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Sample records for high-dose 131itositumomab anti-cd20

  1. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults ≥ 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

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    Gopal, Ajay K.; Rajendran, Joseph G.; Gooley, Ted; Pagel, John M.; Fisher, Darrell R.; Petersdorf, Stephen; Maloney, David G.; Eary, Janet F.; Appelbaum, Frederick R.; Press, Oliver W.

    2007-04-10

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets (≥20K/µL) and neutrophils (≥500/µL) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

  2. [{sup 177}Lu]DOTA-anti-CD20: Labeling and pre-clinical studies

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    Audicio, Paola F., E-mail: paudicio@cin.edu.u [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Castellano, Gustavo, E-mail: gcas@famaf.unc.edu.a [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, 5016 Cordoba (Argentina); Tassano, Marcos R.; Rezzano, Maria E.; Fernandez, Marcelo [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Riva, Eloisa [Clinica Hematologica ' Prof. Dra. L. Diaz' , Hospital de Clinicas. Av. Italia. sn, Montevideo (Uruguay); Robles, Ana; Cabral, Pablo; Balter, Henia; Oliver, Patricia [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay)

    2011-07-15

    Anti-CD20 (Rituximab), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with {sup 177}Lu through a simple method. [{sup 177}Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [{sup 177}Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.

  3. Microenvironment and anti-CD20 based therapies in CLL

    NARCIS (Netherlands)

    Jak, M.

    2012-01-01

    Chronische lymfatische leukemie (CLL) kenmerkt zich door een ophoping van kwaadaardige B-lymfocyten (witte bloedcellen) in bloed, lymfeklieren, milt en beenmerg. Het is niet te genezen omdat CLL-cellen resistent worden tegen behandeling. Margot Jak onderzocht twee typen anti-CD20-antilichamen. Antil

  4. Ofatumumab: a novel monoclonal anti-CD20 antibody

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    Thomas S Lin

    2010-05-01

    Full Text Available Thomas S LinGlaxoSmithKline Oncology R&D, Collegeville, PA, USAAbstract: Ofatumumab, a novel humanized monoclonal anti-CD20 antibody, was recently approved by the FDA for the treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL. Ofatumumab effectively induces complement-dependent cytotoxicity (CDC in vitro, and recent studies demonstrated that ofatumumab also effectively mediates antibody-dependent cellular cytotoxicity (ADCC. Pharmacokinetic studies indicated that increased exposure to the antibody correlated with improved clinical outcome in CLL. Thus, pharmacogenomics may be important in identifying which patients are more likely to respond to ofatumumab therapy, although such studies have not yet been performed. Patients with the high-affinity FCGR3a 158 V/V polymorphism may be more likely to respond to therapy, if ADCC is the primary in vivo mechanism of action of ofatumumab. Patients with increased expression of the complement defense proteins CD55 and CD59 may be less likely to respond if ofatumumab works in vivo primarily via CDC. Patients with increased metabolism and clearance of ofatumumab may have lower exposure and be less likely to respond clinically. Thus, pharmacogenomics may determine the responsiveness of patients to ofatumumab therapy.Keywords: monoclonal antibody, CD20, CLL, NHL, lymphoma

  5. Dosimetry and microdosimetry of {sup 188} Re-anti-CD20 and {sup 131} I-anti-CD20 for the treatment of No Hodgkin lymphomas; Dosimetria y microdosimetria del {sup 188} Re-anti-CD20 y {sup 131} I-anti-CD20 para el tratamiento de linfomas No Hodgkin

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    Torres G, E

    2007-07-01

    The purpose of this investigation was to prepare {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. {sup 188}Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of {sup 188}Re-anti-CD20, {sup 125}I-anti-CD20 (positive control) and {sup 188}Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. {sup 188}Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and {sup 188}Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that {sup 188}Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or

  6. Intrathecal anti-CD20 efficiently depletes meningeal B cells in CNS autoimmunity

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    Lehmann-Horn, Klaus; Kinzel, Silke; Feldmann, Linda; Radelfahr, Florentine; Hemmer, Bernhard; Traffehn, Sarah; Bernard, Claude C A; Stadelmann, Christine; Brück, Wolfgang; Weber, Martin S

    2014-01-01

    Clinical trials revealed that systemic administration of B-cell-depleting anti-CD20 antibodies can hold lesion formation in the early relapsing-remitting phase of multiple sclerosis (MS). Throughout the secondary-progressive (SP) course of MS, pathogenic B cells may, however, progressively replicate within the central nervous system (CNS) itself, which is largely inaccessible to systemic anti-CD20 treatment. Utilizing the murine MS model of experimental autoimmune encephalomyelitis, we show that intrathecal (i.t.) administration of anti-CD20 alone very efficiently depletes meningeal B cells from established CNS lesions. In SP-MS patients, adding i.t. administration of anti-CD20 to its systemic use may be a valuable strategy to target pathogenic B-cell function. PMID:25356419

  7. Efecto de un anticuerpo monoclonal anti CD20 (Rituximab) en trombocitopenia inmune.

    OpenAIRE

    Untama, José; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.; Del Carpio, Daniel; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.

    2012-01-01

    Objetivo: Describir la respuesta terapéutica con un anticuerpo monoclonal anti CD20 (Rituximab), en pacientes con Trombocitopenia Inmune (PTI). Material y métodos: Estudio retrospectivo, descriptivo y observacional tipo serie de casos. Se revisaron las historias clínicas de pacientes adultos con PTI que recibieron el anticuerpo monoclonal anti CD20 (Rituximab), desde diciembre 2005 hasta diciembre 2010. Se definió respuesta: conteo plaquetario >30 mil, por lo menos duplicar el conteo plaqu...

  8. Efficacy of anti-CD20 chi- meric Fab′fragment on pro- liferation of B lymphoma cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The variable domain of heavy chain (VH) and light chain (VL) genes of anti-CD20 monoclonal antibody HI47 were cloned from anti-CD20 ScFv expression vector pCANBTEcd20 by PCR and ligated into vector pYZF to construct chimeric anti-CD20 Fab¢ fragment expression vector pYZFcd20. Chimeric anti-CD20 Fab¢ fragment was expressed in E. coli 16C9 and purified by protein G affinity chromatography. Competitive inhibition assay showed that anti-CD20 Fab¢ fragment inhibited binding of HI47 to CD20 on the surface of Daudi cells. Results from MTT assay indicated that chimeric anti-CD20 Fab¢ fragment inhibited the proliferation of Daudi cells, IC50 = 69 mg/mL. Affinity of chimeric anti-CD20 Fab¢ fragment was determined, Ka was about 8.9′108 (mol/L)-1.

  9. Compartmental and dosimetric studies of anti-CD20 labelled with {sup 188}Re; Estudo compartimental e dosimetrico do Anti-CD20 marcado com {sup 188}Re

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    Kuramoto, Graciela Barrio

    2016-10-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β{sup -} emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β{sup -} emitters as {sup 131}I, {sup 90}Y, {sup 188}Re {sup 177}Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). {sup 188}Re (E{sub β} = 2.12 MeV; E{sub γ} = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, {sup 188}Re can be obtained from a radionuclide generator of {sup 188}W/{sup 188}Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical {sup 188}Re-Anti-CD20, where the radionuclide can be obtained from a generator system {sup 188}W/{sup 188}Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with {sup 188}Re with the marking of the antibody with {sup 90}Y, {sup 131}I, {sup 177}Lu and {sup 99m}Tc (for their similar chemical characteristics) and {sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for {sup 188}Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of {sup 188}Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β{sup -131}I-labeled anti CD20, {sup 177

  10. Dosimetric studies of anti-CD20 labeled with therapeutic radionuclides at IPEN/CNEN-SP

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    Barrio, G.; Dias, C.R.B.R.; Osso Junior, J.A., E-mail: gracielabarrio@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2012-07-01

    Radioimmunotherapy (RIT) makes use of monoclonal antibodies (MAb) labeled with alpha/beta radionuclides for therapeutical purposes, leading to tumor irradiation and destruction, preserving the normal organs on the radiation excess. The therapeutic activity to be injected in a specific patient is based on information obtained in dosimetric studies. Beta emitting radionuclides such as {sup 131}I, {sup 188}Re, {sup 90}Y, {sup 177}Lu and {sup 166}Ho are useful for the development of therapeutic radiopharmaceuticals. Anti-CD20 (Rituximab) is a chimeric MAb directed against antigen surface CD20 on B-lymphocytes, used in non-Hodgkin lymphoma treatment (NHL). The association with beta radionuclides have shown greater therapeutic efficacy. Currently, two radiopharmaceuticals with Anti-CD20 for radioimmunotherapy have FDA approval for NHL treatment: {sup 131}I-AntiCD20 (Bexar) and {sup 90}Y-AntiCD20 (Zevalin). Techniques for the radiolabeling of {sup 188}Re-antiCD20 have been recently developed by IPEN-CNEN/SP in order to evaluate the clinical use of this radionuclide in particular. The use of {sup 188}Re (T{sub 1/2} 17h) produced by the decay of {sup 188}W (T{sub 1/2} 69d), from an {sup 188}W/{sup 188}Re generator system, has represented an alternative to RIT. Beyond high energy beta emission for therapy, {sup 188}Re also emits gamma rays (155keV) suitable for image. The aim of this new project is to compare the labeling of anti-CD20 with {sup 188}Re with the same MAb labeled with {sup 131}I, {sup 177}Lu, {sup 90}Y and even {sup 99m}Tc. The first step in this project is the review of the published data available concerning the labeling of this MAb with different radionuclides, along with data obtained at IPEN, taking into account labeling procedures, labeling yields, reaction time, level and kind of impurities and biodistribution studies. The pharmacokinetic code will be developed in Visual Studio.NET platform through VB.NET and C{sup ++} for biodistribution and dosimetric

  11. Monocytes mediate shaving of B-cell-bound anti-CD20 antibodies

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Jungersen, Mette B; Pedersen, Charlotte D

    2011-01-01

    -mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, in haematological malignancies, such effector mechanisms can be saturated and result in release of malignant B cells with reduced levels of CD20. It has been hypothesized that this is the result of monocyte-mediated shaving of the CD20/RTX...... to mediate partial inhibition. Also, a series of alternative anti-CD20 antibodies representing both type I and type II antibodies were tested for their ability to induce the shaving reaction. These results demonstrate that a monocyte-mediated shaving reaction can lead to complete loss of most anti-CD20...

  12. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

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    Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafò, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núñez, Luis; Macor, Paolo

    2013-01-01

    Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  13. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

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    Nelly Mezzaroba

    Full Text Available Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  14. Production of an active anti-CD20-hIL-2 immunocytokine in Nicotiana benthamiana.

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    Marusic, Carla; Novelli, Flavia; Salzano, Anna M; Scaloni, Andrea; Benvenuto, Eugenio; Pioli, Claudio; Donini, Marcello

    2016-01-01

    Anti-CD20 murine or chimeric antibodies (Abs) have been used to treat non-Hodgkin lymphomas (NHLs) and other diseases characterized by overactive or dysfunctional B cells. Anti-CD20 Abs demonstrated to be effective in inducing regression of B-cell lymphomas, although in many cases patients relapse following treatment. A promising approach to improve the outcome of mAb therapy is the use of anti-CD20 antibodies to deliver cytokines to the tumour microenvironment. In particular, IL-2-based immunocytokines have shown enhanced antitumour activity in several preclinical studies. Here, we report on the engineering of an anti-CD20-human interleukin-2 (hIL-2) immunocytokine (2B8-Fc-hIL2) based on the C2B8 mAb (Rituximab) and the resulting ectopic expression in Nicotiana benthamiana. The scFv-Fc-engineered immunocytokine is fully assembled in plants with minor degradation products as assessed by SDS-PAGE and gel filtration. Purification yields using protein-A affinity chromatography were in the range of 15-20 mg/kg of fresh leaf weight (FW). Glycopeptide analysis confirmed the presence of a highly homogeneous plant-type glycosylation. 2B8-Fc-hIL2 and the cognate 2B8-Fc antibody, devoid of hIL-2, were assayed by flow cytometry on Daudi cells revealing a CD20 binding activity comparable to that of Rituximab and were effective in eliciting antibody-dependent cell-mediated cytotoxicity of human PBMC versus Daudi cells, demonstrating their functional integrity. In 2B8-Fc-hIL2, IL-2 accessibility and biological activity were verified by flow cytometry and cell proliferation assay. To our knowledge, this is the first example of a recombinant immunocytokine based on the therapeutic Rituximab antibody scaffold, whose expression in plants may be a valuable tool for NHLs treatment.

  15. Reassessment of Anti-CD20 Therapy in Lymphoid Malignancies: Impact, Limitations, and New Directions.

    Science.gov (United States)

    Reagan, Patrick M; Friedberg, Jonathan W

    2017-05-15

    The addition of anti-CD20 monoclonal antibodies to the treatment of B-cell malignancies has dramatically affected the field as well as the lives of patients. Rituximab in particular has been combined safely with conventional chemotherapy and has resulted in improved overall survival in major histologic subtypes of B-cell lymphoma and chronic lymphocytic leukemia. It is incorporated into the standard initial treatment of nearly all of these diseases. Novel anti-CD20 antibodies are currently under development. Two of these agents, ofatumumab and obinutuzumab, have been approved for use in certain clinical settings. Research comparing these newer antibodies with rituximab is ongoing. As these newer antibodies are further studied and developed, improvements in response and progression-free survival need to be considered in the context of clinical benefit as well as toxicity, especially in indolent diseases. Research involving rituximab biosimilars is ongoing as well, and recent preliminary data demonstrate similar efficacy and tolerability when compared with rituximab. An additional focus of ongoing research is the use of extended schedules of anti-CD20 monoclonal antibodies, as the optimal duration of therapy remains ill-defined in many histologic subtypes. To maximize the use of these agents, well-validated clinical trial endpoints will need to be carefully considered.

  16. Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

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    Hohlfeld Reinhard

    2011-10-01

    Full Text Available Abstract Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS and neuromyelitis optica (NMO generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods Myelin oligodendrocyte glycoprotein (MOG peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg and cytokine production of CD11b+ antigen presenting cells (APC were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM. Results We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and

  17. Efecto de un anticuerpo monoclonal anti CD20 (Rituximab en trombocitopenia inmune

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    José Untama

    2012-10-01

    Full Text Available Objetivos: Describir la respuesta terapéutica con un anticuerpo monoclonal anti CD20 (Rituximab, en pacientes con Trombocitopenia Inmune (PTI. Material y métodos: Estudio retrospectivo, descriptivo y observacional tipo serie de casos. Se revisaron las historias clínicas de pacientes adultos con PTI que recibieron el anticuerpo monoclonal anti CD20 (Rituximab, desde diciembre 2005 hasta diciembre 2010. Se definió respuesta: conteo plaquetario >30 mil, por lo menos duplicar el conteo plaquetario inicial y no signos de sangrado, y respuesta completa: conteo plaquetario >100 mil y no signos de sangrado. Resultados: Se evaluaron 24 cursos de tratamiento. Hubo respuesta en 18 (75%, en una media de 11,9 semanas (rango 0,7 - 37,4, la duración media de respuesta fue 16 meses (rango 3,3 - 55,3. Se mantuvo la respuesta obtenida en 12 pacientes, seguimiento promedio de 22 meses (rango 4 - 62. Se logró respuesta completa en 13/23 (60% casos, en una media de 17 semanas (rango 0,7 - 62,3, con una duración media de respuesta completa de 10,1 meses (rango 2,3 - 25,2, 5 casos mantuvieron respuesta completa con una media de seguimiento de 20 meses (rango 8 - 29. Conclusiones: Se obtuvo una alta tasa de respuesta al tratamiento con Rituximab (hasta 75% en casos de PTI que fallaron al menos a una línea de tratamiento.

  18. Anti-CD20 treatment of giant cell hepatitis with autoimmune hemolytic anemia.

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    Paganelli, Massimiliano; Patey, Natacha; Bass, Lee M; Alvarez, Fernando

    2014-10-01

    Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined.

  19. A new approach to comparing anti-CD20 antibodies: importance of the lipid rafts in their lytic efficiency

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    Mariam Hammadi

    2010-06-01

    Full Text Available Mariam Hammadi, Jacques-Olivier Pers, Christian Berthou, Pierre Youinou, Anne BordronCentre Hospitalier Universitaire EA2216 and IFR148, Université de Bretagne Occidentale and Université Européenne de Bretagne, BP824, 29609 Brest cedex, FranceAbstract: The view that B lymphocytes are pathogenic in diverse pathological settings is supported by the efficacy of B-cell-ablative therapy in lymphoproliferative disorders, autoimmune diseases and graft rejection. Anti-B-cell antibodies (Abs directed against CD20 have therefore been generated, and of these, rituximab was the first anti-CD20 monoclonal Ab (mAb to be applied. Rituximab-mediated apoptosis, complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity differ from one disease to another, and, for the same disease, from one patient to another. This knowledge has prompted the development of new anti-CD20 mAbs in the hope of improving B-cell depletion. The inclusion of CD20/anti-CD20 complexes in large lipid rafts (LRs enhances the results of some, but not all, anti-CD20 mAbs, and it may be possible to include smaller LRs. Lipid contents of membrane may be abnormal in malignant B-cells, and could explain resistance to treatment. The function of these mAbs and the importance of LRs warrant further investigation. A detailed understanding of them will increase results for B-cell depletion in lymphoproliferative diseases.Keywords: anti-CD20 antibodies, lymphocyte B, lipid rafts, B-cell disorders

  20. Development of a lyophilized formulation for preparing the radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20; Desarrollo de una formulacion liofilizada para la preparacion del radiofarmaco {sup 177}-DOTA-Anti-CD20

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    Serrano E, L. A.

    2015-07-01

    The radiolabeled proteins are molecules of interest in nuclear medicine for their diagnostic and therapeutic application in cancer. Antibodies, such as chimeric monoclonal antibody Anti-CD20 rituximab, have established themselves as suitable vectors of radionuclides (e.g. {sup 177}Lu) , introducing high affinity by the surface antigens over- expressed and widely distributed in cells involved in certain diseases. The aim of this work was to design, optimize and document the production process of radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20 for sanitary registration request to the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). First, a raw material analysis using the Ft-Mir technique and gamma spectrometry was performed. Then, was carried out the development of the lyophilized formulation for the preparation of {sup 177}Lu-DOTA-Anti-CD20, in which an ANOVA was performed where the dependent variable was the radiochemical purity. The optimal pharmaceutical formulation was: 5 mg DOTA-CD20 and 80 mg Mannitol to be reconstituted with 1 m L of acetate buffer 0.25 M, ph 7, with an incubation time of 15 min at 37 degrees Celsius in a dry bath. Once completed the development of the lyophilized formulation, we proceeded to the optimization of the production process, development and validation of the analytical method. Three batches were prepared under protocols of Good Manufacturing Practice, which met pre-established specifications as sterile and endotoxin-free of bacterial formulations, with greater that 95% of radiochemical purity. Currently, is conducting the study of shelf stability. Upon completion of the stability studies, the legal record of {sup 177}Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

  1. Preparation of the radiopharmaceutical {sup 131}I-Anti-CD20 for the treatment of lymphomas; Preparacion del radiofarmaco {sup 131}I-Anti-CD20 para el tratamiento de linfomas

    Energy Technology Data Exchange (ETDEWEB)

    Pantoja H, I.E

    2004-07-01

    At the present time they are considered to the lymphomas like a problem of first magnitude since has happened it is necessary to be the fifth cancer cause in the world. Different treatments focused to the lymphoma like the chemotherapy and the radiotherapy, have been employees to counteract the No-Hodgkin lymphoma, without these they don't exclude the healthy tissue of the toxicity. It is for it that is taking a new direction with the employment of the directed radioimmunotherapy since this it allows to kill wicked cells selectively with radiation dose joined to the apoptosis and cytotoxicity induced by the own one bio molecule. The radioimmunotherapy with radiolabelled antibodies directed to the surface antigen CD20 represents a new modality for the treatment of No-Hodgkin lymphoma and potentially other illnesses. In this work the parameters of optimization are presented for the preparation, control of quality and evaluation of the stability in vitro and in vivo of the monoclonal antibody anti-CD20 labelled with {sup 131} I for the treatment of No-Hodgkin lymphoma. The anti-CD20 labelled by the chloramine-T method with high radiochemical purity (>98%), it is stable in solution for but of a half life of the radionuclide (8.04 days) The {sup 131} I-anti-CD20 doesn't present dehalogenation in vitro (human serum) during 24 h of incubation at 37 C. According to the tests carried out to establish the immunoreactivity, a percentage of union to cells was obtained (B lymphocytes) bigger to 30%. The biodistribution in mice balb/c one hour after their administration, it shows that there is not high reception in mucous neither kidneys, what indicates that the complex is stable in vivo. In conclusion, the radiopharmaceutical {sup 131} I-anti-CD20 was obtained in sterile injectable solution and free of pyrogens with a radiochemical purity bigger to 98% and a specific activity of 296 MBq. The radiolabelled molecule maintains its biological recognition for the receiving

  2. Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

    Directory of Open Access Journals (Sweden)

    Capolla S

    2015-06-01

    Full Text Available Sara Capolla,1 Chiara Garrovo,2 Sonia Zorzet,1 Andrea Lorenzon,3 Enrico Rampazzo,4 Ruben Spretz,5 Gabriele Pozzato,6 Luis Núñez,7 Claudio Tripodo,8 Paolo Macor,1,9 Stefania Biffi2 1Department of Life Sciences, University of Trieste, 2Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Animal Care Unit, Cluster in Biomedicine (CBM scrl, Trieste, Italy; 4Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 5LNK Chemsolutions LLC, Lincoln, NE, USA; 6Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 7Bio-Target, Inc., University of Chicago, Chicago, IL, USA; 8Department of Human Pathology, University of Palermo, Palermo, Italy; 9Callerio Foundation Onlus, Institutes of Biological Researches, Trieste, Italy Abstract: The expectations of nanoparticle (NP-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conflicting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacokinetic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together

  3. Overcoming rituximab drug-resistance by the genetically engineered anti-CD20-hIFN-α fusion protein: Direct cytotoxicity and synergy with chemotherapy

    Science.gov (United States)

    VEGA, GABRIEL G.; FRANCO-CEA, LUZ ARELI; HUERTA-YEPEZ, SARA; MAYANI, HÉCTOR; MORRISON, SHERIE L.; BONAVIDA, BENJAMIN; VEGA, MARIO I.

    2015-01-01

    Treatment of patients with B-NHL with rituximab and CHOP has resulted in significant clinical responses. However, a subset of patients develops resistance to further treatments. The mechanism of unresponsiveness in vivo is not known. We have reported the development of rituximab-resistant clones derived from B-NHL cell lines as models to investigate the mechanism of resistance. The resistant clones exhibit hyper-activated survival/anti-apoptotic pathways and no longer respond to a combination of rituximab and drugs. Recent studies reported the therapeutic efficacy in mice bearing B-cell lymphoma xenografts following treatment with the anti-CD20-hIFNα fusion protein. We hypothesized that the fusion protein may bypass rituximab resistance and inhibit survival signaling pathways. Treatment of the rituximab-resistant clones with anti-CD20-hIFNα, but not with rituximab, IFNα, or rituximab+IFNα resulted in significant inhibition of cell proliferation and induction of cell death. Treatment with anti-CD20-hIFNα sensitized the cells to apoptosis by CDDP, doxorubicin and Treanda. Treatment with anti-CD20-hIFNα inhibited the NF-κB and p38 MAPK activities and induced the activation of PKC-δ and Stat-1. These effects were corroborated by the use of the inhibitors SB203580 (p38 MAPK) and Rottlerin (PKC-δ). Treatment with SB203580 enhanced the sensitization of the resistant clone by anti-CD20-hIFNα to CDDP apoptosis. In contrast, treatment with Rotterin inhibited significantly the sensitization induced by anti-CD20-hIFNα. Overall, the findings demonstrate that treatment with anti-CD20-hIFNα reverses resistance of B-NHL. These findings suggest the potential application of anti-CD20-hIFNα in combination with drugs in patients unresponsive to rituximab-containing regimens. PMID:26398317

  4. Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes.

    Science.gov (United States)

    Hu, Changyun; Ding, Heyuan; Zhang, Xiaojun; Wong, F Susan; Wen, Li

    2013-08-01

    Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease, although B cells also play an important role in T1D development. Both T cell- and B cell-directed immunotherapies have shown efficacy in the prevention and reversal of T1D. However, whether the combined strategy of targeting both T and B cells could further improve therapeutic efficacy remains to be explored. We show that combined treatment with intravenous antihuman CD20 (hCD20) and oral anti-CD3 significantly delays diabetes development in prediabetic hCD20 transgenic NOD mice. More importantly, the combined treatment reverses diabetes in >60% of mice newly diagnosed with diabetes. Further mechanistic studies demonstrated that the addition of oral anti-CD3 to the B-cell depletion therapy synergistically enhances the suppressive function of regulatory T cells. Of note, the oral anti-CD3 treatment induced a fraction of interleukin (IL)-10-producing CD4 T cells in the small intestine through IL-10- and IL-27-producing dendritic cells. Thus, the findings demonstrate that combining anti-CD20 and oral anti-CD3 is superior to anti-CD20 monotherapy for restoring normoglycemia in diabetic NOD mice, providing important preclinical evidence for the optimization of B cell-directed therapy for T1D.

  5. Structural comparison of two anti-CD20 monoclonal antibody drug products using middle-down mass spectrometry.

    Science.gov (United States)

    Wang, Bo; Gucinski, Ashley C; Keire, David A; Buhse, Lucinda F; Boyne, Michael T

    2013-05-21

    Liquid chromatography-mass spectrometry (LC-MS) is an information rich analytical tool that can provide fast, robust and sensitive characterization of protein therapeutics for quality assurance and structural comparison. Herein, structural characterization of two anti-CD20 monoclonal antibodies obtained from two different sources was performed using a middle-down LC-MS strategy to determine if they can be analytically differentiated. Through the use of a specific enzymatic digestion method using IdeS with subsequent LC-MS analysis, we show that the anti-CD20 monoclonal antibody that has been approved by the FDA can be partially characterized and differentiated analytically from an Indian sourced product that lacks FDA approval. In comparison to the FDA-approved product, differential modifications to both the N- and C-termini result in increased charge heterogeneity for the Indian product. In addition, significant differences in the intensities of the observed glycoforms between the two antibodies were detected. While this study assesses only one lot of each of a FDA approved drug product and the Indian sourced drug product, the observed differences may represent process specific fingerprints that could be useful for surveillance purposes.

  6. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice.

    Directory of Open Access Journals (Sweden)

    Ghanashyam Sarikonda

    Full Text Available A recent type 1 diabetes (T1D clinical trial of rituximab (a B cell-depleting anti-CD20 antibody achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin with anti-CD3 antibody (a T cell-directed immunomodulator offers better protection than either entity alone, indicating that novel combination therapies that include a T1D-related autoantigen are possible. To accelerate the identification and development of novel combination therapies that can be advanced into the clinic, we have evaluated the combination of a mouse anti-CD20 antibody with either oral insulin or a proinsulin-expressing DNA vaccine. Anti-CD20 alone, given once or on 4 consecutive days, produced transient B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone (twice weekly for 6 weeks was also ineffective, while proinsulin DNA (weekly for up to 12 weeks showed a trend toward modest efficacy. Combination of anti-CD20 with oral insulin was ineffective in reversing diabetes in NOD mice whose glycemia was controlled with SC insulin pellets; these experiments were performed in three independent labs. Combination of anti-CD20 with proinsulin DNA was also ineffective in diabetes reversal, but did show modest efficacy in diabetes prevention (p = 0.04. In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production.

  7. Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies

    Science.gov (United States)

    Grandjean, Capucine L.; Montalvao, Fabricio; Celli, Susanna; Michonneau, David; Breart, Beatrice; Garcia, Zacarias; Perro, Mario; Freytag, Olivier; Gerdes, Christian A.; Bousso, Philippe

    2016-01-01

    Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment. Relying on intravital two-photon imaging of human CD20-expressing mice, we provide evidence that ADP by Kupffer cells (KC) is a major mechanism for rituximab-mediated B cell depletion. Notably, a glycoengineered anti-mouse CD20 Ab but not its wild-type counterpart triggered potent KC-mediated B cell depletion at low doses. Finally, distinct thresholds for KC phagocytosis were also observed for GA101 (obinutuzumab), a humanized glycoengineered type II anti-CD20 Ab and rituximab. Thus, we propose that enhanced phagocytosis of circulating B cells by KC represents an important in vivo mechanism underlying the improved activity of glycoengineered anti-CD20 mAbs. PMID:27698437

  8. Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies.

    Science.gov (United States)

    Grandjean, Capucine L; Montalvao, Fabricio; Celli, Susanna; Michonneau, David; Breart, Beatrice; Garcia, Zacarias; Perro, Mario; Freytag, Olivier; Gerdes, Christian A; Bousso, Philippe

    2016-10-04

    Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment. Relying on intravital two-photon imaging of human CD20-expressing mice, we provide evidence that ADP by Kupffer cells (KC) is a major mechanism for rituximab-mediated B cell depletion. Notably, a glycoengineered anti-mouse CD20 Ab but not its wild-type counterpart triggered potent KC-mediated B cell depletion at low doses. Finally, distinct thresholds for KC phagocytosis were also observed for GA101 (obinutuzumab), a humanized glycoengineered type II anti-CD20 Ab and rituximab. Thus, we propose that enhanced phagocytosis of circulating B cells by KC represents an important in vivo mechanism underlying the improved activity of glycoengineered anti-CD20 mAbs.

  9. Subcutaneous injections of low doses of humanized anti-CD20 veltuzumab: a phase I study in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kalaycio, Matt E; George Negrea, O; Allen, Steven L; Rai, Kanti R; Abbasi, Rashid M; Horne, Heather; Wegener, William A; Goldenberg, David M

    2016-01-01

    To evaluate the potential of subcutaneous (SC) injections with anti-CD20 antibody veltuzumab in chronic lymphocytic leukemia (CLL), 21 patients received 80, 160, or 320 mg injections every 2 weeks × 4 doses (n = 11) or 160 or 320 mg twice-weekly × 16 doses (n = 10). Treatment was well tolerated with only occasional, mild-moderate, transient injection reactions. Lymphocytosis decreased in all patients (maximum decrease, 5-91%), with 12 patients obtaining >50% decreases. Of 14 patients with lymphadenopathy on CT imaging, 5 (36%) achieved 14-61% reductions (sum of perpendicular diameters). By NCI-WG criteria, two patients achieved partial responses (10%). SC veltuzumab appeared active in all dose groups, with no obvious exposure-response relationship, despite cumulative doses ranging from 320-5120 mg. Overall median progression-free survival was 7.7 months; three patients remained progression-free >1 year (2 ongoing at 2-year study completion). These data suggest further studies of SC veltuzumab in CLL are warranted.

  10. Binding Activity Difference of Anti-CD20 scFv-Fc Fusion Protein Derived from Variable Domain Exchange

    Institute of Scientific and Technical Information of China (English)

    Shusheng Geng; Beifen Shen; Jiannan Feng; Yan Li; Yingxun Sun; Xin Gu; Ying Huang; Yugang Wang; Xianjiang Kang; Hong Chang

    2006-01-01

    Two novel engineered antibody fragments binding to antigen CD20 were generated by fusing a murine IgM-type anti-CD20 single-chain Fv fragment (scFv) to the human IgG1 CH2 (I.e., Cγ2) and CH3 (I.e., Cγ3) domains with the human IgG1 hinge (I.e. Hγ). Given the relationship between structure and function of protein, the 3-D structures of the two engineered antibody fragments were modeled using computer-aided homology modeling method.Furthermore, the relationship between 3-D conformation and their binding activity was evaluated theoretically.Due to the change of active pocket formed by CDRs, the HL23 (VH-Linker-VL-Hγ-Cγ2-Cγ3) remained its activity because of its preserved conformation, while the binding activity of the LH23 (VL-Linker-VH-Hγ-Cγ2-Cγ3) was impaired severely. Experimental studies by flow cytometry and fluorescence microscopy showed that HL23 possessed significantly superior binding activity to CD20-expressing target cells than LH23. That is to say, the order of variable regions could influence the binding activity of the fusion protein to CD20+ cell lines, which was in accordance with the theoretical results. The study highlights the potential relationship between the antibody binding activity and their 3-D conformation, which appears to be worthwhile in providing direction for future antibody design of recombinant antibody.

  11. Anti-CD20 as the B cells targeting agent in the combined therapy to modulate anti-factor VIII immune responses in hemophilia A inhibitor mice

    Directory of Open Access Journals (Sweden)

    Chao Lien eLiu

    2014-01-01

    Full Text Available Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are still lacking. Anti-FVIII neutralizing antibodies circulate for long periods in part due to persistence of memory B cells. Anti-CD20 targets a variety of B cells (pre-B cells to mature/memory cells; therefore, we investigated the impact of B cell depletion on anti-FVIII immune responses in hemophilia A mice using anti-CD20 combined with regulatory T (Treg cell expansion using IL-2/IL-2mAb complexes plus rapamycin. We found that anti-CD20 alone can partially modulate anti-FVIII immune responses in both unprimed and FVIII-primed hemophilia A mice. Moreover, in mice treated with anti-CD20 + IL-2/IL-2mAb complexes + rapamycin + FVIII, anti-FVIII antibody titers were significantly reduced in comparison to mice treated with regimens targeting only B or T cells. In addition, titers remained low after a second challenge with FVIII plasmid . Treg cells and activation markers were transiently and significantly increased in the groups treated with IL-2/IL-2mAb complexes ; however,significant B cell depletion was obtained in anti-CD20-treated groups. Importantly, both FVIII-specific antibody-secreting cells and memory B cells were significantly reduced in mice treated with combination therapy. This study demonstrates that a combination regimen is highly promising as a treatment option for modulating anti-FVIII antibodies and facilitating induction of long-term tolerance to FVIII in hemophilia A mice.

  12. Standardization of methodology to derivatization and radiolabeling of the anti-CD20 monoclonal antibody from bifunctional chelator DOTA-NHS-Ester

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Akanji, Akinkunmi G.; Santos, Josefina S.; Pujatti, Priscilla B.; Couto, Renata M.; Massicano, Felipe; Araujo, Elaine Bortoleti de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], E-mail: adriana.avfernandes@gmail.com

    2009-07-01

    Lymphomas are cancers of the lymphatic system, being the most common the non-Hodgkin lymphoma (NHL). The Radioimmunotherapy (RIT), that increase the cytotoxic effect of monoclonal antibodies (mAb), therefore labeling these Mab with different radioisotopes. RIT combines the specificity of the antibody and the toxicity of the radionuclides. The mAb anti-CD20 is used for treatment of relapse or refractory NHL. The labeling of anti- CD20 with {sup 177}Lu, requires a bifunctional chelating agent that is designed to make a 'connect bridge' between the mAb and the radionuclide. The incorporation of the chelating group in mAb structure is called derivatization. The aim of this work is to study the derivatization of anti-CD20 antibody with DOTA-NHS-ester chelating group and labeling parameters to produce {sup 177}Lu-DOTA-Anti CD20. Five milligrams of anti-CD20 were purified by dialysis against phosphate buffer pH 8.0 and derivatized with DOTA-NHS-ester in 1:250, 1:500 and 1:1000 molar ratios. The reaction was conducted for 1 hour in gently mixing at room temperature and remained under refrigeration for 48 hours. The reaction mixture was purified in gel column Sephadex G-50 ; the aliquots that presented greater protein concentration, were mixed and concentrated. The purified antibody conjugated was added to 111-185MBq (3-5mCi) of {sup 177}LuCl3 diluted in 0.4 M acetate buffer pH 5.5. Radiochemical purity was less than 95% in all the molar ratios, indicating necessity of the purification after the labeling. The mAb derivatized showed stable when stored for to 1 month to 4 deg C and 4 days at -20 deg C. (author)

  13. Multivalent system for therapy of non-Hod king lymphomas based on Anti-CD20 conjugated to gold nanoparticles; Sistema multivalente para terapia de linfomas no-Hodking basado en Anti-CD20 conjugado a nanoparticulas de oro

    Energy Technology Data Exchange (ETDEWEB)

    Miranda O, R. M.

    2014-07-01

    In recent publications has been reported that gold nanoparticles have an effect in reducing the expression of the oncogene Bcl -2 and have a high biocompatibility , this is the importance for using gold nanoparticles for this work. The antibody CD20 is an antibody that specifically binds to that over expressed CD20 antigen on the cell membrane of B lymphoma cell non- Hodgkin (cell line Raji) behold the importance of combining this bio molecule to gold nanoparticles since they have a high specificity with CD20 positive cells , also to carry out the antigen- antibody immunological reactions triggered mediating cell lysis, possibly by cytotoxicity and apoptosis. Therefore, this system must have characteristics of both components to eliminate B cell non- Hodgkin lymphoma.In this work it was studied a multivalent system composed of gold nanoparticles and anti-CD20 antibody, the term multi valency refers to the number of biomolecules attached to the surface of the gold nanoparticle. The synthesis and characterization of the gold nanoparticles and the multivalent system was performed and the effect of the multivalent system on the expression of oncogene Bcl-2 (group of proteins associated with the apoptotic pathway) was evaluated. Characterization of raw materials and the multivalent system was performed using spectroscopic and microscopic techniques, this to verify structural changes in raw materials and thus confirm the formation of CD20 binding to the surface of the nanoparticle gold by the bond between gold and sulfur in the cysteines of CD20. Taking advantage that the metal nanoparticles have the optical property of surface plasmon resonance, the absorption of gold nanoparticles was measured on the UV-Vis as it is affected by the surface molecules bind to it, showing a bathochromic displacement effected. The hydrodynamic diameter of the gold nanoparticles was measured to verify that the antibody is bound to the surface; this evidence was complemented by micrographs

  14. The Different Clinical Effects of Anti-BLyS, Anti-APRIL and Anti-CD20 Antibodies Point at a Critical Pathogenic Role of gamma-Herpesvirus Infected B Cells in the Marmoset EAE Model

    NARCIS (Netherlands)

    Jagessar, S. Anwar; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D.; Oh, Luke; Migone, Thi; Verschoor, Ernst J.; 't Hart, Bert A.

    2013-01-01

    The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephal

  15. Human IgG1 Cγ1 Domain Is Crucial for the Bioactivity of the Engineered Anti-CD20 Antibodies

    Institute of Scientific and Technical Information of China (English)

    Shusheng Geng; Jiannan Feng; Yan Li; Xianjiang Kang; Yingxun Sun; Xin Gu; Ying Huang; Hong Chang; Beifen Shen

    2007-01-01

    In this study, we discussed the necessity of human IgG1 Cγ1 domain for recombinant antibody using computeraided homology modeling method and experimental studies. The heavy (VH) and light (VL) chain variable regions of 1-28, a murine IgM-type anti-CD20 mAb, were ligated by linker peptide (Gly4Ser)3 to form the single-chain Fv fragment (scFv). Then, the engineered antibody (LH1-3) was generated by fusing scFv with the entire IgG1 heavy constant regions. The 3-D structure of LH1-3 was modeled using computer-aided homology modeling method and the binding activity of LH1-3 was evaluated theoretically. Compared to the 3-D structure of the Fv fragment of the parent antibody, the conformation of the active pocket of LH1-3 was remained because of the rigid support of Cγ1.Further experimental results of flow cytometry showed that the engineered anti-CD20 antibody possessed specifically binding activity to CD20-expressing target cells. The anti-CD20 antibody fragments could also mediate complement-dependent cytotoxicity (CDC) of human B-lymphoid cell lines. Our study highlights some interests and advantages of a methodology based on the homology modeling and analysis of molecular structural properties.

  16. Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab' Synthesis.

    Science.gov (United States)

    Zhou, Zhan; Zhang, Jing; Zhang, Yan; Ma, Guanghui; Su, Zhiguo

    2016-01-20

    Conventional preparation strategies for antibody-drug conjugates (ADCs) result in heterogeneous products with various molecular sizes and species. In this study, we developed a homogeneous preparation strategy by site-specific conjugation of the anticancer drug with an antibody fragment. The model drug doxorubicin (DOX) was coupled to the Fab' fragment of anti-CD20 IgG at its permissive sites through a heterotelechelic PEG linker, generating an antibody fragment-drug conjugate (AFDC). Anti-CD20 IgG was digested and reduced specifically with β-mercaptoethylamine to generate the Fab' fragment with two free mercapto groups in its hinge region. Meanwhile, DOX was conjugated with α-succinimidylsuccinate ω-maleimide polyethylene glycol (NHS-PEG-MAL) to form MAL-PEG-DOX, which was subsequently linked to the free mercapto containing Fab' fragment to form a Fab'-PEG-DOX conjugate. The dual site-specific bioconjugation was achieved through the combination of highly selective reduction of IgG and introduction of heterotelechelic PEG linker. The resulting AFDC provides an utterly homogeneous product, with a definite ratio of one fragment to two drugs. Laser confocal microscopy and cell ELISA revealed that the AFDC could accumulate in the antigen-positive Daudi tumor cell. In addition, the Fab'-PEG-DOX retained appreciable targeting ability and improved antitumor activity, demonstrating an excellent therapeutic effect on the lymphoma mice model for better cure rate and significantly reduced side effects.

  17. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients.

    Science.gov (United States)

    Salles, Gilles; Morschhauser, Franck; Lamy, Thierry; Milpied, Noel; Thieblemont, Catherine; Tilly, Hervé; Bieska, Gabi; Asikanius, Elina; Carlile, David; Birkett, Joe; Pisa, Pavel; Cartron, Guillaume

    2012-05-31

    Whereas the chimeric type I anti-CD20 Ab rituximab has improved outcomes for patients with B-cell malignancies significantly, many patients with non-Hodgkin lymphoma (NHL) remain incurable. Obinutuzumab (GA101) is a glycoengineered, humanized anti-CD20 type II Ab that has demonstrated superior activity against type I Abs in vitro and in preclinical studies. In the present study, we evaluated the safety, efficacy, and pharmacokinetics of GA101 in a phase 1 study of 21 patients with heavily pretreated, relapsed, or refractory CD20(+) indolent NHL. Patients received GA101 in a dose-escalating fashion (3 per cohort, range 50/100-1200/2000 mg) for 8 × 21-day cycles. The majority of adverse events (AEs) were grades 1 and 2 (114 of 132 total AEs). Seven patients reported a total of 18 grade 3 or 4 AEs. Infusion-related reactions were the most common AE, with most occurring during the first infusion and resolving with appropriate management. Three patients experienced grade 3 or 4 drug-related infusion-related reactions. The best overall response was 43%, with 5 complete responses and 4 partial responses. Data from this study suggest that GA101 was well tolerated and demonstrated encouraging activity in patients with previously treated NHL up to doses of 2000 mg. This trial is registered at www.clinicaltrials.gov as NCT00517530.

  18. A Review of Obinutuzumab (GA101), a Novel Type II Anti-CD20 Monoclonal Antibody, for the Treatment of Patients with B-Cell Malignancies.

    Science.gov (United States)

    Tobinai, Kensei; Klein, Christian; Oya, Naoko; Fingerle-Rowson, Günter

    2017-02-01

    Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies. Efficacy as monotherapy has been reported in patients with relapsed/refractory indolent and aggressive non-Hodgkin lymphoma (NHL) and in chronic lymphocytic leukemia (CLL) of B-cell origin. Improved outcomes have also been noted when obinutuzumab is added to chemotherapy in patients with B-cell NHL, and superiority over rituximab has been reported with combination therapy in patients with CLL. Ongoing research is focusing on developing options for chemotherapy-free treatment and on new combinations of obinutuzumab with novel targeted agents.

  19. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani; Kenoyer, Aimee L.; Hylarides, Mark; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sophia; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Ted; Laird, Kelley L.; Till, B. G.; Back, Tom; Sandmaier, B. M.; Pagel, John M.; Press, Oliver W.

    2015-03-26

    Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

  20. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  1. Evaluation of the cell death mechanisms activated by the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy; Evaluacion de los mecanismos de muerte celular activados por el radiofarmaco {sup 177}Lu-DOTA-anti-CD20 en un intervalo de dosis de 1 a 5 Gy

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    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G., E-mail: erica.azorin@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2016-10-15

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation

  2. Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

    Directory of Open Access Journals (Sweden)

    Hélène Carpenet

    Full Text Available In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc, an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT. Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%. 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C and in serum (37°C, even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe

  3. Monotherapy with anti-CD20 monoclonal antibody in a heart transplant recipient with sick sinus syndrome and posttransplantation lymphoproliferative disorder: a case report.

    Science.gov (United States)

    Yang, Hsiang-Yu; Ke, Hung-Yen; Hong, Gou-Jieng; Tsai, Yi-Ting; Lin, Chih-Yuan; Li, Chung-Yi; Tsai, Chien-Sung

    2009-10-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with an incidence of 0.8% to 20% in heart transplant (HTx) recipients, and standard treatment may be too toxic in some cases. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies and has been demonstrated effective in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Cardiotoxicity with CHOP remains a major concern for treating HTx recipients with PTLD, however. We present a case of an HTx recipient with sick sinus syndrome and PTLD who was successfully treated with rituximab alone, avoiding the cardiotoxicity of CHOP. The cardiotoxicity induced by CHOP should be kept in mind in HTx recipients with PTLD, especially when there is an existing heart problem in such recipients. Monotherapy with rituximab can be considered a safe choice.

  4. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma

    Science.gov (United States)

    Negrea, George O.; Elstrom, Rebecca; Allen, Steven L.; Rai, Kanti R.; Abbasi, Rashid M.; Farber, Charles M.; Teoh, Nick; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2011-01-01

    Background Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. Design and Methods A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2nd generation anti-CD20 antibody veltuzumab in patients with CD20+ indolent non-Hodgkin’s lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Conclusions Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin’s lymphoma. (Clinicaltrials.gov identifier: NCT00546793) PMID:21173095

  5. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin's lymphoma.

    Science.gov (United States)

    Negrea, George O; Elstrom, Rebecca; Allen, Steven L; Rai, Kanti R; Abbasi, Rashid M; Farber, Charles M; Teoh, Nick; Horne, Heather; Wegener, William A; Goldenberg, David M

    2011-04-01

    Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2(nd) generation anti-CD20 antibody veltuzumab in patients with CD20(+) indolent non-Hodgkin's lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov identifier: NCT00546793).

  6. Orthotopic liver transplantation after successful treatment with anti-CD20 monoclonal antibody (rituximab) for severe steroid-resistant autoimmune hemolytic anemia: a case report.

    Science.gov (United States)

    Annicchiarico, B E; Siciliano, M; Avolio, A W; Agnes, S; Bombardieri, G

    2009-05-01

    Chronic hepatitis C virus (HCV) infection has been associated with a wide number of immunologic disorders, ranging from clinically silent laboratory abnormalities (eg, autoantibody positivity) to severe systemic diseases (eg, cryoglobulinemic vasculitis). Autoimmune hemolytic anemia (AIHA), due to the production of antibodies against erythrocyte membrane antigens, is an uncommon extrahepatic manifestation in the setting of chronic hepatitis C. Herein we have reported the case of a 57-year-old woman with decompensated HCV-related cirrhosis awaiting orthotopic liver transplantation (OLT) who experienced severe AIHA. After 1 month of treatment with prednisone (1 mg/kg body weight/d), there was no significant amelioration of anemia. Rituximab, an anti-CD20 monoclonal antibody that depletes B-lymphocytes reducing serum immunoglobulins, was initiated (375 mg/m(2) IV, weekly for 4 weeks) with a prompt, sustained increase in hemoglobin. The drug was well tolerated; it did not interfere with the course of the liver disease. Thirty-one months after rituximab therapy with resolution of AIHA, the patient successfully underwent OLT using immunosuppression with tacrolimus and low-dose steroids. The patient was discharged on postoperative day 36. No infectious event occurred in the postoperative period. At 18 months follow-up after OLT, there has been no infectious or hematological event. Our experience supported the safety of rituximab use in patients with advanced HCV-related liver disease before OLT.

  7. The study of labeling with Iodine-131 of monoclonal antibody anti-CD20 used for the treatment of non-Hodgkin lymphoma; Estudo de marcacao com Iodo-131 de anticorpo monoclonal anti-CD20 na terapia de linfoma nao-Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Akanji, Akinkunmi Ganiyu

    2006-07-01

    Lymphomas are malignancies of the lymphatic system, described by Thomas Hodgkin in 1932. Traditionally, lymphomas are classified in two basic groups: Hodgkin disease and non-Hodgkin lymphoma (NHL). Patients with NHL were earlier treated with radiotherapy alone or in combination with immunotherapy using monoclonal antibody anti-CD20 (ex., Rituximab-Mabthera, Roche). However, Radioimmunotherapy is a new modality of treatment for patients with NHL, in which cytotoxic radiation from therapeutic radioisotopes is delivered to tumors through monoclonal antibodies. This study focused on labeling conditions of monoclonal antibody anti-CD20 (Rituximab-Mabthera, Roche) with iodine-131, by direct radioiodination method using Chloramine-T as oxidizing agent. Labeling parameters investigated were: Radiochemical purity (RP), method of purification, incubation time, antibody mass, oxidative agent mass, stability in vitro, stability in vivo, immunoreactivity and biological distribution performed in normal Swiss mouse. Product of high radiochemical purity was obtained with no notable difference between the methods applied. No clear evidence of direct influence of incubation time on radiochemical purity of the labeled antibody was observed. Whereas, a clear evidence of direct influence of activity on radiochemical purity of the labeled antibody was observed when antibody mass was varied. After purification, the labeled product presented radiochemical purity of approximately 100 %. Product of superior radiochemical yield was observed when standard condition of labeling was used. The labeled product presented variation in radiochemical purity using five different stabilizer conditions. The condition in which gentisic acid was combined with freeze appears more suitable and capable of minimizing autoradiolysis of the antibody labeled with high therapeutic activity of iodine-131. The labeled product presented low immunoreactivity when compared to the literature. Biological distribution in

  8. Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates

    Directory of Open Access Journals (Sweden)

    Ondřej Lidický

    2015-11-01

    Full Text Available Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb rituximab (RTX. The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX was attached to the N-(2-hydroxypropylmethacrylamide (HPMA-based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5–5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates.

  9. Target antigen density governs the efficacy of anti-CD20-CD28-CD3 ζ chimeric antigen receptor-modified effector CD8+ T cells.

    Science.gov (United States)

    Watanabe, Keisuke; Terakura, Seitaro; Martens, Anton C; van Meerten, Tom; Uchiyama, Susumu; Imai, Misa; Sakemura, Reona; Goto, Tatsunori; Hanajiri, Ryo; Imahashi, Nobuhiko; Shimada, Kazuyuki; Tomita, Akihiro; Kiyoi, Hitoshi; Nishida, Tetsuya; Naoe, Tomoki; Murata, Makoto

    2015-02-01

    The effectiveness of chimeric Ag receptor (CAR)-transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second- and later-generation CARs simultaneously transmit costimulatory signals with CD3ζ signals upon ligation, but may lead to severe adverse effects owing to the recognition of minimal Ag expression outside the target tumor. Currently, the threshold target Ag density for CAR-T cell lysis and further activation, including cytokine production, has not yet been investigated in detail. Therefore, we determined the threshold target Ag density required to induce CAR-T cell responses using novel anti-CD20 CAR-T cells with a CD28 intracellular domain and a CD20-transduced CEM cell model. The newly developed CD20CAR-T cells demonstrated Ag-specific lysis and cytokine secretion, which was a reasonable level as a second-generation CAR. For lytic activity, the threshold Ag density was determined to be ∼200 molecules per target cell, whereas the Ag density required for cytokine production of CAR-T cells was ∼10-fold higher, at a few thousand per target cell. CD20CAR-T cells responded efficiently to CD20-downregulated lymphoma and leukemia targets, including rituximab- or ofatumumab-refractory primary chronic lymphocytic leukemia cells. Despite the potential influence of the structure, localization, and binding affinity of the CAR/Ag, the threshold determined may be used for target Ag selection. An Ag density below the threshold may not result in adverse effects, whereas that above the threshold may be sufficient for practical effectiveness. CD20CAR-T cells also demonstrated significant lytic activity against CD20-downregulated tumor cells and may exhibit effectiveness for CD20-positive lymphoid malignancies. Copyright © 2015 by The American Association of Immunologists, Inc.

  10. Intraläsionale Therapie niedrig maligner primär kutaner B-Zell-Lymphome mit Anti-CD20-Antikörper: Nebenwirkungen korrelieren mit gutem klinischen Ansprechen.

    Science.gov (United States)

    Eberle, Franziska C; Holstein, Julia; Scheu, Alexander; Fend, Falko; Yazdi, Amir S

    2017-03-01

    Die intraläsionale Gabe von Anti-CD20-Antikörpern (Rituximab) wurde als effektive Therapieoption für Patienten mit niedrig malignen primär kutanen B-Zell-Lymphomen beschrieben. Bis heute wurden allerdings keine Parameter identifiziert, welche reproduzierbar ein gutes klinisches Ansprechen dieser Therapie vorhersagen. Ziel dieser Studie ist, sowohl das klinische Ansprechen und die unerwünschten Nebenwirkungen als auch die Patientenwahrnehmung hinsichtlich intraläsionaler Injektionen von anti-CD20-Antikörpern zur Behandlung indolenter primär kutaner B-Zell-Lymphome im Vergleich mit anderen Therapien zu evaluieren. Elf Patienten mit einem primär kutanen B-Zell-Lymphom, namentlich primär kutanes Keimzentrumslymphom (n = 9) und primär kutanes Marginalzonenlymphom (n = 2), welche mittels intraläsionalem Anti-CD20-Antikörper behandelt wurden, wurden retrospektiv evaluiert hinsichtlich der Ansprechrate und unerwünschter Nebenwirkungen sowie in Bezug auf deren Selbsteinschätzung dieser und anderer Therapien des primär kutanen B-Zell-Lymphoms. Patienten, deren primär kutanes B-Zell-Lymphom mittels intraläsionaler Gabe von Anti-CD20-Antikörper behandelt wurde, zeigten ein komplettes oder partielles Ansprechen in 45 % beziehungsweise 27 % aller Patienten. Speziell Patienten mit grippeähnlichen Symptomen nach erfolgter Injektion zeigten ein gutes Ansprechen. Die Mehrheit der Patienten empfand die Therapie mit Rituximab als die beste Therapie im Vergleich zu anderen Therapien wie beispielsweise chirurgische Exzision oder Radiotherapie. Intraläsionales Rituximab ist eine effektive Therapie mit hoher Patientenzufriedenheit. Starke therapiebedingte Nebenwirkungen wie Fieber, Schüttelfrost und Kopfschmerzen nach Gabe von Rituximab könnten als Indikator für gute Wirksamkeit dienen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  11. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Øystein Fluge

    Full Text Available BACKGROUND: Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients. METHODS AND FINDINGS: In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening. CONCLUSION: The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding

  12. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William;

    2010-01-01

    To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug....

  13. The different clinical effects of anti-BLyS, anti-APRIL and anti-CD20 antibodies point at a critical pathogenic role of γ-herpesvirus infected B cells in the marmoset EAE model.

    Science.gov (United States)

    Anwar Jagessar, S; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D; Oh, Luke; Migone, Thi; Verschoor, Ernst J; 't Hart, Bert A

    2013-06-01

    The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys (Callithrix jacchus). By contrast, treatment with mAbs against two essential cytokines in B cell activation growth and survival, i.e. BlyS/BAFF and APRIL, was only partially effective. All three mAbs induced depletion of CD20+ B cells from the circulation, albeit with different kinetics and based on distinct mechanisms of action. In the current study we analyzed whether the different clinical effect of anti-CD20 mAb or the anti-BLyS and anti-APRIL mAbs is due to different depletion of B cells infected with the EBV of marmosets, CalHV3. Employing a novel PCR-based assay, half of the colony of group-housed marmosets was tested positive for CalHV3 DNA in secondary lymphoid organs. The same prevalence was observed in placebo-treated monkeys. In marmosets treated with anti-CD20 mAb the load of CalHV3 DNA in lymphoid organs was substantially reduced, while this was not observed in the monkeys treated with anti-BLyS or anti-APRIL mAbs. To examine the pathogenic role of virus-transformed B cells, we infused EBV-transformed B lymphoblastic cell (BLC) lines presenting the immunodominant MOG34-56 peptide. We observed in the recipients of MOG34-56 pulsed BLC, but not in their fraternal siblings infused with non-pulsed BLC, activation of anti-MOG34-56 T cells and meningeal inflammation. Collectively, the data show that among CD20+ B cells, the herpesvirus-transformed subset has a particularly important pathogenic role in the marmoset EAE model.

  14. Efficacy and safety of an anti-CD20 monoclonal antibody (Reditux™) for the treatment of patients with moderate to severe rheumatoid arthritis following the failure of conventional synthetic disease-modifying anti-rheumatic drugs.

    Science.gov (United States)

    Bhati, Manjeet; Bandyopadhyay, Syamasis

    2016-08-01

    Rituximab (anti-CD20 monoclonal antibody) has shown to improve symptoms in rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). An anti-CD20 monoclonal antibody (Reditux™) developed by Dr. Reddy's Laboratories, India, is currently approved for use both in rheumatology and oncology patients. This retrospective report evaluates the efficacy and safety data from the real-world use of Reditux™ over a 6-month period in Indian patients with RA. All consecutive moderate to severe RA patients who failed therapy with at least two DMARDs including methotrexate (MTX) for 6 months, TNFα inhibitor naive, and willing to take Reditux™ were included. They were prescribed two doses of 1 g Reditux™, at least 15 days apart, with continued stable doses of methotrexate. Efficacy and safety after 24 weeks relative to baseline was assessed using various health assessment variables. A total of 39 patients (mean age of 46 years; 67.5 % females) treated with Reditux™ were evaluated. Statistically significant differences were observed in mean changes of DAS28-CRP, DAS28-ESR, SDAI, HAQ and Patient Global Assessment scores from baseline to 24 weeks (p treatment. The treatment was well tolerated by patients without any clinically relevant serious adverse events over 24 weeks. Though limited by number of patients and retrospective in nature, this analysis serves as a real-world evidence of efficacy and safety of Dr. Reddy's rituximab (Reditux™) in the treatment of csDMARD-failed patients with RA over a 6-month period.

  15. Targeting CD20+ Aggressive B-cell Non-Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice.

    Science.gov (United States)

    Chu, Yaya; Hochberg, Jessica; Yahr, Ashlin; Ayello, Janet; van de Ven, Carmella; Barth, Matthew; Czuczman, Myron; Cairo, Mitchell S

    2015-04-01

    The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti-CD20 CAR-modified, expanded peripheral blood NK cells (exPBNK) following mRNA nucleofection against CD20(+) B-NHL in vitro and in vivo. CAR(+) exPBNK had significantly enhanced in vitro cytotoxicity, compared with CAR(-) exPBNK against CD20(+) Ramos (P CAR(+) exPBNK in response to CD20(+) B-NHL -: specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NOD/SCID/γ-chain(-/-) (NSG) mice, the luciferase signals measured in the CAR(+) exPBNK-treated group were significantly reduced, compared with the signals measured in the untreated mice and in mice treated with the CAR(-) exPBNK. Furthermore, the CAR exPBNK-treated mice had significantly extended survival time (P CAR(-) exPBNK-treated mice (P CAR may have therapeutic potential for treating patients with poor-risk CD20(+) hematologic malignancies. ©2014 American Association for Cancer Research.

  16. Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.

    Science.gov (United States)

    Sharman, Jeff P; Farber, Charles M; Mahadevan, Daruka; Schreeder, Marshall T; Brooks, Heather D; Kolibaba, Kathryn S; Fanning, Suzanne; Klein, Leonard; Greenwald, Daniel R; Sportelli, Peter; Miskin, Hari P; Weiss, Michael S; Burke, John M

    2017-02-01

    Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty-one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high-risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long-term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).

  17. 两种重组抗CD20人源化单克隆抗体定量分析方法的比较及其在药代动力学研究中的应用%Comparison of Two Quantitative Assays for Determination of Rh-anti-CD20 zumab and Their Application to Pharmacokinetic Study

    Institute of Scientific and Technical Information of China (English)

    邓承莲; 邹佳; 欧伦; 董立厚; 宋海峰

    2014-01-01

    An enzyme linked immunosorbent assay ( ELISA ) and a flow cytometry assay ( FCA ) based on Wil2-S cells were developed and systematically compared for quantification of recombinant anti-CD20 humanized monoclonal antibody ( rh-anti-CD20zumab) in biological matrix. The specificity, precision and accuracy of each method at correspondingly different linear range showed good results. For ELISA, the precisions of intra-day and inter-day were both <19 . 5%, the relative error was from-18 . 2% to 17 . 6%;For FCA, the precisions of intra-day and inter-day were both <19. 0%, the relative error was from -18. 9% to 18. 4%. The sensitivity of ELISA was significantly higher than that of FCA. The quantitative ranges of ELISA and FCA methods were 0. 04-5. 0 mg/L and 3. 1-200 mg/L, respectively. The concentrations in serum samples and pharmacokinetics analysis were determined by both of two methods after vein drip administration of rh-anti-CD20zumab in rhesus monkeys. Pharmacokinetics data showed that there was excellent consistency between results obtained by two methods at the given dose. We believe that the novel FCA with high speed and high sensitivity can be used to perform PK and PD study of cell surface antigen-targeted antibody derivatives.%采用酶联免疫吸附分析( ELISA)与基于Wil2-S细胞的流式细胞术( FCA)两种方法对生物基质中的重组抗CD20人源化单克隆抗体(rh-anti-CD20zumab)进行定量分析,并对两种方法进行系统比较。方法学验证结果表明,两种方法均具有良好的特异性、精密度和准确度,但定量范围存在明显差异。 ELISA法批内和批间精密度均小于19.5%,准确度为-18.2%~17.6%;FCA法批内和批间精密度均小于19.0%,准确度为-18.9%~18.4%。二者定量范围分别为0.04~5.0 mg/L和3.1~200 mg/L,ELISA法的灵敏度显著高于FCA法。利用两种方法测定猕猴静脉滴注 rh-anti-CD20zumab后的血药浓度-时间变化并进行药代动力学( PK)分析。结果表明,

  18. Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab.

    Science.gov (United States)

    Yasuhiro, Tomoko; Sawada, Wako; Klein, Christian; Kozaki, Ryohei; Hotta, Shingo; Yoshizawa, Toshio

    2017-03-01

    The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101). ONO/GS-4059 combined with GA101 or RTX was significantly better than the respective monotherapy with tumor growth inhibition (TGI) of 90% for the GA101 combination and 86% for the RTX combination. In contrast, ibrutinib (PCI-32765) combined with RTX did not result in improved efficacy compared with respective monotherapy. Taken together these data indicate that the combination of ONO/GS-4059 with rituximab and particularly obinutuzumab may be an effective treatment for ABC-DLBCL.

  19. Anti CD20 (Rituximab therapy in refractory pediatric rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Joel Reis

    2016-01-01

    Full Text Available Objectives: We aim to report the efficacy and safety of rituximab (RTX in patients diagnosed with juvenile systemic lupus erythematosus (JSLE or juvenile idiopathic arthritis (JIA refractory to conventional treatment. Methods: A retrospective review was made of all medical records of patients with JSLE or JIA treated with RTX between January 2009 and January 2015 in the Pediatric Rheumatology Unit of a central hospital. Results: Five patients, 4 with JSLE and 1 with extended oligoarticular JIA, received 10 cycles of RTX (23 infusions. The scheme of RTX frequently used was 750 mg/m2 two weeks apart. The median follow-up time after receiving the first cycle of RTX was 24 months (12 – 70. The four patients with JSLE were female (three caucasian and one black. The patient with JIA was a caucasian male. The median age at diagnosis was 10 years (16 months – 17years. The median evolution time until receiving RTX was 6 years (5 months – 15 years. Refractory class IV lupus nephritis was the most common indication for receiving RTX. Previous treatment to RTX included nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, immunosuppressive drugs and corticosteroids in all patients and anti-TNFα (etanercept in the patient with JIA. It was possible to reduce the mean oral corticosteroid dose after RTX, ranging from 23 mg/day (20-25mg/day before RTX to 11 mg/day (0–20 mg/day at the last evaluation. Disease activity before RTX and at last evaluation also improved. The SLEDAI score, for JSLE, decreased from a median of 15, 5 (11 – 18 to 3 (0 – 6, and the JADAS-27 score, for JIA, also diminished from 40.4 to 3.5. Adverse events occurred in 2 patients, including delayed second dose after the diagnosis of cryptococcosis and respiratory tract infection with concomitant hypogammaglobulinemia needing of immunoglobulin replacement and antibiotic therapy. Conclusions: Rituximab might have a role in the treatment of JSLE and JIA. However controlled studies and long term follow-up are needed to evaluate its safety and efficacy.

  20. Iodine-131 Tositumomab: (131)I-anti-B1 antibody, (131)I-tositumomab, anti-CD20 murine monoclonal antibody-I-131, B1, Bexxar, (131)I-anti-B1 antibody, iodine-131 tositumomab, iodine-131 anti-B1 antibody, tositumomab.

    Science.gov (United States)

    2003-01-01

    combination with CHOP chemotherapy is underway in the US as first-line therapy in patients with intermediate-grade NHL. Corixa Corporation has initiated a phase II trial of iodine-131 tositumomab in combination with cyclophosphamide, vincristine and prednisone for the treatment of previously untreated low-grade NHL. The trial was initiated while the company was preparing its BLA for Bexxar for use as a single agent for relapsed or refractory NHL. Corixa Corporation intends to pursue additional trials to expand the potential use of iodine-131 tositumomab to other indications, including chronic lymphocytic leukaemia. The agent is also in a clinical trial for preparation in autologous bone marrow transplant patients. The trial is designed to test the combination of iodine-131 tositumomab and chemotherapy. The trial began in 1995 and has so far enrolled 40 patients. In addition, a phase II dose-escalation trial has begun at the University of Nebraska for the combined use of iodine-131 tositumomab and chemotherapy as preparation for autologous bone marrow transplant. Corixa Corporation has received an issued US patent covering methods for administering and dosing radioimmunotherapy for the treatment of B-cell lymphomas. The patent covers iodine-131 tositumomab and other anti-CD20 antibodies used to aid in selective tumour targeting. Corixa Corporation has exclusive rights to the patent.A February 2000 media release from GlaxoSmithKline and Corixa Corporation stated that they had been issued a composition patent relating to radiolabelled monoclonal antibodies (including Bexxar) for the treatment of B-cell lymphomas. On 11 September 2001, IDEC announced that it had filed two separate lawsuits. The first lawsuit is against Corixa Corporation and the University of Michigan on six patents pertaining to products and processes related to radioimmunotherapy. They seek a declaration that Zevalin does not infringe Corixa Corporation's issued US patents. The second lawsuit involves two

  1. 抗CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究%Clinical study of autologous peripheral blood stem cell transplantation combined with anti-CD20 monoclonal antibody in non-Hodgkin lymphoma

    Institute of Scientific and Technical Information of China (English)

    蔡宇; 王椿; 姜杰玲; 杨隽; 颜式可; 万理萍

    2010-01-01

    目的 探讨抗CD20单克隆抗体(利妥昔单抗,商品名:美罗华)联合自体外周血干细胞移植(APBSCT)治疗B细胞非霍奇金淋巴瘤(NHL)的疗效.方法 21例CD20阳性的NHL患者,经过前期治疗,5例达完全缓解(CR),难治性病例为16例,包括11例部分缓解(PR)和5例疾病进展(PD).在自体造血干细胞动员的第1、8天及预处理的-1、+7天每天应用利妥昔单抗375 mg/m2.结果 移植前疾病达到CR的5例患者,无一例复发;移植前处于PR的11例患者,仅1例在移植后6个月疾病复发,其余均无病生存;移植前处于PD的5例患者,2例无病生存.21例患者中位随访24(1~68)个月,复发、死亡4例(19%),其余17例均无病生存,2年无病生存(EFS)和总生存(OS)率均为81.0%.未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响.结论 APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关,作为巩固治疗,能使移植前达CR的患者获得长期生存,提高治愈率;作为强化治疗,可提高缓解率,延长PR患者的EFS及OS.利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建.%Objective To evaluate the efficacy of anti-CD20 monoclonal antibody (Rituximab) combined with autologous hematopoietic stem cell transplant (ASCT) in treatment of the patients with B cell non-Hodgkin lymphoma (NHL). Methods Twenty-one patients with B-cell NHL(CD20 positive) received ASCT with Rituximab at the dose of 385 mg·m-2·d-1 on day 1 and day 8 of mobilization,and day -1 and day +7 of conditioning regimen. Among the 21 patients receiving chemotherapy before the transplant, five cases achieved complete response (CR), eleven cases achieved partial remission (PR), and 5 cases had the progression of disease (PD) after many cycles of chemotherapy. Results The median follow-up was 24 months (1-68 months) in the present study. No relapse occurred among the 5 patients in CR before the

  2. High-Dose Phenobarbital for Ohtahara Syndrome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-05-01

    Full Text Available Oral high-dose phenobarbital therapy was effective in the control of tonic spasms in a 1 month-old-infant with early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome treated at Tokyo Metropolitan Hachioji Children’s Hospital, Tokyo, Japan.

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

    Science.gov (United States)

    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.

  4. High-dose neutron detector project update

    Energy Technology Data Exchange (ETDEWEB)

    Menlove, Howard Olsen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Henzlova, Daniela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    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 increase 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.

  5. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

    Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

    2014-01-01

    BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

  6. High-dose neutron detector project update

    Energy Technology Data Exchange (ETDEWEB)

    Menlove, Howard Olsen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Henzlova, Daniela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    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.

  7. High dose insulin in toxic cardiogenic shock.

    Science.gov (United States)

    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.

  8. Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

    NARCIS (Netherlands)

    Ekhart, G.C. (Corine)

    2008-01-01

    High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation has been developed as a possible curative treatment modality in several solid tumours. A frequently used high-dose regimen in the Netherlands is the CTC regimen, which is a 4-day course of cyclophosphamide, t

  9. Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chia-Yen; Chen, Gregory J.; Tai, Pei-Han; Yang, Yu-Chen [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China); Hsu, Yu-Shen, E-mail: yshsu@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Chang, Mingi, E-mail: mingi.chang@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Hsu, Chuan-Lung, E-mail: fabio@dcb.org.tw [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China)

    2016-05-13

    Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic application in immunotherapy. One of the major strategies of the bsAb platform is the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the other end with affinity for CD19, has been approved in the US and Europe for the treatment of acute lymphoblastic leukemia. However, due to their small size and lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short half-lives in vivo. Additionally, poor solubility, structural instability, and low production yields have also become major challenges in the bulk production process. To overcome these challenges, we have engineered a tetravalent bsAb with bivalent binding specificity for the CD20 and CD3 antigen in an immunoglobulin G (IgG) format. The fusion of the anti-CD3 scFvs to the CD20 antibody via a linker-hinge domain (LHD) results in improved antibody stabilization and properties. Here we demonstrate this antibody's highly efficient cancer cell elimination in a dose-dependent manner in a CD20-expressing B lymphoblastoid cell line in vitro. Our data suggest the potential clinical application of this bsAb for the treatment of CD20-expressing B cell malignancies. - Highlights: • A bispecific antibody (bsAb) can increase immunotherapeutic efficacy. • A tetravalent bsAb with binding specificity for the CD20 and CD3 antigens is proposed. • A linker-hinge domain (LHD) within the bsAb results in improved antibody properties.

  10. Two courses of rituximab (anti-CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.

    2008-01-01

    Background Pemphigus vulgaris (PV) is a severe autoimmune blistering disease involving the skin and mucous membranes. The response to therapy varies greatly amongst patients and treatment may be challenging. Rituximab is a chimeric monoclonal antibody that selectively targets cell surface antigen...

  11. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J;

    2005-01-01

    with a dose regimen of 375 mg/m2 i.v. approximately once weekly for 4 consecutive weeks. Six patients received a fixed dose of 500 mg disregarding their weight supplemented by 100 mg of methylprednisone i.v. or 50-100 mg of Pred given as premedication together with an antihistamine just before infusion...

  12. The anti-CD20 antibody rituximab reduces the Th17 cell response

    NARCIS (Netherlands)

    Veerdonk, F.L. van de; Lauwerys, B.; Marijnissen, R.J.; Timmermans, K.; Padova, F.E. Di; Koenders, M.M.J.F.; Gutierrez-Roelens, I.; Durez, P.; Netea, M.G.; Meer, J.W. van der; Berg, W.B. van den; Joosten, L.A.B.

    2011-01-01

    OBJECTIVE: Rituximab has been shown to be successful in the treatment of rheumatoid arthritis (RA), and this unexpected finding indicates that B cells have an important role in this disease. The present study was undertaken to investigate the mechanism of action of rituximab in RA. METHODS: Twelve p

  13. Dosimetric evaluation of anti-CD20 labelled with {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, Graciela; Osso Junior, Joao A., E-mail: gracielabarrio@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. B-cell lymphoma is a particularly good candidate for radioimmunotherapy because the disease is inherently radiosensitive, malignant cells in the blood, bone marrow, spleen and lymphonodes are accessible, and MAbs have been developed to B-cell surface antigens that do not shed or modulate. Rituximab (RTX), the human IgG1-type chimeric form of the parent murine antibody ibritumomab, is specifically targeted against CD20, a surface antigen expressed by pre-B and mature human B lymphocytes. The use of rhenium-188 from a {sup 188}W/{sup 188}Re generator system represents an attractive alternative radionuclide for therapy. {sup 188}Re is produced from beta decay of the {sup 188}W parent. In addition to the emission of high-energy electrons (E{beta}= 2118 keV), {sup 188}Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of {sup 188}Re, the emission of gamma photon is an added advantage since the biodistribution of {sup 188}Re-labeled antibodies can be evaluated in vivo with a gamma camera. Also, rhenium has chemical properties similar to technetium. Thus, both can be conjugated to antibodies using similar chemistry methods. The objective of this work is to prove the usefulness of this radiopharmaceutical based on dosimetric studies, that are also required by the Brazilian Regulatory Agency (ANVISA). (author)

  14. Effective treatment of refractory pulmonary hemorrhage with monoclonal anti-CD20 antibody (rituximab).

    Science.gov (United States)

    Pinto, Luis Fernando; Candia, Liliana; Garcia, Patricia; Marín, Juan Ignacio; Pachón, Ines; Espinoza, Luis R; Marquez, Javier

    2009-01-01

    We report a 19-year-old female with systemic lupus erythematosus and lupus nephritis who developed pulmonary hemorrhage (PH) refractory to conventional immunosuppressive treatment. She was initially treated with intravenous methylprednisolone and cyclophosphamide pulses. She required mechanical ventilation due to a lack of responsiveness and her disease was considered refractory to conventional treatment. Rituximab was administered and this was followed by clinical improvement in both PH and nephritis. Rituximab may be a useful therapeutic option for the treatment of refractory PH.

  15. Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhijie [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-03-31

    The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

  16. High-Dose Vitamin D May Not Curb Kids' Colds

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_167275.html High-Dose Vitamin D May Not Curb Kids' Colds Study seems ... 18, 2017 (HealthDay News) -- When it comes to vitamin supplements, more is not always better, according to ...

  17. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  18. High-dose dosimetry using natural silicate minerals

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

    2015-07-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  19. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    Hoogendijk, JE; Wokke, JHJ; de Visser, M

    2000-01-01

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Sis patients responded. Side effects w

  20. Relevance of high-dose chemotherapy in solid tumours

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

    2005-01-01

    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

  1. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth Carl)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  2. High dose corticosteroids in severe leptospirosis: a systematic review.

    Science.gov (United States)

    Rodrigo, Chaturaka; Lakshitha de Silva, Nipun; Goonaratne, Ravindi; Samarasekara, Keshinie; Wijesinghe, Indika; Parththipan, B; Rajapakse, Senaka

    2014-12-01

    The role of corticosteroids in the treatment of severe leptospirosis is unclear. The rationale for their use is that, in severe leptospirosis, there is a severe immunological response that is harmful to the host resulting in multi-organ dysfunction, which is potentially offset by the nonspecific immunosuppression of high dose steroids. We conducted a systematic review of studies that have assessed the use of high dose corticosteroids in patients with severe leptospirosis by searching MEDLINE and Scopus SciVerse without any language or time restrictions. We identified five studies, including one open randomized clinical trial, which had assessed the use of high dose steroids in severe leptospirosis. Four studies demonstrated a benefit of corticosteroids in treating severe disease with pulmonary involvement when administered early in the course of the disease, but these studies had several methodological constraints as highlighted in the text. Only the randomized controlled trial study showed that corticosteroids are ineffective and may increase the risk of nosocomial infections. There is no robust evidence to suggest that high dose corticosteroids are effective in severe leptospirosis, and a well-designed randomized clinical trial is needed to resolve this.

  3. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth Carl)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  4. High-dose secondary calibration laboratory accreditation program

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, J.C. [National Institute of Standards and Technology, Gaithersburg, MD (United States)

    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.

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

    Science.gov (United States)

    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 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.

  6. Impairment of memorization by high doses of pyridoxine in man.

    Science.gov (United States)

    Molimard, R; Marillaud, A; Paille, A; Le Devehat, C; Lemoine, A; Dougny, M

    1980-05-01

    Two controlled trials were performed successively to evaluate the effect of high doses of oral pyridoxine on brain performance in man. In trial I, medical students volunteered to take 100 mg, 500 mg of pyridoxine a day or placebo for 10 days. A digit coding test was performed before, and at the end of the treatment period and a third 15 days later. The improvement of performance from the first to the third test (learning effect) was significantly better in the placebo group than in the B6 treated groups. This could be attributed to memorization of skills. Trial II was performed in obese patients starting a low calorie diet in whom vitamins are routinely prescribed. Performance in a work recognition test and in a visual retention test was lower for the group receiving 1 g of pyridoxine a day. Thus, high doses of oral pyridoxine are likely to impair memorization in man. Disturbances of neuro-transmitter metabolism such as increase of GABA production might explain the effect. As the benefit of high doses of pyridoxine has not been well-documented and as the study has suggested that undesired effects may indeed exist, the widespread use of such doses is questionable.

  7. Krait bite requiring high dose antivenom: a case report.

    Science.gov (United States)

    Sharma, Sanjib Kumar; Koirala, Shekhar; Dahal, Gaheraj

    2002-03-01

    Anti snake venom (ASV) is the most specific therapy available for treatment of snakebite envenomation. The ASV available in Nepal are polyvalent ASV produced in India and are effective against envenomation by cobra and krait, the two most common species found in Eastern Nepal. Neurotoxic signs respond slowly and unconvincingly and continuous absorption of venom may cause recurrent neurotoxicity. Therefore, close observation and continuous administration of ASV is essential to save the victim. We report a case of neurotoxic envenomation due to bite by common krait (Bangarus caeruleus). The victim required very high dose of polyvalent ASV for reversal of neurological manifestations.

  8. Physical characteristics of the Selectron high dose rate intracavitary afterloader

    Energy Technology Data Exchange (ETDEWEB)

    Chenery, S.G.A.; Pla, M.; Podgorsak, E.B. (Royal Victoria Hospital, Montreal, Quebec (Canada); McGill Univ., Montreal, Quebec (Canada))

    1985-08-01

    The physics measurements on a Selectron high dose-rate afterloading cobalt-60 unit are reported. The installation was found to be acceptable from the standpoint of radiation safety and cost effectiveness; hospital bed space was saved as treatment could be on an outpatient basis. A source calibration 4% higher than the value stated by the manufacturer was obtained. Measurement of the ratio of exposure rate in water to that in air confirmed the calibration and the applicability of correction factors for routine clinical dosimetry recommended in the literature.

  9. High dose intravenous immunoglobulin may be complicated by myocardial infarction

    Directory of Open Access Journals (Sweden)

    Kolar Vishwanath Vinod

    2014-01-01

    Full Text Available Intravenous immunoglobulin [IVIg] is useful for treating several clinical conditions and is largely considered safe, without major adverse events. Here we report a case of acute ST elevation myocardial infarction associated with high dose IVIg administration in a previously healthy 69-year-old male patient of Guillain Barre syndrome. The case is being reported to emphasize the need for treating physicians to be aware of thrombotic complications associated with IVIg. The thrombotic complications associated with IVIg are reviewed in brief , and the measures to reduce them are discussed.

  10. Spectroscopic gamma camera for use in high dose environments

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. Spectroscopic gamma camera for use in high dose environments

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Yuichiro, E-mail: yuichiro.ueno.bv@hitachi.com [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Fujishima, Yasutake; Kometani, Yutaka [Hitachi Works, Hitachi-GE Nuclear Energy, Ltd., Hitachi-shi, Ibaraki-ken (Japan); Suzuki, Yasuhiko [Measuring Systems Engineering Dept., Hitachi Aloka Medical, Ltd., Ome-shi, Tokyo (Japan); Umegaki, Kikuo [Faculty of Engineering, Hokkaido University, Sapporo-shi, Hokkaido (Japan)

    2016-06-21

    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.

  13. The influence of high doses of radiation in citrine stones

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, M. I. [Universidade Nove de Julho - UNINOVE, Rua Vergueiro 235/249, 01504-001 Sao Paulo (Brazil); Caldas, L. V. E., E-mail: miteixeira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ({sup 60}Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO{sub 2}), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  14. Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

    Directory of Open Access Journals (Sweden)

    Aline Correa de Carvalho

    2013-01-01

    Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

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

    Energy Technology Data Exchange (ETDEWEB)

    Maghraby, A., E-mail: maghrabism@yahoo.com [National Institute of Standards (NIS) - Radiation Dosimetry Department - Tersa st. 12211 Giza, P.O. Box 136 (Egypt); Salama, E. [Physics Department, Faculty of Science, Ain Shams University, 11566 Cairo (Egypt); Mansour, A. [National Center for Radiation Research and Technology, Atomic Energy Authority, Nasr City, Cairo (Egypt)

    2011-12-11

    An EPR investigation of radiation induced radicals in Homotaurine revealed that there are two types of radicals produced after exposure to gamma radiation ({sup 60}Co). 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    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...

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

    Science.gov (United States)

    ... 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 ...

  1. Impact of high dose vitamin C on platelet function

    Science.gov (United States)

    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 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). Collagen and ADP-induced ATP secretion was also not different between the three groups (P > 0.05). Finally, VitC at the higher dose (3 mmol/L) also induced the release of several eicosanoids including thromboxane B2

  2. High-dose irradiation of food; Hochdosisbestrahlung von Lebensmitteln

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, J.F.

    1999-07-01

    Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [German] Die im Rahmen des Projekts erteilten Auftraege betrafen nur solche Lebensmittel, die im Dosisbereich < 10 kGy bestrahlt waren, da der Bereich hoeherer Dosen durch die amerikanischen Untersuchungen abgedeckt war. Als das Joint FAO/IAEA/WHO Expert Committee on Food Irradiation (JECFI) 1980 in Genf tagte, um ueber die gesundheitliche Bewertung bestrahlter Lebensmittel zu beraten, waren jedoch die in den Vereinigten Staaten laufenden, sehr umfangreichen Langzeitversuche mit strahlensterilisiertem Haehnchenfleisch (Dosis 58 kGy) noch nicht abgeschlossen. Das Komitee beschraenkte sich daher auf die Bewertung der vom Internationalen Projekt vorgelegten Ergebnisse. Die Schlussfolgerung 'the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required'beendete die jahrzehntelange Debatte ueber die gesundheitliche Unbedenklichkeit von im niedrigen (bis 1 kGy) und mittleren (1 bis 10 k

  3. The study of conjugation of anti-CD20 monoclonal antibody for labeling with metallic or lanthanides radionuclides; Estudo de conjugacao do anticorpo anti-CD20 para marcacao com radionuclideos metalicos ou lantanideos

    Energy Technology Data Exchange (ETDEWEB)

    Akanji, Akinkunmi Ganiyu

    2012-07-01

    Lymphomas are malignancies or cancers that start from the malign transformation of a lymphocyte in the lymphatic system. Generally, lymphomas start from the lymph nodes or from the agglomeration of the lymphatic tissues, organs like stomach, intestines, in some cases it can involve the bone marrow and the blood, it can also disseminate to other organs. Lymphomas are divided in two major categories: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Patient with NHL are generally treated with radiotherapy alone or combined with immunotherapy using monoclonal antibody rituximab (MabThera Registered-Sign ). Currently, monoclonal antibodies (Acm) conjugated with bifunctional chelate agents and radiolabeled with metallic or lanthanides radionuclides are a treatment reality for patients with NHL by the principle of radioimmunotherapy (RIT). This study focused on the conditions of conjugation of Acm rituximab (MabThera Registered-Sign ) with bifunctional chelating agents DOTA and DTPA. Various parameters were studied: method of Acm purification, conditions of Acm conjugation, the method for determination of number of chelate agent coupled to the Acm, method for purification of the conjugated antibody Acm, conditions of labeling of the conjugated antibody with lutetium-177, method of purification of the radiolabeled immuno conjugate, method of radiochemical purity (RP), specific binding in vitro Raji cells (Human Burkitt) and biological distribution performed in normal Balb-c mouse. The three methodologies employed in pre-purification of Acm (dialysis, size exclusion chromatograph and dial filtration) demonstrated to be efficient; they provided sample recovery exceeding 90%. However, the methodology of dial filtration presents minimal sample loss, and gave the final recovery of the sample in micro liters; thereby facilitating sample use in subsequent experiments. Numbers of chelators attached to the Acm molecule was proportional to the molar ratio studied. When we evaluated the influence of different conditions of conjugation in the number of chelators bounded to the Acm, no notable differences were observed. The RP < 80% was observed in all the methods applied. Purification of the conjugated antibody by dialysis and size exclusion chromatography demonstrated to be efficient, but deficient in terms of high sample volume recovered. The dial filtration was efficient and practical besides it provided sample recovery in micro liters. The optimized conditions for purification of the conjugated antibody preserved the protein integrity. When the conjugated Acm was labeled with lutetium-177 a product with low RP was observed in all molar ratios studied. The methodology used in the control of RP of the radiolabeled antibody was efficient in the discrimination of radiochemical species presented in the reaction mixture. The method of purification of the conjugated antibody applied, proved to be efficient in separating the labeled antibody from free lutetium. The results of specific cell binding studies performed with the conjugated Acm showed high percentage of nonspecific binding. Biological distribution in normal Balb-c mice demonstrated higher uptake of the labeled antibody by kidney and liver. The relatively high uptake observed by bone tissue may indicate some in vivo instability. However, results obtained in this study showed to be close related in literature. Thus, these data confirm the potential of antibody conjugated to DOTA and DTPA labeled with lutetium-177 for radioimmunotherapy of non-Hodgkin lymphoma. (author)

  4. Remote Afterloading High Dose Rate Brachytherapy AMC EXPERIANCES

    Energy Technology Data Exchange (ETDEWEB)

    Park, Su Gyong; Chang, Hye Sook; Choi, Eun Kyong; Yi, Byong Yong [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1992-12-15

    Remote afterloading high dose rate brachytherapy(HDRB) is a new technology and needs new biological principle for time and dose schedule. Here, authors attempt to evaluate the technique and clinical outcome in 116 patients, 590 procedures performed at Asan Medical Center for 3 years. From Sep. 1985 to Aug 1992, 471 procedures of intracavitary radiation in 55 patients of cervical cancer and 26 of nasopharyngeal cancer, 79 intraluminal radiation in 12 of esophageal cancer, 11 of endobronchial cancer and 1 Klatskin tumor and 40 interstitial brachytherapy in 4 of breast cancer, 1 sarcoma and 1 urethral cancer were performed. Median follow-up was 7 months with range 1-31 months. All procedures except interstitial were performed under the local anesthesia and they were all well tolerated and completed the planned therapy except 6 patients. 53/58 patients with cervical cancer and 22/26 patients with nasopharynx cancer achieved CR. Among 15 patients with palliative therapy, 80% achieves palliation. We will describe the details of the technique and results in the text. To evaluate biologic effects of HDRB and optimal time/dose/fractionation schedule, we need longer follow-up. But authors feel that HDRB with proper fractionation schedule may yield superior results compared to the low dose rate brachytherapy considering the advantages of HDRB in safety factor for operator, better control of radiation dose and volume and patients comfort over the low dose brachytherapy.

  5. Shelf-stable food through high dose irradiation

    Science.gov (United States)

    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.

  6. Shelf-stable food through high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Placek, V. E-mail: pla@ujv.cz; Svobodova, V.; Bartonicek, B.; Rosmus, J.; Camra, M

    2004-10-01

    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 deg. 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 deg. 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 Rez 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO{sub x}-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

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

    Science.gov (United States)

    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.

  8. Radiation Parameters of High Dose Rate Iridium -192 Sources

    Science.gov (United States)

    Podgorsak, Matthew B.

    A lack of physical data for high dose rate (HDR) Ir-192 sources has necessitated the use of basic radiation parameters measured with low dose rate (LDR) Ir-192 seeds and ribbons in HDR dosimetry calculations. A rigorous examination of the radiation parameters of several HDR Ir-192 sources has shown that this extension of physical data from LDR to HDR Ir-192 may be inaccurate. Uncertainty in any of the basic radiation parameters used in dosimetry calculations compromises the accuracy of the calculated dose distribution and the subsequent dose delivery. Dose errors of up to 0.3%, 6%, and 2% can result from the use of currently accepted values for the half-life, exposure rate constant, and dose buildup effect, respectively. Since an accuracy of 5% in the delivered dose is essential to prevent severe complications or tumor regrowth, the use of basic physical constants with uncertainties approaching 6% is unacceptable. A systematic evaluation of the pertinent radiation parameters contributes to a reduction in the overall uncertainty in HDR Ir-192 dose delivery. Moreover, the results of the studies described in this thesis contribute significantly to the establishment of standardized numerical values to be used in HDR Ir-192 dosimetry calculations.

  9. Image-guided high dose rate endorectal brachytherapy.

    Science.gov (United States)

    Devic, Slobodan; Vuong, Té; Moftah, Belal; Evans, Michael; Podgorsak, Ervin B; Poon, Emily; Verhaegen, Frank

    2007-11-01

    Fractionated high dose rate endorectal brachytherapy (HDR-EBT) using CT-based treatment planning is an alternative method for preoperative down-sizing and down-staging of advanced rectal adeno-carcinomas. The authors present an image guidance procedure that was developed to ensure daily dose reproducibility for the four brachytherapy treatment fractions. Since the applicator might not be placed before each treatment fraction inside the rectal lumen in the same manner as it was placed during the 3D CT volume acquisition used for treatment planning, there is a shift along the catheter axis that may have to be performed. The required shift is determined by comparison of a daily radiograph with the treatment planning digitally-reconstructed radiograph (DRR). A procedure is developed for DRR reconstruction from the 3D data set used for the treatment planning, and two possible daily longitudinal shifts are illustrated: above and below the planning dose distribution. The authors also describe the procedure for rotational alignment illustrated on a clinical case. Reproduction of the treatment planned dose distribution on a daily basis is crucial for the success of fractionated 3D based brachytherapy treatments. Due to the cylindrical symmetry of the applicator used for preoperative HDR-EBT, two types of adjustments are necessary: applicator rotation and dwell position shift along the applicator's longitudinal axis. The impact of the longitudinal applicator shift prior to treatment delivery for 62 patients treated in our institution is also assessed.

  10. Very high dose phenobarbital for refractory status epilepticus.

    Science.gov (United States)

    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.

  11. High doses of recombinant erythropoietin stimulate platelet production in mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.; Cottrell, M.B.; Clift, R.E.; Cullen, W.C.; Lin, F.K.

    1987-07-01

    Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thrombocytosis were injected with rEpo and the %35S incorporation into platelets was measured. A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) was used as a positive control. rEpo increased isotopic incorporation into platelets of both normal mice and mice in rebound-thrombocytosis, as did TSF, but required large doses (15 U rEpo/mouse). In other mice, hematocrits, platelet counts, platelet sizes, and 24-hr %35S incorporation into platelets were measured 2 days after injection of two equally divided doses of either rEpo or TSF. Significant increases in both platelet sizes and %35S incorporation into platelets were found after injections of 15 U rEpo/mouse or 2.3 U TSF/mouse. These data indicate that rEpo, at high doses, will stimulate platelet production in mice, and may suggest molecular similarities between rEpo and TSF and their ability to compete for common receptor sites on megakaryocytes and their progenitor cells.

  12. Characterization of a silicate glass as a high dose dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Farah, K., E-mail: k.farah@cnstn.rnrt.t [Laboratoire de Radiotraitement. Centre National des Sciences et Technologie Nucleaires, 2020 Sidi-Thabet (Tunisia); Mejri, A.; Hosni, F. [Laboratoire de Radiotraitement. Centre National des Sciences et Technologie Nucleaires, 2020 Sidi-Thabet (Tunisia); Ben Ouada, H. [Laboratoire de Physique et Chimie des Interfaces, Faculte des Sciences de Monastir, 5000 Monastir (Tunisia); Fuochi, P.G.; Lavalle, M. [ISOF-CNR, Via P. Gobetti 101, 40129 Bologna (Italy); Kovacs, A. [Institute of Isotopes, HAS, P.O. Box 77, H-1525 Budapest (Hungary)

    2010-02-21

    Commercial silicate glass has been investigated as a possible high dose dosimeter using an UV-vis spectrophotometer. Glass samples were irradiated by {sup 60}Co gamma rays and the results compared with those obtained with 3.4 and 8.4 MeV electron beams. The irradiated samples showed rapid fading at room temperature immediately after irradiation. In order to improve the stability of absorbance, glass samples were submitted to post-irradiation thermal treatments (150 deg. C for 20 min). The influences of the dose, type and energy of the ionizing radiation on the fading characteristics and on the response of the irradiated and thermally treated glasses were studied. Dependence of the glass response on the temperature during gamma irradiation in the range -3 to 80 deg. C is reported. The reproducibility to reuse glass dosimeter by thermal bleaching the radiation induced colour centres at 300 deg. C for 30 min was also investigated. Calibration curves in the range 0.1-17 kGy were obtained by using in-plant calibration techniques against transfer standard alanine dosimeters in the Tunisian semi-industrial gamma irradiation facility.

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

    Energy Technology Data Exchange (ETDEWEB)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Jae-Hun [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kang, Sang-Wook; Choi, Gi-Hyuk [Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    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 {sup o}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.

  14. High-dose pyridoxine as an 'anti-stress' strategy.

    Science.gov (United States)

    McCarty, M F

    2000-05-01

    Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival.

  15. Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

    Science.gov (United States)

    Wagner, Henry N; Wiseman, Gregory A; Marcus, Carol S; Nabi, Hani A; Nagle, Conrad E; Fink-Bennett, Darlene M; Lamonica, Dominick M; Conti, Peter S

    2002-02-01

    90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for handling body fluids are recommended for health care workers and patients and their family members after (90)Y-ibritumomab tiuxetan administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into clinical practice and expands the role nuclear medicine plays in the care of patients with cancer. Understanding the unique properties of this novel radioimmunoconjugate will facilitate its safe and effective use.

  16. Unexpected and persistent depletion of B lymphocytes CD20 following a minimum dose of anti-CD20 antibody (Rituximab

    Directory of Open Access Journals (Sweden)

    V. Bruzzese

    2011-06-01

    Full Text Available Rituximab is a chemeric murine/human anti-B lymphocyte antigen CD20 monoclonal antibody used in the treatment of rheumatoid arthritis resistant to treatment by one or more anti TNF-alpha therapies (1. The recommended dose for an efficient depletion of the B CD 20 lymphocytes in rheumatoid arthritis is two infusions of 1000 mg, with the second infusion being administered two weeks after the first. At this dose, one obtains a rapid and persistent depletion of CD 20 cells, with repopulation occurring, on the average, in about eight months (2. Here, we present a case of a woman treated with only 50 mg of rituximab, who underwent both a rapid and pronounced reduction of B CD 20 lymphocytes...

  17. "Time sequential high dose of Cytarabine in acute myelocytic leukemia "

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    2003-05-01

    Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Susan C Irvin

    Full Text Available 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. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk.

    Science.gov (United States)

    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.

  1. High doses of vitamin A impair iron absorption

    Directory of Open Access Journals (Sweden)

    Gabriel FR

    2012-10-01

    Full Text Available Fabíola Rainato Gabriel, Vivian MM Suen, Julio Sergio Marchini, José Eduardo Dutra de OliveiraDivision of Clinical Nutrition, Department of Internal Medicine, Ribeirão Preto School of Medicine, São Paulo University, São Paulo, BrazilObjective: The present study aimed to determine the influence of vitamin A on iron absorption when vitamin A and iron are administered together orally compared with the administration of iron alone.Methods: This was a randomized double-blind clinical trial conducted on healthy men with normal red blood cell indices. Five experiments were performed, with iron (10 mg; iron (10 mg plus vitamin A (450, 900 and 1800 µg, and placebo. After an 8-hour fast, basal (T0 blood samples were collected: basal (T0, 2 hours (T1, and 4 hours (T2 after the ingestion of the compounds to be studied. Iron was determined by inductively coupled plasma mass spectrometry. Serum ferritin was determined by an immunometric method, ie, by chemoluminescent enzyme immunoassay. Plasma retinol was measured by high-pressure liquid chromatography. Serum curves and the sum of the area under the curve adjusted to the mixed effects linear model were determined (P < 0.05.Results: Vitamin A at the doses of 450 and 900 µg had a stimulating effect, which, however, did not differ significantly from that of experiment 1 in which iron was used alone. At the dose of 1800 µg, vitamin A had a negative effect on iron absorption.Conclusion: High doses of vitamin A may cause lower serum iron levels, whereas a low dose favors iron absorption.Keywords: iron absorption, serum iron, vitamin A, oral iron, oral supplement

  2. Malignancies in patients treated with high doses of radium-224

    Energy Technology Data Exchange (ETDEWEB)

    Nekolla, E.A. [Federal Office for Radiation Protection (BfS), Neuherberg (Germany); Walsh, L. [Radiobiological Inst., Univ. of Munich (Germany); Schottenhammer, G.; Spiess, H. [Children' s Hospital, Univ. of Munich (Germany)

    2005-07-01

    Several thousand German patients suffering from ankylosing spondylitis, tuberculosis and some other diseases, received multiple injections of the short-lived {alpha}-emitter {sup 224}Ra. The ''Spiess study'' was initiated in the early 1950s to follow the health of 899 persons (278 female, 621 male) who were treated mainly between 1945 and 1955. Most of the high dose patients and nearly all of those treated as children or juveniles (n=217) were included in the study. In June 2003, 152 persons were still alive. The most striking observed health effect, following {sup 224}Ra injections, was a temporal wave of 56 malignant bone tumours with a maximum at about 8 years after exposure which has already been described in several publications. In 2000, a new analysis was performed because an improved dosimetry resulted in modified bone surface doses. The estimated risk coefficient, averaged over all ages at exposure, was found to be in agreement with earlier analyses. However, a statistically significant increase of bone tumour risk with decreasing age at exposure was found. The earlier results, which indicated a reversed protraction factor, were confirmed. A significant excess of non-skeletal solid malignancies has also appeared during the most recent observation decade. In 2004, significant increases of cancer rates were observed for several sites: for breast cancer (31 cases observed vs. 9.1 cases expected), soft tissue malignancies (11 vs. 1.0), thyroid carcinomas (7 vs. 0.9), liver (8 vs. 2.3), kidney (13 vs. 4.6), pancreas (8 vs. 3.9), and bladder cancer (14 vs. 7.7). The 8-fold excess relative risk of mammary cancers in those women exposed as children or juveniles is particularly striking; moreover, 2 cases of breast cancer occurred in men. In 1993, a control group of tuberculosis patients not treated with {sup 224}Ra was established to rule out potential confounding factors - such as chest fluoroscopy - which might bias the breast cancer excess

  3. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients

    DEFF Research Database (Denmark)

    Nielsen, Torben Kjær; Højgaard, Martin; Andersen, Jon Thor Trærup

    2015-01-01

    Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high dose...

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

    Science.gov (United States)

    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 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.

  5. Amphotericin B for cryptococcal meningitis in HIV positive patients: Low dose versus high dose

    Directory of Open Access Journals (Sweden)

    Rajeshwari S

    2007-01-01

    Full Text Available Aim: To compare the safety and efficacy of low dose vs high dose of amphotericin B in cryptococcal meningitis associated with HIV infection. Materials and Methods: Retrospective data of patients admitted with clinical diagnosis with or without microbiological evidence of cryptococcal meningitis was collected from Jan 2000-Mar 2006. Patients′ details were collected in a proforma which included patient′s age, weight, signs and symptoms of disease and microbiological report (blood and CSF analysis. Data also included coexisting disease; concomitant medications taken along with amphotericin B. Adverse drug reactions which occurred during the period of treatment were recorded. Patients were grouped as low dose group and high dose group depending on the dose of amphotericin B given for the treatment of cryptococcal meningitis. Patients who received amphotericin B at doses of 0.33 to 0.64 mg/kg body weight per day were categorized under low dose group and patients who received amphotericin B at doses of 0.7 to 1.1 mg/kg/day were categorized under high dose group. All data were pooled and analyzed between the groups using chi square test. Result: Total number of patients included in the study were 38, 26 in the low dose group and 12 in the high dose group. In the low dose group, 20 were males and six were females, in the high dose group eight were males and four were females. The commonest underlying diseases were tuberculosis (17 in low dose group, nine in high dose group, Pneumocystis carinii (jeroveci pneumonia (16 in low dose group, seven in high dose group and oral candidiasis (eight in low dose group, seven in high dose group, Toxoplasmosis (three in low dose group, one in high dose group, hypertension (1 in group A and diabetes mellitus (1 in group B. Concomitant medication received along with amphotericin B for coexisting diseases in both the groups were antitubercular therapy, cotrimoxazole, antiviral therapy and premedications such as

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

    Directory of Open Access Journals (Sweden)

    Stefano Tamburin

    2017-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 (agedphenobarbital (>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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. A case of percutaneous high dose rate brachytherapy for superior pulmonary sulcus tumor

    Energy Technology Data Exchange (ETDEWEB)

    Asakura, Tamaki; Imamura, Masahiro; Murata, Takashi [Kansai Medical Univ., Moriguchi, Osaka (Japan)] [and others

    1996-07-01

    A 64-year-old man with advanced superior pulmonary sulcus tumor suffered severe unrelieved pain even after chemotherapy, external irradiation and hyperthermia. So we planned to introduce a percutaneous high dose rate brachytherapy using the microselectron HDR {sup 192}Ir. With the estimation using the Pain Score, satisfying pain relief was attainable with a combination of the percutaneous high dose rate brachytherapy and conventional treatment. So the percutaneous high dose rate brachytherapy had the possibility to contribute to the alleviation of the pain. (author)

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

    Science.gov (United States)

    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.

  13. Characterisation of high dose dry powder aerosols by cascade impaction and laser diffraction analysis

    NARCIS (Netherlands)

    Grasmeijer, F.; Hagedoorn, P.; Frijlink, H.W.; De Boer, A.H.

    2011-01-01

    Background: Developments in high dose dry powder inhalationcontinue to challenge the viability of pharmacopoeialmethods for drug aerosol characterisation. Especiallythe occurrence of bounce effects can cause the amount offines (<1 lm) to be highly overestimated in particle sizedistributions (PSDs) o

  14. High-dose dosimetry of beta rays using blue beryl dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do, E-mail: lsatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Bittencour, Jose F., E-mail: Lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear

    2015-07-01

    High dose radiation is widely used in industrial applications as sterilization of medical products, improvement of materials properties, color enhancement of jewelry stones, etc. The radiation dosimetry of high doses is quite important for these applications. In this work we have investigated the usage of blue beryl crystal also known as aquamarine in high dose dosimetry of beta rays. Some works have shown that silicate minerals exhibit a good Thermoluminescent response when irradiated up to 2000 kGy of gamma rays. Here, we have produced small beryl pellets of approximately 5 mm in diameter and 3 mm thickness to measure high doses of beta rays produced at an electron accelerator at IPEN. Twelve beryl dosimeters were made and six of them were irradiated from 10kGy up to 100 kGy. The technique used to create a calibration curve was the thermoluminescence using the glow peak at 310°C. (author)

  15. High-dose Sulbactam Treatment for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant

    Directory of Open Access Journals (Sweden)

    In Beom Jeong

    2016-11-01

    Full Text Available Background Several antibiotics can be used to treat ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii (CRAB-VAP including high-dose sulbactam. However, the effectiveness of high-dose sulbactam therapy is not well known. We report our experience with high-dose sulbactam for treatment of CRAB-VAP. Methods Medical records of patients with CRAB-VAP who were given high-dose sulbactam between May 2013 and June 2015 were reviewed. Results Fifty-eight patients with CRAB-VAP were treated with high-dose sulbactam. The mean age was 72.0 ± 15.2 years, and the acute physiology and chronic health evaluation II (APACHE II score was 15.1 ± 5.10 at the time of CRAB-VAP diagnosis. Early clinical improvement was observed in 65.5% of patients, and 30-day mortality was 29.3%. Early clinical failure (odds ratio [OR]: 8.720, confidence interval [CI]: 1.346-56.484; p = 0.023 and APACHE II score ≥ 14 at CRAB-VAP diagnosis (OR: 10.934, CI: 1.047-114.148; p = 0.046 were associated with 30-day mortality. Conclusions High-dose sulbactam therapy may be effective for the treatment of CRAB-VAP. However, early clinical failure was observed in 35% of patients and was associated with poor outcome.

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

    Science.gov (United States)

    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

  17. High-dose gadolinium-enhanced MRI for diagnosis of meningeal metastases

    Energy Technology Data Exchange (ETDEWEB)

    Kallmes, D.F. [Department of Radiology, Box 170, University of Virginia Health Sciences Center, Charlottesville, VA 22908 (United States); Gray, L. [Department of Radiology, Duke University Medical Center, Durham, NC (United States); Glass, J.P. [Department of Medicine, Veterans Administration Hospital, Gainesville, Florida (United States)

    1998-01-01

    We compared high-dose (0.3 mmol/kg) and standard-dose (0.1 mmol/kg) gadolinium-enhanced MRI for diagnosis of meningeal metastases in 12 patients with suspected meningeal metastases. They were imaged with both standard-dose and high-dose gadolinium. All patients with abnormal meningeal enhancement underwent at least one lumbar puncture for cerebrospinal fluid (CSF) cytology, while patients with normal meningeal enhancement were followed clinically. All patients with negative CSF cytology also were followed clinically. A single observer reviewed all the images, with specific attention to the enhancement pattern of the meninges. Abnormal leptomeningeal enhancement was present in three cases, and abnormal pachymeningeal enhancement in three other patients. All of these patients had abnormal CSF analyses. In two of the three cases of abnormal leptomeningeal enhancement the disease was more evident on high-dose than on standard-dose imaging; in one case the abnormal enhancement was visible only on high-dose imaging. In one of the three cases with abnormal pachymeningeal enhancement, the disease was evident prospectively only with high-dose imaging. (orig.) With 3 figs., 10 refs.

  18. Oxidative stress and innate immunity status in chickens exposed to high dose of ascorbic acid.

    Science.gov (United States)

    Berzina, Nadezhda; Markovs, Jurijs; Dizhbite, Tatiana; Apsite, Mirdza; Vasilyeva, Svetlana; Basova, Nataliya; Smirnova, Galina; Isajevs, Sergejs

    2013-10-01

    The effects of high dose ascorbic acid (10 000 mg·kg(-1) in the diet) and the transition metal on the presence of oxidative stress in the internal organs of growing chicks, as well as on the innate immune system status, were investigated. Supplementation with a high dose of ascorbic acid had pro-inflammatory effects on the intestinal mucosa, and lysozyme levels were decreased significantly in all organs studied. High-dose ascorbic acid caused an imbalance between prooxidative and antioxidative activities and was associated with the generation of semiquinone radicals. We observed that ascorbic acid increased iron and cadmium absorption. When a high dose of ascorbic acid was applied, elevated kidney and intestinal mucosa iron concentrations were observed. The amount of free malondialdehyde in the above organs has increased as well. These data have important implications for the mechanism of the oxidative stress development under the influence of high dose of ascorbic acid, indicating the importance of the side reactions of the mitochondrial electron transport chain with the formation of semiquinone radicals and the role of transition metals in this process.

  19. A Real World Report on Intravenous High-Dose and Non-High-Dose Proton-Pump Inhibitors Therapy in Patients with Endoscopically Treated High-Risk Peptic Ulcer Bleeding

    Directory of Open Access Journals (Sweden)

    Lung-Sheng Lu

    2012-01-01

    Full Text Available Background and Study Aims. The optimal dose of intravenous proton-pump inhibitor (PPI therapy for the prevention of peptic ulcer (PU rebleeding remains controversial. This study aimed to understand the real world experiences in prescribing high-dose PPI and non-high-dose PPI for preventing rebleeding after endoscopic treatment of high-risk PU. Patients and Methods. A total of 220 subjects who received high-dose and non-high-dose pantoprazole for confirmed acute PU bleeding that were successfully treated endoscopically were enrolled. They were divided into rebleeding (n=177 and non-rebleeding groups (n=43. Randomized matching of the treatment-control group was performed. Patients were randomly selected for non-high-dose and high-dose PPI groups (n=44 in each group. Results. Univariate analysis showed, significant variables related to rebleeding were female, higher creatinine levels, and higher Rockall scores (≧6. Before case-control matching, the high-dose PPI group had higher creatinine level, higher percentage of shock at presentation, and higher Rockall scores. After randomized treatment-control matching, no statistical differences were observed for rebleeding rates between the high-dose and non-high-dose groups after case-control matching. Conclusion. This study suggests that intravenous high-dose pantoprazole may not be superior to non-high-dose regimen in reducing rebleeding in high-risk peptic ulcer bleeding after successful endoscopic therapy.

  20. Infused vincristine and adriamycin with high dose methylprednisolone (VAMP) in advanced previously treated multiple myeloma patients.

    Science.gov (United States)

    Forgeson, G. V.; Selby, P.; Lakhani, S.; Zulian, G.; Viner, C.; Maitland, J.; McElwain, T. J.

    1988-01-01

    Forty-five patients with relapsed or refractory multiple myeloma received continuous infusions of vincristine (0.4 mg total dose daily for 4 days) and adriamycin (9 mg m-2 daily for 4 days) with a high dose of methylprednisolone (1 g m-2 i.v. or p.o. daily by 1 h infusion), the VAMP regimen. Sixteen (36%) responded, with a median duration of remission of 11 months and median survival of 20 months. Major toxicities encountered were infective and cardiovascular. Two smaller groups of myeloma patients were treated with high dose methylprednisolone (HDMP) alone, or VAMP plus weekly low dose cyclophosphamide (Cyclo-VAMP). HDMP produced short responses in 25% of patients with less toxicity than VAMP. Cyclo-VAMP was used in a highly selected group of patients who had previously responded to high dose melphalan. It was well tolerated and produced responses in 61% of this group. PMID:3207601

  1. HIGH DOSE FRACTION RADIOTHERAPY FOR MUCOSAL MALIGNANT MELANOMA OF THE HEAD AND NECK

    Institute of Scientific and Technical Information of China (English)

    Liu Xiuying; Li Huiling; Zheng Tianrong; Lin Xiangsong

    1998-01-01

    Objective:To evatuate the results of high dose fraction radiotherapy for mucosal malignant melanoma of the head and neck (HNMM). Methods: From 1984-1994, 35 patients with HNMM were enrolled in this study. Among them, 27 cases localized to the nasal cavity or para-nasal sinus, 8 to the oral cavity. All patients received high dose fraction radiotherapy (6--8 Gy/fraction)with the total dose ranged from 40 to 60 Gy. Results: The minimum follow-up was 2 years (ranged 2-7 years). The overall 3- and 5-year survival rate was 45.7% and 24%,respectively. Conclusion: High dose fraction radiotherapy is effective for local control of HNMM.

  2. High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Bangsbo, Jens

    2014-01-01

    PURPOSE: The purpose of the present study was to investigate the effect of high-dose inhaled terbutaline on muscle strength, maximal sprinting, and time-trial performance in trained men. METHODS: Nine non-asthmatic males with a [Formula: see text] of 58.9 ± 3.1 ml min(-1) kg(-1) (mean ± SEM......) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 × 0.5 mg) or placebo, subjects' maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test...... was not different between treatments (P = 0.236). CONCLUSION: High-dose inhaled terbutaline elicits a systemic response that enhances muscle strength and sprint performance. High-dose terbutaline should therefore continue to be restricted in competitive sport....

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  5. High dose brachytherapy in pediatric oncology; Braquiterapia com alta taxa de dose em oncologia pediatrica

    Energy Technology Data Exchange (ETDEWEB)

    Ferrigno, Robson; Codjaian, Osanna Esther; Novaes, Paulo Eduardo R.S.; Trippe, Nivaldo [Fundacao Antonio Prudente, Sao Paulo, SP (Brazil). Hospital A.C. Camargo. Dept. de Radioterapia

    1995-05-01

    Brachytherapy is a kind of radiotherapy that has been used in the multidisciplinary approach of some pediatric tumors, such as soft tissue sarcomas of the extremities, head and neck and urogenital tract. Recent technological advances in this area lead to development of computerized high dose rate remote afterloading brachytherapy. This type of treatment has some advantages compared to low dose rate brachytherapy traditionally used. This article describes not only the characteristics and advantages of this kind of treatment, but also the preliminary results of the first seven children treated with high dose rate at the Hospital A.C.Camargo. (author) 10 refs., 8 figs.

  6. Statistical behavior of high doses in medical radiodiagnosis; Comportamento estatistico das altas doses em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana Elisa, E-mail: adrianaebarboza@gmail.com, E-mail: elisa@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. Trichoderma species fungemia after high-dose chemotherapy and autologous stem cell transplantation: a case report.

    Science.gov (United States)

    Festuccia, M; Giaccone, L; Gay, F; Brunello, L; Maffini, E; Ferrando, F; Talamo, E; Boccadoro, M; Serra, R; Barbui, A; Bruno, B

    2014-08-01

    We present a case of Trichoderma fungemia with pulmonary involvement in a multiple myeloma patient, who was severely immunocompromised and heavily treated with high-dose melphalan, and underwent autologous hematopoietic cell transplantation. This is the first report, to our knowledge, of proven Trichoderma fungemia, defined by published criteria, successfully treated with voriconazole.

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

    Science.gov (United States)

    González-Azcorra, S. A.; Mota-García, A.; Poitevín-Chacón, M. A.; Santamaría-Torruco, B. J.; Rodríguez-Ponce, M.; Herrera-Martínez, F. P.; Gamboa de Buen, I.; Ruíz-Trejo, C.; Buenfil, A. E.

    2008-08-01

    In this prospective study, rectal dose was measured "in vivo" using TLD-100 crystals (3×3×1 mm3), 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 Cancerología (INCan).

  11. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Juergen;

    2016-01-01

    PURPOSE: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. METHODS AND MATERIALS: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immed...

  12. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    2012-01-01

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university hosp

  13. Daily high doses of fluoxetine for weight loss and improvement in lifestyle before bariatric surgery

    NARCIS (Netherlands)

    Dolfing, JG; Wolffenbuttel, BHR; Oei, HI; ten Hoor-Aukerna, NM; Schweitzer, DH

    2005-01-01

    Background: The number of gastric restrictive bariatric operations is increasing each year, but about one-fifth of patients will become disappointed due to unsatisfactory weight reduction or annoying complications. We questioned whether weight reduction by taking high doses of fluoxetine improves li

  14. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

    NARCIS (Netherlands)

    Borot, Maxence; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

    2015-01-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance.

  15. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

    DEFF Research Database (Denmark)

    Markvardsen, L H; Christiansen, Ingelise; Harbo, T

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

  16. Efficacy of Continuous High Dose Midazolam Infusion in Childhood Refractory Generalized Convulsive Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Afshin Fayyazi

    2011-06-01

    Full Text Available bjeciveProlonged and uncontrolled refractory status epilepticus (SE is a life-threatening medical emergency in children (1,2,3. There is no consensus on the optimal therapy for refractory status epilepticus (1. The aim of this study was to develop a new method for treating patients with refractory status epilepticus.Materials & MethodsTen children with refractory status epilepticus in Mofid Hospital, who did not respond to 10 μg/kg per min of intravenous midazolam, had their dose of midazolam increased to 30 μg/kg per min. All children were monitored for the development of side effects.ResultsTen children with no response to low-dose midazolam were given a higher dose of midazolam, and 5 (50% children had a good response. These patients had significantly different response to high-dose midazolam.One patient in the high-dose midazolam group was intubated and required mechanical ventilation. The duration of stay in the hospital and PICU and on mechanical ventilation in patients with no response to low-dose midazolam following with other drugs was longer than in the high-dose midazolam group.No death occurred in high dose midazolam group.ConclusionHigh-midazolam dose drip infusion is a safe and effective protocol for refractory status epilepticus in children.

  17. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Pennings, S.W.C.; Brouwer, K.M.; Mtaya-Mlangwa, M.; Mugonzibwa, E.; Kuijpers-Jagtman, A.M.; Wagener, F.A.D.T.G.; Hoff, J.W. Von den

    2015-01-01

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between

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

    Science.gov (United States)

    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 (p0.05). 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 (purticaria. 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

  19. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Pennings, S.W.C.; Brouwer, K.M.; Mtaya-Mlangwa, M.; Mugonzibwa, E.; Kuijpers-Jagtman, A.M.; Wagener, F.A.D.T.G.; Hoff, J.W. Von den

    2015-01-01

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between

  20. Maternal high-dose folic acid during pregnancy and asthma medication in the offspring

    NARCIS (Netherlands)

    Zetstra-van der Woude, Priscilla A.; De Walle, Hermien E. K.; Hoek, Annemieke; Bos, H. Jens; Boezen, H. Marike; Koppelman, Gerhard H.; de Jong-van den Berg, Lolkje T. W.; Scholtens, Salome

    2014-01-01

    Purpose Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to inve

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. Irreversible neurological worsening following high-dose corticosteroids in advanced progressive multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

    Background: A course of high-dose corticosteroids has been shown to hasten recovery from a relapse of multiple sclerosis (MS). Some patients with progressive MS ask for a course with corticosteroids outside a relapse, hoping to gain some functional improvement. Objective: To describe 4 patients with

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. Value of recombinant human thyrotropin in high-dose radioiodine therapy: a case report.

    Science.gov (United States)

    Müller, Vika; Bohuslavizki, Karl H; Klutmann, Susanne; Clausen, Malte

    2002-12-01

    We report on a high-dose radioiodine therapy after injection of recombinant human thyrotropin (rhTSH) in a 61-y-old woman with compression of the spinal cord caused by metastasis of a follicular thyroid carcinoma. Fourteen years ago, the patient underwent subtotal thyroidectomy because of multinodular goiter without any histologic evidence for malignant disease, and the patient was put on thyroxine substitution (100 micro g/d). In April 2000, she developed paralysis of the right leg. Morphologic imaging revealed spinal compression caused by a space-occupying lesion within the thoracic spine. Subsequent biopsy and histology demonstrated metastasis of a follicular thyroid carcinoma. Therefore, high-dose radioiodine therapy was scheduled after 4 wk of hormone withdrawal. Within a few days of being off thyroxine, the patient's paralytic symptoms worsened rapidly. The patient was again put on thyroxine, 100 micro g/d, and high-dose radioiodine therapy under stimulation with rhTSH was performed without any side effects. The second high-dose radioiodine therapy 3 mo later, again performed under stimulation with rhTSH, showed significantly less iodine avidity, and thyroglobulin levels fell from 1,024 micro g/L to 361 micro g/L, thereby demonstrating therapeutic efficacy. Thus, rhTSH might be used as a tool not only in the diagnostic application but also in the therapeutic application of (131)I.

  10. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours.

    NARCIS (Netherlands)

    Berkmortel, F. van den; Gidding, C.E.M.; Kanter, M. De; Punt, C.J.A.

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

  11. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    Directory of Open Access Journals (Sweden)

    Mihir Kothari

    2014-01-01

    Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  12. High-dose lidocaine does not affect defibrillation efficacy: implications for defibrillation mechanisms.

    Science.gov (United States)

    Ujhelyi, M R; Sims, J J; Miller, A W

    1998-04-01

    This study assessed the effect of low (10 mg.kg-1.h-1) and very high (18 mg.kg-1.h-1) doses of lidocaine on defibrillation energy requirements (DER) to relate changes in indexes of sodium-channel blockade with changes in DER values using a dose-response study design. In group 1 (control; n = 6 pigs), DER values were determined at baseline and during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 (n = 7), DER values were determined at baseline and during treatment with low-dose lidocaine followed by high-dose lidocaine. In group 3 (n = 3), DER values were determined at baseline and high-dose lidocaine. Group 3 controlled for the order of lidocaine treatment with the addition of high-dose lidocaine after baseline. DER values in group 1 did not change during D5W. In group 2, low-dose lidocaine increased DER values by 51% (P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of baseline values (P = 0.02, low dose vs. high dose). DER values during high-dose lidocaine in group 3 also remained near baseline values (16.2 +/- 2.7 to 12.9 +/- 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidocaine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the lidocaine dose increased. However, the greatest increase in DER occurred when ventricular fibrillation cycle length was minimally affected, demonstrating a negative correlation (P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-response curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refractoriness during ventricular fibrillation may be the electrophysiological mechanism by which high-dose lidocaine limits the adverse effects that low-dose lidocaine has on DER values

  13. A comparative analysis of radiobiological models for cell surviving fractions at high doses.

    Science.gov (United States)

    Andisheh, B; Edgren, M; Belkić, Dž; Mavroidis, P; Brahme, A; Lind, B K

    2013-04-01

    For many years the linear-quadratic (LQ) model has been widely used to describe the effects of total dose and dose per fraction at low-to-intermediate doses in conventional fractionated radiotherapy. Recent advances in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have increased the interest in finding a reliable cell survival model, which will be accurate at high doses, as well. Different models have been proposed for improving descriptions of high dose survival responses, such as the Universal Survival Curve (USC), the Kavanagh-Newman (KN) and several generalizations of the LQ model, e.g. the Linear-Quadratic-Linear (LQL) model and the Pade Linear Quadratic (PLQ) model. The purpose of the present study is to compare a number of models in order to find the best option(s) which could successfully be used as a fractionation correction method in SRT. In this work, six independent experimental data sets were used: CHOAA8 (Chinese hamster fibroblast), H460 (non-small cell lung cancer, NSLC), NCI-H841 (small cell lung cancer, SCLC), CP3 and DU145 (human prostate carcinoma cell lines) and U1690 (SCLC). By detailed comparisons with these measurements, the performance of nine different radiobiological models was examined for the entire dose range, including high doses beyond the shoulder of the survival curves. Using the computed and measured cell surviving fractions, comparison of the goodness-of-fit for all the models was performed by means of the reduced χ (2)-test with a 95% confidence interval. The obtained results indicate that models with dose-independent final slopes and extrapolation numbers generally represent better choices for SRT. This is especially important at high doses where the final slope and extrapolation numbers are presently found to play a major role. The PLQ, USC and LQL models have the least number of shortcomings at all doses. The extrapolation numbers and final slopes of these models do not depend on dose. Their asymptotes

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

    Directory of Open Access Journals (Sweden)

    Jan Muhammad Shah

    2016-10-01

    Full Text Available 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.

  15. Hypertonic saline solution and high-dose furosemide infusion in cardiorenal syndrome: our experience

    Directory of Open Access Journals (Sweden)

    Francesco Ventrella

    2013-03-01

    Full Text Available Introduction Heart failure is frequently complicated by renal failure, and this association is a negative prognostic factor. These patients sometimes present oligo-/anuria and resistance to high-dose furosemide, a condition referred to as the cardiorenal syndrome (CRS. Acute or chronic reductions in left ventricular function result in decreased blood flow, with reduction of renal perfusion and activation of several neurohormonal systems, which cause resistance to diuretic therapy. This condition often requires ultrafiltration, which is an effective, but invasive and expensive procedure. Infusions of hypertonic saline solution (HSS and high-dose furosemide can be an effective alternative. Materials and methods From November 2009 through May 2010, our team treated 20 patients with CRS and resistance to iv boluses of high-dose furosemide. These patients were treated with small-volume (150-250 mL infusions of HSS (NaCl 1.57 – 4.5%, depending on serum Na values and high-dose furosemide twice a day. The aim of this treatment is to modify renal hemodynamics and the water-saline balance in the kidney by counteracting the extracellular fluid accumulation and eliminating symptoms of congestion. Results In 18 patients (90%, urine output was restored and renal function improved during the first hours of treatment. Clinical improvement was evident from the first day of therapy, and there were no adverse events. Two patients (10% did not respond to the treatment: one (who had been in critical condition since admission died; the other required regular sessions of ultrafiltration. Conclusions HSS combined with high-dose furosemide is a safe, effective, low-cost approach to the treatment of CRS that is resistant to diuretic therapy.

  16. Investigating quartz optically stimulated luminescence dose-response curves at high doses

    Energy Technology Data Exchange (ETDEWEB)

    Lowick, Sally E., E-mail: lowick@geo.unibe.c [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Preusser, Frank [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Wintle, Ann G. [Institute of Geography and Earth Sciences, Aberystwyth University, AberystwythSY23 3DB (United Kingdom)

    2010-10-15

    Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose-response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose-response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the '325 {sup o}C' thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses

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

    DEFF Research Database (Denmark)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

    2004-01-01

    OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis......) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood...... pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. RESULTS: Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration...

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

    Science.gov (United States)

    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.

  19. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben;

    2015-01-01

    . Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...... transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling...

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

    Science.gov (United States)

    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.

  1. Synergies Between ' and Cavity Formation in HT-9 Following High Dose Neutron Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Parish, Chad M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saleh, Tarik A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eftink, Benjamin P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-06-01

    Candidate cladding materials for advanced nuclear power reactors including fast reactor designs require materials capable of withstanding high dose neutron irradiation at elevated temperatures. One candidate material, HT-9, through various research programs have demonstrated the ability to withstand significant swelling and other radiation-induced degradation mechanisms in the high dose regime (>50 displacements per atom, dpa) at elevated temperatures (>300 C). Here, high efficiency multi-dimensional scanning transmission electron microscopy (STEM) acquisition with the aid of a three-dimensional (3D) reconstruction and modeling technique is used to probe the microstructural features that contribute to the exceptional swelling resistance of HT-9. In particular, the synergies between ' and fine-scale and moderate-scale cavity formation is investigated.

  2. Simulation two-beam high-dose ion implantation in solid-state targets

    CERN Document Server

    Komarov, A F

    2001-01-01

    The physicomathematical model and the program on the BEAM2HD dynamic modeling make it possible to model the process of the single- or two-beam high-dose ion implantation into the multilayer and multicomponent targets, is developed. The number of layer thereby does not exceed three and the number of various types of atoms in each layer does not exceed seven. The modeling is realized through the Monte-Carlo method. The numerical results of the work on formation of the C sub x sub-> sub 3 N sub y sub-> sub 4 supersolid layers through the nitrogen two-beam high-dose ion implantation into the Si sub 3 N sub 4 /C/Si sub 3 N sub 4 /Si multilayer system are presented

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

    Science.gov (United States)

    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 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 P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  6. Late relapses in primary CNS lymphoma after complete remissions with high-dose methotrexate monotherapy

    Science.gov (United States)

    Ambady, Prakash; Holdhoff, Matthias; Bonekamp, David; Wong, Fay; Grossman, Stuart A

    2015-01-01

    Treatment of patients with newly diagnosed primary CNS lymphomas using high dose methotrexate regimens is reported to yield about 30% long term survivors with minimal neurotoxicity. As in other systemic large cell lymphomas, it is generally assumed that most relapses occur within 5 years of diagnosis. A retrospective review of the Johns Hopkins experience in 52 patients treated between 1995 and 2008 yielded 19 patients (37%) who achieved a complete response and were followed for over 5 years. Four of these patients remained progression-free for over 10 years. However, two of these long-term survivors have now relapsed over 10 years after their initial diagnosis. An analysis of progression and overall survival does not reveal a plateau suggesting that even patients who have not recurred for over 10 years remain at high risk for relapse after treatment with single agent high dose methotrexate. PMID:26507609

  7. Heavy ion time-of-flight ERDA of high dose metal implanted germanium

    Energy Technology Data Exchange (ETDEWEB)

    Dytlewski, N.; Evans, P.J.; Noorman, J.T. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia); Wielunski, L.S. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Div. of Applied Physics; Bunder, J. [New South Wales Univ., Wollongong, NSW (Australia). Wollongong Univ. Coll

    1996-12-31

    With the thick Ge substrates used in ion implantation, RBS can have difficulty in resolving the mass-depth ambiguities when analysing materials composed of mixtures of elements with nearly equal masses. Additional, and complimentary techniques are thus required. This paper reports the use of heavy ion time-of-flight elastic recoil detection analysis (ToF- ERDA), and conventional RBS in the analysis of Ge(100) implanted with high dose Ti and Cu ions from a MEWA ion source . Heavy ion ToF ERDA has been used to resolve, and profile the implanted transition metal species, and also to study any oxygen incorporation into the sample resulting from the implantation, or subsequential reactions with air or moisture. This work is part of a study on high dose metal ion implantation of medium atomic weight semiconductor materials. 13 refs., 6 figs.

  8. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer

    DEFF Research Database (Denmark)

    Appelt, Ane L; Pløen, John; Harling, Henrik

    2015-01-01

    BACKGROUND: Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose...... radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. METHODS: Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions......-0) at all timepoints. The most common late toxicity was bleeding from the rectal mucosa; grade 3 bleeding was reported in two (7%) in 30 patients at 1 year and one (6%) of 17 patients at 2 years. There were no unexpected serious adverse reactions or treatment-related deaths. INTERPRETATION: High-dose...

  9. High-dose rate brachytherapy in the treatment of cancer of the cervix uteri

    Directory of Open Access Journals (Sweden)

    D. A. Aliyev

    2011-01-01

    Full Text Available Analysis of the results of examining and treating 246 patients with Stages IIA-IIIB cancer of the cervix uteri (CCU, receiving specific chemoradiotherapy (CRT at the Department of Radiotherapy, National Oncology Center (Baku, has ascertained that CRT using two high-dose (9 Gy rate brachytherapy fractions and competitive cisplatin chemotherapy is an effective, reasonably safe, and economically sound treatment method for locally advanced CCU. The method shows acceptable toxicity and may be used in routine clinical practice.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis, E-mail: acapellizzon@hcancer.org.br [A.C. Camargo Cancer Center, Sao Paulo, SP (Brazil). Departamento de Radioterapia

    2016-05-15

    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. (author)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  14. Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty

    DEFF Research Database (Denmark)

    Lunn, T H; Andersen, Lasse Østergaard; Kristensen, B B

    2013-01-01

    BACKGROUND: /st>High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip arthroplasty (THA). METHODS: /st>Forty-eight patients undergoing unilateral THA...... well-defined functional discharge criteria. Secondary outcomes were handgrip strength and endurance, pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic-, and hypnotic medicine requirements. The inflammatory response measured by C-reactive protein (CRP) and actual length...

  15. Biological dose estimation for accidental supra-high dose gamma-ray exposure

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y., E-mail: yingchen29@yahoo.com.cn [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Yan, X.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Department of Radiation Safety, Beijing Institute of Nuclear and Chemical Safety, 14 Guan-cun, Dongcheng District, Beijing 100077 (China); Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China)

    2011-09-15

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of {sup 60}Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of {sup 60}Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0{sup -3}D{sup 2}. Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy {gamma}-irradiation from a supra-high dose {sup 60}Co gamma-ray accident.

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

    Science.gov (United States)

    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.

  17. Primary treatment of acromegaly with high-dose lanreotide: a case series

    OpenAIRE

    Cordes Uwe; Both Stefan; Wuster Christian; Omran Wael; Reisch Robert

    2010-01-01

    Abstract Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (A...

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

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Ary A. [Universidade Estadual de Londrina-Depto de Fisica, Rodovia Celso Garcia Cid, km 38, 086051-990 Londrina (Brazil); Vieira, Jose M. [Instituto de Pesquisas Energeticas e Nucleares-IPEN/CNEN-SP, Prof. Lineu Prestes, 2242-Cidade Universitaria, 05508-900 Sao Paulo (Brazil); Hamada, Margarida M. [Instituto de Pesquisas Energeticas e Nucleares-IPEN/CNEN-SP, Prof. Lineu Prestes, 2242-Cidade Universitaria, 05508-900 Sao Paulo (Brazil)], E-mail: mmhamada@ipen.br

    2010-04-15

    A 1 cm{sup 3} cylindrical ionization chamber was developed to measure high doses on line during the sample irradiation in static position, in a {sup 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.

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

    Directory of Open Access Journals (Sweden)

    Gorlin AW

    2016-09-01

    Full Text Available Andrew W Gorlin, David M Rosenfeld, Jillian Maloney, Christopher S Wie, Johnathan McGarvey, Terrence L Trentman Department of Anesthesiology, Mayo Clinic Arizona, Phoenix, AZ, USA Abstract: 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. Keywords: intrathecal pump, epidural, cancer pain

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lucas N. [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Goiania, Goiania -GO (Brazil); Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil); Vieira, Silvio L. [Instituto de Fisica, Universidade Federal de Goias-UFG, Campus Samambaia, Goiania-GO (Brazil); Schimidt, Fernando [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Inhumas, Inhumas-GO (Brazil); Antonio, Patricia L.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil)

    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)

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

    Science.gov (United States)

    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.

  4. Extra-high doses detected in the enamel of human teeth in the Techa riverside region

    Energy Technology Data Exchange (ETDEWEB)

    Shishkina, E.A., E-mail: ElenaA.Shishkina@gmail.com [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Degteva, M.O.; Tolstykh, E.I.; Volchkova, A. [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Ivanov, D.V. [Institute of Metal Physics, Russian Academy of Sciences, 18 S. Kovalevsky Str, 620041 Yekaterinburg (Russian Federation); Wieser, A. [Helmholtz Zentrum Muenchen, German Research Centre for Environmental Health, D-85764 Neuherberg (Germany); Della Monaca, S. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Regina Elena, 00144 Rome (Italy); Fattibene, P. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Nazionale di Fisica Nucleare, 00161 Rome (Italy)

    2011-09-15

    During the long-term study of tooth enamel by EPR dosimetry for population exposed to radiation due to contamination of the Techa River, it was found out that for some of the tooth donors the dose accumulated in tooth enamel could be as high as several tens of Gy. Such doses were absorbed only in tooth enamel and they should not be associated with exposures to other organs or the whole body. The nature of such doses was discussed in a number of previous papers where it was shown that the source of such doses is {sup 90}Sr incorporated in the calcified dental tissues. However, among specialists in radiation dosimetry who were not involved in the biokinetic studies, the nature and dosimetric significance of extra-high doses in tooth enamel are still raising questions. The aim of the current paper is to summarize the accumulated information on extra-high doses in the teeth of the Techa riverside residents, describe the dose levels observed, explain the nature of extra-high doses in the enamel and discuss their informative value. The paper includes an overview of already published findings and an analysis of information collected in the data bank of the Urals Research Center for Radiation Medicine (URCRM), Chelyabinsk, Russia, which has not been published before.

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

    Science.gov (United States)

    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.

  6. Development of computerized dose planning system and applicator for high dose rate remote afterloading irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, T. J. [Keimyung Univ., Taegu (Korea); Kim, S. W. [Fatima Hospital, Taegu (Korea); Kim, O. B.; Lee, H. J.; Won, C. H. [Keimyung Univ., Taegu (Korea); Yoon, S. M. [Dong-a Univ., Pusan (Korea)

    2000-04-01

    To design and fabricate of the high dose rate source and applicators which are tandem, ovoids and colpostat for OB/Gyn brachytherapy includes the computerized dose planning system. Designed the high dose rate Ir-192 source with nuclide atomic power irradiation and investigated the dose characteristics of fabricated brachysource. We performed the effect of self-absorption and determining the gamma constant and output factor and determined the apparent activity of designed source. he automated computer planning system provided the 2D distribution and 3D includes analysis programs. Created the high dose rate source Ir-192, 10 Ci(370GBq). The effective attenuation factor from the self-absorption and source wall was examined to 0.55 of the activity of bare source and this factor is useful for determination of the apparent activity and gamma constant 4.69 Rcm{sup 2}/mCi-hr. Fabricated the colpostat was investigated the dose distributions of frontal, axial and sagittal plane in intra-cavitary radiation therapy for cervical cancer. The reduce dose at bladder and rectum area was found about 20 % of original dose. The computerized brachytherapy planning system provides the 2-dimensional isodose and 3-D include the dose-volume histogram(DVH) with graphic-user-interface mode. emoted afterloading device was built for experiment of created Ir-192 source with film dosimetry within {+-}1 mm discrepancy. 34 refs., 25 figs., 11 tabs. (Author)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 insulin therapy. One patient was discharged with mild anoxic injury thought due to pulseless electrical activity arrest prior to insulin therapy. Three of these 12 patients have been previously described in published case reports. High-dose insulin therapy based on a 1-10 U/kg/h dosing guideline and recommending avoidance of vasopressors appears to be

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

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    Tülay Kaçar Güvel

    2014-10-01

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

  14. Development of Radiation Fusion Technology with Food Technology by the Application of High Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju Won; Kim, Jae Hun; Choi, Jong Il

    2010-04-15

    This study was studied to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering were developed. Irradiation condition to destroy radiation resistant food borne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources were developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not were developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin were developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam were introduced. Results from this research project, the followings are expected. (1) Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. (2) Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of food borne outbreaks. (3) Build of SPS/TBT system against imported products and acceleration of domestic product export

  15. Development of radiation fusion technology with food technology by the application of high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juwoon; Kim, Jaehun; Choi, Jongil; and others

    2012-04-15

    This study was performed to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering was developed. Irradiation condition to destroy radiation resistant foodborne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources was developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not was developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin was developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam was introduced. Results from this research project, the followings are expected. Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of foodborne outbreaks. Build of SPS/TBT system against imported products and acceleration of domestic product export. Systemized

  16. Effects of high dose coffee intake on aerobic power in dragon female athletes

    Directory of Open Access Journals (Sweden)

    Ramin Shabani

    2016-08-01

    Full Text Available Background : There are few studies that consider the effect of high doses of caffeine on aerobic power (VO2max. Also, to date, no study examined the effect of coffee intake on dragon boat paddler specifically on women. The purpose of this study was to investigate the effect of espresso coffee on improvement of aerobic power of dragon boat paddler. Material : Twenty women athletes of Guilan dragon bout team members of Malavan club of port city of Anzali (mean ±SD age, 23.60± 3.49 years; BMI,23.77±1.88kg/m2; body fat, 30.32±4.65% were recruited to this study, after they completed a primary test without consuming any coffee, they consumed 6mg/kg of coffee (espresso or decaffeinated and following that they completed two experimental trials. A randomized, double-blind, repeated-measures, design was employed whereby paddlers complete a 2000m paddling dragon boat ergo-meter. Results : Coffee could improve VO2max (Without coffee =74.40± QUOTE 4.99, Espresso coffee =90.10± QUOTE 6.19, Decaffeinated coffee =91.00± QUOTE 5.67, P≤ QUOTE 0.05. VO2max amount after exercise were significantly higher for both espresso coffee and decaffeinated coffee, when compared with without coffee condition. No significant differences were observed between espresso coffee and decaffeinated coffee (P≤ QUOTE 0.05. Conclusion : The present study shows that both high doses of caffeine (espresso coffee and decaffeinated coffee can enhance VO2max during aerobic exercise including 2000m dragon boat paddling. It seems that some compounds except caffeine in decaffeinated coffee can act improve VO2max. Further studies needed for considering the effect of high doses of coffee on endurance exercises. Also in other age ranges of women athletes and other sport athletes.

  17. Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

    Directory of Open Access Journals (Sweden)

    Xinghui Li

    Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

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

    Science.gov (United States)

    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.

  19. Feasibility and safety of high-dose adenosine perfusion cardiovascular magnetic resonance

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    Holloway Cameron J

    2010-11-01

    Full Text Available Abstract Introduction Adenosine is the most widely used vasodilator stress agent for Cardiovascular Magnetic Resonance (CMR perfusion studies. With the standard dose of 140 mcg/kg/min some patients fail to demonstrate characteristic haemodynamic changes: a significant increase in heart rate (HR and mild decrease in systolic blood pressure (SBP. Whether an increase in the rate of adenosine infusion would improve peripheral and, likely, coronary vasodilatation in those patients is unknown. The aim of the present study was to assess the tolerance and safety of a high-dose adenosine protocol in patients with inadequate haemodynamic response to the standard adenosine protocol when undergoing CMR perfusion imaging. Methods 98 consecutive patients with known or suspected coronary artery disease (CAD underwent CMR perfusion imaging at 1.5 Tesla. Subjects were screened for contraindications to adenosine, and an electrocardiogram was performed prior to the scan. All patients initially received the standard adenosine protocol (140 mcg/kg/min for at least 3 minutes. If the haemodynamic response was inadequate (HR increase Results All patients successfully completed the CMR scan. Of a total of 98 patients, 18 (18% did not demonstrate evidence of a significant increase in HR or decrease in SBP under the standard adenosine infusion rate. Following the increase in the rate of infusion, 16 out of those 18 patients showed an adequate haemodynamic response. One patient of the standard infusion group and two patients of the high-dose group developed transient advanced AV block. Significantly more patients complained of chest pain in the high-dose group (61% vs. 29%, p = 0.009. On multivariate analysis, age > 65 years and ejection fraction Conclusions A substantial number of patients do not show adequate peripheral haemodynamic response to standard-dose adenosine stress during perfusion CMR imaging. Age and reduced ejection fraction are predictors of inadequate

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

    Directory of Open Access Journals (Sweden)

    P Pallavee

    2013-01-01

    Full Text Available 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.

  1. [Stability of high-dose etoposide dilutions for use in hematopoietic stem cell transplantation conditioning regimens].

    Science.gov (United States)

    Bauters, T; Vandenbroucke, J; Commeyne, S

    2015-12-01

    High-dose etoposide is used in conditioning regimens for allogeneic stem cell transplantation. The limited stability of the drug induces barriers for its use for pharmacists, nurses and patients. When using a concentration of 10 mg/mL etoposide in physiologic saline, limitations can be overcome. This study provides stability data for etoposide in a high concentration that can be used in conditioning regimens. The solution was stable for 48h at 5°C, for 48h at 5°C followed by 8h at 25°C and for 24 h at 25°C.

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

    Science.gov (United States)

    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

  3. Intravenous high-dose immunotherapy: practical recommendations for use in the treatment of neurological disimmune diseases

    Directory of Open Access Journals (Sweden)

    N. A. Suponeva

    2015-01-01

    Full Text Available Current publication summarizes main indications and benefits of intravenous high-dose immunotherapy (IHI in the treatment of various autoimmune diseases of the peripheral nervous system. Available products of intravenous immunoglobulin (IVIG on the Russian market are reviewed. Tactics for choosing optimal medication for IHI based on its effectiveness and safety are analyzed. Dosage calculation and way of administration of IVIG are described, beeing of a high practical value in neurologist’s daily work.

  4. MINERALIZATION STUDY OF RENAL RATS FOLLOWING OVARYOHYSTERECTOMY AND ADMINISTRATION HIGH DOSE CALCIUM CARBONATE

    OpenAIRE

    Wiwik Misaco Yuniarti; Ira Sari Yudaniayanti; Nusdianto Triakoso

    2008-01-01

    The aim of this study was to determine the effect of high dose calcium carbonate in rat (Rattus norvegicus) following ovaryohysterectomy. A total of twenty female rats at 13 week-old were used in this study. Following ovaryohitectomy, the animals were randomized in four treatment groups. Group P0 were :fed with standard food only P1, P2 and P2 groups treated with standard food but supplemented calcium carbonate respectively at the dose of 75 mg per animal per day, 225 mg per animal per day , ...

  5. High dose-rate brachytherapy source position quality assurance using radiochromic film.

    Science.gov (United States)

    Evans, M D C; Devic, S; Podgorsak, E B

    2007-01-01

    Traditionally, radiographic film has been used to verify high-dose-rate brachytherapy source position accuracy by co-registering autoradiographic and diagnostic images of the associated applicator. Filmless PACS-based clinics that do not have access to radiographic film and wet developers may have trouble performing this quality assurance test in a simple and practical manner. We describe an alternative method for quality assurance using radiochromic-type film. In addition to being easy and practical to use, radiochromic film has some advantages in comparison with traditional radiographic film when used for HDR brachytherapy quality assurance.

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

    Directory of Open Access Journals (Sweden)

    Mikirova Nina

    2012-09-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

    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.

  8. Application of RADPOS in Vivo Dosimetry for QA of High Dose Rate Brachytherapy

    DEFF Research Database (Denmark)

    Cherpak, A.; Kertzscher Schwencke, Gustavo Adolfo Vladimir; Cygler, J.

    2012-01-01

    Gy. Conclusions: In vivo dosimetry can potentially signal errors in catheter placement or numbering before entire dose is delivered. The demonstrated accuracy of RADPOS dose measurements and its ability to simultaneously measure displacement makes it a powerful tool for HDR brachytherapy treatments for prostate...... cancer, where high dose gradients and movement of the prostate gland can present unique in vivo dosimetry challenges. Financial and technical support has been received from Best Medical Canada and Ascension Technology Corporation. © 2012 American Association of Physicists in Medicine...

  9. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

    OpenAIRE

    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 improve...

  10. High dose 1,25(OH)2D3 inhibits osteoblast mineralization in vitro.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Weitzmann, M Neale

    2012-05-01

    Vitamin D is essential for optimal calcium absorption needed for maintaining normal bone mineral density (BMD). Consequently, vitamin D-deficiency leads to poorly mineralized bone with diminished strength and load bearing capacity. Surprisingly, several animal and clinical studies have identified suppressive effects of high dose vitamin D supplementation on bone formation. These data suggest that while vitamin D is necessary for basal bone homeostasis, excessive concentrations may be detrimental to the skeleton. To further examine the direct effects of high dose vitamin D on the function of osteoblasts we differentiated primary osteoblast precursors and MC3T3 preosteoblastic cells, in the presence of supraphysiological doses of the active metabolite, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In vitro osteoblast mineralization was potently suppressed by high dose 1,25(OH)2D3. To investigate the mechanism we used a bioassay to examine nuclear factor-κB (NF-κB) activation in MC3T3 cells. Although NF-κB agonists are generally potent inhibitors of osteoblast differentiation, surprisingly, 1,25(OH)2D3 dose-dependently suppressed, rather than stimulated, NF-κB activation. Interestingly, 1,25(OH)2D3 also suppressed Smad activation induced by the osteoblast commitment and differentiation factors transforming growth factor-β (TGF-β) and bone morphogenetic protein 2 (BMP2), which may account for the inhibitory activities of 1,25(OH)2D3 on mineralization. Our data suggest that vitamin D has complex pleiotropic effects on osteoblast signal transduction. As the net balance of high dose 1,25(OH)2D3 appears to be an inhibitory action on osteoblasts, our data suggest that the therapeutic value of vitamin D to maximize bone mass through indirect actions on calcium absorption may need to be carefully balanced with potential inhibitory direct effects on mineralizing cells. Our data suggest that indiscriminate over-dosing may be detrimental to bone formation and optimal

  11. A comparison of batch and single wafer high dose arsenic ion implantation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Irwin, R.B.; Filo, A.J.; Kannan, V.C.; Feygenson, A.; Prematta, R.J.

    1989-04-01

    High dose, low energy (4x10/sup 15/ cm/sup -2/ at 15 keV) arsenic ion implantation into silicon was performed in batch and single wafer mode using medium and high current ion implanters. An investigation of implanted and annealed samples by Rutherford backscattering (RBS), transmission electron microscopy (TEM), thermal wave technique, and sheet resistance mapping showed little to no difference of arsenic profiles and residual damage between batch and single wafer implantation conditions when the sample temperature during implantation was kept below 120/sup 0/C. (orig.).

  12. A comparison of batch and single wafer high dose arsenic ion implantation techniques

    Science.gov (United States)

    Irwin, R. B.; Filo, A. J.; Kannan, V. C.; Feygenson, A.; Prematta, R. J.

    1989-04-01

    High dose, low energy (4×10 15 cm -2 at 15 keV) arsenic ion implantation into silicon was performed in batch and single wafer mode using medium and high current ion implanters. An investigation of implanted and annealed samples by Rutherford backscattering (RBS), transmission electron microscopy (TEM), thermal wave technique, and sheet resistance mapping showed little to no difference of arsenic profiles and residual damage between batch and single wafer implantation conditions when the sample temperature during implantation was kept below 120° C.

  13. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma

    DEFF Research Database (Denmark)

    Hagenbeek, Anton; Gadeberg, Ole Vestergaard; Johnson, Peter

    2008-01-01

    Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules...... and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months...

  14. Bone marrow dosimetry using blood-based models for {sup 131}i-anti-cd20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, J. H.; Kim, H. G.; Choi, T. H. [Korea Cancer Center Hospital, Seoul (Korea, Republic of)] (and others)

    2005-07-01

    Accurate estimations of radiation absorbed dose are essential part of evaluating the risks and benefits associated with radiotherapy. Determination of red marrow dose is important because myelotoxicity is often dose limiting in radioimmunotherapy. The aim of this study is to set up the procedures of dosimetry with activities in the blood and whole-body and to estimate the dose of patients according to MIRD schema. Therapy activities of 131I (136, 185, 200 mCi) were administrated to patients (n=3). Blood activity concentrations and whole-body images by gamma camera were collected from patients with non-Hodgkin's lymphoma (5min, 6h, 24h, 48h, 72h, 2week). Two kinds of patient specific approaches based on Sgouros bone marrow dosimetry methodology were considered to estimate bone marrow dose. The mean effective half-life in blood and whole-body were 25.2h and 27.1h respectively and the mean absorbed dose to bone marrow was 0.48Gy (0.22{approx}0.93Gy). The dominant contribution of dose was found to be from bone marrow self-dose (over 60%). The procedures of dosimetry with blood and gamma camera image were established. These enable to estimate the radioimmunotherapy patient's dose retrospectively. Some parts of the procedures need to be elaborated to obtain more accurate dose in the near future.

  15. The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

    Science.gov (United States)

    Mendoza-Pinto, Claudia; Garcia-Carrasco, Mario; Vallejo-Ruiz, Veronica; Taboada-Cole, Alejandro; Muñoz-Guarneros, Margarita; Solis-Poblano, Juan Carlos; Pezzat-Said, Elias; Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis Felipe; de Lara, Luis Vazquez; Ramos-Alvarez, Gloria; Reyes-Leyva, Julio; Lopez-Colombo, Aurelio

    2013-01-01

    OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus. PMID:24473503

  16. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    OBJECTIVES: To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. METHODS: Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  17. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Hasselbalch, Hans K

    2006-01-01

    We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after review...

  18. Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

    Science.gov (United States)

    2016-06-13

    Adult Burkitt Lymphoma; Adult Diffuse Large B-Cell Lymphoma; CD20-Positive Neoplastic Cells Present; Indolent Adult Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma

  19. The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Claudia Mendoza-Pinto

    2013-12-01

    Full Text Available OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05, and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01 and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005 compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03. In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus.

  20. Desensitization with plasmapheresis and anti-Cd20 for ABO incompatible kidney transplantation from living donor: experience of a single center in Italy.

    Science.gov (United States)

    Silvestre, C; Furian, L; Marson, P; Tison, T; Valente, M; Marchini, F; Rossi, B; Bonfante, L; Valerio, F; Cozzi, E; Rigotti, P

    2014-09-01

    Blood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. From July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP+cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. After a mean follow-up of 11.6±10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48±0.29, 1.47±0.18, 1.47±0.27, and 1.5±0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. Desensitization with rituximab, PP, and anti-cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    Science.gov (United States)

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

  2. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Hasselbalch, Hans K;

    2006-01-01

    We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after...... reviewing the efficacy and safety in other autoimmune diseases, we propose that treatment with the B cell-depleting agent Rituximab may become a clinically relevant treatment option in selected cases of GD, particularly when complicated with thyroid-associated ophthalmopathy....

  3. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17–47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  4. Radiomenolysis of the endometrium by high-dose iridium-192 irradiation- clinical and cytomorphologic results

    Energy Technology Data Exchange (ETDEWEB)

    Kucera, H.; Huber, H.; Weghaupt, K.

    1984-04-01

    423 patients with benign recurrent uterine bleeding resistant to other therapy were treated by intracavitary radiotherapy. In all cases there was a contraindication for the operative removal of the uterus. Since 1980 radiomenolysis was performed by high-dose Iridium-192 irradiation (afterloading technique). In 94.3% of our cases with Radium-226 irradiation the bleeding could be treated successfully. Side effects of the irradiation occurred only in a minimal and neglectible percentage. In all cases irradiated with Iridium-192 the bleeding stopped after treatment. Side effects could not be observed. Therefore the intrauterine contact-irradiation therapy with high-dose Iridium-192 should be remembered in cases of uterine bleeding resistant to hormonal therapy or in cases of high risk for operation. With the afterloading device the molestation for the patients could be reduced to a minimum. By intrauterine exfoliative smear performed before and after irradiation the cytomorphologic effect of an Iridium-192 afterloading irradiation was demonstrated. The examinations showed that the cytologic findings were characteristic for the effect if ionizing radiation of the histologically unchanged, not radiosensitive, normal cylindrical epithelium. A marked cellular diathesis and augmentation of size of nuclei and plasma is a characteristic result of the irradiation with Iridium-192.

  5. Dosimetric properties of bio minerals applied to high-dose dosimetry using the TSEE technique

    Energy Technology Data Exchange (ETDEWEB)

    Vila, G. B.; Caldas, L. V. E., E-mail: gbvila@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The study of the dosimetric properties such as reproducibility, the residual signal, lower detection dose, dose-response curve and fading of the thermally stimulated emission exo electronic (TSEE) signal of Brazilian bio minerals has shown that these materials present a potential use as radiation dosimeters. The reproducibility within ± 10% for oyster shell, mother-of-pearl and coral reef samples showed that the signal dispersion is small when compared with the mean value of the measurements. The study showed that the residual signal can be eliminated with a thermal treatment at 300 grades C/1 h. The lower detection dose of 9.8 Gy determined for the oyster shell samples when exposed to beta radiation and 1.6 Gy for oyster shell and mother-of-pearl samples when exposed to gamma radiation can be considered good, taking into account the high doses of this study. The materials presented linearity at the dose response curves in some ranges, but the lack of linearity in other cases presents no problem since a good mathematical description is possible. The fading study showed that the loss of TSEE signal can be minimized if the samples are protected from interferences such as light, heat and humidity. Taking into account the useful linearity range as the main dosimetric characteristic, the tiger shell and oyster shell samples are the most suitable for high-dose dosimetry using the TSEE technique. (Author)

  6. Prognosis of emergency room stabilization of decompensated congestive heart failure with high dose lasix

    Directory of Open Access Journals (Sweden)

    Mahboob Pouraghaei

    2015-06-01

    Full Text Available Objective: Congestive heart failure (CHF has become one of the most important health care problems in western countries. This article focuses on the outpatient diagnosis and management of heart failure. We want to compare the outcome of patients who were treated with high dose diuretics in the emergency department (ED without admission with patients who were admitted to hospital for standard treatment. Methods: This was a randomized prospective clinical trial study. The patients who came to the ED from March 20, 2008 up to August 20, 2008 were divided into two groups randomly. The length of ED stay in the experimental group was documented. Also, readmission and mortality in 6 months and satisfaction in both groups were taken into consideration. All data were analyzed using SPSS 15.0. Results: In experimental group, the rate of recurrent admission, expiration, discharge, clinic visit, and clinic admission was 8%, 4%, 29%, 18%, and 0% respectively. On the other hand, in control group it was 16%, 40%, 18%, 22%, and 2% respectively. Additionally, there was a significant difference between these groups (P = 0.00. Conclusion: This study is the first regional prospective trial to comprehensively examine the therapeutic management in patients with CHF. This study, comparing the high dose diuretic efficacy in the decreasing of hospital stay and readmission; and decreasing mortality rate with routine therapy, showed that there was a significant difference between these two strategies in the mortality rate, readmission, and length of hospital stay (P = 0.00.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sha, Rajib Lochan [Department of Radiation Physics, Indo-American Cancer Institute and Research Centre, Hyderabad (India); Department of Physics, Osmania University, Hyderabad (India); Reddy, Palreddy Yadagiri [Department of Physics, Osmania University, Hyderabad (India); Rao, Ramakrishna [Department of Radiation Physics, MNJ Institute of Oncology and Regional Cancer Center, Hyderabad (India); Muralidhar, Kanaparthy R. [Department of Radiation Physics, Indo-American Cancer Institute and Research Centre, Hyderabad (India); Kudchadker, Rajat J., E-mail: rkudchad@mdanderson.org [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    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.

  8. Mechanical Performance of Ferritic Martensitic Steels for High Dose Applications in Advanced Nuclear Reactors

    Science.gov (United States)

    Anderoglu, Osman; Byun, Thak Sang; Toloczko, Mychailo; Maloy, Stuart A.

    2013-01-01

    Ferritic/martensitic (F/M) steels are considered for core applications and pressure vessels in Generation IV reactors as well as first walls and blankets for fusion reactors. There are significant scientific data on testing and industrial experience in making this class of alloys worldwide. This experience makes F/M steels an attractive candidate. In this article, tensile behavior, fracture toughness and impact property, and creep behavior of the F/M steels under neutron irradiations to high doses with a focus on high Cr content (8 to 12) are reviewed. Tensile properties are very sensitive to irradiation temperature. Increase in yield and tensile strength (hardening) is accompanied with a loss of ductility and starts at very low doses under irradiation. The degradation of mechanical properties is most pronounced at reactor environment, the stress exponent is expected to be approximately one and the steady state creep rate in the absence of swelling is usually better than austenitic stainless steels both in terms of the creep rate and the temperature sensitivity of creep. In short, F/M steels show excellent promise for high dose applications in nuclear reactors.

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

    Directory of Open Access Journals (Sweden)

    Daniel Scheiber

    2015-08-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  11. Agonist substitution--a treatment alternative for high-dose benzodiazepine-dependent patients?

    Science.gov (United States)

    Liebrenz, Michael; Boesch, Lukas; Stohler, Rudolf; Caflisch, Carlo

    2010-11-01

    There is vast evidence for the superiority of agonist treatments (methadone, buprenorphine) over a withdrawal approach in opioid-dependent populations. Little research, however, has been conducted on the same approach for the treatment of high-dose benzodiazepine (BZD) dependence. Even large-scale reviews and meta-analyses discussing treatment strategies for benzodiazepine-dependent patients focus solely upon approaches that aim at achieving abstinence, namely on complete BZD withdrawal. While the types of interventions differ (e.g. gradual benzodiazepine taper with a long or a short half-life benzodiazepine, switching to non-benzodiazepine anxiolytics or prescribing adjunctive medications such as antidepressants or anticonvulsants on an in- or out-patient basis), the common aim of treatment still is total abstinence from benzodiazepines. However, the majority of patients suffering from high-dose BZD dependence do not succeed with long-term abstinence, irrespective of the procedure, and clinicians have been using BZD 'substitution' treatment in such cases for decades. Therefore, we suggest the evaluation of a substitution approach in this group, consisting of maintenance treatment with a slow-onset, long-acting BZD. Advantages of such a procedure may be improved health, less craving, fewer withdrawal complications, reduced anxiety, increased treatment retention, improvements in social functioning and less illegal activity. Cognitive impairments, the most problematic side effects of substitution treatment with benzodiazepines, could possibly be minimized by using an optimal agonist.

  12. Primary treatment of acromegaly with high-dose lanreotide: a case series

    Directory of Open Access Journals (Sweden)

    Cordes Uwe

    2010-03-01

    Full Text Available Abstract Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (Autogel® every four weeks. All patients were German nationals and Caucasian. When the response of our patients was unsatisfactory, the dose was increased sequentially to 90 mg every four weeks, 120 mg every four weeks, 120 mg every three weeks and 180 mg every three weeks. Treatment duration was 12 to 24 months. In all cases, the lanreotide dose was 120 mg every 4 weeks or higher. In five of our patients, growth hormone (GH levels were successfully reduced (in three patients GH Tumor shrinkage or degeneration was observed in the five responding patients. No drug-related adverse events were noted. Conclusions These results suggest that lanreotide at high doses of 120 mg every four weeks or more is an effective first-line therapy for patients with acromegaly that surgery alone cannot treat.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. Evaluation of risk of nephrotoxicity with high dose, extended-interval colistin administration

    Directory of Open Access Journals (Sweden)

    Arun Dewan

    2014-01-01

    Full Text Available Aim: The aim was to evaluate the risk of nephrotoxicity with high-dose, extended-interval regimen of colistin administration in critical ill patients. Materials and Methods: This prospective study was conducted on patients suffering from sepsis due to Gram-negative infection susceptible only to colistin. The dosing schedule for colistin was 9 million units stat followed by 4.5 million units at 12 hourly interval (adjusted as per body weight and renal functions. The serum creatinine and creatinine clearance were estimated at the start of therapy and daily during therapy. Results: Thirty-one patients suffering ventilator associated pneumonia (61.29%, blood stream infections (29.03% and urinary tract infections (9.67% due to Gram-negative multiple drug resistance organisms were assessed. Most commonly isolated organism were Acinetobacter baumannii (54.83%, Klebsiella pneumonia (16.12% and Pseudomonas (29.03%. Five patients (16.12% developed acute kidney injury within 4-5 days of start of therapy and returned to baseline after 6 days with no patient requiring renal replacement therapy or discontinuation of colistin. Conclusion: Our study showed that high-dose, extended-interval colistin can be given to critically ill patients without any significant risk of nephrotoxicity.

  16. High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer.

    Science.gov (United States)

    Vuong, T; Devic, S; Podgorsak, E

    2007-11-01

    In the era of total mesorectal surgery, the issue of radiation toxicity is raised. A novel endocavitary brachytherapy technique was tested as a neoadjuvant treatment for patients with resectable rectal cancer. The objectives of the study were to evaluate the treatment-related toxicity and effects on local recurrence. A dose of 26 Gy was prescribed to the gross tumour volume and intramesorectal deposits seen on magnetic resonance imaging and given over four daily treatments, using the high dose rate delivery system followed by surgery 6-8 weeks later. The study included 93 T3, four T4 and three T2 tumours. Acute proctitis of grade 2 was observed in all patients, but one required transfusion. At a median follow-up time of 60 months, the 5-year actual local recurrence rate was 5%, disease-free survival was 65%, and overall survival was 70%. High dose rate endorectal brachytherapy seems to prevent local recurrence and has a favourable toxicity pattern compared with external beam radiotherapy.

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

    Science.gov (United States)

    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.

  18. Effects of high dose rate gamma radiation on survival and reproduction of Biomphalaria glabrata

    Energy Technology Data Exchange (ETDEWEB)

    Cantinha, Rebeca S.; Nakano, Eliana [Instituto Butantan, Sao Paulo, SP (Brazil). Lab. de Parasitologia], e-mail: rebecanuclear@gmail.com, e-mail: eliananakano@butantan.gov.br; Borrely, Sueli I. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil). Centro de Tecnologia das Radiacoes], e-mail: sborrely@ipen.br; Amaral, Ademir; Melo, Ana M.M.A. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear. Grupo de Estudos em Radioprotecao e Radioecologia (GERAR)], e-mail: amaral@ufpe.br; Silva, Luanna R.S. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia. Lab. de Radiobiologia], e-mail: amdemelo@hotmail.com, e-mail: luannaribeiro_lua@hotmail.com

    2009-07-01

    Ionizing radiations are known as mutagenic agents, causing lethality and infertility. This characteristic has motivated its application on animal biological control. In this context, the freshwater snail Biomphalaria glabrata can be considered an excellent experimental model to study effects of ionizing radiations on lethality and reproduction. This work was designed to evaluate effects of {sup 60}Co gamma radiation at high dose rate (10.04 kGy/h) on B. glabrata. For this purpose, adult snails were selected and exposed to doses ranging from 20 to 100 Gy, with 10 Gy intervals; one group was kept as control. There was not effect of dose rate in the lethality of gamma radiation; the value of 64,3 Gy of LD{sub 50} obtained in our study was similar to that obtained by other authors with low dose rates. Nevertheless, our data suggest that there was a dose rate effect in the reproduction. On all dose levels, radiation improved the production of embryos for all exposed individuals. However, viability indexes were below 6% and, even 65 days after irradiation, fertility was not recovered. These results are not in agreement with other studies using low dose rates. Lethality was obtained in all groups irradiated, and the highest doses presented percentiles of dead animals above 50%. The results demonstrated that doses of 20 and 30 Gy were ideal for population control of B. glabrata. Further studies are needed; nevertheless, this research evidenced great potential of high dose rate gamma radiation on B. glabrata reproductive control. (author)

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

    Science.gov (United States)

    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. Preoperative High-Dose Steroid Has Long-Term Beneficial Effects for Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Syuichi Tetsuka

    2013-01-01

    Full Text Available Previous studies addressing preoperative steroid treatment have revealed that control of myasthenia gravis (MG with steroids prior to surgery appeared to stabilize postoperative status. The purpose of our study was to clarify the clinical benefits of the preoperative programmed high-dose steroid treatment on the long-term outcomes of MG patients. We retrospectively reviewed the records of 171 MG patients who were followed up after undergoing thymectomy in our hospital between 1988 and 2006. One hundred and thirteen patients in the programmed treatment group had received preoperative steroid treatment, while 58 patients received no steroid treatment during the preoperative period. Clinical remission, which was defined as the achievement of the modified pharmacologic remission (PR for at least 1 year, and clinical benefits were compared between the two groups. With regard to the remission after thymectomy, Kaplan-Meier life-table curves for patients in the preoperative steroid treatment group versus those for patients in the no steroid preoperative treatment group revealed a significantly higher probability of the PR in the preoperative steroid treatment group (log-rank test, P<0.01. This study might be the first, as per our knowledge, to indicate that preoperative programmed high-dose steroid treatment has long-term beneficial effects for MG patients.

  1. High-dose steroid therapy for idiopathic optic perineuritis: a case series

    Directory of Open Access Journals (Sweden)

    Mimura Tatsuya

    2010-12-01

    Full Text Available Abstract Introduction It has been reported that the prognosis of optic perineuritis may be poor when initiation of treatment is delayed. Here we report the successful treatment of three patients with idiopathic optic perineuritis, including two in whom initiation of therapy was delayed. Case presentation Three Japanese patients (two women aged 73 and 66 years, and one man aged 27 years presented with loss of vision (for five months, several months, and two months respectively and pain on eye movement in the third case only, and were diagnosed as having idiopathic optic perineuritis. Fat-suppressed T2-weighted magnetic resonance images showed high signal intensity areas around the affected optic nerves, suggesting the presence of optic perineuritis. Two patients received steroid pulse therapy and the third was given high-dose steroid therapy. The visual acuity improved in all three cases. Conclusion High-dose steroid therapy may be effective for idiopathic perineuritis in patients without optic nerve atrophy, even if initial treatment (including moderate-dose steroids has failed.

  2. Donut-shaped high-dose configuration for proton beam radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, H.P.; Lomax, A.J. [Div. of Radiation Medicine, Paul Scherrer Inst., Villigen PSI (Switzerland)

    2005-01-01

    Background: the authors report on the conception and first clinical application of a donut-shaped high-dose configuration for proton therapy (PT). This approach allows one to intensify target volume dose coverage for targets encompassing a critical, dose-limiting structure - like here, the cauda equina -, whilst delivering minimal dose to other healthy structures surrounding the target, thereby reducing the integral dose. Methods and results: intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE. Integral dose was lower by a factor of 3.3 as compared to intensity-modulated radiotherapy with photons (IMXT). Conclusion: IMPT and spot scanning technology allow a potentially clinically useful approach which is also applicable to spare other critical structures passing through a target volume, including spinal cord, optic nerves, chiasm, brain stem, or urethra. (orig.)

  3. High doses of pseudoephedrine hydrochloride accelerate onset of CNS oxygen toxicity seizures in unanesthetized rats.

    Science.gov (United States)

    Pilla, R; Held, H E; Landon, C S; Dean, J B

    2013-08-29

    Pseudoephedrine (PSE) salts (hydrochloride and sulfate) are commonly used as nasal and paranasal decongestants by scuba divers. Anecdotal reports from the Divers Alert Network suggest that taking PSE prior to diving while breathing pure O₂ increases the risk for CNS oxygen toxicity (CNS-OT), which manifests as seizures. We hypothesized that high doses of PSE reduce the latency time to seizure (LS) in unanesthetized rats breathing 5 atmospheres absolute (ATA) of hyperbaric oxygen. Sixty-three male rats were implanted with radio-transmitters that recorded electroencephalogram activity and body temperature. After ≥7-day recovery, and 2 h before "diving", each rat was administered either saline solution (control) or PSE hydrochloride intragastrically at the following doses (mg PSE/kg): 0, 40, 80, 100, 120, 160, and 320. Rats breathed pure O₂ and were dived to 5ATA until the onset of behavioral seizures coincident with neurological seizures. LS was the time elapsed between reaching 5ATA and exhibiting seizures. We observed a significant dose-dependent decrease in the LS at doses of 100-320 mg/kg, whereas no significant differences in LS from control value were observed at doses ≤80 mg/kg. Our findings showed that high doses of PSE accelerate the onset of CNS-OT seizures in unanesthetized rats breathing 5ATA of poikilocapnic hyperoxia. Extrapolating our findings to humans, we conclude that the recommended daily dose of PSE should not be abused prior to diving with oxygen-enriched gas mixes or pure O₂.

  4. Treatment Of Pemphigus Vulgaris With Brief, High-Dose Intravenous Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Farshchian Mahmood

    2004-01-01

    Full Text Available Background: Glucocorticoid therapy remains the mainstay of treatment in pemphigus vulgaris although controversy exists about the optimal regiman. This study was conducted to compare the efficacy of routine oral prednisolone with high dose intravenous glucocorticoids in treatment of pemphigus vulgaris. Methods: A total of 55 patients with pemphigus vulgaris was enrolled in the study. The diagnosis of pemphigus vulgaris was confirmed histologically. The patients were divided into two groups: Group A (26 Patients was treated with high-dose intravenous glucocorticoids and group B or control group (29 patients was treated with routine oral prednisolone. Both groups were followed for at least 20 months after initiation of treatment. Results: The results showed complete clinical cure (without relapse in 20 months follow up in 81% of cases in group A and in 69% of cases in group B (p<0.05. The mean + SD prednisolone daily dose during the 20 months follow up after initiation of treatment was 12+0.38 for A and 15.3 + 1.33 for control group (p<0.05.

  5. The use of very high-doses of baclofen for the treatment of alcohol-dependence: a case series.

    Directory of Open Access Journals (Sweden)

    Renaud ede Beaurepaire

    2014-10-01

    Full Text Available 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, that is to say, more than 300mg per day. The analysis of the charts shows that the very high doses baclofen were justified in almost all the cases. Side effects are analyzed.

  6. [Toxic complications of high-dose polychemotherapy in the transplantation of bone marrow and of peripheral blood stem cells].

    Science.gov (United States)

    Uss, A L; Milanovich, N F; Skriagin, A E; Zmachinskiĭ, V A; Snegir', V M; Batan, Z E; Komarovskaia, M E; Mitskevich, P B; Levin, V I

    1997-01-01

    The authors propose their own system of assessment of high-dose polychemotherapy toxicity. The system was applied to toxic complications of high-dose polychemotherapy in 31 patients with hematological malignancies subjected to allogenic, autologous bone marrow transplantation and transplantation of stem cells from peripheral blood within the scope of different protocols of high-dose polychemotherapy in conditioning regimen. A special scale developed in the Belarus Center for Bone Marrow Transplantation basing on the above system provides prediction of survival in early post-transplantation period.

  7. AMBITION-cm: intermittent high dose AmBisome on a high dose fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa: study protocol for a randomized controlled trial

    OpenAIRE

    Molefi, M; Chofle, AA; Molloy, SF; Kalluvya, S; Changalucha, JM; Cainelli, F; Leeme, T; Lekwape, N; Goldberg, DW; Haverkamp, M; Bisson, GP; Perfect, JR; Letang, E.; Fenner, L.; Meintjes, G

    2015-01-01

    Background Cryptococcal meningitis (CM) is a leading cause of mortality among HIV-infected individuals in Africa. Poor outcomes from conventional antifungal therapies, unavailability of flucytosine, and difficulties administering 14 days of amphotericin B are key drivers of this mortality. Novel treatment regimes are needed. This study examines whether short-course high-dose liposomal amphotericin B (AmBisome), given with high dose fluconazole, is non-inferior (in terms of microbiological and...

  8. Clinical and biochemical characteristics of Cushing’s disease with different suppression rates by high-dose dexamethasone

    Institute of Scientific and Technical Information of China (English)

    唐志清

    2013-01-01

    Objective To analyze the clinical and biochemical characteristics of Cushing’s disease with different suppression rates by high-dose dexamethasone.Methods Two hundred and two consecutive patients with

  9. Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound

    Directory of Open Access Journals (Sweden)

    Yang FY

    2012-02-01

    Full Text Available Feng-Yi Yang1, Ming-Che Teng1, Maggie Lu2, Hsiang-Fa Liang2, Yan-Ru Lee1, Chueh-Chuan Yen3, Muh-Lii Liang4,5, Tai-Tong Wong51Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 2Drug Delivery Laboratory, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 3Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, 4Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, 5Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, TaiwanBackground: High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1-conjugated liposomes selectively to brain tumors.Methods: Firefly luciferase (Fluc-labeled human GBM8401 glioma cells were implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin concentration in the treated brains quantified by fluorometer. Growth of the labeled glioma cells was monitored through noninvasive bioluminescence imaging and finally the brain tissue was histologically examined after sacrifice.Results: Compared with the control group, the animals treated with 5 mg/kg injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin followed by repeated pulsed HIFU not only showed significantly enhanced accumulation of drug at the sonicated tumor site but also a significantly elevated tumor-to-normal brain drug

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

    Energy Technology Data Exchange (ETDEWEB)

    Moussazadeh, Nelson [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katsoulakis, Evangelia [Department of Radiation Oncology, New York Methodist Hospital, Brooklyn, New York (United States); Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bilsky, Mark H. [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Laufer, Ilya, E-mail: lauferi@mskcc.org [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States)

    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

  11. Stress of dying is not suppressed by high-dose morphine or by dementia.

    Science.gov (United States)

    Erkut, Zeynel A; Klooker, Tamira; Endert, Eric; Huitinga, Inge; Swaab, Dick F

    2004-01-01

    Hypothalamo-pituitary-adrenal (HPA)-axis activation is a response of the organism to psychological and physical stress, resulting in elevated levels of glucocorticoids, mainly cortisol in humans. In our previous studies we found post-mortem blood and cerebrospinal fluid (CSF) cortisol levels to be up to 20-fold higher than in vivo levels. Since clinical observations point to similar strong elevations of cortisol in fatally ill patients, we suggested that the high post-mortem cortisol levels might be due to the stress during the process of dying. We hypothesized that if the cortisol rise during dying is due to the psychological stress of the impending death, then the rise in cortisol should be inversely proportional to the degree of dementia, and that high-dose morphine giving analgesia, sedation, and sleep would suppress this response. Therefore, we measured the cortisol levels by radioimmunoassay (RIA) in the post-mortem CSF of 85 Alzheimer patients and 52 controls. In addition, post-mortem serum cortisol of 17 subjects from the Alzheimer group and nine from the control group were measured. The Alzheimer patients were subdivided according to their degree of dementia, as scored on the Reisberg Scale, before their death. All groups were further analyzed for the effect of morphine treatment, as well as for the effects of the confounding factors like age, gender, time, and season of death. Alzheimer patients had significantly higher cortisol levels than controls, both in CSF (mean (nmol/l)+/-SEM: 482+/-32 vs 285+/-30, respectively, plevel of the severely demented Alzheimer group was even significantly higher than that of mildly demented group (508+/-35 vs 225+/-65, p=0.024) and controls (plevels correlated positively with the degree of dementia in the Alzheimer group (r=0.236, p=0.035). High-dose morphine did not cause a suppression of cortisol rise, neither in controls nor in Alzheimer patients. Our results indicate that the extreme elevations of cortisol levels

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

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Bhavana [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Patel, Firuza D., E-mail: firuzapatel@gmail.com [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Chakraborty, Santam; Sharma, Suresh C.; Kapoor, Rakesh [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Aprem, Abi Santhosh [Corporate R and D Division, HLL Lifecare Limited, Karamana, Trivandrum (India)

    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

  13. Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy

    OpenAIRE

    Nakano, Kenji; SATO, YASUYOSHI; TOSHIYASU, TAKASHI; SATO, YUKIKO; INAGAKI, LINA; Tomomatsu, Junichi; Sasaki, Toru; SHIMBASHI, WATARU; FUKUSHIMA, HIROFUMI; YONEKAWA, HIROYUKI; Mitani,Hiroki; Kawabata, Kazuyoshi; Takahashi, Shunji

    2015-01-01

    Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tole...

  14. High-dose misoprostol as an alternative therapy after failed medical abortion.

    Science.gov (United States)

    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.

  15. [Efficacy of early combined high-dose steroid + PGE1 treatment for sudden deafness].

    Science.gov (United States)

    Kubota, Toshinori; Watanabe, Tomoo; Yokota, Masashi; Ito, Tsukasa; Aoyagi, Masaru

    2012-05-01

    The efficacy of combined high-dose steroid and PGE1 treatment initiated immediately after the onset of sudden deafness was analyzed with the outcome of 174 patients begun on treatment within 7 days of the onset of sudden deafness. Four potential prognostic factors (days from onset to treatment, age, initial hearing level, presence of vertigo) and hearing outcome were examined with a multiple logistic regression analysis. Days from onset to treatment and age significantly correlated with hearing improvement. The efficacy of the treatment of patients begun on treatment within 3 days of the onset was significantly better than that of patients on treatment 4-7 days after the onset (p sudden deafness, and started within 3 days of the onset of sudden deafness in patients 50 years old and older.

  16. Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate

    DEFF Research Database (Denmark)

    Niekerk, P.B. van Kooten; Schmiegelow, K.; Schroeder, H.

    2008-01-01

    BACKGROUND AND OBJECTIVE: Through interruption of maintenance treatment with 6-mercaptopurine (6MP), toxicity after high-dose methotrexate (HDMTX) may compromise the efficiency of the treatment of children with acute lymphocytic leukaemia (ALL). We investigated the influence of polymorphisms......-intensity co-treatment (6MP 75 mg/m(2)/d + MTX 20 mg/m(2)/wk) was found associated with increased odds of haematological toxicity (OR's: 3.47-7.88; P's: fever (OR = 2.2; P = 0.004) and interruption maintenance treatment (OR = 15.9; P ....006-0.027), fever (OR = 2.65; P = 0.037) and interruption of maintenance treatment (OR = 3.04; P = 0.032). No convincing associations were found between the MTHFR C677T or A1298C polymorphisms and toxicity. CONCLUSION: Our findings demonstrate that toxicity after HDMTX is influenced by coadministrated...

  17. High dose level radiation therapy for local tumour control in esthesioneuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Guedea, F. [Universidad Autonoma de Barcelona (Spain); Limbergen, E. Van; Bogaert, W. Van Den [University Hospital, Leuven (Belgium). Dept. of Radiotherapy

    1994-12-31

    Esthesioneuroblastoma is an uncommon tumour of neural crest origin arising in the nasal cavity. This paper is a retrospective review of 7 patients with esthesioneuroblastoma treated at a single institution from May 1974 to July 1990. 5 patients were treated with radiation therapy alone and 2 patients were irradiated after surgical resection. No local or regional occurrence was observed in any patient at 6 months, or at 1, 3, 6, 11.5 and 12 years following treatment. One patient died of intercurrent disease 6 years after radiation therapy, 2 patients died of disease, 1 of distant metastasis at 6 months and the other patient of meningeal carcinomatosis and distant metastases 1 year after treatment. One patient is alive with distant metastases 1 year after treatment. None of the patients experienced significant complications of irradiation. High-dose irradiation (60 Gy or more) alone or in combination with resection is an effective local treatment modality for esthesioneuroblastoma. (author).

  18. Effect of high dose of steroid on plateletcount in acute stage of dengue Fever with thrombocytopenia.

    Science.gov (United States)

    Shashidhara, K C; Murthy, K A Sudharshan; Gowdappa, H Basavana; Bhograj, Abhijith

    2013-07-01

    Dengue infection is the most rapidly spreading mosquito-borne viral disease in the world and an estimated 50 million dengue infections reported annually. The pathogenesis of Thrombocytopenia in dengue fever (DF) is not clearly understood. Increased peripheral destruction of antibody coated platelets and acute bone marrow suppression were strongly suspected as the possible mechanism. This often leads to life threatening dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Steroids are used in the treatment of Idiopathic thrombocytopenic purpura to increase the platelet count which is mediated by auto antibodies .This hypothesis would support the use of steroids in dengue fever. The objective of this study was to test whether an intravenous high dose dexamethasone was efficacious in increasing the platelet count in acute stage of dengue fever with thrombocytopenia. During the study period between June 2010 - 2011 in JSS Hospital Mysore, 127 patients were screened for dengue fever with thrombocytopenia (dengue fever.

  19. Long-term high-dose oral morphine in phantom limb pain with no addiction risk

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-01-01

    Full Text Available 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.

  20. No seasonal accumulation of resistant P. falciparum when high-dose chloroquine is used

    DEFF Research Database (Denmark)

    Ursing, Johan; Kofoed, Poul-Erik; Rodrigues, Amabelia

    2009-01-01

    BACKGROUND: Potentially chloroquine resistant P. falciparum, identified by the 76T haplotype in the chloroquine resistance transporter (pfcrt 76T), are highly prevalent throughout Africa. In Guinea-Bissau, normal and double dose chloroquine have respective efficacies of 34% and 78% against P...... increase of pfcrt 76T if the high doses of CQ commonly used are effective. METHODS AND FINDINGS: P. falciparum parasite density, age, sex, the proportion of chloroquine resistance associated haplotypes pfcrt 76T and P. falciparum multidrug resistance gene 1 86Y were assessed in 988 samples collected from...... children between 2002 and 2007. There was no seasonal accumulation of any allele. During the high and low transmission periods the pfcrt 76T proportions were 24% (95% CI, 21-27%) and 26% (95% CI, 20-33%). There was no significant change of pfcrt 76T (OR 1.05, 95% CI; 0.94-1.16 p = 0.39) or pfmdr1 86Y (OR 0...

  1. Experiences of high dose rate interstitial brachytherapy for carcinoma of the mobile tongue

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Hiroshi; Inoue, Toshihiko; Yamazaki, Hideya (Osaka Univ. (Japan). Faculty of Medicine) (and others)

    1994-03-01

    Interstitial brachytherapy was conducted for mobile tongue carcinoma using a high dose rate remote afterloading machine with small [sup 192]I source. Detailed method, named as 'linked double-botton technique', is to approach from submandibular skin by an open-ended stainless steel needles to the tongue lesion, and to replace each needle into flexible nylon tube from the oral cavity. Delivered dose was 60 Gy/10 Fr./5-6 days at the distance 5 mm from the source plane. Ten patients with mobile tongue carcinoma Tl-2N0 were treated with this method from October 1991 through August 1992. Local was uncontrolled in one patient, in whom the lesion was combined with leukoplakia at both lateral borders of the tongue. This was in accordance with the result in low dose rate treatment. This can be a substitute to low dose rate system for treatment of mobile tongue carcinoma. (author).

  2. Characterization of High Dose Mn, Fe, and Ni implantation into p-GaN

    CERN Document Server

    Pearton, S J; Thaler, G; Abernathy, C R; Theodoropoulou, N; Hebard, A F; Chu, S N G; Wilson, R G; Zavada, J M; Polyakov, A Y; Osinsky, A V; Norris, P E; Chow, P P; Wowchack, A M; Hove, J M V; Park, Y D

    2002-01-01

    The magnetization of p-GaN or p-AlGaN/GaN superlattices was measured after implantation with high doses (3-5x10 sup 1 sup 6 cm sup - sup 2) of Mn, Fe, or Ni and subsequent annealing at 700-1000 deg. C. The samples showed ferromagnetic contributions below temperatures ranging from 190-250 K for Mn to 45-185 K for Ni and 80-250 K for Fe. The use of superlattices to enhance the hole concentration did not produce any change in ferromagnetic ordering temperature. No secondary phase formation was observed by x-ray diffraction, transmission electron microscopy, or selected area diffraction pattern analysis for the doses we employed.

  3. High-dose ifosfamide and mesna in advanced breast cancer. A phase II study.

    Science.gov (United States)

    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.

  4. Polycarbonate-based benzo-δ-sultam films for high-dose dosimetry in radiation processing

    Energy Technology Data Exchange (ETDEWEB)

    Feizi, Shazad [University of Tehran, Tehran (India). School of Chemistry; Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ziaie, Farhood [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ghandi, Mehdi [University of Tehran, Tehran (India). School of Chemistry

    2015-05-01

    In this work characteristics of the polycarbonate films with 20 μm in thickness containing different weight percentage of Benzo-δ-sultam were studied for use as a high dose dosimetry system in radiation processing facilities. The sensitivity of the dosimeters and the linearity of dose-response curves were investigated under {sup 60}Co γ-rays in a dose range of 0-100 kGy, and obtained results were compared with the commercial CTA and FWT film dosimeters. The results show that the absorbance at 348 nm depends linearly on the dose in the investigated dose range. The effects of pre-irradiation (shelf-life) and post-irradiation storage in dark and in indirect sunlight are also discussed. The results show that the dosimeters characteristics are stable within 1% at 25 C, 3 months after the irradiation.

  5. Distributive shock due to systemic capillary leak syndrome treated with high-dose immunosuppression.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. MCz diode response as a high-dose gamma radiation dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, F. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Goncalves, J.A.C. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Depto. de Fisica, Pontificia Universidade Catolica de Sao Paulo-PUC/SP, Rua Marques de Paranagua no 111-01303 050 Sao Paulo/SP (Brazil); Khoury, H.J. [Nuclear Energy Department, Universidade Federal de Pernambuco-UFPE, Av. Prof. Luiz Freire no 1000-50740 540 Recife/PE (Brazil); Napolitano, C.M. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Haerkoenen, J. [Helsinki Institute of Physics-HIP, University of Helsinki, 00014 Helsinki (Finland); Bueno, C.C. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Depto. de Fisica, Pontificia Universidade Catolica de Sao Paulo-PUC/SP, Rua Marques de Paranagua no 111-01303 050 Sao Paulo/SP (Brazil)], E-mail: ccbueno@ipen.br

    2008-02-15

    This work presents the preliminary results obtained with a high-resistivity magnetic Czochralski (MCz) silicon diode processed at the Helsinki Institute of Physics as a high-dose gamma dosimeter in radiation processing. The irradiation was performed using a {sup 60}Co source (Gammacell 220, MDS Nordion) within total doses from 100 Gy up to 3 kGy at a dose rate of 3 kGy/h. In this interval, the dosimetric response of the diode is linear with a correlation coefficient (r{sup 2}) higher than 0.993. However, without any irradiation procedure, the device showed a small sensitivity dependence on the accumulated dose. For total dose of 3 kGy, the observed decrease was about 2%. To clarify the origin of this possible radiation damage effect, some studies are under way.

  8. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

    Science.gov (United States)

    Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

    2013-01-01

    Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

  9. Quality control of high-dose-rate brachytherapy: treatment delivery analysis using statistical process control.

    Science.gov (United States)

    Able, Charles M; Bright, Megan; Frizzell, Bart

    2013-03-01

    Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles with 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

    Energy Technology Data Exchange (ETDEWEB)

    Able, Charles M., E-mail: cable@wfubmc.edu [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Bright, Megan; Frizzell, Bart [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States)

    2013-03-01

    Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles with 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.

  11. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    Science.gov (United States)

    Moral, Angel; Moreno, Victoria; Girón, Francisco; El-Qutob, David; Moure, José D; Alcántara, Manuel; Padial, Antonia; Oehling, Alberto G; Millán, Carmen; de la Torre, Fernando

    2016-01-01

    Background Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. Patients and methods A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. Results The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). Conclusion In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. PMID:27418842

  12. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin.

    Science.gov (United States)

    Lundvig, Ditte M S; Pennings, Sebastiaan W C; Brouwer, Katrien M; Mtaya-Mlangwa, Matilda; Mugonzibwa, Emeria; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-08-15

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between epidermal keratinocytes and dermal fibroblasts are essential. We previously demonstrated that curcumin increased reactive oxygen species (ROS) formation and apoptosis in dermal fibroblasts, which could be prevented by pre-induction of the cytoprotective enzyme heme oxygenase (HO)-1. To better understand the effects of curcumin on wound repair, we now assessed the effects of high doses of curcumin on the survival of HaCaT keratinocytes and the role of the HO system. We exposed HaCaT keratinocytes to curcumin in the presence or absence of the HO-1 inducers heme (FePP) and cobalt protoporphyrin (CoPP). We then assessed cell survival, ROS formation, and caspase activation. Curcumin induced caspase-dependent apoptosis in HaCaT keratinocytes via a ROS-dependent mechanism. Both FePP and CoPP induced HO-1 expression, but only FePP protected against curcumin-induced ROS formation and caspase-mediated apoptosis. In the presence of curcumin, FePP but not CoPP induced the expression of the iron scavenger ferritin. Together, our data show that the induction of ferritin, but not HO, protects HaCaT keratinocytes against cytotoxic doses of curcumin. The differential response of fibroblasts and keratinocytes to high curcumin doses may provide the basis for improving curcumin-based wound healing therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The transit dose component of high dose rate brachytherapy: Direct measurements and clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Bastin, K.T.; Podgorsak, M.B.; Thomadsen, B.R. (Univ. of Wisconsin Hospitals and Clinics, Madison, WI (United States))

    1993-07-15

    The purpose was to measure the transit dose produced by a moving high dose rate brachytherapy source and assess its clinical significance. The doses produced from source movement during Ir-192 HDR afterloading were measured using calibrated thermoluminescent dosimeter rods. Transit doses at distances of 0.5-4.0 cm from an endobronchial applicator were measured using a Lucite phantom accommodating 1 x 1 x 6 mm thermoluminescent rods. Surface transit dose measurements were made using esophageal and endobronchial catheters, a gynecologic tandem, and an interstitial needle. No difference was detected in thermoluminescent dosimeter rod responses to 4 MV and Ir-192 spectra (427 nC/Gy) in a range of dose between 2 and 300 cGy. The transit dose at 0.5 cm from an endobronchial catheter was 0.31 cGy/(Curie-fraction) and followed an inverse square fall-off with increasing distance. Surface transit doses ranged from 0.38 cGy/(Curie-fraction) for an esophageal catheter to 1.03 cGy/(Curie-fraction) for an endobronchial catheter. Source velocity is dependent on the interdwell distance and varies between 220-452 mm/sec. A numeric algorithm was developed to calculate total transit dose, and was based on a dynamic point approximation for the moving high dose rate source. This algorithm reliably predicted the empirical transit doses and demonstrated that total transit dose is dependent on source velocity, number of fractions, and source activity. Surface transit doses are dependent on applicator diameter and wall material and thickness. Total transit doses within or outside the desired treatment volume are typically <100 cGy, but may exceed 200 cGy when using a large number of fractions with a high activity source. 9 refs., 8 figs., 1 tab.

  14. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

    Science.gov (United States)

    Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

    2013-11-01

    The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue: A Preliminary Report.

    Science.gov (United States)

    Yennurajalingam, Sriram; Reddy, Akhila; Tannir, Nizar M; Chisholm, Gary B; Lee, Richard Tsong; Lopez, Gabriel; Escalante, Carmen P; Manzullo, Ellen F; Frisbee Hume, Susan; Williams, Janet L; Cohen, Lorenzo; Bruera, Eduardo

    2015-09-01

    Cancer-related fatigue (CRF) is the most common and severe symptom in patients with cancer. The number and efficacy of available treatments for CRF are limited. The objective of this preliminary study was to assess the safety of high-dose Panax ginseng (PG) for CRF. In this prospective, open-label study, 30 patients with CRF (≥4/10) received high-dose PG at 800 mg orally daily for 29 days. Frequency and type of side effects were determined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, Edmonton Symptom Assessment System (ESAS), and Hospital Anxiety and Depression Scale (HADS) were assessed at baseline, day 15, and day 29. Global Symptom Evaluation (GSE) was assessed at day 29. Of the 30 patients enrolled, 24 (80%) were evaluable. The median age was 58 years; 50% were females, and 84% were white. No severe (≥grade 3) adverse events related to the study drug were reported. Of the 24 evaluable patients, 21 (87%) had an improved (by ≥3 points) FACIT-F score by day 15. The mean ESAS score (standard deviation) for well-being improved from 4.67 (2.04) to 3.50 (2.34) (P = .01374), and mean score for appetite improved from 4.29 (2.79) to 2.96 (2.46) (P = .0097). GSE score of PG for fatigue was ≥3 in 15/24 patients (63%) with median improvement of 5. PG is safe and improves CRF fatigue as well as overall quality of life, appetite, and sleep at night. Randomized controlled trials of PG for CRF are justified. © The Author(s) 2015.

  16. The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible.

    Science.gov (United States)

    Monson, Laura A; Cavaliere, Christi M; Deshpande, Sagar S; Ayzengart, Alexander L; Buchman, Steven R

    2012-09-07

    The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague-Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.

  17. Hypertension, high-dose corticosteroids, and renal infiltration in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Andry Juliansen

    2014-11-01

    Full Text Available Background Hypertension is a rarely recognized complication of acute lymphoblastic leukemia (ALL. The incidence of hypertension in ALL patients in Indonesia remains unknown, but the most common risk factors are corticosteroid use during induction-phase chemotherapy and renal leukemic infiltration. Objective To determine the incidence of hypertension in children with ALL, and to assess for associations of high-dose corticosteroids, renal infiltration, and hyperleukocytosis to hypertension. Methods This was a cross-sectional study involving 100 children aged 2-18 years. Subjects were newly diagnosed ALL patients and those underwent induction-phase chemotherapy in the Pediatric Ward or Outpatient Clinic at Cipto Mangunkusumo or Dharmais Hospitals. Results Hypertension occurred in 6 (10% of 60 newly diagnosed ALL patients and 8 (20% of 40 patients who had received high-dose corticosteroids, but the difference was not statistically significant (OR=2.25; 95%CI 0.72 to 7.07; P=0.239. Hypertension was reported in 8 of 29 subjects who received dexamethasone, but in none of the subjects who received prednisone. However, the difference in these subgroups was also not statistically significant. Renal enlargement was found in 1 of 14 hypertensive patients, but it was not associated with hypertension (OR=0.80; 95%CI 0.52 to 1.24; P=0.417. Hyperleukocytosis was also not associated with hypertension (OR= 0.79; 95% CI 0.20 to 3.11; P=1.000. Conclusion The incidence of hypertension in ALL patients was 14%. Hypertension is not associated with renal infiltration or hyperleukocytosis. Furthermore, hypertension is not associated with corticosteroid dose, though is found only in subjects who receive dexamethasone. [Paediatr Indones. 2014;54:372-6.].

  18. Initial Australian experience with high dose indium-111 pentreotide therapy in progressive, symptomatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, R.J.; Keady, M.A.; Johnson, V. [The Peter McCallum Cancer Institute, Melbourne, VIC (Australia). Department of Nuclear Medicine and PET

    1998-06-01

    Full text: Neuroendocrine tumours variably express somatostatin receptors enabling imaging using somatostatin analogues, including In-111 pentreotide. Due to the emission of Auger electrons in the decay of In-1 11, there is the potential to use this agent for therapy. Based on favourable experience with high dose In-111 pentreotide therapy a the University of Rotterdam, a prospective trial of this treatment was performed in 6 patients with progressive, symptomatic neuroendocrine tumours (carcinoid in 4 patients and glucagonoma in 2 patients). Patients were selected based on the presence of uptake at multiple sites on In-1 11 pentreotide scanning with intensity equal to or greater than splenic activity. Follow-up of haematology, endocrine and renal function was performed and serial imaging correlation of index lesions was performed. Three treatments of approximately 6.5 GBq of In-111 pentreotide were administered to each patient over 3-5 months. One pt with bone metastases from carcinoid had an initial flare in symptoms 1 week following treatment but subsequent palliation which lasted 6 months before requiring local radiotherapy. The three remaining carcinoid patients had symptomatic improvement and reduced 5-HIAA levels when abnormal at baseline. Both patients with glucagonoma had symptomatic improvement and reduction in glucagon levels. No patients had evidence of disease progression up to 6 months post-treatment in index lesions with high In-1 11 pentreotide uptake. One lesion with low uptake progressed despite regression in other lesions with high uptake in the same patient Minor transient lymphopaenia was seen following treatment but no clinically significant toxicity was noted. These preliminary results complement European data suggesting good palliation from high dose In-111 pentreotide therapy in patients with high somatostatin receptor expression

  19. Usefulness of high doses of glucocorticoids and hyperbaric oxygen therapy in sudden sensorineural hearing loss treatment.

    Science.gov (United States)

    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

  20. Cancer-associated fibroblasts from lung tumors maintain their immunosuppressive abilities after high-dose irradiation.

    Science.gov (United States)

    Gorchs, Laia; Hellevik, Turid; Bruun, Jack-Ansgar; Camilio, Ketil-Andre; Al-Saad, Samer; Stuge, Tor-Brynjar; Martinez-Zubiaurre, Inigo

    2015-01-01

    Accumulating evidence supports the notion that high-dose (>5 Gy) radiotherapy (RT) regimens are triggering stronger pro-immunogenic effects than standard low-dose (2 Gy) regimens. However, the effects of RT on certain immunoregulatory elements in tumors remain unexplored. In this study, we have investigated the effects of high-dose radiotherapy (HD-RT) on the immunomodulating functions of cancer-associated fibroblasts (CAFs). Primary CAF cultures were established from lung cancer specimens derived from patients diagnosed for non-small cell lung cancer. Irradiated and non-irradiated CAFs were examined for immunomodulation in experiments with peripheral blood mononuclear cells from random, healthy donors. Regulation of lymphocytes behavior was checked by lymphocyte proliferation assays, lymphocyte migration assays, and T-cell cytokine production. Additionally, CAF-secreted immunoregulatory factors were studied by multiplex protein arrays, ELISAs, and by LC-MS/MS proteomics. In all functional assays, we observed a powerful immunosuppressive effect exerted by CAF-conditioned medium on activated T-cells (p > 0.001), and this effect was sustained after a single radiation dose of 18 Gy. Relevant immunosuppressive molecules such as prostaglandin E2, interleukin-6, and -10, or transforming growth factor-β were found in CAF-conditioned medium, but their secretion was unchanged after irradiation. Finally, immunogenic cell death responses in CAFs were studied by exploring the release of high motility group box-1 and ATP. Both alarmins remained undetectable before and after irradiation. In conclusion, CAFs play a powerful immunosuppressive effect over activated T-cells, and this effect remains unchanged after HD-RT. Importantly, CAFs do not switch on immunogenic cell death responses after exposure to HD-RT.

  1. Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson's disease.

    Science.gov (United States)

    Devos, D; Krystkowiak, P; Clement, F; Dujardin, K; Cottencin, O; Waucquier, N; Ajebbar, K; Thielemans, B; Kroumova, M; Duhamel, A; Destée, A; Bordet, R; Defebvre, L

    2007-05-01

    Therapeutic management of gait disorders in patients with advanced Parkinson's disease (PD) can sometimes be disappointing, since dopaminergic drug treatments and subthalamic nucleus (STN) stimulation are more effective for limb-related parkinsonian signs than for gait disorders. Gait disorders could also be partly related to norepinephrine system impairment, and the pharmacological modulation of both dopamine and norepinephrine pathways could potentially improve the symptomatology. To assess the clinical value of chronic, high doses of methylphenidate (MPD) in patients with PD having gait disorders, despite their use of optimal dopaminergic doses and STN stimulation parameters. Efficacy was blindly assessed on video for 17 patients in the absence of L-dopa and again after acute administration of the drug, both before and after a 3-month course of MPD, using a Stand-Walk-Sit (SWS) Test, the Tinetti Scale, the Unified Parkinson's Disease Rating Scale (UPDRS) part III score and the Dyskinesia Rating Scale. An improvement was observed in the number of steps and time in the SWS Test, the number of freezing episodes, the Tinetti Scale score and the UPDRS part III score in the absence of L-dopa after 3 months of taking MPD. The L-dopa-induced improvement in these various scores was also stronger after the 3-month course of MPD than before. The Epworth Sleepiness Scale score fell dramatically in all patients. No significant induction of adverse effects was found. Chronic, high doses of MPD improved gait and motor symptoms in the absence of L-dopa and increased the intensity of response of these symptoms to L-dopa in a population with advanced PD.

  2. High dose rate endobronchial brachytherapy. Results and complications in 189 patients

    Energy Technology Data Exchange (ETDEWEB)

    Taulelle, M.; Chauvet, B.; Vincent, P.; Felix-Faure, C.; Buciarelli, B.; Garcia, R.; Brewer, Y.; Reboul, F. [Clinique Sainte Catherine, Dept. of Radiation Therapy, Avignon (France)

    1998-02-01

    The purpose of this study was to determine the benefit of high dose rate endobronchial brachytherapy in the treatment of obstructive lung cancer. Between September 1990 and March 1995, 189 patients with bronchogenic carcinoma were treated with high dose rate endobronchial brachytherapy. Most patients (63.3%) had received prior treatment and presented with symptomatic bronchial obstruction due to either recurrent or residual endobronchial disease. A small group (12%) was medically unfit for either surgical resection or thoracic radiotherapy and benefited from endobronchial brachytherapy alone for small endobronchial tumours. The remainder of the patients had not been treated previously and endobronchial brachytherapy was performed for life-threatening symptoms requiring emergency obstruction relief before other therapy. Treatment was performed weekly and consisted of three to four 8 to 10 Gy fractions at a radius of 10 mm from the centre of the source. Major symptomatic relief was obtained for haemoptysis (74%), dyspnoea (54%), and cough (54%). Complete endoscopic response was observed in 54% of cases. Median survival was 7 months for the entire group. For small, strictly endobronchial tumours, complete response rate was 96%, median survival 17 months, and 30 month survival 46%, with a plateau starting at 18 months. Grade 3 to 4 toxicities occurred at a rate of 17% and included massive haemoptysis (n=13), bronchial stenosis (n=12), soft tissue necrosis (n=8), and bronchial fistula (n=3). By univariate analysis, no factor was found to be predictive of late pulmonary toxicity. The present study confirms the usefulness of endobronchial brachytherapy in alleviating symptoms caused by endobronchial recurrence of bronchogenic carcinoma. In addition, this therapy can be tried with curative intent in patients who present with small endobronchial tumours and are not candidates for other forms of therapy. (au). 23 refs.

  3. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jee Suk [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Wang, Michael L.C. [Department of Radiation Oncology, National Cancer Centre (Singapore); Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: jsseong@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  4. Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

    Science.gov (United States)

    Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

    2016-11-08

    Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

  5. Factors associated with antipsychotic polypharmacy and high-dose antipsychotics among individuals receiving compulsory treatment in the community.

    Science.gov (United States)

    Gisev, Natasa; Bell, J Simon; Chen, Timothy F

    2014-06-01

    Community treatment orders (CTOs) are a form of compulsory treatment of individuals with a mental illness in the community. The objectives of this study were to determine the demographic, clinical, and treatment plan factors associated with antipsychotic polypharmacy and high-dose antipsychotics among individuals issued with a CTO. This was a secondary analysis of all 377 individuals who were prescribed an antipsychotic, extracted from a retrospective study of 378 individuals issued with a CTO by the New South Wales Mental Health Review Tribunal in Australia in 2009. Deidentified information relating to individuals' treatment plans, demographic, and clinical details were systematically extracted. Of the 377 individuals, 121 (32%) were prescribed antipsychotic polypharmacy and 101 (27%) high-dose antipsychotics. Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for factors associated with antipsychotic polypharmacy and high-dose antipsychotics were computed using binary logistic regression. There was a strong association between the use of antipsychotic polypharmacy and high-dose antipsychotics (P polypharmacy and high-dose antipsychotics in adjusted models. Although first-generation long-acting injectable antipsychotics and clozapine were associated with antipsychotic polypharmacy (adjusted OR, 9.12; 95% CI, 4.21-19.74; adjusted OR, 7.97; 95% CI, 2.93-21.72), oral second-generation antipsychotics and risperidone long-acting injection were associated with high-dose antipsychotics (adjusted OR, 5.67; 95% CI, 2.89-11.12; adjusted OR, 8.14; 95% CI, 3.22-20.53). Therefore, the use of antipsychotic polypharmacy and high-dose antipsychotics among individuals issued with CTOs is associated only with the drugs prescribed in their treatment plans and not their individual demographic and clinical characteristics.

  6. A systematic review of pediatric clinical trials of high dose vitamin D

    Directory of Open Access Journals (Sweden)

    Nassr Nama

    2016-02-01

    Full Text Available Background. Due to inadequate UV exposure, intake of small quantities of vitamin D is recommended to prevent musculoskeletal disease. Both basic science and observational literature strongly suggest that higher doses may benefit specific populations and have non-musculoskeletal roles. Evaluating the evidence surrounding high dose supplementation can be challenging given a relatively large and growing body of clinical trial evidence spanning time, geography, populations and dosing regimens. Study objectives were to identify and summarize the clinical trial literature, recognize areas with high quality evidence, and develop a resource database that makes the literature more immediately accessible to end users. Methods. Medline (1946 to January 2015, Embase (1974 to January 2015, and Cochrane databases (January 2015, were searched for trials. All pediatric (0–18 years trials administering doses higher than 400 IU (<1 year or 600 IU (≥1 year were included. Data was extracted independently by two of the authors. An online searchable database of trials was developed containing relevant extracted information (http://www.cheori.org/en/pedvitaminddatabaseOverview. Sensitivity and utility were assessed by comparing the trials in the database with those from systematic reviews of vitamin D supplementation including children. Results. A total of 2,579 candidate papers were identified, yielding 169 trials having one or more arms meeting eligibility criteria. The publication rate has increased significantly from 1 per year (1970–1979 to 14 per year (2010–2015. Although 84% of the total trials focused on healthy children or known high risk populations (e.g., renal, prematurity, this proportion has declined in recent years due to the rise in trials evaluating populations and outcomes not directly related to the musculoskeletal actions of vitamin D (27% in 2010s. Beyond healthy children, the only pediatric populations with more than 50 participants from

  7. Effect of high dose steroids on oleic acid-induced lung injury in rabbits: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hwa Yeon; Yoo, Seung Min [Chung-Ang University Hospital, Seoul (Korea, Republic of)

    2006-02-15

    The purpose of this study is to evaluate the therapeutic efficacy, on the basis of CT findings, of high dose methyl prednisolone for treating acute lung injury that was induced by oleic acid injection. A total of 30 healthy rabbits (1.8-2.2 kg) were included in this study. Group I included 10 rabbits in which 0.2 mL oleic acid was injected through their ear veins. Group IIa included 10 rabbits in which 30 mg/kg methyl prednisolone and 0.2 mL oleic acid were intravenously injected at the same time. Group IIb included 5 rabbits in which 30 mg/kg methyl prednisolone was injected 6 hours prior to the 0.2 mL oleic acid intravenous injection. The other 5 rabbits (Group III) were injected intravenously with 30 mg/kg methyl prednisolone without the oleic acid. After that, 30 mg/kg methyl prednisolone per every 12 hours was injected in the non-sacrificed rabbits of Group II and Group III. Nonenhanced Chest CT scans were performed prior to the 30 minutes, 4 hours, 24 hours, 48 hours, and 72 hours after the intravenous injection of oleic acid or methyl prednisolone. We randomly sacrificed one rabbit of groups I, II and III 30 minutes, 4 hours, 24 hours, 48 hours and 72 hours after CT scanning. The distribution, extent, and pattern of the lesions on the CT scan were analyzed. The analyzed pattern of the lesions was ground glass attenuation, consolidation and interstitial thickening. Pathologic correlation was then done. The main CT findings of Group I were peripheral, wedge shaped, ill-defined ground glass attenuations and /or consolidations. The pathologic findings of Group I were interstitial or intraalveolar edema, intraalveolar hemorrhage and coagulation necrosis. Diffuse ground glass opacities with interstitial thickening were noted in 20% (n=2/10) of Group I and in 60% (n=9/15) of Group II at the 30 minute CT; however, there was no statistical difference between the two groups ({rho} = 0.09). Consolidations with air bronchogram were noted in 22.2% (2/9) of Group I and in

  8. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    Directory of Open Access Journals (Sweden)

    Moral A

    2016-06-01

    Full Text Available Angel Moral,1 Victoria Moreno,2 Francisco Girón,3 David El-Qutob,4 José D Moure,5 Manuel Alcántara,6 Antonia Padial,7 Alberto G Oehling,8 Carmen Millán,9 Fernando de la Torre10 1Allergy Service, Hospital Virgen del Valle, Toledo, 2Allergy Service, Hospital Blanca Paloma, Huelva, 3Consulta Privada, Granada, 4Allergy Service, Clínica Atenea, Castellón, 5Pediatric Department, Complejo Hospitalario Universitario de Santiago, A Coruña, 6Allergy Service, Complejo Hospitalario de Jaén, Jaén, 7Allergy Service, Hospital Infanta Sofía, Madrid, 8Centro de Alergia y Asma Balear, Mallorca, 9Consulta Privada, Cádiz, 10ALK-Abelló, SA, Madrid, Spain Background: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy.Patients and methods: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months.Results: The most frequent adverse reaction was oral pruritus (13.7% of the patients. Most of the reactions were local (84.7% and immediate (93.5% and occurred during the initiation phase (60.6%. All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417, age (P=0.1801, years since the disease was first

  9. High-dose benzodiazepine dependence: a qualitative study of patients' perception on cessation and withdrawal.

    Science.gov (United States)

    Liebrenz, Michael; Gehring, Marie-Therese; Buadze, Anna; Caflisch, Carlo

    2015-05-13

    Benzodiazepine withdrawal syndrome has been reported following attempts to withdraw even from low or therapeutic doses and has been compared to barbiturate and alcohol withdrawal. This experience is known to deter patients from future cessation attempts. Research on other psychotropic substances shows that the reasons and motivations for withdrawal attempts - as well as the experiences surrounding those attempts - at least partially predict future efforts at discontinuation as well as relapse. We therefore aimed to qualitatively explore what motivates patients to discontinue this medication as well as to examine their experiences surrounding previous and current withdrawal attempts and treatment interventions in order to positively influence future help-seeking behavior and compliance. To understand these patients better, we conducted a series of 41 unstructured, narrative, in-depth interviews among adult Swiss patients with a long-term dependent use of benzodiazepines in doses equivalent to more than 40 mg diazepam per day and/or otherwise problematic use (mixing benzodiazepines, escalating dosage, recreational use or illegal purchase). Mayring's qualitative content analysis was used to evaluate findings. These high-dose benzodiazepine-dependent patients decision to change consumption patterns were affected by health concerns, the feeling of being addicted and social factors. Discontinuation attempts were frequent and not very successful with fast relapse. Withdrawal was perceived to be a difficult, complicated, and highly unpredictable process. The first attempt at withdrawal occurred at home and typically felt better than at the clinic. Inpatient treatment was believed to be more effective with long term treatment (approaches) than short term. Patients preferred gradual reduction of usage to abrupt cessation (and had experienced both). While no clear preferences for withdrawal were found for benzodiazepines with specific pharmacokinetic properties, participants

  10. Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lilleby, Wolfgang, E-mail: wolfgang.lilleby@ous-hf.no [Cancer Clinic, Oslo University Hospital, Norwegian Radiumhospital, Department of Radiotherapy and Oncology, Oslo (Norway); Tafjord, Gunnar; Raabe, Nils K. [Cancer Clinic, Oslo University Hospital, Norwegian Radiumhospital, Department of Radiotherapy and Oncology, Oslo (Norway)

    2012-07-01

    Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgen deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal

  11. Metabolic syndrome in patients with severe mental illness undergoing psychiatric rehabilitation receiving high dose antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Bapu V Ravindranath

    2012-01-01

    Full Text Available Background: To review evidence of chronic antipsychotic medication and the association with metabolic syndrome in mentally ill patients. This evidence was used to analyse a cohort of patients with severe mental illness and to deduce a correlation between the prevalence of metabolic syndrome and their dose regimens. Materials and Methods: Twenty-four male patients undergoing Psychiatric rehabilitation underwent a review of current medication and assessment of risk factors for metabolic syndrome. Assessment criteria was based upon National Cholesterol Education Programme expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III (NCEP ATP III criteria, incorporating waist circumference, raised triglycerides, reduced high density lipoprotein, raised blood pressure and fasting blood glucose. PubMed, Nature and Science Direct databases have been used to compile the medical and scientific background on metabolic syndrome and antipsychotic medication and the effect on patients particularly on high dose. Results: Out of 24 patients, 10 patients (41.7% were receiving high dose antipsychotics (HDA and four were on maximum dosage limits of 100%. 8.3% (2/24 patients were receiving only one first generation antipsychotics (FGA, 37.5% (9/24 patients were receiving only one second generation antipsychotic (SGA, 45.8% patients (11/24 were receiving two or more SGA only, and only one patient was receiving two or more FGA. One patient was receiving a combination of FGA and SGA. PRN ("as needed" therapy was not included in this study as their usage was limited. Clozapine was mostly prescribed in these patients (10/24, 41.6%. Four out of the 24 patients refused blood tests therefore were excluded from the following results. In the patients evaluated, 55% (11/20 had confirmed metabolic syndrome. In these patients with metabolic syndrome, 45.4% (5/11 were on HDA and 27.3% (3/11 were on maximum British National

  12. Mechanisms of Fatal Cardiotoxicity following High-Dose Cyclophosphamide Therapy and a Method for Its Prevention.

    Directory of Open Access Journals (Sweden)

    Takuro Nishikawa

    Full Text Available Observed only after administration of high doses, cardiotoxicity is the dose-limiting effect of cyclophosphamide (CY. We investigated the poorly understood cardiotoxic mechanisms of high-dose CY. A rat cardiac myocardial cell line, H9c2, was exposed to CY metabolized by S9 fraction of rat liver homogenate mixed with co-factors (CYS9. Cytotoxicity was then evaluated by 3-(4,5-dimethyl-2-thiazolyl¬2,5-diphenyl¬2H-tetrazolium bromide (MTT assay, lactate dehydrogenase release, production of reactive oxygen species (ROS, and incidence of apoptosis. We also investigated how the myocardial cellular effects of CYS9 were modified by acrolein scavenger N-acetylcysteine (NAC, antioxidant isorhamnetin (ISO, and CYP inhibitor β-ionone (BIO. Quantifying CY and CY metabolites by means of liquid chromatography coupled with electrospray tandem mass spectrometry, we assayed culture supernatants of CYS9 with and without candidate cardioprotectant agents. Assay results for MTT showed that treatment with CY (125-500 μM did not induce cytotoxicity. CYS9, however, exhibited myocardial cytotoxicity when CY concentration was 250 μM or more. After 250 μM of CY was metabolized in S9 mix for 2 h, the concentration of CY was 73.6 ± 8.0 μM, 4-hydroxy-cyclophosphamide (HCY 17.6 ± 4.3, o-carboxyethyl-phosphoramide (CEPM 26.6 ± 5.3 μM, and acrolein 26.7 ± 2.5 μM. Inhibition of CYS9-induced cytotoxicity occurred with NAC, ISO, and BIO. When treated with ISO or BIO, metabolism of CY was significantly inhibited. Pre-treatment with NAC, however, did not inhibit the metabolism of CY: compared to control samples, we observed no difference in HCY, a significant increase of CEPM, and a significant decrease of acrolein. Furthermore, NAC pre-treatment did not affect intracellular amounts of ROS produced by CYS9. Since acrolein seems to be heavily implicated in the onset of cardiotoxicity, any competitive metabolic processing of CY that reduces its transformation to acrolein

  13. Pathological characteristics of spine metastases treated with high-dose single-fraction stereotactic radiosurgery.

    Science.gov (United States)

    Katsoulakis, Evangelia; Laufer, Ilya; Bilsky, Mark; Agaram, Narasimhan P; Lovelock, Michael; Yamada, Yoshiya

    2017-01-01

    OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant

  14. Acute administration of high dose trimetazidine inhibits pentylenetetrazol-induced seizures in rats

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    Serkan GURGUL

    2017-03-01

    Full Text Available Objective: Resistant epilepsy is widely seen in clinical settings manipulate the researchers to pursuit novel anti-epileptic treatments. Although trimetazidine (TMZ is commonly used in the treatment of angina and ischemic diseases, it is considered that the drug may be beneficial in the treatment of epileptic seizures and convulsions. We aimed to evaluate electrophysiologically the protective effects of high dose acute TMZ on epileptic seizures and convulsions in a rat model of epilepsy induced by pentilentetrazol (PTZ. Method: Forty-eight male Sprague-Dawley rats were used for the EEG evaluation (Group-A; n=24 and behavioral assessment (Group-B; n=24. Grup-A1 and Grup-B1 were determined as control group and given no medication. 35 mg/kg (Group-A2, -A3 and -A4 and 70 mg/kg (Group-B2, -B3 and -B4 of PTZ were administered intraperitoneally (ip. so as to generate seizures and convulsions. Group-A2 and Group-B2 were treated with saline. 40 mg/kg (Grup-A3 and Grup-B3 and 80 mg/kg of TMZ (Group-A4 and Group-B4 were administered to the treatment groups by ip. Brain malondialdehyde (MDA levels, spike-percentage values, Racine’s Convulsion Scale (RCS scores and "first myoclonic jerk (FMJ" latencies of each rat were determined. Results: Brain MDA levels, spike-percentage values, RCS scores, and FMJ latencies of Group-A2 and Group-B2 were significantly increased compared to those of the control’s (Grup-A1 and Grup-B1 (P<0.05 for all comparisons. However, in TMZ treated groups (Group-A3 and -A4; Group-B3 and -B4 the elevated values of these parameters were found to be significantly decreased (P<0.05 for all comparisons. Conclusions: This study has demonstrated that the high dose acute TMZ administration may prevent PTZ-induced seizures and convulsions in rats. Furthermore, it can be also said that TMZ has a neuroprotective effects on oxidative stress associated with PTZ. Therefore, it may be considered for use with therapeutic purposes of TMZ in

  15. High-dose ibuprofen therapy associated with esophageal ulceration after pneumonectomy in a patient with cystic fibrosis: a case report

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    Anbar Ran D

    2004-09-01

    Full Text Available Abstract Background Lung disease in patients with cystic fibrosis is thought to develop as a result of airway inflammation, infection, and obstruction. Pulmonary therapies for cystic fibrosis that reduce airway inflammation include corticosteroids, rhDNase, antibiotics, and high-dose ibuprofen. Despite evidence that high-dose ibuprofen slows the progression of lung disease in patients with cystic fibrosis, many clinicians have chosen not to use this therapy because of concerns regarding potential side effects, especially gastrointestinal bleeding. However, studies have shown a low incidence of gastrointestinal ulceration and bleeding in patients with cystic fibrosis who have been treated with high-dose ibuprofen. Case presentation The described case illustrates a life-threatening upper gastrointestinal bleed that may have resulted from high-dose ibuprofen therapy in a patient with CF who had undergone a pneumonectomy. Mediastinal shift post-pneumonectomy distorted the patient's esophageal anatomy and may have caused decreased esophageal motility, which led to prolonged contact of the ibuprofen with the esophagus. The concentrated effect of the ibuprofen, as well as its systemic effects, probably contributed to the occurrence of the bleed in this patient. Conclusions This report demonstrates that gastrointestinal tract anatomical abnormalities or dysmotility may be contraindications for therapy with high-dose ibuprofen in patients with cystic fibrosis.

  16. Taurine-EVA copolymer-paraffin rods dosimeters for EPR high-dose radiation dosimetry

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    Maghraby Ahmed M.

    2014-03-01

    Full Text Available Taurine/EPR rods (3 × 10 mm have been prepared by a simple technique in the laboratory where taurine powder was mixed with a molten mixture of paraffin wax and an ethylene vinyl acetate (EVA copolymer. The binding mixture EVA/Paraffin does not present interference or noise in the EPR signal before or after irradiation. The rods show good mechanical properties for safe and multi-use handling. An EPR investigation of radiation induced radicals in taurine rods 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 and modulation amplitude were studied and optimized. Response of taurine to different radiation doses (1.5-100 kGy was studied and found to follow a linear relationship up to 100 kGy. Radiation induced radicals in taurine persists and showed a noticeable stability over 94 days following irradiation. Uncertainities associated with the evaluation of radiation doses using taurine dosimeters were discussed and tabulated. It was found that taurine possesses good dosimetric properties using EPR spectroscopy in high doses in addition to its simple spectrum.

  17. Inhibitory Effect of High Dose of the Flavonoid Quercetin on Amygdala Electrical Kindling in Rats

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    Tourandokht Baluchnejadmojarad

    2010-05-01

    Full Text Available A B S T R A C T Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. Therefore, the anti-convulsant effect of a high dose of quercetin was evaluated in amygdala kindling model in male rats. Methods: Rats were divided into sham-operated group, quercetintreated SH, kindled, and quercetin-treated kindled rats. Quercetin was administered i.p. one day before amygdale kindling for 3 weeks (40 mg/kg/day. The parameters seizure stage, AD duration, the latency to the onset of stage 4, and the duration of stage 5 were analyzed. Results: The results showed that quercetin pretreatment causes a lower seizure intensity in treated kindled rats (p<0.05-0.01, a lower after-discharge duration (p<0.05-0.01, and a higher latency to stage IV (p<0.05 as compared to untreated kindled ones. Discussion: To conclude, chronic administration of quercetin inhibits amygdala electrical kindling and more studies are warranted to clarify its underlying mechanisms.

  18. Current situation of high-dose-rate brachytherapy for cervical cancer in Brazil

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    Silva, Rogerio Matias Vidal da; Souza, Divanizia do Nascimento, E-mail: rmv.fisica@gmail.com [Universidade Federal de Sergipe (UFS), Sao Cristovao, SE (Brazil); Pinezi, Juliana Castro Dourado [Pontificia Universidade Catolica de Goias (PUC-Goias), Goiania, GO (Brazil); Macedo, Luiz Eduardo Andrade [Hospital Chama, Arapiraca, AL (Brazil)

    2014-05-15

    To assess the current situation of high-dose-rate (HDR) brachytherapy for cancer of the cervix in Brazil, regarding apparatuses, planning methods, prescription, fractionation schedule and evaluation of dose in organs at risk. Materials and methods: in the period between March/2012 and May/2013, a multiple choice questionnaire was developed and sent to 89 Brazilian hospitals which perform HDR brachytherapy. Results: sixty-one services answered the questionnaire. All regions of the country experienced a sharp increase in the number of HDR brachytherapy services in the period from 2001 to 2013. As regards planning, although a three-dimensional planning software was available in 91% of the centers, conventional radiography was mentioned by 92% of the respondents as their routine imaging method for such a purpose. Approximately 35% of respondents said that brachytherapy sessions are performed after teletherapy. The scheme of four 7 Gy intracavitary insertions was mentioned as the most frequently practiced. Conclusion: the authors observed that professionals have difficulty accessing adjuvant three-dimensional planning tools such as computed tomography and magnetic resonance imaging. (author)

  19. High Dose Rate Brachytherapy as a Treatment Option in Endobronchial Tumors

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    Ali Hosni

    2016-01-01

    Full Text Available Purpose. To report our experience with high dose rate endobronchial brachytherapy (HDR-EBBT and to assess its efficacy and tolerability with possibility of its use in selected cases with curative intent. Method. Retrospective review of patients with endobronchial tumors treated at our institution in 2007–2013 with HDR-EBBT. Subjective response and treatment related toxicity were extracted from patients’ records. Clinical response was evaluated by chest CT +/− bronchoscopy 2-3 months after treatment. Local control (LC and overall survival (OS were analyzed. Results. Overall 23 patients were identified. Ten patients were treated with curative intent, in 8 of them HDR-EBBT was combined with external beam radiotherapy. Short term palliation was as follows: dyspnea (13/15, cough (12/14, and hemoptysis (3/3. Seventeen patients were evaluated, of whom 9 (53% showed complete response. Four patients developed local failure (only 1 of them treated with curative intent and were salvaged with HDR-EBBT (n=1, chemotherapy (n=2, and laser (n=1. Among patients treated with curative intent, the 2-year LC and OS were 89% and 67%, respectively, and 2 out of 4 deaths were cancer-related. Late toxicity included bronchial stenosis (n=1. Only 1 patient had fatal hemoptysis and postmortem examination indicated local recurrence. Conclusion. HDR-EBBT is promising treatment with tolerable complication if used in properly selected patients.

  20. Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.

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    Tomohito Sato

    Full Text Available Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg up to 24 h (1, 6, 12, or 24 h after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure.

  1. [A Quality Assurance (QA) System with a Web Camera for High-dose-rate Brachytherapy].

    Science.gov (United States)

    Hirose, Asako; Ueda, Yoshihiro; Oohira, Shingo; Isono, Masaru; Tsujii, Katsutomo; Inui, Shouki; Masaoka, Akira; Taniguchi, Makoto; Miyazaki, Masayoshi; Teshima, Teruki

    2016-03-01

    The quality assurance (QA) system that simultaneously quantifies the position and duration of an (192)Ir source (dwell position and time) was developed and the performance of this system was evaluated in high-dose-rate brachytherapy. This QA system has two functions to verify and quantify dwell position and time by using a web camera. The web camera records 30 images per second in a range from 1,425 mm to 1,505 mm. A user verifies the source position from the web camera at real time. The source position and duration were quantified with the movie using in-house software which was applied with a template-matching technique. This QA system allowed verification of the absolute position in real time and quantification of dwell position and time simultaneously. It was evident from the verification of the system that the mean of step size errors was 0.31±0.1 mm and that of dwell time errors 0.1±0.0 s. Absolute position errors can be determined with an accuracy of 1.0 mm at all dwell points in three step sizes and dwell time errors with an accuracy of 0.1% in more than 10.0 s of the planned time. This system is to provide quick verification and quantification of the dwell position and time with high accuracy at various dwell positions without depending on the step size.

  2. Survival of tumor cells after proton irradiation with ultra-high dose rates

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    Belka Claus

    2011-10-01

    Full Text Available Abstract Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD, respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional continuous irradiation mode do not differ significantly.

  3. Perioperative high-dose-rate brachytherapy in the treatment of recurrent malignant gliomas

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    Fabrini, Maria Grazia; Pasqualetti, Francesco; Grespi, Silvia [Div. of Radiation Oncology, ' ' S. Chiara' ' Pisa Hospital (Italy); Perrone, Franco [Div. of Health Physics, ' ' S. Chiara' ' Pisa Hospital (Italy); De Franco, Lucia; Vannozzi, Riccardo [Div. of Neurosurgery, ' ' S. Chiara' ' Pisa Hospital (Italy); Cionini, Luca [Div. of Radiation Oncology, ' ' S. Chiara' ' Pisa Hospital (Italy); Pisa Univ. (Italy)

    2009-08-15

    Purpose: To assess the feasibility and effectiveness of perioperative high-dose-rate brachytherapy for recurrent malignant gliomas. Patients and Methods: Between 2005 and 2008, 21 patients (14 males and seven females) with relapsed malignant glioma underwent a second surgery followed by a brachytherapy implant in the surgical cavity. Median age was 60 years, and median Karnofsky performance status 80. A single fraction of 18 Gy specified at 5 mm depth was administered perioperatively. Then, the applicator was removed nonsurgically. Mean postoperative hospitalization time was 3 days. Results: At the time of analysis, 15 patients (71%) had died and six (29%) were alive. Median follow-up was 32.3 months. Median overall survival from diagnosis amounted to 21.7 months. Median survival after recurrence was 8.0 months, and 6-month progression-free survival 42%. Patients were stratified into classes according to the prognostic recursive partitioning analysis. Conclusion: Perioperative brachytherapy has proven to be safe and well tolerated in patients with recurrent malignant glioma. No severe toxicity was reported, and the treatment has proven to be effective in symptomatic recurrences of malignant gliomas. (orig.)

  4. Determination of the tissue inhomogeneity correction in high dose rate Brachytherapy for Iridium-192 source

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    Barlanka Ravikumar

    2012-01-01

    Full Text Available In Brachytherapy treatment planning, the effects of tissue heterogeneities are commonly neglected due to lack of accurate, general and fast three-dimensional (3D dose-computational algorithms. In performing dose calculations, it is assumed that the tumor and surrounding tissues constitute a uniform, homogeneous medium equivalent to water. In the recent past, three-dimensional computed tomography (3D-CT based treatment planning for Brachytherapy applications has been popularly adopted. However, most of the current commercially available planning systems do not provide the heterogeneity corrections for Brachytherapy dosimetry. In the present study, we have measured and quantified the impact of inhomogeneity caused by different tissues with a 0.015 cc ion chamber. Measurements were carried out in wax phantom which was employed to measure the heterogeneity. Iridium-192 (192 Ir source from high dose rate (HDR Brachytherapy machine was used as the radiation source. The reduction of dose due to tissue inhomogeneity was measured as the ratio of dose measured with different types of inhomogeneity (bone, spleen, liver, muscle and lung to dose measured with homogeneous medium for different distances. It was observed that different tissues attenuate differently, with bone tissue showing maximum attenuation value and lung tissue resulting minimum value and rest of the tissues giving values lying in between those of bone and lung. It was also found that inhomogeneity at short distance is considerably more than that at larger distances.

  5. On the use of multi-dimensional scaling and electromagnetic tracking in high dose rate brachytherapy.

    Science.gov (United States)

    Götz, Theresa Ida; Ermer, Maximilian; Salas-Gonzalez, D; Kellermeier, Markus; Strnad, Vratislav; Bert, Christoph; Hensel, Bernhard; Tome, Ana Maria; Lang, Elmar W

    2017-08-30

    High Dose Rate Brachytherapy (HDR-BT) affords a frequent reassurance of the precise dwell positions of the radiation source. The corresponding dwell position determinations are realized with an electromagnetic tracking system (EMT). Because the treatment extends over several days, repeated dwell position determinations refer to varying coordinate systems centered in the field generator of the EMT system. After surgical implantation of the catheters a computed tomography (CT) X-ray image is taken followed by an immediate dwell position determination by the EMT system. The CT image serves to generate a treatment plan which determines dwell positions and dwell times for the radiation treatment. However, CT - and EMT - coordinates refer to different coordinate systems, hence an external reference is usually employed. The current investigation proposes a multi-dimensional scaling transformation of both data sets to estimate dwell positions without any external reference. Furthermore, the related distributions of dwell positions are characterized by uni - or bi - modal heavy - tailed distributions. The latter are well represented by alpha - stable distributions. The newly proposed data analysis provides dwell position deviations with high accuracy, and, furthermore, offers a convenient visualization of the actual shapes of the catheters which guide the radiation source during the treatment. © 2017 Institute of Physics and Engineering in Medicine.

  6. Clinical outcome of high-dose-rate interstitial brachytherapy in patients with oral cavity cancer

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    Lee, Sung Uk; Cho, Kwan Ho; Moon, Sung Ho; Choi, Sung Weon; Park, Joo Yong; Yun, Tak; Lee, Sang Hyun; Lim, Young Kyung; Jeong, Chi Young [National Cancer Center, Goyang (Korea, Republic of)

    2014-12-15

    To evaluate the clinical outcome of high-dose-rate (HDR) interstitial brachytherapy (IBT) in patients with oral cavity cancer. Sixteen patients with oral cavity cancer treated with HDR remote-control afterloading brachytherapy using 192Ir between 2001 and 2013 were analyzed retrospectively. Brachytherapy was administered in 11 patients as the primary treatment and in five patients as salvage treatment for recurrence after the initial surgery. In 12 patients, external beam radiotherapy (50-55 Gy/25 fractions) was combined with IBT of 21 Gy/7 fractions. In addition, IBT was administered as the sole treatment in three patients with a total dose of 50 Gy/10 fractions and as postoperative adjuvant treatment in one patient with a total of 35 Gy/7 fractions. The 5-year overall survival of the entire group was 70%. The actuarial local control rate after 3 years was 84%. All five recurrent cases after initial surgery were successfully salvaged using IBT +/- external beam radiotherapy. Two patients developed local recurrence at 3 and 5 months, respectively, after IBT. The acute complications were acceptable (< or =grade 2). Three patients developed major late complications, such as radio-osteonecrosis, in which one patient was treated by conservative therapy and two required surgical intervention. HDR IBT for oral cavity cancer was effective and acceptable in diverse clinical settings, such as in the cases of primary or salvage treatment.

  7. Salvage high-dose-rate brachytherapy for isolated vaginal recurrence of endometrial cancer.

    Science.gov (United States)

    Baek, Sungjae; Isohashi, Fumiaki; Yamaguchi, Hiroko; Mabuchi, Seiji; Yoshida, Ken; Kotsuma, Tadayuki; Yamazaki, Hideya; Tanaka, Eiichi; Sumida, Iori; Tamari, Keisuke; Otani, Keisuke; Seo, Yuji; Suzuki, Osamu; Yoshioka, Yasuo; Kimura, Tadashi; Ogawa, Kazuhiko

    We have retrospectively analyzed the outcomes of high-dose-rate (HDR) brachytherapy as a salvage therapy for vaginal recurrence of endometrial cancer. From 1997 to 2012, salvage HDR brachytherapy was performed in 43 patients. The median age was 64 years (range, 41-88 years). HDR brachytherapy was performed by interstitial brachytherapy in 34 patients (79%) and by intracavity brachytherapy in nine patients (21%). Seventeen (40%) of the 43 patients were treated with external beam radiotherapy. The median followup period was 58 months (range, 6-179 months). The 5-year overall survival (OS), progression-free survival (PFS), and local control rates (LC) were 84%, 52%, and 78%, respectively. Patients who received brachytherapy with external beam radiotherapy experienced no nodal recurrence (0 of 17 patients), whereas 23% of the patients (6 of 26 patients) who received brachytherapy alone experienced nodal recurrence (p = 0.047). The pathologic grade at the time of initial surgery (G1-2 vs. G3) was found to be a significant prognostic factor for both OS and PFS. The respective 5-year OS was 96% vs. 40% (p endometrial cancer. Pathologic grade, age, and modality were significant prognostic factors. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  8. Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

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    Gay, H A [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Allison, R R [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Downie, G H [Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Mota, H C [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Austerlitz, C [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Jenkins, T [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States); Sibata, C H [Department of Radiation Oncology, Brody School of Medicine at East Carolina University, Greenville, NC (United States)

    2007-06-07

    A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

  9. MINERALIZATION STUDY OF RENAL RATS FOLLOWING OVARYOHYSTERECTOMY AND ADMINISTRATION HIGH DOSE CALCIUM CARBONATE

    Directory of Open Access Journals (Sweden)

    Wiwik Misaco Yuniarti

    2008-06-01

    Full Text Available The aim of this study was to determine the effect of high dose calcium carbonate in rat (Rattus norvegicus following ovaryohysterectomy. A total of twenty female rats at 13 week-old were used in this study. Following ovaryohitectomy, the animals were randomized in four treatment groups. Group P0 were :fed with standard food only P1, P2 and P2 groups treated with standard food but supplemented calcium carbonate respectively at the dose of 75 mg per animal per day, 225 mg per animal per day , and 450 mg per animal per day. The calcium carbonate supplement were given daily in the morning for 42 days. The experimental animals were sacrificed at 21 week-old. Calcium and phosphor level in sinister kidneys were determined by spectrofotometric method. The data obtained from this study were analysed using one way analysis of variance. No significant difference was observed in calcium level among four treatment groups, with the lowest level were found in P3 group. However, the phosphor level of P1 was significantly lower than those of P2 and P3 groups. The highest phosphor level was observed in P3 group, indicating a phosphorous retension and the signs of renal failure.

  10. High dose of maternal folic acid supplementation is associated to infant asthma.

    Science.gov (United States)

    Yang, Liu; Jiang, Liwen; Bi, Meirong; Jia, Xiaodong; Wang, Youqing; He, Chuan; Yao, Yao; Wang, Jun; Wang, Zhiping

    2015-01-01

    Maternal folic acid supplementation had a positive effect on preventing neural tube defects (NTDs), but its effects in infant asthma remained unclear. A hospital-based case-control study was conducted with outpatients between March 2010 and March 2011 including 150 onset infant asthma cases and 212 controls, together with a meta-analysis involving 14,438 participants, was performed. The association between maternal folic acid supplementation and the risk of infant asthma was not significant either in the meta-analysis (OR = 1.06, 95% CI =0.99-1.14) or in the case-control study (OR = 0.72, 95% CI =0.37-1.39). However, quantitative analysis of the supplementation dose demonstrated that the risk of infant asthma significantly increased for the infants whose mother were with high-dose supplementation (>72,000 µg•d; OR = 3.16, 95% CI =1.15-8.71) after adjusting for confounding factors in the case-control study. Meanwhile, the risk of infant asthma significantly decreased for the infants whose mother were with low-dose supplementation (folic acid supplementation for mother during pregnancy was associated with an increased risk of infant asthma, whereas supplementation with a relatively low-dose was associated with a decreased risk of infant asthma. These findings should be further investigated in a large population.

  11. Advancement in high dose therapy and autologous stem cell rescue in lymphoma

    Institute of Scientific and Technical Information of China (English)

    Alessandro; Isidori; Cristina; Clissa; Federica; Loscocco; Barbara; Guiducci; Sara; Barulli; Lara; Malerba; Elisa; Gabucci; Giuseppe; Visani

    2015-01-01

    A lthough advanced stage aggressive non-Hodgkin’slymphomas and Hodgkin’s disease are thought to be che-motherapy-responsive cancers, a considerable number of patients either relapse or never attain a remission. High-dose therapy(HDT) followed by autologous stem cell transplantation(ASCT) is often the only possibility of cure for most of these patients. However, many controversial issues still remain with respect to HDT/ASCT for lymphomas, including its role for, the optimal timing of transplantation, the best conditioning regimen and the potential use of localized radiotherapy or immunologic methods to decrease post-transplant recurrence. Recently, mainly due to the unavailability of carmustine, several novel conditioning protocols have been clinically developed, with the aim of improving the overall outcome by enhancing the anti-lymphoma effect and, at the same time, by reducing short and long-term toxicity. Furthermore, the better safety profiles of novel approaches would definitively allow patients aged more than 65-70 years to benefit from this therapeutic option. In this review, we will briefly discuss the most relevant and recent data available regarding HDT/ASCT in lymphomas.

  12. High-Dose Neutron Detector Development Using 10B Coated Cells

    Energy Technology Data Exchange (ETDEWEB)

    Menlove, Howard Olsen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Henzlova, Daniela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-11-08

    During FY16 the boron-lined parallel-plate technology was optimized to fully benefit from its fast timing characteristics in order to enhance its high count rate capability. To facilitate high count rate capability, a novel fast amplifier with timing and operating properties matched to the detector characteristics was developed and implemented in the 8” boron plate detector that was purchased from PDT. Each of the 6 sealed-cells was connected to a fast amplifier with corresponding List mode readout from each amplifier. The FY16 work focused on improvements in the boron-10 coating materials and procedures at PDT to significantly improve the neutron detection efficiency. An improvement in the efficiency of a factor of 1.5 was achieved without increasing the metal backing area for the boron coating. This improvement has allowed us to operate the detector in gamma-ray backgrounds that are four orders of magnitude higher than was previously possible while maintaining a relatively high counting efficiency for neutrons. This improvement in the gamma-ray rejection is a key factor in the development of the high dose neutron detector.

  13. High-dose-rate interstitial brachytherapy for the treatment of penile carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Petera, J.; Odrazka, K.; Zouhar, M.; Bedrosova, J.; Dolezel, M. [Dept. of Oncology and Radiotherapy, Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic)

    2004-02-01

    Background: interstitial low-dose-rate (LDR) brachytherapy allows conservative treatment of T1-T2 penile carcinoma. High-dose-rate (HDR) is often considered to be dangerous for interstitial implants because of a higher risk of complications, but numerous reports suggest that results may be comparable to LDR. Nevertheless, there are no data in the literature available regarding HDR interstitial brachytherapy for carcinoma of the penis. Case report: a 64-year-old man with T1 NO MO epidermoid carcinoma of the glans is reported. Interstitial HDR brachytherapy was performed using the stainless hollow needle technique and a breast template for fixation and good geometry. The dose delivered was 18 x 3 Gy twice daily. Results: after 232 days from brachytherapy, the patient was without any evidence of the tumor, experienced no serious radiation-induced complications, and had a fully functional organ. Conclusion: HDR interstitial brachytherapy is feasible in selected case of penis carcinoma, when careful planning and small single fractions are used. (orig.)

  14. Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.

    Science.gov (United States)

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure.

  15. Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic melanoma?

    Science.gov (United States)

    Dillman, Robert O; Barth, Neil M; VanderMolen, Louis A; Mahdavi, Khosrow; McClure, Stephanie E

    2012-08-01

    For more than 20 years interleukin-2 (IL2) was the preferred treatment for medically fit metastatic melanoma patients, but recently two new agents, ipilimumab and vemurafenib, were approved for stage IV disease. Single-institution data were used to determine the long-term survival rate for IL2-treated melanoma patients, and whether use of inpatient IL2 had declined recently. Between May 1987 and April 2010, 150 patients were hospitalized for high-dose, intravenous (i.v.) IL2. The average number of IL2 patients increased from 5.4 per year during 1987-1991 to 5.8 during 1992-1997 after regulatory approval of IL2, to 8.3 during 1998-2006 after a marketing indication in metastatic melanoma was granted, but dropped to 3.0 during 2007-2010. At the time of treatment, median age was 52 years; 27% were 60 years of age or older. At the time of analysis 122 patients were deceased. Median survival from the start date of IL2 treatment was 15.6 months, with a 20% 5-year survival. Among patients enrolled in clinical trials, there were as many nonresponders who survived 5 years as responders, which is consistent with a delayed immunotherapy benefit. In the absence of long-term survival data for these newer agents, IL2 probably should still be the preferred initial treatment for most patients with metastatic melanoma who are medically fit.

  16. Severe neuroleptic malignant syndrome: successful treatment with high-dose lorazepam and diazepam: a case report.

    Science.gov (United States)

    Tsai, Meng-Chang; Huang, Tiao-Lai

    2010-01-01

    Neuroleptic malignant syndrome (NMS) is an idiosyncratic and potentially fatal adverse complication of antipsychotic medications and other dopamine-modulating agents. It is characterized by hyperthermia, muscle rigidity, autonomic dysfunction and alteration in mental status. Here, we report a patient with severe NMS who was successfully treated with highdose lorazepam and diazepam. A 61-year-old man with bipolar I disorder was admitted to the hospital because of manic episodes. Fever, muscle rigidity, tachycardia, diaphoresis, elevated blood pressure and delirium occurred following intramuscular injection of haloperidol and NMS was diagnosed. Supportive treatment included hydration, alkalinized fluids and correction of abnormal electrolytes without the use of dantrolene, dopaminergic agents or electroconvulsive therapy. The Francis-Yacoub NMS rating scale was employed for evaluation of clinical improvement, and scores were 55 on the first day and 0 at discharge. The patient was followed up for 6 months and was free of NMS. In conclusion, this is the first report of rapid relief of NMS with high-dose lorazepam and diazepam in a Taiwanese patient.

  17. Dietary intake of high-dose biotin inhibits spermatogenesis in young rats.

    Science.gov (United States)

    Sawamura, Hiromi; Ikeda, Chieko; Shimada, Ryoko; Yoshii, Yui; Watanabe, Toshiaki

    2015-02-01

    To characterize a new function of the water-soluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats.

  18. Impact of surface curvature on dose delivery in intraoperative high-dose-rate brachytherapy.

    Science.gov (United States)

    Oh, Moonseong; Wang, Zhou; Malhotra, Harish K; Jaggernauth, Wainwright; Podgorsak, Matthew B

    2009-01-01

    In intraoperative high-dose-rate (IOHDR) brachytherapy, a 2-dimensional (2D) geometry is typically used for treatment planning. The assumption of planar geometry may cause serious errors in dose delivery for target surfaces that are, in reality, curved. A study to evaluate the magnitude of these errors in clinical practice was undertaken. Cylindrical phantoms with 6 radii (range: 1.35-12.5 cm) were used to simulate curved treatment geometries. Treatment plans were developed for various planar geometries and were delivered to the cylindrical phantoms using catheters inserted into Freiburg applicators of varying dimension. Dose distributions were measured using radiographic film. In comparison to the treatment plan (for a planar geometry), the doses delivered to prescription points were higher on the concave side of the geometry, up to 15% for the phantom with the smallest radius. On the convex side of the applicator, delivered doses were up to 10% lower for small treated areas (5 catheters). Our measurements have shown inaccuracy in dose delivery when the original planar treatment plan is delivered with a curved applicator. Dose delivery errors arising from the use of planar treatment plans with curved applicators may be significant.

  19. Spinal cord injuries in older children: is there a role for high-dose methylprednisolone?

    Science.gov (United States)

    Arora, Bhawana; Suresh, Srinivasan

    2011-12-01

    We present a retrospective case series of 15 children (aged 8-16 years) with blunt traumatic spinal cord injury who were treated with methylprednisolone as per the National Acute Spinal Cord Injury Study protocol. Of all patients, 12 (80%) were male. Causes were sports injuries (n = 9), motor vehicle crashes (n = 2), and falls (n = 4). Most injuries were nonskeletal (n = 14), and all patients had incomplete injury of the spinal cord. The most common location of tenderness was cervical (n = 7). Of the 15 patients, methylprednisolone was initiated within 3 hours in 13 patients and between 3 and 8 hours in 2 patients. All patients received the medication for 23 hours as per the National Acute Spinal Cord Injury Study protocol. Of the 15 patients, 13 recovered completely by 24 hours and were discharged with a diagnosis of spinal cord concussion. One patient had compression fracture of T5 and T3-T5 spinal contusion but no long-term neurological deficit. One patient was discharged with diagnosis of C1-C3 spinal cord contusion (by magnetic resonance imaging) and had partial recovery at 2 years after injury. All patients with a diagnosis of cord concussion had normal plain films of the spine and computed tomographic and magnetic resonance imaging findings. None of the patients had any associated major traumatic injuries to other organ systems. The high-dose steroid therapy did not result in any serious bacterial infections.

  20. Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Qing Zhang; Ting-Ting Zheng; Jian-Cun Zhen; Xiao-Hui Niu

    2016-01-01

    Background:High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is "gold standard" therapy for osteosarcoma.Plasma concentrations of methotrexate (MTX) are closely related to its efficacy and toxicity.Delayed excretion of MTX can lead to serious adverse reactions that may result in treatment cessation,irreversible organ damage,and death.This study focused on the incidence of delayed excretion of MTX in Chinese osteosarcoma patients.Methods:A total of 1277 osteosarcoma patients were treated with HD-MTX chemotherapy (4291 cycles) from 2010 to 2015.Factors that could influence delayed excretion of MTX (gender,age,number of chemotherapy cycles,and serum concentration of MTX) were analyzed.Results:The incidence of delayed excretion of MTX (serum concentrations at 24 h [C24 h] >5 μmol/L) and severe delayed excretion of MTX (C24 h >20 μmol/L) were 6.19% and 0.86% per patient,and 2.31% and 0.26% per cycle of treatment,respectively.The incidence of severe delayed excretion of MTX was associated with gender,age,and C24 h.Conclusions:Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX.An optimal individualized rescue strategy can be created with consideration of gender,age,and C24 h.

  1. 3D-printed applicators for high dose rate brachytherapy: Dosimetric assessment at different infill percentage.

    Science.gov (United States)

    Ricotti, Rosalinda; Vavassori, Andrea; Bazani, Alessia; Ciardo, Delia; Pansini, Floriana; Spoto, Ruggero; Sammarco, Vittorio; Cattani, Federica; Baroni, Guido; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

    2016-12-01

    Dosimetric assessment of high dose rate (HDR) brachytherapy applicators, printed in 3D with acrylonitrile butadiene styrene (ABS) at different infill percentage. A low-cost, desktop, 3D printer (Hamlet 3DX100, Hamlet, Dublin, IE) was used for manufacturing simple HDR applicators, reproducing typical geometries in brachytherapy: cylindrical (common in vaginal treatment) and flat configurations (generally used to treat superficial lesions). Printer accuracy was investigated through physical measurements. The dosimetric consequences of varying the applicator's density by tuning the printing infill percentage were analysed experimentally by measuring depth dose profiles and superficial dose distribution with Gafchromic EBT3 films (International Specialty Products, Wayne, NJ). Dose distributions were compared to those obtained with a commercial superficial applicator. Measured printing accuracy was within 0.5mm. Dose attenuation was not sensitive to the density of the material. Surface dose distribution comparison of the 3D printed flat applicators with respect to the commercial superficial applicator showed an overall passing rate greater than 94% for gamma analysis with 3% dose difference criteria, 3mm distance-to-agreement criteria and 10% dose threshold. Low-cost 3D printers are a promising solution for the customization of the HDR brachytherapy applicators. However, further assessment of 3D printing techniques and regulatory materials approval are required for clinical application. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  2. High-Dose Amoxicillin with Clavulanate for the Treatment of Acute Otitis Media in Children

    Directory of Open Access Journals (Sweden)

    Chia-Huei Chu

    2014-01-01

    Full Text Available Objective. This study uses the acute otitis media clinical practice guideline proposed in 2004 as a reference to evaluate whether antibiotics doses that are in line with the recommendations lead to better prognosis. The study also attempts to clarify possible factors that influence the outcome. Study Design. Retrospective cohort study. Subjects and Methods. A total of 400 children with acute otitis media were enrolled. The dosage of amoxicillin was considered to be appropriate when in accord with clinical practice guidelines, that is, 80–90 mg/kg/day. The outcome was defined according to the description of tympanic membrane on medical records. Multivariate logistic regression was used to analyze the relationship between antibiotic dosage and prognosis after adjusting for baseline factors. Results. The majority of prescriptions were under dosage (89.1% but it was not noticeably associated with outcome (P= 0.41. The correlation between under dosage and poor prognosis was significant in children below 20 kg with bilateral acute otitis media (odds ratio 1.63; 95% CI 1.02–2.59, P=0.04. Conclusion. Treating acute otitis media in children, high-dose amoxicillin with clavulanate as recommended in the clinical practice guideline was superior to conventional doses only in children under 20 kg with bilateral diseases.

  3. Response of Soil Microbial Community to a High Dose of Fresh Olive Mill Wastewater

    Institute of Scientific and Technical Information of China (English)

    J.L.MORENO; F.BASTIDA; M.A.S(A)NCHEZ-MONEDERO; T.HERN(A)NDEZ; C.GARC(I)A

    2013-01-01

    An incubation experiment was designed in order to determine the further microbiological response to an addition (500 m3 ha-1)of fresh olive mill wastewater (FOMWW) in a soil that has been frequently amended with uncontrolled doses of OMWW since the 1990s in an active disposal site (ADS soil).To achieve this aim,the phospholipid fatty acid (PLFA) profiles,microbial biomass C (Cmic),and dehydrogenase (DHA) and urease activities (URA) were monitored at the beginning (T0),3 h (T1) and 97 d (Tf,i.e.,the end) of incubation after FOMWW addition.After the FOMWW addition,an increase in the ratio of fungal to bacterial PLFAs was observed in ADS soil.Moreover,a relative increase of monounsaturated fatty acids (MUFAs) with respect to saturated fatty acids (SATFA) was found in the ADS soil.An increase of the Gram-positive to Gram-negative ratio was observed in this soil at the end of the incubation.While DHA and Cmic increased in the ADS soil after FOMWW addition,URA showed a decrease.Fungi and Gram-positive bacterial biomass experienced an increase after addition of a high dose of FOMWW in laboratory conditions.

  4. Sleep is more sensitive to high doses of caffeine in the middle years of life.

    Science.gov (United States)

    Robillard, Rébecca; Bouchard, Maude; Cartier, Annick; Nicolau, Laurence; Carrier, Julie

    2015-06-01

    During the middle years of life, sleep becomes more fragile and its sensitivity to psychostimulants may increase. This study evaluated the effects of 200 mg and 400 mg of caffeine on sleep in young and middle-aged adults. The sleep of 22 young (23.5 ± 1.9 years) and 24 middle-aged (51.7 ± 11.5 years) adults was recorded using polysomnography in two conditions (placebo and caffeine) in a double-blind cross-over design. Compared to placebo, caffeine increased sleep latency, shortened total sleep duration and reduced sleep efficiency. At the higher dose, these effects were more pronounced in middle-aged than in young adults. Furthermore, the higher dose of caffeine increased absolute stage 1 sleep in young adults, whereas it decreased absolute stage 2 sleep in middle-aged adults. Caffeine also induced dose-dependent increases in relative stage 1 sleep and reductions in absolute and relative slow wave sleep and absolute rapid eye movement sleep in both age groups. There was no dose- or age-related modulation of the effects of caffeine on quantified electroencephalographic measures. These results indicate that, compared to young adults, middle-aged adults are generally more sensitive to the effects of a high dose of caffeine on sleep quantity and quality.

  5. Aging of magnesium stearate under high doses gamma irradiation and oxidative conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lebeau, D.; Beuvier, L.; Cornaton, M. [CEA, DEN, DPC, SECR, LRMO, F-91191 Gif-sur-Yvette (France); Miserque, F. [CEA, DEN, DPC, SCCME, LECA, F-91191 Gif-sur-Yvette (France); Tabarant, M. [CEA, DEN, DPC, SEARS, LISL, F-91191 Gif-sur-Yvette (France); Esnouf, S. [CEA, DEN, DPC, SECR, LRMO, F-91191 Gif-sur-Yvette (France); Ferry, M., E-mail: muriel.ferry@cea.fr [CEA, DEN, DPC, SECR, LRMO, F-91191 Gif-sur-Yvette (France)

    2015-05-15

    Highlights: • Magnesium stearate was radio-oxidized at very high doses using gamma-rays. • H{sub 2} emission was estimated as a function of the integrated dose. • Modifications in the organic solid were followed as a function of the integrated dose. • A non-exhaustive degradation mechanism of magnesium stearate was proposed. - Abstract: In nuclear waste packages conditioning processes, magnesium stearate is widely used because of its high lubricating properties. For safety purposes, the radiolytic degradation of these organic materials has to be better understood to be able to predict their aging in repository conditions. This study reports the radiolytic degradation of magnesium stearate, using gamma-rays at room temperature and under air. Modifications were followed using different analytical tools (XPS, ATR-FTIR, ICP-AES, ATG and mass spectrometry). It has been observed that molecules mainly formed up to 1000 kGy of gamma irradiation dose under radio-oxidation are alkanes, hydroperoxides, double bonds in the aliphatic chain, carboxylates with aliphatic chain shorter than the one of stearate and ketones. At a dose of 4000 kGy, dicarboxylic acids are observed: the formation of these molecules needs a dose of at least 1000 kGy to be created under radio-oxidation. These observations allow us to propose a non-exhaustive degradation mechanism of magnesium stearate under gamma-irradiation at room temperature and under air.

  6. Acute arterial thrombosis associated with inadvertent high dose of tranexamic acid

    Directory of Open Access Journals (Sweden)

    Surjya Prasad Upadhyay

    2013-01-01

    Full Text Available Tranexamic acid (TA act as anti-fibrinolytic agent and is widely used to limit bleeding in clinical practice. Tranexemic acid bind with plasminogen and prevent its conversion to plasmin, which limits the fibrinolytic pathway, so there is a theoretical risk of increasing thrombosis with high or prolonged therapy with TA. We encountered a case of acute arterial thrombosis following inadvertent administration of high dose of TA. A 27-years-old male with no other co-morbidity was ordered intravenous 1 gm TA to control excessive bleeding from previous bladder injury, but by mistake, he received 10 gm of TA. The patient developed signs and symptoms of acute ischemia in the right lower limb, which was diagnosed as acute iliac arterial thrombosis by computed tomography (CT angiography. The patient was managed with systemic heparinization, fasciotomy for impending gangrene and other supportive care following which he recovered fully within a few days. Caution should be exercised for all prophylactic use, especially with high dosage or prolonged therapy with TA.

  7. Comparison of commercial thermoluminescent readers regarding high-dose high-temperature measurements

    CERN Document Server

    Bilski, P; Obryk, B; Hodyr, K

    2014-01-01

    Three different thermoluminescent measuring systems have been compared with respect to the differences in temperature profiles, spectral sensitivities, as well as linearity of dose response characteristics. The comparison was performed using the Harshaw 3500, Riso DA-20 and RA94 TLD readers. The instruments were tested for the readouts of highly irradiated LiF:Mg,Cu,P (MCP) TL detectors, which require readout up to 550 C, in case of doses exceeding 1 kGy. It was found that the Harshaw 3500 can be used, without any additional light attenuation, for the measurements of MCP detectors exposed to doses up to about 5 Gy. For the other two readers the upper dose limit is about 5 times lower. It was also found that the Harshaw 3500 shows the best thermal stability considering the peak maximum position. For the ultra-high doses the differences in the spectral characteristics of the applied optical filters and photomultipliers, in conjunction with an evolution of the MCP TL emission spectrum with increasing dose, signi...

  8. High-dose intravenous immunoglobulin in inflammatory myopathies: experience based on controlled clinical trials.

    Science.gov (United States)

    Dalakas, M C

    2003-10-01

    Controlled clinical trials with high-dose intravenous immunoglobulin (IVIg) have been conducted in patients with DM and IBM, but not PM. A double-blind placebo-controlled study in DM patients, resistant or partially responsive to conventional therapies, showed that IVIg is very effective in improving both the muscle strength and the skin rash. The clinical benefit, which was impressive in patients with early disease, was associated with improvement in the muscle cytoarchitecture. Quantitative histological studies in repeated muscle biopsies showed a statistically significant increased in the size of muscle fibers and the number of capillaries with normalization of the capillary diameter. Resolution of the aberrant immunopathological parameters including interception of complement activation products and downregulation of T cells, ICAM-I, VCAM, TGF-beta and MHC-I molecules was also noted. In IBM, IVIg showed marginal, and non statistically significant, improvements in muscle strength. Up to 20% of patients however, demonstrated clinical improvement with increased activities of daily living while certain muscle groups, such as the muscles of swallowing, showed significant improvements compared to placebo implying mild regional benefits. In PM, small uncontrolled series have shown improvements in muscle strength in up to 70% of the IVIg-treated patients. Because PM, as a stand-alone clinical entity, is a very rare disease, completion of controlled trials will be very difficult.

  9. Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans.

    Science.gov (United States)

    Johnson, Matthew W; MacLean, Katherine A; Caspers, Michael J; Prisinzano, Thomas E; Griffiths, Roland R

    2016-04-01

    Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

  10. High-dose insulin inhibits gap junction intercellular communication in vascular smooth muscle cells.

    Science.gov (United States)

    Bian, Ou; Zhang, Haishan; Guan, Qigang; Sun, Yingxian; Zeng, Dingyin

    2015-07-01

    Gap junction intercellular communication (GJIC) is important in mediating intercellular substance and signal transmission. Connexin (Cx)43 is a major component involved in GJIC in vascular tissue and its abnormal expression is closely associated with various vascular diseases. Insulin resistance is the central component of metabolic syndrome, and high doses of insulin can affect vascular function through multiple pathways, resulting in cardiovascular disease. However, the effects of insulin on GJIC function and connexin (Cx)43 expression in vascular smooth muscle cells (VSMCs) remain unclear. Following treatment of VSMCs with different doses of insulin, a fluorescence recovery after photobleaching (FRAP) assay was performed to evaluate GJIC function in treated VSMCs. The results showed that high‑dose insulin suppressed GJIC function. Western blot assays further demonstrated that high‑dose insulin induced the phosphorylation of Cx43 at s368 and downregulated the expression of Cx43. H2O2 release assays demonstrated that high‑dose insulin treatment significantly elevated the cellular H2O2 level. In addition, compared with cells treated with high‑dose insulin, pretreatment with catalase significantly restored the cellular GJIC function, decreased the phosphorylation level of Cx43 at s368, and enhanced Cx43 expression. In conclusion, these data indicate that high‑dose insulin inhibits cellular GJIC function through the oxidative stress‑activated signaling pathway. This phenomenon may also constitute a potential mechanism underlying the pathogenesis of insulin resistance and its complications.

  11. Prediction of mechanical properties of compacted binary mixtures containing high-dose poorly compressible drug.

    Science.gov (United States)

    Patel, Sarsvatkumar; Bansal, Arvind Kumar

    2011-01-17

    The aim of the study was to develop, compare and validate predictive model for mechanical property of binary systems. The mechanical properties of binary mixtures of ibuprofen (IBN) a poorly compressible high dose drug, were studied in presence of different excipients. The tensile strength of tablets of individual components viz. IBN, microcrystalline cellulose (MCC), and dicalcium phosphate dihydrate (DCP) and binary mixtures of IBN with excipients was measured at various relative densities. Prediction of the mechanical property of binary mixtures, from that of single components, was attempted using Ryshkewitch-Duckworth (R-D) and Percolation theory, by assuming a linear mixing rule or a power law mixing rule. The models were compared, and the best model was proposed based on the distribution of residuals and the Akaike's information criterion. Good predictions were obtained with the power law combined with linear mixing rule, using R-D and Percolation models. The results indicated that the proposed model can well predict the mechanical properties of binary system containing predominantly poorly compressible drug candidate. The predictions of these models and conclusions can be systematically generalized to other pharmaceutical powders.

  12. Comparative dosimetry of GammaMed Plus high-dose rate 192 Ir brachytherapy source

    Directory of Open Access Journals (Sweden)

    Patel N

    2010-01-01

    Full Text Available The comparative dosimetry of GammaMed (GM Plus high-dose rate brachytherapy source was performed by an experiment using 0.1-cc thimble ionization chamber and simulation-based study using EGSnrc code. In-water dose measurements were performed with 0.1-cc chamber to derive the radial dose function (r = 0.8 to 20.0 cm and anisotropy function (r = 5.0 cm with polar angle from 10° to 170°. The nonuniformity correction factor for 0.1-cc chamber was applied for in-water measurements at shorter distances from the source. The EGSnrc code was used to derive the dose rate constant (L, radial dose function g L (r and anisotropy function F(r, q of GM Plus source. The dosimetric data derived using EGSnrc code in our study were in very good agreement relative to published data for GM Plus source. The radial dose function up to 12 cm derived from measured dose using 0.1-cc chamber was in agreement within ±3% of data derived by the simulation study.

  13. High-dose weekly fractionation radiotherapy in advanced cancer of the uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Browde, S.; Nissenbaum, M.; De Moor, N.G. (University of the Witwatersrand, Johannesburg (South Africa))

    1984-07-07

    A trial comparing two different radiotherapy techniques and schedules is the treatment of 83 patients with advanced cancer of the uterine cervix (stage IIIB) employing external irradiation alone is described. The one technique, used routinely in this department, employed a conventional daily fractionation schedule while the other used a high-dose weekly fractionation regimen. The techniques are described. The aim of the trial was to compare the efficacy and morbidity of these two methods of treatment. Dose distribution curves in cross-section and midsagittal planes are shown and calculations or equivalent doses at various selected points using Ellis's nominal single-dose formula are tabulated. The 2-year survival figures were 33% for the daily fractionation technique and 22% for the weekly regimen. Serious late complication rates were 6% for the daily regimen and 22% for the weekly schedule. These differences are not statistically significant. Late complication rates in the weekly fractionation regimen appeared to be lower than figures quoted by other authors. Local control within the irradiated volume was better in the group treated by the daily fractionation method.

  14. A new model of biodosimetry to integrate low and high doses.

    Directory of Open Access Journals (Sweden)

    Mònica Pujol

    Full Text Available Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy, the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberration-among-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation.

  15. Dosimetric perturbations of a lead shield for surface and interstitial high-dose-rate brachytherapy.

    Science.gov (United States)

    Candela-Juan, Cristian; Granero, Domingo; Vijande, Javier; Ballester, Facundo; Perez-Calatayud, Jose; Rivard, Mark J

    2014-06-01

    In surface and interstitial high-dose-rate brachytherapy with either (60)Co, (192)Ir, or (169)Yb sources, some radiosensitive organs near the surface may be exposed to high absorbed doses. This may be reduced by covering the implants with a lead shield on the body surface, which results in dosimetric perturbations. Monte Carlo simulations in Geant4 were performed for the three radionuclides placed at a single dwell position. Four different shield thicknesses (0, 3, 6, and 10 mm) and three different source depths (0, 5, and 10 mm) in water were considered, with the lead shield placed at the phantom surface. Backscatter dose enhancement and transmission data were obtained for the lead shields. Results were corrected to account for a realistic clinical case with multiple dwell positions. The range of the high backscatter dose enhancement in water is 3 mm for (60)Co and 1 mm for both (192)Ir and (169)Yb. Transmission data for (60)Co and (192)Ir are smaller than those reported by Papagiannis et al (2008 Med. Phys. 35 4898-4906) for brachytherapy facility shielding; for (169)Yb, the difference is negligible. In conclusion, the backscatter overdose produced by the lead shield can be avoided by just adding a few millimetres of bolus. Transmission data provided in this work as a function of lead thickness can be used to estimate healthy organ equivalent dose saving. Use of a lead shield is justified.

  16. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Deeg, H.J. (Fred Hutchinson Cancer Research Center, Seattle, WA); Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.

    1982-04-01

    Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given either as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to to 4 X 10/sup 8/ cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single-dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis.In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after in vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

  17. Engraftment of DLA-nonidentical unrelated canine marrow after high-dose fractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Deeg, H.J.; Storb, R.; Shulman, H.M.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.

    1982-04-01

    Marrow transplants were carried out between unrelated DLA-nonidentical dogs. Recipients were conditioned for transplantation by total body irradiation (TBI) given eigher as a single dose of 9 Gy (900 rad) or fractionated in three increments of 6 Gy (600 rad) each at intervals of 48 hr. All recipients received marrow, less than or equal to 4 x 10(8) cells/kg, and no buffy coat cells. No immunosuppression was given after grafting. All 10 dogs given single dose total body irradiation failed to show engraftment and died with marrow aplasia and infectious complications (median survival 12 days). In contrast, all 10 dogs given fractionated TBI had sustained engraftment and died with graft-versus-host disease (GVHD) and infectious complications (median survival 12.5 days). None of the dogs died from radiation-induced gastroenteritis. In conclusion, resistance to DLA-nonidentical unrelated marrow grafts can be abrogated by high-dose TBI. This technique may allow hemopoietic engraftment even after i vitro manipulation of the marrow such as lymphocyte depletion by cell separation or treatment with anti-T cell antisera.

  18. Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'

    Science.gov (United States)

    Salter, Bill J.; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

    2011-04-01

    Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min-1) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach.

  19. Fabrication of the Supplemental Surveillance Capsules to Construct the Data of High-dose Irradiation Embrittlement

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Ki; Maeng, Young Jae; Kim, Kyung Sik; Lim, Mi Joung; Yoo, Choon Sung; Kim, Byoung Chul [Korea Reactor Integrity Surveillance Technology, Daejeon (Korea, Republic of)

    2015-10-15

    In order to monitor the neutron irradiation embrittlement of the reactor vessel material, the surveillance program should be implemented during the reactor operation through the plant life. This surveillance program requires the surveillance capsules which contain the various test specimens, thermal monitors, and neutron dosimeters. For PWRs in Korea, total six surveillance capsules are installed before plant operation and are programmed to be withdrawn and tested periodically in accordance with the surveillance program. The surveillance capsules are typically installed in the downcomer region and are located closer to the reactor core than the vessel wall in order to get more accelerated embrittlement characteristics of the vessel material. The supplemental surveillance capsules were fabricated to obtain the data of high-dose irradiation embrittlement. All test specimens in the capsules were made with the archive material of Hanbit Units 3 and 4. The supplemental capsules were designed to have the same outside dimensions as the capsules of Hanbit Unit 1 and were installed in Hanbit Unit 1. The withdrawal schedule will be calculated.

  20. High dose thermoluminescence dosimetry performance of Sol-gel synthesized TiO{sub 2} phosphors

    Energy Technology Data Exchange (ETDEWEB)

    Salas J, Ch. J.; Cruz V, C. [Universidad de Sonora, Departamento de Investigacion en Polimeros y Materiales, Apdo. Postal 130, 83000 Hermosillo, Sonora (Mexico); Castillo U, D. M.; Flores M, K. [Universidad de Sonora, Departamento de Ciencias Quimico Biologicas, Apdo. Postal 130, 83000 Hermosillo, Sonora (Mexico); Bernal, R. [Universidad de Sonora, Departamento de Investigacion en Fisica, Apdo. Postal 5-088, 83190 Hermosillo, Sonora (Mexico); Castano, V. M., E-mail: castillouzeta@gmail.com [UNAM, Instituto de Fisica, Centro de Fisica Aplicada y Tecnologia Avanzada, Apdo. Postal 1-1010, Queretaro, Qro. (Mexico)

    2015-10-15

    Full text: TiO{sub 2} is a ceramic material with many applications due to their different crystalline phases (rutile, anatase and brookite). It has attracted attention in several fields because their high mechanical strength, chemical stability and ion-conducting properties. Moreover, in recent years, some research groups gained interest in the thermoluminescence features of TiO{sub 2} concerning their potential use as thermoluminescence dosimeter. In this work, we present experimental results obtained in the first stage of a long-term research project focused in the synthesis of TiO{sub 2} phosphors for dosimetric applications. The thermoluminescent characterization of samples was carried out after being exposed to beta particle irradiation. TiO{sub 2} was prepared by alkoxide sol-gel route using titanium tetrabutoxide as precursor, ethanol, water and ammonia as catalyst. Pellet-shaped samples were annealed at 700 degrees C for 6 h in air atmosphere followed by slow cooling, and then were exposed to radiation doses from 25 to 400 Gy. The glow curves display maxima located at 103 and 238 degrees C when a 5 C/s heating rate is used. From the experimental results here presented, we conclude that TiO{sub 2} is a promising material to develop high dose Tl dosimeters. (Author)

  1. High-dose vaginal metronidazole for recurrent bacterial vaginosis--a pilot study.

    Science.gov (United States)

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

    2014-04-01

    The purpose of this study was to evaluate high-dose intravaginal metronidazole, with or without miconazole, in enhancing cure rates in women with recurrent BV. A total of 43 women with symptomatic recurrent BV were enrolled in a 4-arm study comparing 500 mg versus 750 mg of metronidazole, with or without miconazole, intravaginally for 7 days. Test of cure by saline wet mount and 10% potassium chloride microscopy, pH, Gram stain for Nugent score, and yeast culture were performed 3 times after treatment: 3 to 7 days, 30 to 35 days, and 60 to 70 days. Overall cure rate for the entire group was 92.6% at visit 2, 62.1% at visit 3, and 51.4% at visit 4. At visit 2, there was no difference in cure rates among patients who received metronidazole 750 mg ± miconazole daily (90.5%) compared with metronidazole 500 mg ± miconazole daily (85%). At visit 3, there was a significant improvement in cure rates among patients who received metronidazole 750 mg ± miconazole daily (78.9%) compared with metronidazole 500 mg ± miconazole daily (44.4%) (p 4 or pH > 4.4) at the first visit alter treatment-predicted recurrence. The addition of miconazole did not enhance BV response rates. Cure rates for BV were high in this refractory cohort and seemed dose dependent.

  2. High dose chemotherapy with stem cell support in thetreatment of testicular cancer

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Testicular germ cell cancer (TGCC) is rare form ofmalignant disease that occurs mostly in young manbetween age 15 and 40. The worldwide incidence ofTGCC is 1.5 per 100000 man with the highest rates inNorth Europe. After discovery of cisplatin cure ratesof TGCC are very favorable between 90%-95% andunlike most solid tumors, cure rate for metastatic TGCCis around 80%. Metastatic TGCC is usually treatedwith 3-4 cycles of bleomycin, etoposide, cisplatinumchemotherapy with or without retroperitoneal surgeryand cure rates with this approach are between 41% inpoor risk group and 92% in good risk group of patients.Cure rates are lower in relapsed and refractory patientsand many of them will die from the disease if not curedwith first line chemotherapy. High dose chemotherapy(HDCT) approach was used for the first time during the1980s. Progress in hematology allowed the possibility tokeep autologous haematopoietic stem cells alive ex-vivoat very low temperatures and use them to repopulatethe bone marrow after sub-lethal dose of intesivemyeloablative chemotherapy. Despite the fact thatthere is no positive randomized study to prove HDCTconcept, cure rates in relapsed TGCC are higher afterhigh dose therapy then in historical controls in studieswith conventional treatment. Here we review clinicalstudies in HDCT for TGCC, possibilities of mobilisingsufficient number of stem cells and future directions inthe treatment of this disease.

  3. Retraction of colonies and structures of Aspergillus Spp. as a possible high dose sensor

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Valeria B., E-mail: valeriabborges@hotmail.com [Coordenacao dos Programas de Pos-Graduacao em Processos Quimicos e Bioquimicos (EQ/UFRJ), Rio de Janeiro, RJ (Brazil). Escola de Quimica; Vital, Helio C., E-mail: vital@ctex.eb.br [Centro Tecnologico do Exercito (DDQBN/CTEx), Rio de Janeiro, RJ (Brazil). Div. de Defesa Quimica, Biologica e Nuclear. Secao de Defesa Nuclear; Moraes, Aurea M.L., E-mail: ltbbf@ioc.fiocruz.br [Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Departamento de Micologia

    2013-07-01

    Changes in the length of macro-and microscopic structures of irradiated Aspergillus spp. colonies were investigated in this work in search for correlations with radiation dose. Effects related to growth and morphology produced by exposure to radiation doses ranging from 0.0 up to 8.0 kGy on strains of A. flavus (CMT 00079), A. parasiticus (CMT 00064) and A ochraceus (CMT 00145) were analyzed. Fungal colonies were inoculated on fresh peanut seeds and incubated for 5 days at 25°C. On the sixth day the samples were irradiated and moved to Petri dishes containing PDA culture medium where they remained incubated for 7 days at 25°C Post irradiation growth was periodically monitored by visual inspections and measurements of mycelial diameters. In addition, microscopic analyses were performed to determine the length of the major structures of the colonies. It has been found that irradiation causes a decrease in the diameter of colonies as well as in the length of microscopic structures of the fungus. The amount of retraction has been found to be strongly correlated to radiation dose. Such findings hint at the possibility of using in situ Aspergillus spp. colonies as high-dose living dosimeters in the event of massive radiation exposures. (author)

  4. The effect of intraarterial high-dose cisplatin on lymph nodes in oral and oropharyngeal cancer

    Directory of Open Access Journals (Sweden)

    A F Kovács

    2012-01-01

    Full Text Available Aim of Study: To assess the effect of strictly local treatment [intraarterial chemotherapy (iaCHT with high-dose cisplatin and parallel neutralization] in the primary oral and oropharyngeal cancer (OOSCC on the dependent cervical lymph nodes. Patients and Methods: Seventeen consecutive patients with OOSCC and clinically positive necks underwent a prospective blinded comparison of two pre-surgical fluor18-deoxyglucose (FDG-positron emission tomography (PET examinations: baseline examination 1 week before and follow-up examination 3 weeks after iaCHT. Maximal standardized uptake (SUVmax values of lymph nodes were measured and compared with each other and histopathology. Results: The SUVmax value of the primary and all neck lymph nodes with uptake decreased significantly. Twelve/17 patients having metastases revealed significant decrease (P = 0.03, and benign lymph nodes showed non-significant decrease of the SUVmax. All neck lymph nodes with uptake and nodal metastases showed a significant reduction (P = 0.004 of standard uptake values (SUV. Conclusion: A regional effect of intraarterial cisplatin is proven. To date, it is not clear whether this is due to decreasing inflammatory reaction or a translymphatic anti-neoplastic effect.

  5. High doses of gamma radiation suppress allergic effect induced by food lectin

    Science.gov (United States)

    Vaz, Antônio F. M.; Souza, Marthyna P.; Vieira, Leucio D.; Aguiar, Jaciana S.; Silva, Teresinha G.; Medeiros, Paloma L.; Melo, Ana M. M. A.; Silva-Lucca, Rosemeire A.; Santana, Lucimeire A.; Oliva, Maria L. V.; Perez, Katia R.; Cuccovia, Iolanda M.; Coelho, Luana C. B. B.; Correia, Maria T. S.

    2013-04-01

    One of the most promising areas for the development of functional foods lies in the development of effective methods to reduce or eliminate food allergenicity, but few reports have summarized information concerning the progress made with food irradiation. In this study, we investigated the relationship between allergenicity and molecular structure of a food allergen after gamma irradiation and evaluate the profile of the allergic response to irradiated allergens. Cramoll, a lectin isolated from a bean and used as a food allergen, was irradiated and the possible structural changes were accompanied by spectrofluorimetry, circular dichroism and microcalorimetry. Subsequently, sensitized animals subjected to intragastric administration of non-irradiated and irradiated Cramoll were treated for 7 days. Then, body weight, leukocytes, cytokine profiles and histological parameters were also determined. Cramoll showed complete inhibition of intrinsic activity after high radiation doses. Changes in fluorescence and CD spectra with a simultaneous collapse of the tertiary structure followed by a pronounced decrease of native secondary structure were observed after irradiation. After oral challenge, sensitized mice demonstrate an association between Cramoll intake, body weight loss, eosinophilia, lymphocytic infiltrate in the gut and Eotaxin secretion. Irradiation significantly reduces, according to the dose, the effects observed by non-irradiated food allergens. We confirm that high-dose radiation may render protein food allergens innocuous by irreversibly compromising their molecular structure.

  6. A New Model of Biodosimetry to Integrate Low and High Doses

    Science.gov (United States)

    Pujol, Mònica; Barquinero, Joan-Francesc; Puig, Pedro; Puig, Roser; Caballín, María Rosa; Barrios, Leonardo

    2014-01-01

    Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy, the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberration-among-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation. PMID:25461738

  7. Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

    Science.gov (United States)

    Hassan, M; Oberg, G; Björkholm, M; Wallin, I; Lindgren, M

    1993-01-01

    The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used.

  8. A Case of Type 2 Amiodarone-Induced Thyrotoxicosis That Underwent Total Thyroidectomy under High-Dose Steroid Administration

    Directory of Open Access Journals (Sweden)

    Koshi Hashimoto

    2015-01-01

    Full Text Available Amiodarone is used commonly and effectively in the treatment of arrhythmia; however, it may cause thyrotoxicosis categorized into two types: iodine-induced hyperthyroidism (type 1 amiodarone-induced thyrotoxicosis (AIT and destructive thyroiditis (type 2 AIT. We experienced a case of type 2 AIT, in which high-dose steroid was administered intravenously, and we finally decided to perform total thyroidectomy, resulting in a complete cure of the AIT. Even though steroid had been administered to the patient (maximum 80 mg of prednisolone, the operation was performed safely and no acute adrenal crisis as steroid withdrawal syndrome was found after the operation. Few cases of type 2 AIT that underwent total thyroidectomy with high-dose steroid administration have been reported. The current case suggests that total thyroidectomy should be taken into consideration for patients with AIT who cannot be controlled by medical treatment and even in those under high-dose steroid administration.

  9. SU-E-T-315: The Change of Optically Stimulated Luminescent Dosimeters (OSLDs) Sensitivity by Accumulated Dose and High Dose

    Energy Technology Data Exchange (ETDEWEB)

    Han, S; Jung, H; Kim, M; Ji, Y; Kim, K [University of Science and Technology, Daejeon (Korea, Republic of); Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Choi, S; Park, S; Yoo, H [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yi, C [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2014-06-01

    Purpose: The objective of this study is to evaluate radiation sensitivity of optical stimulated luminance dosimeters (OSLDs) by accumulated dose and high dose. Methods: This study was carried out in Co-60 unit (Theratron 780, AECL, and Canada) and used InLight MicroStar reader (Landauer, Inc., Glenwood, IL) for reading. We annealed for 30 min using optical annealing system which contained fluorescent lamps (Osram lumilux, 24 W, 280 ∼780 nm). To evaluate change of OSLDs sensitivity by repeated irradiation, the dosimeters were repeatedly irradiated with 1 Gy. And whenever a repeated irradiation, we evaluated OSLDs sensitivity. To evaluate OSLDs sensitivity after accumulated dose with 5 Gy, We irradiated dose accumulatively (from 1 Gy to 5 Gy) without annealing. And OSLDs was also irradiated with 15, 20, 30 Gy to certify change of OSLDs sensitivity after high dose irradiation. After annealing them, they were irradiated with 1Gy, repeatedly. Results: The OSLDs sensitivity increased up to 3% during irradiating seven times and decreased continuously above 8 times. That dropped by about 0.35 Gy per an irradiation. Finally, after 30 times irradiation, OSLDs sensitivity decreased by about 7%. For accumulated dose from 1 Gy to 5 Gy, OSLDs sensitivity about 1 Gy increased until 4.4% after second times accumulated dose compared with before that. OSLDs sensitivity about 1 Gy decreased by 1.6% in five times irradiation. When OSLDs were irradiated ten times with 1Gy after irradiating high dose (10, 15, 20 Gy), OSLDs sensitivity decreased until 6%, 9%, 12% compared with it before high dose irradiation, respectively. Conclusion: This study certified OSLDs sensitivity by accumulated dose and high dose. When irradiated with 1Gy, repeatedly, OSLDs sensitivity decreased linearly and the reduction rate of OSLDs sensitivity after high dose irradiation had dependence on irradiated dose.

  10. Labour induction with an intermediate-dose oxytocin regimen has advantages over a high-dose regimen.

    Science.gov (United States)

    Manjula, B G; Bagga, R; Kalra, J; Dutta, S

    2015-05-01

    A total of 200 women planned for labour induction were randomised to receive high-dose oxytocin (6 mU/min with similar increments every 45 min) or intermediate-dose oxytocin (3 mU/min with similar increments every 45 min). Oxytocin solution was prepared with 30 units in 500 ml saline with which the infusion rate in ml/h is numerically equal to oxytocin in mU/min. We observed that the caesarean rate (18% vs 6%, p = 0.009), contraction abnormalities (35% vs 14%, p = 0.0005) and neonatal bilirubin levels (7.99 ± 2.70 vs 6.80 ± 2.65, p = 0.002) were higher with high-dose than with intermediate-dose. The induction-delivery interval (IDI) was similar (10 h 13 min with high-dose and 11 h 5 min with intermediate-dose; p = 0.237, NS). Nulliparous women benefited more with intermediate-dose as the caesarean rate was higher with high-dose (24.6% vs 7.9%, p = 0.011). Although the caesarean rate was higher in multiparous women with high-dose oxytocin, it was statistically not significant (5.7% vs 2.7%; p = 0.609). Oxytocin regimens for labour induction are usually high-dose (4-6 mU/min) or low-dose (1-1.5 mU/min). The former is associated with more contraction abnormalities and the latter with prolonged IDI; both result in an increased caesarean rate. In order to offset these disadvantages, an intermediate- dose regimen was selected. The increment interval of 45 min was selected in accordance with the pharmacokinetics of oxytocin. We observed a lower caesarean rate when compared with the high-dose regimen, without any increase in the IDI. Hence, we propose that the intermediate-dose oxytocin regimen should be preferred to the high-dose regimen for labour induction.

  11. Study of teflon pads as high doses dosemeters; Estudo de pastilhas de teflon como dosimetros de doses altas

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Maria Ines; Caldas, Linda V.E., E-mail: miteixeira@ipen.br, E-mail: lcaldas@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-11-01

    The aim of this work is to study the Teflon, which is used as a binder in the manufacture of dosimetric tablets, for the feasibility of this material as high dose dosemeter. In this paper we used the technique of thermally stimulated luminescence (OSL) to characterize the dosimetric properties of Teflon. Teflon samples were exposed to different doses of radiation, using a source of gamma radiation ({sup 60}Co). It was obtained dose-response curve between 100 Gy to 50 kGy and reproducibility of OSL response. The preliminary results show that Teflon is a useful material to high dose dosimetry.

  12. Teflon pastille use in high dose dosimetry; Utilizacao de pastilhas de teflon em dosimetria de doses altas

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Maria Ines [Associacao Educacional Nove de Julho (UNINOVE), Sao Paulo, SP (Brazil); Caldas, Linda V.E., E-mail: miteixeira@ipen.b, E-mail: lcaldas@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-10-26

    This paper study the Teflon, which is used as aglomerant in the confection of dosimetric pastilles, for the viabilization of this material as high dose dosimeter. This paper used the OSL technique for the characterization of dosimetric properties of Teflon. The doses-response curve has been obtained for {sup 60}Co radiation between 100 Gy and 50 kGy, and the OSL answer reproducibility. The preliminary results shown that the Teflon is a material which can be used for high dose dosimetry

  13. High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was perfor...

  14. Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: a potential role in preservation of beta-cell mass.

    Science.gov (United States)

    Baidal, D A; Ricordi, C; Garcia-Contreras, M; Sonnino, A; Fabbri, A

    2016-07-01

    Several studies have evaluated the role of inflammation in type 1 diabetes (T1D). The safety profile and anti-inflammatory properties of high dose omega-3 fatty acids combined with Vitamin D supplementation make this therapy a possible candidate for T1D intervention trials. Herein, we describe the case of a 14-year-old boy with new onset T1D treated with high dose Omega-3 and vitamin D3. By 12 months, peak C-peptide increased to 0.55 nmol/L (1.66 ng/mL) corresponding to a 20% increment from baseline and AUC C-peptide was slightly higher compared to 9 months (0.33 vs. 0.30 nmol/L/min) although remaining slightly lower than baseline. Combination high-dose Omega-3 fatty acids and high-dose vitamin D3 therapy was well tolerated and may have beneficial effects on beta-cell function. Randomized controlled trials could be of assistance to determine whether this therapy may result in the preservation of beta-cell function in patients with new onset T1D.

  15. Monte Carlo Dosimetry of the 60Co BEBIG High Dose Rate for Brachytherapy.

    Directory of Open Access Journals (Sweden)

    Luciana Tourinho Campos

    Full Text Available The use of high-dose-rate brachytherapy is currently a widespread practice worldwide. The most common isotope source is 192Ir, but 60Co is also becoming available for HDR. One of main advantages of 60Co compared to 192Ir is the economic and practical benefit because of its longer half-live, which is 5.27 years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading brachytherapy machine (MultiSource®; it has the option to use either the 60Co or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co source (model Co0.A86, which is referred to as the new BEBIG 60Co HDR source and is a modified version of the 60Co source (model GK60M21, which is also from BEBIG.The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate the required treatment-planning parameters. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, which is a part of EGS++ that allows calculating the radial dose function around the source. The spectrum to simulate 60Co was composed of two photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used; the contribution of the electrons to the dose is negligible because of the full absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon cross-section library was used in subsequent simulations, and the photoelectric effect, pair

  16. Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms

    Institute of Scientific and Technical Information of China (English)

    Wei-Dong Du; Song-Bai Zheng; Zu-Rong Yuan; Jian Sun; Jian-Xiong Tang; Ai-Qun Cheng; Da-Ming Shen; Chun-Jin Huang; Xiao-Hua Song; Xiao-Feng Yu

    2003-01-01

    AIM: To observe the therapeutic efficacy of high-dose Vitamin C (Vit. C) on acute pancreatitis (AP), and to explore its potential mechanisms.METHODS: Eghty-four AP patients were divided into treatment group and control group, 40 healthy subjects were taken as a normal group. In the treatment group,Vit. C (10 g/day) was given intravenously for 5 days,whereas in the control group, Vit. C (1 g/day) was given intravenously for 5 days. Symptoms, physical signs, duration of hospitalization, complications and mortality rate were monitored. Meanwhile, serum amylase, urine amylase and leukocyte counts were also determined. The concentration of plasma vitamin C (P-VC), plasma lipid peroxide (P-LPO),plasma vitamin E (P-VE), plasma β-carotene (P-13-CAR),whole blood glutathione (WB-GSH) and the activity of erythrocyte surperoxide dimutase (E-SOD) and erythrocyte catalase (E-CAT) as well as T lymphocyte phenotype were measured by spectrophotometry in the normal group and before and after treatment with Vit. C in the treatment and the control group.RESULTS: Compared with the normal group, the average values of P-VC, P-VE, P-β-CAR, WB-GSH and the activity of E-SOD and E-CAT in AP patients were significantly decreased and the average value of P-LPO was significantly increased, especially in severe acute pancreatitis (SAP) patients (P<0.05. P-VC, P=0.045; P-VE, P=0.038; P=0.041;P-β-CAR, P=0.046; WB-GSH, P=0.039; E-SOD, P=0.019;E-CAT, P =0.020; P-LPO, P =0.038). Compared with the normal group, CD3 and CD4 positive cells in AP patients were significantly decreased. The ratio of CD4/CD8 and CD4 positive cells were decreased, especially in SAP patients (P<0.05. CD4/CD8, P =0.041; CD4, P =0.019). Fever and vomiting disappeared, and leukocyte counts and amylase in urine and blood become normal quicker in the treatment group than in the control group. Moreover, patients in treatment group also had a higher cure rate, a lower complication rate and a shorter in-ward days compared with

  17. Monte Carlo Dosimetry of the 60Co BEBIG High Dose Rate for Brachytherapy

    Science.gov (United States)

    Campos, Luciana Tourinho; de Almeida, Carlos Eduardo Veloso

    2015-01-01

    Introduction The use of high-dose-rate brachytherapy is currently a widespread practice worldwide. The most common isotope source is 192Ir, but 60Co is also becoming available for HDR. One of main advantages of 60Co compared to 192Ir is the economic and practical benefit because of its longer half-live, which is 5.27 years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading brachytherapy machine (MultiSource®); it has the option to use either the 60Co or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co source (model Co0.A86), which is referred to as the new BEBIG 60Co HDR source and is a modified version of the 60Co source (model GK60M21), which is also from BEBIG. Objective and Methods The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate the required treatment-planning parameters. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, which is a part of EGS++ that allows calculating the radial dose function around the source. The spectrum to simulate 60Co was composed of two photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used; the contribution of the electrons to the dose is negligible because of the full absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon cross-section library was used in subsequent simulations, and the

  18. Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Christina [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany); Engenhart-Cabillic, Rita; Vorwerk, Hilke [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Schmidt, Michael; Huhnt, Winfried; Blank, Eyck; Sidow, Dietrich; Buchali, Andre [Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany)

    2017-02-15

    Using prospectively collected patient-related, dose-related, and pulmonary function test (PFT) data before radiotherapy (RT) and at several follow-up visits after RT, the time course of PFT changes after high-dose radio(chemo)therapy and influencing factors were analyzed. From April 2012 to October 2015, 81 patients with non-small-cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), or esophageal carcinoma where treated with high-dose radio(chemo)therapy. PFT data were collected before treatment and 6 weeks, 12 weeks, and 6 months after RT. The influence of patient- and treatment-related factors on PFT was analyzed. Mean forced expiratory volume in 1 s (FEV1) constantly declined during follow-up (p = 0.001). In total, 68% of patients had a reduced FEV1 at 6 months. Mean vital capacity (VC) didn't change during follow-up (p > 0.05). Mean total lung capacity (TLC) showed a constant decline after RT (p = 0.026). At 6 months, 60% of patients showed a decline in VC and 73% in TLC. The mean diffusion capacity for carbon monoxide (DLCO) declined at 6 and 12 weeks, but recovered slightly at 6 months (p < 0.0005). At 6 months, 86% of patients had a reduced DLCO. After treatment, the partial pressure of CO{sub 2} in the blood (pCO{sub 2}) was increased and pO{sub 2} was decreased (p > 0.05). Only the pretreatment PFT classification had a significant influence on the post-RT FEV1. DLCO seems to be the most reliable indicator for lung tissue damage after thoracic RT. Ventilation parameters appear to be less reliable. Concerning patient- or treatment-related factors, no reliable conclusion can be drawn regarding which factors may be relevant. (orig.) [German] Patientenbezogene, therapiebezogene und Lungenfunktionsdaten (''pulmonary function test'', PFT) wurden vor Radiotherapie (RT) und an verschiedenen Nachsorgeterminen nach RT prospektiv gesammelt, um PFT-Veraenderungen sowie Einflussfaktoren nach Hochdosis-Radio(chemo)therapie zu

  19. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

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    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G. [Duesseldorf Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Laws, H.J.; Kaik, B. van; Goebel, U. [Duesseldorf Univ. (Germany). Abt. Paediatrische Haematologie und Onkologie; Burdach, S. [Halle Univ. (Germany). Abt. Paediatrie; Juergens, H. [Muenster Univ. (Germany). Abt. Paediatrische Hematologie und Onkologie

    1999-10-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (<2 years after diagnosis) or multifocal relapse. Patients and Method: As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Duesseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) oder Double-ME with whole lung irradiation up to 18 Gy (without TBI). Results: The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy. Conclusion: High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion. (orig.) [German] Hintergrund: Ewing-Tumoren sind radio- und chemosensibel. Im metastasierten Stadium ist die Prognose schlecht. Patienten mit Knochen- oder Knochenmarkinfiltration haben nach drei Jahren eine

  20. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Demanes, D. Jeffrey, E-mail: jdemanes@mednet.ucla.edu [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, CA (United States); Martinez, Alvaro A.; Ghilezan, Michel [William Beaumont Hospital, Royal Oak, MI (United States); Hill, Dennis R.; Schour, Lionel; Brandt, David [California Endocurietherapy, Oakland, CA (United States); Gustafson, Gary [William Beaumont Hospital, Royal Oak, MI (United States)

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  1. Endocrine function following high dose proton therapy for tumors of the upper clivus

    Energy Technology Data Exchange (ETDEWEB)

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  2. Tensile stress corrosion cracking of type 304 stainless steel irradiated to very high dose

    Energy Technology Data Exchange (ETDEWEB)

    Chung, H. M.; Ruther, W. E.; Strain, R. V.; Shack, W. J.

    2001-09-01

    Certain safety-related core internal structural components of light water reactors, usually fabricated from Type 304 or 316 austenitic stainless steels (SSs), accumulate very high levels of irradiation damage (20--100 displacement per atom or dpa) by the end of life. The data bases and mechanistic understanding of, the degradation of such highly irradiated components, however, are not well established. A key question is the nature of irradiation-assisted intergranular cracking at very high dose, i.e., is it purely mechanical failure or is it stress-commotion cracking? In this work, hot-cell tests and microstructural characterization were performed on Type 304 SS from the hexagonal fuel can of the decommissioned EBR-11 reactor after irradiation to {approximately}50 dpa at {approximately}370 C. Slow-strain-rate tensile tests were conducted at 289 C in air and in water at several levels of electrochemical potential (ECP), and microstructural characteristics were analyzed by scanning and transmission electron microcopies. The material deformed significantly by twinning and exhibited surprisingly high ductility in air, but was susceptible to severe intergranular stress corrosion cracking (IGSCC) at high ECP. Low levels of dissolved O and ECP were effective in suppressing the susceptibility of the heavily irradiated material to IGSCC, indicating that the stress corrosion process associated with irradiation-induced grain-boundary Cr depletion, rather than purely mechanical separation of grain boundaries, plays the dominant role. However, although IGSCC was suppressed, the material was susceptible to dislocation channeling at low ECP, and this susceptibility led to poor work-hardening capability and low ductility.

  3. False-negative urine human chorionic gonadotropin in molar pregnancy: " The high-dose hook effect" !

    Directory of Open Access Journals (Sweden)

    Sujata Narendra Datti

    2015-01-01

    Full Text Available Failure to detect pregnancy in the emergency situations can have important consequences. These include missing of ectopic pregnancy (the leading cause of first-trimester pregnancy-related maternal death, administration of medications contraindicated in pregnancy, fetal radiation exposure, and medico legal problems. This in turn has led to the dictum to check for pregnancy in all women of child-bearing age group. Urine pregnancy (human chorionic gonadotropin [hCG] test is the commonly used test to rule out pregnancy and has been reported by Griffey et al. in their study to achieve 100% sensitivity and 99.2% specificity in a clinical setting, resulting in a positive predictive value of 98.3% and a negative predictive value of nearly 100%. However, the sensitivity is influenced not only by the quantity of β hCG but on its variants that vary with different weeks of pregnancy. β hCG is present in several variant forms that change in their concentrations at different stages of pregnancy. In spite of its high sensitivity, in the presence of molar pregnancy that is associated with very high levels of β hCG it fails to detect the antigen (β hCG. This is explained by the phenomenon known as "high-dose hook effect" which further leads to delay in diagnosis and treatment. This can be overcome by dilution of the sample. In such cases, diagnosis will be made by serum β hCG and ultrasound (USG. Here, we present a case of gravida 2 para 1 living 1 with 2΍ months amenorrhea with bleeding p/v and pain abdomen of 20 days duration whose urine β hCG was repeatedly negative and diagnosis was made by serum β hCG and USG.

  4. Clinical implementation of a novel applicator in high-dose-rate brachytherapy treatment of esophageal cancer

    Directory of Open Access Journals (Sweden)

    Ivan M. Buzurovic

    2016-08-01

    Full Text Available Purpose : In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA and the initial clinical experience in high-dose-rate (HDR brachytherapy treatment of esophageal cancer, using this applicator. Material and methods: Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio-opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient’s response to the treatment were elaborated as well. Results : The experiments showed sub-millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons. Conclusions : The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can

  5. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

    Energy Technology Data Exchange (ETDEWEB)

    Shwetha, Bondel [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Ravikumar, Manickam, E-mail: drravikumarm@gmail.com [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Supe, Sanjay S.; Sathiyan, Saminathan [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Lokesh, Vishwanath [Department of Radiotherapy, Kidwai, Memorial Institute of Oncology, Bangalore (India); Keshava, Subbarao L. [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India)

    2012-04-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  6. Single versus multichannel applicator in high-dose-rate vaginal brachytherapy optimized by inverse treatment planning.

    Science.gov (United States)

    Bahadur, Yasir A; Constantinescu, Camelia; Hassouna, Ashraf H; Eltaher, Maha M; Ghassal, Noor M; Awad, Nesreen A

    2015-01-01

    To retrospectively compare the potential dosimetric advantages of a multichannel vaginal applicator vs. a single channel one in intracavitary vaginal high-dose-rate (HDR) brachytherapy after hysterectomy, and evaluate the dosimetric advantage of fractional re-planning. We randomly selected 12 patients with endometrial carcinoma, who received adjuvant vaginal cuff HDR brachytherapy using a multichannel applicator. For each brachytherapy fraction, two inverse treatment plans (for central channel and multichannel loadings) were performed and compared. The advantage of fractional re-planning was also investigated. Dose-volume-histogram (DVH) analysis showed limited, but statistically significant difference (p = 0.007) regarding clinical-target-volume dose coverage between single and multichannel approaches. For the organs-at-risk rectum and bladder, the use of multichannel applicator demonstrated a noticeable dose reduction, when compared to single channel, but statistically significant for rectum only (p = 0.0001). For D2cc of rectum, an average fractional dose of 6.1 ± 0.7 Gy resulted for single channel vs. 5.1 ± 0.6 Gy for multichannel. For D2cc of bladder, an average fractional dose of 5 ± 0.9 Gy occurred for single channel vs. 4.9 ± 0.8 Gy for multichannel. The dosimetric benefit of fractional re-planning was demonstrated: DVH analysis showed large, but not statistically significant differences between first fraction plan and fractional re-planning, due to large inter-fraction variations for rectum and bladder positioning and filling. Vaginal HDR brachytherapy using a multichannel vaginal applicator and inverse planning provides dosimetric advantages over single channel cylinder, by reducing the dose to organs at risk without compromising the target volume coverage, but at the expense of an increased vaginal mucosa dose. Due to large inter-fraction dose variations, we recommend individual fraction treatment plan optimization.

  7. Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements

    Science.gov (United States)

    Whitaker, May

    2016-01-01

    Purpose Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. Material and methods This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. Results The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. Conclusions The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected. PMID:27504129

  8. High dose rate interstitial brachytherapy in soft tissue sarcomas: technical aspect

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Mi Son; Kang, Seung Hee; Kim, Byoung Suck; Oh, Young Taek [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1999-03-01

    To discuss the technical aspect of interstitial brachytherapy including method of implant, insertion time of radioactive source, total radiation dose, and complication, we reviewed patients who had diagnoses of soft tissue sarcoma and were treated by conservative surgery, interstitial implant and external beam radiation therapy. Between May 1995 and Dec. 1997, the patients with primary or recurrent soft tissue sarcoma underwent surgical resection (wide margin excision) and received radiotherapy including interstitial brachytherapy. Catheters were placed with regular intervals of 1-1.5 cm immediately after tumor removal and covering the critical structures, such as neurovascular bundle or bone, with gelform, muscle, or tissue expander in the cases where the tumors were close to those structures. Brachytherapy consisted of source axis with 2-2.5 Gy/fraction, twice a day, starting on 6th day after the surgery. Within one month after the surgery, total dose of 50-55 Gy was delivered to the tumor bed with wide margin by the external beam radiotherapy. All patients completed planned interstitial brachytherapy without acute side effects directly related with catheter implantation such as infection or bleeding. With median follow up duration of 25 months (range 12-41 months), no local recurrences were observed. And there was no severe form of chromic complication (RTOG/EORTC grade 3 or 4). The high dose rate interstitial brachytherapy is easy and safe way to minimize the radiation dose delivered to the adjacent normal tissue and to decrease radiation induced chronic morbidity such as fibrosis by reducing the total dose of external radiotherapy in the management of soft tissue sarcoma with conservative surgery.

  9. Relativistic electrons high doses at International Space Station and Foton M2/M3 satellites

    Science.gov (United States)

    Dachev, T. P.; Tomov, B.; Matviichuk, Yu.; Dimitrov, Pl.; Bankov, N.

    2009-12-01

    The paper presents observation of relativistic electrons. Data are collected by the Radiation Risk Radiometer-Dosimeters (R3D) B2/B3 modifications during the flights of Foton M2/M3 satellites in 2005 and 2007 as well as by the R3DE instrument at the European Technology Exposure Facility (EuTEF) on the Columbus External Payload Adaptor at the International Space Station (ISS) in the period February 20 - April 28, 2008. On the Foton M2/M3 satellites relativistic electrons are observed more frequently than on the ISS because of higher (62.8°) inclination of the orbit. At both Foton satellites the usual duration of the observations are a few minutes long. On the ISS the duration usually is about 1 min or less. The places of observations of high doses due to relativistic electrons are distributed mainly at latitudes above 50° geographic latitude in both hemispheres on Foton M2/M3 satellites. A very high maximum is found in the southern hemisphere at longitudinal range 0°-60°E. At the ISS the maximums are observed between 45° and 52° geographic latitude in both hemispheres mainly at longitudes equatorward from the magnetic poles. The measured absolute maximums of dose rates generated by relativistic electrons are found to be as follows: 304 μGy h -1 behind 1.75 g cm -2 shielding at Foton M2, 2314 μGy h -1 behind 0.71 g cm -2 shielding at Foton M3 and 19,195 μGy h -1 (Flux is 8363 cm -2 s -1) behind les than 0.4 g cm -2 shielding at ISS.

  10. Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hideya [Toyonaka Municipal Hospital, Osaka (Japan); Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Inoue, Toshihiko [Osaka Univ., Suita (Japan). Graduate School of Medicine; Furukawa, Souhei; Kakimoto, Naoya [Osaka Univ., Suita (Japan). Graduate School of Dentistry

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

  11. High dose rates obtained outside ISS in June 2015 during SEP event.

    Science.gov (United States)

    Dachev, T P; Tomov, B T; Matviichuk, Yu N; Dimitrov, Pl G; Bankov, N G

    2016-06-01

    The R3DR2 instrument performed measurements in the European Space Agency (ESA) EXPOSE-R2 platform outside the Russian "Zvezda" module of the International Space Station (ISS) in the period 24 October 2014-11 January 2016. It is the Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2015a). Took place in November 2014, this was the first attempt to monitor a small solar energetic particle (SEP) event outside ISS using the Liulin-type DES (Dachev et al., 2015d). In this study, we describe the dosimetric characteristics of the largest SEP event, observed on 22 June 2015 with the R3DR2 instrument outside ISS. The main finding of this study is that SEP protons with a minimum energy of approximately 7MeV at the surface of the R3DR2 detector produced high dose rates, reaching >5000µGyh(-1), while the inner radiation belt maximum dose was at the level of 2200µGyh(-1). If a virtual external vehicle activity (EVA) was performed in the same period of the SEP maximum on 22 June 2015, the doses obtained in the skin of cosmonauts/astronauts can reach 2.84mGy after 6.5h, which is similar to the average absorbed dose inside ISS for 15days (Reitz et al., 2005). A comparison with other extreme events measured with Liulin-type instruments shows that SEPs similar to that observed on 22 June 2015 could be one of the most dangerous events for the cosmonauts/astronauts involved in EVA. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  12. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

    Science.gov (United States)

    Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

  13. Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial

    Science.gov (United States)

    Mikkelsen, Torben S.; Sparreboom, Alex; Cheng, Cheng; Zhou, Yinmei; Boyett, James M.; Raimondi, Susana C.; Panetta, John C.; Bowman, W. Paul; Sandlund, John T.; Pui, Ching-Hon; Relling, Mary V.; Evans, William E.

    2011-01-01

    Purpose To determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m2) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG1-7) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes. Methods From June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m2) as either a 24-hour infusion or a 4-hour infusion at two pediatric hospitals in the United States. The primary outcome measures were the accumulation of MTXPG1-7 in leukemia cells and the antileukemic effects (eg, inhibition of de novo purine synthesis in bone marrow ALL cells, and decrease in circulating ALL cells). Results The 24-hour infusion resulted in significantly higher amounts of MTXPG1-7 in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/109 cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG1-7 accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/109 cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG1-7 but greater antileukemic effects with the longer infusion (median decrease in leukemia cells: 88.4% v 51.8%, P = .0075). In contrast, infusion duration had no significant impact on MTXPG1-7 accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation. Conclusion Shortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes. PMID:21444869

  14. Pharmacokinetics of high doses of cyanocobalamin administered by intravenous injection for 26 weeks in rats.

    Science.gov (United States)

    Nava-Ocampo, Alejandro A; Pastrak, Aleksandra; Cruz, Tony; Koren, Gideon

    2005-01-01

    1. High doses of vitamin B12 (cyanocobalamin) may be therapeutically effective to treat neurological alterations secondary to a wide range of disease states. The aim of the present study was to evaluate the effect of dose and repeated administration on the pharmacokinetics of cyanocobalamin in rats. 2. Forty-eight rats were randomly assigned to receive 1, 5, 25 or 100 mg/kg cyanocobalamin for 182 days (26 weeks). Cyanocobalamin plasma levels were quantified by HPLC on days 1, 85 and 182 of treatment and were analysed by means of non-compartment pharmacokinetic (PK) analysis. In addition, population PK analysis was used to fit cyanocobalamin plasma concentrations to time by means of a two-compartment model for intravascular administration. 3. The half-life of cyanocobalamin ranged from approximately 20 to 50 min, clearance ranged from 4.5 to 9 mL/min and the volume of distribution at steady state ranged from 140 to 470 mL. A statistically significant negative relationship existed between the dose of cyanocobalamin and the normalized area under the plasma concentration-time curve (AUC). This non-linearity was not exhibited in population PK analysis. No evidence of toxicity was observed. 4. At very high and prolonged doses (up to 100 mg/kg for 26 weeks), intravascular administration of cyanocobalamin in rats follows a two-compartment kinetic model and cyanocobalamin undergoes extensive extravascular distribution. The negative relationship between dose and normalized AUC is compatible with possible saturation of tubular reabsorption, thus increasing renal clearance at higher doses.

  15. High-dose phenobarbital or erythropoietin for the treatment of perinatal asphyxia in term newborns.

    Science.gov (United States)

    Avasiloaiei, Andreea; Dimitriu, Cristina; Moscalu, Mihaela; Paduraru, Luminita; Stamatin, Maria

    2013-10-01

    The aim of this study was to compare two neuroprotective strategies to supportive care in the treatment of perinatal asphyxia. A total of 67 term newborns with perinatal asphyxia were included and randomized into three groups: one group received supportive treatment; another group received a single dose of 40 mg/kg phenobarbital; and the third received three daily doses of 1000 IU/kg erythropoietin. The following parameters were analyzed: gestational age, birthweight, Apgar scores, cord blood pH, total serum antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). The newborns were included in the follow-up program and examined up to 18 months of age. TAS was higher in the erythropoietin group than in the other groups. SOD and GPx were lower for infants treated with phenobarbital or erythropoietin compared to control infants. MDA was lower in the erythropoietin group compared to the other groups, although the difference was not statistically significant (P > 0.05). The mortality rate was lower in the phenobarbital and erythropoietin groups (both 4.6%) than in the control group (17.4%). Long-term neurologic follow up showed a high incidence of sequelae in the control group compared to the phenobarbital and erythropoietin groups. Follow-up results were better in the phenobarbital group than in the erythropoietin group for motor and cognitive function at 3 and 6 months and worse for expressive language. At 18 months, however, the differences between these two groups were not significant. High-dose phenobarbital or erythropoietin along with supportive treatment has a positive influence on the outcome of newborns with perinatal asphyxia. Phenobarbital has the advantage of low cost and simplicity. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  16. High Dose Astaxanthin Lowers Blood Pressure and Increases Insulin Sensitivity in Rats: Are These Effects Interdependent?

    Directory of Open Access Journals (Sweden)

    Harry G. Preuss, Bobby Echard, Eiji Yamashita, Nicholas V. Perricone

    2011-01-01

    Full Text Available The present investigation in Sprague-Dawley rats (SD was designed to examine effects of astaxanthin (Asta at different doses on elevated blood pressure (BP and glucose-insulin perturbations produced by heavy sucrose ingestion. We also examined effects of Asta on BP during restraint stress. SD were divided into six groups each containing eight rats. All SD ate a basic diet of ground regular rat chow with sucrose added at 30% w/w. The Control group received only the basic diet containing added sucrose, while the other five groups each received the same diet with added test material: captopril, (30 mg/Kg, pioglitazone (15.0 mg/Kg, low Asta (25 mg/Kg, medium Asta (50 mg/kg or high Asta (100 mg/Kg. Many tests were carried out to examine the mechanisms behind the effects of Asta on BP (serum ACE activity, losartan challenge, and LNAME challenge and the glucose-insulin system (glucose tolerance, HOMA measurement, and insulin challenge. In SD, a relatively low dose of Asta decreased SBP, but produced no major changes in the glucose-insulin system simulating results from a previous study using Zucker Fatty Rats. Increasing the dose of Asta resulted in both a lowering of elevated systolic BP and enhanced insulin sensitivity determined by many different estimations. BP lowering was consistent with changes in the renin-angiotensin (RAS and nitric oxide (NO systems. At the examined doses of each, captopril lowered BP in SD without influencing glucose-insulin metabolism, whereas pioglitazone favorably affected glucose-insulin metabolism while showing essentially no effects on BP. Accordingly, Asta beneficially affects both sucrose-induced elevations of BP and insulin resistance at relatively high doses in SD. Also, Asta at higher doses lessens restraint stress, whereas, captopril and pioglitazone did not at the doses examined, even though they influenced the BP and glucose-insulin systems respectively.

  17. High dose chemotherapy with autologous stem cell transplantation in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Popp, Henning

    2007-06-01

    Full Text Available Background: High-dose chemotherapy (HDT with autologous stem cell transplantation (ASCT plays an important role in the treatment of aggressive non-Hodgkin’s lymphoma (NHL. We report on a retrospective analysis of all patients with diffuse large B-cell lymphoma who were consecutively treated with HDT followed by ASCT at the University Hospital of Bonn, Germany, between 1996 and 2004. Methods: A total of 25 patients were transplanted for biopsy-proven diffuse large B-cell lymphoma (DLBCL. Eight patients received up-front HDT as first-line therapy, four patients received HDT due to incomplete response to conventional induction chemotherapy, and six patients were treated for primary refractory disease. Seven patients had recurrent lymphoma. Results: A complete remission (CR was achieved in 14 of 25 patients (56%. Estimated 3-year survival for patients treated with upfront HDT, chemosensitive patients with incomplete response to first line therapy, and patients with chemosensitive relapsed disease was 87.5%, 50.0% and 60.0%, respectively. In contrast, no patient with primary refractory disease or relapsed disease lacking chemosensitivity lived longer than 8 months. Chemosensitivity was the only significant prognostic factor for overall survival (OS in multivariate analysis. Conclusions: Our results confirm that HDT and ASCT is a highly effective therapy in patients with DLBCL leading to long-term survival in a substantial proportion of patients. Patients treated upfront for high-risk disease, incomplete response to conventional first-line therapy, or for chemosensitive relapse have a good prognosis. In contrast, patients with primary chemorefractory disease and patients with relapsed disease lacking chemosensitivity do not benefit from HDT with ASCT.

  18. Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Niraj H., E-mail: nmehta@mednet.ucla.edu [University of California, Los Angeles, Los Angeles, California (United States); Kamrava, Mitchell; Wang, Pin-Chieh; Steinberg, Michael; Demanes, Jeffrey [University of California, Los Angeles, Los Angeles, California (United States)

    2013-07-15

    Purpose: To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Methods and Materials: Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). Results: A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). Conclusions: A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

  19. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    Science.gov (United States)

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.; Kasap, S. O.

    2014-02-01

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm3+) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm3+-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm3+-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm2+ to Sm3+ reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm2+ to Sm3+ reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  20. Addition of phenylephrine to high-dose insulin in dihydropyridine overdose does not improve outcome.

    Science.gov (United States)

    Engebretsen, Kristin M; Morgan, Matthew W; Stellpflug, Samuel J; Cole, Jon B; Anderson, Christopher P; Holger, Joel S

    2010-10-01

    Vasopressors are commonly used for calcium channel blocker (CCB)-induced cardiogenic shock after calcium and high-dose insulin (HDI). Vasopressor therapy is frequently used in combination with HDI to increase blood pressure and improve outcome. However, no studies have compared the efficacy of HDI to the combination of a vasopressor and HDI in dihydropyridine overdose. We conducted a study to compare the efficacy of HDI to phenylephrine (PE) plus HDI in a porcine model of dihydropyridine toxicity. Cardiogenic shock was induced by administering a nifedipine (NP) infusion of 0.0125 mcg/kg/min until a point of toxicity, defined as a 25% decrease in the baseline product of mean arterial pressure (MAP) × cardiac output (CO). Each arm was resuscitated with 20 mL/kg of saline (NS). The nifedipine infusion continued throughout a 4-h resuscitation protocol. The HDI group was titrated up to 10 units/kg/h of insulin and the HDI/PE group was titrated up to a dose of HDI 10 units/kg/h plus PE 3.6 mcg/kg/min. No baseline differences were found among groups including time to toxicity. Survival was not different between the HDI and HDI/PE arms. When comparing the HDI to the HDI/PE arm no differences were found for cardiac index (CI) (p = 0.06), systemic vascular resistance (p = 0.34), heart rate (HR) (p = 0.95), mean arterial pressure (p = 0.99), pulmonary vascular resistance (PVR) (p = 0.07), or base excess (p = 0.36). In this model of nifedipine-induced cardiogenic shock, the addition of PE to HDI therapy did not improve mortality, cardiac output, blood pressure, systemic vascular resistance (SVR), or base excess.

  1. Online pretreatment verification of high-dose rate brachytherapy using an imaging panel

    Science.gov (United States)

    Fonseca, Gabriel P.; Podesta, Mark; Bellezzo, Murillo; Van den Bosch, Michiel R.; Lutgens, Ludy; Vanneste, Ben G. L.; Voncken, Robert; Van Limbergen, Evert J.; Reniers, Brigitte; Verhaegen, Frank

    2017-07-01

    Brachytherapy is employed to treat a wide variety of cancers. However, an accurate treatment verification method is currently not available. This study describes a pre-treatment verification system that uses an imaging panel (IP) to verify important aspects of the treatment plan. A detailed modelling of the IP was only possible with an extensive calibration performed using a robotic arm. Irradiations were performed with a high dose rate (HDR) 192Ir source within a water phantom. An empirical fit was applied to measure the distance between the source and the detector so 3D Cartesian coordinates of the dwell positions can be obtained using a single panel. The IP acquires 7.14 fps to verify the dwell times, dwell positions and air kerma strength (Sk). A gynecological applicator was used to create a treatment plan that was registered with a CT image of the water phantom used during the experiments for verification purposes. Errors (shifts, exchanged connections and wrong dwell times) were simulated to verify the proposed verification system. Cartesian source positions (panel measurement plane) have a standard deviation of about 0.02 cm. The measured distance between the source and the panel (z-coordinate) have a standard deviation up to 0.16 cm and maximum absolute error of  ≈0.6 cm if the signal is close to sensitive limit of the panel. The average response of the panel is very linear with Sk. Therefore, Sk measurements can be performed with relatively small errors. The measured dwell times show a maximum error of 0.2 s which is consistent with the acquisition rate of the panel. All simulated errors were clearly identified by the proposed system. The use of IPs is not common in brachytherapy, however, it provides considerable advantages. It was demonstrated that the IP can accurately measure Sk, dwell times and dwell positions.

  2. A method for verification of treatment times for high-dose-rate intraluminal brachytherapy treatment

    Directory of Open Access Journals (Sweden)

    Muhammad Asghar Gadhi

    2016-06-01

    Full Text Available Purpose: This study was aimed to increase the quality of high dose rate (HDR intraluminal brachytherapy treatment. For this purpose, an easy, fast and accurate patient-specific quality assurance (QA tool has been developed. This tool has been implemented at Bahawalpur Institute of Nuclear Medicine and Oncology (BINO, Bahawalpur, Pakistan.Methods: ABACUS 3.1 Treatment planning system (TPS has been used for treatment planning and calculation of total dwell time and then results were compared with the time calculated using the proposed method. This method has been used to verify the total dwell time for different rectum applicators for relevant treatment lengths (2-7 cm and depths (1.5-2.5 cm, different oesophagus applicators of relevant treatment lengths (6-10 cm and depths (0.9 & 1.0 cm, and a bronchus applicator for relevant treatment lengths (4-7.5 cm and depth (0.5 cm.Results: The average percentage differences between treatment time TM with manual calculation and as calculated by the TPS is 0.32% (standard deviation 1.32% for rectum, 0.24% (standard deviation 2.36% for oesophagus and 1.96% (standard deviation 0.55% for bronchus, respectively. These results advocate that the proposed method is valuable for independent verification of patient-specific treatment planning QA.Conclusion: The technique illustrated in the current study is an easy, simple, quick and useful for independent verification of the total dwell time for HDR intraluminal brachytherapy. Our method is able to identify human error-related planning mistakes and to evaluate the quality of treatment planning. It enhances the quality of brachytherapy treatment and reliability of the system.

  3. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications.

    Science.gov (United States)

    Shwetha, Bondel; Ravikumar, Manickam; Supe, Sanjay S; Sathiyan, Saminathan; Lokesh, Vishwanath; Keshava, Subbarao L

    2012-01-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  4. 3D-printed surface mould applicator for high-dose-rate brachytherapy

    Science.gov (United States)

    Schumacher, Mark; Lasso, Andras; Cumming, Ian; Rankin, Adam; Falkson, Conrad B.; Schreiner, L. John; Joshi, Chandra; Fichtinger, Gabor

    2015-03-01

    In contemporary high-dose-rate brachytherapy treatment of superficial tumors, catheters are placed in a wax mould. The creation of current wax models is a difficult and time consuming proces.The irradiation plan can only be computed post-construction and requires a second CT scan. In case no satisfactory dose plan can be created, the mould is discarded and the process is repeated. The objective of this work was to develop an automated method to replace suboptimal wax moulding. We developed a method to design and manufacture moulds that guarantee to yield satisfactory dosimetry. A 3D-printed mould with channels for the catheters designed from the patient's CT and mounted on a patient-specific thermoplastic mesh mask. The mould planner was implemented as an open-source module in the 3D Slicer platform. Series of test moulds were created to accommodate standard brachytherapy catheters of 1.70mm diameter. A calibration object was used to conclude that tunnels with a diameter of 2.25mm, minimum 12mm radius of curvature, and 1.0mm open channel gave the best fit for this printer/catheter combination. Moulds were created from the CT scan of thermoplastic mesh masks of actual patients. The patient-specific moulds have been visually verified to fit on the thermoplastic meshes. The masks were visually shown to fit onto the thermoplastic meshes, next the resulting dosimetry will have to be compared with treatment plans and dosimetry achieved with conventional wax moulds in order to validate our 3D printed moulds.

  5. High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial.

    Science.gov (United States)

    Ganmaa, Davaasambuu; Munkhzul, Baatar; Fawzi, Wafaie; Spiegelman, Donna; Willett, Walter C; Bayasgalan, Purev; Baasansuren, Erkhembayar; Buyankhishig, Burneebaatar; Oyun-Erdene, Sereeter; Jolliffe, David A; Xenakis, Theodoros; Bromage, Sabri; Bloom, Barry R; Martineau, Adrian R

    2017-09-01

    Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. To determine the effect of high-dose vitamin D3 on response to antimicrobial therapy for PTB and to evaluate the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D3. We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D3 (n = 190) or placebo (n = 200) during intensive-phase antituberculosis treatment. The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P vitamin D3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1: rs4646536) (adjusted hazard ratio ≥ 1.47; P for interaction ≤ 0.02). Vitamin D3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

  6. Bystander effect between zebrafish embryos in vivo induced by high-dose X-rays.

    Science.gov (United States)

    Choi, V W Y; Ng, C Y P; Kobayashi, A; Konishi, T; Suya, N; Ishikawa, T; Cheng, S H; Yu, K N

    2013-06-18

    We employed embryos of the zebrafish, Danio rerio, for our studies on the in vivo bystander effect between embryos irradiated with high-dose X-rays and naive unirradiated embryos. The effects on the naive whole embryos were studied through quantification of apoptotic signals at 25 h post fertilization (hpf) through the terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay followed by counting the stained cells under a microscope. We report data showing that embryos at 5 hpf subjected to a 4-Gy X-ray irradiation could release a stress signal into the medium, which could induce a bystander effect in partnered naive embryos sharing the same medium. We further demonstrated that this bystander effect (induced through partnering) could be successfully suppressed through the addition of the nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) into the medium but not through the addition of the CO liberator tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). This shows that NO was involved in the bystander response between zebrafish embryos induced through X-ray irradiation. We also report data showing that the bystander effect could be successfully induced in naive embryos by introducing them into the irradiated embryo conditioned medium (IECM) alone, i.e., without partnering with the irradiated embryos. The IECM was harvested from the medium that had conditioned the zebrafish embryos irradiated at 5 hpf with 4-Gy X-ray until the irradiated embryos developed into 29 hpf. NO released from the irradiated embryos was unlikely to be involved in the bystander effect induced through the IECM because of the short life of NO. We further revealed that this bystander effect (induced through IECM) was rapidly abolished through diluting the IECM by a factor of 2× or greater, which agreed with the proposal that the bystander effect was an on/off response with a threshold.

  7. High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

    Energy Technology Data Exchange (ETDEWEB)

    Kaprealian, Tania [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Weinberg, Vivian [Biostatistics and Computational Biology Core, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Speight, Joycelyn L. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Gottschalk, Alexander R. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Hsu, I.-Chow, E-mail: IHsu@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States)

    2012-01-01

    Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy Multiplication-Sign 3 fractions (patient group 1) and 950 cGy Multiplication-Sign 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy Multiplication-Sign 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy Multiplication-Sign 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score {>=}7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

  8. Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements.

    Science.gov (United States)

    Poder, Joel; Whitaker, May

    2016-06-01

    Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected.

  9. Dosimetry audits in Brazil for {sup 192}Ir high dose rate brachytherapy systems

    Energy Technology Data Exchange (ETDEWEB)

    Rosa, L.A.R. da; Paiva, E. de.; Goncalves, M.G.; Velasco, A.F.; Di Prinzio, R.; Dovales, A.C.M.; Freire, B.L.V.; Brito, R.R.A.; Giannoni, R.A.; Castelo, L.H.R. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Marechal, M.H.H. [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao de Instalacoes Radiativas (CORAD)

    2005-03-15

    In Brazil, among 200 radiotherapy centres, 30 have high dose rate (HDR) {sup 192}Ir brachytherapy systems. In August 2001, the Brazilian National Nuclear Energy Commission (CNEN) started a biennial audit program to those centres having HDR systems. This program consists of visiting each centre in order to investigate the radiation protection aspects of the centres and also to measure the intensity of the brachytherapy source, in terms of air kerma strength, with a well type chamber specially designed for HDR {sup 192} Ir sources. The audit dosimetry results are compared to measurements carried out by the local institution physicist and to the source intensity value provided by the manufacturer. Two methods have been used by the Brazilian physicists for HDR {sup 192}Ir brachytherapy source dosimetry, namely the employment of a farmer type chamber calibrated according to the interpolation methodology and the use of a well type chamber to provide direct intercomparison. The larger difference obtained was 18.9% and it can be explained in terms of the lack of knowledge of the institution physicist about the interpolation methodology using the farmer type chamber. Another difference of 5.82% was found as being the lack of an updated calibration factor for the clinic well type chamber. On the basis of these results, CNEN is able to establish a maximum deviation value for the dosimetry of HDR system. Additionally, with this program the radiotherapy services have an opportunity to have their HDR {sup 192}Ir sources calibrated and to test the validity of the calibration factors for their own well type chambers, using their calibrated sources. (author)

  10. Automated high-dose rate brachytherapy treatment planning for a single-channel vaginal cylinder applicator

    Science.gov (United States)

    Zhou, Yuhong; Klages, Peter; Tan, Jun; Chi, Yujie; Stojadinovic, Strahinja; Yang, Ming; Hrycushko, Brian; Medin, Paul; Pompos, Arnold; Jiang, Steve; Albuquerque, Kevin; Jia, Xun

    2017-06-01

    High dose rate (HDR) brachytherapy treatment planning is conventionally performed manually and/or with aids of preplanned templates. In general, the standard of care would be elevated by conducting an automated process to improve treatment planning efficiency, eliminate human error, and reduce plan quality variations. Thus, our group is developing AutoBrachy, an automated HDR brachytherapy planning suite of modules used to augment a clinical treatment planning system. This paper describes our proof-of-concept module for vaginal cylinder HDR planning that has been fully developed. After a patient CT scan is acquired, the cylinder applicator is automatically segmented using image-processing techniques. The target CTV is generated based on physician-specified treatment depth and length. Locations of the dose calculation point, apex point and vaginal surface point, as well as the central applicator channel coordinates, and the corresponding dwell positions are determined according to their geometric relationship with the applicator and written to a structure file. Dwell times are computed through iterative quadratic optimization techniques. The planning information is then transferred to the treatment planning system through a DICOM-RT interface. The entire process was tested for nine patients. The AutoBrachy cylindrical applicator module was able to generate treatment plans for these cases with clinical grade quality. Computation times varied between 1 and 3 min on an Intel Xeon CPU E3-1226 v3 processor. All geometric components in the automated treatment plans were generated accurately. The applicator channel tip positions agreed with the manually identified positions with submillimeter deviations and the channel orientations between the plans agreed within less than 1 degree. The automatically generated plans obtained clinically acceptable quality.

  11. Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

    Science.gov (United States)

    Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

    2015-01-01

    Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

  12. High-Dose Lanreotide in the Treatment of Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Frank Van Fraeyenhove

    2014-03-01

    Full Text Available Pancreatic neuroendocrine tumors (NETs, including poorly differentiated carcinomas (NECs, are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel®. In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0. Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs.

  13. Brachytherapy for early oral tongue cancer: low dose rate to high dose rate.

    Science.gov (United States)

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Furukawa, Souhei; Kakimoto, Naoya; Shimizutani, Kimishige; Inoue, Toshihiko

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n = 341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer.

  14. Impact of violated high-dose refuge assumptions on evolution of Bt resistance.

    Science.gov (United States)

    Campagne, Pascal; Smouse, Peter E; Pasquet, Rémy; Silvain, Jean-François; Le Ru, Bruno; Van den Berg, Johnnie

    2016-04-01

    Transgenic crops expressing Bacillus thuringiensis (Bt) toxins have been widely and successfully deployed for the control of target pests, while allowing a substantial reduction in insecticide use. The evolution of resistance (a heritable decrease in susceptibility to Bt toxins) can pose a threat to sustained control of target pests, but a high-dose refuge (HDR) management strategy has been key to delaying countervailing evolution of Bt resistance. The HDR strategy relies on the mating frequency between susceptible and resistant individuals, so either partial dominance of resistant alleles or nonrandom mating in the pest population itself could elevate the pace of resistance evolution. Using classic Wright-Fisher genetic models, we investigated the impact of deviations from standard refuge model assumptions on resistance evolution in the pest populations. We show that when Bt selection is strong, even deviations from random mating and/or strictly recessive resistance that are below the threshold of detection can yield dramatic increases in the pace of resistance evolution. Resistance evolution is hastened whenever the order of magnitude of model violations exceeds the initial frequency of resistant alleles. We also show that the existence of a fitness cost for resistant individuals on the refuge crop cannot easily overcome the effect of violated HDR assumptions. We propose a parametrically explicit framework that enables both comparison of various field situations and model inference. Using this model, we propose novel empiric estimators of the pace of resistance evolution (and time to loss of control), whose simple calculation relies on the observed change in resistance allele frequency.

  15. High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized, Multicenter Study.

    Science.gov (United States)

    Giustina, Andrea; Mazziotti, Gherardo; Cannavò, Salvatore; Castello, Roberto; Arnaldi, Giorgio; Bugari, Giovanna; Cozzi, Renato; Ferone, Diego; Formenti, Anna Maria; Gatti, Enza; Grottoli, Silvia; Maffei, Pietro; Maffezzoni, Filippo; Montini, Marcella; Terzolo, Massimo; Ghigo, Ezio

    2017-07-01

    Increase in drug frequency or dose is recommended for acromegaly patients with partial response to long-acting somatostatin receptor ligands (SRLs). However, the efficacy and safety data with lanreotide (LAN) Autogel (LAN-ATG) at high dose (HD) or high frequency (HF) are still scanty. To evaluate the biochemical efficacy and safety of HF and HD LAN-ATG in patients with active acromegaly. Twenty-four-week prospective, multicenter, randomized, open-label trial. Thirty patients with active acromegaly, partial responders to SRLs, were randomized to HF (120 mg/21 days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. Normalization of serum insulin-like growth factor-I (IGF-I) and reduction in random growth hormone (GH) values < 1.0 µg/L, reduction in serum IGF-I and GH from baseline, differences in biochemical response between HF and HD LAN-ATG, adverse events. IGF-I decreased significantly (P = 0.007) during the 24-week treatment, with greater decrease in HD (P = 0.03) vs HF group (P = 0.08). Normalization in IGF-I values occurred in 27.6% of patients (P = 0.016 vs baseline), without a significant difference between HF and HD groups (P = 0.59). The decrease in serum IGF-I significantly correlated with serum LAN values (P = 0.04), and normalization of IGF-I was predicted by baseline IGF-I values (P = 0.02). Serum GH values did not change significantly (P = 0.22). Overall, 19 patients (63.3%) experienced adverse events, all being mild to moderate and transient, without differences between the two therapeutic arms. HF and HD LAN-ATG regimens are effective in normalizing IGF-I values in about one-third of patients with active acromegaly inadequately controlled by long-term conventional SRLs therapy.

  16. High-dose lanreotide in the treatment of poorly differentiated pancreatic neuroendocrine carcinoma: a case report.

    Science.gov (United States)

    Van Fraeyenhove, Frank; Meireson, Nathalie; Terriere, Luc; Willemsen, Paul; Kunnen, Jan; Mattelaer, Caroline; Van Acker, Frank; Schrijvers, Dirk

    2014-01-01

    Pancreatic neuroendocrine tumors (NETs), including poorly differentiated carcinomas (NECs), are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs) have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel(®). In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0). Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days) contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs.

  17. Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer.

    Science.gov (United States)

    Fiorino, Claudio; Sanguineti, Giuseppe; Cozzarini, Cesare; Fellin, Gianni; Foppiano, Franca; Menegotti, Loris; Piazzolla, Anna; Vavassori, Vittorio; Valdagni, Riccardo

    2003-11-15

    To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage T1-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V(50-70) values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V(50) below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V(50) and V(70) was confirmed by multivariate analyses. The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and V70 to 25-30%.

  18. The efficiency of high dose botulinum toxin type-A in the treatment of cerebral palsy

    Directory of Open Access Journals (Sweden)

    Alper İbrahim Dai

    2014-03-01

    Full Text Available Objective: Cerebral palsy is the most common cause of severe physical disability in childhood. Botulinum toxin type A (BTX-A, has rapidly gained acceptance as a different treatment for spasticity. However, no consensus exists among clinicians about optimal dose of BTX-A in pediatric patients. Doses of 2-6 U/ kg bodyweight with a maximum total dose of 29U/kg have been reported. This study was conducted due to uncertain dosage rage in pediatric use. Method: In this study, 12 patients with cerebral palsy and spastic eqinus foot deformity who referred to our center, were treated with BTX-A in the dosage of 25 U/kg. After treatment of BTX-A, patients were followed up total of 6 months. Three months after treatment, Gross motor functional measurement (GMFM and Modified Ashwort scale (MAS were done. At the same time, questionnaires (PCQ were filled for possible side effects. Results: Average age of 6 girls and 6 boys were 4.5 ± 2.8 years. GMFM and MAS were done before and 3 months after treatment and were found statistically significant (p<0.05. Muscle soreness was the most common symptom at PCQ forms. Conclusion: Using these two objective scales and PCQ form, high dose of BTX-A treatment was found statistically successful. Larger dose of BTX-A was used which was considered safe, effective and better tolerated by children. Titration of the dose of BTX-A, should be individualized for each patient due to different level of spasticity affecting patients in different ways. J Clin Exp Invest 2014; 5 (1: 93-97

  19. A Comparative Study of Vaginal Misoprostol and High Dose Intravenous Oxytocin for Second Trimester Pregnancy Termination

    Directory of Open Access Journals (Sweden)

    M. Rajaee

    2010-04-01

    Full Text Available Introduction & Objective: Second trimester labor induction is a major problem in obstetrics and is the cause of two-thirds of all abortion related complications and more than half of the maternal deaths associated with abortion. The goal of this study was to compare the effectiveness of vaginal misoprostol and intravenous oxytocin for termination of second trimester pregnancy.Materials & Methods: One hundred women were allocated in a randomized controlled way to one of the two induction groups: oxytocin group patients initially received an infusion of 50 units of oxytocin in 500 ml of ringer over 3 hours, 1 hour of no oxytocin followed by alternating 3 hours of oxytocin with 1 hour of rest. Oxytocin was increased by 50 units in each successive period until a final concentration of 300 units per 500 ml has been reached. Another group received 200 µg misoprostol tablets in posterior fornix vagina and was repeated after 12 hours if needed. The two groups were compared for induction to delivery intervals and their safety during induction. Results: The success rate within 24 hours of induction was 94% in the misoprostol group and 86% in oxytocin group (p= 0.182. The mean induction to delivery time was significantly longer in the oxytocin group compared with the misoprostol group.(13.5 versus 9.93 hours ; P=0.0057. Retained placenta requiring curettage was lower in the misoprostol group than the oxytocin group.Conclusion: Intravaginal misoprostol is more effective than high dose intravenous oxytocin in women with second trimester termination.

  20. Marital Relationship and Its Associated Factors in Veterans Exposed to High Dose Chemical Warfare Agents

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2008-06-01

    Full Text Available Objective: The aim of this study was to determine the associates of marital relationship in mustard exposed veterans.Materials and Methods: Two hundred ninety two married Iranian mustard exposed veterans, who had been exposed to single high dose mustard gas in Iraq-Iran war, were assessed for marital adjustment with Revised Dyadic Adjustment Scale (RDAS. Census sampling was done. The patients' quality of life (SF-36, spirometric measures and war related data were also extracted.Results: A total of 189 subjects (65% completed our study. The mean (±SD of the RDAS Total score, RDAS Dyadic Consensus , RDAS Affectional Expression, RDAS Dyadic Satisfaction , and RDAS Dyadic Cohesion were 50.61 (8.16, 16.67 (2.77, 7.62 (1.84, 14.76 (3.39, and 11.54 (3.79, respectively. RDAS Dyadic satisfaction was correlated with SF-36 and all its sub-scores (p<0.05. RDAS total score showed significant correlation with SF-36 total score and most of its sub-scores (p<0.05. RDAS affective expression was significantly correlated with role limitation, social function, general mental health, vitality, General health perceptions, physical composite score (PCS and mental composite score (MCS (p<0.05. RDAS dyadic consensus was not correlated with any SF-36 sub-scores.Conclusion: Veterans health team including physicians, psychologists and/or psychiatrists should know that poorer marital satisfaction is linked with lower quality of life scores, late after mustard exposure, although marital relationship is independent of spirometric findings, age, duration from exposure and comorbidity score.

  1. High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.

    Directory of Open Access Journals (Sweden)

    Hee Jin Shim

    Full Text Available Ionizing radiation (IR treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis.

  2. Proconvulsant effects of high doses of venlafaxine in pentylenetetrazole-convulsive rats

    Directory of Open Access Journals (Sweden)

    J.G. Santos Junior

    2002-04-01

    Full Text Available Venlafaxine, an atypical antidepressant drug, has been used to treat several neurological disorders, presenting excellent efficacy and tolerability. Clinical seizures after venlafaxine treatment have occasionally been reported when the drug was used at very high doses or in combination with other medications. The aim of the present study was to investigate the convulsant effects of venlafaxine in rats under controlled laboratory conditions. Adult male Wistar rats (8 per group receiving venlafaxine or saline at the doses of 25-150 mg/kg were subjected 30 min later to injections of pentylenetetrazole at the dose of 60 mg/kg. The animals receiving 75, 100 and 150 mg/kg venlafaxine presented increased severity of convulsion when compared to controls (P = 0.02, P = 0.04, and P = 0.0004, respectively. Indeed, an increased percentage of death was observed in these groups (50, 38, and 88%, respectively when compared to the percentage of death in the controls (0%. The group receiving 150 mg/kg showed an reduction in death latency (999 ± 146 s compared to controls (1800 ± 0 s; cut-off time. Indeed, in this group, all animals developed seizures prior to pentylenetetrazole administration. Surprisingly, the groups receiving venlafaxine at the doses of 25 and 50 mg/kg showed a tendency towards an increase in the latency to the first convulsion. These findings suggest that venlafaxine at doses of 25 and 50 mg/kg has some tendency to an anticonvulsant effect in the rat, whereas doses of 75, 100 and 150 mg/kg presented clear proconvulsant effects in rats submitted to the pentylenetetrazole injection. These findings are the first report in the literature concerning the role of venlafaxine in seizure genesis in the rat under controlled conditions.

  3. Clinical study on treatment of rectal carcinoma with Chinese herbal medicine and high dose fluorouracil emulsion via rectal infusion.

    Institute of Scientific and Technical Information of China (English)

    王晨光

    1999-01-01

    Objective: To study the clinical significance of rectal infusion of Chinese herbal medicine (CHM) plus high dose fluorouracil emulsion in treating rectal carcinoma. Methods: 86 patients of rectal carcinoma were randomly divided into CHM plus chemotherapy group and single chemotherapy group, and the

  4. Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions

    DEFF Research Database (Denmark)

    Mikkelsen, Torben Stamm; Mamoudou, Aissata Diop; Tuckuviene, Ruta

    2014-01-01

    Alkalized hydration is used as supportive care to prevent renal toxicity during infusions with high-dose methotrexate (HDMTX). In children with acute lymphoblastic leukemia (ALL), the hydration is commonly initiated 4 hours before start of the methotrexate (MTX) infusion. To test if longer durati...

  5. High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding: a meta-analysis.

    Science.gov (United States)

    Wu, Liu-Cheng; Cao, Yun-Fei; Huang, Jia-Hao; Liao, Cun; Gao, Feng

    2010-05-28

    To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding. PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model. Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929). Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

  6. HIGH-DOSE CHEMOTHERAPY WITH STEM-CELL REINFUSION AND GROWTH-FACTOR SUPPORT FOR SOLID TUMORS

    NARCIS (Netherlands)

    DEVRIES, EGE; DEGRAAF, H; VANDERGRAAF, WTA; MULDER, NH; Boonstra, A.

    1995-01-01

    With the help of stem cell reinfusion and hematopoietic growth factors, it is possible to get up to a ten-fold dose increase for certain chemotherapeutic drugs, A number of reasons may have made high-dose chemotherapy less dangerous and the fore more acceptable in a more upfront treatment setting, O

  7. Short-term response of sleep-potentiated spiking to high-dose diazepam in electric status epilepticus during sleep.

    Science.gov (United States)

    Sánchez Fernández, Iván; Hadjiloizou, Stavros; Eksioglu, Yaman; Peters, Jurriaan M; Takeoka, Masanori; Tas, Emir; Abdelmoumen, Imane; Rotenberg, Alexander; Kothare, Sanjeev V; Riviello, James J; Loddenkemper, Tobias

    2012-05-01

    We describe the short-term effects of high-dose oral diazepam on sleep-potentiated epileptiform activity in patients with electric status epilepticus during sleep. We enrolled patients treated with high-dose oral bedtime diazepam from 2001-2009. We defined spike percentage as the percentage of 1-second bins containing at least one spike, and calculated it during three randomly selected 5-minute samples of wakefulness throughout the day and during the first 5 minutes of every hour of non-rapid eye movement sleep at night. In this study, patients were considered to demonstrate sleep-potentiated epileptiform activity when their spike percentage during sleep was increased by ≥50% compared with wakefulness. Twenty-nine children (18 boys) were included (median age, 7.4 years). Twenty-four hours after receiving high-dose diazepam, epileptiform activity was significantly reduced (76.7% at baseline vs 40.8% 24 hours after high-dose diazepam; Wilcoxon signed ranks test, Z = -4.287, P status epilepticus during sleep.

  8. Adaptive planning strategy for high dose rate prostate brachytherapy—a simulation study on needle positioning errors

    NARCIS (Netherlands)

    Borot, Maxence; Denis de Senneville, B; Maenhout, M; Hautvast, G; Binnekamp, D; Lagendijk, J J W; van Vulpen, M; Moerland, M A

    2016-01-01

    The development of magnetic resonance (MR) guided high dose rate (HDR) brachytherapy for prostate cancer has gained increasing interest for delivering a high tumor dose safely in a single fraction. To support needle placement in the limited workspace inside the closed-bore MRI, a single-needle MR-co

  9. Effect of high-dose dexamethasone on perioperative lactate levels and glucose control : a randomized controlled trial

    NARCIS (Netherlands)

    Ottens, Thomas H.; Nijsten, Maarten W. N.; Hofland, Jan; Dieleman, Jan M.; Hoekstra, Miriam; van Dijk, Diederik; van der Maaten, Joost M. A. A.

    2015-01-01

    Introduction: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of

  10. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer (TM) disposable high-dose dry powder inhaler

    NARCIS (Netherlands)

    de Boer, Anne H.; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

    Objectives To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer (TM) dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Methods Comparison

  11. Early ambulance initiation versus in-hospital initiation of high dose clopidogrel in ST-segment elevation myocardial infarction

    NARCIS (Netherlands)

    Postma, S.; Dambrink, J.H.; Ottervanger, J.P.; Gosselink, A.T.M.; Koopmans, P.C.; Berg, J.M. van den; Suryapranata, H.; Hof, A.W. van 't

    2014-01-01

    Pre-hospital infarct diagnosis gives the opportunity to start anti-platelet and anti-thrombotic agents before arrival at the PCI centre. However, more evidence is necessary to demonstrate whether high dose (HD) clopidogrel (600 mg) administered in the ambulance is associated with improved initial pa

  12. High-dose-rate prostate brachytherapy based on registered transrectal ultrasound and in-room cone-beam CT images

    NARCIS (Netherlands)

    Even, Aniek J.G.; Nuver, Tonnis T.; Westendorp, Hendrik; Hoekstra, Carel J.; Slump, C.H.; Minken, Andre W.

    2014-01-01

    Purpose To present a high-dose-rate (HDR) brachytherapy procedure for prostate cancer using transrectal ultrasound (TRUS) to contour the regions of interest and registered in-room cone-beam CT (CBCT) images for needle reconstruction. To characterize the registration uncertainties between the two ima

  13. CLINICAL-EXPERIENCE WITH HIGH-DOSE TUMOR-NECROSIS-FACTOR-ALPHA IN REGIONAL THERAPY OF ADVANCED MELANOMA

    NARCIS (Netherlands)

    LEJEUNE, F; LIENARD, D; EGGERMONT, A; KOOPS, HS; KROON, B; GERAIN, J; ROSENKAIMER, F; SCHMITZ, P

    1994-01-01

    Isolated perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-t

  14. High-dose corticosterone after fear conditioning selectively suppresses fear renewal by reducing anxiety-like response.

    Science.gov (United States)

    Wang, Hongbo; Xing, Xiaoli; Liang, Jing; Bai, Yunjing; Lui, Zhengkui; Zheng, Xigeng

    2014-09-01

    Exposure therapy is widely used to treat anxiety disorders, including posttraumatic stress disorder (PTSD). However, preventing the return of fear is still a major challenge after this behavioral treatment. An increasing number of studies suggest that high-dose glucocorticoid treatment immediately after trauma can alleviate the symptoms of PTSD in humans. Unknown is whether high-dose glucocorticoid treatment following fear conditioning suppresses the return of fear. In the present study, a typical fear renewal paradigm (AAB) was used, in which the fear response to an auditory cue can be restored in a novel context (context B) when both training and extinction occur in the same context (context A). We trained rats for auditory fear conditioning and administered corticosterone (CORT; 5 and 25mg/kg, i.p.) or vehicle with different delays (1 and 24h). Forty-eight hours after drug injection, extinction was conducted with no drug in the training context, followed by a test of tone-induced freezing behavior in the same (AAA) or a shifted (AAB) context. Both immediate and delayed administration of high-dose CORT after fear conditioning reduced fear renewal. To examine the anxiolytic effect of CORT, independent rats were trained for cued or contextual fear conditioning, followed by an injection of CORT (5 and 25mg/kg, i.p.) or vehicle at a 1 or 24h delay. One week later, anxiety-like behavior was assessed in the elevated plus maze (EPM) before and after fear expression. We found that high-dose CORT decreased anxiety-like behavior without changing tone- or context-induced freezing. These findings indicate that a single high-dose CORT administration given after fear conditioning may selectively suppress fear renewal by reducing anxiety-like behavior and not by altering the consolidation, retrieval, or extinction of fear memory.

  15. High-Dose, Extended-Interval Gentamicin and Tobramycin for Pediatric Inpatients: A Survey of Canadian Hospital Pharmacists.

    Science.gov (United States)

    Roy, Caitlin; Gray, Carolyn; Ruda, Lisa; Bell, Ali; Bolt, Jennifer

    2016-01-01

    The use of high-dose, extended-interval aminoglycosides, a common practice in adult populations, is less well established for pediatric patients. In younger populations, these drugs are often administered according to a multiple daily dosing method. To characterize prescribing practices for aminoglycosides in pediatric inpatients across Canada, with a focus on high-dose, extended-interval regimens. This study was based on an electronic survey of pharmacists representing Canadian health care delivery organizations that provided pediatric inpatient services, which was distributed in March 2015. Questions focused on demographic characteristics; indications for high-dose, extended-interval tobramycin or gentamicin; use of these regimens in patients with particular comorbidities; empiric dosing; monitoring parameters; and the extent of pharmacists' authority to independently prescribe doses and order monitoring parameters for aminoglycosides at their respective institutions. Forty-five (48%) of the 94 prospective participants responded to the survey. Of these 45 respondents, 35 (78%) indicated that their respective health regions used high-dose, extended-interval tobramycin or gentamicin in pediatric inpatients. The patient characteristics for use of such regimens were varied. The median reported doses were 10 mg/kg for pulmonary exacerbation in cystic fibrosis, 7 mg/kg for urinary tract infection, and 8 mg/kg for febrile neutropenia. Thirty-one (89%) of the 35 respondents using these regimens reported that they monitored serum levels, and 27 (77%) reported monitoring for nephrotoxicity. With regard to prescriptive authority, 7 (16%) of the 45 respondents indicated that pharmacists were authorized to independently adjust dosing at their institutions, and pharmacists at 14 (31%) of 45 sites were authorized to order monitoring parameters. High-dose, extended-interval aminoglycoside therapy was frequently used for pediatric patients across Canada, although the dosages and

  16. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Directory of Open Access Journals (Sweden)

    Daniel G Zhang

    Full Text Available MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF and conventional flattened 6MV photon beams were used. High dose rate (HDR brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL would be needed.

  17. Direction-Modulated Brachytherapy for High-Dose-Rate Treatment of Cervical Cancer. I: Theoretical Design

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dae Yup [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, California (United States); Webster, Matthew J. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Physics, University of California San Diego, La Jolla, California (United States); Scanderbeg, Daniel J.; Yashar, Catheryn; Choi, Dongju; Song, Bongyong [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Devic, Slobodan [Medical Physics Unit, McGill University, Montréal, Québec (Canada); Department of Radiation Oncology, Jewish General Hospital, Montréal, Québec (Canada); Ravi, Ananth [Department of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Song, William Y., E-mail: wyjsong@gmail.com [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Medical Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-07-01

    Purpose: To demonstrate that utilization of the direction-modulated brachytherapy (DMBT) concept can significantly improve treatment plan quality in the setting of high-dose-rate (HDR) brachytherapy for cervical cancer. Methods and Materials: The new, MRI-compatible, tandem design has 6 peripheral holes of 1.3-mm diameter, grooved along a nonmagnetic tungsten-alloy rod (ρ = 18.0 g/cm{sup 3}), enclosed in Delrin tubing (polyoxymethylene, ρ = 1.41 g/cm{sup 3}), with a total thickness of 6.4 mm. The Monte Carlo N-Particle code was used to calculate the anisotropic {sup 192}Ir dose distributions. An in-house-developed inverse planning platform, geared with simulated annealing and constrained-gradient optimization algorithms, was used to replan 15 patient cases (total 75 plans) treated with a conventional tandem and ovoids (T and O) applicator. Prescription dose was 6 Gy. For replanning, we replaced the conventional tandem with that of the new DMBT tandem for optimization but left the ovoids in place and kept the dwell positions as originally planned. All DMBT plans were normalized to match the high-risk clinical target volume V100 coverage of the T and O plans. Results: In general there were marked improvements in plan quality for the DMBT plans. On average, D2cc for the bladder, rectum, and sigmoid were reduced by 0.59 ± 0.87 Gy (8.5% ± 28.7%), 0.48 ± 0.55 Gy (21.1% ± 27.2%), and 0.10 ± 0.38 Gy (40.6% ± 214.9%) among the 75 plans, with best single-plan reductions of 3.20 Gy (40.8%), 2.38 Gy (40.07%), and 1.26 Gy (27.5%), respectively. The high-risk clinical target volume D90 was similar, with 6.55 ± 0.96 Gy and 6.59 ± 1.06 Gy for T and O and DMBT, respectively. Conclusions: Application of the DMBT concept to cervical cancer allowed for improved organ at risk sparing while achieving similar target coverage on a sizeable patient population, as intended, by maximally utilizing the anatomic information contained in 3-dimensional

  18. Patient-specific dose calculation methods for high-dose-rate iridium-192 brachytherapy

    Science.gov (United States)

    Poon, Emily S.

    In high-dose-rate 192Ir brachytherapy, the radiation dose received by the patient is calculated according to the AAPM Task Group 43 (TG-43) formalism. This table-based dose superposition method uses dosimetry parameters derived with the radioactive 192Ir source centered in a water phantom. It neglects the dose perturbations caused by inhomogeneities, such as the patient anatomy, applicators, shielding, and radiographic contrast solution. In this work, we evaluated the dosimetric characteristics of a shielded rectal applicator with an endocavitary balloon injected with contrast solution. The dose distributions around this applicator were calculated by the GEANT4 Monte Carlo (MC) code and measured by ionization chamber and GAFCHROMIC EBT film. A patient-specific dose calculation study was then carried out for 40 rectal treatment plans. The PTRAN_CT MC code was used to calculate the dose based on computed tomography (CT) images. This study involved the development of BrachyGUI, an integrated treatment planning tool that can process DICOM-RT data and create PTRAN_CT input initialization files. BrachyGUI also comes with dose calculation and evaluation capabilities. We proposed a novel scatter correction method to account for the reduction in backscatter radiation near tissue-air interfaces. The first step requires calculating the doses contributed by primary and scattered photons separately, assuming a full scatter environment. The scatter dose in the patient is subsequently adjusted using a factor derived by MC calculations, which depends on the distances between the point of interest, the 192Ir source, and the body contour. The method was validated for multicatheter breast brachytherapy, in which the target and skin doses for 18 patient plans agreed with PTRAN_CT calculations better than 1%. Finally, we developed a CT-based analytical dose calculation method. It corrects for the photon attenuation and scatter based upon the radiological paths determined by ray tracing

  19. Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer

    Science.gov (United States)

    Draghini, Lorena; Casale, Michelina; Trippa, Fabio; Anselmo, Paola; Arcidiacono, Fabio; Fabiani, Stefania; Italiani, Marco; Chirico, Luigia; Muti, Marco

    2017-01-01

    Purpose To report our experience on high-dose-rate brachytherapy (HDR-BT) in patients with stage I-III endometrial cancer unfit to surgery. Material and methods Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95), median Karnofsky performance status 90% (range, 60-100). Histology was endometrial adenocarcinoma in 14 (82%), and non-endometrial in 3 (18%) patients. In 15 (88%) patients, clinical stage was I and in remaining 2 (12%) was III. All patients were evaluated with computed tomography (CT) and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC) was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression. Results Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT) combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131), 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS) at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adenocarcinoma) LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma) was 100% at 1 and 6 years (p = 0.05). Two (12%) patients had G2 acute toxicity and two others (12%) G1 late toxicity. Conclusions Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection), it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology. PMID:28533799

  20. Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer

    Directory of Open Access Journals (Sweden)

    Lorena Draghini

    2017-04-01

    Full Text Available Purpose : To report our experience on high-dose-rate brachytherapy (HDR-BT in patients with stage I-III endometrial cancer unfit to surgery. Material and methods : Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95, median Karnofsky performance status 90% (range, 60-100. Histology was endometrial adenocarcinoma in 14 (82%, and non-endometrial in 3 (18% patients. In 15 (88% patients, clinical stage was I and in remaining 2 (12% was III. All patients were evaluated with computed tomography (CT and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression. Results : Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131, 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adeno­carcinoma LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma was 100% at 1 and 6 years (p = 0.05. Two (12% patients had G2 acute toxicity and two others (12% G1 late toxicity. Conclusions : Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection, it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology.

  1. Performance assessment of the BEBIG MultiSource high dose rate brachytherapy treatment unit.

    Science.gov (United States)

    Palmer, Antony; Mzenda, Bongile

    2009-12-21

    A comprehensive system characterisation was performed of the Eckert & Ziegler BEBIG GmbH MultiSource High Dose Rate (HDR) brachytherapy treatment unit with an (192)Ir source. The unit is relatively new to the UK market, with the first installation in the country having been made in the summer of 2009. A detailed commissioning programme was devised and is reported including checks of the fundamental parameters of source positioning, dwell timing, transit doses and absolute dosimetry of the source. Well chamber measurements, autoradiography and video camera analysis techniques were all employed. The absolute dosimetry was verified by the National Physical Laboratory, UK, and compared to a measurement based on a calibration from PTB, Germany, and the supplied source certificate, as well as an independent assessment by a visiting UK centre. The use of the 'Krieger' dosimetry phantom has also been evaluated. Users of the BEBIG HDR system should take care to avoid any significant bend in the transfer tube, as this will lead to positioning errors of the source, of up to 1.0 mm for slight bends, 2.0 mm for moderate bends and 5.0 mm for extreme curvature (depending on applicators and transfer tube used) for the situations reported in this study. The reason for these errors and the potential clinical impact are discussed. Users should also note the methodology employed by the system for correction of transit doses, and that no correction is made for the initial and final transit doses. The results of this investigation found that the uncorrected transit doses lead to small errors in the delivered dose at the first dwell position, of up to 2.5 cGy at 2 cm (5.6 cGy at 1 cm) from a 10 Ci source, but the transit dose correction for other dwells was accurate within 0.2 cGy. The unit has been mechanically reliable, and source positioning accuracy and dwell timing have been reproducible, with overall performance similar to other existing HDR equipment. The unit is capable of high

  2. Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

    Science.gov (United States)

    DeZern, Amy E.; Zahurak, Marianna; Symons, Heather; Cooke, Kenneth; Jones, Richard J.; Brodsky, Robert A.

    2017-01-01

    Severe aplastic anemia (SAA) is a life-threatening hematopoietic stem cell disorder that is treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IST). The management of patients with refractory SAA after IST is a major challenge. Alternative donor BMT is the best chance for cure in refractory SAA, but morbidity and mortality from graft failure and complications of graft-versus-host disease (GVHD) have limited enthusiasm for this approach. Here, we employed post-transplantation high-dose cyclophosphamide in an effort to safely expand the donor pool in 16 consecutive patients with refractory SAA who did not have a matched sibling donor. Between July 2011 and August 2016, 16 patients underwent allogeneic (allo) BMT for refractory SAA from 13 haploidentical donors and 3 unrelated donors. The nonmyeloablative conditioning regimen consisted of antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation. Post-transplantation cyclophosphamide 50 mg/kg/day i.v. on days +3 and +4 was administered for GVHD prophylaxis. Additionally, patients received mycophenolate mofetil on days +5 through 35 and tacrolimus from day +5 through 1 year. The median age of the patients at the time of transplantation was 30 (range, 11 to 69) years. The median time to neutrophil recovery over 1000 × 103/mm3 for 3 consecutive days was 19 (range, 16 to 27) days, to red cell engraftment was 25 (range, 2 to 58) days, and to last platelet transfusion to keep platelets counts over 50 × 103/mm3 was 27.5 (range, 22 to 108) days. Graft failure, primary or secondary, was not seen in any of the patients. All 16 patients are alive, transfusion independent, and without evidence of clonality. The median follow-up is 21 (range, 3 to 64) months. Two patients had grade 1 or 2 skin-only acute GVHD. These same 2 also had mild chronic GVHD of the skin/mouth requiring systemic steroids. One of these GVHD patients was able to come off all IST by 15 months and the

  3. High-dose infliximab for treatment of pediatric ulcerative colitis: A survey of clinical practice

    Institute of Scientific and Technical Information of China (English)

    Roy Nattiv; Janet M Wojcicki; Elizabeth A Garnett; Neera Gupta; Melvin B Heyman

    2012-01-01

    AIM:TO assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis (UC).METHODS:A 19-item survey was distributed to subscribers of the pediatric gastroenterology (PEDSGI)listserv.Responses were submitted anonymously and results compiled in a secure website.RESULTS:A total of 113 subscribers (88% based in the United States) responded (101 pediatric gastroenterology attendings and 12 pediatric gastroenterology fellows).There were 46% in academic medical institutions and 39% in hospital-based practices.The majority (91%) were treating >10 patients with UC; 13% were treating >100 patients with UC; 91% had prescribed infliximab (IFX) 5 mg/kg for UC; 72% had prescribed IFX 10 mg/kg for UC.Using a 5-point Likert scale,factors that influenced the decision not to increase IFX dosing in patients with UC included:"improvement on initial dose of IFX" (mean:3.88) and "decision to move to colectomy" (3.69).Lowest mean Likert scores were:"lack of guidelines or literature regarding increased IFX dosing" (1.96) and "insurance authorization or other insurance issues" (2.34)."Insurance authorization or other insurance issues" was identified by 39% as at least somewhat of a factor (Likert score ≥ 3) in their decision not to increase the IFX dose.IFX 10 mg/kg was more commonly used for the treatment of pediatric UC among responders based in the United States (75/100) compared to non-United States responders (6/13,P =0.047).Induction of remission was reported by 78% of all responders and 81% reported maintenance of remission with IFX 10 mg/kg.One responder reported one death with IFX 10 mg/kg.CONCLUSION:IFX 10 mg/kg is more commonly used in the United States to treat pediatric UC.Efficacy and safety data are required to avoid insurance barriers for its use.

  4. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Science.gov (United States)

    Zhang, Daniel G; Feygelman, Vladimir; Moros, Eduardo G; Latifi, Kujtim; Zhang, Geoffrey G

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

  5. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-09-01

    Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

  6. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Tinkle, Christopher L.; Weinberg, Vivian [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chen, Lee-May [Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California (United States); Littell, Ramey [Gynecologic Oncology, The Permanente Medical Group, San Francisco, California (United States); Cunha, J. Adam M.; Sethi, Rajni A. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chan, John K. [Gynecologic Oncology, California Pacific Medical Center, San Francisco, California (United States); Hsu, I-Chow, E-mail: ichow.hsu@ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, California (United States)

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  7. Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

    Directory of Open Access Journals (Sweden)

    Y. Sobita Devi

    2011-12-01

    Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

  8. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

    Science.gov (United States)

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-02-01

    Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

  9. Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Larissa J. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States)

    2012-12-01

    Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure

  10. Neoadjuvant multidrug chemotherapy including High-Dose Methotrexate modifies VEGF expression in Osteosarcoma: an immunohistochemical analysis

    Directory of Open Access Journals (Sweden)

    Rosa Michele A

    2010-02-01

    Full Text Available Abstract Background Angiogenesis plays a role in the progression of osteosarcoma, as well as in other mesenchymal tumors and carcinomas, and it is most commonly assessed by vascular endothelial growth factor (VEGF expression or tumor CD31-positive microvessel density (MVD. Tumor VEGF expression is predictive of poor prognosis, and chemotherapy can affect the selection of angiogenic pattern. The aim of the study was to investigate the clinical and prognostic significance of VEGF and CD31 in osteosarcoma, both at diagnosis and after neoadjuvant chemotherapy, in order to identify a potential role of chemotherapy in angiogenic phenotype. Methods A retrospective analysis was performed on 16 patients with high grade osteosarcoma. In each case archival pre-treatment biopsy tissue and post-chemotherapy tumor specimens were immunohistochemically stained against CD31 and VEGF, as markers of angiogenic proliferation both in newly diagnosed primary osteosarcoma and after multidrug chemotherapy including high-dose methotrexate (HDMTX. The correlation between clinicopathological parameters and the degree of tumor VEGF and CD31 expression was statistically assessed using the χ2 test verified with Yates' test for comparison of two groups. Significance was set at p Results Expression of VEGF was positive in 11 cases/16 of cases at diagnosis. Moreover, 8 cases/16 untreated osteosarcomas were CD31-negative, but the other 8 showed an high expression of CD31. VEGF expression in viable tumor cells after neoadjuvant chemotherapy was observed in all cases; in particular, there was an increased VEGF expression (post-chemotherapy VEGF - biopsy VEGF in 11 cases/16. CD31 expression increased in 11 cases/16 and decreased in 3 cases after chemotherapy. The data relating to the change in staining following chemotherapy appear statistically significant for VEGF expression (p p > 0,05. Conclusions Even if the study included few patients, these results confirm that VEGF and CD

  11. Comparison of low-dose and high-dose cosyntropin stimulation testing in children.

    Science.gov (United States)

    Cemeroglu, Ayse Pinar; Kleis, Lora; Postellon, Daniel C; Wood, Michael A

    2011-04-01

      There is no consensus among pediatric endocrinologists in using low-dose (LD) versus high-dose (HD) cosyntropin to test for secondary/tertiary adrenal insufficiency. This paper compares LD and HD cosyntropin stimulation testing in children for evaluation of hypothalamic-pituitary-adrenal axis (HPAA) and suggests a new peak cortisol cut-off value for LD stimulation testing to avoid false positivity.   Data of 36 children receiving LD (1 µg) and HD (249 µg) cosyntropin consecutively during growth hormone (GH) stimulation testing were analyzed in two groups. Group A were patients who passed GH stimulation testing and were not on oral, inhaled or intranasal steroids (intact hypothalamic-pituitary axis, n= 19). Group B were patients who failed GH stimulation testing and/or were on oral, inhaled or intranasal steroids (impaired hypothalamic-pituitary axis, n= 17).   In group A, the mean peak cortisol response in LD cosyntropin was 18.5 ± 2.4 µg/dL and that for the HD cosyntropin was 24.8 ± 3.1 µg/dL (r: 0.76, P≤ 0.05). In group B, the mean peak cortisol response in LD cosyntropin was 15.7 ± 6.1 µg/dL and that for HD cosyntropin was 21.7 ± 7.9 µg/dL (r: 0.98, P≤ 0.05). When a standard cut-off of 18 µg/dL was used, 37% of the patients with intact HPAA failed LD cosyntropin testing, but a cut-off of 14 µg/dL eliminated false positive results.   LD cosyntropin stimulation testing results should be interpreted cautiously when used alone to prevent unnecessary long-term treatment. Using a lower cut-off for LD (≥14 µg/dL) seems to avoid false positive results and still detects most cases of impaired HPAA. © 2011 The Authors.Pediatrics International © 2011 Japan Pediatric Society.

  12. Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer

    Science.gov (United States)

    Hitchcock, Kathryn E; Nichols, R Charles; Morris, Christopher G; Bose, Debashish; Hughes, Steven J; Stauffer, John A; Celinski, Scott A; Johnson, Elizabeth A; Zaiden, Robert A; Mendenhall, Nancy P; Rutenberg, Michael S

    2017-01-01

    unresectable cancers is feasible after high-dose [59.4 Gy (RBE)] proton radiotherapy with a high rate of local control, acceptable surgical morbidity, and a median survival of 24 mo. PMID:28503258

  13. High-Dose-Rate intraluminal brachytherapy for biliary obstruction by secondary malignant biliary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Won Sup; Kim, Tae Hyun; Yang, Dae Sik; Choi, Myung Sun; Kim, Chul Yong [College of Medicine, Korea Univ., Seoul (Korea, Republic of)

    2003-03-01

    To analyze the survival period, prognostic factors and complications of patients having under gone high-dose-rate intraluminal brachytherapy (HDR-ILB) as a salvage radiation therapy, while having a catheter, for percutaneous transhepatic biliary drainage (PTBD), inserted due to biliary obstruction caused by a secondary malignant biliary tumor. A retrospective study was performed on 24 patients having undergone HDR-ILB, with PTBD catheter insertion, between December 1992 and August 2001, Their median age was 58.5, ranging from 35 to 82 years. The primary cancer site were the stomach, gallbladder, liver, pancreas and the colon, with 12, 6, 3, 2 and 1 cases, respectively. Eighteen patients were treated with external beam radiation therapy and HDR-ILB, while six were treated with HDR-ILB only. The total external beam, and brachytherapy radiations dose were 30-61.2 and 9-30 Gy, with median doses of 50 and 15 Gy, respectively. Of the 24 patients analyzed, 22 died during the follow-up period, with a median survival of 7.3 months. The 6 and 12 months survival rates were 54.2 (13 patients) and 20.8% (5 patients), respectively. The median survivals for stomach and gallbladder cancers were 7.8 and 10.2 months, respectively. According to the univariate analysis, a significant factor affecting survival of over one year was the total radiation dose (over 50 Gy) (0=0.0200), with all the patients surviving more than one year had been irradiated with more than 50 Gy. The acute side effects during the radiation therapy were managed with conservative treatment. During the follow-up period, 5 patients showed symptoms of cholangitis due to the radiation therapy. An extension to the survival of those patients treated with HDR-ILB is suggested compared to the median historical survival of those patients treated with external biliary drainage. A boost radiation dose could be effectively given, by performing HDR-ILB, which is a prognostic factor. In addition, the acute complications of

  14. Concomitant cervical and transperineal parametrial high-dose-rate brachytherapy boost for locally advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Caroline Bailleux

    2016-01-01

    Full Text Available Purpose: There is no consensus for parametrial boost technic while both transvaginal and transperineal approaches are discussed. A prototype was developed consisting of a perineal template, allowing transperineal needle insertion. This study analyzed acute toxicity of concomitant cervical and transperineal parametrial high-dose-rate brachytherapy (HDRB boost for locally advanced cervical cancer. Material and methods: From 01.2011 to 12.2014, 33 patients (pts presenting a locally advanced cervical cancer with parametrial invasion were treated. After the first course of external beam radiation therapy with cisplatinum, HDRB was performed combining endocavitary and interstitial technique for cervical and parametrial disease. Post-operative delineation (CTV, bladder, rectum, sigmoid and planification were based on CT-scan/MRI. HDRB was delivered in 3-5 fractions over 2-3 consecutive days. Acute toxicities occurring within 6 months after HDRB were retrospectively reviewed. Results: Median age was 56.4 years (27-79. Clinical stages were: T2b = 23 pts (69.7%, T3a = 1 pt (3%, T3b = 6 pts (18.2%, and T4a = 3 pts (9.1%. Median HDRB prescribed dose was 21 Gy (21-27. Median CTVCT (16 pts and HR-CTV MRI (17 pts were 52.6 cc (28.5-74.3, 31.9 cc (17.1-58, respectively. Median EQD2αβ10 for D90CTV and D90HR-CTV were 82.9 Gy (78.2-96.5, 84.8 Gy (80.6-91.4, respectively. Median EQD2αβ3 (CT/MRI for D2cc bladder, rectum and sigmoid were 75.5 Gy (66.6-90.9, 64.4 Gy (51.9-77.4, and 60.4 Gy (50.9-81.1, respectively. Median follow-up was 14 months (ranged 6-51. Among the 24 pts with MFU = 24 months, 2-year LRFS rate, RRFS, and OS were 86.8%, 88.8%, and 94.1%, respectively. The rates of acute genitourinary and gastrointestinal toxicities were 36% (G1 dysuria = 8 pts, G2 infection = 2 pt, G3 infection = 2 pts, and 27% (G1 diarrhea = 9 pts, respectively. One patient presented vaginal bleeding at the time of applicator withdrawal (G3-blood transfusion; no bleeding was

  15. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ost, Piet, E-mail: piet.ost@ugent.be [Department of Radiotherapy, Ghent University Hospital (Belgium); Cozzarini, Cesare [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital (Belgium); Fiorino, Claudio [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Potter, Bruno [Department of Radiotherapy, Ghent University Hospital (Belgium); Briganti, Alberto [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Nagler, Evi V.T. [Department of Nephrology, Ghent University Hospital (Belgium); Montorsi, Francesco [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Fonteyne, Valerie [Department of Radiotherapy, Ghent University Hospital (Belgium); Di Muzio, Nadia [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy)

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  16. High-Dose-Rate Prostate Brachytherapy Consistently Results in High Quality Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    White, Evan C.; Kamrava, Mitchell R.; Demarco, John; Park, Sang-June; Wang, Pin-Chieh; Kayode, Oluwatosin; Steinberg, Michael L. [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, California (United States); Demanes, D. Jeffrey, E-mail: jdemanes@mednet.ucla.edu [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, California (United States)

    2013-02-01

    Purpose: We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. Methods and Materials: Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. Results: The mean prostate ultrasound volume was 38.7 {+-} 13.4 cm{sup 3} (range: 11.7-108.6 cm{sup 3}). The mean CTV was 75.1 {+-} 20.6 cm{sup 3} (range: 33.4-156.5 cm{sup 3}). The mean D90 was 109.2% {+-} 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% {+-} 0.05%, 99.5% {+-} 0.8%, 25.4% {+-} 4.2%, and 7.8% {+-} 1.4%. The mean dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} for organs at risk were: Urethra: 107.3% {+-} 3.0%, 101.1% {+-} 14.6%, and 47.9% {+-} 34.8%; bladder wall: 79.5% {+-} 5.1%, 69.8% {+-} 4.9%, and 64.3% {+-} 5.0%; bladder balloon: 70.3% {+-} 6.8%, 59.1% {+-} 6.6%, and 52.3% {+-} 6.2%; rectum: 76.3% {+-} 2.5%, 70.2% {+-} 3.3%, and 66.3% {+-} 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. Conclusions: HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

  17. Colza cell autophagy induced of high dose of industrial sewage sludge

    Science.gov (United States)

    Lasoued, Najla; Guenole Bilal, Issam; Rejeb, Saloua; Bilal, Essaid; Rejeb, Nejib

    2013-04-01

    This preliminary study is to evaluate the effects on colza of land application of industrial sludge containing heavy metals especially lead and chromium. We are interested in high doses spreading 100t/ha to better observe the phenomena of induced transformations on colza by the absorption of heavy metals. We used the technique for ultrastructural observation in a transmission electron microscope. The colza cells show a compaction and marginalization of nuclear chromatin, nuclear membrane and cytoplasmic convolution and condensation of cytoplasm. The kernel then fragments, each fragment are surrounded by a jacket. Some cytoplasmic and nuclear elements are released and are phagocytized by neighboring cells. We observed vacuolation of the cytoplasm and the formation of autophagic vesicles. The two main ways to cell death are apoptosis and autophagy. Apoptosis was not seen in plant yet. At the nucleus level cell death main characteristics are the nuclear blebbing and fragmentation. At the molecular level, caspases activity (VPE for plants, or metacaspases I and II), chromatin condensation, degradation of DNA detected by TUNEL assay and DNA laddering detected by comet test are the main events. Autophagy is the major degradation and recycling process in cells. Its aim is to address part of the cytoplasm or organelles to the proteasome. In macro-Autophagy a specific feature is the double membrane structure that we can see in electron microscopy. This membrane is known to fusion with the lysosome/vacuole where this is in process. As a rule, the vacuole grows more and more until no organelles remains. Small lytic vacuoles appear in increasing quantity also. Autophagosomes tend to be pushed against the membrane and wall of the cell. Sometime in the literature it was describe a permeabilization or a tonoplast disruption; this is the last stage called mega-autophagy. The stress generated by heavy metals in industrial sludge spreading, produces in colza cells programmed death

  18. Limitations of the TG-43 formalism for skin high-dose-rate brachytherapy dose calculations

    Energy Technology Data Exchange (ETDEWEB)

    Granero, Domingo, E-mail: dgranero@eresa.com [Department of Radiation Physics, ERESA, Hospital General Universitario, 46014 Valencia (Spain); Perez-Calatayud, Jose [Radiotherapy Department, La Fe University and Polytechnic Hospital, Valencia 46026 (Spain); Vijande, Javier [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100, Spain and IFIC (UV-CSIC), Paterna 46980 (Spain); Ballester, Facundo [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States)

    2014-02-15

    Purpose: In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Methods: Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR{sup 60}Co and {sup 192}Ir sources and a hypothetical {sup 169}Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. Results: For a 5 cm × 5 cm{sup 192}Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about −3%. When the source was positioned at the skin surface, dose differences were smaller than −1% for {sup 60}Co and {sup 192}Ir, yet −3% for {sup 169}Yb. For the interstitial implant, dose differences at the skin surface were −7% for {sup 60}Co, −0.6% for {sup 192}Ir, and −2.5% for {sup 169}Yb. Conclusions: This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either {sup 60}Co and {sup 192}Ir. For

  19. Dosimetric Evaluation of High-Dose-Rate Interstitial Brachytherapy Boost Treatments for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Froehlich, Georgina [Semmelweis Univ., Budapest (Hungary); Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary); Agoston, Peter; Loevey, Jozsef; Somogyi, Andras; Fodor, Janos; Polgar, Csaba; Major, Tibor [Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary)

    2010-07-15

    Purpose: to quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. Material and methods: treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D{sub min}) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D{sub r}) and urethra (D{sub u}), dose to volume of 2 cm{sup 3} of the rectum (D{sub 2ccm}), and 0.1 cm{sup 3} and 1% of the urethra (D{sub 0.1ccm} and D1) were determined. Nonparametric correlation analysis was performed between these parameters. Results: the median number of needles was 16, the mean prostate volume (V{sub p}) was 27.1 cm{sup 3}. The mean V90, V100, V150, and V200 were 90%, 97%, 39% and 13%, respectively. The mean D90 was 109%, and the D{sub min} was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D{sub 2ccm} = 49% for the rectum, D{sub 0.1ccm} = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D{sub r}, D{sub 2ccm}) = 0.69, R(D{sub u}, D{sub 0.1ccm}) = 0.64, R(D{sub u}, D1) = 0.23. Conclusion: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose

  20. Resuscitation after severe burn injury using high-dose ascorbic acid: a retrospective review.

    Science.gov (United States)

    Kahn, Steven Alexander; Beers, Ryan J; Lentz, Christopher W

    2011-01-01

    Resuscitation of burn victims with high-dose ascorbic acid (vitamin C [VC]) was reported in Japan in the year 2000. Benefits of VC include reduction in fluid requirements, resulting in less tissue edema and body weight gain. In turn, these patients suffer less respiratory impairment and reduced requirement for mechanical ventilation. Despite these results, few burn centers resuscitate patients with VC in fear that it may increase the risk of renal failure. A retrospective review of 40 patients with greater than 20% TBSA between 2007 and 2009 was performed. Patients were divided into two groups: one received only lactated Ringer's (LR) solution and another received LR solution plus 66 mg/kg/hr VC. Both groups were resuscitated with the Parkland formula to maintain stable hemodynamics and adequate urine output (>0.5 ml/kg/hr). Patients with >10-hour delay in transfer to the burn center were excluded. Data collected included age, gender, weight, %TBSA, fluid administered in the first 24 hours, urine output in the first 24 hours, and Acute Physiology and Chronic Health Evaluation II score. PaO2 in millimeters mercury:%FIO2 ratio and positive end-expiratory pressure were measured at 12-hour intervals, and hematocrit was measured at 6-hour intervals. Comorbidities, mortality, pneumonia, fasciotomies, and renal failure were also noted. After 7 patients were excluded, 17 patients were included in the VC group and 16 in the LR group. VC and LR were matched for age (42 ± 16 years vs 50 ± 20 years, P = .2), burn size (45 ± 21%TBSA vs 39 ± 15%TBSA, P = .45), Acute Physiology and Chronic Health Evaluation II (17 ± 7 vs 18 ± 8, P = .8), and gender. Fluid requirements in the first 24 hours were 5.3 ± 1 ml/kg/%TBSA for VC and 7.1 ± 1 ml/kg/%TBSA for LR (P < .05). Urine output was 1.5 ± 0.4 ml/kg/hr for VC and 1 ± 0.5 ml/kg/hr for LR (P < .05). Vasopressors were needed in four VC patients and nine LR patients (P = .07). VC patients required vasopressors to maintain mean