare movement disorder characterized by chaotic eye movements, myoclonus, and ataxia associated with severe irritability. Different treatment modalities including steroids and cyclophosphamide have been tried in the past often with significant side effects and variable success. Here we present 11 children, diagnosed with OMS between 1999 and 2005 and treated with high dose dexamethasone pulses. Main symptoms at presentation were opsoclonus (11/11), ataxia and/or myoclonus (11/11), irritability (10/11) associated with a neuroblastoma in four children. Number of dexamethasone pulses ranged from 6 to 60 pulses. No major side effects were reported. In 6/11 children a complete and sustained remission of OMS symptoms was achieved after 6 to 29 pulses of dexamethasone. Two children from this group have a normal development and no neurological sequelae. Two further children have minor delays in fine- and gross-motor skills. Two children despite a complete recovery of OMS symptoms have persisting developmental problems. 5/11 children still require regular dexamethasone pulses in addition to daily prednisolone (n = 1) or have received cyclophosphamide pulses meanwhile (n = 2). All children continue to have developmental and neurological difficulties. In summary treatment with high dose pulsatile dexamethasone appears to be safe and beneficial in a subgroup of patients with OMS.

  11. Reirradiation using high-dose-rate brachytherapy in recurrent carcinoma of uterine cervix.

    PubMed

    Mahantshetty, Umesh; Kalyani, Nikhil; Engineer, Reena; Chopra, Supriya; Jamema, Swamidas; Ghadi, Yogesh; Deshpande, Deepak; Shrivastava, Shyamkishore

    2014-01-01

    To assess the feasibility of reirradiation with image-based high-dose-rate brachytherapy in previously irradiated patients with recurrent carcinoma of uterine cervix. Thirty previously irradiated patients diagnosed with central recurrence were treated with reirradiation. Martinez Universal Perineal Implant Template was used in 24 patients and Vienna applicator in 6 patients. Median interval between two radiation schedules was 25 months. Median delivered dose was 42 Gy equivalent dose at 2 Gy (EQD2; interquartile range, 37-46 Gy EQD2). All 30 patients tolerated reirradiation well. Complete response was seen in 23 (76%) patients. With a median followup of 25 months, 2-year local control, disease-free survival, and overall survival were 44%, 42%, and 52%, respectively. Fifteen patients developed local recurrences; Local control rate was significantly higher with doses >40 Gy EQD2 (52% vs. 34%; p = 0.05). Disease-free survival was better for patients with longer interval (>25 months) between two radiotherapy schedules. Grade III radiation proctitis and cystitis was seen in 3 patients each, and Grade II small bowel toxicity was seen in 3 patients. Reirradiation using high-dose-rate brachytherapy is feasible with acceptable outcomes in isolated local recurrence deemed unsuitable for surgery. The outcome is better with higher doses. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  12. Application of melt granulation technology to enhance tabletting properties of poorly compactible high-dose drugs.

    PubMed

    Lakshman, Jay P; Kowalski, James; Vasanthavada, Madhav; Tong, Wei-Qin; Joshi, Yatindra M; Serajuddin, Abu T M

    2011-04-01

    Using metformin HCl as the model drug and hydroxypropylcellulose (HPC) as the polymeric excipient, a melt granulation (MG) process that employs a twin-screw extruder has been developed to enhance compactibility of poorly compactible high-dose drug substances. A high (90%) drug-load tablet formulation, containing 1025 mg of active pharmaceutical ingredients and 109 mg of excipients, was produced. Drug-polymer-powder mixtures were melt granulated at a temperature above glass transition of HPC (130°C) but below melting point of metformin HCl (224°C). MG was compared with modified wet granulation (WG) and solvent granulation (SG) processes. Under identical compression force, the hardness of tablets produced was MG>SG>WG and the friability was MGhigh-dose drugs and combination products by decreasing the need for relatively large amounts of excipients generally used to overcome physicochemical limitations of drug substances. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1553-1565, 2011.

  13. 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. Published by Elsevier Ltd.

  14. Visual Outcome after Treatment with High Dose Intravenous Methylprednisolone in Indirect Traumatic Optic Neuropathy.

    PubMed

    Pokharel, S; Sherpa, D; Shrestha, R; Shakya, K; Shrestha, R; Malla, O K; Pradhananga, C L; Pokhrel, R P; Shrestha, P

    2016-01-01

    Traumatic optic neuropathy is an acute injury of the optic nerve due to trauma. It is an ocular emergency, requiring early treatment though there is no proven standard treatment protocol for the condition. Various studies have shown improvement in vision after intravenous steroids, but not statistically significant. Studies have revealed even optical decompression surgery is not the ultimate treatment because of no significant improvement of vision. Our study aims to assess visual outcome after high dose (1 gram) of intravenous methylprednisolone in cases with indirect optic neuropathy. This was a non-randomized interventional study carried out in Kathmandu Medical College Teaching Hospital from May 1st 2013- June 1st 2014. There were 10 cases with indirect traumatic optic neuropathy included in the study. Four cases received IV methylprednisolone and six cases were observed without steroid treatment. Traumatic optic neuropathy was observed more in males[8 (80%)]with higher number in age group 21-30 years old. The visual recovery after intravenous steroid treatment was rapid and beneficial in cases with vision better than Non Perception of Light (NPL), even in cases presented 4 days after the trauma. There was rapid and beneficial improvement in visual acuity after high dose of intravenous steroid treatment in cases with indirect traumatic optic neuropathy with vision better than Non Perception of Light (NPL).

  15. Introduction of novel 3D-printed superficial applicators for high-dose-rate skin brachytherapy.

    PubMed

    Jones, Emma-Louise; Tonino Baldion, Anna; Thomas, Christopher; Burrows, Tom; Byrne, Nick; Newton, Victoria; Aldridge, Sarah

    Custom-made surface mold applicators often allow more flexibility when carrying out skin brachytherapy, particularly for small treatment areas with high surface obliquity. They can, however, be difficult to manufacture, particularly if there is a lack of experience in superficial high-dose-rate brachytherapy techniques or with limited resources. We present a novel method of manufacturing superficial brachytherapy applicators utilizing three-dimensional (3D)-printing techniques. We describe the treatment planning process and the process of applicator manufacture. The treatment planning process, with the introduction of a pre-plan, allows for an "ideal" catheter arrangement within an applicator to be determined, exploiting varying catheter orientations, heights, and curvatures if required. The pre-plan arrangement is then 3D printed to the exact specifications of the pre-plan applicator design. This results in improved target volume coverage and improved sparing of organs at risk. Using a pre-plan technique for ideal catheter placement followed by automated 3D-printed applicator manufacture has greatly improved the entire process of superficial high-dose-rate brachytherapy treatment. We are able to design and manufacture flexible, well-fitting, superior quality applicators resulting in a more efficient and improved patient pathway and patient experience. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  16. High-dose-rate brachytherapy boost for prostate cancer: rationale and technique.

    PubMed

    Morton, Gerard C

    2014-10-01

    High-dose-rate brachytherapy (HDR) is a method of conformal dose escalation to the prostate. It can be used as a local boost in combination with external beam radiotherapy, with a high degree of efficacy and low rate of long term toxicity. Data consistently reports relapse free survival rates of greater than 90% for intermediate risk patients and greater than 80% for high risk. Results are superior to those achieved with external beam radiotherapy alone. A wide range of dose and fractionation is reported, however, we have found that a single 15 Gy HDR combined with hypofractionated radiotherapy to a dose of 37.5 Gy in 15 fractions is well tolerated and is associated with a long term relapse-free survival of over 90%. Either CT-based or trans-rectal ultrasound-based planning may be used. The latter enables treatment delivery without having to move the patient with risk of catheter displacement. We have found it to be an efficient and quick method of treatment, allowing catheter insertion, planning, and treatment delivery to be completed in less than 90 minutes. High-dose-rate boost should be considered the treatment of choice for many men with high and intermediate risk prostate cancer.

  17. 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

  18. Refractory metabolic acidosis as a complication of high-dose midazolam infusion for pediatric status epilepticus.

    PubMed

    Federman, Myke D; Kelly, Robert; Harrison, Rick E

    2009-01-01

    The use of midazolam for the treatment of status epilepticus in children has generally been shown to be well tolerated and safe. Furthermore, encouraging efficacy has been observed when pediatric patients with status epilepticus have received continuous intravenous infusions of midazolam. A 9-year-old girl was treated with high-dose, continuous intravenous infusion of midazolam for the management of refractory status epilepticus. The patient developed a severe hyperchloremic, non-anion gap metabolic acidosis and resultant hemodynamic compromise, necessitating significant inotropic support and the initiation of a vasopressor infusion. We speculate that this complication was due to the preparation of parenteral midazolam with hydrochloric acid. The midazolam infusion was stopped, and, in less than 5 hours, the patient's metabolic acidosis resolved. The patient's inotropic and vasopressor infusions could only be weaned after discontinuing the use of high-dose midazolam. Although this complication was observed in only 1 pediatric patient with cortical dysplasia, caution and close clinical and laboratory surveillance should be exercised when administering continuous intravenous infusions of midazolam to pediatric patients.

  19. Transmission Electron Microscopy of XDR Mycobacterium tuberculosis Isolates Grown on High Dose of Ofloxacin

    PubMed Central

    Arjomandzadegan, Mohammad; Sadrnia, Maryam; Titov, Leonid; Surkova, Larissa; Sarmadian, Hossein; Ghasemikhah, Reza; Hosseiny, Hossein

    2017-01-01

    The aim of the study was to investigate behavior of resistant Mycobacterium tuberculosis (MTB) isolates under a high dose of ofloxacin and its morphological changes. 19 extensively drug resistant (XDR) clinical isolates of MTB were grown on Löwenstein–Jensen medium containing progressively increasing concentrations of ofloxacin (2, 4, 8, 16, 32 mg/L). Ultra-structure analyses of resistant isolates grown on ofloxacin were conducted by transmission electron microscopy (TEM). Fixation was carried out by 4% glutaraldehyde in 0.1 M sodium cacodylate buffer on 300 mesh carbon formvar copper grid. The samples were negatively stained with uranium acetate suspension. All 19 XDR MTB isolates were grown and formed colonies successfully on 2, 4, 8 mg/L, seven isolates on 16 mg/L, and four isolates on 32 mg/L ofloxacin. Morphological changes and unusual forms were detected in 8, 16 and 32 mg/L ofloxacin at 43%, 76.5% and 81% of cells, respectively. Swollen form (protoplast like), ghost-like cell, degraded forms, and in a few cases, detached cytoplasm from cell wall were clearly detected in high drug concentrations in comparison to control. Changes in morphology were increased with increasing ofloxacin concentrations (p < 0.05). Some XDR isolates could be successfully grown on high doses of ofloxacin (32 mg/L), but with changes in morphology. It was concluded that several magnitudes of the drug doses could not prevent growth of drug resistant forms. PMID:28157163

  20. 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.

  1. 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

  2. High-dose chemotherapy with autologous peripheral blood stem cell support for recurrent primary AFP-producing intracranial germinoma

    PubMed Central

    Ziske, Carsten; Mezger, Jörg; Jiménez, Carlos; Kleinschmidt, Rolf; Pels, Hendrik; Schlegel, Uwe; Schmidt-Wolf, Ingo G.H.

    2003-01-01

    We report of a 34-year old man with second intracranial relapse of a suprasellar germinoma. Despite of extensive pretreatment with radiation and conventional chemotherapy relapse occurred and was treated with sequential high-dose chemotherapy followed by transfusion of autologous peripheral stem cells. The high-dose chemotherapy course was complicated by refractory derailment of pineal gland insufficiency. The patient achieved a complete remission after high dose chemotherapy which lasted for 13 months. Subsequently, he developed a third relapse and died. PMID:19675701

  3. Acidified sodium chlorite as an alternative to chlorine for elimination of salmonella on alfalfa seeds.

    PubMed

    Liao, C-H

    2009-01-01

    The health and environmental hazard associated with the use of chlorine for food processing has 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. Contaminated seeds containing approximately 1.5 x 10(7) CFU/g of Salmonella were treated with ASC or Ca(OCl)(2) at different concentrations and for different periods of time. Results showed that the efficacy of ASC and Ca(OCl)(2) for elimination of Salmonella on contaminated seeds could be improved greatly by extending the treatment time from the traditional 15 to 45 min. Treatment of seeds with 800 ppm of ASC for 45 min reduced the number of Salmonella by 3.9 log units, approximately 1.2 log units higher than that treated with 20000 ppm of Ca(OCl)(2). Treatment of seeds with a lower concentration (100 to 400 ppm) of ASC for 45 min reduced the number of Salmonella by 1.3 to 2.2 log units. Soaking alfalfa seeds in 800 ppm of ASC for 45 min did not affect seed germination. However, soaking seeds in 20000 ppm of Ca(OCl)(2) for 45 min reduced seed germination by 20%. Unlike Ca(OCl)(2), antimicrobial efficiency of ASC was not affected by pre-exposure to alfalfa seeds. Data presented also showed that Salmonella on newly inoculated seeds that had been stored at 4 degrees C for less than 7 d were more sensitive to sanitizer treatment than those on seeds that had been stored for 4 wk or longer.

  4. Reducing levels of Listeria monocytogenes contamination on raw salmon with acidified sodium chlorite.

    PubMed

    Su, Yi-Cheng; Morrissey, Michael T

    2003-05-01

    The antimicrobial activity of acidified sodium chlorite (ASC) against Listeria monocytogenes in salmon was studied. Raw salmon (whole fish and fillets) inoculated with L. monocytogenes (10(3) CFU/cm2 or 10(4) CFU/g) were washed with ASC solution (50 ppm) for 1 min and stored at -18 degrees C for 1 month (whole salmon) or in ice for 7 days (fillets). L. monocytogenes populations were determined for whole salmon after frozen storage and for fillets on days 1, 3, 5, and 7 of storage. A wash with ASC solution followed by ASC glazing did not reduce L. monocytogenes on the skin of whole salmon during frozen storage. However, the wash resulted in an L. monocytogenes reduction of 0.5 log CFU/g for salmon fillets. The populations of L. monocytogenes in fillets increased slowly during ice storage, but the growth of these populations was retarded by ASC ice. By day 7, the populations were 0.25 log units smaller in fillets stored in ASC ice and 0.62 log units smaller in fillets that had been washed with ASC solution and stored in ASC ice than in control fillets. Treatment with ASC also reduced total plate counts (TPCs) by 0.43 log CFU/cm2 on the skin of whole salmon and by 0.31 log CFU/g in fillets. The TPCs for skin decreased during frozen storage but increased gradually for fillets stored at 5 degrees C or in ice. However, TPCs of ASC-treated samples were lower than those for controls at any point during the study. Washing with ASC solution significantly (P < 0.05) reduced TPCs on the skin of whole salmon and in fillets, as well as L. monocytogenes in fillets. The antimicrobial activity of ASC was enhanced when salmon was washed with ASC solution and stored in ASC ice.

  5. Acidified sodium chlorite solution as an antimicrobial treatment for rainbow trout (Oncorhynchus mykiss) fillets.

    PubMed

    Kamireddy, N; Kenney, P B; Jittinandana, S; Slider, S D

    2008-05-01

    Minimizing microbial growth and maintaining overall quality are priorities for intervention strategies that extend the shelf life of fresh, aquatic foods. Four treatments included a control (fresh fillets), water, 50 ppm of acidified sodium chlorite (ASC), and 1,000 ppm of ASC. Fillets were stored at 1 to 2 degrees C for 0, 8, and 15 days. A significant (P < 0.05) interaction between treatment and storage time was observed for psychrotrophic counts. The increase in psychrotrophic counts with storage time was less for fillets treated with ASC, regardless of ASC concentration. Aerobic plate counts were not affected (P > 0.05) by intervention; however, a significant increase in counts was observed during storage (P < 0.05). Fillet pH, moisture, fat, thiobarbituric acid-reactive substances, fatty acid composition, color, cook yield, and shear force were not affected (P > 0.05) by intervention. Thiobarbituric acid-reactive substances decreased (P < 0.05) during storage. Percentages of individual fatty acids were constant, with the exception of C15 and C20:2; they decreased with storage to 15 days. Percent fat, L* (lightness) and b* (yellowness) values, and cook yield increased (P < 0.05) during storage. Fillet pH, moisture, a* (redness) value, and shear force did not change (P > 0.05) with storage to 15 days. Based on these data, 50 ppm of ASC performed equally as well as 1,000 ppm of ASC. The value of ASC is as a decontaminant; however, fillets in this study had low psychrotrophic counts pretreatment (2.3 log CFU/cm2) and posttreatment (2.03 log CFU/cm2), which did not demonstrate ASC's effectiveness as a decontaminant.

  6. [High dose cinobufocini in attenuation and treatment of infection and granulocytopenia during combined chemotherapy of malignant blood diseases].

    PubMed

    Yue, B B

    1992-03-01

    The use of high dose Cinobufocini in attenuation and treatment of infection and granulocytopenia during combined chemotherapy was observed in patients with malignant blood diseases. The study was designed in such a way that each patient served as self control. The patients, 18 males and 12 females, aged 16-66 (average 34), 62 experiments in 20 patients with acute leukemia, 8 with malignant lymphoma and 2 with multiple myeloma were observed. In patients with the treatment of high dose Cinobufocini, infection was significantly decreased and the number of granulocytes was not markedly changed before and after the treatment. The observation demonstrated that high dose Cinobufocini can significantly reduce the risk of infection and degree and duration of granulocytopenia associated with chemotherapy of patients with malignant blood diseases. The use of high dose Cinobufocini is simple and convenient and with very little side effects.

  7. Randomised crossover trial of tripotassium dicitrato bismuthate versus high dose cimetidine for duodenal ulcers resistant to standard dose of cimetidine.

    PubMed

    Lam, S K; Lee, N W; Koo, J; Hui, W M; Fok, K H; Ng, M

    1984-07-01

    Of 212 patients with duodenal ulcer treated with four weeks of one gram daily cimetidine, 25 had ulcers which underwent no reduction in size despite treatment. The effects of tripotassium dicitrato bismuthate (TDB) tablet four times a day or cimetidine 1.6 g daily on the healing of these cimetidine resistant ulcers were compared in a randomised crossover trial. Ten of 12 patients on tripotassium dicitrato bismuthate and five of 13 patients on high dose cimetidine had complete healing (p less than 0.02). On crossing over, seven of the eight ulcers not healed by high dose cimetidine completely healed with TDB in another four weeks, and one of the two ulcers not healed by TDB healed with high dose cimetidine. Overall, TDB healed 85% of cimetidine resistant ulcers, whereas high dose cimetidine healed 40% (p less than 0.006). Tripotassium dicitrato bismuthate is recommended for cimetidine resistant duodenal ulcers.

  8. 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

  9. [Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously].

    PubMed

    Fievet, Patrick; Coppin, Mathilde; Brazier, François; Lefèvre, Magali; Stephan, Robin; Demontis, Renato

    2012-02-01

    Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m(2)), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) <20% and/or serum ferritin of less than 100 μg/L. Patients received treatment by ESA in 16 cases out of 29. One month after treatment, hemoglobin (Hb) increased significantly (11.4±1.6 vs 10.4±1.4 g/dL, P=0.0003) along with a significant increase in TSAT (21.3±7.3 vs 13.3±3.8%, P=0.000003) and serum ferritin (286±253 vs 91±60 μg/L, P=0.00005). Six patients had a serum ferritin greater than 500 μg/L after treatment, which may put them at risk of iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self

  10. Oral high-dose multivitamins and minerals after myocardial infarction: a randomized trial.

    PubMed

    Lamas, Gervasio A; Boineau, Robin; Goertz, Christine; Mark, Daniel B; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L; Lindblad, Lauren; Lewis, Eldrin F; Drisko, Jeanne; Lee, Kerry L

    2013-12-17

    Whether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown. To assess whether oral multivitamins reduce cardiovascular events and are safe. Double-blind, placebo-controlled, 2 x 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) SETTING: 134 U.S. and Canadian academic and clinical sites. 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 mol/L (2.0 mg/dL) or less. Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo. The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events. There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety). High-dose oral multivitamins and

  11. 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

  12. [Vitamin B12 deficiency associated with high doses od metformin in older people diabetic].

    PubMed

    Sánchez, Hugo; Masferrer, Dominique; Lera, Lydia; Arancibia, Estrella; Angel, Barbara; Albala, Cecilia

    2014-06-01

    The aim of the study was to estimate if B12 deficiency is associated with the use of metformin in the elderly diabetics. Case-control study in diabetic OP. Cases (n = 137) were defined as elderly with B12 < 221 pmol/L and controls (n = 279) elderly with B12 > 221 pmol/L. Four categories of metformin use were defined: non-users, ≤850 mg/day, > 850 and < 2,550 mg/day and ≥2,550 mg/day. Metformin ≥2,550 mg/day was high doses considered. The crude OR for B12 deficiency and consumption of Metformin were calculated. Logistic regression models were developed to explore the association between B12 deficiency and metformin dose. The research protocol was approved by the Ethics Committee of INTA. The age of cases and controls was (70.2 years vs 68.6 years (p < 0.05). The 62% were women in cases vs 74.9% in controls (p < 0.05). The 73% of cases and 76% of controls used metformin (p < 0.05) the average consumption of metformin was de 1,954.3 mg/day (SD: 1,063.2) in cases and 1,696.6 mg/day (SD: 1,074.4) in controls (p < 0.05). The use of 2,550 mg/day was observed in 29.2% of cases and 19.3% for controls (p < 0.05). It was observed that OP who consumed high doses of metformin had 1.9 times the risk of B12 deficiency (OR: 1.9; 95%CI: 1,08- 3,30). These results show a strong association between high doses of metformin and low levels of vitamin B12 in diabetic elderly. This project was funded by FONIS SA11I2092. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  13. Enhanced neurodegeneration after a high dose of methamphetamine in Adenosine A3 receptor Null mutant mice

    PubMed Central

    Shen, Hui; Luo, Yu; Yu, Seong-Jin; Wang, Yun

    2011-01-01

    Previous reports have indicated that adenosine A3 receptor (A3R) knockout mice are more sensitive to ischemic or hypoxic brain injury. The purpose of this study was to examine if suppression of A3R expression is associated with increase in sensitivity to injury induced by a high dose of methamphetamine (Meth). Adult male A3R null mutant (−/−) mice and their controls (+/+) were injected with 4 doses (2 hours apart) of Meth (10 mg/kg) or saline. Animals were placed in a behavioral activity chamber, equipped with food and water, for 52 hours starting from one day after injections. The first 4 hours were used for studying exploratory behaviors and the next 48 hours were used to measure locomotor activity. High doses of Meth equally reduced the 4-hour exploratory behavior in −/− and +/+ mice. Meth suppressed locomotor activity between 4 and 52 hours in both groups, with a greater reduction being found in the −/− mice. Brain tissues were collected at 3 days after the Meth or saline injections. Meth treatment reduced striatal dopamine (DA) levels in both +/+ and −/− mice, examined by HPLC, with an increase in DOPAC/DA ratio being found only in −/− animals. Meth also significantly increased ionized calcium-binding adaptor molecule 1 (Iba-1) and cleaved caspase-3 level in striatum as well as Iba-1 and TNFα mRNA expression in nigra in −/−, compared to +/+, mice. Previous studies have shown that pharmacological suppression of VMAT2 by reserpine enhanced Meth toxicity by increasing cytosolic DA and inflammation. A significant reduction in striatal VMAT2 expression was found in −/− mice, compared to +/+ mice, suggesting that increase in sensitivity to Meth injury in −/− mice may be related to a reduction in VMAT2 expression in these mice. In conclusion, our data suggest that A3R −/− mice are more sensitive to high doses of Meth. PMID:21867746

  14. 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

  15. 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

  16. High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study

    PubMed Central

    Spooner, Luke; Fernandes, Kimberly; Martins, Diana; Juurlink, David; Mamdani, Muhammad; Paterson, J. Michael; Singh, Samantha; Gomes, Tara

    2016-01-01

    Aims To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity. Design Interventional time-series analysis. Setting Ontario, Canada, from 2003 to 2014. Participants Ontario Drug Benefit (ODB) beneficiaries aged 15 to 64 years from 2003 to 2014. Interventions Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010) and implementation of Ontario’s Narcotics Safety and Awareness Act (NSAA; November 2011). Measurements Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions. Findings Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03) which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43). Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7%) over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68) or enactment of the NSAA (p-value = .59). Conclusions Although the

  17. 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

  18. 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

  19. 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

  20. High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study.

    PubMed

    Fernandes, Kimberly; Martins, Diana; Juurlink, David; Mamdani, Muhammad; Paterson, J Michael; Spooner, Luke; Singh, Samantha; Gomes, Tara

    2016-01-01

    To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity. Interventional time-series analysis. Ontario, Canada, from 2003 to 2014. Ontario Drug Benefit (ODB) beneficiaries aged 15 to 64 years from 2003 to 2014. Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010) and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011). Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions. Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03) which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43). Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7%) over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68) or enactment of the NSAA (p-value = .59). Although the Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain led

  1. High-dose immunosuppressant alters the immunological status of New Zealand white rabbits following skin transplantation

    PubMed Central

    CHENG, PEILUN; ZHONG, LIMING; JIANG, ZESHENG; WANG, YAN; PAN, MINGXIN; GAO, YI

    2015-01-01

    The aim of this study was to investigate the effect of an immunosuppressant on the immunological status of New Zealand white rabbits after skin grafting, and to evaluate a method for monitoring the immunological status of subjects with skin transplants. The rabbits were randomly divided into allograft rejection, autograft tolerance, nontransplant, allograft low-dose immunosuppressant and allograft high-dose immunosuppressant groups. The rabbits in the low- and high-dose immunosuppressant groups were treated with cyclosporine A intravenously 8 h prior to skin transplantation and once daily following transplantation at doses of 2 and 25 mg/kg, respectively. At 12 days after skin transplantation, the spleens of donor (female) rabbits and recipient (male) rabbits were harvested for the preparation of single-cell suspensions. The splenocytes from recipient and donor rabbits were labeled with 0.3 or 6 µM carboxy fluorescein diacetate succinimidyl ester, respectively, and a mixed cell suspension was prepared. The final preparation was intravenously injected into recipient New Zealand white rabbits. The ratio of the two fluorescently labeled cell populations in the peripheral blood was measured using flow cytometry at 1, 2, 4 and 8 h after the injection, and the cell death rate was calculated. Histological analysis was also performed on samples collected at the time of splenectomy. The cell death rates of the allograft rejection and low-dose immunosuppressant groups reached their highest levels 8 h after the injection of spleen cell suspension. Allogeneic spleen cells from donor male rabbits were almost completely removed within 8 h of injection. The cell death rate increased slowly in the nontransplant, autograft and high-dose immunosuppressant groups without specificity. This study provides a specific method for the in vivo monitoring of the immunological status of patients after skin grafting. This method can quickly and accurately detect the immunological status of

  2. 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

  3. Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

    SciTech Connect

    Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

    2008-07-01

    Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m{sup 2}) on Days 1-4 and either mitomycin C (10 mg/m{sup 2}) or cisplatin (75 mg/m{sup 2}) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m{sup 2}) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age {<=}64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes.

  4. 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

  5. High dose versus low dose oxytocin for augmentation of delayed labour.

    PubMed

    Mori, Rintaro; Tokumasu, Hironobu; Pledge, Debbie; Kenyon, Sara

    2011-10-05

    A major cause of failure to achieve spontaneous vaginal birth is delay in labour caused by presumed inefficient uterine action. High dose may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. To compare starting dose and increment of amount of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high dose of oxytocin improves labour outcomes and the effect on both maternal/neonatal outcomes and women's birth experiences. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2011) and reference lists of retrieved studies. We included all randomised and quasi-randomised controlled trials for women in delayed in labour requiring augmentation by oxytocin comparing high starting and increment dose (defined as starting dose and increment of equal to or more than 4 mU per minute) with low dose (defined as starting dose and an increment of less than 4 mU per minute. Increase interval: between 15 and 40 minutes. The separation of low and high doses is based on an arbitrary decision. Three review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. We included four studies involving 660 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in rate of caesarean section (risk ratio (RR) 0.53; 95% CI 0.38 to 0.75, four trials, 650 women) and an increase in the rate of spontaneous vaginal birth (RR 1.37; 95% CI 1.15 to 1.64, two trials, 350 women). There were no significant differences for neonatal mortality, hyperstimulation, chorioamnionitis, epidural

  6. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy.

    PubMed

    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.

  7. High-Dose Subcutaneous Immunoglobulin in Patients With Multifocal Motor Neuropathy: A Nursing Perspective.

    PubMed

    Rasutis, Vilija M; Katzberg, Hans D; Bril, Vera

    Multifocal motor neuropathy (MMN), an immune neuromuscular condition causing progressive weakness, usually responds to immune-mediated treatments, including intravenous immunoglobulin (IVIG). Fifteen patients with MMN receiving IVIG were enrolled in an open-label, single-center trial and switched to 20% subcutaneous immunoglobulin (SCIG) using a smooth transition protocol (ie, changing the therapy without interruption or impact on the intended outcome of the therapy). Patients received individualized training and support based on motivation and ability to learn, follow directions, and maintain compliance. Although some patients required assistance during the training phase, most managed self-infusion and reported satisfaction in managing therapy autonomously. Educating patients with neuropathies to self-infuse high-dose SCIG at home and with flexibility in dosing schedules was successfully demonstrated in this patient group.

  8. High doses of (-)-epigallocatechin-3-gallate from green tea induces cardiac fibrosis in mice.

    PubMed

    Cai, Yi; He, Shu-Qiao; Hong, Hui-Qi; Cai, Yue-Peng; Zhao, Li; Zhang, Mei

    2015-12-01

    Tea is the most consumed beverage in the world. (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, is effective in the prevention of several chronic diseases, and is marketed as part of many dietary supplements. We have now examined the myocardiotoxic effect of high doses of EGCG in mice. EGCG (500 and 1000 mg/kg·d) induced cardiac collagen synthesis and fibrosis-related protein expression, such as connective tissue growth factor (CTGF) and fibronectin (FN) in mice. Moreover, EGCG decreased the protein expression of p-AMPK and increased the levels of p-p70S6 K and p-S6. This is the first evidence that high oral doses of EGCG could induce cardiac fibrosis, and shed new light on the understanding of EGCG-mediated myocardiotoxicity.

  9. Cerebral toxoplasmosis after tandem high-dose chemotherapy and autologous hematopoietic cell transplant for neuroblastoma.

    PubMed

    Voegele, Laura; Cheerva, Alexandra C; Bertolone, Salvatore

    2013-03-01

    Toxoplasmosis is a well-recognized life-threatening complication of hematopoietic cell transplantation (HCT). This report describes a pediatric patient with stage 4 neuroblastoma who developed cerebral toxoplasmosis after tandem high-dose chemotherapy with autologous HCT. Toxoplasmosis is rare in patients undergoing autologous HCT; however, tandem autologous HCT is more immunosuppressive than a single autologous HCT. Toxoplasmosis is a potential complication in autologous as well as allogeneic transplants, and should be considered in any post-HCT patient with neurological dysfunction. Rapid diagnosis and immediate antimicrobial treatment are crucial to avoid morbidity and mortality. Evaluation of toxoplasma serology should be standard in all patients undergoing tandem autologous HCT and seropositive patients should be started on appropriate prophylactic therapy.

  10. Single high dose-large field irradiation in drug resistant non-Hodgkin's lymphoma

    SciTech Connect

    Scarantino, C.W.; Greven, K.M.; Buss, D.H.

    1988-05-01

    Single high dose-large field irradiation (SHD-LFI), also described as half-body irradiation (HBI), has previously been reported as an effective modality for the palliation of symptoms in a number of solid tumors. This report concerns the ability of SHD-LFI to produce palliation of symptoms and/or objective response in patients with drug resistant non-Hodgkin's lymphoma (NHL). From 1981 to 1984, 34 patients with advanced drug resistant NHL were treated with SHD-LFI either to the whole abdomen (24 patients) or to the upper half body (10 patients). Overall, 19 of 23 patients achieved symptomatic improvement, while objective response was noted in 23 of 30 patients. We noted subjective and objective response in all histologies, and duration of response was not significantly different. Our results suggest a beneficial role for the early and judicious use of SHD-LFI in NHL.

  11. Perceived efficacy and satisfaction of patients with subcutaneous hypoallergenic high-dose house dust mite extract.

    PubMed

    Roger Reig, A; Ibero Iborra, M; Carrillo Díaz, T; López Abad, R; Sánchez Moreno, V; Álvarez Nieto, J; Cancelliere, N

    2017-05-01

    The efficacy and safety of subcutaneous immunotherapy with modified, high-dose, major allergen house dust mite extract is widely supported by double-blind, placebo-controlled studies. However, little is known regarding patient-perceived efficacy and satisfaction. An observational, retrospective, multicentre study in patients treated with Acaroid(®) was conducted to assess the efficacy and degree of satisfaction of the patients after the first six months of treatment with it. All the clinical study procedures were performed according to the routine clinical practice. This study demonstrates that Acaroid(®) is effective and well tolerated. The patients' condition demonstrated a clear and marked improvement in the first 6 months after treatment initiation. Patients treated with Acaroid(®) were very satisfied, with a correlation to improvement in patient-perceived symptoms and the administration of treatment by a healthcare professional.

  12. Effect of High Doses of Radiation on Human Neutrophil Chemotaxis, Phagocytosis and Morphology

    PubMed Central

    Holley, Thomas R.; Van Epps, Dennis E.; Harvey, Ronald L.; Anderson, Robert E.; Williams, Ralph C.

    1974-01-01

    Human neutrophils were exposed to varying amounts of ionizing radiation up to 1,000,000 rad and evaluated as to their ability to respond to chemotactic stimuli and phagocytize and kill bacteria. Striking morphologic and functional resistance to radiation was apparent. At doses up to 5,000 rad there was little or no impairment of chemotaxis. As the dosage increased to 50,000 rad, chemotaxis decreased to approximately 50% of nonirradiated control values. At very high doses of radiation (250,000 to 1,000,000 rad) neutrophils failed to respond significantly to chemotactic stimuli. Effects of radiation as measured by phagocytosis and the degree of ultrastructural change paralleled the chemotaxis results. ImagesFig 3Fig 4AFigs 4B-CFig 1Fig 2 PMID:4596654

  13. Temozolomide-Associated Bronchiolitis Obliterans Organizing Pneumonia Successfully Treated with High-Dose Corticosteroid

    PubMed Central

    Kim, Tae-Ok; Kang, Hyun-Wook; Chi, Su-Young; Ban, Hee-Jung; Kwon, Yong-Soo; Kim, Kyu-Sik; Kim, Yu-Il; Lim, Sung-Chul; Kim, Young-Chul

    2012-01-01

    Temozolomide is an oral alkylating agent with clinical activity against glioblastoma multiforme (GM). It is generally well-tolerated and has few pulmonary side effects. We report a case of temozolomide-associated brochiolitis obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid treatment. A 56-yr-old woman presented with a 2-week history of exertional dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy with temozolomide. After the 1st cycle, progressive dyspnea was gradually developed. Chest radiograph showed diffuse patchy peribronchovascular ground-glass opacities in both lungs. Conventional dose of methylprednisolone (1 mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung biopsy findings were compatible with BOOP, the patient's clinical course was more aggravated until hospital day 5. After the dose of methylprednisolone was increased (500 mg/day for 5 days) radiologic findings were improved dramatically. PMID:22468112

  14. Depth profile study of Ti implanted Si at very high doses

    NASA Astrophysics Data System (ADS)

    Olea, J.; Pastor, D.; Toledano-Luque, M.; Mártil, I.; González-Díaz, G.

    2011-09-01

    A detailed study on the resulting impurity profile in Si samples implanted with high doses of Ti and subsequently annealed by pulsed-laser melting (PLM) is reported. Two different effects are shown to rule the impurity profile redistribution during the annealing. During the melting stage, the thickness of the implanted layer increases while the maximum peak concentration decreases (box-shaped effect). On the contrary, during the solidifying stage, the thickness of the layer decreases and the maximum peak concentration increases (snow-plow effect). Both effects are more pronounced as the energy density of the annealing increases. Moreover, as a direct consequence of the snow-plow effect, part of the impurities is expelled from the sample through the surface.

  15. High-dose inhaled corticosteroids or addition of theophylline in patients with poorly controlled asthma?

    PubMed

    Celis, Pilar; Rada, Gabriel

    2015-08-19

    There are several management strategies for patients with poorly controlled asthma despite usual treatment. Increasing doses of inhaled corticosteroids or adding theophylline are among the therapeutic alternatives. However, the latter is associated with important adverse effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including four pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether theophylline or high-dose inhaled corticosteroids constitute a better alternative for symptomatic control or reduction in exacerbations in poorly controlled asthmatic patients because the certainty of the evidence is very low.

  16. Primary Urethral Plasmacytoma Treated with High-Dose-Rate Brachytherapy: A Case Report.

    PubMed

    Stein, Johannes; Latz, Stefan; Ellinger, Jörg; Hauser, Stefan; Sailer, Verena; Oelmann-Avendano, Jan; Marx, Christian; Brossart, Peter; Wolf, Dominik; Müller, Stephan C

    2016-01-01

    Primary urethral solitary plasmacytoma is a very rare variant of extramedullary plasmacytoma. In total, only 9 cases have been reported so far. Patients were treated either by surgery or by external radiation therapy. Here, we report on a 22-year-old man, initially presenting with a palpable induration at the penis, intermittent dysuria and haematospermia, which was due to histologically confirmed solitary urethral kappa-restricted plasmacytoma. The patient subsequently underwent percutaneous and endo-urethral high-dose-rate brachytherapy with a total dose of 42 Gy applied in 14 fractions. Besides an uncomplicated urinary tract infection and hyperpigmentation of the penis, the patient tolerated the radiotherapy well and is still free of disease after 15 months follow-up. © 2016 S. Karger AG, Basel.

  17. [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.

  18. High-dose Rate Electronic Brachytherapy: A Nonsurgical Treatment Alternative for Nonmelanoma Skin Cancer

    PubMed Central

    Patel, Rakesh; Werschler, William Philip; Ceilley, Roger I.; Strimling, Robert

    2016-01-01

    The authors summarized data from a group of physicians with experience using high-dose rate electronic brachytherapy for the treatment of nonmelanoma skin cancer. The data have been published or presented in abstract format at national dermatology and radiation oncology meetings. The data included 1,822 treated lesions from 2009 to 2014 in patients ranging in age from 52 to 104 years. Most lesions were basal cell carcinoma (57%) or squamous cell carcinoma (38%) less than 2cm in size (97%). Median follow-up at the various centers ranged from 4 to 16 months, and results yielded an extremely low recurrence rate of less than one percent. Results show that within the confines of this follow up period, electronic brachytherapy is an effective, convenient, nonsurgical treatment option for patients with nonmelanoma skin cancer with few recurrences and excellent cosmetic results. PMID:28210385

  19. 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

  20. High-dose intravenous therapy with immune globulin before delivery for idiopathic thrombocytopenic purpura.

    PubMed Central

    Adderley, R. J.; Rogers, P. C.; Shaw, D.; Wadsworth, L. D.

    1984-01-01

    A 15-year-old girl with a 9-year history of idiopathic thrombocytopenic purpura resistant to high-dose steroid therapy and to splenectomy was admitted to hospital at 35 weeks' gestation with a platelet count of 10 X 10(9)/L. The bleeding time was normal, and measures of platelet aggregation were nearly so. Treatment with high intravenous doses of polyvalent immune globulin led to a rise in the platelet count to more than 110 X 10(9)/L within 5 days. An elective cesarean section was performed through the lower uterine segment with good hemostasis. After delivery the platelet count fell to its former level, but no postpartum bleeding occurred. There was a brief episode of thrombocytopenia in the infant, with some petechiae but no other hemorrhagic manifestations. No untoward effects of the immune globulin infusion were observed in either mother or daughter. PMID:6423252

  1. The trail of the development of high-dose-rate brachytherapy for cervical cancer in Japan.

    PubMed

    Inoue, Toshihiko

    2003-07-01

    The differences in radiotherapeutic treatment systems for cervical cancer between the United States and Japan can be attributed either to the tolerance of high-risk organs, or dosimetry itself. High-dose-rate (HDR) brachytherapy is the standard treatment for uterine cervix carcinoma in Japan. In addition, HDR Co-60 afterloading machines have been gradually replaced with Ir-192 micro-source afterloading machines during the past ten years. This implies that it has now become impossible to conduct a prospective comparative study of HDR versus low-dose-rate (LDR) brachytherapy for cervical cancer in Japan. An examination of the history of HDR intracavitary radiotherapy for uterine cervix carcinoma in Japan led us to the conclusion that HDR intracavitary brachytherapy for the treatment of cervical cancer is as effective as LDR intracavitary brachytherapy in terms of both survival and complications. In Japan, studies on the former can be drawn from a long experience of more than 35 years.

  2. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects.

    PubMed

    Smithline, Howard A; Donnino, Michael; Greenblatt, David J

    2012-02-04

    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. This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. The AUC₀₋₁₀ hr and C(max) values increased nonlinearly between 100 mg and 1500 mg. The slope of the AUC₀₋₁₀ hr vs dose, as well as the C(max) vs dose, plots are steepest at the lowest thiamine doses. 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. ClinicalTrials.gov: NCT00981877.

  3. 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

  4. A standard graphite calorimeter for dosimetry in brachytherapy with high dose rate 192Ir sources

    NASA Astrophysics Data System (ADS)

    Guerra, A. S.; Loreti, S.; Pimpinella, M.; Quini, M.; D'Arienzo, M.; Astefanoaei, I.; Caporali, C.; Bolzan, C.; Pagliari, M.

    2012-10-01

    Within the framework of the JRP06 European project ‘Increasing Cancer Treatment Efficacy Using 3D Brachytherapy’, a prototype of a graphite standard calorimeter for the measurement of the absorbed dose rate to water, \\dot {D}_w , for 192Ir sources used in high dose rate (HDR) brachytherapy has been developed at the Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI). The calorimeter was tested at the Sant'Andrea Hospital in Rome, where \\dot {D}_w measurements were performed in the quasi-adiabatic mode of operation using an 192Ir MicroSelectron® HDR V2 source. The \\dot {D}_w measurements showed a reproducibility of about 1%, while the combined standard uncertainty on the \\dot {D}_w value at the distance of 1 cm from the source was estimated as 1.4%, lower than the uncertainty of \\dot {D}_w determined from the reference air-kerma rate.

  5. 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

  6. Primary central nervous system lymphoma: implication of high-dose chemotherapy followed by auto-SCT.

    PubMed

    Reddy, N; Savani, B N

    2012-10-01

    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.

  7. High-dose ifosfamide and mesna in advanced breast cancer. A phase II study.

    PubMed

    Sanchiz, F; Milla, A

    1990-01-01

    Thirty-two patients with metastatic breast cancer had previously been treated with chemotherapy (including anthracyclines). They were included in a trial to receive 6 g/m3 ifosfamide, mixed with 6 g/m2 mesna in 1000 ml saline infusion, infused over 4 h. Therapy was repeated every 21 days; the dose was reduced by 50%. Twenty-eight patients could be evaluated. An average of 4.2 cycles (range 2-8) was applied. One patient (4%) showed complete remission. Ten patients (36%) had a partial response. Ten patients (36%) experienced SD and the remaining patients (25%) PD. We conclude that high-dose ifosfamide shows activity in this group of pretreated patients and merits further investigation.

  8. 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

  9. Distributive shock due to systemic capillary leak syndrome treated with high-dose immunosuppression

    PubMed Central

    Sheehan, James Robert; Keating, Liza; Chan, Antoni; Walden, Andrew

    2013-01-01

    A female patient in her 60s presented with a history of malaise, chills, headache and vomiting. She was in shock on presentation with a high haematocrit and a low albumin with evidence of rhabdomyolysis. Severe limb and truncal oedema developed with worsening hypotension leading to intensive care unit admission for multiple organ support. Extensive radiological, microbiological and immunological work up was negative with the exception of a monoclonal gammopathy. A review of patient investigations led to a diagnosis of Clarkson's disease. Treatment with high-dose methylprednisolone and intravenous immunoglobulins led to a rapid decline in the creatine kinase (CK) level and vasopressor requirements. The patient was discharged home on long-term terbutaline and has made a good recovery. PMID:23576661

  10. High-dose misoprostol as an alternative therapy after failed medical abortion.

    PubMed

    Li, Yiu-Tai; Hou, Guang-Qiong; Chen, Tien-Hui; Chu, Yi-Chih; Lin, Ta-Chin; Kuan, Long-Ching; Lin, Mau; Huang, Shu-Feng; Chen, Fu-Min; Kuo, Tsung-Cheng

    2008-12-01

    The aim of this study was to determine the complete abortion rate for the vaginal administration of high-dose misoprostol after a failed medical abortion. When their medical abortions failed after the conventional oral administration of mifepristone and misoprostol, participants then received 1,000 microg of misoprostol vaginally. The efficacy and side effects of this treatment were evaluated. Twenty-seven women who failed to abort after the conventional administration of mifepristone and misoprostol were enrolled in this trial. Fourteen days after the vaginal administration of 1,000 microg misoprostol, the overall complete expulsion rate had reached 88.8% (24/27). Most adverse effects were mild to moderate and did not require treatment. The vaginal administration of 1,000 microg misoprostol as a salvage therapy after a failed medical abortion appears to be a safe and highly effective alternative to surgical intervention.

  11. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

    PubMed Central

    Little, A; Levy, R; Chuaqui-Kidd, P; Hand, D

    1985-01-01

    The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improvement in a subgroup of relatively poor compliers. These were older and had intermediate levels of plasma choline. It is suggested that the effects of lecithin are complex but that there may be a "therapeutic window" for the effects of lecithin in the condition and that this may be more evident in older patients. PMID:3897460

  12. Long-term treatment of tumor-operated mice with high doses of alpha-difluoromethylornithine.

    PubMed

    de Lustig, E S; Klein, S; Fuchs, A; Algranati, I D

    1986-01-01

    Mice inoculated subcutaneously with a mammary adenocarcinoma M3cell suspension and submitted 10 to 15 days later to the surgical removal of primary tumors have been chosen in our laboratory as the experimental model to study the effect of several drugs on metastasis spreading. A 90-day treatment of tumor-operated mice with high doses of alpha-difluoromethylornithine showed, in addition to a marked decrease of lung metastases, several side effects including a loss of body weight, a delay of surgical wound healing and a reduced number of megakaryocytes in bone marrow. The measurement of ceruloplasmin in serum has indicated that treated animals contained increased levels of this oxidase activity in spite of the polyamine depletion caused by alpha-difluoromethylornithine. These results rule out a direct correlation between ceruloplasmin activity and polyamine concentration.

  13. Distributive shock due to systemic capillary leak syndrome treated with high-dose immunosuppression.

    PubMed

    Sheehan, James Robert; Keating, Liza; Chan, Antoni; Walden, Andrew

    2013-04-09

    A female patient in her 60s presented with a history of malaise, chills, headache and vomiting. She was in shock on presentation with a high haematocrit and a low albumin with evidence of rhabdomyolysis. Severe limb and truncal oedema developed with worsening hypotension leading to intensive care unit admission for multiple organ support. Extensive radiological, microbiological and immunological work up was negative with the exception of a monoclonal gammopathy. A review of patient investigations led to a diagnosis of Clarkson's disease. Treatment with high-dose methylprednisolone and intravenous immunoglobulins led to a rapid decline in the creatine kinase (CK) level and vasopressor requirements. The patient was discharged home on long-term terbutaline and has made a good recovery.

  14. Effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats

    PubMed Central

    Henriques, Helene Nara; de Carvalho, Ana Carolina Bergmann; Filho, Porphirio José Soares; Pantaleão, José Augusto Soares; Guzmán-Silva, Maria Angélica

    2011-01-01

    The aim of this study was evaluate the effect of prolonged use of high dose of tibolone on the vagina of ovariectomized rats. Bilateral ovariectomy was performed on 14 rats weighing 250 g. Thirty days later, vaginal smears were collected verifying the menopause status by anoestrus cytology. Rats were divided randomly into groups: experimental rats (n = 9) received 1 mg tibolone/day orally and control rats (n = 6) received placebo (carboxymethylcellulose). After 150 days, all rats were sedated and euthanized by cervical displacement. The vagina was removed, fixed in 10% buffered formalin, sampled and processed for paraffin embedding. Histological sections were stained with haematoxylin and eosin, picrosirius red, periodic acid Schiff (PAS) and PAS-diastase, and Weigert's resorcin–fuchsin. Cell proliferation was analysed by immunohistochemistry to detect Ki67. Histomorphometric analyses were performed for epithelial thickness, per cent area of collagen fibres and blood vessels, mast cells and Ki67-positive nuclei per mm of basal membrane. Means and standard error of means were calculated, and data were compared using the Mann–Whitney test, with significance level at P < 0.05. In the vagina, epithelial thickness, number of Ki67-positive nuclei per mm of basal membrane, number of vessels and number of mast cells were significantly higher in the tibolone group when compared with the control group. Furthermore, the content of glycogen and glycoproteins in the vaginal epithelium was modified by tibolone. Tibolone administered in high dose and for a long period has a trophic effect, reversing vaginal atrophy, and has no dysplastic or neoplastic effect in the vagina of ovariectomized rats. PMID:21518049

  15. High-dose oral medroxyprogesterone for inappropriate hypersexuality in elderly men with dementia: a case series.

    PubMed

    Cross, Bethany S; DeYoung, G Robert; Furmaga, Kevin M

    2013-01-01

    To retrospectively examine the utility of high-dose oral medroxyprogesterone (MPA) for the treatment of inappropriate hypersexuality (IH) in elderly men with dementia. Ten men aged 65 years or older (median 79.5 years, range 65-93 years) were identified from all admissions at a 170-bed tertiary referral psychiatric hospital between December 2005 and January 2011. Admission records were used to identify subjects who received at least 100 mg daily of oral MPA. The primary outcome of successful treatment was chart documentation of a substantial decline in IH, such that subjects could return to preadmission residence. Data were collected to assess trends in dose, adverse effects, use of other symptom-modifying medications prior to MPA initiation, and successful return to preadmission placement. A trial serotoneric agent was used in 70% of subjects prior to MPA initiation. Sixty percent of subjects failed a trial of an antipsychotic, while 40% did not have response to the use of both a serotonergic agent and an antipsychotic before MPA was initiated. The average daily dose of MPA was 300 mg (range 100-400 mg/day). No adverse effects were documented from physician, nursing, or behavioral health rounding notes; however, adverse effects may not have been systematically assessed at the time of MPA administration. Seventy percent of subjects experienced favorable changes in target behaviors from MPA. Few data exist on effective therapy options for treatment of IH. The minimum concentration of MPA needed to suppress IH in the male body is unknown. MPA was titrated upward, with the efficacy measure being a decrease in inappropriate behaviors. Use of MPA likely contributed to decreased IH; however, other factors involved in hospitalization could have contributed to improved behavior. While requiring further study, high-dose (100-400 mg/day) oral MPA may represent an effective and well-tolerated treatment option for subjects displaying IH.

  16. Tumour induction in rats following exposure to short-term high dose aristolochic acid I.

    PubMed

    Cui, Min; Liu, Zhi-Hong; Qiu, Qi; Li, Heng; Li, Lei-Shi

    2005-01-01

    The purpose of this study was to assess the carcinogenic activity of aristolochic acid I (AAI) in short-term high doses. Forty-four female Sprague-Dawley rats were randomly assigned to two groups. A dose of 50 mg/kg/day AAI was administrated to rats in the experimental group by gavage consecutively for 3 days, while the control group received only distilled water, after which renal function and pathological changes were assessed. At day 8 post-treatment AAI had induced elevations of both plasma urea and creatinine, coupled with increased urine production, urinary proteins, glucose and N-acetyl-beta-glucosaminidase. At 1, 3 and 6 months post-treatment renal function and urinary parameters for the experimental group approached baseline values. However, tumours and preneoplastic proliferation were both observed at 6 months for the experimental group. The rate of occurrence of preneoplastic proliferation in the kidneys was 100% (14/14); the rate of occurrence of renal tumours was 28.6% (4/14), which included three mesenchymal tumours and one case of renal oncocytoma; the rate of occurrence of extrarenal tumours was 7.1% (1/14), which was a case of mammary duct carcinoma. Renal preneoplastic proliferation and renal tumours, as well as extrarenal tumours, were not observed in control rats during the 6 months. These results differ from previous reports in that tumours originating from both epithelial and mesenchymal tissues were found, which may be attributed to the duration of treatment and the dosage of the drug. These data indicate that AAI administered in an acute manner at high doses does in fact have carcinogenic properties.

  17. High-Dose Filgrastim Treatment of Nonregenerative Pancytopenia Associated With Chronic Canine Ehrlichiosis.

    PubMed

    Palacios, Mauricio; Arteaga, Rafael; Calvo, Gustavo

    2017-03-01

    To report the management and outcome of a dog with canine monocytic ehrlichiosis and nonregenerative pancytopenia, with high doses of filgrastim. An 8-year-old male, mixed-breed dog, weighing 5.6kg, presented with a 1-month history of hyporexia, adynamia, and a weight loss of approximately 1kg. The general condition of the dog was observed to be poor as follows: lethargy, tachycardia, marked pallor of the mucous membranes, petechiae on the abdomen, hepatosplenomegaly, and cervical lymphadenopathy. A complete blood count analysis revealed severe leukopenia, thrombocytopenia, and anemia. A direct immunofluorescence assay using anti-Ehrlichia canis-immunoglobin G (1:400) yielded positive result. The dog was diagnosed with nonregenerative pancytopenia associated with canine monocytic ehrlichiosis. The dog presented poor prognostic signs (neutropenia, thrombocytopenia, and severe anemia). The dog was treated with antibiotics and a short course of high-dose filgrastim (50µg/kg, SC, q 48h for 4 days) to stimulate bone marrow response, prednisone to decrease peripheral platelet destruction, and an iron supplement to compensate for the iron deficiency in the bone deposits. Although temporary side effects associated with filgrastim use, such as bone pain, bleeding, and the worsening of thrombocytopenia, were observed, the treatment improved the clinical course and the cell counts in less than a month. The treatment protocol used in this case might be an alternative for treating cases of severe myelosuppression. This treatment plan can substantially change the clinical course of the disease for the better, compared to conventional treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Efficacy, Dose Reduction, and Resistance to High-dose Fluticasone in Patients with Eosinophilic Esophagitis

    PubMed Central

    Butz, Bridget K.; Wen, Ting; Gleich, Gerald J.; Furuta, Glenn T.; Spergel, Jonathan; King, Eileen; Kramer, Robert E.; Collins, Margaret H.; Stucke, Emily; Mangeot, Colleen; Jackson, W. Daniel; O’Gorman, Molly; Abonia, J. Pablo; Pentiuk, Scott; Putnam, Philip E.; Rothenberg, Marc E.

    2014-01-01

    Background & Aims We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms. Methods We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants 3–30 years old with active EoE. Twenty-eight participants received FP and 14 received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary endpoint was histologic evidence for CR. Secondary endpoints were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness. Results After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P=.0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P=.041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects that did not respond to FP. Conclusions Daily administration of a high dose of FP induces histologic remission in 65%–77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%–93% of patients that initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance

  19. High-dose gallium-67 therapy in patients with relapsed acute leukaemia: a feasibility study.

    PubMed Central

    Jonkhoff, A. R.; Plaizier, M. A.; Ossenkoppele, G. J.; Teule, G. J.; Huijgens, P. C.

    1995-01-01

    Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia. Images Figure 2 PMID:8519674

  20. Nephrotoxicity of high-dose ifosfamide/carboplatin/etoposide in adults undergoing autologous stem cell transplantation.

    PubMed

    Agaliotis, D P; Ballester, O F; Mattox, T; Hiemenz, J W; Fields, K K; Zorsky, P E; Goldstein, S C; Perkins, J B; Rosen, R M; Elfenbein, G J

    1997-11-01

    The objective of this study was to evaluate nephrotoxicity in adult patients treated with high-dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation. We conducted a retrospective analysis of clinical and laboratory data from 131 patients with various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation as part of a phase I/II therapeutic trial. Abnormalities in glomerular filtration were evaluated by measuring peak creatinine levels and tubular dysfunction by the lowest recorded serum levels of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and after autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were > 1.5 mg/dL but < 3.0 mg/dL in 37% and levels were > 3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3.0 mg/dL in 25% of patients and were > 3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those receiving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potassium, and magnesium levels immediately after chemotherapy, and they remained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between < 0.008 and < 0.001). This is the largest adult population study documenting the incidence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.

  1. 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

  2. High dose droperidol and QT prolongation: analysis of continuous 12-lead recordings

    PubMed Central

    Calver, Leonie; Isbister, Geoffrey K

    2014-01-01

    Aims To investigate the QT interval after high dose droperidol using continuous 12-lead Holter recordings. Methods This was a prospective study of patients given droperidol with a continuous Holter recording. Patients were recruited from the DORM II study which included patients with aggression presenting to the emergency department. Patients initially received 10 mg droperidol as part of a standardized sedation protocol. An additional 10 mg dose was given after 15 min if required and further doses at the clinical toxicologist's discretion. Continuous 12-lead Holter recordings were obtained for 2–24 h utilizing high resolution digital recordings with automated QT interval measurement. Electrocardiograms were extracted hourly from Holter recordings. The QT interval was plotted against heart rate (HR) on the QT nomogram to determine if it was abnormal. QTcF (Fridericia's HR correction) was calculated and >500 ms was defined as abnormal. Results Forty-six patients had Holter recordings after 10–40 mg droperidol and 316 QT–HR pairs were included. There were 32 abnormal QT measurements in four patients, three given 10 mg and one 20 mg. In three of the four patients QTcF >500 ms but only in one taking methadone was the timing of QTcF >500 ms consistent with droperidol dosing. Of the three other patients, one took amphetamines, one still had QT prolongation 24 h after droperidol and one took a lamotrigine overdose. No patient given >30 mg had a prolonged QT. There were no arrhythmias. Conclusion QT prolongation was observed with high dose droperidol. However, there was little evidence supporting droperidol being the cause and QT prolongation was more likely due to pre-existing conditions or other drugs. PMID:24168079

  3. Usefulness of high doses of glucocorticoids and hyperbaric oxygen therapy in sudden sensorineural hearing loss treatment.

    PubMed

    Narozny, Waldemar; Sicko, Zdzislaw; Przewozny, Tomasz; Stankiewicz, Czeslaw; Kot, Jacek; Kuczkowski, Jerzy

    2004-11-01

    We investigated the effect of pharmacologic (steroids, vasodilators, vitamins, and Betaserc) and hyperbaric oxygen therapy on patients with sudden sensorineural hearing loss. The pharmacologic arm of the study consisted of 52 patients with defined sudden sensorineural hearing loss treated simultaneously in the ENT Department and National Center for Hyperbaric Medicine of the Medical University of Gdansk, Poland, from 1997 to 2000 (Group A). The hyperbaric oxygen therapy consisted of exposure to 100% oxygen at a pressure of 250 kPa for a total of 60 minutes in a multiplace hyperbaric chamber. The control group included 81 patients with defined sudden sensorineural hearing loss treated in the ENT Department, Medical University of Gdansk, from 1980 to 1996 (Group B). Both groups were comparable regarding the age of the patients, season of hearing loss occurrence, tinnitus and vestibular symptom frequency, delay before therapy, and average threshold loss before the start of treatment. The treatment results (hearing gain) were estimated using pure-tone audiometry. We retrospectively analyzed the audiograms of all patients. Patients from Group A (blood flow-promoting drugs, glucocorticoids in high doses, betahistine, and hyperbaric oxygen therapy) showed significantly better recovery of hearing levels compared with those from Group B (blood flow-promoting drugs and glucocorticoids in low doses) at seven frequencies (500, 1,000, 2,000, 3,000, 4,000, 6,000, and 8,000 Hz) (p < 0.05) and four groups of frequencies (pure-tone average, high-tone average, pure middle-tone average, and overall average) (p < 0.05). Percentage hearing gain in all investigated frequencies was also better in Group A versus Group B, and the differences were statistically significant (p < 0.05). We conclude that hyperbaric oxygen therapy with high doses of glucocorticoids improves the results of conventional sudden sensorineural hearing loss treatment and should be recommended. In addition, the best

  4. Healing of ulcers due to cryofibrinogenemia with colchicine and high-dose pentoxifylline.